{ "classification_aggregates": [ { "aggregate": true, "id": "__aggregate__", "label": "All granted", "type": "grant" } ], "papers": [ { "abstract": "Pancreatic ductal adenocarcinoma (PDAC) frequently harbors co-occurring alterations in KRAS, TP53, CDKN2A, and SMAD4, yet how clinically prevalent driver combinations shape kinase dependencies remains incompletely understood. To systematically interrogate genotype-dependent and shared vulnerabilities, we generated Drosophila models representing dominant PDAC driver contexts, including 2-hit (KRAS-TP53) and 3-hit (KRAS-TP53-CDKN2A or KRAS-TP53-SMAD4) genotypes, and conducted comparative whole-animal genetic screening using organismal viability as a phenotypic readout. This approach identified both genotype-specific modifiers and a subset of kinases whose suppression consistently improved viability across distinct genetic contexts, enabling prioritization of conserved candidates for cross-species validation. Among these, the Drosophila kinase Drak, orthologous to human STK17A/STK17B, emerged as a recurrent shared vulnerability. Functional validation in three-dimensional spheroid cultures of human PDAC cell lines representing distinct driver genotypes demonstrated that STK17B perturbation impairs spheroid growth across models. Transcriptomic profiling further revealed coordinated downregulation of gene sets linked to DNA replication and E2F-driven cell-cycle programs upon STK17B knockdown. Together, these findings establish a genotype-informed screening framework for systematic discovery of shared and context-dependent kinase dependencies in PDAC, and nominate STK17B as a conserved genetic vulnerability across dominant driver contexts.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Han", "last_name": "Hai", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Ooshio", "name": null }, { "creator_type": "author", "first_name": "Hui", "last_name": "Jiang", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Taiga", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Jiayi", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Tongwei", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Ryodai", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.70522" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42680696" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Sep 1", "date_precision": "day", "issue": "", "normalized_date": "2026-09-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Genotype-Informed Whole-Animal Kinome Screening Reveals Shared Kinase Vulnerabilities Across Driver Contexts in PDAC.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Impaired cutaneous wound healing is a major clinical burden, particularly among older individuals and patients with diabetes. Lysophosphatidic acid (LPA) is a bioactive phospholipid with known roles in cell proliferation, migration, and vascular formation; however, its mechanistic contribution in wound repair has not been systematically characterized. Therefore, this study aimed to determine whether topical LPA accelerates wound closure in a murine full-thickness excisional wound model and to elucidate the underlying cellular and molecular mechanisms. METHODS: Full-thickness excisional wounds were created on the dorsal skin of mice, and LPA or vehicle was applied once daily. Wound closure was assessed over 13 days using digital planimetry. Bulk RNA sequencing, quantitative reverse transcription polymerase chain reaction, immunofluorescence, flow cytometry, vascular permeability, and tissue hypoxia assays were employed to delineate the underlying mechanisms. Published single-cell RNA sequencing data from mouse skin were re-analyzed to map LPA receptor expression. RESULTS: Topical LPA accelerated the closure of full-thickness excisional skin wounds. Transcriptomic analysis identified upregulation of gene programs associated with vasculature development and extracellular matrix organization. LPA markedly increased endothelial cell numbers and vessel density. Critically, the vessels formed in LPA-treated wounds subsequently displayed elevated pericyte coverage, reduced permeability, and decreased tissue hypoxia, indicating functional vascular maturation. Concurrently, fibroblast-associated matrix genes were upregulated, collagen deposition was accelerated, and lymphangiogenesis was promoted at the wound site. Single-cell analysis implicated LPAR1 in fibroblasts and LPAR4/LPAR6 in endothelial cells as candidate mediators of these effects. CONCLUSIONS: LPA promotes both vascular maturation and fibroblast activation during wound repair, distinguishing it from classical pro-angiogenic factors. These findings establish LPA as a mechanistically distinct therapeutic candidate and suggest a novel approach for targeting vascular maturation in cutaneous wound care.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takara", "name": null }, { "creator_type": "author", "first_name": "Aika", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Naoi", "last_name": "Hosoe", "name": null }, { "creator_type": "author", "first_name": "Miku", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Takenao", "last_name": "Chino", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Sonoda", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Lamri", "last_name": "Lynda", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Yotsuya", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s41232-026-00441-5" }, "pmcid": { "normalized": "PMC13523234" }, "pmid": { "normalized": "42661212" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Aug 28", "date_precision": "day", "issue": "1", "normalized_date": "2026-08-28", "pages": "", "proceedings_title": null, "publisher": "", "title": "Inflammation and regeneration", "volume": "46", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Lysophosphatidic acid promotes cutaneous wound healing through vascular maturation and fibroblast activation in a murine model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Multiple system atrophy is a fatal, sporadic alpha-synucleinopathy characterized by glial cytoplasmic inclusions in oligodendrocytes. No causative gene for multiple system atrophy has been identified to date. Whole-genome sequencing was performed for a patient with familial multiple system atrophy, in whom an AGG repeat expansion in BIN1 was identified. Based on this finding, we screened for the AGG repeat expansion in BIN1 in a cohort comprising 224 patients with clinically diagnosed multiple system atrophy, 67 patients with pathologically confirmed multiple system atrophy, and control groups including 574 blood samples and 65 brain samples from neurologically healthy individuals. The pathological analysis was performed for four cases with the repeat expansion and five cases without the repeat expansion. The biochemical analysis was performed for nine control subjects, ten cases without the repeat expansion, and eight cases with the repeat expansion. Long-read sequencing identified an AGG repeat expansion in the first intron of BIN1 in the proband. Patients with multiple system atrophy carried a higher frequency of repeat expansions exceeding 80 repeats in the pathological multiple system atrophy group compared to the brain control group (frequency: 13.4% vs. 0%; odds ratio: infinity; 95% confidence interval [CI], 2.1 to infinity; P = 0.003, Fisher's exact test). In contrast, the difference of frequency did not reach statistical significance in the clinical multiple system atrophy group compared to the blood control group (frequency: 4.5% vs 2.4%; odds ratio: 1.87; 95% CI, 0.8 to 4.5; P = 0.16, Fisher's exact test). Neuropathological analysis revealed BIN1-positive glial cytoplasmic inclusions more frequently in the brains of patients with repeat expansions. In immunoblot analysis, insoluble BIN1 were increased in the brains of multiple system atrophy irrespective of repeat status. Our findings indicate that the AGG repeat expansion in BIN1 and BIN1 protein aggregation plays an important role in the pathogenesis of multiple system atrophy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kodai", "last_name": "Kume", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kurashige", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Itabashi", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Akagi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Kikumoto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tamada", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Kamada", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ayaki", "name": null }, { "creator_type": "author", "first_name": "Yuishin", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Yabe", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/brain/awag194" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42663379" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Aug 28", "date_precision": "day", "issue": "", "normalized_date": "2026-08-28", "pages": "awag194", "proceedings_title": null, "publisher": "", "title": "Brain : a journal of neurology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "AGG repeat expansion and aggregation of BIN1 in multiple system atrophy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neuromesodermal progenitors (NMPs) produce the spinal cord and musculoskeleton in the elongating anterior-posterior axis. In vivo, NMPs possess dual potency, coinciding with regions co-expressing SOX2 and Brachyury (TBXT). In vitro, SOX2/TBXT co-expressing cells can be produced from pluripotent cells and, like their in vivo counterparts, can produce neural tube and somitic mesoderm. However, the functional characteristics of in vitro SOX2/TBXT co-expressing cells remain unclear, confounding comparisons with in vivo data. To address this, we developed a dual Sox2/Tbxt reporter mouse ESC line. SOX2/TBXT reporter-positive cells emerge in vitro from pluripotent populations with dynamics that mirror their appearance in the embryo. Purified SOX2/TBXT co-expressing populations can differentiate towards neurectoderm or mesoderm, including lateral mesoderm upon BMP stimulation. In gastruloids, quantitative live imaging shows that WNT or NOTCH inhibition rapidly leads to downregulation of TBXT expression and diminished axial extension. We show that clonally plated SOX2/TBXT co-expressing cells are bipotent NMPs that can also self-propagate. By combining clonal analysis with mathematical inference, we identify two thresholds of TBXT and/or SOX2 expression, switching clonal output from neural- to mesoderm-biased, and from mesoderm-biased to mesoderm-specified. Image analysis of embryonic NMPs supports a model whereby SOX2 and TBXT independently influence neuromesodermal differentiation. Thus, this Sox2/Tbxt double reporter cell line highlights unsuspected heterogeneity in NMPs, and together with image analysis of embryonic SOX2/TBXT levels, challenges the assumption that neuromesodermal fate choice is primarily governed by mutual antagonism between SOX2/TBXT.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Anahi", "last_name": "Binagui-Casas", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Granes", "name": null }, { "creator_type": "author", "first_name": "Alberto S.", "last_name": "Ceccarelli", "name": null }, { "creator_type": "author", "first_name": "Matthew", "last_name": "French", "name": null }, { "creator_type": "author", "first_name": "Filip J.", "last_name": "Wymeersch", "name": null }, { "creator_type": "author", "first_name": "Rosa Portero", "last_name": "Migueles", "name": null }, { "creator_type": "author", "first_name": "Jennifer", "last_name": "Annoh", "name": null }, { "creator_type": "author", "first_name": "Yali", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Eleni P.", "last_name": "Karagianni", "name": null }, { "creator_type": "author", "first_name": "Frederick C. K.", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Raffee", "last_name": "Wright", "name": null }, { "creator_type": "author", "first_name": "A. Sophie", "last_name": "Brumm", "name": null }, { "creator_type": "author", "first_name": "Daniel Lopez", "last_name": "Ramajo", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null }, { "creator_type": "author", "first_name": "Sally", "last_name": "Lowell", "name": null }, { "creator_type": "author", "first_name": "Osvaldo", "last_name": "Chara", "name": null }, { "creator_type": "author", "first_name": "Valerie", "last_name": "Wilson", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pbio.3003960" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42640957" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brachyury Protein", "descriptor_ui": "D000098908", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Fetal Proteins", "descriptor_ui": "D005326", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mouse Embryonic Stem Cells", "descriptor_ui": "D000066450", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": true }, { "descriptor": "SOXB1 Transcription Factors", "descriptor_ui": "D055748", "major_topic": false }, { "descriptor": "T-Box Domain Proteins", "descriptor_ui": "D020825", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Aug 25", "date_precision": "day", "issue": "8", "normalized_date": "2026-08-25", "pages": "e3003960", "proceedings_title": null, "publisher": "", "title": "PLoS biology", "volume": "24", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Brachyury expression levels predict lineage potential and axis-forming ability of in vitro-derived neuromesodermal progenitors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Diurnal and nocturnal mammals are thought to share a functionally equivalent suprachiasmatic nucleus (SCN), the central circadian pacemaker, because standard measures look broadly similar across species. However, coarse readouts do not test when the SCN can be reset or how timing is coordinated across SCN space. We used long-duration ex vivo recordings, optogenetic perturbation, and single-cell calcium phase mapping to compare network dynamics in the nocturnal laboratory mouse (Mus musculus) and the diurnal four-striped grass mouse (Rhabdomys pumilio). Rhabdomys SCN molecular clock rhythms exhibited a longer intrinsic period than Mus and reached a different phase relationship to daily stimulation. Direct SCN stimulation at defined circadian times produced species-specific resetting responses, including a pronounced mid-subjective-day delay in Rhabdomys when Mus responses were minimal. Calcium phase mapping revealed a graded dorsomedial-to-ventrolateral progression in Rhabdomys and a sharper transition in Mus. Thus, coarse SCN similarity does not necessarily imply conserved pacemaker dynamics across species.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Vanessa", "last_name": "Muhl", "name": null }, { "creator_type": "author", "first_name": "Daniela", "last_name": "Lopez-Lorenzo", "name": null }, { "creator_type": "author", "first_name": "Farina", "last_name": "Pourmir", "name": null }, { "creator_type": "author", "first_name": "Samantha O.", "last_name": "Sweck", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Jeff R.", "last_name": "Jones", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2026.117005" }, "pmcid": { "normalized": "PMC13451902" }, "pmid": { "normalized": "42571271" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Aug 21", "date_precision": "day", "issue": "8", "normalized_date": "2026-08-21", "pages": "117005", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "29", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Circadian pacemaker dynamics differ between diurnal and nocturnal mammals.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Porphyromonas (P.) gingivalis is a Gram-negative anaerobic bacterium with exceptionally high pathogenicity among periodontal pathogens. It is associated not only with periodontal disease but also with various systemic diseases, including Alzheimer's disease, rheumatoid arthritis, and atherosclerosis. Therefore, early detection of this bacterium is crucial for enabling subsequent treatment and prevention of such conditions. Herein, we report a chromogenic release-based assay system utilizing calcium carbonate microspheres and a dye-labeled peptide that is selectively cleaved by an Arg-specific protease called gingipain (RgpB) that is secreted by P. gingivalis. By utilizing the reactive anhydride functional groups of poly(isobutylene-alt-maleic anhydride), we simultaneously achieved the conjugation of the dye-labeled peptide and its immobilization onto calcium carbonate microspheres. Through optimization of the peptide sequence and the surface modification density on calcium carbonate microspheres, the assay of RgpB detection with the absorbance of supernatant exhibited a low limit of detection of 0.25 nM, as well as high storage stability and selectivity for P. gingivalis. The measurements obtained with this assay system for clinical gingival crevicular fluid samples showed a high correlation (Pearson's r = 0.79) with qPCR results. This assay system offers an on-site, visual means to monitor P. gingivalis activity without requiring specialized instrumentation.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Zhicheng", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Lubna", "last_name": "Amer", "name": null }, { "creator_type": "author", "first_name": "Natalia O.", "last_name": "Tjokro", "name": null }, { "creator_type": "author", "first_name": "Diego F.", "last_name": "Trujillo", "name": null }, { "creator_type": "author", "first_name": "Jan", "last_name": "Potempa", "name": null }, { "creator_type": "author", "first_name": "Anthony J.", "last_name": "O'Donoghue", "name": null }, { "creator_type": "author", "first_name": "Casey", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Jesse V.", "last_name": "Jokerst", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/advs.77102" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42610650" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Aug 18", "date_precision": "day", "issue": "", "normalized_date": "2026-08-18", "pages": "e77102", "proceedings_title": null, "publisher": "", "title": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Protease-Triggered Chromogenic Release From Peptide-Modified Calcium Carbonate Microspheres Enables Colorimetric Detection of Porphyromonas gingivalis Activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Diabetes is highly heterogeneous, rendering traditional type 1 and type 2 classification insufficient for optimizing treatment strategy. This mini-review examines data-driven clustering-categorizing adult-onset diabetes into five subtypes: SAID (severe autoimmune), SIDD (severe insulin-deficient), SIRD (severe insulin-resistant), MOD (moderate obesity-related), and MARD (mild age-related)-within the context of East Asian populations. East Asians exhibit a distinct \"Asian phenotype\" characterized by impaired insulin secretion and visceral fat accumulation at lower body mass index levels. Meta-analyses reveal a significantly higher proportion of the SIDD subtype in East Asians compared to Caucasians, driven by ancestry-specific genetic variants affecting beta-cell function and tissue-specific gene expression. Furthermore, complication risks differ between regions; while the SIRD cluster remains the primary risk for metabolic dysfunction-associated steatotic liver disease (MASLD) and nephropathy across populations, East Asian SIDD patients face significantly higher risks of chronic kidney disease and sarcopenia than their Caucasian counterparts. These findings emphasize that while clustering provides a robust framework for risk stratification, clinical application in East Asians requires modifications accounting for unique body compositions and pathophysiology. Integrating subtype-guided strategies-such as early intensive insulin therapy for SIDD and multifaceted insulin sensitivity improvement for SIRD-represents a critical step toward personalized medicine to eradicate diabetes complications in East Asians.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Michio", "last_name": "Shimabukuro", "name": null }, { "creator_type": "author", "first_name": "Kiriko", "last_name": "Watanabe-Shimoji", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1210/clinem/dgag338" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42605192" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Aug 17", "date_precision": "day", "issue": "", "normalized_date": "2026-08-17", "pages": "dgag338", "proceedings_title": null, "publisher": "", "title": "The Journal of clinical endocrinology and metabolism", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Data-Driven Diabetes Clustering in East Asians: Pathological Heterogeneity and Personalized Medicine.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "TIE2 is an endothelial receptor tyrosine kinase (RTK) essential for vascular integrity, and constitutively active TIE2 mutants are involved in venous malformations (VMs). VMs are currently treated by surgery or sclerotherapy, but effective pharmacologic options remain limited, especially for surgically challenging Blue Rubber Bleb Nevus Syndrome (BRBNS). TIE2 activation has typically been assessed by immunoblotting of phosphoproteins, yet scalable assays applicable to pharmacological evaluation are still lacking. Here, we present a bioluminescence resonance energy transfer (BRET) biosensor that quantifies receptor-proximal TIE2 activation by monitoring recruitment of GRB2, a major adaptor in RTK signaling. This BRET sensor detects angiopoietin-1 (ANG-1) at physiological plasma concentrations and is compatible with a high-throughput format. Furthermore, it captures constitutive activity of TIE2 mutants associated with VMs and enables pharmacological evaluation of TIE2 variants. Notably, the T1105N-T1106P variant, frequently observed in BRBNS, exhibited relatively higher sensitivity to the clinical oncology drugs regorafenib and lenvatinib. To validate selected BRET-defined pharmacological profiles in an endothelial context, we used HUVEC-derived HUEhT-2 cells and established endothelial TIE2-GRB2 BRET measurements, followed by downstream AKT/ERK signaling analysis and tube formation assays. These endothelial assays largely supported the selected HEK293T BRET findings, particularly the pharmacological profile of T1105N-T1106P mutant, at receptor-proximal, downstream signaling, and functional levels. Together, this BRET-based biosensor establishes a two-step framework: HEK293T BRET enables efficient primary profiling, whereas endothelial assays provide orthogonal validation to support biological interpretation. This framework offers a practical strategy for prioritizing pharmacological candidates for further endothelial and in vivo validation toward therapeutic development.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hitomi", "last_name": "Matsutani", "name": null }, { "creator_type": "author", "first_name": "Atsuro", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Izumi-Tamura", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Muto", "name": null }, { "creator_type": "author", "first_name": "Akihide", "last_name": "Yoshimi", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Kiyonori", "last_name": "Harii", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takushima", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Mine", "last_name": "Ozaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10456-026-10071-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42593687" } }, "mesh": [ { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": true }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Human Umbilical Vein Endothelial Cells", "descriptor_ui": "D061307", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Receptor, TIE-2", "descriptor_ui": "D042787", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Vascular Malformations", "descriptor_ui": "D054079", "major_topic": true }, { "descriptor": "Veins", "descriptor_ui": "D014680", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Aug 13", "date_precision": "day", "issue": "4", "normalized_date": "2026-08-13", "pages": "59", "proceedings_title": null, "publisher": "", "title": "Angiogenesis", "volume": "29", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "A high-sensitivity TIE2-GRB2 BRET platform for functional and pharmacologic profiling of pathogenic variants associated with venous malformations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Rapid eye movement (REM) sleep is thought to be a cortical state closer to wakefulness than non-REM sleep, yet a few brain regions regulate both states. This study identifies the glutamatergic neurons in the lateral periaqueductal gray (LPAG) that are specifically activated during wakefulness and REM sleep, as demonstrated by fiber photometry and optic tetrode recordings. Chemogenetic inhibition of LPAG vesicular glutamate transporter 2 (Vglut2) neurons reduced REM sleep and wakefulness while boosting non-REM sleep; their activation induced wakefulness, with high theta power and immobility. Chemogenetic suppression of the LPAG-sublaterodorsal tegmental nucleus projection curtailed REM sleep, and its optogenetic activation triggered REM sleep, proving that this pathway drives REM sleep. Meanwhile, LPAG(Vglut2) neurons promoted wakefulness through outputs to the locus coeruleus and ventral gigantocellular reticular nucleus, as supported by optogenetic manipulations. Overall, the results show that LPAG(Vglut2) circuits govern both REM sleep and wakefulness, uncovering a crucial region involved in the regulation of both REM sleep and wakefulness.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yi-Qun", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Wei-Xiang", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Liang", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Jian-Bo", "last_name": "Jiang", "name": null }, { "creator_type": "author", "first_name": "Wen-Ying", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Ke", "last_name": "Shi", "name": null }, { "creator_type": "author", "first_name": "Sebastien", "last_name": "Arthaud", "name": null }, { "creator_type": "author", "first_name": "Ling-Xi", "last_name": "Kong", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Wei-Min", "last_name": "Qu", "name": null }, { "creator_type": "author", "first_name": "Pierre-Herve", "last_name": "Luppi", "name": null }, { "creator_type": "author", "first_name": "Zhi-Li", "last_name": "Huang", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2026.117821" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42585020" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Aug 12", "date_precision": "day", "issue": "8", "normalized_date": "2026-08-12", "pages": "117821", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "45", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Control of REM sleep and wakefulness by lateral periaqueductal gray glutamatergic neurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dendritic spine dysfunction may contribute to the etiology and symptom expression of neuropsychiatric disorders. The intimate relationship between spine morphology and function suggests that decoding disease-related abnormalities from spine morphology can aid in developing synapse-targeted interventions. Here, we describe a population analysis of dendritic spine nanostructure applied to the objective grouping of multiple mouse models of neuropsychiatric disorders. This method has identified two major groups of spine phenotypes linked to schizophrenia and autism spectrum disorder (ASD). An increase in spine subpopulation with small volumes characterized the spines of schizophrenia-associated mouse models, whereas a spine subset with large volumes increased in ASD models. Schizophrenia-associated mouse models showed higher similarity in spine morphology, driven by reduced size and growth of nascent spines. The expression of Ecrg4, a gene encoding small secretory peptides, was increased in schizophrenia-associated mouse models, and functional studies confirmed its critical involvement in impaired spine dynamics and shape. These results suggest that population-level spine analysis provides rich insights into heterogeneous spine pathology, facilitating the identification of new molecular targets related to core synaptic dysfunction.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yutaro", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Qingrui", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Go", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Atsu", "last_name": "Aiba", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Okabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.109083" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42576600" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Schizophrenia", "descriptor_ui": "D012559", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Aug 11", "date_precision": "day", "issue": "", "normalized_date": "2026-08-11", "pages": "RP109083", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "14", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Spine nanostructure profiling of cultured neurons from mouse models reveals a schizophrenia-linked role for Ecrg4.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although second near-infrared (NIR-II) photoacoustic (PA) imaging affords deep tissue penetration, developing efficient contrast agents remains challenging due to a lack of suitable optical absorbers. Herein, we report semiconducting polymer nanoparticles (SPNs) for dual-modal PA and NIR fluorescence imaging, featuring a high optical absorption coefficient at 1064 nm that facilitates excitation via high-power Nd:YAG lasers. Phantom evaluations revealed a linear PA signal correlation, with a low detection limit of 0.05 cm(-1). In vivo studies in tumor-bearing mice demonstrated passive SPN accumulation in tumor tissue, successfully visualized by both PA and NIR fluorescence imaging. These results indicate that SPNs are promising contrast agents for dual-modal imaging.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Saya", "last_name": "Akasaka", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Shintate", "name": null }, { "creator_type": "author", "first_name": "Manami", "last_name": "Miyashita", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Tsubata", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/boe.604939" }, "pmcid": { "normalized": "PMC13481065" }, "pmid": { "normalized": "42609955" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Aug 1", "date_precision": "day", "issue": "8", "normalized_date": "2026-08-01", "pages": "4378-4389", "proceedings_title": null, "publisher": "", "title": "Biomedical optics express", "volume": "17", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "1064 nm-absorbing semiconducting polymer nanoparticles for multimodal photoacoustic and fluorescence imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The discovery and development of high-performance catalysts, which is crucial across all catalysis areas, requires advanced technologies and innovative approaches. Recently, machine learning (ML) has shown promise in accelerating this process, but its capability and examples of discovery of truly novel catalysts have remained limited. In this study, we describe an ML approach that goes beyond the traditional element pool, incorporating elements that have not been previously studied, to develop highly efficient catalysts for ethanol synthesis via CO2 hydrogenation. Starting with an initial data set of 58 catalysts (274 data points obtained at reaction temperatures ranging from 240-400 degrees C), we conducted 24 iterations of a closed-loop discovery system (ML predictions + experimental validation), testing a total of 555 catalysts (2477 data points), and building a large experimental data set. More than 50 catalysts with superior activity were discovered through this data-driven approach. The multielemental Pd(0.8)-Au(0.3)/K(2.5)-Sr(1)-Fe(20)-Zn(4)-Cd(2)-Yb(1)-Re(1)/CeO2(25%)-ZrO2 catalyst, where the numbers in parentheses represent weight percent (wt %), was identified as the most effective catalyst for ethanol synthesis (ethanol space-time yield: 8.2 mmol gcat-1 h-1 with a CO2 conversion of 57.6% and an ethanol selectivity of 23.2% under reaction conditions of 360 degrees C, 4 MPa, 12 L gcat-1 h-1, H2/CO2 = 3/1). Comprehensive characterizations, including in situ/operando techniques such as X-ray absorption spectroscopy (XAS), ambient-pressure X-ray photoelectron spectroscopy (AP-XPS), and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), enable us to highlight the critical roles of each constituting element in improving ethanol synthesis efficiency.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Pengfei", "last_name": "Du", "name": null }, { "creator_type": "author", "first_name": "Abdellah", "last_name": "Ait El Fakir", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Mine", "name": null }, { "creator_type": "author", "first_name": "Bin", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Hongli", "last_name": "Pan", "name": null }, { "creator_type": "author", "first_name": "Chenxi", "last_name": "He", "name": null }, { "creator_type": "author", "first_name": "Nazmul Hasan Md", "last_name": "Dostagir", "name": null }, { "creator_type": "author", "first_name": "Yuriko", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Jorg W. A.", "last_name": "Fischer", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Anzai", "name": null }, { "creator_type": "author", "first_name": "Giles", "last_name": "Allison", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Toyoshima", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kondoh", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Christophe", "last_name": "Coperet", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Toyao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.6c06886" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42444444" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jul 29", "date_precision": "day", "issue": "29", "normalized_date": "2026-07-29", "pages": "31154-31170", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "148", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Machine Learning-Assisted Development of High-Performance Ethanol Synthesis Catalysts via CO2 Hydrogenation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Catalytic N(2)O decomposition in the presence of O(2) is a key process for addressing environmental challenges, such as greenhouse gas emissions and ozone layer depletion. However, the identification of efficient catalysts for this reaction remains challenging owing to the limitations of conventional methods. In this study, we employ a machine learning approach designed to accelerate the discovery of effective direct N(2)O decomposition catalysts. Starting with 51 catalysts and conducting 37 cycles of a closed-loop discovery system (machine-learning prediction + experiment), 633 catalysts are experimentally tested. Over 10 multi-elemental catalysts exhibiting superior activity are identified, surpassing the performance of the originally identified best catalyst. Among them, Rh(1)-Pd(2)/ZrO(2)_EP exhibits the highest catalytic performance for N(2)O decomposition. Through control experiments and a combination of ex situ and in situ characterizations, we identify the essential role of each component within the catalyst system.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Chenxi", "last_name": "He", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Mine", "name": null }, { "creator_type": "author", "first_name": "Yuan", "last_name": "Jing", "name": null }, { "creator_type": "author", "first_name": "Tsz Lok", "last_name": "Wan", "name": null }, { "creator_type": "author", "first_name": "Jialei", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Junxian", "last_name": "Qin", "name": null }, { "creator_type": "author", "first_name": "Ningqiang", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Taketoshi", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Anzai", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Toyoshima", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kondoh", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Toyao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-026-75902-z" }, "pmcid": { "normalized": "PMC13522588" }, "pmid": { "normalized": "42660907" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jul 28", "date_precision": "day", "issue": "1", "normalized_date": "2026-07-28", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "17", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Data-driven catalyst design for direct catalytic N(2)O decomposition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "There is a global need for bioimage analysis (BIA) as advances in life sciences increasingly rely on cutting-edge imaging systems that have dramatically expanded the complexity and dimensionality of biological images. Turning these data into scientific discoveries requires scientists with effective data management skills and knowledge of state-of-the-art image processing and data analysis, in other words, bioimage analysts. The Global BioImage Analysts' Society (GloBIAS) aims to enhance the profile of bioimage analysts as a key role in science and research. To better understand the needs and geographical representation of the BIA community, a worldwide survey was conducted, and 290 responses were collected across people from all career stages and continents. The survey underscores a strong interest of the BIA community in the activities proposed by GloBIAS to address shortcomings in work environment, funding, and scientific activities, and the enthusiasm of the community to actively contribute to the growth and sustainability of GloBIAS as a scientific society.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Laura R.", "last_name": "de la Ballina", "name": null }, { "creator_type": "author", "first_name": "Christa G.", "last_name": "Walther", "name": null }, { "creator_type": "author", "first_name": "Nicholas D.", "last_name": "Condon", "name": null }, { "creator_type": "author", "first_name": "Alessandro A.", "last_name": "Felder", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Schatz", "name": null }, { "creator_type": "author", "first_name": "Bettina", "last_name": "Schmerl", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Clara", "last_name": "Prats", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Klemm", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Paula", "last_name": "Sampaio", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Tischer", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Rocco", "last_name": "D'Antuono", "name": null }, { "creator_type": "author", "first_name": "Beth A.", "last_name": "Cimini", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Haase", "name": null }, { "creator_type": "author", "first_name": "Agustin A.", "last_name": "Corbat", "name": null }, { "creator_type": "author", "first_name": "Florian", "last_name": "Levet", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/jmi.70153" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42504951" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jul 27", "date_precision": "day", "issue": "", "normalized_date": "2026-07-27", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of microscopy", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "GloBIAS survey results - An insight into the global bioimage analysis community.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Homotypic targeting is the inherent ability of cells to preferentially interact with cells of the same type, a phenomenon seen in cell adhesion, tissue formation and immune responses. However, its potential remains underexploited. Here we report a strategy to substantially enhance homotypic targeting through extracellular vesicles secreted by cells. By engineering the surface of small extracellular vesicles (sEVs) with lanthanides, we amplify specific cell-sEV interactions by more than 25-fold, enabling the selective capture of sEVs by cells of the same lineage even in the presence of excess off-target sEVs. We term this effect 'super homotypic targeting'. Super homotypic targeting provides a means to distinguish sEVs of different origins within highly heterogeneous sEV populations and enables two applications: using cells to detect specific sEVs and using sEVs to detect specific cells, specifically demonstrated here in the context of cancer detection from blood samples. Super homotypic targeting could hold potential for diagnostics, immunotherapy, drug delivery, rejuvenation and tissue engineering.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Huai-Song", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Tianben", "last_name": "Ding", "name": null }, { "creator_type": "author", "first_name": "Yuhong", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Fabio", "last_name": "Lisi", "name": null }, { "creator_type": "author", "first_name": "Yuqi", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Yaqi", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Xin-Yuan", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Zi-Wei", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Jing-Lian", "last_name": "Su", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Natsumi Tiffany", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Anel", "last_name": "Umirbaeva", "name": null }, { "creator_type": "author", "first_name": "Hongwei", "last_name": "Guo", "name": null }, { "creator_type": "author", "first_name": "Yin-Yu", "last_name": "Yan", "name": null }, { "creator_type": "author", "first_name": "Fu-Han", "last_name": "Gao", "name": null }, { "creator_type": "author", "first_name": "Jia-Jing", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yasutaka", "last_name": "Kitahama", "name": null }, { "creator_type": "author", "first_name": "Petra", "last_name": "Paie", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Kenbun", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Abdullah N.", "last_name": "Alodhayb", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Nitta", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Yatomi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Ya", "last_name": "Ding", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null }, { "creator_type": "author", "first_name": "Dino", "last_name": "Di Carlo", "name": null }, { "creator_type": "author", "first_name": "Shiro", "last_name": "Suetsugu", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Goda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41551-026-01743-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42486903" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jul 22", "date_precision": "day", "issue": "", "normalized_date": "2026-07-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature biomedical engineering", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Super homotypic targeting by surface engineering of extracellular vesicles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Wavelike motion mediated by chemotactic signaling occurs in various biological phenomena including neutrophil swarms, wound healing, and amoeba aggregates. However, the macroscopic transition from independent to collective cellular behavior remains unclear, including how to quantify the response of individual cells to a developing chemotactic wave. Recent advances in molecular imaging allow concurrent observation of cyclic adenosine monophosphate (cAMP) concentrations and cell movement at individual resolution. Employing particle image velocimetry (PIV), a scheme to extract Eulerian velocity vector fields in fluids, we derived velocity fields at different Gaussian blurring levels and found that while original fluorescent images reflect cell movement, blurred versions highlight cAMP wave propagation. We identified the phase of cAMP signal wave dynamics and analyzed the interplay between single-cell motility and cAMP wave development. The extracted velocity fields at single-cell resolution show an almost antipodal relationship to those of the cAMP wave characterized by the blurred image, with an angle close to 180 degrees during the rise of the wave when the spiral wave is well developed. Furthermore, single-cell dynamics collectively move toward the crest of the coming cAMP wave but rest (with randomized directionality) in the troughs between waves, akin to \"surfing of the collectives\".", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "18H05413", "label": "18H05413", "researcher": "Tamiki Komatsuzaki", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" }, { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Sulimon", "last_name": "Sattari", "name": null }, { "creator_type": "author", "first_name": "Md Motaleb", "last_name": "Hossain", "name": null }, { "creator_type": "author", "first_name": "Udoy S.", "last_name": "Basak", "name": null }, { "creator_type": "author", "first_name": "Mikito", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-026-61774-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42471391" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": true }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Rheology", "descriptor_ui": "D012212", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jul 18", "date_precision": "day", "issue": "", "normalized_date": "2026-07-18", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Collective surfing of single cells on a chemo-attractant wave using multiscale Eulerian velocity vector field.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A long-standing challenge in phylogenomics has been the resolution of relationships originated from ancient radiations. In these cases, phenomena such as incomplete lineage sorting can increase the support for conflicting resolutions. Most of the diversity in the Class Bivalvia originated during an Ordovician radiation; indeed, several deep relationships among Bivalvia have not been fully resolved yet. Traditionally, Heterodonta clusters the Subclasses Archiheterodonta and Euheterodonta; however, recent analyses supported Archiheterodonta as sister to the other Subclass Palaeoheterodonta (A + P). Until now, Archiheterodonta was the last major Bivalvia clade lacking a genome assembly: we sequenced the genome of Cardita leana (Archiheterodonta, Carditidae) and inferred the phylogeny from a supermatrix including 64 bivalve species. Although different methods supported Heterodonta, many genes (27% of the dataset) favoured Archiheterodonta + Palaeoheterodonta (A + P). This discordance could not be ascribed to any systematic phylogenetic biases. However, divergence times obtained from the respective supporting genes datasets placed the origin of Heterodonta significantly deeper than the origin of A + P, appearing inconsistent with the fossil record. This suggests that genes supporting Heterodonta reflect ancestral polymorphisms that persisted in Archiheterodonta and Heterodonta lineages through incomplete lineage sorting. Overall, we suggested a phylogenomic framework to study deep radiations and showed that A + P represents a plausible hypothesis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Alessandro", "last_name": "Formaggioni", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Federico", "last_name": "Plazzi", "name": null }, { "creator_type": "author", "first_name": "Marco", "last_name": "Passamonti", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cla.70056" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42470186" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jul 18", "date_precision": "day", "issue": "", "normalized_date": "2026-07-18", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cladistics : the international journal of the Willi Hennig Society", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Clues of ancient incomplete lineage sorting during bivalve evolution undermine support for Heterodonta.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Triple-negative breast cancer (TNBC) lacks effective molecularly targeted therapies. Here, we identify branched-chain amino acid (BCAA) metabolism as a selective vulnerability in human TNBC, particularly in the claudin-low subtype. TNBC cells show greater dependence on BCAAs than other breast cancer subtypes, and intracellular BCAA levels are heterogeneous within tumors in vivo. Cells with high BCAA levels exhibit enhanced sphere formation and cancer stem cell potential in xenograft models. BCAT1, a cytoplasmic BCAA aminotransferase, is upregulated in claudin-low TNBC and enables tumor growth by promoting BCAA production from branched-chain ketoacids. BCAT1 knockdown impairs TNBC growth in vivo, and high BCAT1 expression predicts poor prognosis in patient cohorts. Conversely, BCAA catabolism via the BCKDH complex is suppressed in TNBC, and reactivation of BCKDH by BCKDK knockout blocks clonogenic growth. These findings reveal BCAA metabolic balance as a key regulator of TNBC stemness and malignancy.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kenkyo", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Ririko", "last_name": "Shinonaga", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Hsin", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Maeno", "name": null }, { "creator_type": "author", "first_name": "Kayo", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Haruki", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Imotani", "name": null }, { "creator_type": "author", "first_name": "John", "last_name": "Glushka", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Kaji", "name": null }, { "creator_type": "author", "first_name": "Jun-Ichiro", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Ayuna", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2026.117630" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42418320" } }, "mesh": [ { "descriptor": "Amino Acids, Branched-Chain", "descriptor_ui": "D000597", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Metabolic Reprogramming", "descriptor_ui": "D000097784", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": true }, { "descriptor": "Transaminases", "descriptor_ui": "D000637", "major_topic": false }, { "descriptor": "Triple Negative Breast Neoplasms", "descriptor_ui": "D064726", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jul 8", "date_precision": "day", "issue": "7", "normalized_date": "2026-07-08", "pages": "117630", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "45", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Distinct metabolic dependency on BCAA defines cancer stemness and malignancy in human triple-negative breast cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Text Correction [...].", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuya", "last_name": "Izubuchi", "name": null }, { "creator_type": "author", "first_name": "Naoi", "last_name": "Hosoe", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tatsunobu", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Matsumine", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biomedicines14071520" }, "pmcid": { "normalized": "PMC13405609" }, "pmid": { "normalized": "42512126" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jul 7", "date_precision": "day", "issue": "7", "normalized_date": "2026-07-07", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biomedicines", "volume": "14", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Correction: Izubuchi et al. Antitumor Effects of PD-1 Blockade Combined with Mild Hyperthermia in a Murine Osteosarcoma Model. Biomedicines 2026, 14, 341.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Orexin neurons regulate physiological functions, such as energy homeostasis, wakefulness, and motivated behaviors. However, studies linking orexin neuron activity to behavior via selectively activating/inactivating these inputs in a temporally controlled manner in rats are scarce. Here, we examined the role that orexin neurons play in motivated behavior in transgenic rats using cell type-specific fiber photometry and optogenetic manipulation. Using chemogenetics, we found that motivation for a reward increased when orexin neurons were activated. Furthermore, during motivated behavior, orexin neuron activity changed dynamically: Activity increased during reward prediction and decreased after reward receipt. When an unexpected event occurred (i.e., not obtaining an expected reward), increased orexin activity was sustained. Notably, orexin activity strengthened with increasing effort. Optogenetic inhibition of orexin neuron activation during reward prediction and treatment with an orexin 1-receptor antagonist reduced reward-seeking behavior. Therefore, orexin is crucial for linking predicted expectations with motivated behavior. Moreover, optimization of orexin activity is necessary to overcome difficulties during motivated behaviors.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yutao", "last_name": "Dong", "name": null }, { "creator_type": "author", "first_name": "Sheikh Mizanur", "last_name": "Rahaman", "name": null }, { "creator_type": "author", "first_name": "Wenjun", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Ayumu", "last_name": "Inutsuka", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Rinako", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Matsuzaki", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Madoka", "last_name": "Isobe", "name": null }, { "creator_type": "author", "first_name": "Shuntaro", "last_name": "Izawa", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Kiyofumi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mizoguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2520677123" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42372152" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Motivation", "descriptor_ui": "D009042", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Orexin Receptor Antagonists", "descriptor_ui": "D000068796", "major_topic": false }, { "descriptor": "Orexin Receptors", "descriptor_ui": "D064446", "major_topic": false }, { "descriptor": "Orexins", "descriptor_ui": "D000068797", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Transgenic", "descriptor_ui": "D055647", "major_topic": false }, { "descriptor": "Reward", "descriptor_ui": "D012201", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jul 7", "date_precision": "day", "issue": "27", "normalized_date": "2026-07-07", "pages": "e2520677123", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "123", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Reward prediction is encoded by orexin neuron activity during motivated behavior.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Animals balance staying in a favorable environment with exploring new ones. In C. elegans chemotaxis, the process by which worms migrate toward an attractant has been extensively studied. However, what happens after they reach it remains largely unexplored, partly because conventional assays immobilize worms at the point of arrival. Here, we quantitatively analyzed chemotactic behavior upon reaching an attractive odor source using an immobilization-free chemotaxis assay. We observed that 62% animals left the isoamyl alcohol region after initially approaching it, a behavior we termed \"leaving behavior.\" Quantitative analysis revealed that leaving behavior represents a distinct locomotor state compared with free-moving, high-concentration odor avoidance, and approach behavior. To test whether leaving behavior is related to olfactory adaptation, we analyzed mutants in adaptation-related genes. The proportion of leaving behavior was significantly increased in egl-4 loss-of-function mutants compared with wild-type animals, whereas arr-1 mutants showed no significant difference. These results suggest that egl-4 negatively regulates leaving behavior, suggesting a role for this kinase in stabilizing post-arrival behavioral states beyond its known function in olfactory adaptation. Our findings indicate that chemotaxis involves dynamic behavioral transitions even after reaching an attractant, consistent with an exploration-exploitation trade-off framework.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shiori", "last_name": "Onoue", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.64898/2026.07.01.734387" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jul 7", "date_precision": "day", "issue": null, "normalized_date": "2026-07-07", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2026 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000504" ] }, "title": "Immobilization-free chemotaxis analysis reveals the novel behavioral mode of \"leaving\" in Caenorhabditis elegans.", "url": "", "zotero": { "item_type": "preprint" } }, { "abstract": "Nucleic acid aptamers are promising next-generation experimental and therapeutic drugs for uncharacterized biomolecules and intractable diseases. However, efficient aptamer selection remains challenging. We have developed a functional selection method termed extracellular vesicle (EV)-SELEX that efficiently selects DNA aptamers for G protein-coupled receptors (GPCRs), a major class of drug targets via ligand-dependent GPCR endocytosis and subsequent release of GPCR-containing EVs. Using this method, we obtained Dapt-muR, a DNA aptamer that had a high affinity to mu-opioid receptor (MOR) (K(d) approximately 28 nM) but no other types of opioid receptors. In unmodified form, Dapt-muR acted as a morphine-like, naloxone-sensitive MOR agonist, inhibiting cAMP accumulation in cultured cells and reducing Ca(2+) influx in primary striatal neurons. Furthermore, Dapt-muR selectively bound to the MOR-rich spinal cord dorsal horn and produced an analgesic effect following intrathecal administration in mice. These findings demonstrate that EV-SELEX is a powerful method for selecting DNA aptamers for target GPCRs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsushi J.", "last_name": "Ikemoto", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kamikubo", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Uta", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Kirinoki", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Kiriyama", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Miyajima", "name": null }, { "creator_type": "author", "first_name": "Hakushun", "last_name": "Sakairi", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Tabata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-026-10525-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42414537" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aptamers, Nucleotide", "descriptor_ui": "D052157", "major_topic": true }, { "descriptor": "Extracellular Vesicles", "descriptor_ui": "D000067128", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Receptors, Opioid, mu", "descriptor_ui": "D017450", "major_topic": true }, { "descriptor": "SELEX Aptamer Technique", "descriptor_ui": "D052156", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jul 7", "date_precision": "day", "issue": "1", "normalized_date": "2026-07-07", "pages": "861", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "9", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Efficient and specific selection of high-affinity DNA aptamers targeting mu-opioid receptor via functional extracellular vesicles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We systematically explored PEG alternatives by synthesizing a combinatorial library of nine copolymers composed of three hydrophilic monomers including oligo(ethylene glycol) methyl ether methacrylate and 2-(methylsulfinyl)ethyl methacrylate and three hydrophobic monomers. These copolymers were evaluated for their hydrophobicity by reversed-phase chromatography and LCST behavior, and for their biodistribution. Extended hydrophilic brushes enhanced blood retention and tumor accumulation. For copolymers with the longest brushes, hydrophobic side chains minimally influenced kidney accumulation, whereas kidney accumulation of copolymers with medium-length brushes was strongly influenced. Liver accumulation of the copolymers was hardly affected by the hydrophobic side chain, except for the copolymer with the longest brushes and the most hydrophobic side chains, which showed increased liver accumulation. This study highlights the critical role of hydrophilic brushes and hydrophobic side chains in modulating biodistribution of polymeric carriers and provides a foundation for rational design of drug delivery systems.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mayu", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Noa", "last_name": "Kamatani", "name": null }, { "creator_type": "author", "first_name": "Mizuho", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Sakama", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Mukai", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.biomac.6c00159" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42400508" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drug Carriers", "descriptor_ui": "D004337", "major_topic": true }, { "descriptor": "Hydrophobic and Hydrophilic Interactions", "descriptor_ui": "D057927", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Polyethylene Glycols", "descriptor_ui": "D011092", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": true }, { "descriptor": "Polymethacrylic Acids", "descriptor_ui": "D011109", "major_topic": true }, { "descriptor": "Tissue Distribution", "descriptor_ui": "D014018", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jul 4", "date_precision": "day", "issue": "", "normalized_date": "2026-07-04", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biomacromolecules", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Effect of Hydrophilic Brush Length and Hydrophobic Chain on Biodistribution of Polymethacrylate-Based Statistical Copolymers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: Previous studies demonstrated that preeclampsia (PE) with proteinuria is associated with concurrent renal injury. However, it is unclear how renal damage that occurs during pregnancy changes after delivery. This study was conducted to assess postpartum renal impairment in women with PE and to examine its possible link to the subsequent development of chronic kidney disease (CKD). STUDY DESIGN: We conducted a retrospective cohort study analyzing a group of women with PE and proteinuria (PE-UP (+)) (N = 30). Control data were obtained from normotensive participants at 35 weeks of gestation (N = 20) and 12 weeks postpartum (N = 15). MAIN OUTCOME MEASURES: Serum hyaluronan (glycocalyx injury), urinary podocalyxin (podocyte injury), urinary liver-type fatty acid-binding protein (L-FABP) and N-acetyl-beta-D-glucosaminidase (NAG) (tubular injury) were measured at PE diagnosis and at 12 weeks postpartum. RESULTS: Based on the urinary protein/creatinine ratio (UPCR) at 12 weeks postpartum, the PE-UP (+) group was stratified into the PE-UP improved group (UPCR <0.15 g/g Cr; N = 20) and PE-UP persistent group (UPCR >/=0.15 g/g Cr; N = 10). The urinary L-FABP and NAG levels in the PE-UP improved group were significantly lower than those in the PE-UP persistent group. In contrast, the levels of hyaluronan and podocalyxin remained significantly elevated in both PE subgroups compared to those in the postpartum controls. CONCLUSIONS: Postpartum women with PE and prolonged proteinuria exhibit residual tubular dysfunction. Women with PE in whom proteinuria has resolved may still have residual glomerular damage at 12 weeks postpartum. The clinical trial described in this paper was registered at the UMIN Clinical Trials Registry under registration number UMIN000058351. URL of registration: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000066708.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazumasa", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Tomohito", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Kohmura-Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Morioka", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Kazushi", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.preghy.2026.101496" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42378806" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jun 30", "date_precision": "day", "issue": "", "normalized_date": "2026-06-30", "pages": "101496", "proceedings_title": null, "publisher": "", "title": "Pregnancy hypertension", "volume": "45", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Persistent postpartum proteinuria, renal dysfunction, and future chronic kidney disease risk in women with preeclampsia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The in situ hybridization chain reaction (isHCR) visualizes RNA across multiple spatial scales, from organs to subcellular structures, in diverse samples. We previously proposed a rapid protocol, EC-isHCR, for Drosophila embryos and ovaries. Whether EC-isHCR retains the features of conventional isHCR, including wide-spatial-scale analyses in various samples, however, has remained unclear. Here, we show that EC-isHCR enables robust RNA detection in a broad range of samples, such as whole-mount fruit fly, parasitoid wasp, and aphid preparations; paraffin sections of trout; frozen mouse sections; and human cultured cells. Moreover, EC-isHCR enabled detection of subcellular RNA localization. EC-isHCR also visualized association of RNA with phase-separated condensates in fruit fly embryos and detected the protrusion-enriched mRNA in HeLa cells. To broaden the applicability of EC-isHCR, we developed an automated probe design tool (https://github.com/ShuntaYorimoto/hcrkit). By combining this tool with EC-isHCR, we provide a fast and versatile framework to visualize mRNAs. This framework will help reduce the barrier to using fast isHCR and thereby facilitate research across diverse areas of the life sciences.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kozono", "name": null }, { "creator_type": "author", "first_name": "Kyohei", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Shunta", "last_name": "Yorimoto", "name": null }, { "creator_type": "author", "first_name": "Taisei", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Hibiki", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Qingyin", "last_name": "Qian", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Hoshino", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Kamiyama", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Sanaki", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Asaoka", "name": null }, { "creator_type": "author", "first_name": "Sonoko", "last_name": "Ohsawa", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Yuka W.", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Shigenobu", "name": null }, { "creator_type": "author", "first_name": "Ryusuke", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ymeth.2026.06.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42372957" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Ovary", "descriptor_ui": "D010053", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jun 29", "date_precision": "day", "issue": "", "normalized_date": "2026-06-29", "pages": "S1046-2023(26)00154-4", "proceedings_title": null, "publisher": "", "title": "Methods (San Diego, Calif.)", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "EC-isHCR: A rapid method for in situ hybridization chain reaction in diverse animal samples.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Medium-sized therapeutics such as nucleic acids and peptides often exhibit poor membrane permeability, posing a major barrier to efficient intracellular delivery. To address this challenge, we previously developed a light-driven molecular machine based on a tetraphenylethene derivative (TPE-C8-N) that enables carrier-free intracellular delivery of biomolecules under light irradiation. However, the molecular mechanism underlying light-induced membrane permeabilization remains unclear. Here, we combined cellular experiments with multiscale molecular dynamics (MD), path-sampling, and umbrella-sampling simulations to establish a structure-dependent strategy for controlling membrane permeabilization induced by photoresponsive TPE derivatives. A series of derivatives, TPE-Cn-N (n = 4, 8, 12, and 16), was synthesized to examine the effect of alkyl chain length on intracellular delivery. Cellular experiments showed that TPE-C8-N localizes to the plasma membrane and exhibits the highest endocytosis-independent delivery efficiency, whereas longer-chain derivatives tend to form intracellular aggregates and rely more strongly on endocytosis-mediated uptake, demonstrating that alkyl chain length enables switching between distinct intracellular delivery pathways. Coarse-grained MD simulations revealed that alkyl chain length governs the self-assembly morphology of TPE molecules on the membrane, with TPE-C8-N forming linear assemblies that induce pronounced membrane curvature. Furthermore, rare-event simulations using infinityRETIS and umbrella sampling showed that TPE-C8-N modestly promotes pore nucleation and accumulates more strongly near the pore than TPE-C16-N, suggesting that multiple TPE-C8-N molecules can cooperatively enhance photoisomerization-induced membrane perturbation. However, TPE-C8-N does not stabilize expanded open pores, supporting transient membrane-defect formation rather than persistent pore stabilization as the primary permeabilization mechanism. These results provide molecular-level and thermodynamic insights into light-induced membrane permeabilization and establish design guidelines for light-driven intracellular delivery systems.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Reo", "last_name": "Kadowaki", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Daniel Tianhou", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Wenting", "last_name": "Huo", "name": null }, { "creator_type": "author", "first_name": "Huiying", "last_name": "Mu", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Shinoda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsabm.6c00634" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42345519" } }, "mesh": [ { "descriptor": "Biocompatible Materials", "descriptor_ui": "D001672", "major_topic": true }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Membrane Permeability", "descriptor_ui": "D002463", "major_topic": true }, { "descriptor": "Ethylenes", "descriptor_ui": "D005030", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": true }, { "descriptor": "Materials Testing", "descriptor_ui": "D008422", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jun 25", "date_precision": "day", "issue": "", "normalized_date": "2026-06-25", "pages": "", "proceedings_title": null, "publisher": "", "title": "ACS applied bio materials", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Structure-Dependent Modulation of Light-Induced Membrane Permeabilization by Photoresponsive Tetraphenylethene Derivatives Revealed through Multiscale Simulations and Cellular Experiments.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reproductive function in female mammals is largely orchestrated by the hypothalamic-pituitary-gonadal axis, which generates rhythmic hormonal fluctuations underlying the estrous cycle. Part of this cycle, the preovulatory LH surge, is tightly gated by the circadian system. The suprachiasmatic nucleus (SCN)-the central circadian clock-plays a critical role in this temporal regulation and among SCN-derived signals, neuropeptides such as arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) have been proposed to mediate this process. Notably, most SCN neurons are GABAergic; however, the contribution of SCN-derived GABAergic transmission in the female reproductive system remains unclear. To investigate the role of GABAergic output from the SCN, we first performed AAV-mediated SCN ablation in Vgat-IRES-Cre mice (Vgat; encoding the vesicular GABA transporter), resulting in disrupted estrous cycles. To assess GABAergic transmission from specific SCN populations, we next examined Avp-Vgat(-/-) and Vip-Vgat(-/-) mice, in which the Vgat gene is selectively deleted in AVP or VIP neurons. Vip-Vgat(-/-) females showed regular cycles. However, Avp-Vgat(-/-) females exhibited marked disruptions, and AAV-mediated Vgat rescue in AVP neurons in the SCN (SCN-AVP) restored normal estrous cycles. Anterograde tracing revealed dense SCN-AVP terminals in the anteroventral periventricular nucleus (AVPV), which contains kisspeptin neurons, but few projections to other major reproductive neuroendocrine populations. These findings suggest GABAergic output from SCN-AVP neurons stabilizes the estrous cycle, potentially via kisspeptin neurons in the AVPV, thereby highlighting that GABAergic signaling also contributes to female reproductive regulation alongside AVP and VIP.Significance Statement The circadian system must precisely coordinate the timing of ovulation, and is essential for maintaining a stable estrous cycle. Although most neurons in the master clock are GABAergic, their role in reproductive control remains unknown. Here, our study identifies GABAergic signaling from arginine vasopressin neurons in the master clock as a key regulator of the estrous cycle. Loss of this signaling disrupts estrous cyclicity, and its restoration rescues regular cycling. This finding highlights GABA release from arginine vasopressin neurons as an additional component of reproductive control, alongside established peptidergic regulators such as arginine vasopressin and vasoactive intestinal peptide. This work advances our understanding of how the brain's circadian system organizes complex reproductive physiology through multiple neural output pathways.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mizuki", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "George E.", "last_name": "Bentley", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Mieda", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Takahiro J.", "last_name": "Nakamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.2328-25.2026" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42336663" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arginine Vasopressin", "descriptor_ui": "D001127", "major_topic": true }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Estrous Cycle", "descriptor_ui": "D030762", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "GABAergic Neurons", "descriptor_ui": "D059330", "major_topic": true }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": true }, { "descriptor": "Hypothalamic-Pituitary-Gonadal Axis", "descriptor_ui": "D000094365", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": true }, { "descriptor": "Vasoactive Intestinal Peptide", "descriptor_ui": "D014660", "major_topic": false }, { "descriptor": "Vesicular Inhibitory Amino Acid Transport Proteins", "descriptor_ui": "D050495", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jun 23", "date_precision": "day", "issue": "", "normalized_date": "2026-06-23", "pages": "e2328252026", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "GABAergic signaling from arginine vasopressin neurons in the suprachiasmatic nucleus is essential for maintaining the estrous cycle in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Accurate blood vessel morphology analysis is essential for understanding vascular system development and pathology. Although advanced imaging technologies. have enabled the rapid acquisition of complex vascular images, quantitative analysis methods have not kept pace. Importantly, current methods cannot accurately represent vessels with complex curved structures and variable diameters, and the existing software lacks efficient automation for large datasets. RESULTS: In this study, we developed PAVSAT (Python-based Auto Vessel Segmentation Analysis Tool), an automated computational system for quantifying vascular structures by integrating deep learning-based segmentation, image processing, and graph theory. The system employs a YOLOv8 architecture trained on confocal immunofluorescence microscopy images of CD31-stained vascular structures, followed by skeletonization to extract the vessel centerlines. A novel branch-point detection algorithm identifies bifurcations by analyzing local connectivity patterns and performs dense, segment-wise vessel diameter profiling through repeated perpendicular sampling along the locally estimated vessel orientation. To mitigate systematic detection errors at tile boundaries, we implemented a boundary-aware overlapping tiling scheme in which images are processed with spatial offsets and outputs merged to ensure that each sinusoid is analyzed under optimal central-tile conditions. Ablation analysis confirmed that this overlapping integration substantially reduced undetected vessels (by 40.5 and 81.0% in two independent samples) with only marginal increases in false-positive detections (2.2 and 6.3%, respectively), indicating a clearly favorable trade-off between sensitivity and specificity. A graph-based representation converts the vascular structures into nodes and edges for network analysis. Validation against expert manual measurements demonstrated detection rates of 91-98% and measurement accuracy of 89-93% within 10 pixels of the manual measurements, with no detectable systematic bias between automated and manual diameters (mean difference < 0.3 pixels, paired t-test and Wilcoxon p > 0.2 for both samples) and strong agreement (Pearson r > 0.94). CONCLUSIONS: PAVSAT successfully identified complex branching patterns, measured the diameters along curved vessels, and generated quantitative data suitable for large-scale studies, thereby facilitating vascular biology, development, and pathology research.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ryozo", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Naoi", "last_name": "Hosoe", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takara", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Lamri", "last_name": "Lynda", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12859-026-06505-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42332561" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Blood Vessels", "descriptor_ui": "D001808", "major_topic": true }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": true }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jun 22", "date_precision": "day", "issue": "", "normalized_date": "2026-06-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "BMC bioinformatics", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "PAVSAT: an automated blood vessel analysis tool using deep learning-based segmentation and image processing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Autism spectrum disorder (ASD) is a neurodevelopmental disorder shaped by genetic factors such as copy number variations (CNVs) and immunological factors such as maternal infection. However, most studies on the development of genetic ASD have focused on neurological aspects, and the role of immunity in genetic ASD remains unclear. Here, we demonstrate increased gammadelta T cells in the brains of 15q11-13 duplication (15q dup) mice, which model a common CNV associated with ASD. Elevated CXCL16 in the brains of 15q dup mice promoted gammadelta T cell infiltration, specifically of Vgamma6(+) gammadelta T cells that produce IL-17A. Deletion of Vgamma6(+) gammadelta T cells throughout development or treatment with neutralizing antibodies against Vgamma6 or IL-17A increased social behavior in 15q dup mice. These findings suggest that immune dysregulation contributes to social behavior deficits in 15q dup mice, consistent with observations in maternal immune activation models, and may represent a potential target for interventions for ASD-associated differences in social behavior.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Natsumi", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Koyomi", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Ako", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Yamamuro", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Nitahara", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Makino", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Nesta", "last_name": "Amagiri", "name": null }, { "creator_type": "author", "first_name": "Mahiro", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Ayame", "last_name": "Nagafuchi", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kawazoe", "name": null }, { "creator_type": "author", "first_name": "Minami", "last_name": "Serino", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Takao", "name": null }, { "creator_type": "author", "first_name": "Kakeru", "last_name": "Takenobu", "name": null }, { "creator_type": "author", "first_name": "Yasunobu", "last_name": "Yoshikai", "name": null }, { "creator_type": "author", "first_name": "Kazufumi", "last_name": "Kunimura", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Makinodan", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takumi", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciimmunol.adz8466" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42319913" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autism Spectrum Disorder", "descriptor_ui": "D000067877", "major_topic": true }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "Chemokine CXCL16", "descriptor_ui": "D000075743", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Interleukin-17", "descriptor_ui": "D020381", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell, gamma-delta", "descriptor_ui": "D016692", "major_topic": true }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jun 19", "date_precision": "day", "issue": "120", "normalized_date": "2026-06-19", "pages": "eadz8466", "proceedings_title": null, "publisher": "", "title": "Science immunology", "volume": "11", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "CXCL16-mediated recruitment of gammadelta T cells to the brain reduces sociability in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stress disturbs physiological and psychological homeostasis across species. In mammals, stress reduces male courtship motivation, but the underlying neuronal mechanisms remain poorly understood. Here, we establish a Drosophila model in which confinement to a small space without complete immobilization-termed small-space (SS) stress-suppresses male courtship behavior. Because stress modulates dopamine signaling in both vertebrates and invertebrates, we examined its role in SS-stress-induced courtship suppression. Pharmacological inhibition and genetic manipulations revealed that dopamine synthesis, release, and reception are required to maintain-but not initiate-the SS-stress-induced suppression of male courtship. Furthermore, dopamine release to and reception within the mushroom body-a brain region involved in higher-order sensory processing-were essential for sustaining courtship inhibition after stress. This SS stress paradigm provides a robust framework for elucidating dopamine-mediated mechanisms that support persistent behavioral changes after stress and contribute to a deeper understanding of the neurobiological basis of stress-related sexual dysfunction.", "classifications": [ { "id": "21H00434", "label": "21H00434", "researcher": "Takaomi Sakai", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tomohito", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Rana", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kitamoto", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2026.115906" }, "pmcid": { "normalized": "PMC13196396" }, "pmid": { "normalized": "42181280" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jun 19", "date_precision": "day", "issue": "6", "normalized_date": "2026-06-19", "pages": "115906", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "29", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of dopamine signaling in male courtship suppression induced by confinement stress in Drosophila.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Near-infrared photoimmunotherapy (NIR-PIT) is an innovative cancer treatment modality that was approved in Japan in 2020 for the treatment of unresectable locally advanced or locally recurrent head and neck cancer. This therapy uses an antibody-dye conjugate (Ab-IR700), which consists of a monoclonal antibody targeting a specific cell-surface antigen and a phthalocyanine-based near-infrared dye, IR700, that functions as a photosensitizer. After selective accumulation in tumor tissue, Ab-IR700 is irradiated with 690 nm NIR light, which initiates a photochemical reaction that selectively damages the cell membrane of target cells, thereby inducing immunogenic cell death. Its high tumor selectivity and therapeutic efficacy establish NIR-PIT as a promising next-generation cancer therapy. However, its further application to deep-seated solid tumors remains challenging, and will require IR700 analogs and novel dye scaffolds that can be activated by longer-wavelength light to achieve greater tissue penetration and that offer greater photochemical activation efficiency. This review covers the activation mechanism of IR700, the mechanisms of cytotoxicity of NIR-PIT, emerging applications of NIR-PIT in oncology and infectious diseases, the range of dye delivery vehicles, and the development of new dyes for NIR-PIT.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Fuse", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Orie", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d6cb00132g" }, "pmcid": { "normalized": "PMC13306961" }, "pmid": { "normalized": "42370300" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jun 17", "date_precision": "day", "issue": "", "normalized_date": "2026-06-17", "pages": "", "proceedings_title": null, "publisher": "", "title": "RSC chemical biology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Recent advances in near-infrared dye conjugates for near-infrared photoimmunotherapy (NIR-PIT): enhancing therapeutic efficacy and immune mechanisms.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genomes have maintained relatively stable gene sets during evolution, while chromosome organization and genome size vary drastically, even among vertebrates. Changes in genome size are often attributed to variable amounts of repetitive sequences, including transposable elements. However, it remains poorly understood what allows such drastic changes and how they affect various components of the genome and their functions. Elasmobranchs, including sharks, rays, and skates, exhibit high among-species variation of genome size and high within-species variation of chromosome length, offering a unique study system. In this study, we present the first whole genome sequences of the whitebelly skate with relatively small genome size among elasmobranchs (2.2 Gb) and the red stingray. These chromosome-scale assemblies enable the assessment of genomic compositions including centromeres and non-coding elements, which reveal notable profiles of tRNA loci and unbiased intragenomic distribution of transposons in elasmobranch genomes. Comparative analyses across these species reveal a shared genomic architecture characterized by correlations of intergenic and intronic sequence lengths with chromosome sizes, with repetitive element accumulation in elongated regions. To assess whether elements beyond repetitive elements scale with genome size, we analyze tandem gene duplications and find they also tend to increase with genome expansion. In the quest of tandem genes, we characterize the first batoid HoxC cluster supported by transcriptional evidence in the red stingray genome, which has undergone extensive repetitive element invasion to unexpectedly co-localize with the HoxB cluster on a sex chromosome. Our study demonstrates an inclusive analysis encompassing both coding and non-coding regions, adaptable to diverse vertebrate taxa and a basis for molecular-level understanding on phenotypic diversity of elasmobranchs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Kuraku", "name": null }, { "creator_type": "author", "first_name": "Yawako W.", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Misawa", "name": null }, { "creator_type": "author", "first_name": "Yohey", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Mitsutaka", "last_name": "Kadota", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Waichiro", "last_name": "Godo", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Isobe", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Shirasawa", "name": null }, { "creator_type": "author", "first_name": "Akane", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/gr.281149.125" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42303448" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DNA Transposable Elements", "descriptor_ui": "D004251", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": true }, { "descriptor": "Genome Size", "descriptor_ui": "D059646", "major_topic": true }, { "descriptor": "Repetitive Sequences, Nucleic Acid", "descriptor_ui": "D012091", "major_topic": false }, { "descriptor": "Sharks", "descriptor_ui": "D012754", "major_topic": true }, { "descriptor": "Skates, Fish", "descriptor_ui": "D012860", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jun 16", "date_precision": "day", "issue": "", "normalized_date": "2026-06-16", "pages": "gr.281149.125", "proceedings_title": null, "publisher": "", "title": "Genome research", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Tracing genome size dynamics in sharks and rays with inclusive sequence analysis by the Squalomix Consortium.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During morphogenesis, cell divisions are precisely regulated in space and time. The biological objectives achieved by such regulation are not fully understood. Here, by applying a newly developed lineage-reconstruction pipeline to Drosophila pupal wing, we reveal that the wing is composed of distinct cell groups that differ in division number, timing, and spatial positioning relative to wing veins. We show that the frequencies of these lineages, together with their initial cell sizes and growth profiles, converge to achieve a highly conserved average cell size. Our data further suggest that distance from veins provides spatial information that biases where distinct lineages arise, and that loss of veins caused by perturbation of EGFR signaling suppresses a specific lineage and disrupts cell-size control. Finally, our results point to a multiscale organization of division patterns, in which vein-associated spatial information is integrated with local neighbor effects in a manner that would mitigate mechanical instability within the tissue. Together, these findings delineate a cell-size control mechanism based on coordinated divisions of distinct cell groups that supports robust morphogenesis and functional tissue design.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kaoru", "last_name": "Sugimura", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Takayanagi", "name": null }, { "creator_type": "author", "first_name": "Toshinori", "last_name": "Namba", "name": null }, { "creator_type": "author", "first_name": "Zeping", "last_name": "Qu", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.205474" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42374939" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": true }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cell Size", "descriptor_ui": "D048429", "major_topic": true }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": true }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": true }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Veins", "descriptor_ui": "D014680", "major_topic": true }, { "descriptor": "Wings, Animal", "descriptor_ui": "D014921", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jun 15", "date_precision": "day", "issue": "12", "normalized_date": "2026-06-15", "pages": "dev205474", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "153", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell size control emerges from the vein-dependent coordinated divisions of distinct cell groups in Drosophila wing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Sean L.", "last_name": "Meharry", "name": null }, { "creator_type": "author", "first_name": "Antoine", "last_name": "Borensztejn", "name": null }, { "creator_type": "author", "first_name": "Nathalie", "last_name": "Gaudreault", "name": null }, { "creator_type": "author", "first_name": "Jordan", "last_name": "Lucas", "name": null }, { "creator_type": "author", "first_name": "Gabe", "last_name": "Medrash", "name": null }, { "creator_type": "author", "first_name": "Lisa", "last_name": "Schaefbauer", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Toloudis", "name": null }, { "creator_type": "author", "first_name": "Anya", "last_name": "Wallace", "name": null }, { "creator_type": "author", "first_name": "Brian", "last_name": "Whitney", "name": null }, { "creator_type": "author", "first_name": "Lyndsay", "last_name": "Wilhelm", "name": null }, { "creator_type": "author", "first_name": "Yoav", "last_name": "Ben-Simon", "name": null }, { "creator_type": "author", "first_name": "Jean-Marie", "last_name": "Burel", "name": null }, { "creator_type": "author", "first_name": "Jianxu", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Kevin W.", "last_name": "Eliceiri", "name": null }, { "creator_type": "author", "first_name": "Anika", "last_name": "Gruneboom", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Josh", "last_name": "Moore", "name": null }, { "creator_type": "author", "first_name": "William", "last_name": "Moore", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Davide", "last_name": "Panzeri", "name": null }, { "creator_type": "author", "first_name": "Curtis T.", "last_name": "Rueden", "name": null }, { "creator_type": "author", "first_name": "Bosiljka", "last_name": "Tasic", "name": null }, { "creator_type": "author", "first_name": "Graham T.", "last_name": "Johnson", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41592-026-03130-w" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42298069" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jun 15", "date_precision": "day", "issue": "", "normalized_date": "2026-06-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature methods", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Search, organize, aggregate and share image data with BioFile Finder (BFF).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chimeric antigen receptor (CAR) T cell therapy faces many challenges against solid tumors including T cell exhaustion and poor CAR durability. Here, we show that engaging the CAR T cell endogenous T cell receptor (TCR) using an oncolytic virus enhances CAR T cell functionality, durability, and therapy. Upon combination therapy of solid tumors with CAR T cells and vesicular stomatitis virus (VSV), a subpopulation of antiviral, TCR-primed CAR T cells was generated with enhanced effector functions, altered activation states, and differential gene and protein expression when compared to non-TCR-primed CAR T cells. Single-cell RNA sequencing showed clonal expansion of anti-VSV CAR T cells and enhancement of effector-associated genes with VSV-mediated CAR T cell expansion. CD4 T cells played a pivotal role in the development of these TCR-primed CAR T cells. These results provide a strong rationale both for a novel use of systemic oncolytic virotherapy and for directly exploiting the CAR T cell TCR to fine tune the CAR T cell phenotype and function.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Olivia", "last_name": "Liseth", "name": null }, { "creator_type": "author", "first_name": "Elizabeth", "last_name": "Appleton", "name": null }, { "creator_type": "author", "first_name": "Benjamin", "last_name": "Kendall", "name": null }, { "creator_type": "author", "first_name": "Jill", "last_name": "Thompson", "name": null }, { "creator_type": "author", "first_name": "Thanich", "last_name": "Sangsuwannukul", "name": null }, { "creator_type": "author", "first_name": "Jason", "last_name": "Tonne", "name": null }, { "creator_type": "author", "first_name": "Rosa Maria", "last_name": "Diaz", "name": null }, { "creator_type": "author", "first_name": "Laura", "last_name": "Evgin", "name": null }, { "creator_type": "author", "first_name": "Anton", "last_name": "Patrikeev", "name": null }, { "creator_type": "author", "first_name": "Nicolas", "last_name": "Sarbia", "name": null }, { "creator_type": "author", "first_name": "Shane", "last_name": "Foo", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Harrington", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Alan", "last_name": "Melcher", "name": null }, { "creator_type": "author", "first_name": "Richard", "last_name": "Vile", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.aef5331" }, "pmcid": { "normalized": "PMC13240226" }, "pmid": { "normalized": "42247513" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunotherapy, Adoptive", "descriptor_ui": "D016219", "major_topic": true }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Oncolytic Virotherapy", "descriptor_ui": "D050130", "major_topic": false }, { "descriptor": "Oncolytic Viruses", "descriptor_ui": "D050504", "major_topic": true }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": true }, { "descriptor": "Receptors, Chimeric Antigen", "descriptor_ui": "D000076962", "major_topic": true }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jun 5", "date_precision": "day", "issue": "23", "normalized_date": "2026-06-05", "pages": "eaef5331", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "12", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Engagement of the TCR against an oncolytic virus generates a population of effector CAR T cells with potent antitumor activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Blood-brain barrier (BBB) disruption significantly exacerbates secondary injury following ischemic stroke. Although lysophosphatidic acid (LPA) is known to regulate vascular stability, its specific role in preserving BBB integrity during cerebral ischemia remains unclear. Here, we investigated the neuroprotective effects of LPA using a mouse model of distal middle cerebral artery occlusion (dMCAO). Eight- to ten-week-old female C57BL/6 mice received 10 mg/kg LPA intraperitoneally immediately after ischemia, and outcomes were assessed at 48 h after dMCAO via infarct volumetry, edema quantification, BBB permeability assays (Evans blue and FITC-dextran), and transcriptomic analyses. We demonstrate that LPA treatment significantly reduced infarct volume by approximately 60% and attenuated cerebral edema at 48 h post-ischemia; This protection was accompanied by preserved BBB integrity and maintained endothelial claudin-5 expression in the ischemic territory. Single-cell analysis identified selective and sustained expression of the LPA4 receptor in ischemic vascular endothelial cells. Crucially, the protective effects of LPA on infarct size and BBB permeability were abolished in LPA4 receptor-knockout mice. These findings indicate that LPA preserves BBB integrity and mitigates ischemic brain injury via an endothelial LPA4 receptor-dependent mechanism, identifying the LPA-LPA4 signaling axis as a promising therapeutic target for reducing secondary brain injury in ischemic stroke.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shintaro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takara", "name": null }, { "creator_type": "author", "first_name": "Naoi", "last_name": "Hosoe", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Lamri", "last_name": "Lynda", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Sonoda", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Kikuta", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12975-026-01451-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42228231" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood-Brain Barrier", "descriptor_ui": "D001812", "major_topic": false }, { "descriptor": "Brain Ischemia", "descriptor_ui": "D002545", "major_topic": true }, { "descriptor": "Capillary Permeability", "descriptor_ui": "D002199", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Infarction, Middle Cerebral Artery", "descriptor_ui": "D020244", "major_topic": false }, { "descriptor": "Lysophospholipids", "descriptor_ui": "D008246", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neuroprotective Agents", "descriptor_ui": "D018696", "major_topic": true }, { "descriptor": "Receptors, Lysophosphatidic Acid", "descriptor_ui": "D049368", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jun 2", "date_precision": "day", "issue": "3", "normalized_date": "2026-06-02", "pages": "61", "proceedings_title": null, "publisher": "", "title": "Translational stroke research", "volume": "17", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Lysophosphatidic Acid Reduces Ischemic Brain Injury by Attenuating Vascular Permeability Through LPA4 Receptor Signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although radiochromic films are widely used for two-dimensional radiation measurements, the radiation-induced polymerization that produces their radiochromic response remains incompletely characterized. In this study, we investigated the radiation-induced chemical and structural changes in the active layer of a currently available radiochromic film (Gafchromic(TM)EBT4) using Raman spectroscopy in relation to dose-dependent radiochromic reactions. By examining the Raman shift spectra across an absorbed dose range of up to 20 Gy, the analysis revealed consistent and systematic modifications in the vibrational bands associated with the polymeric active layer. After normalization using the 1530 cm(-1)peak that was specifically observed in EBT4, a key Raman peak around 1455 cm(-1)was identified as a highly sensitive marker of dose response, showing distinct, monotonic intensity increases with increasing radiation dose. The clear separation between dose levels confirms that this principal vibrational feature directly reflects the underlying diacetylene polymerization and radical formation mechanisms triggered by ionizing radiation. The dose-response behavior was well described by a simple increasing curve that showed a shape similar to that of the green color intensity. These new findings, including the successful normalization based on the 1530 cm(-1)reference peak, provide an important basis for elucidating the molecular-level mechanisms underlying the radiochromic reactions in EBT-series films.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hassna", "last_name": "Bantan", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Samayeh", "last_name": "Azariasl", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yasuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1088/2057-1976/ae711b" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42167279" } }, "mesh": [ { "descriptor": "Dose-Response Relationship, Radiation", "descriptor_ui": "D004307", "major_topic": false }, { "descriptor": "Film Dosimetry", "descriptor_ui": "D005373", "major_topic": true }, { "descriptor": "Polymerization", "descriptor_ui": "D058105", "major_topic": false }, { "descriptor": "Radiation Dosage", "descriptor_ui": "D011829", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jun 1", "date_precision": "day", "issue": "3", "normalized_date": "2026-06-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biomedical physics & engineering express", "volume": "12", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Investigation of post-irradiation molecular changes in LiPCDA-based radiochromic film (Gafchromic EBT4) using Raman spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that promotes tear secretion from the lacrimal gland. PACAP is known to be involved in corneal injury repair, but as the mechanism underlying its effects remains unclear, we used a mouse corneal wound-injury model and cultured human corneal epithelial cells to investigate further. PAC1 receptor (PAC1-R) mRNA and associated immunoreactivity were detected in the mouse corneal epithelium. In corneal wound-injury model mice, PACAP eye drops significantly reduced the injured area 12 h after the wound insult compared to control, and this effect was abolished by co-treatment with a PACAP receptor antagonist. Corneal healing was delayed in the heterozygous PACAP knockout and PAC1-R knockout mice. Despite attenuation of corneal healing following the surgical removal of the lacrimal gland in wild-type (WT) mice, PACAP eye drops significantly improved corneal repair. In vitro, PACAP treatment significantly reduced the injury area in cultured human corneal epithelial cells, and this effect was abolished by Ara-C, a cell proliferation inhibitor. Results of DNA whole-genome microarray analysis suggested that the nuclear receptor NR4A1 is crucial for corneal epithelial proliferation. THPN, which induces the nuclear export of NR4A1, suppressed the PACAP-induced proliferation of human corneal epithelial cells and inhibited corneal repair in mice. These data suggest that PACAP stimulates corneal repair by promoting corneal epithelial proliferation via PAC1-R and NR4A1 transcriptional activity. These findings suggest that PACAP could be a promising candidate for eye-drop medication to treat corneal injuries, including dry eye syndrome.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Michio", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Nakamachi", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Shibato", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Dora", "last_name": "Reglodi", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Takasaki", "name": null }, { "creator_type": "author", "first_name": "Randeep", "last_name": "Rakwal", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Shioda", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Takenoya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-026-54554-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42204250" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Corneal Injuries", "descriptor_ui": "D065306", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": true }, { "descriptor": "Epithelium, Corneal", "descriptor_ui": "D019573", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": true }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I", "descriptor_ui": "D051237", "major_topic": false }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Wound Healing", "descriptor_ui": "D014945", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 May 27", "date_precision": "day", "issue": "", "normalized_date": "2026-05-27", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Pituitary adenylate cyclase-activating polypeptide (PACAP) promotes regeneration of corneal epithelial cells possibly via the NR4A1 signaling pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Torpor is a state of hypometabolism accompanied by a reduction in body temperature, which serves as a survival strategy enabling animals to endure harsh environments. While the circadian clock is thought to regulate the timing of torpor, the underlying neural mechanisms remain unclear. Here, we show that inhibitory neurotransmission via gamma-aminobutyric acid (GABA) in the central circadian clock, suprachiasmatic nucleus (SCN), is crucial for encoding the timing of torpor induction in female mice. Optogenetic activation of GABAergic neurons in the SCN projecting to the preoptic area (POA) suppresses torpor. These SCN neurons form monosynaptic connections with two distinct types of POA neurons: excitatory neurons that promote torpor induction, and inhibitory neurons that suppress the activity of these excitatory neurons. Furthermore, the disconnection of neural output in the SCN abolishes the timing of torpor. Retrograde tracing revealed that arginine vasopressin (Avp) neurons in the SCN innervate the POA, and selective deletion of vesicular GABA transporter in Avp neurons of the SCN leads to impaired torpor induction. This hypothalamic neuronal circuit is crucial in ensuring the survival of animals during harsh environmental conditions.", "classifications": [ { "id": "21H00422", "label": "21H00422", "researcher": "Daisuke Ono", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sheikh Mizanur", "last_name": "Rahaman", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Chang-Ting", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Chi Jung", "last_name": "Hung", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Mieda", "name": null }, { "creator_type": "author", "first_name": "Takahiro J.", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-026-73374-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42173901" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arginine Vasopressin", "descriptor_ui": "D001127", "major_topic": false }, { "descriptor": "Circadian Clocks", "descriptor_ui": "D057906", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "GABAergic Neurons", "descriptor_ui": "D059330", "major_topic": true }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Preoptic Area", "descriptor_ui": "D011301", "major_topic": true }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": true }, { "descriptor": "Torpor", "descriptor_ui": "D064348", "major_topic": true }, { "descriptor": "Vesicular Inhibitory Amino Acid Transport Proteins", "descriptor_ui": "D050495", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 May 22", "date_precision": "day", "issue": "", "normalized_date": "2026-05-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "GABAergic projections from the suprachiasmatic nucleus to the preoptic area regulate the timing of torpor in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Encapsulation of single cells within uniform hydrogel microcapsules enables controlled three-dimensional culture and quantitative analysis of cell behavior; however, most existing approaches rely on microfluidic devices or complex encapsulation processes that limit accessibility. Here, we introduce emulsion-templated gel embedding (ETE), a microfluidics-free method that embeds cells within uniform gelatin beads using prefabricated bead templates to predefine capsule size prior to encapsulation. In ETE, cells and monodisperse gelatin beads are co-encapsulated within water-in-oil droplets generated by particle-templated emulsification (PTE), followed by thermal dissolution and re-gelation of the gelatin to form cell-laden beads of defined size. The resulting cell-laden gelatin beads can subsequently serve as templates for agarose shell formation, yielding hollow-core agarose microcapsules after gelatin dissolution. Cells encapsulated within microcapsules via ETE exhibit proliferation comparable to microfluidic-derived capsules, indicating that simplified processing does not compromise biological performance. By defining capsule size through prefabricated gelatin templates rather than relying on microfluidic flow control during encapsulation, ETE provides a practical and reproducible strategy for generating uniform hydrogel microcapsules for cell culture and biomedical applications.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Natsuko", "last_name": "Otaki", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Goda", "name": null }, { "creator_type": "author", "first_name": "Pooja", "last_name": "Shukla", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Kirisako", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsbiomaterials.5c02129" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42166640" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Capsules", "descriptor_ui": "D002214", "major_topic": false }, { "descriptor": "Cell Encapsulation", "descriptor_ui": "D000079585", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Emulsions", "descriptor_ui": "D004655", "major_topic": false }, { "descriptor": "Gelatin", "descriptor_ui": "D005780", "major_topic": false }, { "descriptor": "Hydrogels", "descriptor_ui": "D020100", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microfluidics", "descriptor_ui": "D044085", "major_topic": false }, { "descriptor": "Sepharose", "descriptor_ui": "D012685", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 May 21", "date_precision": "day", "issue": "", "normalized_date": "2026-05-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "ACS biomaterials science & engineering", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Emulsion-Templated Gel Embedding: A Microfluidics-Free Method for Scalable Cell Encapsulation in Hydrogel Microcapsules.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In living cells, the control of molecular diffusion is pivotal for highly fluidic membranes to serve as substrates for biochemical reactions and cytoskeletal assemblies. Lateral diffusion in membranes depends on a highly diverse and homeostatically controlled lipid composition. This complexity has limited our understanding of how diffusivity in biological membranes is regulated. In this study, we show that lipid diffusion in model membranes decreases markedly in the presence of cytosolic extracts. The reduction in lipid diffusivity can be pharmacologically inhibited by targeting phospholipase D (PLD). Conversely, lipid diffusivity was reduced when PLD alone was added to the membrane. Phosphatidic acid (PA), a direct product of PLD, diffuses slowly, and its presence reduces the diffusivity of surrounding lipids. Furthermore, we found that PLD controls the lateral diffusion of a myristoylated protein PKBR1 in Dictyostelium cells, possibly through auxiliary electrostatic interactions between cationic residues located near the lipidated tail and anionic phospholipids. In line with the role of PKBR1 in regulating phosphatidylinositol(3,4,5)-trisphosphates (PIP3), PLD overexpression suppressed the size and lifetime of PIP3 microdomains as well as the sensitivity of GPCR-mediated PIP3 elevation. Our results underscore the importance of PLD and its product PA as regulators of lipidated protein diffusivity, facilitating the dynamical lateral organization of phosphoinositides in the plasma membrane.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Gen", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Chihuku", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Hashimura", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Mina", "last_name": "Fujishiro", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Yanagisawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2608790123" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42127117" } }, "mesh": [ { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": true }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": true }, { "descriptor": "Diffusion", "descriptor_ui": "D004058", "major_topic": false }, { "descriptor": "Phosphatidic Acids", "descriptor_ui": "D010712", "major_topic": false }, { "descriptor": "Phospholipase D", "descriptor_ui": "D010739", "major_topic": true }, { "descriptor": "Protozoan Proteins", "descriptor_ui": "D015800", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 May 19", "date_precision": "day", "issue": "20", "normalized_date": "2026-05-19", "pages": "e2608790123", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "123", "year": 2026 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000365" ] }, "title": "Phospholipase D regulates on-membrane diffusivity of a myristoylated protein and defines the PIP3 patch territory.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Although yogurt consumption has been associated with favorable metabolic outcomes, its effect on continuous glucose dynamics and gut microbiota composition remains unclear. OBJECTIVES: This study aims to evaluate the effects of daily yogurt intake on glucose dynamics and gut microbiota composition in healthy adults, and to examine baseline host factors associated with interindividual variability in glycemic response. METHODS: This single-arm, 84-d intervention study involved 303 Japanese adults without a prior diabetes diagnosis consuming 200 g of plain yogurt daily at breakfast. Continuous glucose monitoring (CGM) was used to assess mean glucose levels, standard deviation (SD, and an autocorrelation-based index (AC_Var). Fecal samples were collected at baseline and postintervention for 16S rRNA gene sequencing. Associations between baseline clinical, microbial, and genetic characteristics and changes in the CGM-derived measures were evaluated. Differential abundance analysis was used to identify microbial taxa altered by the intervention. RESULTS: Mean glucose levels decreased progressively, with a reduction of 4.06 mg/dL [95% confidence interval (CI): 2.97 mg/dL, 5.14 mg/dL] by the final period. Significant decreases were also observed in SD (-0.86 mg/dL; 95% CI: -1.32 mg/dL, -0.41 mg/dL) and AC_Var (-0.0059; 95% CI: -0.010, -0.0017). Several baseline gut bacterial genera, including Gemmiger, Veillonella, Alistipes, and Butyricicoccus, were significantly associated with changes in the CGM-derived measures. After the intervention, increases were observed in the genera Blautia, Faecalibacterium, and Coprococcus, as well as in the phylum Firmicutes, whereas decreases were noted in Prevotella, Oscillospira, and the phylum Bacteroidetes. CONCLUSIONS: Daily yogurt consumption was associated with improvements in glucose dynamics and significant remodeling of the gut microbiota. Baseline microbiota profiles were linked to interindividual differences in glycemic response. These findings suggest the potential role of the gut microbiome in modulating the metabolic effects of yogurt and underscore the value of personalized dietary strategies.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hikaru", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Chida", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Toshimitsu", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Fujino", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.tjnut.2026.101572" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42162795" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Blood Glucose", "descriptor_ui": "D001786", "major_topic": true }, { "descriptor": "Continuous Glucose Monitoring", "descriptor_ui": "D000095583", "major_topic": false }, { "descriptor": "Feces", "descriptor_ui": "D005243", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gastrointestinal Microbiome", "descriptor_ui": "D000069196", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "RNA, Ribosomal, 16S", "descriptor_ui": "D012336", "major_topic": false }, { "descriptor": "Yogurt", "descriptor_ui": "D015014", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 May 19", "date_precision": "day", "issue": "", "normalized_date": "2026-05-19", "pages": "101572", "proceedings_title": null, "publisher": "", "title": "The Journal of nutrition", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Associations between Yogurt Consumption, Gut Microbiota Composition, and Glucose Dynamics: A Single-Arm 84-Day Intervention Study Using Continuous Glucose Monitoring.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Patients and their families without medical knowledge may find professional health care information difficult to understand. The use of large language models (LLMs) to simplify and translate complex medical content holds promise for improving comprehension while reducing the burden on health care providers tasked with delivering explanations. OBJECTIVE: This study aims to evaluate the quality of information leaflets generated using commercially available LLMs. METHODS: Informational texts on post-intensive care syndrome were generated using 6 different LLMs and 4 prompt designs with varying levels of instructional guidance. Clinical practice guideline documents were uploaded and provided to the models as reference context, reflecting a pragmatic clinical scenario without model tuning or advanced retrieval pipelines. In total, 72 texts were generated (6 models x 4 prompts x 3 outputs). After excluding texts shorter than 500 characters (n=16) and those without explicit mention of post-intensive care syndrome (n=3), 53 texts remained. To enable balanced human evaluation across model-prompt combinations, the longest eligible response from each pair was selected (4 prompts x 4 models; n=16). Following independent expert review by 2 medical specialists, 7 texts were excluded, leaving 9 texts for final analysis. Ten individuals, including health care professionals and nonmedical personnel, assessed the texts using a 10-point Likert scale across multiple quality domains. An LLM-based parallel assessment was also conducted, and scores were compared across models and evaluator groups. RESULTS: In the human evaluation of the selected 9 texts, the generated texts achieved an average score of 6.8 or higher across all evaluation criteria, with no potentially harmful content identified. The text generated by LLaMA 3 70B, using a step-by-step approach combined with text-augmented prompting based on clinical guidelines, received the highest overall score, whereas the lowest-rated text was produced using a simple prompt without text augmentation. Although no consistent trends were observed across LLMs or prompt engineering strategies, text-augmented prompting was generally associated with higher evaluation scores. Ratings differed between professional and nonprofessional evaluators. Given the feasibility-driven screening process and the resulting limited sample size, the findings should be interpreted as exploratory and descriptive rather than definitive estimates of overall model performance. CONCLUSIONS: Among the selected texts included in the final human evaluation, informational materials generated using commercially available LLMs were generally rated as acceptable by human evaluators, and none contained harmful content. These findings suggest that LLMs may support the development of patient-facing informational materials under feasibility-constrained conditions, although further validation with larger and more diverse samples is warranted.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Nanami", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Oami", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Hanai", "name": null }, { "creator_type": "author", "first_name": "Taka-Aki", "last_name": "Nakada", "name": null } ], "identifiers": { "doi": { "normalized": "10.2196/81606" }, "pmcid": { "normalized": "PMC13175452" }, "pmid": { "normalized": "42133866" } }, "mesh": [ { "descriptor": "Critical Illness", "descriptor_ui": "D016638", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Large Language Models", "descriptor_ui": "D000098342", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 May 14", "date_precision": "day", "issue": "", "normalized_date": "2026-05-14", "pages": "e81606", "proceedings_title": null, "publisher": "", "title": "JMIR formative research", "volume": "10", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Use of Commercially Available Large Language Models to Generate Information Leaflets on Post-Intensive Care Syndrome: Clinical Utility Assessment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Muzi", "last_name": "Ge", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Jingdi", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Maryam Chaib", "last_name": "De Mares", "name": null }, { "creator_type": "author", "first_name": "Emmanuel George", "last_name": "Kifaro", "name": null }, { "creator_type": "author", "first_name": "Gizachew Haile", "last_name": "Gidamo", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null }, { "creator_type": "author", "first_name": "Andrew H.", "last_name": "Moeller", "name": null }, { "creator_type": "author", "first_name": "Zhibin", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Jianshi", "last_name": "Jin", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/ismejo/wrag122" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42127415" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 May 13", "date_precision": "day", "issue": "", "normalized_date": "2026-05-13", "pages": "wrag122", "proceedings_title": null, "publisher": "", "title": "The ISME journal", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Standardized and batch effect-independent technologies enable global collaboration in microbiome research.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: A growing body of evidence suggests that male infertility is a precursor to future health problems. This study aimed to develop a unique circulating biomarker that could contribute to the diagnosis of male infertility. MATERIALS AND METHODS: The study included 114 adult male participants aged 20-50 years who underwent sperm collection for in vitro fertilization and embryo transfer at Nagoya University Hospital, Gifu University Hospital, and Misao Ladies Hospital. RESULTS: Circulating VEGF-A and sFlt-1 levels did not differ significantly between men with normal and abnormal semen parameters. In contrast, proteomic analysis identified VEGFR1/2-related proteins associated with sperm motility, among which soluble MCAM/CD146 was significantly elevated in participants with abnormal semen parameters (84.0 [20.9-183.8] pg/mL vs 352.7 [115.8-1236.3] pg/mL, p<0.0001), and in similar those with reduced sperm motility (106.5 [25.1-282.6] pg/mL vs 352.7 [125.5-1133.4] pg/mL, p<0.0001). Receiver operating characteristic analysis demonstrated the diagnostic potential of soluble MCAM/CD146, with an area under the curve of 0.787, 66.7% sensitivity, and 78.6% specificity at the optimal threshold, supporting its role as a candidate biomarker for male infertility. CONCLUSIONS: Circulating soluble MCAM/CD146 may represent a potential biomarker associated with abnormal semen parameters.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakatochi", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Sei", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Furusawa", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Mishiro-Sato", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Katagiri", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Kyohei", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Furui", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kajiyama", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Okura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1177/00045632261454320" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42120337" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 May 12", "date_precision": "day", "issue": "", "normalized_date": "2026-05-12", "pages": "45632261454320", "proceedings_title": null, "publisher": "", "title": "Annals of clinical biochemistry", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Proteomic profiling identifies circulating soluble MCAM/CD146 as a candidate biomarker for abnormal semen parameters in male infertility.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Though whole-genome duplication (WGD) contributes to cancer progression, the mechanism of post-WGD cell proliferation remains unclear. Here, using 6-day live-imaging, we analyzed the proliferation dynamics of more than 150 post-WGD HCT116 cell lineages. A quantitative comparison of mitotic patterns and cell fates between proliferative and non-proliferative lineages revealed that multipolar chromosome segregation in early mitosis is a potential key factor limiting the proliferative capacity of post-WGD progenies. Multipolar chromosome segregation correlated with suppressed post-WGD cell viability, particularly when accompanied by drastic chromosome loss or when it repeatedly occurred. Tracing proliferative lineages elucidated that they proliferated mainly by imposing the risk of multipolar chromosome segregation on one of two sub-lineages that formed after the first bipolar division. Meanwhile, a considerable proportion of proliferative lineages consisted entirely of progeny of early multipolar chromosome segregation events. Our results highlight key cellular events that determine the proliferation dynamics and diversity of post-WGD progenies, providing a fundamental reference for understanding WGD-associated biological processes.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Guang", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Inoko", "name": null }, { "creator_type": "author", "first_name": "Kaito", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Sumire", "last_name": "Ishida-Ishihara", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Funahashi", "name": null }, { "creator_type": "author", "first_name": "Masanao", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/bio.062568" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42108858" } }, "mesh": [ { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": true }, { "descriptor": "Chromosome Segregation", "descriptor_ui": "D020090", "major_topic": false }, { "descriptor": "Gene Duplication", "descriptor_ui": "D020440", "major_topic": true }, { "descriptor": "Genome, Human", "descriptor_ui": "D015894", "major_topic": true }, { "descriptor": "HCT116 Cells", "descriptor_ui": "D045325", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 May 11", "date_precision": "day", "issue": "", "normalized_date": "2026-05-11", "pages": "bio.062568", "proceedings_title": null, "publisher": "", "title": "Biology open", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000503" ] }, "title": "Profiling cell proliferation after whole-genome duplication in human cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Left-right (L-R) symmetry is a fundamental feature of bilaterian body plans, yet how it is actively maintained and corrected during development remains poorly understood. In the ascidian Ciona, embryos transiently exhibit clockwise tail twisting that is progressively reduced but stabilizes at a residual angle of approximately 10 degrees . Inhibition of retinoic acid signaling or neuromuscular activity eliminated this residual twist, restoring full bilateral symmetry. Myofibrils in both left and right muscles adopted the same left-handed helical orientation, and mechanical modeling showed that this architecture generates net torque sufficient to stabilize residual twisting against full symmetry restoration. These findings reveal how bilaterian embryos balance symmetry restoration with morphogenetic asymmetry.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki S.", "last_name": "Kogure", "name": null }, { "creator_type": "author", "first_name": "Misaki K.", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/1873-3468.70358" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42108758" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 May 10", "date_precision": "day", "issue": "", "normalized_date": "2026-05-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "FEBS letters", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Residual tail twisting in ascidian larvae is stabilized by asymmetric myofibrils that resist bilateral symmetry restoration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Collective cell migration is essential in various physiological processes, including embryonic development, wound healing, and cancer metastasis. However, the mechanisms by which individual cells achieve coordinated movement remain elusive. Here, we demonstrate that zonula occludens-1 (ZO-1), a scaffolding protein of tight junctions (TJs), dynamically translocates to form cell-extracellular matrix (ECM) adhesion complexes, podosomes, at the basal cell surface during migration. Extracellular signal-regulated kinase (ERK) activation triggers the translocation of ZO-1 to podosomes, where ZO-1 promotes invasive migration. ZO-1 also contributes to ERK activation dynamics within the cell collective, thereby influencing collective migratory behavior. In this work, we elucidate the dual roles of ZO-1 in coordinating intercellular signaling and invasive movement, providing insights into the mechanisms that integrate individual cell behaviors into a cohesive collective migration.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Sayuki", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Asayuki", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Tetsuhisa", "last_name": "Otani", "name": null }, { "creator_type": "author", "first_name": "Mikio", "last_name": "Furuse", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-026-72840-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42106316" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Podosomes", "descriptor_ui": "D000069261", "major_topic": true }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Tight Junctions", "descriptor_ui": "D019108", "major_topic": true }, { "descriptor": "Zonula Occludens-1 Protein", "descriptor_ui": "D062826", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 May 9", "date_precision": "day", "issue": "", "normalized_date": "2026-05-09", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000499" ] }, "title": "ZO-1 shuttles between apical junctional complexes and podosomes by riding ERK activation waves.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The phase III APPLE trial evaluated the efficacy of adding bevacizumab to atezolizumab with carboplatin plus pemetrexed (APP) for individuals with advanced nonsquamous non-small cell lung cancer (NSCLC). We here report the long-term outcomes of this trial with 3.5 years of follow-up. METHODS: Patients with advanced nonsquamous NSCLC were randomized 1:1 to receive APP or APP plus bevacizumab (APPB). Stratification factors were clinical stage, driver oncogenes, and PD-L1 expression. Endpoints included progression-free survival, overall survival (OS), and safety. RESULTS: A total of 412 patients were enrolled; 1 patient was excluded from the intention-to-treat population. Of the remaining patients, 287 patients were classified as driver oncogene-negative and 124 as driver oncogene-positive. The updated median OS was 28.0 months in the APPB arm and 25.7 months in the APP arm, with a hazard ratio (HR) of 0.88 (95% confidence interval [CI], 0.70-1.10). For the driver oncogene-negative population, the median OS was 27.6 months in the APPB arm and 27.8 months in the APP arm (HR of 0.96 [95% CI, 0.73-1.27]), with the corresponding values for the driver oncogene-positive population being 28.0 and 20.8 months (HR of 0.71 [95% CI, 0.47-1.08]). Safety profiles did not change from earlier analysis. CONCLUSIONS: The addition of bevacizumab to APP did not improve OS in patients with advanced nonsquamous NSCLC. In the driver oncogene-positive subgroup, favorable OS trend was observed in the bevacizumab arm, highlighting its potential as a treatment option for individuals who have failed molecular-targeted therapy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshimasa", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Junji", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Daga", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Hataji", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Takehito", "last_name": "Shukuya", "name": null }, { "creator_type": "author", "first_name": "Haruhiro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Motoko", "last_name": "Tachihara", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Tsuya", "name": null }, { "creator_type": "author", "first_name": "Kazushige", "last_name": "Wakuda", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Yanagitani", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Morihito", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kozuki", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yuriko", "last_name": "Takahata", "name": null }, { "creator_type": "author", "first_name": "Tadaaki", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Isamu", "last_name": "Okamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.lungcan.2026.109447" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42127535" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal, Humanized", "descriptor_ui": "D061067", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": true }, { "descriptor": "Bevacizumab", "descriptor_ui": "D000068258", "major_topic": false }, { "descriptor": "Carboplatin", "descriptor_ui": "D016190", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Pemetrexed", "descriptor_ui": "D000068437", "major_topic": false }, { "descriptor": "Survival Analysis", "descriptor_ui": "D016019", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 May 8", "date_precision": "day", "issue": "", "normalized_date": "2026-05-08", "pages": "109447", "proceedings_title": null, "publisher": "", "title": "Lung cancer (Amsterdam, Netherlands)", "volume": "217", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Final overall survival analysis of the APPLE study: atezolizumab and platinum-pemetrexed with or without bevacizumab for metastatic nonsquamous non-small cell lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sleep is a fundamental physiological state that is widely conserved across diverse animal species. Caenorhabditis elegans exhibits developmentally timed sleep (DTS) and stress-induced sleep (SIS), which meet the behavioral definition of sleep and are regulated by molecular mechanisms shared with other animals. Here, we studied the sleep-regulating functions of UNC-80, which forms a complex with NCA-1 and NCA-2 (hereafter collectively referred to as NCA), and UNC-79. We found that the unc-80 loss-of-function (lf) mutants experienced lower quiescence and a more fragmented and longer DTS than the wild type. The unc-80(lf) mutants also showed lower quiescence during SIS immediately after heat stress, and fragmented SIS. After that, however, quiescence remained higher for a longer time, resulting in a higher total quiescence than observed in the wild type. Similar sleep defects were observed in nca(lf) and unc-79(lf) mutants, indicating that these genes have common functions in sleep regulation. Deprivation of SIS immediately after heat stress in the wild type resulted in a sleep pattern similar to that of the unc-80(lf) mutants, suggesting that sleep immediately after stress might be essential and thus is under strong homeostatic regulation and that the prolonged DTS and SIS of the unc-80(lf) mutants might be rebound sleep. Our findings elucidated that NCA, UNC-79, and UNC-80 are necessary for stabilizing sleep and suggest the importance of the early period of sleep.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kamijo", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/g3journal/jkag112" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42084332" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": true }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": true }, { "descriptor": "Heat-Shock Response", "descriptor_ui": "D018869", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": true }, { "descriptor": "Sleep Duration", "descriptor_ui": "D000094362", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 May 5", "date_precision": "day", "issue": "", "normalized_date": "2026-05-05", "pages": "jkag112", "proceedings_title": null, "publisher": "", "title": "G3 (Bethesda, Md.)", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "The NALCN channel complex is necessary for stabilizing sleep in Caenorhabditis elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The demand for recombinant proteins is rising and various systems for protein production have been developed, including cultured cells, yeast, and bacteria. This study explores the use of Daphnia, a small crustacean, as a host for recombinant protein production. Daphnia can be cultured easily and inexpensively. We aimed to accumulate recombinant proteins in its eggs. This research aimed to identify the signal peptides necessary for transporting vitellogenin into Daphnia eggs and to develop a system for transporting recombinant proteins into the eggs using these signals. A fusion protein of GFP (Green Fluorescent Protein) with a predicted transport signal sequence was expressed in D. magna, and we confirmed that GFP is secreted into the hemolymph. Additionally, a specific region of about 300 amino acids, presumed necessary for binding to vitellogenin receptors, was added to the fusion GFP and expressed outside the ovaries, resulting in strong GFP fluorescence in the eggs. These results indicate that by fusing signals for protein secretion and those that enable uptake into eggs, recombinant protein can be encapsulated into the eggs. This system shows promise as a simple and cost-effective method for producing recombinant proteins by accumulating them in Daphnia eggs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Fransiscus Jason", "last_name": "Wiguna", "name": null }, { "creator_type": "author", "first_name": "Nikko", "last_name": "Adhitama", "name": null }, { "creator_type": "author", "first_name": "Pijar", "last_name": "Religia", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbiotec.2026.04.015" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42092404" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": true }, { "descriptor": "Daphnia magna", "descriptor_ui": "D000096602", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Ovum", "descriptor_ui": "D010063", "major_topic": false }, { "descriptor": "Protein Sorting Signals", "descriptor_ui": "D021382", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": true }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": true }, { "descriptor": "Vitellogenins", "descriptor_ui": "D014819", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 May 4", "date_precision": "day", "issue": "", "normalized_date": "2026-05-04", "pages": "S0168-1656(26)00137-9", "proceedings_title": null, "publisher": "", "title": "Journal of biotechnology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Production and accumulation of recombinant protein via vitellogenin transport pathway in Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human herpesviruses exhibit diverse pathogenic outcomes and the molecular reasons are not fully understood. Human herpesvirus 6B (HHV-6B) causes exanthema subitum and encephalitis, whereas the closely related HHV-6A is typically asymptomatic. Here, we show that cellular APOBEC3 enzymes restrict HHV-6A replication but not HHV-6B. HHV-6B expresses higher levels of the U28 protein, which binds multiple APOBEC3 proteins and promotes their relocalization and degradation. In contrast, HHV-6A fails to counteract APOBEC3 activity and accumulates extensive mutations in both cell- and patient-derived viral genomes. Individual APOBEC3 gene ablation enhances HHV-6A replication and reduces the viral mutation burden. Together, our studies suggest that differential susceptibility to APOBEC3 restriction may help to shape the evolvability and clinical manifestations of HHV-6A and HHV-6B.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Salma", "last_name": "Aktar", "name": null }, { "creator_type": "author", "first_name": "Jing Rin", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Mansaku", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Bochao", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Nagamata", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Tetsushi", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Reuben S.", "last_name": "Harris", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-026-71951-6" }, "pmcid": { "normalized": "PMC13134964" }, "pmid": { "normalized": "42067535" } }, "mesh": [ { "descriptor": "APOBEC Deaminases", "descriptor_ui": "D000071478", "major_topic": false }, { "descriptor": "Cytidine Deaminase", "descriptor_ui": "D003564", "major_topic": true }, { "descriptor": "Cytosine Deaminase", "descriptor_ui": "D043525", "major_topic": true }, { "descriptor": "Genome, Viral", "descriptor_ui": "D016679", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Herpesvirus 6, Human", "descriptor_ui": "D015654", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Roseolovirus Infections", "descriptor_ui": "D019349", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 May 1", "date_precision": "day", "issue": "1", "normalized_date": "2026-05-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "17", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "A viral APOBEC3 antagonist distinguishes HHV-6A from HHV-6B.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although numerous phosphorylation sites on herpes simplex virus 1 (HSV-1) proteins have been identified through phosphoproteomic analyses, their virological significance remains largely unclear. Here, we developed an evolution-guided prioritization strategy that integrates phosphoproteomic data with residue-level conservation across the genus Simplexvirus to identify phosphorylation sites as candidates for functional relevance. Applying this strategy to a previously reported phosphoproteomic data set, we identified 46 phosphorylation sites with a conservation level of 88% or higher. Among them, we focused on two phosphorylation sites, UL6 Tyr-234 and UL7 Tyr-89, which are conserved in 100% and 88% of Simplexvirus species, respectively. Phosphomimetic mutations at either site significantly reduced progeny virus yields in cultured cells, suggesting that phosphorylation at these sites can function as an inhibitory switch regulating HSV-1 replication. In agreement with this, in-depth analyses of phosphorylation at UL7 Tyr-89 during HSV-1 infection revealed that the phosphomimetic mutation led to phenotypes similar to those of the UL7 null mutation in virion morphogenesis, HSV-1 replication in the central nervous system (CNS) and eyes of mice, as well as CNS pathogenicity and ocular pathogenic manifestations. Notably, the non-phosphorylatable mutation at this site had little effect on HSV-1 infection in cultured cells, whereas it significantly reduced HSV-1 replication and pathogenicity in the CNS, but not in the eyes of mice. These results suggest that our strategy effectively prioritizes phosphorylation sites for functional investigation and that phosphorylation at UL7 Tyr-89 serves as a context-dependent inhibitory switch, fine-tuning UL7 activity in a tissue-specific manner, particularly in the CNS. IMPORTANCE: Intricate phosphorylation-dependent regulatory mechanisms enable viruses to diversify the functions of their proteins, profoundly shaping viral replication and pathogenicity. Although phosphoproteomic analyses have produced an expanding catalog of phosphorylation sites on viral proteins, a considerable proportion of these modifications are likely non-functional. This creates a pressing need for a prioritization strategy to predict functionally relevant phosphorylation sites. To address this, we developed an evolution-guided prioritization strategy that integrates phosphoproteomic data with genus-level conservation. Using this strategy, we prioritized two tyrosine phosphorylation sites for functional analysis. Notably, phosphorylation at one of these sites, UL7 Tyr-89, functions as a tissue-specific regulatory mechanism that fine-tunes UL7 activity and modulates herpes simplex virus 1 replication and pathogenicity in the central nervous system. This strategy provides a practical framework for prioritizing candidate regulatory sites for functional investigation in viral replication and pathogenicity.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Tannaka", "name": null }, { "creator_type": "author", "first_name": "Ryoji", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Shio", "name": null }, { "creator_type": "author", "first_name": "Shaocong", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Kousuke", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00200-26" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42059620" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": true }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Matrix Proteins", "descriptor_ui": "D014763", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": true }, { "descriptor": "Virulence", "descriptor_ui": "D014774", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Apr 30", "date_precision": "day", "issue": "", "normalized_date": "2026-04-30", "pages": "e0020026", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Evolution-guided prioritization identifies a tissue-specific phosphorylation switch on herpes simplex virus 1 UL7 regulating viral replication and pathogenicity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Embryogenesis begins with a zygote-a single cell with two pronuclei that separately enclose maternal and paternal chromosomes. The functional significance of the separation of parental chromosomes into distinct pronuclei remains unexplored, despite the fact that one-pronuclear biparental zygotes are used clinically(1-3). Here, using a combination of mouse zygote manipulation, quantitative imaging and theoretical approaches, we show a cytoplasm-mediated competition mechanism between separate parental pronuclei that ensures developmental potential. This mechanism limits pronuclear volume and prevents epigenetic mark dysregulation, including loss of trimethylated histones. One-pronuclear biparental zygotes lack this mechanism, resulting in a reduced rate of development to term. This low developmental potential can be partially rescued by competition-based or drug-based restoration of epigenetic marks. This study provides a spatial mechanism linking fertilization to the establishment of the full developmental potential for the next generation, highlighting caveats in clinical use of one-pronuclear biparental zygotes.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hirohisa", "last_name": "Kyogoku", "name": null }, { "creator_type": "author", "first_name": "Mitsusuke", "last_name": "Tarama", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Matsuwaka", "name": null }, { "creator_type": "author", "first_name": "Tappei", "last_name": "Mishina", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Kumon", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Azusa", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Tomoya S.", "last_name": "Kitajima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41586-026-10417-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42056509" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": true }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": true }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fertilization", "descriptor_ui": "D005306", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Zygote", "descriptor_ui": "D015053", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Apr 29", "date_precision": "day", "issue": "", "normalized_date": "2026-04-29", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000492" ] }, "title": "Cytoplasmic competition between separate parental pronuclei in zygotes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Circadian rhythms are generated by the periodic transcriptional regulation of a group of clock genes by the transcription factors clock circadian regulator (CLOCK) and basic helix-loop-helix ARNT-like 1 (BMAL1). Intracellular circadian rhythms are regulated by multiple signaling pathways. The calcium signaling pathway especially plays an important role in the rhythmic regulation of clock genes; however, the precise molecular mechanisms underlying calcium signaling-mediated rhythmic transcriptional regulation remain largely unclear. Here, we found that calcium-responsive transactivator (CREST) plays an important role in activating period circadian regulator 1 (Per1) and D-box binding PAR bZIP transcription factor (Dbp) gene expression by increasing intracellular calcium ion concentrations and rhythmic transcriptional regulation of these genes. Importantly, CREST increases the promoter activity of Per1 and Dbp by forming a complex with CLOCK and BMAL1. Finally, we found that CREST binds to the E-box-containing promoters of Per1 and Dbp. Taken together, we conclude that the formation of CREST and CLOCK/BMAL1 complexes at the E-boxes of the Per1 and Dbp promoters increases their mRNA expression in response to increased intracellular calcium ion concentrations.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Daiki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Takuzo", "last_name": "Shimo", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2026.153859" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42085778" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "ARNTL Transcription Factors", "descriptor_ui": "D056930", "major_topic": true }, { "descriptor": "Basic-Leucine Zipper Transcription Factors", "descriptor_ui": "D050976", "major_topic": true }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": true }, { "descriptor": "CLOCK Proteins", "descriptor_ui": "D056926", "major_topic": true }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": true }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Period Circadian Proteins", "descriptor_ui": "D056950", "major_topic": true }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Trans-Activators", "descriptor_ui": "D015534", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": true }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Apr 27", "date_precision": "day", "issue": "", "normalized_date": "2026-04-27", "pages": "153859", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "821", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "CREST regulates the Ca(2+) signaling-mediated circadian transcriptional rhythms of the Per1 and Dbp promoters by coactivating with CLOCK/BMAL1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The pathophysiology of allergic rhinitis involves vasodilation and increased vascular permeability. Current treatments primarily target inflammatory mediators, with a limited focus on vascular abnormalities. We aimed to investigate whether lysophosphatidic acid (LPA), which regulates vascular stability through its receptor, LPAR4, could ameliorate allergic symptoms by normalizing vascular function. METHODS: A mouse model of ragweed-induced allergic rhinitis was treated with LPA. We assessed the sneezing frequency, serum immunoglobulin E (IgE) levels, eosinophil infiltration, vascular permeability, and vessel morphology. In vitro studies were performed to examine the protective effects of LPA on histamine-induced endothelial barrier disruption. Transcriptome analysis of nasal vascular endothelial cells was performed to identify the underlying molecular mechanisms. RESULTS: LPA administration significantly reduced the frequency of sneezing and eosinophil infiltration without affecting serum IgE levels. The Evans blue extravasation assay demonstrated that LPA treatment significantly reduced vascular permeability in the nasal tissue, while immunofluorescence analysis of nasal blood vessels showed normalization of vessel diameter. In vitro, LPA pre-treatment significantly protected against histamine-induced endothelial gap formation. Transcriptome analysis revealed that LPA normalized the expression of genes involved in interleukin (IL)-4/IL-13 signaling, platelet activation, and cell junction organization pathways. CONCLUSIONS: LPA signaling uniquely addresses both vascular permeability and vasodilation in allergic rhinitis and represents a novel therapeutic approach that targets vascular abnormalities rather than immune responses. The ability of LPA to simultaneously normalize multiple vascular parameters suggests its potential as a complementary treatment for allergic diseases.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Anna", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Naoi", "last_name": "Hosoe", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takara", "name": null }, { "creator_type": "author", "first_name": "Lamri", "last_name": "Lynda", "name": null }, { "creator_type": "author", "first_name": "Ryozo", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Yukinori", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Shigeharu", "last_name": "Fujieda", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.alit.2026.03.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42034529" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Apr 24", "date_precision": "day", "issue": "", "normalized_date": "2026-04-24", "pages": "S1323-8930(26)00041-9", "proceedings_title": null, "publisher": "", "title": "Allergology international : official journal of the Japanese Society of Allergology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Lysophosphatidic acid mitigates vascular permeability and allergic rhinitis in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Understanding the spatiotemporal dynamics of protein synthesis and degradation is important for establishing how cells maintain protein homeostasis. Conventional methods for detecting newly synthesized proteins include metabolic labeling with radioactive [(35)S]methionine (Met) or the incorporation of l-azidohomoalanine (AHA) or l-homopropargylglycine followed by fluorescent labeling via copper(I)-catalyzed click chemistry. However, these methods typically require cell fixation, making them unsuitable for live-cell imaging. Here, we describe a fluorescence imaging technique to monitor newly synthesized proteins in living cells by utilizing a strain-promoted azide-alkyne cycloaddition (SPAAC) reaction, in which l-AHA-containing proteins are labeled with fluorescent dyes conjugated to dibenzocyclooctyne (DBCO). We synthesized orange-emitting tetramethylrhodamine (TAMRA)-DBCO and far-red-emitting silicon rhodamine (SiR)-DBCO. TAMRA-DBCO enabled the visualization of newly synthesized proteins and their time-dependent degradation throughout the entire cell. SiR-DBCO was similarly effective, but was mainly distributed to the cytoplasm. The time-dependent decrease of TAMRA-DBCO fluorescence intensity in living cells was suppressed by lysosomal enzyme inhibitors and a proteasome inhibitor, suggesting that newly synthesized proteins are degraded via both pathways. Moreover, imaging of drug-induced senescent cells with TAMRA-DBCO suggested that senescent cells have a lower protein degradation ability than nonsenescent cells. These methods should be useful for investigating protein homeostasis in living cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shun", "last_name": "Sumitani", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Orie", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Fan-Yan", "last_name": "Wei", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Kuchitsu", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.bioconjchem.5c00645" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42030520" } }, "mesh": [ { "descriptor": "Alkynes", "descriptor_ui": "D000480", "major_topic": false }, { "descriptor": "Azides", "descriptor_ui": "D001386", "major_topic": false }, { "descriptor": "Click Chemistry", "descriptor_ui": "D057930", "major_topic": false }, { "descriptor": "Cycloaddition Reaction", "descriptor_ui": "D061565", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": true }, { "descriptor": "Proteolysis", "descriptor_ui": "D059748", "major_topic": true }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Apr 24", "date_precision": "day", "issue": "", "normalized_date": "2026-04-24", "pages": "", "proceedings_title": null, "publisher": "", "title": "Bioconjugate chemistry", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000522" ] }, "title": "Visualizing Newly Synthesized Proteins and Their Degradation Dynamics by Using Long-Wavelength-Emitting Fluorescent Dye-DBCO Conjugates.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Senescence of T cells is strongly linked to organismal aging through two interconnected processes: chronic low-grade inflammation and reduced immune surveillance of senescent cells. T cells are particularly vulnerable to thymic involution, hematopoietic stem cell aging, repeated homeostatic proliferation, chronic antigenic stimulation, and metabolic and mitochondrial dysfunction. As a result, aged T cells may lose their capacity to combat infection and eliminate senescent cells, while also contributing to inflammaging through the production of inflammatory cytokines. Recent preclinical studies in murine models have demonstrated that modulation of T-cell immunosenescence can ameliorate age-related diseases. These approaches include PD-1/PD-L1 blockade, senolytic chimeric antigen receptor T (CAR-T) cells, and CXCL4/platelet factor 4 (PF4). In addition, early-stage human clinical studies of caloric restriction, low-dose mTOR inhibition, thymic regeneration, and mesenchymal stromal/stem cell (MSC) therapy suggest that interventions targeting immunosenescence may provide health benefits. Moreover, in murine models of Alzheimer's disease, T cells infiltrating the brain may exert either disease-promoting or protective effects depending on the disease stage, highlighting an important point of intersection between T-cell-mediated immunosenescence and brain aging. This review summarizes the basic concepts of immunosenescence, the molecular basis of immune surveillance of senescent cells, age-associated T-cell subsets, their links to brain aging, and interventional strategies aimed at clinical translation, with particular emphasis on T-cell biology and the transcriptional regulatory network driven by NR4a.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masaki", "last_name": "Ohyagi", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s41232-026-00419-3" }, "pmcid": { "normalized": "PMC13107656" }, "pmid": { "normalized": "42032757" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Apr 24", "date_precision": "day", "issue": "1", "normalized_date": "2026-04-24", "pages": "", "proceedings_title": null, "publisher": "", "title": "Inflammation and regeneration", "volume": "46", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Senescence of T cells and organ aging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "IL-10-producing B cells exert immunosuppressive effects, yet their low abundance and poor in vitro viability have limited their therapeutic application. Here, we developed a stromal coculture system using MS5 cells engineered to express human CD40L, BAFF, and IFN-beta1 (MS5-3F, for \"3 factors\"), which enables robust induction and greater than 1000-fold expansion of human IL-10-producing B cells. The expanded cells showed phenotypic and transcriptional profiles characteristic of unswitched (IgM+) plasmablasts and potently suppressed CD4+ T cell proliferation in an IL-10-dependent manner. MS5-3F-expanded B cells also increased the frequency of regulatory T cells in vitro, an effect that was not abrogated by IL-10/IL-10R blockade, suggesting contributions from additional mechanisms. IL-10 production originated predominantly from naive B cells, rather than memory B cells. Furthermore, B cells from patients with systemic lupus erythematosus, despite impaired IL-10 production under conventional conditions, were efficiently differentiated into IL-10-producing B cells using this system. The expanded cells showed minimal IgG-secreting output. Our platform offers a scalable strategy for generating human regulatory B cells, laying the foundation for B cell-based immunotherapies.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Imabayashi", "name": null }, { "creator_type": "author", "first_name": "Akemi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Yada", "name": null }, { "creator_type": "author", "first_name": "Airi", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Rinka", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Kurasawa", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Sungyeon", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Niiro", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci.insight.197393" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42018652" } }, "mesh": [ { "descriptor": "B-Cell Activating Factor", "descriptor_ui": "D053264", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": true }, { "descriptor": "CD40 Ligand", "descriptor_ui": "D023201", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interferon-beta", "descriptor_ui": "D016899", "major_topic": false }, { "descriptor": "Interleukin-10", "descriptor_ui": "D016753", "major_topic": true }, { "descriptor": "Lupus Erythematosus, Systemic", "descriptor_ui": "D008180", "major_topic": false }, { "descriptor": "Stromal Cells", "descriptor_ui": "D017154", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Apr 22", "date_precision": "day", "issue": "8", "normalized_date": "2026-04-22", "pages": "e197393", "proceedings_title": null, "publisher": "", "title": "JCI insight", "volume": "11", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "A stromal platform for robust expansion of functional IL-10-producing B cells for immune regulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Suguru", "last_name": "Torimitsu", "name": null }, { "creator_type": "author", "first_name": "Hisahiro", "last_name": "Ikari", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Tsuneya", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Hirotaro", "last_name": "Iwase", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Yohsuke", "last_name": "Makino", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00414-026-03809-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42014522" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Apr 22", "date_precision": "day", "issue": "", "normalized_date": "2026-04-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of legal medicine", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Automated femoral measurement from postmortem computed tomographic images using artificial intelligence for forensic stature estimation in a Japanese population.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Whole-genome duplication (WGD) of diploid cells triggers various cell fates, such as cell death, cell cycle arrest, and proliferation with chromosome instability, contributing to broad bioprocesses, including differentiation, tumorigenesis, or aging. However, factors determining the post-WGD cell fates remain largely unknown. In this study, we found that cytokinesis failure (CF) and mitotic slippage (MS), two major routes of WGD induction, differentially affected post-WGD viability and proliferation in human cells. Quantitative live imaging revealed poorer survivability of cells upon multipolar chromosome segregation at the first mitosis after MS than CF. Chromosome-specific labeling showed that the inefficient sister chromatid separation upon MS caused more skewed homologous chromosome distribution than CF. The skewed homologue distribution frequently led to physical isolation (>10 mum) of the centrosomes from all homologous centromeres, hindering these centrosomes from capturing any of these homologues. The difference in the frequency of this nullisomic chromosome segregation between MS and CF at least partially explained their difference in the viability of the subsequent daughter cells. Moreover, artificial separation of sister chromatids upon MS improved the evenness of homologue distribution, suppressed nullisomic homologue segregation in the following mitosis, and significantly restored the viability of their daughter cells. These results demonstrate the geometric arrangement of homologous chromosomes, defined by the presence or absence of sufficient sister chromatid separation upon WGD, as a key factor determining the proliferative characteristics of subsequent progenies. Our findings would provide a clue to understanding the route-dependent outcomes of WGD in cell fate determination in different bioprocesses.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masaya", "last_name": "Inoko", "name": null }, { "creator_type": "author", "first_name": "Guang", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2524135123" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41984834" } }, "mesh": [ { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": true }, { "descriptor": "Centrosome", "descriptor_ui": "D018385", "major_topic": false }, { "descriptor": "Chromatids", "descriptor_ui": "D002842", "major_topic": true }, { "descriptor": "Chromosome Segregation", "descriptor_ui": "D020090", "major_topic": true }, { "descriptor": "Cytokinesis", "descriptor_ui": "D048749", "major_topic": false }, { "descriptor": "Gene Duplication", "descriptor_ui": "D020440", "major_topic": true }, { "descriptor": "Genome, Human", "descriptor_ui": "D015894", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Apr 21", "date_precision": "day", "issue": "16", "normalized_date": "2026-04-21", "pages": "e2524135123", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "123", "year": 2026 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000485" ] }, "title": "Sister chromatid separation determines the proliferative properties upon whole-genome duplication via homologous chromosome arrangement.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human herpesvirus 6B (HHV-6B) is the most prevalent HHV-6 species in humans and is associated with roseola infantum, febrile seizures, and increased morbidity following reactivation in immunocompromised patients. Herpesviruses frequently modulate NF-kappaB, a central regulator of inflammatory gene expression, to promote viral gene expression and replication. The HHV-6A tegument protein U14 activates NF-kappaB, but whether this activity is conserved in HHV-6B and contributes to infection-associated outputs has remained unclear. Here, we evaluated HHV-6A and HHV-6B U14 in a transient NF-kappaB reporter assay and examined U14 function during HHV-6B infection using two independent U14-targeting shRNAs. Both U14 orthologs activated an NF-kappaB reporter. During HHV-6B infection in MT-4 cells, U14 knockdown reduced phosphorylation of p65 (Ser536) and was accompanied by decreased mRNA levels of the immediate-early viral gene IE2 and the early viral genes U27 and U38, as well as reduced release of viral genomes into culture supernatants. U14 knockdown also reduced IL-2, IL-6, and IL-8 transcript levels, consistent with attenuation of an NF-kappaB-linked cytokine transcriptional program. Together, these results extend U14-mediated NF-kappaB activation to HHV-6B and link U14 depletion to reduced viral gene expression and productive replication.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Khoir", "last_name": "Amaliin", "name": null }, { "creator_type": "author", "first_name": "Aila", "last_name": "Gulijiahani", "name": null }, { "creator_type": "author", "first_name": "Mansaku", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/1348-0421.70059" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42015664" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Viral", "descriptor_ui": "D015967", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Herpesvirus 6, Human", "descriptor_ui": "D015654", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interleukin-6", "descriptor_ui": "D015850", "major_topic": false }, { "descriptor": "Interleukin-8", "descriptor_ui": "D016209", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": true }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Roseolovirus Infections", "descriptor_ui": "D019349", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": true }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Apr 21", "date_precision": "day", "issue": "", "normalized_date": "2026-04-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "Microbiology and immunology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Conserved U14-Mediated NF-kappaB Activation in Human Herpesvirus 6A and 6B.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuya", "last_name": "Kawabata", "name": null }, { "creator_type": "author", "first_name": "Sayuri", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Ohdake", "name": null }, { "creator_type": "author", "first_name": "Epifanio", "last_name": "Bagarinao", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Harutsugu", "last_name": "Tatebe", "name": null }, { "creator_type": "author", "first_name": "Riki", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Ishigaki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Tokuda", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Hirohisa", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13195-026-02056-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42010440" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glial Fibrillary Acidic Protein", "descriptor_ui": "D005904", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Longitudinal Studies", "descriptor_ui": "D008137", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neuropsychological Tests", "descriptor_ui": "D009483", "major_topic": false }, { "descriptor": "Spatial Navigation", "descriptor_ui": "D065854", "major_topic": true }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Virtual Reality", "descriptor_ui": "D000076142", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Apr 20", "date_precision": "day", "issue": "", "normalized_date": "2026-04-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "Alzheimer's research & therapy", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "VR-based path integration predicts individual risk of rapid cortical decline: a one-year longitudinal study in cognitively unimpaired adults.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer cells sustain glycolysis despite oxygen availability, creating an acidic microenvironment via proton and lactate export, but how they survive acid stress is unclear. We show that severe acidification (pH 5.6) induces necroptosis, whereas moderate acidity (pH 6.8) prevents death and enables anchorage-independent survival and tumor initiation. RNA sequencing of suspended cells at pH 6.8 revealed activation of respiratory chain complex and complement pathways, consistent with adaptation to this pH. A genome-wide CRISPR-Cas9 knockout screen in PANC1 cells under chronic acidity identified FAM129C as a regulator of acid tolerance and survival. In xenografts, FAM129C overexpression reduced PIGR expression, implicating this axis in tumor growth and immune infiltration. Anti-PD-L1 plus a complement inhibitor showed synergistic anti-tumor activity in PIGR-overexpressing tumors. Thus, acidic stress engages a pathway that allows cancer cells to evade necroptosis and promote tumor plasticity, providing potential avenues for therapeutic intervention targeting pH-dependent cell-death pathways.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Manami", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Bo", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Motoaki", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "FeiFei", "last_name": "Cai", "name": null }, { "creator_type": "author", "first_name": "Runmei", "last_name": "Cui", "name": null }, { "creator_type": "author", "first_name": "Ritsuko", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Suzuka", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Ayana", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Cayla", "last_name": "Boycott", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Miyuki", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Chisato", "last_name": "Iwabuchi-Yoshida", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Aki", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Rika", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Futoshi", "last_name": "Kuribayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Sando", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Yanai", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Yachie", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Osawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2026.117226" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41997144" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Apr 16", "date_precision": "day", "issue": "", "normalized_date": "2026-04-16", "pages": "117226", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Tolerance to extracellular acidic pH facilitates tumor plasticity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The clinical success of chimeric antigen receptor T cell (CAR T cell) therapy in hematologic malignancies has prompted its application for refractory solid tumors, including glioblastoma (GBM). However, CAR T cell trials against solid tumors have failed to show clinical efficacy thus far. Here, we show that the dysfunction of CAR T cells in GBM is attributed, at least, in part, to glucose deficiency in the tumor microenvironment (TME) driven by the substantial consumption of glucose by cancer cells. Engineering CAR T cells to continuously express glucose transporter 3 (GLUT3), a high-affinity glucose transporter, restored their cytokine production and killing activity. However, although CAR T cells with stable GLUT3 expression induced tumor reduction in a preclinical GBM model, their overactivation led to adverse events and mouse death. In contrast, on-demand GLUT3-expressing CAR T cells, in which GLUT3 transcription was driven by the nuclear translocation of nuclear factor of activated T cells (NFAT) as a consequence of target antigen stimulation, exhibited enhanced metabolic fitness and increased antitumor efficacy, leading to long-lasting tumor control in intracranial human GBM cell xenograft models while preventing adverse events. We propose that on-demand enhancement of metabolic fitness, such as at the time of exposure to tumor antigens, is a concept for boosting the antitumor efficacy of CAR T cells against solid tumors.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Junya", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Nina Yi-Tzu", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Sachi", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Nishinakamura", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Itahashi", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mizoguchi", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Shiraki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Fumiharu", "last_name": "Ohka", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Motomura", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Ryuzo", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Natsume", "name": null }, { "creator_type": "author", "first_name": "Ryuta", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Hiroyoshi", "last_name": "Nishikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/scitranslmed.adu3532" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41984929" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain Neoplasms", "descriptor_ui": "D001932", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Glioblastoma", "descriptor_ui": "D005909", "major_topic": true }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Glucose Transporter Type 3", "descriptor_ui": "D051274", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunotherapy, Adoptive", "descriptor_ui": "D016219", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Receptors, Chimeric Antigen", "descriptor_ui": "D000076962", "major_topic": true }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": true }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Apr 15", "date_precision": "day", "issue": "845", "normalized_date": "2026-04-15", "pages": "eadu3532", "proceedings_title": null, "publisher": "", "title": "Science translational medicine", "volume": "18", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "On-demand GLUT3 expression augments CAR T cell metabolic fitness and antitumor efficacy in preclinical models of glioblastoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Shape-encoded hydrogel microparticles (SHMPs) offer robust sensitivity and multiplexing capacity in immunoassays. However, their analysis has conventionally required labor-intensive imaging-based methods. Although flow-through analysis has been explored as an alternative approach, its throughput and sensitivity remain limited. In this study, we developed a high-throughput and highly sensitive multiplex immunoassay platform by integrating SHMPs with acoustofluidic focusing. Acoustofluidic focusing is a powerful technique that enables high-throughput analysis owing to its capability to densely align micro-objects. Since hydrogel materials are challenging to accurately align by acoustofluidic focusing, we optimized the flow rate as well as the amplitude and frequency of acoustic standing waves to achieve precise and dense particle alignment. The precise alignment of SHMPs in microchannels allowed reliable code recognition and fluorescence signal detection. Also, densely aligned SHMPs offered an 8-fold higher analysis throughput than previously studied flow-through methods, even at low flow rates. The synergistic effects of sufficient dwell time provided by acoustofluidic focusing at low flow rates and the high sensitivity of SHMPs achieved a 61.5-fold enhancement in the detection limit compared to commercial devices using flow-through analysis. The feasibility of multiplex detection was further validated through spike-in experiments, yielding recovery rates within 100 +/- 20% for all four protein targets. Finally, we assayed cytokines in clinical samples from drug allergy and healthy groups and successfully identified significant differences in the cytokine levels.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jun Hee", "last_name": "Choi", "name": null }, { "creator_type": "author", "first_name": "Dong Min", "last_name": "Shin", "name": null }, { "creator_type": "author", "first_name": "Jiwoo", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Min Ju", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Min-Ho", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Min Jung", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Sangwook", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Ki Wan", "last_name": "Bong", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acssensors.5c03744" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41984547" } }, "mesh": [ { "descriptor": "Acoustics", "descriptor_ui": "D000162", "major_topic": true }, { "descriptor": "High-Throughput Screening Assays", "descriptor_ui": "D057166", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogels", "descriptor_ui": "D020100", "major_topic": true }, { "descriptor": "Immunoassay", "descriptor_ui": "D007118", "major_topic": false }, { "descriptor": "Microfluidic Analytical Techniques", "descriptor_ui": "D046210", "major_topic": true }, { "descriptor": "Microspheres", "descriptor_ui": "D008863", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Apr 15", "date_precision": "day", "issue": "", "normalized_date": "2026-04-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "ACS sensors", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Acoustofluidic Focusing for High-Throughput and Sensitive Analysis of Shape-Encoded Hydrogel Microparticles in Multiplex Immunoassay.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although glycerol is a ubiquitous metabolite in mammalian systems, its cellular metabolic pathways and functions have not been fully elucidated. Here, we find that elevated extracellular glycerol modulates intracellular metabolism and pro-inflammatory responses of macrophages. In pro-inflammatory macrophages stimulated with lipopolysaccharide, glycerol is taken up through glycerol channels including Aquaporin 3 (AQP3) and metabolized to glycerol-3-phosphate (G3P), which is then converted to dihydroxyacetone phosphate by glycerol-3-phosphate dehydrogenase 2 (GPD2). This glycerol-driven pathway enhances mitochondrial ATP production, potentially by supplying electrons to the electron transport chain (ETC) via GPD2, and by upregulating the transcription of genes encoding ETC complexes.　In addition, glycerol supplementation elevates intracellular acetyl-CoA levels, promotes histone acetylation at the promoters of pro-inflammatory cytokine genes, and consequently increases cytokine gene expression, suggesting enhanced pro-inflammatory response. In vivo experiments, macrophage-specific AQP3 conditional knockout mice exhibit reduced weight gain and adipose tissue inflammation in a high-fat diet-induced obesity model. Our findings provide novel insights into the metabolic regulation and macrophage inflammation by extracellular glycerol.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Manami", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Hishiki", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Hara-Chikuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s44319-026-00747-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41981083" } }, "mesh": [ { "descriptor": "Acetyl Coenzyme A", "descriptor_ui": "D000105", "major_topic": false }, { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aquaporin 3", "descriptor_ui": "D051400", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Glycerol", "descriptor_ui": "D005990", "major_topic": true }, { "descriptor": "Glycerolphosphate Dehydrogenase", "descriptor_ui": "D005993", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": true }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": true }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Apr 14", "date_precision": "day", "issue": "", "normalized_date": "2026-04-14", "pages": "", "proceedings_title": null, "publisher": "", "title": "EMBO reports", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Glycerol enhances mitochondrial metabolism and inflammatory response in pro-inflammatory macrophages.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Methane (CH(4)) combustion under lean conditions is a critical reaction for controlling unburned hydrocarbon emissions in natural gas engines. However, the development of highly active and sulfur-tolerant catalysts remains a major challenge due to the severe deactivation caused by sulfur compounds such as SO(2). In this study, we adopted a machine-learning (ML)-guided strategy to accelerate the discovery of CH(4) combustion catalysts that are tolerant to sulfur poisoning. Starting from 16 initial catalysts and conducting 24 cycles of a closed-loop discovery system (ML prediction + experiment), a total of 300 multielemental catalysts were experimentally evaluated under identical conditions in the presence of SO(2). Through this approach, over 30 catalysts exhibiting high CH(4) conversion and excellent sulfur tolerance were identified. Among them, Pd(2)-Ru(0.4)-Ir(0.3)-Pt(0.3)/ZrO(2)_JRC3_RC-100 demonstrated the highest catalytic performance. Control experiments and comprehensive characterizations, including in situ/operando spectroscopy, revealed the individual and synergistic roles of each component in enhancing both activity and resistance to sulfur poisoning.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuan", "last_name": "Jing", "name": null }, { "creator_type": "author", "first_name": "Kah Wei", "last_name": "Ting", "name": null }, { "creator_type": "author", "first_name": "Junxian", "last_name": "Qin", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Tajima", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Anzai", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Mine", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Toyoshima", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kondoh", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Toyao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.6c01560" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41961999" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Apr 10", "date_precision": "day", "issue": "", "normalized_date": "2026-04-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Machine-Learning-Guided Discovery of CH(4) Combustion Catalysts Operating in the Presence of SO(2).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In many mammals, early interactions between caregivers and offspring involve rich physical contact during which offspring typically remain calm near the caregiver. Such contact is thought to support emotional regulation during infancy, but how prior experience shapes these mechanisms remains unclear. Here, we show that back stroking induces a calming response in human infants and mouse pups, with reduced movement. In mouse pups, back stroking further reduces heart rate, facilitates sleep onset, and attenuates stress-induced corticosterone elevations. These sleep-promoting and stress-buffering effects are absent in artificially reared pups deprived of postnatal maternal care, suggesting that early experience tunes the calming response to stroking. Transcriptomic analysis reveals reduced hypothalamic expression of the calcium channel subunit gene Cacna1b in artificially reared pups, and knockdown of hypothalamic Cacna1b in maternally reared pups abolishes stroking-induced calming. Thus, early-life maternal care and associated physical contact may shape hypothalamic circuits supporting behavioral and physiological regulation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sachine", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Harauma", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Moriguchi", "name": null }, { "creator_type": "author", "first_name": "Yousuke", "last_name": "Tsuneoka", "name": null }, { "creator_type": "author", "first_name": "Kimiya", "last_name": "Narikiyo", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Miyanishi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Funato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-026-10012-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41963499" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Calcium Channels, L-Type", "descriptor_ui": "D020746", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Maternal Behavior", "descriptor_ui": "D008425", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Apr 10", "date_precision": "day", "issue": "", "normalized_date": "2026-04-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000528" ] }, "title": "Early-life maternal care is required for the typical development of calming responses to back stroking.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: Proliferative vitreoretinopathy (PVR) remains associated with a poor prognosis despite advances in vitreoretinal surgery. In the absence of effective adjunctive therapies, this study aimed to characterize vitreous metabolic alterations in PVR to better understand its pathophysiology. METHODS: Untargeted metabolomic profiling was conducted on vitreous humor samples from 38 eyes that underwent surgery: PVR (grade C, n = 10), rhegmatogenous retinal detachment (RRD; grades A and B, n = 18), and controls undergoing intraocular lens (IOL) scleral fixation (n = 10). Metabolites were analyzed using capillary electrophoresis-mass spectrometry. Metabolic profiles were compared pairwise among the three groups with multiple testing correction, and pathway enrichment analysis was performed. RESULTS: RRD demonstrated no disease-specific metabolic signature relative to controls after multiple testing correction. In contrast, PVR exhibited a distinct metabolic profile compared with both RRD and controls. Pathway enrichment analysis revealed upregulation of amino acid and nitrogen metabolism-including arginine and proline metabolism, glycine and serine metabolism, the urea cycle, ammonia recycling, alanine metabolism, and the malate-aspartate shuttle-consistent with increased biosynthetic demand. Pathways related to fibrosis and stress responses were also enriched. CONCLUSIONS: This study shows that PVR exhibits a unique metabolic signature distinct from RRD, characterized by the activation of metabolic pathways that support increased energy demand, cellular proliferation, stress responses, and fibrotic remodeling. These findings provide insights into the metabolic mechanisms associated with the progression from RRD to PVR, suggesting potential therapeutic targets to prevent fibrosis and aberrant cell proliferation.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuto", "last_name": "Kawamata", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Takehito", "last_name": "Iwase", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Nizawa", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Tatsumi", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1167/iovs.67.4.21" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41960964" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Retinal Detachment", "descriptor_ui": "D012163", "major_topic": false }, { "descriptor": "Vitreoretinopathy, Proliferative", "descriptor_ui": "D018630", "major_topic": true }, { "descriptor": "Vitreous Body", "descriptor_ui": "D014822", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Apr 1", "date_precision": "day", "issue": "4", "normalized_date": "2026-04-01", "pages": "21", "proceedings_title": null, "publisher": "", "title": "Investigative ophthalmology & visual science", "volume": "67", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolomic Profiling of Vitreous Humor Reveals Distinct Metabolic Signatures in Proliferative Vitreoretinopathy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: In recent years, much research has been conducted on ultrasound diagnosis of breast tumors using convolutional neural networks (CNNs). While many CNNs for breast tumor classification have been investigated, previous studies have evaluated them using data from the same institution that provided the CNN training data. This may have biased the accuracy of the CNNs. To perform a fairer evaluation, we compared the accuracy of CNNs with that of human experts using a multicenter external validation cohort. Additionally, previous studies used fewer than about 2000 images to train CNNs, whereas this study used 16,530 images. METHODS: We trained a 2-class (benign, malignant) classification CNN and a 4-class (breast cancer, fibroadenoma, simple cyst, and other benign tumors) classification CNN using 16,530 images. Using data from a multicenter external validation cohort, we compared the classification accuracy of the developed CNNs to that of human experts. RESULTS: The 2-class classification CNN achieved an accuracy of 88.1%. The benign/malignant classification from the 4-class classification CNN achieved an accuracy of 86.3%. Human experts achieved an accuracy of 83.2%. Thus, the 2-class classification CNN was slightly more accurate than the benign/malignant classification from the 4-class classification CNN. Both developed CNNs were more accurate than human experts. CONCLUSION: The CNNs developed using a large-scale breast ultrasound image database achieved higher accuracy than that of human experts in evaluation using multicenter external validation cohort data.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Toshikazu", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Sadako-Tanaka", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Kouzou", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Morishima", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Tsugawa", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Uematsu", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Kudo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10396-026-01631-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41886212" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Mar 26", "date_precision": "day", "issue": "", "normalized_date": "2026-03-26", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of medical ultrasonics (2001)", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparison of breast ultrasound image classification accuracy between convolutional neural networks and human experts using multicenter external validation cohort data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Current fluorescent protein-based multiplexed cell labeling techniques suffer from limited discrimination power due to stochastic color selection and large gene sizes from tandem repeats of multiple fluorescent proteins. We developed Caterpie, a rationally designed system using engineered split fluorescent proteins that enables deterministic identification of 20 distinct cell populations with 97% accuracy and reduced gene sizes. Through computational structure-guided design, we engineered enhanced split mNeonGreen3A and split sfCherry3C variants that achieve performance comparable to split CFP2, the best-performing split fluorescent protein. Our systematic library of trichromatic 11th beta-strand tags with up to 12 tandem repeats enables predictable, high-fidelity labeling for precise cell targeting. This technology addresses critical limitations in simultaneous identification of multiple defined cell populations.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mamoru", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Kinjo", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Brian", "last_name": "Kuhlman", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.crmeth.2026.101363" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41895260" } }, "mesh": [ { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": true }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Mar 26", "date_precision": "day", "issue": "", "normalized_date": "2026-03-26", "pages": "101363", "proceedings_title": null, "publisher": "", "title": "Cell reports methods", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Intensity modulation of trichromatic split fluorescent proteins for live cell mapping.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Beyond their well-established roles in type 3 immunity, RORgammat(+) innate immune cells are also essential for secondary lymphoid organ (SLO) formation and gut homeostasis. However, the transcriptional mechanisms governing RORgammat expression in these cells, including group 3 innate lymphoid cells (ILC3s), lymphoid tissue inducer (LTi) cells, and antigen-presenting cells (APCs), remain largely unresolved. Here, we identified two key cis-regulatory elements within conserved non-coding sequences (CNS)9 and 11 in the Rorc locus, which were sequentially utilized during differentiation. Initially, Runx-binding sites in CNS11 established chromatin accessibility as early as the hematopoietic stem cell (HSC) stage. Disruption of this chromatin priming prevented subsequent transcriptional activation, thereby abolishing the initial induction of RORgammat in these cells. At later stages, CNS9 played a critical role, particularly in the development of RORgammat(+) APCs, contributing to colonic peripheral Treg (pTreg) cell induction. This hierarchical transcriptional regulation was essential for SLO formation and postnatal type 3 immunity and for restraining excessive intestinal type 2 immune responses through pTreg cell induction.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takuma", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Miyuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Reo", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Taisho", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Koh-Hei", "last_name": "Sonoda", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Sumiya", "name": null }, { "creator_type": "author", "first_name": "Ruiqi", "last_name": "Shao", "name": null }, { "creator_type": "author", "first_name": "Mikita", "last_name": "Suyama", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Taniuchi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kojo", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.immuni.2026.02.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41881028" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigen-Presenting Cells", "descriptor_ui": "D000938", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Nuclear Receptor Subfamily 1, Group F, Member 3", "descriptor_ui": "D057132", "major_topic": true }, { "descriptor": "Regulatory Sequences, Nucleic Acid", "descriptor_ui": "D012045", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": true }, { "descriptor": "Transcriptional Activation", "descriptor_ui": "D015533", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Mar 24", "date_precision": "day", "issue": "", "normalized_date": "2026-03-24", "pages": "S1074-7613(26)00054-3", "proceedings_title": null, "publisher": "", "title": "Immunity", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "A hierarchical Rorc(gammat) cis-regulatory cascade orchestrates differentiation of RORgammat(+) innate immune cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Early animal embryos must balance the efficiency with the accuracy of mitotic control. However, the extent of mitotic errors that can be safely endured at different stages of development is unclear. In this study, using a recently developed photoswitchable CENP-E inhibitor, we introduce transient mitotic errors at various developmental windows and systematically address their organismal effects. Upon CENP-E inhibition in the pre-gastrula period, embryos suffer gradual aggravation of developmental defects as the duration of the inhibition extends. Conversely, embryos tolerate several hours of consecutive CENP-E inhibition in the gastrula period, frequently achieving full development. Live imaging reveals that chromosome misalignment caused by CENP-E inhibition results in a modest mitotic delay in the gastrula, but not in the early pre-gastrula period, suggesting the gradual functionalization of the spindle assembly checkpoint (SAC) at this stage. This mitotic delay helps alleviate, though not perfectly resolve, polar chromosome misalignment before anaphase onset. Importantly, pharmacological suppression of SAC renders gastrula embryos inviable upon CENP-E inhibition. Therefore, despite its leaky nature, the embryonic SAC contributes to partial mitotic error correction, which proves essential to manage consecutive mitotic perturbations. Our results demonstrate the power of optochemical approaches in understanding the robust control of dynamic processes in development.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akira", "last_name": "Matsura", "name": null }, { "creator_type": "author", "first_name": "Miyu", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Tamaoki", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Kotani", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-026-09871-w" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41866436" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromosomal Proteins, Non-Histone", "descriptor_ui": "D002868", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Gastrula", "descriptor_ui": "D005775", "major_topic": false }, { "descriptor": "M Phase Cell Cycle Checkpoints", "descriptor_ui": "D059566", "major_topic": true }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false }, { "descriptor": "Spindle Apparatus", "descriptor_ui": "D008941", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Mar 23", "date_precision": "day", "issue": "", "normalized_date": "2026-03-23", "pages": "", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Optochemical elucidation of a critical role of the incomplete spindle assembly checkpoint in zebrafish development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Due to remarkably stereotyped development and small numbers of cells, ascidian embryos are invaluable as models for investigating the principles of chordate development at single-cell resolution. Established model species of ascidians, such as Ciona spp. and Phallusia mammillata, are primarily distributed in temperate waters, and natural populations become scarce in the summer due to rising water temperatures. However, Phallusia philippinensis is a tropical/subtropical species that is closely related to P. mammillata and shares the feature of highly transparent embryos, which facilitates live imaging and optical analyses. Its accessibility in warm-water habitats makes P. philippinensis a promising alternative model for imaging-based analyses, particularly in tropical regions or during in summer. We present comprehensive genomic transcriptomic resources that have been resolved according to the developmental stage for P. philippinensis. The assembled genome spans 150.2 Mb and comprises 407 contigs with an N50 of 909 kb and a GC content of 42.0%. Transcriptomes from 5 organs and 9 distinct embryonic stages were used to construct a gene model, which revealed 20,928 genes with a high BUSCO completeness score of 88.6%. Functional annotations were assigned to 16,507 genes using the UniProt and RefSeq databases. We integrated these resources into a new constructed genomic browser, which can be used easily by all researchers. These new resources are immediately applicable to comparative developmental studies of gene expression and regulation in ascidian embryos and will comprehensively cover the off-season of reproduction for model ascidians.", "classifications": [ { "id": "21H00440", "label": "21H00440", "researcher": "Kohji Hotta", "type": "grant" }, { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shunsuke O.", "last_name": "Miyasaka", "name": null }, { "creator_type": "author", "first_name": "Takumi T.", "last_name": "Shito", "name": null }, { "creator_type": "author", "first_name": "Noburu", "last_name": "Sensui", "name": null }, { "creator_type": "author", "first_name": "Euichi", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/g3journal/jkag057" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41866321" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": true }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": true }, { "descriptor": "Molecular Sequence Annotation", "descriptor_ui": "D058977", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true }, { "descriptor": "Tropical Climate", "descriptor_ui": "D014329", "major_topic": false }, { "descriptor": "Urochordata", "descriptor_ui": "D014561", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Mar 20", "date_precision": "day", "issue": "", "normalized_date": "2026-03-20", "pages": "jkag057", "proceedings_title": null, "publisher": "", "title": "G3 (Bethesda, Md.)", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Genomic and Transcriptomic Resources for the Tropical Ascidian Phallusia philippinensis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Adipocyte spheroids offer a promising three-dimensional (3D) cell culture model for obesity research, as they reproduce the structure and cell-cell interaction of adipose tissue more accurately compared to two-dimensional (2D) cultures. However, the mass production of uniform, small adipocyte spheroids remains challenging, limiting their use in large-scale analyses, such as drug screening. Here, we develop a method that combines simple microfluidics with templated emulsification to enable the large-scale production of small, uniform adipocyte spheroids. By encapsulating preadipocytes in hollow agarose microcapsules and incubating them for 2 days, we reproducibly generated more than 100,000 uniform spheroids with diameters of approximately 60 mum. These preadipocytes were subsequently differentiated into adipocyte spheroids through an 8-day induction period. This platform facilitates large-scale 3D analysis for obesity research and can be adapted to produce various other spheroid and organoid models, broadening its utility in biomedical research.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ruri", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Kirisako", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Yoneshiro", "name": null }, { "creator_type": "author", "first_name": "Juro", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsbiomaterials.6c00142" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41813637" } }, "mesh": [ { "descriptor": "Adipocytes", "descriptor_ui": "D017667", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Capsules", "descriptor_ui": "D002214", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": true }, { "descriptor": "Cell Culture Techniques, Three Dimensional", "descriptor_ui": "D000087603", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Hydrogels", "descriptor_ui": "D020100", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microfluidic Analytical Techniques", "descriptor_ui": "D046210", "major_topic": true }, { "descriptor": "Microfluidics", "descriptor_ui": "D044085", "major_topic": false }, { "descriptor": "Spheroids, Cellular", "descriptor_ui": "D018874", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Mar 11", "date_precision": "day", "issue": "", "normalized_date": "2026-03-11", "pages": "", "proceedings_title": null, "publisher": "", "title": "ACS biomaterials science & engineering", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Large-Scale Production of Uniform, Small Adipocyte Spheroids in Hydrogel Microcapsules Using a Microfluidic Flow-Focusing Device.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Near-infrared (NIR) light-responsive molecules are important tools in life sciences due to high tissue transparency and low phototoxicity in this wavelength region. However, conventional compounds are generally activated via S(0)-S(1) transition, which requires relatively high-energy excitation. Here, in order to extend the excitation wavelength into the NIR region, we designed and synthesized Ru pi-arene complexes of 6pi/18pi tautomeric benziphthalocyanines (BPcs), aiming to utilize the low-energy singlet-triplet transition of these complexes for activation. Experimental studies revealed that selective pi-coordination of Ru to the benzene ring of BPcs disrupts the strongly NIR-absorptive, 18pi-electron aromatic structure of BPcs. Nevertheless, the Ru-BPc complexes still exhibit weak and broad absorption in the NIR region, derived from singlet-triplet transition with a metal-to-ligand charge-transfer character, as indicated by theoretical calculations. NIR irradiation of Ru-BPcs at >800 nm led to efficient dissociation of Ru, releasing BPcs with strong NIR absorption and fluorescence. Thus, these complexes exhibit OFF/ON-type activation via NIR-induced Ru release due to S(0)-T(1) transition.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Orie", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Toriumi", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Uchiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d5sc09646d" }, "pmcid": { "normalized": "PMC13019363" }, "pmid": { "normalized": "41908628" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Mar 10", "date_precision": "day", "issue": "", "normalized_date": "2026-03-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "Chemical science", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Near-infrared (NIR)-responsive activation of Ru-benziphthalocyanine complexes via singlet-triplet transition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cells continuously communicate through dynamic cell-cell contacts. Tools for visualizing these dynamic interactions in living cells are essential to the study of fundamental biological processes in multicellular organisms. Here, we present two fluorescent indicators, Gachapin and Gachapin-C, for visualizing dynamic cell-cell contact. Gachapin visualizes not only static but also dynamic contacts. Multiplexed imaging combining green Gachapin with spectrally distinct indicators allows simultaneous monitoring of contact dynamics, cytoskeletal assembly, and intracellular signaling during cell movement. Furthermore, the formation and disruption of contacts between neuronal processes can be visualized. Gachapin-C enables contact visualization with a single indicator component, whereas previous indicators required two components introduced into different cells. This feature allows Gachapin-C to monitor contacts between processes originating from a single cell. We expect Gachapin and Gachapin-C will serve as useful tools for providing deeper insights into cell-cell contact-mediated processes.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Kanadome", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Hoshino", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Jitsuki", "name": null }, { "creator_type": "author", "first_name": "Hidehiko", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.crmeth.2025.101292" }, "pmcid": { "normalized": "PMC12946757" }, "pmid": { "normalized": "41579865" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": true }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Feb 23", "date_precision": "day", "issue": "2", "normalized_date": "2026-02-23", "pages": "101292", "proceedings_title": null, "publisher": "", "title": "Cell reports methods", "volume": "6", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Fluorescent indicators for visualizing dynamic contact between cells and between processes originating from a single cell.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Brian D.", "last_name": "Stadinski", "name": null }, { "creator_type": "author", "first_name": "Elizabeth A.", "last_name": "Mills", "name": null }, { "creator_type": "author", "first_name": "Preston A.", "last_name": "Humphries", "name": null }, { "creator_type": "author", "first_name": "Sarah B.", "last_name": "Cleveland", "name": null }, { "creator_type": "author", "first_name": "Parker", "last_name": "Dow", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Yue Ru", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Byron B.", "last_name": "Au-Yeung", "name": null }, { "creator_type": "author", "first_name": "Gerald P.", "last_name": "Morris", "name": null }, { "creator_type": "author", "first_name": "Juan Carlos", "last_name": "Zuniga-Pflucker", "name": null }, { "creator_type": "author", "first_name": "Robert A.", "last_name": "Campbell", "name": null }, { "creator_type": "author", "first_name": "Eric R.", "last_name": "Griffiths", "name": null }, { "creator_type": "author", "first_name": "Eric S.", "last_name": "Huseby", "name": null }, { "creator_type": "author", "first_name": "Wan-Lin", "last_name": "Lo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41590-026-02469-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41714739" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Feb 19", "date_precision": "day", "issue": "", "normalized_date": "2026-02-19", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature immunology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Author Correction: Age-dependent Zap70 expression in thymocytes regulates selection of the neonatal regulatory T cell repertoire.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUNDS: The cellular slime mold Dictyostelium discoideum is a widely used model system for studying basic processes in cell and developmental biology. While genetic tools, such as targeted gene disruption by homologous recombination and genome editing using CRISPR/Cas9, are well-established in D. discoideum, efficient methods for conditional loss-of-function studies are limited. Here, we developed a nanobody-based degron system for D. discoideum based on ALFA-tagged protein recruitment to the Skp1-Cullin-F-box (SCF) complex. RESULTS: ALFA-tagged Histone H1 was efficiently degraded by expressing anti-ALFA nanobody (NbALFA) fused to the D. discoideum FbxD F-box domain ('dictyGrad-ALFA'). Cell type-specific targeting was achieved by expressing dictyGrad-ALFA under prestalk- and prespore-specific gene promoters. Furthermore, targeting of adenylyl cyclase A (ACA) resulted in the expected aggregation-deficient phenotype, validating the efficacy of dictyGrad-ALFA-mediated protein depletion. Cell type-specific ACA degradation delayed development but eventually resulted in normal fruiting bodies. Our ALFA-tag approach was further used for conditional knockdown in combination with the auxin-inducible degron 2 (AID2) system, which relies on indole-3-acetic acid (IAA)-dependent binding between NbALFA-mAID and a OsTIR-F-box-Skp1A fusion protein. We obtained efficient IAA-induced degradation in prestalk cells; however, efficiency was low in other cell types. CONCLUSIONS: Together, these systems pave the way for conditional and cell type-specific protein degradation in D. discoideum, enabling functional analyses of genes essential for growth and development.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hidenori", "last_name": "Hashimura", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Fujishiro", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Toyoko", "last_name": "Sugita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kuwana", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12860-026-00572-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41714934" } }, "mesh": [ { "descriptor": "Degrons", "descriptor_ui": "D000097791", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": true }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": true }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Proteolysis", "descriptor_ui": "D059748", "major_topic": false }, { "descriptor": "Protozoan Proteins", "descriptor_ui": "D015800", "major_topic": true }, { "descriptor": "Single-Domain Antibodies", "descriptor_ui": "D061905", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Feb 19", "date_precision": "day", "issue": "", "normalized_date": "2026-02-19", "pages": "", "proceedings_title": null, "publisher": "", "title": "BMC molecular and cell biology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "A nanobody-based degron system for targeted protein knockdown in Dictyostelium discoideum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Circadian clock genes are best known for regulating circadian rhythms, but they also play crucial roles in memory processes. This suggests that memory is modulated by neural networks containing clock neurons, although the underlying mechanisms remain unclear. In Drosophila melanogaster, approximately 240 clock neurons are grouped into at least eight distinct clusters. Among them, the dorsal-lateral neurons (LNds) are required for maintaining long-term memory (LTM). In contrast, the neuropeptide Pigment-dispersing factor (Pdf), expressed in both small and large ventral-lateral neurons (s-LNvs and l-LNvs, respectively), functions as a circadian output signal and is also essential for maintaining LTM. In addition, Pdf-expressing neurons (hereafter, Pdf neurons) release neurotransmitters other than Pdf, which are involved in LTM consolidation. However, the specific transmitters used by LNds and Pdf neurons in LTM processing have remained unknown. Here, we show that octopamine signaling from LNds is essential for LTM maintenance, whereas octopamine in Pdf neurons is essential for LTM consolidation. Temporally restricted knockdown of Tyramine beta hydroxylase (Tbh), the gene encoding the enzyme required for octopamine synthesis, disrupted LTM maintenance when targeted in LNds, whereas it impaired LTM consolidation when targeted in Pdf neurons. Notably, Tbh knockdown in LNds or Pdf neurons had minimal effects on circadian behavioral rhythms or sleep. These findings reveal that octopamine released from specific subtypes of clock neurons independently regulates distinct phases of LTM in Drosophila.", "classifications": [ { "id": "21H00434", "label": "21H00434", "researcher": "Takaomi Sakai", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuto", "last_name": "Kurata", "name": null }, { "creator_type": "author", "first_name": "Taishi", "last_name": "Yoshii", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pgen.1012045" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41701772" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Circadian Clocks", "descriptor_ui": "D057906", "major_topic": true }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": true }, { "descriptor": "Memory, Long-Term", "descriptor_ui": "D057567", "major_topic": true }, { "descriptor": "Mixed Function Oxygenases", "descriptor_ui": "D006899", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Octopamine", "descriptor_ui": "D009655", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Feb 17", "date_precision": "day", "issue": "2", "normalized_date": "2026-02-17", "pages": "e1012045", "proceedings_title": null, "publisher": "", "title": "PLoS genetics", "volume": "22", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Octopamine signaling from clock neurons plays dual roles in Drosophila long-term memory.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The chicken (Gallusgallus) has long served as a vital model in developmental biology and agriculture. Recent advancements in genome editing, particularly through germ cell-mediated techniques, have significantly enhanced the generation of transgenic and gene-edited chickens. This review summarizes the development of avian gene-editing, including various germ cell ablation methods to improve germline transmission, as well as strategies for producing sterile surrogate recipients. We compare physical, chemical, irradiation-based, and genetic approaches for endogenous germ cell ablation, with a focus on emerging inducible sterility systems such as DAZL-iCaspase9 and gSAMURAI. We also highlight applications in non-chicken avian species and discuss future directions for avian genome engineering and surrogate host technologies.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yi-Chen", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.pep.2026.106903" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41713821" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Biotechnology", "descriptor_ui": "D001709", "major_topic": true }, { "descriptor": "Chickens", "descriptor_ui": "D002645", "major_topic": true }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": true }, { "descriptor": "Genetic Engineering", "descriptor_ui": "D005818", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Feb 17", "date_precision": "day", "issue": "", "normalized_date": "2026-02-17", "pages": "106903", "proceedings_title": null, "publisher": "", "title": "Protein expression and purification", "volume": "240", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Sterile chicken hosts for germline transmission: A review of recipient preparation strategies in avian biotechnology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Skeletal forms in vertebrates have been regarded as good models of morphological diversification. Fish fins show great diversity in form, with their supporting skeletal structure being classified into soft rays and spiny rays. In fish evolution, spiny-ray morphologies are known to be sometimes extremely modified; however, it remains unknown how the developmental mechanisms of spiny rays have contributed to their morphological diversification. By using the rainbowfish Melanotaenia praecox for examination of the extracellular matrix (ECM) and cell dynamics of spiny-ray development, we demonstrate that spiny-ray development is independent of the actinotrichia (needle-shaped collagen polymers at the tip of fins), which are known as an important ECM in soft-ray morphogenesis. Furthermore, we found that in the thorny spiny ray of the filefish Stephanolepis cirrhifer, the lateral protrusions are associated with BMP-positive osteoblast condensation, as in the spiny-ray tips in M. praecox and S. cirrhifer. Taken together, our findings reveal that osteoblast distribution and signaling-molecule intensity would contribute to spiny-ray modification. In comparison to soft ray development, the independence from actinotrichia in spiny rays would facilitate growth direction change, leading to their morphological diversification. This suggests that variation in cell distribution and ECM usage may be important contributors to morphological diversification, not only in Acanthomorpha, but also in other animal taxa.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhide", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Junpei", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Kamimura", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Sasano", "name": null }, { "creator_type": "author", "first_name": "Gembu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ansai", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Funayama", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-026-69180-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41690953" } }, "mesh": [ { "descriptor": "Animal Fins", "descriptor_ui": "D058500", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": false }, { "descriptor": "Bone Morphogenetic Proteins", "descriptor_ui": "D019485", "major_topic": false }, { "descriptor": "Collagen", "descriptor_ui": "D003094", "major_topic": true }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": false }, { "descriptor": "Fishes", "descriptor_ui": "D005399", "major_topic": true }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Osteoblasts", "descriptor_ui": "D010006", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Feb 14", "date_precision": "day", "issue": "", "normalized_date": "2026-02-14", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Actinotrichia-independent developmental mechanisms of spiny rays facilitate the morphological diversification of Acanthomorpha fish fins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Animals remain awake in unfamiliar environments to assess potential safety threats, a process involving changes in neuronal activity within sleep-wake regulatory brain regions. However, the specific circuits and neurotransmitters involved remain poorly understood. Here, we show that neurotensin (NTS) peptides in corticotropin-releasing factor (CRF) neurons of the lateral part of the interstitial nucleus of the posterior limb of the anterior commissure (IPACL) play a key role in maintaining wakefulness in response to environmental changes. Activation of IPACL(CRF) neurons increased wakefulness, whereas their inhibition or deletion of NTS reduced wakefulness in novel environments. These neurons are activated in response to exposure to a novel environment and project primarily to the substantia nigra pars reticulata (SNr) and release NTS, which modulates wakefulness. These findings suggest that NTS signaling from IPACL(CRF) neurons to the SNr is essential for sustaining wakefulness in unfamiliar or changing environments.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Chi Jung", "last_name": "Hung", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Sheikh Mizanur", "last_name": "Rahaman", "name": null }, { "creator_type": "author", "first_name": "Mikiyasu", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Jiahui", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Fukatsu", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Bito", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Takemoto-Kimura", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2521268123" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41650227" } }, "mesh": [ { "descriptor": "Amygdala", "descriptor_ui": "D000679", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Corticotropin-Releasing Hormone", "descriptor_ui": "D003346", "major_topic": false }, { "descriptor": "Environment", "descriptor_ui": "D004777", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neurotensin", "descriptor_ui": "D009496", "major_topic": true }, { "descriptor": "Substantia Nigra", "descriptor_ui": "D013378", "major_topic": false }, { "descriptor": "Wakefulness", "descriptor_ui": "D014851", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Feb 10", "date_precision": "day", "issue": "6", "normalized_date": "2026-02-10", "pages": "e2521268123", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "123", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Neurotensin in the extended amygdala maintains wakefulness in novel environments.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) contribute to the pathogenesis of traumatic brain injury (TBI), yet the cell type-specific roles of UPR pathways remain poorly understood. We previously identified endothelial cells (ECs) as a primary site of IRE1 pathway activation following brain injury. In this study, we investigated the role of endothelial IRE1 signaling in TBI using EC-specific IRE1 conditional knockout mice subjected to cortical ablation. Loss of IRE1 in ECs exacerbated blood-brain barrier (BBB) disruption, enhanced immune cell infiltration, amplified neuroinflammation, and expanded neuronal damage, ultimately leading to worsened neurological outcomes. RNA-sequencing revealed enrichment of interferon-related programs and identified Cxcl10 as an endothelial chemokine linked to the exacerbated leukocyte recruitment in endothelial IRE1 deficiency. Treatment with the chemical chaperone tauroursodeoxycholic acid (TUDCA) suppressed Cxcl10 expression both in vitro and in vivo, and significantly improved motor function following TBI. These findings reveal a critical role for endothelial IRE1 signaling in maintaining BBB integrity and restraining inflammation during the acute phase of TBI. Modulation of ER stress in brain ECs may represent a promising and accessible therapeutic strategy for reducing secondary injury after TBI.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Qiyan", "last_name": "Fan", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Takarada-Iemata", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Loc Dinh", "last_name": "Nguyen", "name": null }, { "creator_type": "author", "first_name": "Nahoko", "last_name": "Okitani", "name": null }, { "creator_type": "author", "first_name": "RongRong", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Tamatani", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Iwawaki", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Hori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41419-026-08461-2" }, "pmcid": { "normalized": "PMC12921219" }, "pmid": { "normalized": "41663365" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood-Brain Barrier", "descriptor_ui": "D001812", "major_topic": true }, { "descriptor": "Brain Injuries, Traumatic", "descriptor_ui": "D000070642", "major_topic": true }, { "descriptor": "Chemokine CXCL10", "descriptor_ui": "D054357", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum Stress", "descriptor_ui": "D059865", "major_topic": false }, { "descriptor": "Endoribonucleases", "descriptor_ui": "D004722", "major_topic": true }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neuroinflammatory Diseases", "descriptor_ui": "D000090862", "major_topic": true }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Taurochenodeoxycholic Acid", "descriptor_ui": "D013655", "major_topic": false }, { "descriptor": "Unfolded Protein Response", "descriptor_ui": "D056811", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Feb 9", "date_precision": "day", "issue": "1", "normalized_date": "2026-02-09", "pages": "210", "proceedings_title": null, "publisher": "", "title": "Cell death & disease", "volume": "17", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Endothelial IRE1 signaling maintains blood-brain barrier integrity and limits neuroinflammation after traumatic brain injury.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Adult-onset neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease that is pathologically characterized by eosinophilic hyaline intranuclear inclusions, mainly in astrocytes, and cerebral white matter degeneration. However, the pathogenesis underlying these neuropathological findings remains unclear. We previously reported an autopsy case of adult-onset NIID with characteristic perivascular findings. In that case, the perivascular areas were preserved despite cerebral white matter damage but dense glial fibrillary acidic protein-immunoreactive astrocytic processes were observed around the blood vessels. The present study examined 2 additional cases and confirmed that the above findings were common in patients with adult-onset NIID. To investigate the underlying pathophysiology behind these findings, immunohistochemistry was performed for proteins located in the astrocytic end-feet. In the cerebral white matter of all NIID cases, there was an altered distribution of aquaporin 4 (AQP4) with increased AQP4-immunopositive areas compared to control cases. These results suggest that the interaction between astrocytes and blood vessels, particularly involving water homeostasis, may be impaired in the cerebral white matter of patients with NIID.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Yoshii", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ayaki", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Tomohisa", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Terada", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Umemura", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Oeda", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Toyooka", "name": null }, { "creator_type": "author", "first_name": "Nobuhisa", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Harutoshi", "last_name": "Fujimura", "name": null }, { "creator_type": "author", "first_name": "Takakuni", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Nobukatsu", "last_name": "Sawamoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Hanakawa", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Hideto", "last_name": "Senzaki", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Riki", "last_name": "Matsumoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jnen/nlag002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41651466" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aquaporin 4", "descriptor_ui": "D051401", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": true }, { "descriptor": "Blood Vessels", "descriptor_ui": "D001808", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intranuclear Inclusion Bodies", "descriptor_ui": "D045586", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neurodegenerative Diseases", "descriptor_ui": "D019636", "major_topic": true }, { "descriptor": "White Matter", "descriptor_ui": "D066127", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Feb 6", "date_precision": "day", "issue": "", "normalized_date": "2026-02-06", "pages": "nlag002", "proceedings_title": null, "publisher": "", "title": "Journal of neuropathology and experimental neurology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Astrocyte-vascular interactions are disturbed in cerebral white matter of adult-onset neuronal intranuclear inclusion disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The neocortex is essential for higher-order brain functions such as cognition, perception, language, and motor control. Although extracellular signal-regulated kinase (ERK) activity in neurons has been well studied for its role in memory formation, its activity patterns in the awake mice brain remain unclear. This study aimed to investigate the spatiotemporal dynamics of ERK activity in neocortical neurons of awake mice using in vivo imaging. We used Forster resonance energy transfer (FRET)-based biosensor and two-photon microscopy to examine ERK activity in vivo through a cranial window. Visual cortical neurons exhibited NMDA receptor-dependent ERK activation in response to visual stimuli. Beyond stimulus-induced activation, we discovered spontaneous and stochastic ERK activation patterns categorized as single, multi-pulsatile, and sustained activations, which were consistent across various cortical regions, including the visual and somatosensory cortices. Furthermore, synchronized ERK activation among neurons was observed, suggesting a coordinated ERK activation mechanism within neuronal networks that may contribute to sensory information processing. These findings reveal a highly dynamic ERK activation in neocortical cells and provide new insights regarding the functional role of ERK in the awake brain.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ceylin", "last_name": "Zeybek", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Yukinaga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2026.105032" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41638362" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": true }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence, Multiphoton", "descriptor_ui": "D036641", "major_topic": false }, { "descriptor": "Neocortex", "descriptor_ui": "D019579", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Photic Stimulation", "descriptor_ui": "D010775", "major_topic": false }, { "descriptor": "Receptors, N-Methyl-D-Aspartate", "descriptor_ui": "D016194", "major_topic": false }, { "descriptor": "Stochastic Processes", "descriptor_ui": "D013269", "major_topic": false }, { "descriptor": "Visual Cortex", "descriptor_ui": "D014793", "major_topic": false }, { "descriptor": "Wakefulness", "descriptor_ui": "D014851", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Feb 2", "date_precision": "day", "issue": "", "normalized_date": "2026-02-02", "pages": "105032", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000477" ] }, "title": "In Vivo Two-Photon Imaging Reveals Stochastic and Synchronized Extracellular Signal-Regulated Kinase Dynamics in Neurons of Awake Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Osteosarcoma remains largely refractory to immune checkpoint inhibitor (ICI) monotherapy, and strategies to modulate the tumor immune microenvironment are being actively explored. Mild hyperthermia has been reported to influence antitumor immune responses; however, its impact in combination with PD-1 blockade in osteosarcoma has not been well characterized. Methods: Murine LM8 osteosarcoma cells were subjected to mild thermal stimulation, and changes in PD-L1 expression were evaluated. LM8-bearing mice were treated with mild hyperthermia, anti-PD-1 antibody, or their combination. Tumor growth, lung metastasis, and survival were assessed. Tumor-infiltrating immune cells were profiled using single-cell RNA sequencing to descriptively characterize immune-associated transcriptional features under each treatment condition. Results: Mild thermal stimulation (42 degrees C, 30 min) increased PD-L1 expression in LM8 cells in vitro. In vivo, combination therapy significantly suppressed primary tumor growth compared with control (chi(2) = 29.75, p = 1.6 x 10(-6)) and reduced lung metastasis burden, with a significant decrease in metastatic nodules (p < 0.01). Kaplan-Meier analysis demonstrated a significant survival benefit in the combination group (log-rank p < 0.001). Single-cell RNA sequencing revealed an increased proportion of CD8(+) T cells with reduced exhaustion-associated gene expression and a shift toward pro-inflammatory (M1-like) macrophage transcriptional profiles. Conclusions: PD-1 blockade combined with mild hyperthermia was associated with enhanced antitumor efficacy and immune-associated transcriptional remodeling in a murine osteosarcoma model, supporting further preclinical evaluation of this combination strategy.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuya", "last_name": "Izubuchi", "name": null }, { "creator_type": "author", "first_name": "Naoi", "last_name": "Hosoe", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tatsunobu", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Matsumine", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biomedicines14020341" }, "pmcid": { "normalized": "PMC12937843" }, "pmid": { "normalized": "41751240" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Feb 1", "date_precision": "day", "issue": "2", "normalized_date": "2026-02-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biomedicines", "volume": "14", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Antitumor Effects of PD-1 Blockade Combined with Mild Hyperthermia in a Murine Osteosarcoma Model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Diurnal and nocturnal mammals occupy opposite temporal niches, but whether the suprachiasmatic nucleus (SCN), the central circadian pacemaker, follows the same intrinsic rules for timing adjustment and network coordination across species is unknown. Because SCN clock gene rhythms and population-level activity measurements look broadly similar across species, the prevailing interpretation in comparative studies has been that temporal niche differences are implemented upstream or downstream of the SCN. However, these coarse readouts do not test how clock resetting depends on circadian phase or how neuronal timing is coordinated across SCN space. Here, we combined long-duration ex vivo SCN recordings with optogenetic stimulation to compare SCN network dynamics in the nocturnal mouse (Mus musculus) and the diurnal four-striped grass mouse (Rhabdomys pumilio). Rhabdomys SCN molecular clock rhythms exhibited a longer intrinsic period and, under the same daily stimulation protocol, converged on a larger absolute phase angle relative to the stimulus. Molecular clock phase response curves differed in overall structure across circadian time between species, including pronounced early subjective day delays in Rhabdomys when Mus responses were minimal. Phase mapping of single-cell SCN calcium rhythms revealed species-specific spatial timing organization, with a graded dorsomedial-to-ventrolateral phase progression in Rhabdomys and a sharper transition in Mus. The Mus and Rhabdomys SCN can thus appear similar by coarse readouts yet diverge in phase-dependent molecular clock resetting and network timing organization. These results indicate that models placing temporal niche divergence solely outside the SCN are mechanistically incomplete.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Vanessa", "last_name": "Muhl", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Jeff R.", "last_name": "Jones", "name": null } ], "identifiers": { "doi": { "normalized": "10.64898/2026.01.28.702429" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jan 29", "date_precision": "day", "issue": null, "normalized_date": "2026-01-29", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Diurnality reconfigures circadian network dynamics in the suprachiasmatic nucleus.", "url": "", "zotero": { "item_type": "preprint" } }, { "abstract": "Functional neural circuits are sculpted by strengthening frequently used synapses and removing unnecessary connections. At birth, cerebellar Purkinje cells receive inputs with similar synaptic strengths from multiple climbing fibers (CFs). During postnatal development, a single \"winner\" CF is selectively strengthened and expands its dendritic innervation territory, while somatic \"loser\" synapses are eliminated. Here, we report that deleting metabotropic glutamate receptor 1 (mGluR1) or protein kinase Cgamma (PKCgamma) in mice disrupts this selective strengthening and territory expansion of \"winner\" CFs during early development. This impairment leads to weaker synaptic transmission and diminished dendritic innervation territory of \"winner\" CFs at later stages. Notably, \"winner\" CF synapses in these mutants exhibit impaired long-term potentiation, reduced AMPA receptor expression, and simpler postsynaptic organizations. These findings reveal a previously unappreciated role for mGluR1-PKCgamma signaling, besides its established role in eliminating \"loser\" CFs, in promoting the functional and structural maturation of \"winner\" CF synapses.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Miwako", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Takei", "name": null }, { "creator_type": "author", "first_name": "Atsu", "last_name": "Aiba", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2425460123" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41576075" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": true }, { "descriptor": "Long-Term Potentiation", "descriptor_ui": "D017774", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Nerve Fibers", "descriptor_ui": "D009412", "major_topic": true }, { "descriptor": "Protein Kinase C", "descriptor_ui": "D011493", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Receptors, AMPA", "descriptor_ui": "D018091", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jan 27", "date_precision": "day", "issue": "4", "normalized_date": "2026-01-27", "pages": "e2425460123", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "123", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "mGluR1 signaling is necessary for strengthening winner climbing fiber inputs in the developing mouse cerebellum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Some animals, such as primates and insects have color vision including sensitivity to red light (red vision). Red vision is basically achieved through opsins sensitive to the red region (red opsins), which independently evolved in different lineages. In dragonfly red vision, which is known to sense longer-wavelength light compared with humans, however, the underlying opsins and the spectral tuning mechanism are largely unknown. Here we investigated dragonfly opsins and found that RhLWA2s are the longest-wavelength-sensitive opsins, so-called red opsins in dragonflies. Spectroscopic analysis of the recombinant pigment of RhLWA2 from Asiagomphus melaenops (Am_RhLWA2) revealed that it has an absorption maximum at 580 nm and exhibits bistability, indicating that Am_RhLWA2 is the longest-wavelength-sensitive bistable opsin to date. Mutational analysis of Am_RhLWA2 revealed that position 292 is responsible for the red shift. The spectral tuning site as well as the mechanism for the red shift (S292A) is shared with that of mammalian red opsins, showing parallel evolution between mammalian and insect green/red opsins, and the substitution from Ala to Val (A292V) in a dragonfly lineage further enhanced the red sensitivity to near-infrared region. Furthermore, we succeeded in engineering red-shifted Am_RhLWA2 mutant having an absorption maximum at 590 nm by introducing V211C mutation. Cultured cells expressing the red-shifted Am_RhLWA2 mutant exhibited significant Ca(2+) responses to 738 nm light, showing the potential of near-infrared sensitive optogenetic tools to control GPCR-signaling. Based on the analysis of body coloration of a related dragonfly species, the longer-wavelength sensitivity of Am_RhLWA2 could confer an advantage in sex recognition. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-025-06017-9.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00018-025-06017-9" }, "pmcid": { "normalized": "PMC12824042" }, "pmid": { "normalized": "41559344" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Color Vision", "descriptor_ui": "D055253", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Odonata", "descriptor_ui": "D063191", "major_topic": true }, { "descriptor": "Opsins", "descriptor_ui": "D055355", "major_topic": true }, { "descriptor": "Red Light", "descriptor_ui": "D000095742", "major_topic": false }, { "descriptor": "Rod Opsins", "descriptor_ui": "D017299", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jan 20", "date_precision": "day", "issue": "1", "normalized_date": "2026-01-20", "pages": "66", "proceedings_title": null, "publisher": "", "title": "Cellular and molecular life sciences : CMLS", "volume": "83", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Dragonfly red opsins share a common tuning mechanism with mammalian red opsins and further enhancement of near-infrared sensitivity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The interplay of sleep quality, social hierarchy, and social isolation remains elusive. We evaluated such interplay using two mouse lines: C57BL/6J (B6) mice with relatively weak social hierarchy, and ICRxB6 F1 hybrid mice with relatively robust social hierarchy. Considering the potential effects of group housing on sleep - both through direct physical contact and other social interactions, which complicates interpretation-we designed a neighbor-housing condition that eliminates effects of direct physical contact while preserving social context. Under this condition, sleep architecture did not differ significantly between dominant and subordinate mice of either line. Under the single-housing condition, sleep differences emerged, some of which depended on both social rank and mouse line. In both mouse lines, single housing had opposite effects on oscillatory activities during sleep between dominant and subordinate mice. Notably, single housing significantly increased rapid eye movement sleep (REMS) amount only in subordinate B6 mice, but not in subordinate F1 hybrids or dominant mice of either lines, suggesting a genetically modulated sensitivity to social conditions. Our findings suggest complicated interactions between social environment, social hierarchy, and genetic factors in REMS regulation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naoko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-32402-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41554797" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hierarchy, Social", "descriptor_ui": "D006608", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Sleep, REM", "descriptor_ui": "D012895", "major_topic": true }, { "descriptor": "Social Dominance", "descriptor_ui": "D012930", "major_topic": false }, { "descriptor": "Social Environment", "descriptor_ui": "D012931", "major_topic": true }, { "descriptor": "Social Isolation", "descriptor_ui": "D012934", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jan 19", "date_precision": "day", "issue": "1", "normalized_date": "2026-01-19", "pages": "871", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "16", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Social rank and social environment combinedly affect REM sleep in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Living with COVID-19 requires continued vigilance against the spread and emergence of variants of concern (VOCs). Rapid and accurate saliva diagnostic testing, alongside basic public health responses, is a viable option contributing to effective transmission control. Nevertheless, our knowledge regarding the dynamics of SARS-CoV-2 infection in saliva is not as advanced as our understanding of the respiratory tract. Here, we analyzed longitudinal viral load data of SARS-CoV-2 in saliva samples from 144 patients with mild COVID-19 (a combination of our collected data and published data). Using a mathematical model, we quantified individual-level viral dynamics and stratified them into three groups using a clustering approach. Notably, the three groups exhibited distinct differences in viral RNA detection durations: 11.5 days (95% CI: 10.6-12.4), 17.4 days (16.6-18.2), and 30.0 days (28.1-31.8), respectively. Surprisingly, this stratified grouping remained unexplained despite our analysis of 47 types of clinical data, including basic demographic information, clinical symptoms, results of blood tests, and vital signs. Additionally, we quantified the expression levels of 92 micro-RNAs in a subset of saliva samples, but these also failed to explain the observed stratification, although the mir-1846 level may have been weakly correlated with peak viral load. Our study provides insights into SARS-CoV-2 infection dynamics in saliva, highlighting the challenges in predicting the duration of viral RNA detection without indicators that directly reflect an individual's immune response, such as antibody induction. Given the significant individual heterogeneity in the kinetics of saliva viral shedding, identifying biomarker(s) for viral shedding patterns will be crucial for improving public health interventions in the era of living with COVID-19.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hyeongki", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Yoshimura", "last_name": "Raiki", "name": null }, { "creator_type": "author", "first_name": "Shoya", "last_name": "Iwanami", "name": null }, { "creator_type": "author", "first_name": "Kwangsu", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Ejima", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Yoshitsugu", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Umeyama", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Miyazawa", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Watashi", "name": null }, { "creator_type": "author", "first_name": "Christopher B.", "last_name": "Brooke", "name": null }, { "creator_type": "author", "first_name": "Ruian", "last_name": "Ke", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Iwami", "name": null }, { "creator_type": "author", "first_name": "Taiga", "last_name": "Miyazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.96032" }, "pmcid": { "normalized": "PMC12810952" }, "pmid": { "normalized": "41543519" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Longitudinal Studies", "descriptor_ui": "D008137", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": false }, { "descriptor": "RNA, Viral", "descriptor_ui": "D012367", "major_topic": false }, { "descriptor": "Saliva", "descriptor_ui": "D012463", "major_topic": true }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true }, { "descriptor": "Viral Load", "descriptor_ui": "D019562", "major_topic": false }, { "descriptor": "Virus Shedding", "descriptor_ui": "D017201", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jan 16", "date_precision": "day", "issue": "", "normalized_date": "2026-01-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "13", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Stratification of viral shedding patterns in saliva of COVID-19 patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The development of efficient strategies for constructing cyclic organosilicon frameworks is considered of great importance because of their structural diversity and synthetic utility. Herein, we report a SmI(2)/Sm-mediated silacyclization of unsaturated organic compounds with readily available dichlorosilanes and -disilanes, enabling convenient access to 4-7-membered silacyclic compounds. Mechanistic investigations indicate that the reaction involves silyl radical intermediates and proceeds via a reductive radical-polar crossover (RRPCO) pathway. The present findings showcase the broad potential of Sm reagents in Si horizontal line C bond formation, providing a versatile strategy for constructing diverse silicon-containing frameworks.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Zhengwei", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Daigo", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Mizota", "name": null }, { "creator_type": "author", "first_name": "Leo", "last_name": "Onishi", "name": null }, { "creator_type": "author", "first_name": "Huiying", "last_name": "Mu", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Akiya", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/chem.202503424" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41543218" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jan 16", "date_precision": "day", "issue": "", "normalized_date": "2026-01-16", "pages": "e03424", "proceedings_title": null, "publisher": "", "title": "Chemistry (Weinheim an der Bergstrasse, Germany)", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "SmI(2)/Sm-Induced Reductive Silacyclization of Alkene/Diene Derivatives Using Dichlorosilanes or 1,2-Dichlorodisilanes via Reductive Radical-Polar Crossover.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Abnormal accumulation of alpha-synuclein (alpha-syn) is a central pathologic hallmark of synucleinopathies such as Parkinson's disease (PD), with rapid eye movement sleep behavior disorder (RBD) widely recognized as a prodromal manifestation of these disorders. Although several mouse models recapitulate the alpha-syn pathology, most fail to reproduce the brainstem-originating pathology propagation proposed by Braak and do not exhibit the RBD-like phenotypes expected in the prodromal phase. Here, we focused on the G51D mutation of alpha-syn, a familial PD-associated variant that leads to early disease onset and severe clinical symptoms. We microinjected G51D mutant alpha-syn fibrils into the pontine tegmental area of the brainstem in mice, a region critically involved in REM sleep regulation, and evaluated the effects on sleep architecture, pathologic progression, and motor function. Our results revealed that microinjection of G51D fibrils into the brainstem induces more extensive pathologic changes compared with wild-type fibrils and leads to the sequential emergence of RBD-like behaviors, motor deficits, and dopaminergic neuronal loss. These findings support the hypothesis that the G51D mutation worsens disease severity and establish this model as a valuable tool for investigating the mechanisms underlying synucleinopathies and their prodromal symptoms.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Yasugaki", "name": null }, { "creator_type": "author", "first_name": "Ami", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Hibiki", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Ikenaka", "name": null }, { "creator_type": "author", "first_name": "Cesar", "last_name": "Aguirre", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Kousuke", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2026.105023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41548850" } }, "mesh": [ { "descriptor": "alpha-Synuclein", "descriptor_ui": "D051844", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain Stem", "descriptor_ui": "D001933", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Dopaminergic Neurons", "descriptor_ui": "D059290", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "REM Sleep Behavior Disorder", "descriptor_ui": "D020187", "major_topic": true }, { "descriptor": "Synucleinopathies", "descriptor_ui": "D000080874", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jan 16", "date_precision": "day", "issue": "", "normalized_date": "2026-01-16", "pages": "105023", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "A novel brainstem-targeted G51D alpha-synuclein fibril-injected mouse model exhibits sequential emergence of sleep and motor dysfunction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Coronavirus disease 2019 (COVID-19) pneumonia is prevalent in the elderly infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, the mechanisms underlying its age-dependent pathogenesis remain unclear. In this study, we established a mouse-adapted SARS-CoV-2 strain infected Nr4a3-Tocky mouse model to examine T-cell dynamics associated with disease severity. Nr4a3-Tocky mice allow the analysis of the dynamics and induction of antigen-reactive T cells following antigen recognition in vivo using fluorescent Timer protein. SARS-CoV-2-infected adult mice exhibited transient body weight loss and recovery, whereas aged mice developed severe pneumonia. BALF viral RNA was comparable between 1-4 days post-infection (d.p.i.), but declined in adults at 5 d.p.i. Aged mice displayed stronger inflammation as indicated by scRNA-seq, and higher levels of inflammatory cytokines (TNF-alpha, CCL2, CXCL10 and IL-6) in BALF correlated with weight loss. Timer analysis revealed induction of antigen-reactive T cells in the adult lungs at 5 and 8 d.p.i., which inversely correlated with disease severity. Additionally, S-specific IFN-gamma (+) CD8 (+) T cells were detected at 5 d.p.i. in adults, whereas detection of antigen-specific T cells was delayed in aged mice. These results suggest that the coexistence of age-related lung inflammation and delayed induction of antigen-specific T cells is linked to more severe pneumonia, while earlier T-cell responses are associated with improved viral control and milder disease. In this study, we utilized a novel mouse model enabling characterization of antigen-reactive T cells in the local tissue, and investigated inflammatory responses in the lung together with lung-infiltrating virus-specific T cells, finding the dynamics of these immunological parameters associated with the age of the mice. Our analysis provides new insights into understanding how age-related T-cell dysfunction is associated with the severity of SARS-CoV-2 pneumonia.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Rise", "last_name": "Kurokawa", "name": null }, { "creator_type": "author", "first_name": "Chatherine Silas", "last_name": "Mtali", "name": null }, { "creator_type": "author", "first_name": "Innocent John", "last_name": "Daniel", "name": null }, { "creator_type": "author", "first_name": "Thorbjorg", "last_name": "Einarsdottir", "name": null }, { "creator_type": "author", "first_name": "Omnia", "last_name": "Reda", "name": null }, { "creator_type": "author", "first_name": "Nobuko", "last_name": "Irie", "name": null }, { "creator_type": "author", "first_name": "Wajihah", "last_name": "Sakhor", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Niimura", "name": null }, { "creator_type": "author", "first_name": "Mitsuyoshi", "last_name": "Takatori", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sugata", "name": null }, { "creator_type": "author", "first_name": "Chanidapa Adele", "last_name": "Tye", "name": null }, { "creator_type": "author", "first_name": "Yorifumi", "last_name": "Satou", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Takushi", "last_name": "Nomura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.ppat.1013866" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41533733" } }, "mesh": [ { "descriptor": "Age Factors", "descriptor_ui": "D000367", "major_topic": false }, { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bronchoalveolar Lavage Fluid", "descriptor_ui": "D001992", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false }, { "descriptor": "Severity of Illness Index", "descriptor_ui": "D012720", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jan 14", "date_precision": "day", "issue": "1", "normalized_date": "2026-01-14", "pages": "e1013866", "proceedings_title": null, "publisher": "", "title": "PLoS pathogens", "volume": "22", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamics of lung-infiltrating virus-specific T cells associated with age-dependent SARS-CoV-2 pneumonia severity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Seo", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Masumoto", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Takeru", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Ise", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Sugino", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Zen-Ichi", "last_name": "Tanei", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Bunsho", "last_name": "Asayama", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Yoshinao", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/pin.70064" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41533502" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jan 14", "date_precision": "day", "issue": "", "normalized_date": "2026-01-14", "pages": "e70064", "proceedings_title": null, "publisher": "", "title": "Pathology international", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Pitfall of the Diagnosis of Extramedullary Tumor: A Case of Intracranial Mesenchymal Tumor, FET::CREB Fusion-Positive Occurring in an Atypical Clinical Setting.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Interleukin-17-producing gammadeltaT cells (gammadeltaT17 cells) play a dual role in immune regulation, serving as both protectors in various tissues and orchestrators of inflammatory responses in autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), a rodent model of multiple sclerosis. However, the ontology and repertoires of encephalitogenic gammadeltaT17 cells remain unclear. In this study, we demonstrate that the encephalitogenicity of gammadeltaT17 cells is conferred through microfold cell (M cell)-dependent uptake of commensal bacteria in Peyer's patches. Specifically, CXCR6(hi)Vgamma6(+)Vdelta1(+) invariant gammadeltaT17 cells are activated by specific commensal bacteria such as Lactobacillus spp., which stimulate TCR of CXCR6(hi)Vgamma6(+)Vdelta1(+) invariant gammadeltaT17 cells. During the early stages of EAE, gammadeltaT17 cells infiltrate the central nervous system (CNS), initiating a type 17 inflammatory response. Our findings illustrate that Peyer's patch M cells serve as a critical bridge, linking the pathological association between commensal bacteria and the onset of CNS inflammation.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Seiga", "last_name": "Komiyama", "name": null }, { "creator_type": "author", "first_name": "Rae", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Saeki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kinashi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Oguchi", "name": null }, { "creator_type": "author", "first_name": "Kokona", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Onawa", "name": null }, { "creator_type": "author", "first_name": "Ako", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Kisara", "last_name": "Hattori-Muroi", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Fujimura", "name": null }, { "creator_type": "author", "first_name": "Yuyo", "last_name": "Ka", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Watarai", "name": null }, { "creator_type": "author", "first_name": "Tsuneyasu", "last_name": "Kaisho", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Udagawa", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Hase", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2506550123" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41512014" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Encephalomyelitis, Autoimmune, Experimental", "descriptor_ui": "D004681", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Interleukin-17", "descriptor_ui": "D020381", "major_topic": false }, { "descriptor": "Lactobacillus", "descriptor_ui": "D007778", "major_topic": false }, { "descriptor": "M Cells", "descriptor_ui": "D000092303", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Peyer's Patches", "descriptor_ui": "D010581", "major_topic": true }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell, gamma-delta", "descriptor_ui": "D016692", "major_topic": true }, { "descriptor": "Th17 Cells", "descriptor_ui": "D058504", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jan 13", "date_precision": "day", "issue": "2", "normalized_date": "2026-01-13", "pages": "e2506550123", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "123", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "M cell-dependent commensal uptake confers encephalitogenic phenotypes on gammadeltaT17 cells in Peyer's patches.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Retinitis pigmentosa (RP) is an inherited progressive retinal degeneration that shows symptoms of night blindness, visual field loss, declining of vision and eventually, blindness. Currently, gene therapy and retinal prosthesis are available, but the indication for these treatments is limited. In this study, we report on the development of a diagnostic and prognostic model for RP based on large-scale deep learning (DL) models pre-trained with fundus images. The EfficientNetB4 model performed best in diagnosing RP with an AUC of 0.94. The diagnosis of RP with this model is superior in cases with good vision. For visual prognosis, we applied machine learning survival analysis to DL-derived image features and clinical metadata, using a strict patient-level split to avoid data leakage. The hybrid model combining imaging and clinical data outperformed models based on either modality alone, especially in female patients. Time-dependent AUC analysis showed that prognostic performance was highest between 500 and 1400 days after examination. SHAP-based interpretability analysis revealed that the features contributing to RP diagnosis and those associated with prognosis were distinct. While our findings demonstrate the added value of fundus images in visual outcome prediction, further validation using external and multi-center datasets is necessary for clinical translation.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Koya", "last_name": "Homma", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Kawamata", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41746-025-02311-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41507439" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jan 8", "date_precision": "day", "issue": "", "normalized_date": "2026-01-08", "pages": "", "proceedings_title": null, "publisher": "", "title": "NPJ digital medicine", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Leveraging large scale deep learning models for diagnosis and visual outcome prediction in retinitis pigmentosa.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The systematic culling of male layer chicks raises ethical concerns, leading to bans in Germany and other European countries and spurring the search for reliable in-ovo sexing methods. Most existing strategies rely on integration of exogenous DNA or are limited to specific chicken strains, and none meet commercial requirements. Here, we present a broadly applicable in-ovo sexing method that avoids exogenous DNA integration. We developed precision-bred chickens with targeted disruption of the Z-linked SLC45A2 gene, which encodes a transporter essential for pigmentation. Hemizygous knockout females (ZW; SLC45A2(KO/W)) exhibited eye depigmentation at embryonic day 7 (E7), whereas heterozygous knockout males (ZZ; SLC45A2(KO/+)) retained normal pigmentation. This clear visual dimorphism enables accurate sexing by routine egg candling. Fertility and reproductive performance of knockouts were comparable to wild-type chickens, and genotyping confirmed 100% prediction accuracy. Unlike many current technologies, our approach requires no complex instrumentation and allows early detection during incubation. This work provides a practical and ethical solution to chick sexing, with significant advantages for commercial hatcheries. More broadly, this study illustrates the potential of precision breeding to address pressing animal welfare concerns in the modern poultry industry.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yi-Chen", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Shuo-Wen", "last_name": "Hsu", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Shimokita", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fbioe.2026.1785893" }, "pmcid": { "normalized": "PMC13079324" }, "pmid": { "normalized": "41993716" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026", "date_precision": "year", "issue": "", "normalized_date": "2026", "pages": "1785893", "proceedings_title": null, "publisher": "", "title": "Frontiers in bioengineering and biotechnology", "volume": "14", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Eye pigmentation-based in-ovo chicken sexing via precision breeding.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reactive sulfur species (RSS), which include various persulfides and polysulfides, are generated by multiple enzymes in vivo and play critical roles in mammalian physiological processes such as redox signaling, metabolic regulation, radical scavenging and anti-inflammatory responses. Cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3MST) are well known to mediate endogenous production of hydrogen sulfide (H(2)S), and, together with the mitochondrial isoform of cysteinyl-tRNA synthetase (CARS2), are proposed to be major sources of intracellular persulfides and polysulfides. In mitochondria, enzymes involved in the sulfide oxidation pathway, including sulfide:quinone oxidoreductase (SQOR), persulfide dioxygenase (ETHE1) and thiosulfate sulfurtransferase (TST), also contribute to maintaining and regulating intracellular persulfide levels. Selective inhibitors targeting these enzymes are expected to be powerful tools for elucidating the functions of RSS, as well as having therapeutic potential. In this review, we present a comprehensive overview of these enzymes, focusing on their reaction mechanisms and inhibitors.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ko", "last_name": "Hirabayashi", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Orie", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fphys.2026.1764165" }, "pmcid": { "normalized": "PMC12926118" }, "pmid": { "normalized": "41736950" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026", "date_precision": "year", "issue": "", "normalized_date": "2026", "pages": "1764165", "proceedings_title": null, "publisher": "", "title": "Frontiers in physiology", "volume": "17", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Enzymes that generate and regulate intracellular persulfides and polysulfides: mechanistic insights and inhibitors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: The immune response to non-pathogenic fungi entering the skin remains largely unknown. In this study, we focused on the fermentative filamentous fungus Aspergillus oryzae (Ao), which is traditionally utilized in Japan. METHODS: Mice were subcutaneously inoculated with the Ao conidia and skin-draining lymph nodes were harvested over time for flow cytometry to evaluate various immune cell subsets. Quantitative reverse transcription-PCR was also conducted to assess the cytokine expression (IFN-gamma, IL-4, IL-6, IL-10, IL-12, IL-17, TGF-beta, TNF-alpha) at 4 or 7 days after Ao inoculation. To detect antigen-specific antibody production, mice were immunized with Ao and/or ovalbumin in aluminum hydroxide adjuvant, and sera were collected at day -1, 14, and 35 for ELISA. Fluorescence immunohistostaining was employed to visualize the structural reorganization of the lymph nodes. Active cutaneous anaphylaxis reaction was assessed for the impact of Ao inoculation on allergic response. RESULTS: We observed a marked enlargement of skin-draining lymph nodes and increased immune cell numbers within days. Notably, this was characterized by a marked increase in the number of activated B cells and type 2 resident dendritic cells. These responses were partially reproduced by Ao cell wall components and purified beta-glucans; the Ao-dependent downregulation of Dectin-1 expression on dendritic cells supports these findings. However, live Ao elicited the most pronounced lymph node response, as heat inactivation and the cell wall fraction clearly attenuated it, suggesting that other components are also necessary. Ao appears to induce a relatively mild response in the lymph nodes, characterized by a marked increase in IL-4 expression, whereas other cytokines were suppressed or unaltered. In the long term, Ao entry elicited immune memory with antibody production specific to the conidial proteins and beta-glucan, although it did not enhance the antibody against another antigen/adjuvant. Furthermore, we found that pre-inoculation with Ao inhibited allergic responses. This is consistent with the novel effects of Ao inoculation, which reduces the CD301b(+) dendritic cells in lymph nodes while increases their PD-L1 expression. CONCLUSION: Transdermal Ao entry clearly induces adaptive immunity in draining lymph nodes. However, the response is not necessarily intense and shows an immunomodulatory aspect with less harmful or even beneficial effects, potentially suppressing allergic diseases.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Thanh Dat", "last_name": "Ta", "name": null }, { "creator_type": "author", "first_name": "Madoka", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Kasuga", "name": null }, { "creator_type": "author", "first_name": "Midori", "last_name": "Shida", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Kotani", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Hayasaka", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Tomura", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Umemoto", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2026.1815568" }, "pmcid": { "normalized": "PMC13310732" }, "pmid": { "normalized": "42375367" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aspergillus oryzae", "descriptor_ui": "D001236", "major_topic": true }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Immunomodulation", "descriptor_ui": "D056747", "major_topic": true }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026", "date_precision": "year", "issue": "", "normalized_date": "2026", "pages": "1815568", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "17", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Transdermal entry of a non-pathogenic filamentous fungus Aspergillus oryzae induces an immunomodulatory response in skin-draining lymph nodes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Influenza remains a global public health concern, and although the antiviral drug oseltamivir is widely used to treat infections, questions regarding its actual antiviral efficacy and clinical benefits remain. Here, we evaluated the effects of oseltamivir on viral shedding dynamics in the context of experimental influenza infection. We analyzed individual participant data, including viral load, time to symptom alleviation, and laboratory test measurements, obtained from three publicly available clinical trials involving experimental infections with influenza A and B viruses. We applied mathematical modeling and estimated parameters using a nonlinear mixed-effects model to capture viral infection dynamics. Our analysis revealed that, compared with placebo groups, the oseltamivir-treated groups tended to have lower values in terms of viral load area under the curve, duration of infection, peak viral titer, and time to peak; however, most of these differences were not significant; and no dose-dependent effects were observed. Moreover, there was no significant correlation between time to symptom alleviation and viral load. Some laboratory test parameters showed opposing correlations with symptom-related and viral load-related outcomes. These findings are consistent with distinct mechanisms underlying the symptom-alleviating effects of oseltamivir and its antiviral activity. Our findings suggest that the availability of individual-level data for public use is essential because it enables the evaluation of mechanisms in clinical trials and the development of more appropriate outcome measures.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Marwa", "last_name": "Akao", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Tatematsu", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Iwami", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Shoya", "last_name": "Iwanami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0342676" }, "pmcid": { "normalized": "PMC12890086" }, "pmid": { "normalized": "41666202" } }, "mesh": [ { "descriptor": "Antiviral Agents", "descriptor_ui": "D000998", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Influenza A virus", "descriptor_ui": "D009980", "major_topic": false }, { "descriptor": "Influenza B virus", "descriptor_ui": "D009981", "major_topic": false }, { "descriptor": "Influenza, Human", "descriptor_ui": "D007251", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Oseltamivir", "descriptor_ui": "D053139", "major_topic": true }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false }, { "descriptor": "Viral Load", "descriptor_ui": "D019562", "major_topic": false }, { "descriptor": "Virus Shedding", "descriptor_ui": "D017201", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026", "date_precision": "year", "issue": "2", "normalized_date": "2026", "pages": "e0342676", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "21", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Modeling viral shedding and symptom outcomes in oseltamivir-treated experimental influenza infection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sporadic Parkinson's disease (PD) is typically a late-onset disorder caused by a combination of genetics, environment, and aging, manifesting when the loss of midbrain dopaminergic neurons exceeds a critical threshold, usually after the age of 50. Conversely, early-onset PD, as observed in cases linked to parkin (PRKN) gene mutations, suggests mechanisms involving either accelerated postnatal neuron loss or an insufficient number of neurons at birth. Patients with the 22q11.2 deletion syndrome (DS) have a significantly higher prevalence of early-onset PD. The absence of known genes associated with hereditary PD in the deleted region suggests the involvement of novel, non-traditional risk factors. This could potentially implicate the neurodevelopmental origin of dopaminergic neurons arising from the floor plate. To investigate this hypothesis, we generated midbrain organoids from induced pluripotent stem cells derived from a patient with 22q11.2 DS. The organoids recapitulated key aspects of in vivo neurogenesis, revealing enhanced differentiation of dopaminergic neurons in 22q11.2DS- and PRKN-derived organoids compared to controls on days 28 and 56 of culture. These findings suggest that, in early-onset PD patients with 22q11.2 DS or PRKN mutation, enhanced neurogenesis could result in reduced number of dopaminergic neurons during early development. The organoids of early-onset PD demonstrated that progenitors undergo enhanced differentiation at an early stage. This suggests that the atypical developmental process could reduce progenitors before there are enough mature dopaminergic neurons. This in turn indicates that the onset of PD may occur as early as the embryonic stage.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Syugo", "last_name": "Ueki", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Tohge", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tamada", "name": null }, { "creator_type": "author", "first_name": "Mitsuaki", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Yakushiji", "name": null }, { "creator_type": "author", "first_name": "Haruhisa", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fncel.2026.1906023" }, "pmcid": { "normalized": "PMC13472798" }, "pmid": { "normalized": "42601939" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026", "date_precision": "year", "issue": "", "normalized_date": "2026", "pages": "1906023", "proceedings_title": null, "publisher": "", "title": "Frontiers in cellular neuroscience", "volume": "20", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Neurogenesis defects in iPSC-derived midbrain organoids of early-onset Parkinson's disease with 22q11.2 deletion syndrome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "KMT2C mutations are strongly associated with autism spectrum disorder (ASD). Whereas multiplexed CRISPR screens show complete KMT2C knockout impairs neuronal differentiation, mixed-genotype pools cannot exclude non-autonomous paracrine effects. Furthermore, the functional effect of partial loss of function remains unclear. Here, we targeted KMT2C via shRNA knockdown in single-genotype cultures of human induced pluripotent stem cell-derived neural stem cells. Reduced KMT2C expression decreased the neuronal markers MAP2, HuC/D, and DCX. Our results demonstrate that partial, strictly cell-autonomous KMT2C insufficiency impairs neuronal stem cell differentiation into neurons, modeling the haploinsufficiency observed in patients to reveal a neurodevelopmental pathogenesis for ASD.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masaya", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Mita", "name": null }, { "creator_type": "author", "first_name": "Yuuri", "last_name": "Ikeuchi", "name": null }, { "creator_type": "author", "first_name": "Hotaka", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.17912/micropub.biology.002149" }, "pmcid": { "normalized": "PMC13345183" }, "pmid": { "normalized": "42421807" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026", "date_precision": "year", "issue": "", "normalized_date": "2026", "pages": "", "proceedings_title": null, "publisher": "", "title": "microPublication biology", "volume": "2026", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "KMT2C Knockdown impairs neuronal differentiation in human induced pluripotent stem cell-derived neural stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Quantum dot single-particle tracking (QD-SPT), a powerful tool for analyzing membrane domains that are critical to various cellular processes, is widely used in membrane molecular dynamics research. QDs, which possess both a broad excitation range and a narrow emission bandwidth, are inherently suited for multicolor imaging at various wavelengths. However, applying multicolor QD-SPT with multiple biomolecular targets has been challenging due to the limited methods for specifically conjugating QDs to biomolecules. Here, we propose a DNA hybridization-based QD labeling method that generates several specific interactions based on sequence. QD fused with 20-mer oligo DNA specifically labeled membrane lipid 1,2-dipalmitoyl-sn-glycero-3-phosphatidylethanolamine (DPPE) covalently bound to complementary oligo DNA, forming a stable label that is suitable for SPT. The combination of polyA-polyT sequence as the linker oligo caused more QDs to fuse to DPPE compared with a random sequence linker. Oligo DNA-based QD-SPT accurately reflected the diffusion dynamics of DPPE measured using the single-fluorescence tracking technique and was compatible with conventional QD-SPT utilizing secondary antibody Fab. Using different pairs of oligo DNA sequences, we successfully achieved multicolor QD-SPT that distinguishes the lateral diffusion of DPPE and a membrane protein, GABA(A) receptor (GABA(A)R), within the same cell. The oligo DNA-based QD labeling method developed in this study is anticipated to substantially advance simultaneous multicolor QD-SPT of different living cell membrane molecules specific to DNA sequences.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shigeo", "last_name": "Sakuragi", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Boxiao", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Katagiri", "name": null }, { "creator_type": "author", "first_name": "Miyu", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Chisato", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Iona", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Teramura", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v23.0013" }, "pmcid": { "normalized": "PMC13310573" }, "pmid": { "normalized": "42371582" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026", "date_precision": "year", "issue": "2", "normalized_date": "2026", "pages": "e230013", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "23", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Oligo DNA-based quantum dot (QD) single-particle tracking for multicolor single-molecule imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stress-related disorders, such as depression and anxiety, have been one of the most important medical issues. Accumulating evidence suggests that the activation of the pituitary adenylate cyclase-activating polypeptide and its receptor PAC1 are involved in the stress axis and the development of stress-related disorders. We recently developed PA-915, a small-molecule, non-peptide, high-affinity PAC1 antagonist, and demonstrated that it significantly suppresses anxiety-like behavior in acute stress-induced mice. In this study, we aimed to investigate the behavioral effects of PA-915 in chronic stress-induced mouse models of depression, which included repeated social defeat stress, repeated corticosterone administration, and social isolation rearing. PA-915 ameliorated the increased immobility time in the forced swim test in these stress-induced mice. In repeated social defeat stress mice, PA-915 improved anxiety-like and depression-like behaviors and cognitive dysfunction, as assessed by the light-dark, open field, elevated plus maze, sucrose preference, forced swim, Y-maze, and novel object recognition tests. In addition, we evaluated the usefulness of PA-915 as an antidepressant and compared it with ketamine and fluoxetine. In the sucrose preference test, an antidepressant-like effect was observed for 8 weeks in mice that received a single dose of PA-915, which was a similar effect observed with ketamine. In non-stressed control mice, PA-915 did not induce behavioral abnormalities, such as hyperlocomotion, cognitive dysfunction, or dependency. The present results show that PA-915 improves anxiety-like behaviors and cognitive impairment and exerts rapid and long-lasting antidepressant effects in chronic stress-induced mouse models of anxiety and depression, proposing a promising treatment option for stress-related disorders.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Takasaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Atsuro", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Yamano", "name": null }, { "creator_type": "author", "first_name": "Manato", "last_name": "Ikuta", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Takeshita", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Taisei", "last_name": "Oguri", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Asaka", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Nunomura", "name": null }, { "creator_type": "author", "first_name": "Bangzhong", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Shinsaku", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Toyooka", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takumi", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41380-025-03209-4" }, "pmcid": { "normalized": "PMC12815653" }, "pmid": { "normalized": "40908362" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antidepressive Agents", "descriptor_ui": "D000928", "major_topic": true }, { "descriptor": "Anxiety", "descriptor_ui": "D001007", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Corticosterone", "descriptor_ui": "D003345", "major_topic": false }, { "descriptor": "Depression", "descriptor_ui": "D003863", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Ketamine", "descriptor_ui": "D007649", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Maze Learning", "descriptor_ui": "D018782", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I", "descriptor_ui": "D051237", "major_topic": true }, { "descriptor": "Social Defeat", "descriptor_ui": "D000083703", "major_topic": false }, { "descriptor": "Social Isolation", "descriptor_ui": "D012934", "major_topic": false }, { "descriptor": "Stress, Psychological", "descriptor_ui": "D013315", "major_topic": true }, { "descriptor": "Swimming", "descriptor_ui": "D013550", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "1014-1026", "proceedings_title": null, "publisher": "", "title": "Molecular psychiatry", "volume": "31", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Rapid and long-lasting antidepressant-like effects of the pituitary adenylate cyclase-activating polypeptide receptor antagonist PA-915 in chronic stress mouse models.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: To evaluate whether photocurable gelatin can provide effective hemostasis under stringent conditions in a rabbit partial nephrectomy model, in comparison with conventional fibrin glue. METHODS: A standardized partial nephrectomy model was established in ten male Japanese white rabbits by creating an 8-mm parenchymal defect. Animals were randomly assigned to receive either fibrin glue (Group A, n = 5) or photocurable gelatin activated by visible light using a ruthenium photoinitiator (Group B, n = 5). Blood loss before and after agent application was quantified, and the requirement for additional suturing was recorded. Histological evaluation was performed 7 days postoperatively. RESULTS: There was no significant difference in control bleeding between the two groups prior to agent application. After treatment, bleeding volume was significantly lower in the photocurable gelatin group than in the fibrin glue group. All rabbits treated with fibrin glue required additional suturing to achieve hemostasis, whereas none of the rabbits treated with photocurable gelatin required suturing. Histological analysis demonstrated milder inflammatory infiltration at the resection surface in the photocurable gelatin group. CONCLUSIONS: Under experimentally stringent conditions in which fibrin glue alone was insufficient, photocurable gelatin achieved effective hemostasis without the need for additional suturing. These findings suggested that photocurable gelatin has the physical robustness required to overcome the limitations of conventional fibrin sealants and may represent a promising adjunct for hemostasis in nephron-sparing surgery.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shinchi", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Ojima", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Yoshine", "last_name": "Mayumi", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Segawa", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Yanagida", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Horiguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/iju.70484" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42053358" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Loss, Surgical", "descriptor_ui": "D016063", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Fibrin Tissue Adhesive", "descriptor_ui": "D015718", "major_topic": true }, { "descriptor": "Gelatin", "descriptor_ui": "D005780", "major_topic": true }, { "descriptor": "Hemostasis, Surgical", "descriptor_ui": "D006488", "major_topic": true }, { "descriptor": "Hemostatics", "descriptor_ui": "D006490", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Nephrectomy", "descriptor_ui": "D009392", "major_topic": true }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "e70484", "proceedings_title": null, "publisher": "", "title": "International journal of urology : official journal of the Japanese Urological Association", "volume": "33", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Photocurable Gelatin Provides Superior Hemostasis Compared With Fibrin Glue Under Stringent Conditions in a Rabbit Partial Nephrectomy Model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Treatment-resistant schizophrenia (TRS) affects 20%-30% of individuals diagnosed with schizophrenia and is effectively managed with clozapine. However, the molecular and cellular mechanisms that underlie its efficacy remain largely unclear. We previously generated induced pluripotent stem cell (iPSC) lines from a unique pair of monozygotic twins with TRS. One twin responded to clozapine (CLZ-res), while the other did not (CLZ-non-res). Building on our previous study of these twins, we included healthy controls and focused on the early developmental stages of neuronal differentiation. To investigate the phenotypic differences in the developmental stages of neural cells between patient-derived cells, we differentiated each iPSC line-from both patients and healthy individuals-into neural stem cells (NSCs) and subsequently induced the differentiation of NSCs into neurons. Our results demonstrated that NSCs derived from patients' iPSC lines exhibited impaired neuronal differentiation, with a more pronounced reduction in differentiation observed in CLZ-non-res cells than in CLZ-res cells. RNA sequencing analysis revealed significant differences in the expression of genes involved in neuronal development between CLZ-res and CLZ-non-res cells. These findings suggest that the differences in neuronal development may contribute to the variability in clozapine responsiveness. Although this study is limited to a single twin pair, this unique human model provides valuable insights into the molecular and cellular mechanisms underlying differential clozapine responses, offering a promising framework for the development of effective treatments for patients with TRS.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shotaro", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Yuuri", "last_name": "Ikeuchi", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Mita", "name": null }, { "creator_type": "author", "first_name": "Hikari", "last_name": "Takei", "name": null }, { "creator_type": "author", "first_name": "Nanaka", "last_name": "Gotoda-Nishimura", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Hotaka", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/npr2.70097" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41866870" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Antipsychotic Agents", "descriptor_ui": "D014150", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Clozapine", "descriptor_ui": "D003024", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": true }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Schizophrenia, Treatment-Resistant", "descriptor_ui": "D000090663", "major_topic": true }, { "descriptor": "Twins, Monozygotic", "descriptor_ui": "D014430", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jun", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "e70097", "proceedings_title": null, "publisher": "", "title": "Neuropsychopharmacology reports", "volume": "46", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Differential Neuronal Development in iPSC-Derived Neural Stem Cells From Monozygotic Twin Cases With Treatment-Resistant Schizophrenia and Discordant Responses to Clozapine.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND/PURPOSE: Surgical site infection (SSI) is a serious complication of artificial arthroplasty. Its relationship with dental infections and the necessity of preoperative dental screening remains debated. This study examined the relationship between oral condition and risk of SSI, along with preoperative tooth extraction effect, in patients undergoing artificial arthroplasty. MATERIALS AND METHODS: Patients undergoing artificial hip or knee arthroplasty between April 2018 and September 2021 were retrospectively examined for age, sex, surgical site, surgical procedure, surgical time, preoperative hemoglobin level, white blood cell count, albumin level, creatinine level, remaining teeth, apical lesions ≥3 mm, periodontal pockets ≥4 mm, root fractures, residual roots, local infection symptoms in the oral cavity, preoperative or postoperative tooth extraction, and SSI occurrence. Tooth extraction effects on SSI incidence were analyzed using propensity score matching. RESULTS: The study included 3950 patients from 30 facilities. SSI occurred in 79 patients (2.0 %). Multivariate analysis identified surgery time and oral infection symptoms as significant risk factors. SSI occurred in 75 of 3793 patients without preoperative tooth extraction (2.0 %) and in 4 of 157 patients with tooth extraction (2.6 %), with no significant difference. However, in 292 propensity-matched patients, SSI incidences were 2.7 % and 6.2 % with and without preoperative extraction, respectively, indicating that preoperative infectious tooth removal may reduce SSI risk. Conversely, SSI occurred in three of seven patients (42.9 %) with tooth extraction within 60 days post-surgery, highlighting its risks. CONCLUSION: Oral infections increase SSI risk after artificial arthroplasty. Preoperative tooth extraction is recommended to reduce this risk.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryoji", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Sakiko", "last_name": "Soutome", "name": null }, { "creator_type": "author", "first_name": "Naohisa", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Akita", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Narihiro", "last_name": "Hirahara", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Hideto", "last_name": "Imura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hokita", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kusafuka", "name": null }, { "creator_type": "author", "first_name": "Kousuke", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Matsusue", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Nakahara", "name": null }, { "creator_type": "author", "first_name": "Kanae", "last_name": "Niimi", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Mitsunobu", "last_name": "Otsuru", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Rokutanda", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Shimanishi", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tsurumaki", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Ueki", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Madoka", "last_name": "Funahara", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Nagato", "last_name": "Natsume", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jds.2025.07.022" }, "pmcid": { "normalized": "PMC12825470" }, "pmid": { "normalized": "41585180" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "88-95", "proceedings_title": null, "publisher": "", "title": "Journal of dental sciences", "volume": "21", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Multi-institutional observational study on the relationship between oral infection focus and surgical site infection in artificial arthroplasty and the clinical significance of tooth extraction: An analysis using propensity score matching.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: To predict the risk of diabetic macular edema (DME) onset and to identify features of the risk subgroups. DESIGN: Population-based observational study with a case-control design. SUBJECTS AND CONTROLS: Health checkup and diagnosis data from the JMDC claims database (January 2005-July 2020), one of the largest Japanese epidemiological databases, were used. From 272 337 individuals diagnosed with type 2 diabetes (International Classification of Diseases, 10th Revision E11), we analyzed 2368 pairs of DME and non-DME individuals, which matched 1:1 by the balancing score calculated from regression analysis of DME with sex, age, months of observation, number of checkups, duration of diabetes, and months until the first checkup. METHODS: We employed a multivariate Cox proportional hazards model, regularized Cox models, and a random survival forest (RSF). These models were trained via ID-level bootstrap resampling using 43 health checkup variables (missing ratio <50%) and 404 high-incidence diseases within 6 months, along with age, sex, and duration of diabetes mellitus, to assess DME risk. Temporal changes in RSF-predicted risk scores were analyzed using nonlinear modeling techniques. MAIN OUTCOME MEASURES: Concordance index (C-index), integrated Brier score (IBS), and cumulative/dynamic mean area under the receiver operating characteristic curve (AUC). RESULTS: Thirteen checkup items and 44 disease history variables were significantly associated with the onset of DME. The RSF identified 43.8% of DME cases >5 years prior to onset, with a specificity of 85.5%. The RSF achieved median C-index, IBS, and mean AUC values of 0.694 (95% confidence interval, 0.688-0.697), 0.181 (0.179-0.184), and 0.750 (0.739-0.756), respectively, outperforming both multivariate and univariate Cox models. Three distinct DME risk subgroups were suggested by temporal changes in the RSF-predicted risk score. Predictors of DME onset varied markedly among these subgroups. In the explicit high-risk subgroup, urinary protein and urinary sugar were highly important, and liver function-related blood tests, such as alanine transaminase and gamma-gultamyltransferase, were also ranked high in variable importance metrics. Anemia-related laboratory tests were associated with DME development only in this subgroup. CONCLUSIONS: Random survival forest demonstrated superior performance in relative risk prediction of DME using health checkup data. External validation remains an essential prerequisite before any clinical application. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Chida", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Hananoe", "name": null }, { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Koshizaka", "name": null }, { "creator_type": "author", "first_name": "Yoshiro", "last_name": "Maezawa", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Takatsuna", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Tatsumi", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Hanae", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Hanai", "name": null }, { "creator_type": "author", "first_name": "Koutaro", "last_name": "Yokote", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Asanuma", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xops.2026.101262" }, "pmcid": { "normalized": "PMC13355755" }, "pmid": { "normalized": "42437110" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "101262", "proceedings_title": null, "publisher": "", "title": "Ophthalmology science", "volume": "6", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Early Prediction of Diabetic Macular Edema via Machine Learning Survival Analysis on Checkup Data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Negative-pressure wound therapy (NPWT) is widely used in clinical practise to enhance wound healing; however, its biological effects on intact skin remain poorly understood. Given the expanding applications of NPWT, understanding its impact beyond open wounds is increasingly important. This study aimed to evaluate the biological responses of intact skin to negative-pressure, specifically focusing on epithelial-mesenchymal transition (EMT). The effects of negative-pressure loading were assessed using an in vitro model of non-diabetic human keratinocytes and an in vivo model of intact diabetic mouse skin. Human keratinocytes exposed to negative-pressure exhibited increased expression of thrombospondin-1 (THBS1), transforming growth factor-beta 1 (TGF-beta1), plasminogen activator inhibitor-1 (PAI-1), and hypoxia-inducible factor 1-alpha (HIF-1alpha), alongside decreased epithelial markers and increased mesenchymal markers. These EMT-related changes were mitigated by inhibiting the THBS1-TGF-beta1 interaction. Similarly, in diabetic mice, intermittent negative-pressure loading applied to intact dorsal skin significantly increased THBS1 and TGF-beta1 levels, resulting in epidermal and dermal thickening, and promoted hypoxic, prothrombotic and angiogenic responses, as evidenced by increased HIF-1alpha, PAI-1, fibrinogen and vascular endothelial growth factor expression. These findings suggest that negative-pressure loading can induce EMT-like responses and tissue remodelling in intact skin primarily via mechanisms involving the THBS1-TGF-beta1 signalling axis. This study expands the understanding of the biological influence of NPWT beyond traditional wound treatment applications, potentially informing future therapeutic considerations and safety guidelines.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Toshifumi", "last_name": "Yamashiro", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Yoshine", "last_name": "Mayumi", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Azuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/iwj.70859" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41840929" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Experimental", "descriptor_ui": "D003921", "major_topic": true }, { "descriptor": "Diabetic Foot", "descriptor_ui": "D017719", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Epithelial-Mesenchymal Transition", "descriptor_ui": "D058750", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Negative-Pressure Wound Therapy", "descriptor_ui": "D054843", "major_topic": true }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": true }, { "descriptor": "Thrombospondin 1", "descriptor_ui": "D019700", "major_topic": true }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": true }, { "descriptor": "Wound Healing", "descriptor_ui": "D014945", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "e70859", "proceedings_title": null, "publisher": "", "title": "International wound journal", "volume": "23", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Negative-Pressure Induces Epithelial-Mesenchymal Transition via Thrombospondin-1 Upregulation in Intact Diabetic Skin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Synapse elimination during development is crucial for refining neural circuits by removing excess synapses formed around birth. In the neonatal cerebellum, Purkinje cells (PCs) are initially innervated by multiple climbing fibers (CFs) with similar synaptic strengths. During subsequent postnatal development, a single CF is strengthened and retained, while the other CFs are eliminated. Here, our PC-specific RNAi knockdown (KD) screening revealed that fibronectin type III domain containing 3B (FNDC3B), an endoplasmic reticulum protein, was involved in CF synapse elimination from around postnatal day 9 (P9) in mice. We showed that FNDC3B mRNA was expressed in PCs during CF synapse elimination. In PC-selective FNDC3B conditional knockout (FNDC3B-cKO) mice, CF synapse elimination from P10 was impaired, and the extension of CFs along PC dendrites was reduced at P21. However, these phenotypes were recovered by P40. In contrast, parallel fiber-mediated excitatory synaptic inputs and inhibitory synaptic inputs to PCs were not affected in FNDC3B-cKO mice. These results suggest that FNDC3B facilitates CF synapse elimination during postnatal development, highlighting a new role of FNDC3B in the developing brain.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Celine Louise", "last_name": "Mercier", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Okuno", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Matsuyama", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Kushibe", "name": null }, { "creator_type": "author", "first_name": "Henry", "last_name": "Denny", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Miwako", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Meiko", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/ejn.70411" }, "pmcid": { "normalized": "PMC12828876" }, "pmid": { "normalized": "41574767" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": true }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": false }, { "descriptor": "Fibronectins", "descriptor_ui": "D005353", "major_topic": true }, { "descriptor": "Golgi Apparatus", "descriptor_ui": "D006056", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Nerve Fibers", "descriptor_ui": "D009412", "major_topic": true }, { "descriptor": "Neurodevelopment", "descriptor_ui": "D000099203", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": true }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jan", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "e70411", "proceedings_title": null, "publisher": "", "title": "The European journal of neuroscience", "volume": "63", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "The ER/Golgi Protein FNDC3B Facilitates Climbing Fibre to Purkinje Cell Synapse Elimination in the Developing Mouse Cerebellum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Spermatogenesis, the complex developmental process of male germ cell proliferation, differentiation, and maturation, is the basis of male fertility. In the seminiferous tubules of the testes, spermatozoa are constantly generated from spermatogonial stem cells through a stereotyped sequence of divisions. The basic physiological principles, however, that control seminiferous tubule function remain poorly, if at all, defined. Here, we address cell type-specific seminiferous tubule signaling in vitro and in vivo. By monitoring changes in cellular Ca2+ concentration at high spatiotemporal resolution, we show that the three cell types that build the seminiferous epithelium-Sertoli, peritubular, and germ cells-each display unique Ca2+ signaling patterns. We reveal the underlying mechanisms and demonstrate that Sertoli cell Ca2+ signals are under gonadotropin regulation. Together, our experimental findings provide insights into seminiferous tubule signaling, its mechanistic basis, and its endocrine control.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Justine A.", "last_name": "Fischoeder", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Fleck", "name": null }, { "creator_type": "author", "first_name": "Jerome", "last_name": "Schröer", "name": null }, { "creator_type": "author", "first_name": "Christopher", "last_name": "Wiesbrock", "name": null }, { "creator_type": "author", "first_name": "Lina", "last_name": "Kenzler", "name": null }, { "creator_type": "author", "first_name": "Christoph", "last_name": "Weber-Hamacher", "name": null }, { "creator_type": "author", "first_name": "Ilian", "last_name": "Schröder", "name": null }, { "creator_type": "author", "first_name": "Melissa", "last_name": "Franke", "name": null }, { "creator_type": "author", "first_name": "Stefanie", "last_name": "Kurth", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Strauch", "name": null }, { "creator_type": "author", "first_name": "Guiscard", "last_name": "Seebohm", "name": null }, { "creator_type": "author", "first_name": "Dorit", "last_name": "Merhof", "name": null }, { "creator_type": "author", "first_name": "Johannes", "last_name": "Stegmaier", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Jennifer", "last_name": "Spehr", "name": null }, { "creator_type": "author", "first_name": "Marc", "last_name": "Spehr", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pbio.3003910" }, "pmcid": { "normalized": "PMC13399359" }, "pmid": { "normalized": "42497164" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Seminiferous Tubules", "descriptor_ui": "D012671", "major_topic": true }, { "descriptor": "Sertoli Cells", "descriptor_ui": "D012708", "major_topic": false }, { "descriptor": "Spermatogenesis", "descriptor_ui": "D013091", "major_topic": false }, { "descriptor": "Spermatozoa", "descriptor_ui": "D013094", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "e3003910", "proceedings_title": null, "publisher": "", "title": "PLoS biology", "volume": "24", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell type-specific Ca2+ signals govern mouse seminiferous tubule physiology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: We investigated the role of GLI3, a transcription factor highly expressed in the pathogenic THY1(+)CD34(-) sublining subset of rheumatoid arthritis synovial fibroblasts (RASFs), in regulating their pathogenic behavior. METHODS: GLI3 protein levels were quantified in freshly isolated RASF subsets by Western blotting. Bulk RASFs were subjected to siRNA-mediated knockdown (KD) of GLI3 or GLI1, followed by RNA sequencing. The effects of GANT61 on RASF proliferation, cell-cycle progression, migration, viability, and apoptosis were assessed using EdU/PI analysis, scratch assays, CCK-8 assays, and Annexin V/PI flow cytometry. RESULTS: GLI3 expression was enriched in THY1(+)CD34(-) RASFs at both mRNA and protein levels. GLI3 KD increased GLI1 expression and upregulated genes involved in inflammation, matrix remodeling, and cell cycle regulation, including IL6, IL11, IL24, IL33, MMP3, PLAU, CCNA2, and E2F1. Pathway enrichment analysis revealed activation of ECM-receptor interaction, PI3K-Akt, and TNF signaling. Co-silencing GLI1 with GLI3 blunted the induction of IL11, IL24, IL33, CCNA2, E2F1, and PLAU observed with GLI3 KD alone, indicating that GLI1 mediates a subset of the transcriptional effects induced by GLI3 loss. GANT61 suppressed CCNA2 and E2F1 expression, inhibited RASF proliferation and migration, and did not markedly increase apoptosis. CONCLUSION: GLI3 functions as a negative regulator of GLI1 and its downstream targets that drive the pathogenic behavior of RASFs. Targeting the GLI1-GLI3 axis may represent a promising therapeutic strategy to modulate fibroblast-driven inflammation and joint destruction in RA.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Komiya", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Tagawa", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Iwai", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Takahara", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Hosoya", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Yasuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/1756-185x.70690" }, "pmcid": { "normalized": "PMC13238299" }, "pmid": { "normalized": "42246142" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Arthritis, Rheumatoid", "descriptor_ui": "D001172", "major_topic": true }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": true }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": true }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synovial Membrane", "descriptor_ui": "D013583", "major_topic": true }, { "descriptor": "Zinc Finger Protein GLI1", "descriptor_ui": "D000071676", "major_topic": true }, { "descriptor": "Zinc Finger Protein Gli3", "descriptor_ui": "D000074290", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "e70690", "proceedings_title": null, "publisher": "", "title": "International journal of rheumatic diseases", "volume": "29", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Reciprocal Regulation of GLI1 and GLI3 Fine Tunes the Pathogenic Behavior of Synovial Fibroblasts in Rheumatoid Arthritis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Social behaviors rely on the integration of multiple sensory cues. Among these, ultrasonic vocalizations (USVs) serve as primary auditory cues in rodents. Although the function of USVs has been extensively studied in pup-female and male-female interactions, their role in male-male interactions remain to be elucidated. We tested whether adult male mice recognize male-emitted USVs as social cues using a two-choice playback paradigm. We demonstrated that male mice preferred male-emitted USVs and that oxytocin signaling is essential for perceiving male-emitted USVs. This study provides new insights into the neural mechanisms of male-male social behavior.", "classifications": [ { "id": "18H05416", "label": "18H05416", "researcher": "Hitoshi Hashimoto", "type": "grant" }, { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Takefumi", "last_name": "Kikusui", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphs.2025.11.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41390191" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Choice Behavior", "descriptor_ui": "D002755", "major_topic": true }, { "descriptor": "Cues", "descriptor_ui": "D003463", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Oxytocin", "descriptor_ui": "D010121", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": true }, { "descriptor": "Ultrasonic Waves", "descriptor_ui": "D000069453", "major_topic": false }, { "descriptor": "Ultrasonics", "descriptor_ui": "D014465", "major_topic": false }, { "descriptor": "Vocalization, Animal", "descriptor_ui": "D014828", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "23-28", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "160", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Male mice recognize male-emitted ultrasonic vocalizations in a two-choice test via oxytocin signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The stay-at-home orders, lockdowns, and states of emergency of the Coronavirus Infectious Disease emerged in 2019 (COVID-19) pandemic have affected the mental health of school-aged children. Previous reports of psychological distress in adolescents during the pandemic have been mixed, however, with some reports showing increases in psychological distress and others suggesting decreases. To accurately assess the impact of the pandemic, we need to be able to compare psychological assessments longitudinally, both before and during the pandemic. However, current statistical methods have limitations for reconstructing the complex trajectory of psychological states as captured by short-item questionnaires. METHODS AND FINDINGS: In this study, we analyzed monthly Kessler 6-item Psychological Distress Scale (K6) questionnaire responses collected from 16- to 18-year-old high school students participating in the population-neuroscience Tokyo TEEN Cohort (pn-TTC) in Japan (1,278 responses from 84 participants). Participants included 42 males and 42 females. The pn-TTC is a population-based longitudinal study conducted in Tokyo, Japan that follows children to investigate their developmental and mental health trajectories. In addition to conventional statistical approaches that summarize multiple questionnaire items into a composite score, we applied \"energy landscape analysis,\" a method derived from statistical physics that models multivariate psychological states as a dynamic system of interactions among K6 questionnaire items, to visualize longitudinal changes in psychological distress before and during the COVID-19 pandemic (July 2019 to September 2021). Here, we define the depressive and healthy states as configurations in which all six K6 items are above or below each participant's individual mean, respectively. Before the pandemic, the healthy state occurred 11.0 times as frequently as the depressive state. In contrast, during the pandemic, the relative frequency of the healthy state increased to 18.2, 18.5, and 15.0 times that of the depressive state, respectively. The evolving energy landscape revealed an association between the pandemic period and a lower likelihood of being in a depressive state. We also identified two groups of students with different K6 dynamics and energy landscapes. The first group consisted of 61 participants whose total K6 score was relatively low (less than 5) and stable over time, and the second group consisted of 23 participants whose total K6 score was higher (with most being higher than 5) and less stable. The latter group showed a greater change in cortical thickness in the caudal part of the middle frontal gyrus (cMFG) (t-statistic = -2.36, p-value = 0.019, q-value = 0.048) and the temporal pole (TP) (t = 3.08, p = 0.0023, q = 0.012), as measured by magnetic resonance imaging, in the direction of accelerated adolescent brain development. Because all participants lived in Tokyo, generalizability remains limited, and as the association between psychological states and brain development is descriptive, future studies in diverse cohorts are needed to examine causality. CONCLUSIONS: By revealing associations between the COVID-19 pandemic and lower levels of psychological distress and healthier mental health states, our work demonstrates the potential of using dynamical systems theory, such as the energy landscape analysis, to interpret health and disease metrics in psychology and psychiatry. This approach may improve mental health surveillance for the next pandemic.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Daiki", "last_name": "Tatematsu", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Masato S.", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Ezaki", "name": null }, { "creator_type": "author", "first_name": "Lin", "last_name": "Cai", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Naohiro", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Kiyoto", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Iwami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pmed.1004884" }, "pmcid": { "normalized": "PMC12826503" }, "pmid": { "normalized": "41569975" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "East Asian People", "descriptor_ui": "D000095225", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Longitudinal Studies", "descriptor_ui": "D008137", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mental Health", "descriptor_ui": "D008603", "major_topic": false }, { "descriptor": "Pandemics", "descriptor_ui": "D058873", "major_topic": false }, { "descriptor": "Psychological Distress", "descriptor_ui": "D000079225", "major_topic": true }, { "descriptor": "Schools", "descriptor_ui": "D012574", "major_topic": false }, { "descriptor": "Stress, Psychological", "descriptor_ui": "D013315", "major_topic": true }, { "descriptor": "Students", "descriptor_ui": "D013334", "major_topic": true }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "e1004884", "proceedings_title": null, "publisher": "", "title": "PLoS medicine", "volume": "23", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Psychological distress among Japanese high school students during the COVID-19 pandemic: An energy landscape analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Appropriate processing of aversive information is essential for survival. We previously demonstrated that serotonin neurons in the median raphe nucleus (MRN) play a key role in such processing; however, MRN responses to predictive cues of aversive events remain unclear. Here, we found that the MRN serotonin neurons were activated by aversive air-puff stimuli but not by auditory cues predicting the air puff. Moreover, delayed activation of the ventral hippocampus-projecting MRN serotonin neurons, together with subsequent 5-HT(2A) receptor signaling, was required for aversion. These findings shed light on the roles of the hippocampus-projecting MRN serotonin neurons and elucidate their molecular mechanisms.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hinako", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Harune", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Shirakawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphs.2025.12.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41554598" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Avoidance Learning", "descriptor_ui": "D001362", "major_topic": true }, { "descriptor": "Cues", "descriptor_ui": "D003463", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": true }, { "descriptor": "Raphe Nuclei", "descriptor_ui": "D011903", "major_topic": true }, { "descriptor": "Receptor, Serotonin, 5-HT2A", "descriptor_ui": "D044402", "major_topic": false }, { "descriptor": "Serotonergic Neurons", "descriptor_ui": "D059326", "major_topic": true }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "91-96", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "160", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Delayed response of the median raphe serotonin neurons projecting to the ventral hippocampus to aversive stimuli.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alopecia areata (AA) is an autoimmune skin disorder that causes hair loss. Squaric acid dibutylester (SADBE) is used for AA treatment as a topical immunotherapy that promotes hair growth by inducing allergic contact dermatitis in skin lesions. However, the mechanism of action remains unclear. C3H/HeJ mice spontaneously develop AA, and SADBE application induces hair growth at the lesion on day 28. In healthy young mice treated with SADBE, hair growth was observed after day 14. Fluorescent immunostaining of SADBE-treated skin tissues revealed a remarkable accumulation of macrophages in the dermis on day 3. These macrophages were divided into 3 subsets that formed a layered structure; in particular, CD206(+)F4/80(+) cells were localized near the dermal papilla. Flow cytometric analysis also showed these 3 subsets in SADBE-treated skin on day 3. Macrophage depletion by intradermal clodronate injection inhibited SADBE-induced hair growth, suggesting macrophage dependency. A single SADBE application induced hair growth without sensitization, indicating that the acute inflammation mediated by innate immune cells was sufficient. Hair growth by repeated SADBE application in AA-affected mice closely correlated with the increase of CD206(+) macrophages. These findings suggest that innate immune cells, particularly macrophages, play an important role in SADBE-induced hair growth, which would be potential targets in novel therapies for AA.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Koichi", "last_name": "Tomii", "name": null }, { "creator_type": "author", "first_name": "Madoka", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Nan-Jun", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Umemoto", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Hayasaka", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Tomura", "name": null }, { "creator_type": "author", "first_name": "Arata", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Riichiro", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xjidi.2025.100420" }, "pmcid": { "normalized": "PMC12590135" }, "pmid": { "normalized": "41209844" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "100420", "proceedings_title": null, "publisher": "", "title": "JID innovations : skin science from molecules to population health", "volume": "6", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Squaric Acid Dibutylester Promotes Innate Immune-Driven Hair Growth with CD206(+) Macrophage Accumulation in the Dermis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Accumulating evidence suggests that microduplications of the VIPR2 gene are strongly associated with schizophrenia. VIPR2 encodes vasoactive intestinal peptide receptor 2 (VPAC2). However, cell-type-specific actions of VPAC2 overexpression with respect to schizophrenia remain unclear. Therefore, we aimed to determine the effects of human VPAC2 overexpression in neurons on cognition-related behaviors and prefrontal cortex dendritic morphology in mice. We crossed a Tau-Cre mouse line, which targets neuronal recombinase activity, with a newly generated double transgenic mouse line containing tetracycline-responsive element-human VPAC2-IRES-mCherry and ROSA:LNL:tTA. Immunohistochemical and Western blot analyses revealed that VPAC2 was overexpressed in neurons throughout the brain. Mice that overexpressed VPAC2 showed impaired performance in the novel object recognition test. Furthermore, VPAC2-overexpressing mice exhibited significant reductions in brain weight and the length, branch number, and complexity of arborization of prefrontal cortex pyramidal neuron dendrites. RNA sequencing analysis revealed that VPAC2 overexpression may affect signaling pathways involved in regulating stem cell pluripotency, cell cycle, and actin cytoskeleton. Quantitative PCR analysis also confirmed increased expression of the X-linked lymphocyte-regulated 3B gene, which regulates dendritic morphogenesis and spine assembly. These results suggest that VPAC2 overexpression in neurons has a detrimental effect on brain development, which leads to impaired neural circuitry and cognitive function.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ami", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Miyaoka", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Koan", "name": null }, { "creator_type": "author", "first_name": "Zihao", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Lu", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Ishimoto", "name": null }, { "creator_type": "author", "first_name": "Nobumasa", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "James A.", "last_name": "Waschek", "name": null }, { "creator_type": "author", "first_name": "Shinsaku", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Tanimoto", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphs.2025.12.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41554595" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cognitive Dysfunction", "descriptor_ui": "D060825", "major_topic": true }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": true }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": true }, { "descriptor": "Receptors, Vasoactive Intestinal Peptide, Type II", "descriptor_ui": "D051239", "major_topic": true }, { "descriptor": "Schizophrenia", "descriptor_ui": "D012559", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "111-121", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "160", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Neuron-specific overexpression of human vasoactive intestinal peptide receptor 2 in mice causes cognitive dysfunction and abnormal dendritic morphology in the prefrontal cortex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This study evaluated glyoxal fixation for whole-brain serial section imaging using the FAST (block-face serial microscopy tomography) system. Glyoxal-fixed mouse brains exhibited slight shrinkage compared with paraformaldehyde-fixed brains but showed no appreciable variations over time. Notably, glyoxal provided an approximately 11-fold higher autofluorescence, facilitating precise focal plane identification and high-contrast label-free structural imaging. We observed that 4 days of fixation ensured tissue rigidity for smooth sectioning and intact section retrieval. Furthermore, the application of an autofluorescence quenching reagent enabled clear post hoc c-Fos immunostaining. Thus, glyoxal fixation is a powerful tool for multiscale label-free 3D brain mapping.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Haruka", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphs.2026.05.009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42303348" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "Brain Mapping", "descriptor_ui": "D001931", "major_topic": true }, { "descriptor": "Fixatives", "descriptor_ui": "D005404", "major_topic": true }, { "descriptor": "Formaldehyde", "descriptor_ui": "D005557", "major_topic": false }, { "descriptor": "Glyoxal", "descriptor_ui": "D006037", "major_topic": true }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": true }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-fos", "descriptor_ui": "D016760", "major_topic": false }, { "descriptor": "Tissue Fixation", "descriptor_ui": "D016707", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "130-135", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "161", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Glyoxal fixation is applicable to whole-brain serial section imaging in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The circadian clock allows organisms to anticipate environmental changes that are driven by the earth's rotation, and synchronizes with this cycle using light(1). The clock extracts relevant parameters of illumination, responding selectively to intensities at twilight and above, and to the number of photons counted over an extended time window(2-8). These hallmark properties are thought to manifest in the brain(9). Here, we report that they emerge within specific neurons of the eye. These M1 intrinsically photosensitive retinal ganglion cells (ipRGCs) detect light directly, using a receptor called melanopsin, and indirectly, through circuits driven by rod and cone photoreceptors(10). We find that the balance of intrinsic and extrinsic drives varies widely across M1s, and the population accounts for the dynamic range of circadian photoregulation. Both singly and collectively, M1s approach the level of temporal integration observed behaviorally. The cellular and behavioral levels match when the pupillary light reflex-another M1-driven function-shapes the light that M1s receive. This work reveals how the first steps of sensory processing are precisely formatted for specific tasks. It also introduces bioluminescence-based methods for identifying photosensitive neurons without desensitization, allowing their mechanistic study under physiological conditions.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Elliott S.", "last_name": "Milner", "name": null }, { "creator_type": "author", "first_name": "Hannah A.", "last_name": "Blume", "name": null }, { "creator_type": "author", "first_name": "S. Navid", "last_name": "Mousavi", "name": null }, { "creator_type": "author", "first_name": "Michael C.", "last_name": "Brown", "name": null }, { "creator_type": "author", "first_name": "Franklin", "last_name": "Caval-Holme", "name": null }, { "creator_type": "author", "first_name": "Nguyen-Minh", "last_name": "Viet", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Michael Tri H.", "last_name": "Do", "name": null } ], "identifiers": { "doi": { "normalized": "10.64898/2025.12.30.695276" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Dec 30", "date_precision": "day", "issue": null, "normalized_date": "2025-12-30", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Retinal Origins of Circadian Photoregulation's Specialized Dynamic Range and Temporal Integration.", "url": "", "zotero": { "item_type": "preprint" } }, { "abstract": "Collective cell migration is fundamental to tissue homeostasis and underlies biological processes such as wound healing and cancer invasion. Previous work has proposed governing equations to describe how chemical and mechanical inputs regulate these movements, but the quantitative validity of such models remains to be thoroughly assessed. Here, we developed a machine-learning framework that infers the governing equation from live-cell imaging data. Applied to epithelial sheet migration driven by MAPK/ERK, our approach quantitatively predicted single-cell movement from local chemical and mechanical cues. Examination of the learned equations further indicated that cells process environmental signals by computing their spatiotemporal derivatives. Moreover, when applied to individual cells, our framework revealed cell-cell heterogeneity in the underlying migratory rules. Our framework offers a powerful tool for predictive modeling of multicellular dynamics in both physiological and pathological settings.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuto", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Asakura", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Honda", "last_name": "Naoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1013854" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41460949" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mechanotransduction, Cellular", "descriptor_ui": "D040542", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Dec 29", "date_precision": "day", "issue": "12", "normalized_date": "2025-12-29", "pages": "e1013854", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "21", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Inverse modeling unveils governing law of mechano-chemical dynamics of epithelial migration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: We investigated the association between children's waking time and bedtime and contents of home meals, focusing on 'skipping breakfast' and 'meal of staple food, main dish, and side dish' (SMS meal). METHODS: A cross-sectional survey concerning children's lifestyle habits and dietary habits was conducted at seven primary schools within Saga Prefecture in northern Kyushu, Japan, with 2457 parents/guardians participating. Logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of sleep hours, wake-up time, and bedtime, with breakfast skipping and having SMS meals. RESULTS: Elementary schoolchildren sleeping for ≥9 hours were more likely to have parents/guardians in their 30s, who were full-time parents and maintained a healthy diet. Wake-up times and bedtimes were significantly associated with breakfast skipping frequency. Compared to the wake-up time from 6:30 to 6:59, ORs for the frequency of skipping breakfast was 0.52 (95% CI: 0.36-0.74, p < 0.001), for those waking before 6:29 and 2.23 (95% CI: 1.64-3.04; p < 0.001) for those waking after 7:00.Frequency of skipping breakfast decreased with earlier bedtimes. Compared to bedtimes from 21:00 to 21:59, ORs for having SMS meals were 0.64 for those with bedtimes before 21:00 (95% CI: 0.25-1.64) and 2.35 for those with bedtimes after 22:00 (95% CI: 1.77-3.11, p < 0.001). Compared to wake-up times from 6:30 to 6:59, waking up both before 6:29 (OR = 0.77, 95% CI: 0.63-0.94, p < 0.01) and at 7:00 or after (OR = 1.30, 95% CI: 1.00-1.69, p = 0.05) were associated with breakfast and dinner with SMS meals. A statistical interaction existed between wake-up time/bedtime and breakfast skipping. Compared to those waking before 6:30 and sleeping before 22:00, waking after 7:00 and sleeping after 22:00 was associated with skipping breakfast (OR = 2.11, 95% CI: 1.48-3.01; p for interaction = 0.04). Thus, children should sleep before 22:00 and wake up before 7:00 to prevent breakfast skipping and ensure a well-balanced diet with SMS meals. The 'Early to Bed, Early to Rise, and Don't Forget Your Breakfast' initiative significantly improved elementary schoolchildren's eating habits. CONCLUSIONS: Sleep hours, bedtime, and wake-up times are important factors affecting Japanese schoolchildren's dietary habits, specifically in terms of breakfast skipping and having SMS meals.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Aya", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Chieko", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/children13010030" }, "pmcid": { "normalized": "PMC12840127" }, "pmid": { "normalized": "41597038" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Dec 25", "date_precision": "day", "issue": "1", "normalized_date": "2025-12-25", "pages": "", "proceedings_title": null, "publisher": "", "title": "Children (Basel, Switzerland)", "volume": "13", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Sleep Hours, Wake-Up Time, Bedtime, Breakfast Skipping, and Japanese-Style Diet (Staple Food, Main Dish, and Side Dish): A Cross-Sectional Study of Schoolchildren in Saga Prefecture.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "CaMKII predominantly assembles into a 12-meric ring assembly, primarily consisting of alpha and beta isoforms in the brain. Previous biochemical studies reported varying ratios of these CaMKII variants across different brain regions and developmental stages. However, direct evidence for the formation of CaMKIIalpha/beta heterooligomers within a 12-meric ring assembly has been lacking at the single-molecule level. Here, we employ high-speed atomic force microscopy to visualize the conformational dynamics of forebrain-mimicked CaMKIIalpha/beta at a 3:1 ratio. Our findings reveal that the alpha and beta subunits are intermixed within the 12-meric ring assembly, with a probability exceeding 83% that beta subunits are positioned adjacently. Furthermore, in the activated state, CaMKIIalpha/beta heterooligomers form a stable kinase domain complex via interactions between adjacent CaMKIIbeta subunits, resulting in a long-lasting structure with an exposed target binding site. Collectively, our observations provide insights into the structural role of CaMKIIbeta subunits within the CaMKIIalpha/beta heterododecamer.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Matsushima", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Sumikama", "name": null }, { "creator_type": "author", "first_name": "Taisei", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Mizuho", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Nagasawa", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Sumino", "name": null }, { "creator_type": "author", "first_name": "Holger", "last_name": "Flechsig", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Ogoshi", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Kodera", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Mikihiro", "last_name": "Shibata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-66527-9" }, "pmcid": { "normalized": "PMC12738698" }, "pmid": { "normalized": "41444226" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinase Type 2", "descriptor_ui": "D054732", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy, Atomic Force", "descriptor_ui": "D018625", "major_topic": true }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Protein Multimerization", "descriptor_ui": "D055503", "major_topic": false }, { "descriptor": "Protein Subunits", "descriptor_ui": "D021122", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Dec 24", "date_precision": "day", "issue": "1", "normalized_date": "2025-12-24", "pages": "10603", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Structural dynamics of mixed-subunit CaMKIIalpha/beta heterododecamers filmed by high-speed AFM.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Subarachnoid hemorrhage is a life-threatening cerebrovascular event, and cerebral vasospasm remains a major cause of poor neurological outcomes. Clazosentan, an endothelin-A receptor antagonist, has been recently approved in Japan to reduce post-subarachnoid hemorrhage vasospasm; however, recurrent vasospasm after cessation of therapy has occasionally been reported, which underlying mechanisms remain unclear. Moreover, endothelin-A receptor is also expressed on pericytes; however, the effects of clazosentan on microvascular endothelin-A receptor remain unexplored. In this study, we employed a rat subarachnoid hemorrhage model to investigate the temporal dynamics of vasospasm and endothelin-A receptor expression in both large arteries and microvessels, and to evaluate the effects of clazosentan administration. Sprague-Dawley rats were assigned to naive controls, subarachnoid hemorrhage with saline, or subarachnoid hemorrhage with continuous clazosentan administration for 7 days via osmotic pumps. Vasospasm was assessed by arterial wall thickness, and endothelin-A receptor expression was quantified using immunohistochemistry and immunofluorescence, including staining with alpha-SMA, CD31, and PDGF-beta. Clazosentan significantly attenuated vasospasm in the middle and anterior cerebral arteries, and recurrent vasospasm was observed 3 days after cessation of clazosentan, coinciding with sustained upregulation of endothelin-A receptor in these vessels. In microvessels, pericyte density transiently decreased, peaking at a nadir on day 3 post-subarachnoid hemorrhage, while endothelin-A receptor expression on pericytes was highest at the same time point, and further elevated by clazosentan treatment. These findings indicate that clazosentan induces endothelin-A receptor upregulation in both macro- and microcirculation, potentially contributing to recurrent vasospasm after treatment, and highlight the critical role of pericytes in post-subarachnoid hemorrhage vascular regulation.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuyuan", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Kawabori", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Shuho", "last_name": "Gotoh", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Tatezawa", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Taishi", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Yo", "last_name": "Nakahara", "name": null }, { "creator_type": "author", "first_name": "Erika", "last_name": "Yoshie", "name": null }, { "creator_type": "author", "first_name": "Zheng", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Fujimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.2176/jns-nmc.2025-0185" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41423235" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dioxanes", "descriptor_ui": "D004146", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Endothelin A Receptor Antagonists", "descriptor_ui": "D065130", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microcirculation", "descriptor_ui": "D008833", "major_topic": true }, { "descriptor": "Microvessels", "descriptor_ui": "D055806", "major_topic": false }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": true }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Receptor, Endothelin A", "descriptor_ui": "D044022", "major_topic": true }, { "descriptor": "Subarachnoid Hemorrhage", "descriptor_ui": "D013345", "major_topic": true }, { "descriptor": "Sulfonamides", "descriptor_ui": "D013449", "major_topic": true }, { "descriptor": "Tetrazoles", "descriptor_ui": "D013777", "major_topic": true }, { "descriptor": "Vasospasm, Intracranial", "descriptor_ui": "D020301", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Dec 20", "date_precision": "day", "issue": "", "normalized_date": "2025-12-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "Neurologia medico-chirurgica", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Clazosentan Affects Temporal Profile of Endothelin-A Expression in Macro- and Microcirculation after Subarachnoid Hemorrhage.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hypoglycemia and hyperglycemia are common complications among critically ill patients. Maintaining blood glucose levels in the normal range is crucial but challenging due to complex influencing factors. This study aimed to develop a machine learning model that predicts hypo- or hyperglycemia 6 h in advance in patients admitted to the intensive care unit (ICU). We analyzed electronic health records of 8,853 ICU patients (1,350,097 records) from a single center in Japan (2010-2022). Hypoglycemia and hyperglycemia were defined as blood glucose levels /= 180 mg/dL (10 mmol/L), respectively. We developed prediction models using routinely collected ICU data, including demographic, physiological, laboratory, and treatment variables. Machine learning models were developed using eXtreme Gradient Boosting (XGBoost), random forest, neural networks, and logistic regression. The XGBoost model demonstrated the highest performance with an area under the curve (AUC) of 0.939 and an F1 score of 0.520 for predicting hypoglycemia and an AUC of 0.919 and an F1 score of 0.702 for predicting hyperglycemia. It also achieved high calibration and net benefit. The machine learning models, notably the XGBoost algorithm, accurately predicted glucose abnormalities in critically ill ICU patients. These findings support its potential as a tool for early detection and proactive management of dysglycemia in critical care.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yu", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Oami", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Taka-Aki", "last_name": "Nakada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-29860-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41413111" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Blood Glucose", "descriptor_ui": "D001786", "major_topic": false }, { "descriptor": "Critical Illness", "descriptor_ui": "D016638", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hyperglycemia", "descriptor_ui": "D006943", "major_topic": true }, { "descriptor": "Hypoglycemia", "descriptor_ui": "D007003", "major_topic": true }, { "descriptor": "Intensive Care Units", "descriptor_ui": "D007362", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Dec 18", "date_precision": "day", "issue": "", "normalized_date": "2025-12-18", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Accurate prediction of hypoglycemia and hyperglycemia using machine learning in critically ill patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transcriptional regulation arises from the dynamic and combinatorial actions of multiple regulatory factors on genomic DNA. Although many epigenomic regulators have been identified, the precise order in which these factors accumulate at individual gene loci to activate transcription remains unclear. Here we show a single-cell data integration framework that infers the binding order of multiple chromatin factors at single-cell resolution. Central to this framework is sci-mtChIL-seq, a scalable single-cell method that simultaneously profiles genome-wide binding of RNA polymerase II (RNAPII) and diverse epigenomic regulators. By defining transcriptional states through RNAPII occupancy and integrating multiple sci-mtChIL-seq datasets, we systematically link the combinatorial patterns of transcription factor binding, histone modifications and chromatin remodeling. This framework reveals the temporal coordination among chromatin factors during transcriptional activation, providing a powerful approach to uncover context-dependent epigenomic dynamics and the principles of gene regulation in complex cellular systems.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takeru", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Tomimatsu", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurumizaka", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-67016-9" }, "pmcid": { "normalized": "PMC12711870" }, "pmid": { "normalized": "41408042" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Chromatin Assembly and Disassembly", "descriptor_ui": "D042002", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": true }, { "descriptor": "Epigenome", "descriptor_ui": "D000081122", "major_topic": true }, { "descriptor": "Epigenomics", "descriptor_ui": "D057890", "major_topic": true }, { "descriptor": "Histone Code", "descriptor_ui": "D042421", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "RNA Polymerase II", "descriptor_ui": "D012319", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Dec 17", "date_precision": "day", "issue": "1", "normalized_date": "2025-12-17", "pages": "11006", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Reconstructing epigenomic dynamics through a single-cell multi-epigenome data integration framework.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The global circulation of SARS-CoV-2 in human populations has driven the emergence of Omicron subvariants, which have become highly diversified through recombination. In late 2024, SARS-CoV-2 Omicron XEC variant emerged from the recombination of two JN.1 progeny, KS.1.1 and KP.3.3, and became predominant worldwide. Here, we investigate virological features of the XEC variant. Epidemic dynamics modeling suggests that spike substitutions in XEC mainly contribute to its increased viral fitness. Additionally, four licensed antivirals are effective against XEC. Although the fusogenicity of XEC spike is comparable to that of the JN.1 spike, the intrinsic pathogenicity of XEC in male hamsters is significantly higher than that of JN.1. Notably, we find that the nucleocapsid R204P mutation of XEC enhances inflammation through NF-kappaB activation. Recent studies suggest that the evolutionary potential of spike protein is reaching its limit. Indeed, our findings highlight the critical role of non-spike mutations in the future evolution of SARS-CoV-2.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shuhei", "last_name": "Tsujino", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Deguchi", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Taha Y.", "last_name": "Taha", "name": null }, { "creator_type": "author", "first_name": "Hesham", "last_name": "Nasser", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Julia", "last_name": "Rosecrans", "name": null }, { "creator_type": "author", "first_name": "Rigel", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Yoshimatsu", "name": null }, { "creator_type": "author", "first_name": "Melanie", "last_name": "Ott", "name": null }, { "creator_type": "author", "first_name": "Terumasa", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Takasuke", "last_name": "Fukuhara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-67455-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41392175" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antiviral Agents", "descriptor_ui": "D000998", "major_topic": false }, { "descriptor": "Coronavirus Nucleocapsid Proteins", "descriptor_ui": "D000086462", "major_topic": true }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Cricetinae", "descriptor_ui": "D006224", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true }, { "descriptor": "Spike Glycoprotein, Coronavirus", "descriptor_ui": "D064370", "major_topic": false }, { "descriptor": "Virulence", "descriptor_ui": "D014774", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Dec 14", "date_precision": "day", "issue": "", "normalized_date": "2025-12-14", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "A non-spike nucleocapsid R204P mutation in SARS-CoV-2 Omicron XEC enhances inflammation and pathogenicity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "CD4(+) tissue-resident memory T (T(RM)) cells contribute to host defense and to the pathogenesis of chronic inflammatory diseases, but the molecules that direct their differentiation are unknown. We found that the transcription factor hepatic leukemia factor (HLF) could direct the tissue residency program and function of CD4(+) T(RM) cells. HLF simultaneously up-regulated tissue retention receptors, down-regulated tissue egress receptors, and promoted proinflammatory CD4(+) T(RM) cells by inducing Bhlhe40, and all of these processes were associated with changes in chromatin accessibility. Genetic deletion of Hlf inhibited CD4(+) T(RM) cell generation and ameliorated airway tissue inflammation in vivo. HLF(+) CD4(+) T(RM) cells isolated from inflamed airway tissue in humans had a tissue residency signature and expressed inflammatory cytokines. We conclude that HLF may act as a central regulator of proinflammatory CD4(+) T(RM) cell development and function.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Kiuchi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nemoto", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yagyu", "name": null }, { "creator_type": "author", "first_name": "Ami", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Iwamura", "name": null }, { "creator_type": "author", "first_name": "Hikaru", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Masuo", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Shuhe", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Okuno", "name": null }, { "creator_type": "author", "first_name": "Takahisa", "last_name": "Hishiya", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Kokubo", "name": null }, { "creator_type": "author", "first_name": "Kanae", "last_name": "Ohishi", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Shinmi", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Sonobe", "name": null }, { "creator_type": "author", "first_name": "Tomohisa", "last_name": "Iinuma", "name": null }, { "creator_type": "author", "first_name": "Syuji", "last_name": "Yonekura", "name": null }, { "creator_type": "author", "first_name": "Tomomasa", "last_name": "Yokomizo", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Onodera", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Tatsuaki", "last_name": "Tsuruyama", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Kurashima", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Mato", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Motoko Yagi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Damon J.", "last_name": "Tumes", "name": null }, { "creator_type": "author", "first_name": "Toyoyuki", "last_name": "Hanazawa", "name": null }, { "creator_type": "author", "first_name": "Toshinori", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Hirahara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.adp0714" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41379973" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": true }, { "descriptor": "Basic-Leucine Zipper Transcription Factors", "descriptor_ui": "D050976", "major_topic": false }, { "descriptor": "CD4-Positive T-Lymphocytes", "descriptor_ui": "D015496", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunologic Memory", "descriptor_ui": "D007156", "major_topic": true }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory T Cells", "descriptor_ui": "D000091246", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Dec 11", "date_precision": "day", "issue": "6778", "normalized_date": "2025-12-11", "pages": "eadp0714", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "390", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Hepatic leukemia factor directs tissue residency of proinflammatory memory CD4(+) T cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Axial rotation (AR), a morphogenetic movement that reshapes the body axis, is widely observed in chordates, including mice and rats. AR involves complex three-dimensional deformations; however, its geometric characteristics and regulatory mechanisms remain poorly understood. Here, using the chordate Ciona robusta (Ciona intestinalis type A), we demonstrate that AR consists of two differentially regulated components-leftward bending and clockwise twisting along the anterior-posterior axis. A comparison between chorionated and dechorionated embryos revealed that dechorionation randomized the bending direction, while twisting remained consistently clockwise. Inhibition of TGF-beta signaling with SB431542 randomized both deformations. Quantitative analysis of twisting angles indicated uniform clockwise twisting along the axis, peaking during the tailbud stage and proceeding in the tail region, independent of the tip, trunk, or myofibril patterning. Although overall twisting was reduced under TGF-beta inhibition, the tail exhibited disorganized twisting. The sum of absolute twisting-angle differences in every 10 mum remained comparable to the wild type (WT). This suggests that twisting is intrinsically generated, while TGF-beta signaling aligns local twisting into a coordinated global direction. Our findings dissected the mechanisms of AR in Ciona and highlight the multilayered regulation underlying the morphogenesis of the chordate body plan and providing a foundation for understanding its biomechanical and molecular bases.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki S.", "last_name": "Kogure", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2025.12.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41386418" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzamides", "descriptor_ui": "D001549", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": true }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": true }, { "descriptor": "Dioxoles", "descriptor_ui": "D004149", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": true }, { "descriptor": "Rotation", "descriptor_ui": "D012399", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Dec 10", "date_precision": "day", "issue": "", "normalized_date": "2025-12-10", "pages": "S0012-1606(25)00339-2", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Axial Rotation Comprises Concurrent Twisting and Bending as Distinct Morphogenetic Components in Ciona.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Immune checkpoint inhibitors (ICIs) with platinum-doublet chemotherapy (Chemo-ICIs) are used as the standard treatment for advanced non-small cell lung cancer (NSCLC) with performance status (PS) 0 to 1. However, patients with PS2 are often excluded from clinical trials, leading to an evidence gap that makes it difficult to select the optimal treatment strategy. The efficacy and safety of first-line Chemo-ICIs in PS2 remain unclear. PATIENTS AND METHODS: This multicenter retrospective cohort study analyzed real-world data of 2425 patients with stage IV NSCLC and PS0 to 2 without driver oncogenes. Propensity score matching was used to compare outcomes between patients receiving Chemo and those receiving Chemo-ICIs. Primary endpoints included progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), and the incidence of grade >/= 3 adverse events. RESULTS: Among 424 patients with PS2 (median age 71 years; 73% men), 56 received Chemo-ICIs and 117 received Chemo. After matching, median PFS was significantly longer in the Chemo-ICIs group (5.7 vs. 2.3 months; hazard ratio [HR] 0.58 [0.36-0.93]; P = .025), and ORR was higher (43% vs. 21%; P = .02). OS showed a non-significant trend toward improvement (8.0 vs. 6.0 months; HR 0.75 [0.47-1.19]; P = .219). Rates of grade >/= 3 adverse events were comparable (50.0% vs. 43.6%; P = .514). CONCLUSIONS: Chemo-ICIs significantly improved PFS and ORR compared to Chemo in patients with NSCLC with PS2 without higher toxicity. These findings highlight the clinical relevance of chemoimmunotherapy in patients with PS2 and may help bridge the evidence gap in existing treatment guidelines.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shunichi", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Takehito", "last_name": "Shukuya", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohtsu", "name": null }, { "creator_type": "author", "first_name": "Taichi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Toi", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Teruhumi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Teppei", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Tamiya", "name": null }, { "creator_type": "author", "first_name": "Motoko", "last_name": "Tachihara", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Otsubo", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Sakata", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Isamu", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cllc.2025.12.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41483952" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": true }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Follow-Up Studies", "descriptor_ui": "D005500", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Checkpoint Inhibitors", "descriptor_ui": "D000082082", "major_topic": true }, { "descriptor": "Immunotherapy", "descriptor_ui": "D007167", "major_topic": true }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Survival Rate", "descriptor_ui": "D015996", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Dec 9", "date_precision": "day", "issue": "", "normalized_date": "2025-12-09", "pages": "S1525-7304(25)00330-4", "proceedings_title": null, "publisher": "", "title": "Clinical lung cancer", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Multicenter Real-World Data on First-Line Chemoimmunotherapy in Patients With Advanced Non-Small Cell Lung Cancer and Performance Status 2: WJOG18424L.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takanori", "last_name": "Kawabata", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Tsuzuki", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Tatsukawa", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.alit.2025.11.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41330846" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Dec 1", "date_precision": "day", "issue": "", "normalized_date": "2025-12-01", "pages": "S1323-8930(25)00118-2", "proceedings_title": null, "publisher": "", "title": "Allergology international : official journal of the Japanese Society of Allergology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Corrigendum to \"Black-box optimization in immunology and beyond: A practical guide to algorithms and future directions\" [Allergol Int 74 (2025) 549-62].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent advancements in machine learning have increased studies predicting neurological outcomes following spinal cord injury (SCI). However, there is limited research on predictive models for bladder and bowel dysfunction outcomes postinjury. This study aims to develop predictive models for bladder and bowel dysfunction outcomes in patients with traumatic SCI and integrate the models into a web application. This study utilized data from 4181 patients with traumatic SCI, registered in the Japan Association of Rehabilitation Database between 1991 and 2015, to develop and validate predictive models. The explanatory variables were categorized into three groups: neurological findings at admission (such as American Spinal Injury Association scores and Functional Independence Measure scores), patient background (including demographics, comorbidities, and insurance status), and SCI pathology (including injury mechanism, vertebral fractures, surgical history, presence of ossification of the posterior longitudinal ligament/OLF, and time to admission). Feature selection was performed using Boruta, excluding features with more than 25% missing values. The target variables were the bladder and bowel functions at discharge, classified into a binary outcome of whether natural urination and defecation were possible. Machine learning models were implemented using PyCaret, and model performance was evaluated using the area under the curve (AUC). Shapley Additive Explanation (SHAP) values assessed the contribution of individual features. A total of 3,949 cases were analyzed, with an average age of 50.3 years. The model with the highest accuracy for predicting bladder function was the gradient boosting model, achieving an AUC of 0.9064 on the test data. For predicting bowel function, the gradient boosting model showed the highest accuracy with an AUC of 0.8714. The top three key predictive factors identified using SHAP values included L3 motor function, time from injury to admission, and the Functional Independence Measure bowel management score, which were common predictors for both bladder and bowel function. The web application of the predictive models can be found at https://takakikitamura-bladder-prediction.hf.space/ and https://takakikitamura-bowel-prediction.hf.space. In conclusion, we developed a predictive model for bladder and bowel dysfunction outcomes after traumatic SCI using machine learning, confirming its high predictive accuracy. Critical predictors included L3 motor function, time from injury to admission, and the degree of bowel dysfunction, all of which were relevant for predicting both bladder and bowel function. These models were made publicly available as a web application.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takaki", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Furuya", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Juntaro", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Toki", "name": null }, { "creator_type": "author", "first_name": "Kyota", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Yazaki", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Gushiken", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Shiga", "name": null }, { "creator_type": "author", "first_name": "Kazuhide", "last_name": "Inage", "name": null }, { "creator_type": "author", "first_name": "Yawara", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Sumihisa", "last_name": "Orita", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Ohtori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1177/08977151251401550" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41334701" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Dec 1", "date_precision": "day", "issue": "", "normalized_date": "2025-12-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of neurotrauma", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of Prognostic Models for Bladder and Bowel Dysfunction in Traumatic Spinal Cord Injury Patients Using Machine Learning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Autonomous bioluminescence systemsgenetically encoded platforms that integrate luciferase enzymes with complete substrate biosynthetic pathwayshave emerged as transformative tools for real-time, noninvasive imaging in living systems. Unlike conventional substrate-dependent bioluminescence, these systems provide continuous light emission without external substrates, enabling long-term monitoring with minimal phototoxicity compared to the use of fluorescence. Here, we present a critical perspective on recent advances in the two best-characterized autonomous systems: bacterial and fungal bioluminescence systems. We assess their molecular mechanisms, protein engineering strategies, and emerging applications in single-cell imaging, multicolor biosensing, and whole-organism monitoring. By comparing their strengths and limitations, we highlight persistent challenges, such as low quantum yield in bacterial bioluminescence and substrate availability constraints in fungal bioluminescence, and discuss strategies to address themincluding AI-guided mutagenesis, de novo protein design, and metabolic pathway optimization. We conclude by outlining application-driven design targets for the next generation of autonomous bioluminescent systems in biomedical research, environmental monitoring, and synthetic biology.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Subhan Hadi", "last_name": "Kusuma", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacsau.5c01072" }, "pmcid": { "normalized": "PMC12648314" }, "pmid": { "normalized": "41311942" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Nov 24", "date_precision": "day", "issue": "11", "normalized_date": "2025-11-24", "pages": "5237-5252", "proceedings_title": null, "publisher": "", "title": "JACS Au", "volume": "5", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Autonomous Bioluminescence Systems: From Molecular Mechanisms to Emerging Applications.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Liver transplantation is almost the only way to save patients with end-stage liver disease. Particularly, living donor liver transplantation (LDLT) has gained importance in recent years thanks to the shorter waiting times and better graft quality than with deceased donor liver transplantation (DDLT). However, some patients experience graft loss due to unexpected infections, sepsis, or immune-mediated rejection of the transplanted organ. An urgent need exists to clarify which patients experience graft loss. Several models have been proposed, but most analyze the classic DDLT, and knowledge about LDLT is lacking. In this study, we retrospectively analyzed clinical data from 748 patients who underwent LDLT. By adapting machine learning methods, we predicted early graft loss (within 180 days postoperatively) with better performance than conventional models. The model enabled us to stratify a highly heterogeneous sample of patients into five groups. By focusing on survival time, we next categorized the patients into three groups with early, intermediate, and late or no graft loss. Notably, we identified the intermediate-loss group as a distinct population similar to the early-loss population but with different survival times. Additionally, by proposing a hierarchical prediction method, we developed an approach to distinguish these populations using data up to 30 days postoperatively. Our findings will enable the early identification of individuals at risk of graft loss, particularly those in the early- and intermediate-loss groups. This will allow for appropriate patient care, such as switching to DDLT, identifying other living donors for LDLT, or preparing for re-transplantation, leading to a bottom-up improvement in transplant success rates.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Raiki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Takeru", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Toshima", "name": null }, { "creator_type": "author", "first_name": "Takasuke", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Katsuhito", "last_name": "Fujiu", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Iwami", "name": null }, { "creator_type": "author", "first_name": "Tomoharu", "last_name": "Yoshizumi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1013734" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41284646" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Graft Rejection", "descriptor_ui": "D006084", "major_topic": true }, { "descriptor": "Graft Survival", "descriptor_ui": "D006085", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver Transplantation", "descriptor_ui": "D016031", "major_topic": true }, { "descriptor": "Living Donors", "descriptor_ui": "D019520", "major_topic": true }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Postoperative Period", "descriptor_ui": "D011184", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Nov 24", "date_precision": "day", "issue": "11", "normalized_date": "2025-11-24", "pages": "e1013734", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "21", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Prediction of graft loss in living donor liver transplantation during the early postoperative period.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Metamorphosis is a key event in development that is conserved in many marine organisms. Ciona intestinalis type A induces metamorphosis through the settlement of papillae onto the substrate. The papilla consists of collocytes (CCs), primary sensory neurons (PSNs), and axial columnar cells (ACCs), but it remains unclear whether PSNs alone can induce metamorphosis. Manipulating single neurons is crucial for elucidating the neural network system that drives metamorphosis. In this study, we developed an optogenetic system in which ChrimsonR, a red-shifted mutant of channelrhodopsin, was expressed exclusively in PSNs, enabling metamorphosis to be induced by light stimulation. A Ciona-optimized self-cleaving peptide, T2A, was used to co-express the Ca(2+) indicator GCaMP6s, allowing us to monitor neural activity during light stimulation. Activation of PSNs alone induced a series of metamorphic events, including epidermal backward movement, mesenchymal cell extravasation, and tail regression. Furthermore, we confirmed that metamorphosis proceeded to the juvenile stage. Metamorphosis was induced even with intermittent light stimulation, and the total stimulation time required for its initiation was approximately 6 minutes. The optogenetic system developed in this study may significantly contribute to elucidating the link between neuronal function and metamorphosis at the single-cell level.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Nozomu M.", "last_name": "Totsuka", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2025.11.014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41274435" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": true }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Metamorphosis, Biological", "descriptor_ui": "D008675", "major_topic": true }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": true }, { "descriptor": "Sensory Receptor Cells", "descriptor_ui": "D011984", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Nov 20", "date_precision": "day", "issue": "", "normalized_date": "2025-11-20", "pages": "S0012-1606(25)00321-5", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Optogenetic activation of primary sensory neurons induces metamorphosis in Ciona.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIMS/HYPOTHESIS: Available methods for predicting the onset and progression of diabetic kidney disease (DKD) and end-stage kidney disease (ESKD) are not yet ready for clinical application. We used a Japanese diabetes cohort study (J-DREAMS) to examine whether the Ahlqvist et al diabetes clustering is useful for stratifying DKD or ESKD outcomes independent of known risk factors in real-world settings. METHODS: Data-driven cluster analysis using k-means was performed based on GAD antibody levels, age at diagnosis, BMI, HbA(1c) and HOMA2 estimates of beta cell function and insulin resistance in 12,093 individuals with type 1 or type 2 diabetes. The risk of developing DKD/ESKD was analysed using Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS: Diabetes clustering classified individuals in the J-DREAMS cohort into five subtypes, the clinical characteristics of which were comparable to those of the previously reported five subtypes. Kaplan-Meier curve analysis showed that events for chronic kidney disease (CKD) stages 3b, 4 and 5 were highest in the severe insulin-resistant diabetes subtype. The Cox proportional hazards model showed that the severe insulin-resistant diabetes subtype had significant HRs after correction for multiple confounding factors. The Cox proportional hazards model showed that each subtype had a diverse combination of factors associated with CKD stage 3b and proteinuria events. CONCLUSIONS/INTERPRETATION: Data-driven analysis provides diabetes subtyping, which can predict the probability of developing DKD/ESKD; each subtype has diverse combinations of factors predisposing to DKD development and progression. Data-driven diabetes subtyping to predict the likelihood of developing DKD/ESKD and mitigating predisposing factors may help personalise prevention strategies.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kiriko", "last_name": "Watanabe-Shimoji", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Ohsugi", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Junichiro J.", "last_name": "Kazama", "name": null }, { "creator_type": "author", "first_name": "Kohjiro", "last_name": "Ueki", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Shimabukuro", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00125-025-06594-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41247492" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 1", "descriptor_ui": "D003922", "major_topic": true }, { "descriptor": "Diabetes Mellitus, Type 2", "descriptor_ui": "D003924", "major_topic": true }, { "descriptor": "Diabetic Nephropathies", "descriptor_ui": "D003928", "major_topic": true }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin Resistance", "descriptor_ui": "D007333", "major_topic": false }, { "descriptor": "Kaplan-Meier Estimate", "descriptor_ui": "D053208", "major_topic": false }, { "descriptor": "Kidney Failure, Chronic", "descriptor_ui": "D007676", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Proportional Hazards Models", "descriptor_ui": "D016016", "major_topic": false }, { "descriptor": "Registries", "descriptor_ui": "D012042", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Nov 17", "date_precision": "day", "issue": "", "normalized_date": "2025-11-17", "pages": "", "proceedings_title": null, "publisher": "", "title": "Diabetologia", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Diverse combination of factors associated with the development of diabetic kidney disease among data-driven diabetes subtypes: analysis of the J-DREAMS registry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jid.2025.10.579" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41217311" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Nov 11", "date_precision": "day", "issue": "", "normalized_date": "2025-11-11", "pages": "S0022-202X(25)03458-X", "proceedings_title": null, "publisher": "", "title": "The Journal of investigative dermatology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic Network Biomarker Analysis Reveals Predisease State in Atopic Dermatitis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stimulus-responsive nanocarriers are good candidates for targeted drug delivery. Herein, inspired by the existence of a clear threshold number of arginine residues in oligoarginines for cell-penetrating peptide (CPP) activity, we developed a strategy to control the CPP activity by changing the local arginine density for thermo-responsive targeting. We constructed polymeric micelles whose shell consists of a thermo-responsive polymer based on N-isopropylacrylamide, with a low density of arginine moieties (named Arg-TRM). At physiological temperature (37 degrees C), internalization of Arg-TRM into cells was small and comparable to that of micelle without arginine. In contrast, upon heating at 42 degrees C, the arginine density on the micellar surface was increased by thermo-responsive shrinkage of the shell, thereby switching on the CPP activity and enabling efficient cellular uptake. The response of Arg-TRM at 42 degrees C occurred within a few minutes and the intracellular uptake was rapidly enhanced from 5 min after the heating. This response was transient, thus enabling reversible control of the enhancement by heating. As proof-of-concept, we show that intravenously administered Arg-TRM was effectively accumulated in one ear of a normal mouse by local heating. These results indicate that Arg-TRM is a promising drug carrier for on-demand targeted drug delivery in response to mild external heating.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Sota", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nagase", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42004-025-01707-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41188588" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Nov 4", "date_precision": "day", "issue": "1", "normalized_date": "2025-11-04", "pages": "325", "proceedings_title": null, "publisher": "", "title": "Communications chemistry", "volume": "8", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Thermo-responsive targeting of polymeric micelles by controlling the cellular uptake based on the change of their surface arginine density.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although the SARS-CoV-2 pandemic has subsided with the widespread rollout of vaccines, emerging variants continue to pose significant public health challenges. While current diagnostic technologies can sensitively detect specific variants, there is an increasing need for broad-spectrum detection methods that are less affected by viral mutations. In particular, the development of diagnostic techniques that are not only broadly applicable but also rapid and cost-effective is highly desirable for large-scale screening and long-term surveillance. In this study, the applicability of a noncompetitive fluorescence polarization aptamer assay (NC-FPAA) was evaluated for detecting SARS-CoV-2, including both the wild-type strain and various variants. Two fluorescently labeled aptamers, a 77-mer (K1) and a 51-mer (M40), previously reported to have broad affinity for spike proteins of different SARS-CoV-2 variants, were used as probes. Detection experiments were conducted using eight SARS-CoV-2 variants, and specificity was further assessed using influenza viruses. The results demonstrate that NC-FPAA has the potential to serve as a diagnostic tool for the rapid, simple, and low-cost detection of multiple SARS-CoV-2 variants, thereby supporting broad and effective viral surveillance.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Chang", "last_name": "Yu-Ting", "name": null }, { "creator_type": "author", "first_name": "Rigel", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Ayuko", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Mao", "last_name": "Fukuyama", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Kasuya", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Takasuke", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Shigemura", "name": null }, { "creator_type": "author", "first_name": "Akihide", "last_name": "Hibara", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Maeki", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Tokeshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsomega.5c06304" }, "pmcid": { "normalized": "PMC12593997" }, "pmid": { "normalized": "41210733" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Nov 4", "date_precision": "day", "issue": "43", "normalized_date": "2025-11-04", "pages": "51228-51235", "proceedings_title": null, "publisher": "", "title": "ACS omega", "volume": "10", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Noncompetitive Fluorescence Polarization Aptamer Assay for Detecting SARS-CoV‑2 Variants.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The RING-H2 type E3 ligase Praja family is composed of E3 ubiquitin-protein ligases Praja1 and Praja2, which promote the degradation of substrates through the ubiquitin-proteasome system. Both paralogs contribute to neuronal maturation and differentiation, indicating a significant role in the nervous system. Aggregation-prone proteins associated with neurodegenerative diseases, including TAR DNA-binding protein 43 (TDP-43) and alpha-synuclein, are degraded and/or suppressed by Praja1. Furthermore, the expression level of the microtubule-associated protein tau (MAPT) gene, which is frequently mutated in Alzheimer's disease, is regulated by Praja2. Although the Praja family has been shown to recognize various aggregation-prone proteins as substrates, it has not been determined whether tau, a key protein that aggregates in tauopathies, is also recognized by Praja proteins. In this study, we show that Praja1, but not Praja2, recognizes tau as a candidate substrate. We observed that the tau protein level in human neuroblastoma SH-SY5Y cells decreased depending on the E3 ligase activity of Praja1. Furthermore, the in vivo/in vitro ubiquitination assay showed that Praja1 ubiquitinates tau, indicating that it is a target substrate. Next, by combining ancestral sequence reconstruction and mutational analysis, we revealed that the Praja1-tau interaction began just after the duplication of the Praja family in the common ancestor of placentals. Lastly, to test whether this interaction is disrupted under pathological conditions, P301L tau was introduced, resulting in a degradation similar to that of wild-type tau. These results reveal an unidentified mechanism of tau proteostasis by Praja1 and may provide insight into the pathogenesis of neurodegenerative diseases, including tauopathy.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shiho", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Onodera", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Imadegawa", "name": null }, { "creator_type": "author", "first_name": "Hikaru", "last_name": "Kurahashi", "name": null }, { "creator_type": "author", "first_name": "Mizuho", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Asahi", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Soeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/febs.70303" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41182881" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Proteolysis", "descriptor_ui": "D059748", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": true }, { "descriptor": "Ubiquitin-Protein Ligases", "descriptor_ui": "D044767", "major_topic": true }, { "descriptor": "Ubiquitination", "descriptor_ui": "D054875", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Nov 3", "date_precision": "day", "issue": "", "normalized_date": "2025-11-03", "pages": "", "proceedings_title": null, "publisher": "", "title": "The FEBS journal", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "E3 ligase Praja1 mediates ubiquitination and degradation of microtubule-associated protein tau.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Prader-Willi syndrome (PWS) is a genomic imprinting disorder caused by the loss of function of the paternal chromosome 15q11-13, resulting in a spectrum of symptoms associated with hypothalamic dysfunction. PWS patients lack the expression of paternally expressed genes (PEGs) in the 15q11-13 locus but possess an epigenetically silenced set of these genes in the maternal allele. Thus, activation of these silenced genes can serve as a therapeutic target for PWS. Here, we leverage CRISPR-based epigenome editing system to modulate the DNA methylation status of the PWS imprinting control region (PWS-ICR) in induced pluripotent stem cells (iPSCs) derived from PWS patients. Successful demethylation in the PWS-ICR restores the PEG expression from the maternal allele and reorganizes the methylation patterns in other PWS-associated imprinted regions beyond the PWS-ICR. Remarkably, these corrected epigenomic patterns and PEG expression are maintained following the differentiation of these cells into hypothalamic organoids. Finally, the single-cell transcriptomic analysis of epigenome-edited organoids demonstrates a partial restoration of the transcriptomic dysregulation observed in PWS. This study highlights the utility of epigenome editing technology as a therapeutic approach in addressing PWS and potentially other imprinting disorders.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akisa", "last_name": "Nemoto", "name": null }, { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Fuyuki", "last_name": "Miya", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Hiroi", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Hirosato", "last_name": "Ideno", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Saitoh", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Kosaki", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Okuno", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-64932-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41152294" } }, "mesh": [ { "descriptor": "Chromosomes, Human, Pair 15", "descriptor_ui": "D002884", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Epigenome", "descriptor_ui": "D000081122", "major_topic": true }, { "descriptor": "Epigenome Editing", "descriptor_ui": "D000098986", "major_topic": false }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": true }, { "descriptor": "Genomic Imprinting", "descriptor_ui": "D018392", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "Prader-Willi Syndrome", "descriptor_ui": "D011218", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Oct 28", "date_precision": "day", "issue": "1", "normalized_date": "2025-10-28", "pages": "9442", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Rescue of imprinted genes by epigenome editing in human cellular models of Prader-Willi syndrome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Clonally expanded CD8(+) T cells may contribute to Alzheimer's disease (AD) pathology through interactions with brain-resident cells. However, the functional impact of AD-specific T cell receptor (TCR) clonotypes remains unclear. Here, we demonstrate that CD8(+) T cells undergo clonal expansion in early-stage AD mouse models, App(NL-G-F) and 5xFAD, and that their depletion reduces amyloid plaque accumulation. Expanded TCR-expressing CD8(+) T cells preferentially infiltrate the brain, exacerbating plaque deposition. Moreover, brain-infiltrating CD8(+) T cells impair microglial transition into disease-associated states, suppressing amyloid clearance via CCL5-CCR5 signaling. Pharmacological blockade of CCL5 attenuates amyloid deposition, whereas CCL5 administration aggravates pathology. Notably, T cell depletion at later disease stages exacerbates amyloid pathology, suggesting a temporal shift in their function. Early-stage CD8(+) T cells exhibit cytotoxic and effector profiles, whereas late-stage cells acquire tissue-resident and exhausted phenotypes. This temporal switch-from pathogenic to protective roles-highlights the stage-specific contribution of CD8(+) T cells to AD and their potential as therapeutic targets.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masaki", "last_name": "Ohyagi", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Iizuka-Koga", "name": null }, { "creator_type": "author", "first_name": "Setsuko", "last_name": "Mise-Omata", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-64503-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41145447" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": true }, { "descriptor": "Amyloid beta-Peptides", "descriptor_ui": "D016229", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": true }, { "descriptor": "Chemokine CCL5", "descriptor_ui": "D018946", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microglia", "descriptor_ui": "D017628", "major_topic": false }, { "descriptor": "Plaque, Amyloid", "descriptor_ui": "D058225", "major_topic": true }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false }, { "descriptor": "Receptors, CCR5", "descriptor_ui": "D019713", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Oct 27", "date_precision": "day", "issue": "1", "normalized_date": "2025-10-27", "pages": "9458", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Stage-specific roles of clonally expanded CD8(+) T cells in regulating amyloid pathology in Alzheimer's disease models.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Xevinapant is an orally bioavailable antagonist of select members of the inhibitor of apoptosis protein (IAP) family. Despite promising phase II data, combining xevinapant with chemoradiotherapy (CRT) failed to improve outcomes in the phase III TrilynX trial when combined with CRT for locally-advanced head and neck squamous cell cancer (SCCHN). In immunocompetent mouse models of SCCHN, xevinapant plus CRT maintained or improved locoregional control, but in a CD8+ T-cell-independent manner. On addition of xevinapant to CRT, numbers of tumour-infiltrating cytotoxic CD8+ T-cells and NK cells were reduced, with remaining CD8+ T-cells characterised by PD-1hi CD38hi expression and Nr4a3 dynamics consistent with non-responsiveness to antigenic re-stimulation. Furthermore, combination treatment significantly downregulated gene expression associated with immune-related pathways, increased levels of immunodysregulatory acute phase proteins and decreased levels of necroptosis mediator RIPK3. Overall, xevinapant plus CRT has an immunosuppressive effect on the tumour-immune microenvironment which may explain its lack of clinical benefit.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Charleen Chan Wah", "last_name": "Hak", "name": null }, { "creator_type": "author", "first_name": "Emmanuel C.", "last_name": "Patin", "name": null }, { "creator_type": "author", "first_name": "Anton", "last_name": "Patrikeev", "name": null }, { "creator_type": "author", "first_name": "Annalisa", "last_name": "Nicastri", "name": null }, { "creator_type": "author", "first_name": "Zuza", "last_name": "Kozik", "name": null }, { "creator_type": "author", "first_name": "Holly", "last_name": "Baldock", "name": null }, { "creator_type": "author", "first_name": "Joan N.", "last_name": "Kyula-Currie", "name": null }, { "creator_type": "author", "first_name": "Victoria", "last_name": "Roulstone", "name": null }, { "creator_type": "author", "first_name": "Amarin", "last_name": "Wongariyapak", "name": null }, { "creator_type": "author", "first_name": "Valentina", "last_name": "Gifford", "name": null }, { "creator_type": "author", "first_name": "Tencho", "last_name": "Tenev", "name": null }, { "creator_type": "author", "first_name": "Elizabeth S.", "last_name": "Appleton", "name": null }, { "creator_type": "author", "first_name": "Lisa C.", "last_name": "Hubbard", "name": null }, { "creator_type": "author", "first_name": "Shane", "last_name": "Foo", "name": null }, { "creator_type": "author", "first_name": "Malin", "last_name": "Pedersen", "name": null }, { "creator_type": "author", "first_name": "Jyoti S.", "last_name": "Choudhary", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Alan A.", "last_name": "Melcher", "name": null }, { "creator_type": "author", "first_name": "Antonio", "last_name": "Rullan", "name": null }, { "creator_type": "author", "first_name": "Kevin J.", "last_name": "Harrington", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/2767-9764.crc-25-0604" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41123992" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": true }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Chemoradiotherapy", "descriptor_ui": "D059248", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Head and Neck Neoplasms", "descriptor_ui": "D006258", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Squamous Cell Carcinoma of Head and Neck", "descriptor_ui": "D000077195", "major_topic": true }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": true }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Oct 22", "date_precision": "day", "issue": "", "normalized_date": "2025-10-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer research communications", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Xevinapant plus chemoradiotherapy negatively sculpts the tumour immune microenvironment in head and neck cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recalled memories become transiently labile and require stabilization(1-3). The mechanism for stabilizing memories of survival-critical experiences, which are often emotionally salient and repeated, remains unclear(4). Here we identify an astrocytic ensemble that is transcriptionally primed by emotional experience and functionally triggered by repeated experience to stabilize labile memory. Using a novel brain-wide Fos tagging and imaging method, we found that astrocytic Fos ensembles were preferentially recruited in regions with neuronal engrams(5) and were more widespread during fear recall than during conditioning. We established the induction mechanism of the astrocytic ensemble, which involves two steps: (1) an initial fear experience that induces day-long, slow astrocytic state changes with noradrenaline receptor upregulation; and (2) enhanced noradrenaline responses during recall, a repeated experience, enabling astrocytes to integrate coincident signals from local engrams and long-range noradrenergic projections, which induce secondary astrocytic state changes, including the upregulation of Fos and the neuromodulatory molecule IGFBP2. Pharmacological and genetic perturbation of the astrocytic ensemble signalling modulate engrams, and memory stability and precision. The astrocytic ensemble thus acts as a multiday trace in a subset of astrocytes after experience-dependent neural activity, which are eligible to capture future repeated experiences for stabilizing memories.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Dewa", "name": null }, { "creator_type": "author", "first_name": "Kodai", "last_name": "Kaseda", "name": null }, { "creator_type": "author", "first_name": "Aoi", "last_name": "Kuwahara", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Kubotera", "name": null }, { "creator_type": "author", "first_name": "Ayato", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Awata", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Komori", "name": null }, { "creator_type": "author", "first_name": "Mika A.", "last_name": "Holtz", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Henrik", "last_name": "Skibbe", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Tatsushi", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Genri", "last_name": "Numata", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Eiki", "last_name": "Takimoto", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41586-025-09619-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41094146" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": true }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Fear", "descriptor_ui": "D005239", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": true }, { "descriptor": "Mental Recall", "descriptor_ui": "D011939", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Norepinephrine", "descriptor_ui": "D009638", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-fos", "descriptor_ui": "D016760", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Oct 15", "date_precision": "day", "issue": "", "normalized_date": "2025-10-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The astrocytic ensemble acts as a multiday trace to stabilize memory.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Machine learning studies for Raman imaging have addressed the differentiability of normal and diseased states in biomedical applications by grouping a set of Raman spectra in terms of spectral similarity over the sample. However, Raman imaging provides both chemical information relevant to the underlying chemical species and their spatial distribution across the biological samples. Utilizing both the chemical and spatial information may further discriminate the sample states more than just using the spectral similarity free from the spatial structure. Here, we develop a Raman image analysis method integrating spatial and chemical information. The crux of our method is to introduce a measure to quantify spatial heterogeneity among Raman spectra at each pixel, and to classify Raman images using information theory, based not directly on the Raman spectra themselves at individual pixels but on the spatial heterogeneity in the spectral space over the surroundings. In this paper, we applied the method to a set of liver tissues dissected from non-alcoholic fatty liver disease (NAFLD) rat model, each of which is pathologically classified into normal, nonalcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), respectively. We show how the pathologically-identified liver states can be further classified using chemical information, and both chemical and spatial information. All NASH tissues that are belonging to a same cluster in spectral similarity are found to be further divided into substates that correlate the progression of the NAFLD disease, and subtle contamination of bloods that often prevents from appropriate pathological judgments. The potential of a use of both chemical and spatial information in Raman imaging is expected to enhance the differentiability of disease states of biological samples.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ryoya", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Jean-Emmanuel", "last_name": "Clement", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-17495-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41083533" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Non-alcoholic Fatty Liver Disease", "descriptor_ui": "D065626", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Oct 13", "date_precision": "day", "issue": "1", "normalized_date": "2025-10-13", "pages": "35216", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Integrating spatial and chemical information enhances differentiation of non-alcoholic steatohepatitis states in Raman imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The standard of care for unresectable, locally advanced non-small-cell lung cancer (NSCLC) is chemoradiotherapy followed by durvalumab. This study (Evolution trial WJOG11819L) aimed to evaluate the efficacy and safety of radiotherapy-free pembrolizumab and chemotherapy in patients with unresectable, locally advanced NSCLC with a PD-L1 tumour proportion score (TPS) of 50% or higher. METHODS: This prospective, multicentre, single-arm, phase 2 study was conducted in nine institutes in Japan. Inclusion criteria were age 20 years or older, histologically confirmed unresectable, locally advanced NSCLC with a PD-L1 TPS of 50% or higher, an Eastern Cooperative Oncology Group performance status of 0 or 1, at least one measurable lesion, no previous systemic therapy, and adequate organ function. Patients received intravenous induction therapy comprising pembrolizumab 200 mg every 3 weeks plus platinum-based chemotherapy for four cycles: either cisplatin 75 mg/m(2) or carboplatin (area under the curve [AUC] 5 for non-squamous NSCLC, AUC 6 for squamous NSCLC) plus pemetrexed 500 mg/m(2) (non-squamous NSCLC) or nanoparticle albumin-bound paclitaxel 100 mg/m(2) on days 1, 8, and 15 (squamous NSCLC). This was followed by maintenance therapy comprising intravenous pembrolizumab (200 mg) with or without intravenous pemetrexed (500 mg/m(2)) every 3 weeks for up to 2 years. The primary endpoint was 2-year progression-free survival and was assessed in the full analysis set (ie, all patients who met the eligibility criteria and received at least one dose of study treatment). The safety analysis set included all patients who received at least one dose of study treatment and had at least one post-treatment safety assessment. This trial was registered with ClinicalTrials.gov (NCT04153734) and is complete. FINDINGS: Between May 18, 2020, and Feb 22, 2022, 21 patients were assessed for eligibility and all were enrolled. Median age was 73 years (IQR 68-80); 16 (76%) patients were male; race and ethnicity data were not collected. Three (14%) patients discontinued and 18 (86%) patients completed the induction therapy; eight (38%) patients discontinued during maintenance therapy and ten (48%) patients completed the maintenance therapy. Median follow-up was 32.5 months (IQR 26.2-39.5). The 2-year progression-free survival rate was 67% (90% CI 46-83). The most common grade 3 or worse adverse events were neutropenia (eight [38%] of 21 patients), leukopenia (four [19%]), and pneumonia (three [14%]). Serious adverse events occurred in seven (33%) patients. No treatment-related deaths were reported. INTERPRETATION: These findings suggest that pembrolizumab combined with platinum-based chemotherapy, without radiotherapy, might provide a feasible and promising alternative treatment strategy for patients with unresectable, locally advanced NSCLC with a PD-L1 TPS of 50% or higher. FUNDING: Merck Sharp & Dohme.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akito", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Taira", "last_name": "Ninomaru", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Yoshihito", "last_name": "Kogure", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Katakami", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kijima", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Terufumi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Sawada", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Seto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Isamu", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/s1470-2045(25)00462-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41082893" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal, Humanized", "descriptor_ui": "D061067", "major_topic": true }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": true }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": true }, { "descriptor": "Carboplatin", "descriptor_ui": "D016190", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Cisplatin", "descriptor_ui": "D002945", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Paclitaxel", "descriptor_ui": "D017239", "major_topic": false }, { "descriptor": "Prospective Studies", "descriptor_ui": "D011446", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Oct 10", "date_precision": "day", "issue": "", "normalized_date": "2025-10-10", "pages": "S1470-2045(25)00462-0", "proceedings_title": null, "publisher": "", "title": "The Lancet. Oncology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Radiotherapy-free pembrolizumab combined with chemotherapy for locally advanced non-small-cell lung cancer with PD-L1 tumour proportion score of 50% or higher (Evolution trial): a multicentre, single-arm, phase 2 study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cryptococcal meningitis is a fungal infection in patients with compromised CD4 T cell function. CD4 T cells provide killing signals to macrophages, principally IFNgamma, to limit intracellular fungal replication. However, CD4 T cells may also drive inflammatory tissue damage. Yet, it is not fully understood how fungal-specific CD4 T cells infiltrate the brain and how they influence functional phenotypes of CNS-resident myeloid cells. In the current work, we develop a mouse model to track fungal-specific CD4 T cells and determine their influence on microglia. We found IFNgamma+ fungal-specific CD4 T cells have limited TCR signalling and characterise a population of inflammatory microglia that upregulate MHCII and IFNgamma-regulated genes during infection. Inflammatory microglia have poor fungicidal capacity and significantly expand during infection, a process that depends on CD4 T cell infiltration. Taken together, these data identify the early inflammatory consequences of fungal-specific CD4 T cell infiltration and identify proliferating microglia as important drivers of brain inflammation during infection.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sofia", "last_name": "Hain", "name": null }, { "creator_type": "author", "first_name": "Man Shun", "last_name": "Fu", "name": null }, { "creator_type": "author", "first_name": "Lucy", "last_name": "Wigg", "name": null }, { "creator_type": "author", "first_name": "Lorna", "last_name": "George", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Lecky", "name": null }, { "creator_type": "author", "first_name": "Alexander J.", "last_name": "Whitehead", "name": null }, { "creator_type": "author", "first_name": "Erin", "last_name": "Clipston", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Marcel", "last_name": "Wuthrich", "name": null }, { "creator_type": "author", "first_name": "Bruce", "last_name": "Klein", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Julie", "last_name": "Rayes", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Bending", "name": null }, { "creator_type": "author", "first_name": "Rebecca A.", "last_name": "Drummond", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-64034-5" }, "pmcid": { "normalized": "PMC12511619" }, "pmid": { "normalized": "41068074" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "CD4-Positive T-Lymphocytes", "descriptor_ui": "D015496", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cryptococcus neoformans", "descriptor_ui": "D003455", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Interferon-gamma", "descriptor_ui": "D007371", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Meningitis, Cryptococcal", "descriptor_ui": "D016919", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Microglia", "descriptor_ui": "D017628", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Oct 9", "date_precision": "day", "issue": "1", "normalized_date": "2025-10-09", "pages": "8995", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Brain-infiltrating CD4 T cells drive inflammatory microglia proliferation during cryptococcal meningitis in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Foxp3(+) regulatory T (T(reg)) cell repertoire carries age-dependent biases, with neonatal subsets enriched for highly self-reactive clones. However, the thymocyte features distinguishing neonatal from adult T(reg) selection remain unclear. Here, we show that neonatal double-positive mouse thymocytes, unlike their adult counterparts, fail to upregulate Zap70 during thymic selection, creating a calcium signaling bottleneck. This attenuated Zap70-dependent signaling limits negative selection, allowing highly self-reactive clones to evade deletion. Modulating Zap70 expression alters this balance; reducing Zap70 in adults rescues development of these clones, whereas increasing Zap70 in neonates enforces their deletion. Similarly, enhancing neonatal calcium signaling via increased LAT Y136-mediated PLCgamma1 activation promotes clonal deletion. Analysis of pediatric human thymi reveals that ZAP70 expression remains low during the first year of life, aligning with the peak window for thymic T(reg) cell development. These findings suggest that age-dependent Zap70 expression regulates negative selection and thymic T(reg) cell development.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Brian D.", "last_name": "Stadinski", "name": null }, { "creator_type": "author", "first_name": "Elizabeth A.", "last_name": "Mills", "name": null }, { "creator_type": "author", "first_name": "Preston A.", "last_name": "Humphries", "name": null }, { "creator_type": "author", "first_name": "Sarah B.", "last_name": "Cleveland", "name": null }, { "creator_type": "author", "first_name": "Parker", "last_name": "Dow", "name": null }, { "creator_type": "author", "first_name": "Koura", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Yue Ru", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Byron B.", "last_name": "Au-Yeung", "name": null }, { "creator_type": "author", "first_name": "Gerald P.", "last_name": "Morris", "name": null }, { "creator_type": "author", "first_name": "Juan Carlos", "last_name": "Zuniga-Pflucker", "name": null }, { "creator_type": "author", "first_name": "Robert A.", "last_name": "Campbell", "name": null }, { "creator_type": "author", "first_name": "Eric R.", "last_name": "Griffiths", "name": null }, { "creator_type": "author", "first_name": "Eric S.", "last_name": "Huseby", "name": null }, { "creator_type": "author", "first_name": "Wan-Lin", "last_name": "Lo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41590-025-02292-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41057723" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Age Factors", "descriptor_ui": "D000367", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Clonal Deletion", "descriptor_ui": "D017637", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Phospholipase C gamma", "descriptor_ui": "D051966", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": true }, { "descriptor": "Thymocytes", "descriptor_ui": "D060168", "major_topic": true }, { "descriptor": "Thymus Gland", "descriptor_ui": "D013950", "major_topic": true }, { "descriptor": "ZAP-70 Protein-Tyrosine Kinase", "descriptor_ui": "D051746", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Oct 7", "date_precision": "day", "issue": "", "normalized_date": "2025-10-07", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature immunology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Age-dependent Zap70 expression in thymocytes regulates selection of the neonatal regulatory T cell repertoire.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The exposome, an individual's lifelong environmental exposure, profoundly impacts health. Somatic tissues undergo functional decline with age, exhibiting characteristic ageing phenotypes, including hair greying and cancer. However, the specific genotoxins, signals and cellular mechanisms underlying each phenotype remain largely unknown. Here we report that melanocyte stem cells (McSCs) and their niche coordinately determine individual stem cell fate through antagonistic, stress-responsive pathways, depending on the type of genotoxic damage incurred. McSC fate tracking in mice revealed that McSCs undergo cellular senescence-coupled differentiation (seno-differentiation) in response to DNA double-strand breaks, resulting in their selective depletion and hair greying, and effectively protecting against melanoma. Conversely, carcinogens can suppress McSC seno-differentiation, even in cells harbouring double-strand breaks, by activating arachidonic acid metabolism and the niche-derived KIT ligand, thereby promoting McSC self-renewal. Collectively, the fate of individual stem cell clones-expansion versus exhaustion-cumulatively and antagonistically governs ageing phenotypes through interaction with the niche.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Mohri", "name": null }, { "creator_type": "author", "first_name": "Jialiang", "last_name": "Nie", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Morinaga", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Aoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yamanashi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Nanba", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Sakura", "last_name": "Kirino", "name": null }, { "creator_type": "author", "first_name": "Kouji", "last_name": "Kobiyama", "name": null }, { "creator_type": "author", "first_name": "Ken J.", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Tamio", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Namiki", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Seita", "name": null }, { "creator_type": "author", "first_name": "Emi K.", "last_name": "Nishimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41556-025-01769-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41053225" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cell Self Renewal", "descriptor_ui": "D000066673", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": false }, { "descriptor": "DNA Breaks, Double-Stranded", "descriptor_ui": "D053903", "major_topic": false }, { "descriptor": "Hair Color", "descriptor_ui": "D006200", "major_topic": true }, { "descriptor": "Melanocytes", "descriptor_ui": "D008544", "major_topic": true }, { "descriptor": "Melanoma", "descriptor_ui": "D008545", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Skin Neoplasms", "descriptor_ui": "D012878", "major_topic": true }, { "descriptor": "Stem Cell Niche", "descriptor_ui": "D055153", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Oct 6", "date_precision": "day", "issue": "", "normalized_date": "2025-10-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature cell biology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Antagonistic stem cell fates under stress govern decisions between hair greying and melanoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Biomolecular condensates, or so-called membraneless organelles, transition from liquid into more solid-like states over time, contributing to the development of pathological conditions. The present study proposes a simple method using photoactive yellow protein (PYP) and its specific fluorescent covalent ligands to distinguish between the liquid and solid states of protein condensates in live cells. The method, compatible with fluorescence-activated cell sorting (FACS), correlates the stiffness of specific protein condensates with their accessibility to PYP ligands, enabling quantitative multicolor monitoring of condensate solidification. We applied this technique to 12 phase-separating proteins and their mutants, finding that TDP-43, particularly its A315T mutant linked to familial amyotrophic lateral sclerosis, most readily forms solid aggregates. Furthermore, this FACS-compatible strategy enabled the isolation of distinct cell populations based on condensate states, allowing for subsequent proteomic and transcriptomic analyses. Our findings demonstrate that condensate solidification is accompanied by the upregulated expression of extracellular matrix proteins, suggesting a previously unrecognized link between solid aggregate formation and extracellular matrix hardening.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Asmaa M. A. S.", "last_name": "Farrag", "name": null }, { "creator_type": "author", "first_name": "Koshiro", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Misao", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Mitarai", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Kamikawa", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Abo", "name": null }, { "creator_type": "author", "first_name": "Vaibhav Pal", "last_name": "Singh", "name": null }, { "creator_type": "author", "first_name": "Changyi", "last_name": "Cui", "name": null }, { "creator_type": "author", "first_name": "Lu", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Fumiyoshi", "last_name": "Ishidate", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Motonari", "last_name": "Uesugi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.5c07340" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41034691" } }, "mesh": [ { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": true }, { "descriptor": "Biomolecular Condensates", "descriptor_ui": "D000091582", "major_topic": true }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Phase Transition", "descriptor_ui": "D044367", "major_topic": false }, { "descriptor": "Photoreceptors, Microbial", "descriptor_ui": "D020283", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Oct 1", "date_precision": "day", "issue": "", "normalized_date": "2025-10-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Live-Cell Monitoring and Omics Analysis of Liquid-Solid Transitions of Biomolecular Condensates.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although previous studies reported that the herpes simplex virus 2 (HSV-2) UL13 protein kinase mediates the phosphorylation of elongation factor 1delta (EF-1delta) in infected cells, we found here that individual expression of UL13 was insufficient to induce phosphorylation of EF-1delta in mammalian cells. This led us to hypothesize that HSV-2 UL13 requires viral cofactors for full kinase activity and prompted us to identify such cofactors. Our results were as follows. (i) Co-expression of UL13 with UL55 or Us10 significantly enhanced phosphorylation of EF-1delta compared to UL13 alone. (ii) UL13 was co-precipitated with UL55 or Us10 upon co-expression, and its kinase activity was significantly increased in their presence, as demonstrated by in vitro kinase assays. (iii) In HSV-2-infected cells, UL13 was co-precipitated with Us10 and UL55. (iv) The UL55-null mutation significantly reduced phosphorylation of EF-1delta in HSV-2-infected cells, whereas the Us10-null mutation had little effect; however, the double-null mutation further decreased the phosphorylation compared to the UL55-null mutation alone. (v) The UL55-null mutation, but not the Us10-null mutation, significantly reduced HSV-2 replication and cell-cell spread in U2OS cells to levels comparable to those observed with the UL13 kinase-dead mutation. These results suggest that UL55 acts as a principal activator of UL13 in HSV-2-infected cells, whereas Us10 serves as an auxiliary activator. Moreover, the role of UL13 kinase activity in HSV-2 replication and cell-cell spread in U2OS cells appears to be largely dependent on UL55.IMPORTANCEHerpesviruses encode conserved protein kinases (CHPKs) that often target cellular cyclin-dependent kinase (CDK) phosphorylation sites. CHPKs from beta- and gammaherpesviruses can exhibit these CDK-like functions even when individually expressed in mammalian cells. In contrast, CHPKs from alphaherpesviruses display these CDK-like functions in infected cells, but not upon individual expression, suggesting that they require additional viral factors to exhibit full kinase activity. In this study, we focused on HSV-2 UL13, an alphaherpesvirus CHPK, and identified HSV-2 UL55 and Us10 as viral activators of UL13. In HSV-2-infected cells, UL55 functions as a principal activator of UL13, while Us10 serves as an auxiliary activator. Importantly, the contribution of UL13 kinase activity to HSV-2 replication and cell-cell spread appears to be largely dependent on the presence of UL55. Our findings uncover a previously unrecognized mechanism of CHPK regulation in alphaherpesviruses and provide new insights into the evolutionary diversification of viral kinase control.", "classifications": [ { "id": "21H00417", "label": "21H00417", "researcher": "Yuhei Maruzuru", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Shio", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01165-25" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41025809" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Herpesvirus 2, Human", "descriptor_ui": "D018258", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immediate-Early Proteins", "descriptor_ui": "D017874", "major_topic": false }, { "descriptor": "Peptide Elongation Factor 1", "descriptor_ui": "D020648", "major_topic": true }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Kinases", "descriptor_ui": "D011494", "major_topic": true }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": true }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Sep 30", "date_precision": "day", "issue": "", "normalized_date": "2025-09-30", "pages": "e0116525", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of viral activators of the HSV-2 UL13 protein kinase.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lysosomal pH is a crucial intracellular parameter for evaluating cellular metabolism, as even minor fluctuations are closely associated with various physiological disorders. Ratiometric fluorescent probes have been developed for monitoring lysosomal pH changes through molecular imaging. However, most of the reported probes suffer from limitations such as inadequate intracellular calibration and short excitation and emission wavelengths, which hinder their accurate pH quantification and restrict their applicability in vivo. Here we report a ratiometric fluorescent probe HeCypH, which was synthesized via a simple approach, to track pH fluctuations. The probe design relies on a hemicyanine scaffold fused with an intramolecular oxazinane ring, which undergoes a pH-responsive ring-opening process. Under acidic conditions, the open-ring form HeCypH-O exhibits two red/near-infrared emission peaks at 615 nm and 722 nm. Confocal fluorescence imaging in living cells revealed that HeCypH selectively localizes in lysosomes and enables ratiometric measurement of intracellular pH with high precision. Moreover, the excellent pH sensitivity, reversibility, and red-shifted emissions of HeCypH make it well suited for real-time monitoring of pH fluctuations and deep-tissue bioimaging in a mouse model.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Huiying", "last_name": "Mu", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d5tb01801c" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41020596" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Infrared Rays", "descriptor_ui": "D007259", "major_topic": false }, { "descriptor": "Lysosomes", "descriptor_ui": "D008247", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Sep 29", "date_precision": "day", "issue": "", "normalized_date": "2025-09-29", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of materials chemistry. B", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "A ratiometric fluorescent probe with dual red/near-infrared emissions for monitoring lysosomal pH fluctuations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The response of cell populations to external stimuli plays a central role in biological mechanical processes such as epithelial wound healing and developmental morphogenesis. Wave-like propagation of a signal of ERK MAP kinase has been shown to direct collective migration in one direction; however, the mechanism based on continuum mechanics under a traveling wave is not fully understood. To elucidate how the traveling wave of the ERK kinase signal directs collective migration, we constructed the mechanical model of the epithelial cell monolayer by considering the signal-dependent coordination of contractile stress and cellular orientation. The proposed model was studied by using an optogenetically controlled cell system where we found that local signal activation induces changes in cell density and orientation with the direction of propagation. The net motion of the cell population occurred relative to the wave, and the migration velocity showed a maximum in resonance with the velocity of the ERK signal wave. The presented mechanical model was further validated in an in vitro wound healing process.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Fukuyama", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Ebata", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Ienaga", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Motomu", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Kidoaki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Yusuke T.", "last_name": "Maeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d5sm00403a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41020443" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": true }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Wound Healing", "descriptor_ui": "D014945", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Sep 29", "date_precision": "day", "issue": "", "normalized_date": "2025-09-29", "pages": "", "proceedings_title": null, "publisher": "", "title": "Soft matter", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Why epithelial cells collectively move against a traveling signal wave.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The initial activation of naive CD8(+) T cells induces three major transcription factor pathways, NFAT, NFkappaB, and AP-1, predominantly regulated by T-cell receptor (TCR) signaling. Downstream of the TCR, the Tec family tyrosine kinase ITK modulates the transcriptional response in T cells by differentially affecting the kinetics and magnitude of activation of these three transcription factors. How signaling through ITK regulates the duration and/or termination of TCR signaling has not been investigated. To address this, we utilized the \"Nr4a3-Tocky\" reporter mouse which provides information on the kinetics of TCR signaling over time courses from hours to days. OT-I CD8(+) Nr4a3-Tocky T cells were stimulated with peptide ligands of varying affinities, and cells were assayed for a panel of surface and intracellular markers of activation and differentiation at multiple time points post-stimulation. As previously reported, at early time points ITK signaling enhanced the kinetics and magnitude of expression of these markers. At later time points the absence of ITK led to persistent expression of several proteins, indicating an important role for ITK in the termination of TCR-dependent transcriptional responses. Using a dual ITK/ RLK inhibitor (PRN694) at 24h post OVA peptide stimulation it was found that this function of ITK was required in the first 24 hours. These findings reveal a possible key negative regulatory mechanism that is programmed in the first day of activation but impacts CD8(+) T cell gene expression patterns days later.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Josh", "last_name": "Hunkins", "name": null }, { "creator_type": "author", "first_name": "Zoe K.", "last_name": "Bedrosian", "name": null }, { "creator_type": "author", "first_name": "Uddeep", "last_name": "Chaudhury", "name": null }, { "creator_type": "author", "first_name": "Alayna", "last_name": "Rosales", "name": null }, { "creator_type": "author", "first_name": "Mary J.", "last_name": "Michaels", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Abhyudai", "last_name": "Singh", "name": null }, { "creator_type": "author", "first_name": "Leslie J.", "last_name": "Berg", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/2025.09.22.677398" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Sep 24", "date_precision": "day", "issue": null, "normalized_date": "2025-09-24", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Regulation of TCR-induced Transcriptional Kinetics by Interleukin 2-inducible T Cell Kinase (ITK) in CD8(+) T cells.", "url": "", "zotero": { "item_type": "preprint" } }, { "abstract": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is still circulating among humans, leading to the continuous evolution. SARS-CoV-2 Omicron JN.1 evolved from a distinct SARS-CoV-2 lineage, BA.2.86, and spread rapidly worldwide. It is unclear why BA.2.86 did not become dominant and was quickly replaced by JN.1, which possesses one amino acid substitution in the spike protein (S:L455S) and two in the non-spike proteins NSP6 and ORF7b (NSP6:R252K and ORF7b:F19L) compared to BA.2.86. Here, we utilized recombinant viruses to elucidate the impact of these mutations on the virological characteristics of JN.1. We found that the mutation in the spike attenuated viral replication, while the non-spike mutations acted synergistically to enhance replication. This suggests that the mutations in the non-spike proteins compensate for the one in the spike, improving viral fitness, as the mutations in the spike contribute to further immune evasion. Our findings suggest that functional changes in both the spike and non-spike proteins are necessary for the evolution of SARS-CoV-2, enabling evasion of adaptive immunity within the human population while sustaining replication. IMPORTANCE: Because the spike protein is strongly associated with certain virological properties of SARS-CoV-2, such as immune evasion and infectivity, most previous studies on SARS-CoV-2 variants have focused on spike protein mutations. However, the non-spike proteins also contribute to infectivity, as observed throughout the evolution of Omicron subvariants. In this study, we demonstrate a \"trade-off\" strategy in SARS-CoV-2 Omicron JN.1 in which the reduced infectivity caused by spike mutation is compensated by non-spike mutations. Our results provide insight into the evolutionary scenario of the emerging virus in the human population.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shuhei", "last_name": "Tsujino", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Naganori", "last_name": "Nao", "name": null }, { "creator_type": "author", "first_name": "Kaho", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Yume", "last_name": "Mimura", "name": null }, { "creator_type": "author", "first_name": "Jingshu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Rigel", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Yoshimatsu", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Matsuno", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takasuke", "last_name": "Fukuhara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00908-25" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40985731" } }, "mesh": [ { "descriptor": "Amino Acid Substitution", "descriptor_ui": "D019943", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Genetic Fitness", "descriptor_ui": "D056084", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true }, { "descriptor": "Spike Glycoprotein, Coronavirus", "descriptor_ui": "D064370", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Nonstructural Proteins", "descriptor_ui": "D017361", "major_topic": true }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Sep 23", "date_precision": "day", "issue": "", "normalized_date": "2025-09-23", "pages": "e0090825", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Evolution of BA.2.86 to JN.1 reveals that functional changes in non-structural viral proteins are required for fitness of SARS-CoV-2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The immune system presents some of the most complex challenges in biology, encompassing nonlinear interactions, high-dimensional regulatory mechanisms, and substantial variability across individuals and contexts. As a result, traditional model-driven approaches often fall short in optimizing experimental conditions or therapeutic strategies. Black-box optimization methods-particularly Bayesian optimization (BO) and evolutionary algorithms (EAs)-offer powerful tools for guiding biological discovery when mechanistic understanding is incomplete or intractable. These algorithms iteratively propose informative experiments by learning from noisy, expensive, and sparse data, enabling efficient exploration of vast experimental spaces. In this review, we provide a comprehensive overview of black-box optimization methodologies and their applications in life science, with a particular focus on immunology and allergy research. We detail how black-box optimization is transforming various stages of biomedical R&D, from molecular design (e.g., antibodies, peptides) and gene circuit tuning to culture protocol optimization and patient-specific dose adjustment. We highlight key algorithmic advances, including constrained, multi-objective, parallel and high-dimensional BO, as well as recent developments such as grey-box optimization and transfer learning. Practical considerations, such as software tools and reproducibility-enhancing checklists, are also discussed. By integrating black-box optimization with automated experimentation platforms and high-throughput biological systems, researchers can accelerate discovery, personalize interventions, and systematically optimize complex immunological processes. We argue that black-box optimization will become a foundational component of experimental design and decision-making in the life sciences, bridging computational strategies with biological insight in increasingly adaptive and interpretable ways.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takanori", "last_name": "Kawabata", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Tsuzuki", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Tatsukawa", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.alit.2025.08.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40987703" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": true }, { "descriptor": "Allergy and Immunology", "descriptor_ui": "D000486", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bayes Theorem", "descriptor_ui": "D001499", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Sep 22", "date_precision": "day", "issue": "", "normalized_date": "2025-09-22", "pages": "S1323-8930(25)00090-5", "proceedings_title": null, "publisher": "", "title": "Allergology international : official journal of the Japanese Society of Allergology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Black-box optimization in immunology and beyond: A practical guide to algorithms and future directions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Maintaining water balance is a prerequisite for all organisms. Euryhaline elasmobranchs face the severest water-influx potential in fresh water (FW), as they retain high concentrations of urea even in hypotonic environments. To elucidate how they overcome this osmotic challenge, we assessed urine output in conscious euryhaline red stingrays (Hemitrygon akajei). Following acclimation to 5% diluted seawater, the stingrays increased urinary output by 87-fold-the greatest change observed in vertebrates-partly due to 6.8-fold increase in glomerular filtration rate (GFR). In the nephron, expressions of Aquaporin-1 (Aqp1), Aqp3, and Aqp15 were strongly downregulated in FW, indicating that tubular diuresis bridges the gap between GFR and final urine volume. Meanwhile, FW-acclimation upregulated Aqp1 and Aqp4 in the distinct bundle structure, which promotes urea reabsorption. Euryhaline elasmobranchs resolve the huge osmotic challenge of FW by excreting massive amounts of water and retaining osmolytes including urea through coordinated regulation of GFR and Aqp expressions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naotaka", "last_name": "Aburatani", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Marty Kwok-Shing", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Kuraku", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Waichiro", "last_name": "Godo", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Hyodo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2025.113274" }, "pmcid": { "normalized": "PMC12496175" }, "pmid": { "normalized": "41054505" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Sep 19", "date_precision": "day", "issue": "9", "normalized_date": "2025-09-19", "pages": "113274", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "28", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Extensive urine production in euryhaline red stingray for adaptation to hypoosmotic environments.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hematopoietic stem cells (HSCs) possess unique characteristics that distinguish them from other hematopoietic progenitor cells, including self-renewal capacity, multipotency, stress response, metabolism, and deep quiescence. Recent advances have significantly enhanced our understanding of the epigenomic states that define these properties. HSCs undergo profound changes in their three-dimensional (3D) genome reorganization throughout development, differentiation, and responses to stimuli. Recent advancements in chromatin conformation capture techniques that require only a small number of cells have provided detailed insights into these dynamic processes. This review explores the latest discoveries in the 3D genome reorganization in HSCs, with a focus on chromatin remodeling during key transitions, including fetal-to-adult development, quiescence-to-activation, differentiation, and aging. We discuss the roles of key transcription factors, epigenetic modifiers, and structural proteins in shaping the 3D genome landscape. Additionally, we examine how alterations in the 3D genome organization impact HSC function and dysfunction in hematological disorders. Finally, we highlight future directions in this rapidly evolving field, emphasizing the potential implications of 3D genome research for targeted therapies in hematology.Teaser Abstract: Hematopoietic stem cells (HSCs) are defined by self-renewal, multipotency, stress response, metabolism, and quiescence. Advances in chromatin conformation capture reveal how their 3D genome organization changes during development, activation, differentiation, and aging. This review covers chromatin remodeling, key transcription factors, epigenetic modifiers, and structural proteins in shaping HSC genome architecture, and how its disruption contributes to hematological disorders, highlighting therapeutic prospects.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihiro", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Kirito", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Takayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.exphem.2025.105249" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40975221" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Chromatin Assembly and Disassembly", "descriptor_ui": "D042002", "major_topic": true }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Genome, Human", "descriptor_ui": "D015894", "major_topic": true }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Sep 18", "date_precision": "day", "issue": "", "normalized_date": "2025-09-18", "pages": "105249", "proceedings_title": null, "publisher": "", "title": "Experimental hematology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Three-dimensional Genome Reorganization in Hematopoietic Stem Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A key issue in the post-COVID-19 pandemic era is the ongoing administration of COVID-19 vaccines. Repeated vaccination is essential for preparing against currently circulating and newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. However, optimizing vaccination strategies is crucial to efficiently manage medical resources and establish an effective vaccination framework. Therefore, a strategy to identify poor responders with lower sustained antibody titers would be beneficial because these individuals should be considered high priority for revaccination. We investigated longitudinal antibody titer data in a cohort of 2526 people in Fukushima, Japan, collected between April 2021 and November 2022. Using mathematical modeling and machine learning, we stratified the time-course patterns of antibody titers after two primary doses and one booster dose of COVID-19 messenger RNA vaccines. We identified three populations, which we refer to as the durable, the vulnerable, and the rapid-decliner populations, and approximately half of the participants remained in the same population after the booster dose. The rapid-decliner population experienced earlier infections than the others. Furthermore, when comparing spike protein-specific immunoglobulin G (IgG) titers, spike protein-specific IgA titers, and SARS-CoV-2-specific T cell responses between participants who experienced subsequent infections after booster vaccination and those who did not, we found that spike protein-specific IgA titers were lower during the early stage after booster vaccination in participants who went on to become infected with SARS-CoV-2. This approach could be used to inform policy decisions on vaccine distribution to maximize population-level immunity both in future pandemics and in the post-COVID-19 pandemic era.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hyeongki", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kwang Su", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Kosaku", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Yurie", "last_name": "Kobashi", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Tani", "name": null }, { "creator_type": "author", "first_name": "Yuzo", "last_name": "Shimazu", "name": null }, { "creator_type": "author", "first_name": "Tianchen", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Omata", "name": null }, { "creator_type": "author", "first_name": "Moe", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Yoshika", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Morihito", "last_name": "Takita", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Morioka", "name": null }, { "creator_type": "author", "first_name": "Katsuhiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Sagou", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Yudai", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Risa Yokokawa", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Kodama", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Kamiyama", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Takasuke", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Shibuya", "name": null }, { "creator_type": "author", "first_name": "Tadaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Iwami", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Tsubokura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/scitranslmed.adv4214" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40961221" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Antibodies, Viral", "descriptor_ui": "D000914", "major_topic": true }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "COVID-19 Vaccines", "descriptor_ui": "D000086663", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunization, Secondary", "descriptor_ui": "D007117", "major_topic": false }, { "descriptor": "Immunoglobulin G", "descriptor_ui": "D007074", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Longitudinal Studies", "descriptor_ui": "D008137", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true }, { "descriptor": "Spike Glycoprotein, Coronavirus", "descriptor_ui": "D064370", "major_topic": false }, { "descriptor": "Vaccination", "descriptor_ui": "D014611", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Sep 17", "date_precision": "day", "issue": "816", "normalized_date": "2025-09-17", "pages": "eadv4214", "proceedings_title": null, "publisher": "", "title": "Science translational medicine", "volume": "17", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Longitudinal antibody titers measured after COVID-19 mRNA vaccination can identify individuals at risk for subsequent infection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Embryonic diapause is a temporary suspension of proliferation in mammalian pre-implantation embryos, allowing for reactivation later. Cells in mouse diapause embryos enter the G0 phase within 7 days of diapause initiation. Here, we show that approximately 5% of cells in embryonic tissues continue to proliferate even after 7 days of diapause. Transcriptome and phenotypic analyses reveal that p53 facilitated DNA damage repair via p21-mediated cell cycle arrest and regulated epiblast cell numbers via Bax-mediated apoptosis. Moreover, epiblast cell numbers strongly correlated with reactivation rates, with deviations from optimal levels impairing successful reactivation. Our findings call into question the conventional view that all cells in diapause embryos uniformly enter G0. We established epiblast characteristics as predictive factors for determining reactivation success, the defining event of diapause.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" }, { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Megumi", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Hinako", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Teppei", "last_name": "Shimamura", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Katsuyoshi", "last_name": "Takaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2025.116298" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40971292" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "bcl-2-Associated X Protein", "descriptor_ui": "D051028", "major_topic": false }, { "descriptor": "Cell Count", "descriptor_ui": "D002452", "major_topic": false }, { "descriptor": "Cell Cycle Checkpoints", "descriptor_ui": "D059447", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p21", "descriptor_ui": "D050759", "major_topic": false }, { "descriptor": "Diapause", "descriptor_ui": "D000074767", "major_topic": true }, { "descriptor": "DNA Repair", "descriptor_ui": "D004260", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": true }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Germ Layers", "descriptor_ui": "D005855", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Sep 17", "date_precision": "day", "issue": "10", "normalized_date": "2025-09-17", "pages": "116298", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "44", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "p53-mediated regulation of epiblast cell numbers predicts reactivation during mouse embryonic diapause.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Microglia, the resident macrophages in the central nervous system (CNS), have been intensively studied using rodent genetic models, including the Cre-loxP system. Among them are tamoxifen (TAM)-inducible CX3C chemokine receptor 1 (Cx3cr1)-Cre mouse lines (Cx3cr1(CreERT2)), which have enabled in-depth analyses of the biological features and functions of myeloid cells, including microglia. Occasionally, these Cx3cr1(CreERT2) tools have yielded conflicting biological outcomes, the underlying mechanism of which remains unclear. Here, we comparatively characterized the two available Cx3cr1(CreERT2) lines (Cx3cr1(CreERT2(Litt)) and Cx3cr1(CreERT2(Jung))). We find a mouse line-specific and TAM-dependent persistent induction of cyclin-dependent kinase inhibitor 1A (CDKN1A, also known as p21) in microglia of Cx3cr1(CreERT2(Litt)) mice, but not in those of Cx3cr1(CreERT2(Jung)) mice, which affects experimental readouts with altered proliferative capacity. Furthermore, aberrant cellular alterations observed in postnatal Cx3cr1(CreERT2(Litt)) microglia are mitigated by a functional inhibition of CDKN1A. Together, these findings underscore the significance of mouse line-specific phenomena that alter microglial outcomes in a CDKN1A-dependent manner.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ayato", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Shintaku", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Saeki", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Marco", "last_name": "Prinz", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kishi", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Masuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2025.116267" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40928945" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "CX3C Chemokine Receptor 1", "descriptor_ui": "D000073883", "major_topic": true }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p21", "descriptor_ui": "D050759", "major_topic": true }, { "descriptor": "Integrases", "descriptor_ui": "D019426", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microglia", "descriptor_ui": "D017628", "major_topic": true }, { "descriptor": "Tamoxifen", "descriptor_ui": "D013629", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Sep 9", "date_precision": "day", "issue": "9", "normalized_date": "2025-09-09", "pages": "116267", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "44", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Cyclin-dependent kinase inhibitor 1A mediates mouse line- and fate-dependent cellular responses in Cx3cr1-Cre genetic tools.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Post-Intensive Care Syndrome (PICS) is a serious condition involving physical weakness, depression, and cognitive impairment that develop during or after an intensive care unit (ICU) stay, often resulting in long-term declines in quality of life. Patients with acute respiratory distress syndrome (ARDS) and severe COVID-19 are at particularly high risk, yet the molecular mechanisms underlying PICS remain poorly understood. Here, we identify impaired Apelin-APJ signaling as a potential contributor to PICS pathogenesis via disruption of inter-organ homeostasis. Using a mouse model combining acute lung injury and hindlimb immobilization, we observed PICS-like features including muscle atrophy, lung inflammation, and neurobehavioral abnormalities such as anxiety-like behavior and special working memory. Single-cell RNA sequencing in brain revealed upregulation of gene programs associated with Alzheimer disease, depression, and neuroinflammation, particularly in endothelial cells and microglia. Concurrently, Apelin-APJ signaling was downregulated in skeletal muscle. These changes were exacerbated in Apelin-deficient mice and attenuated by muscle-specific Apelin overexpression, which also reduced systemic IL-6 and restored circulating Apelin levels. In ARDS survivors with severe COVID-19, ICU-acquired weakness (ICU-AW) was associated with reduced plasma Apelin and elevated IL-6 levels. Transcriptomic profiling of peripheral blood mononuclear cells from ICU-AW patients showed gene expression signatures linked to depression and neurodegeneration, mirroring murine findings. These data suggest that impaired Apelin-APJ signaling may play a role in PICS pathophysiology. While skeletal muscle appears to contribute to systemic Apelin levels, further studies are needed to clarify tissue-specific roles. Modulating this pathway could offer a therapeutic strategy to mitigate long-term outcomes in ICU survivors.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yumiko", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Yasuha", "last_name": "Kinugasa", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Nukiwa", "name": null }, { "creator_type": "author", "first_name": "Mara Anais Llamas", "last_name": "Covarrubias", "name": null }, { "creator_type": "author", "first_name": "Khin Kyaemon", "last_name": "Thwin", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Yonezaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Fujino", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Kubodera", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Kotani", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Furuyashiki", "name": null }, { "creator_type": "author", "first_name": "Josef", "last_name": "Penninger", "name": null }, { "creator_type": "author", "first_name": "Arthur S.", "last_name": "Slutsky", "name": null } ], "identifiers": { "doi": { "normalized": "10.1165/rcmb.2025-0028oc" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40920972" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apelin", "descriptor_ui": "D000073861", "major_topic": true }, { "descriptor": "Apelin Receptors", "descriptor_ui": "D000075244", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Critical Illness", "descriptor_ui": "D016638", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Sep 8", "date_precision": "day", "issue": "", "normalized_date": "2025-09-08", "pages": "", "proceedings_title": null, "publisher": "", "title": "American journal of respiratory cell and molecular biology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Protective Role of Apelin in a Mouse Model of Post-Intensive Care Syndrome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In conventional drug discovery, particularly for small molecules, investigating a small compound that matches the structure of the target molecule and alters its activity has been a crucial process. On the other hand, artificially regulating the activity of a target molecule that is inherently present in cells or organisms and involved in a physiological function can cause various side effects. One possible approach to overcoming this side effect problem is to explore molecules that affect the behavior or motility of molecules related to diseases. If a screening method is developed to search for drugs that target only specific motions of the target molecules, a new concept of motility-targeted drug discovery will be created. In this review article, single-molecule live imaging -a core technology for analyzing the motility of molecules in living cells and organisms -is introduced by describing examples of single-molecule imaging, such as membrane receptors and RNAs. The potential of single-molecule imaging to contribute to drug discovery is also discussed.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1146/annurev-pharmtox-062624-025717" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40911773" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drug Discovery", "descriptor_ui": "D055808", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "Single Molecule Imaging", "descriptor_ui": "D000072760", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Sep 5", "date_precision": "day", "issue": "", "normalized_date": "2025-09-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "Annual review of pharmacology and toxicology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Possible Direction of Drug Discovery Based on Single-Molecule Live Imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fragile X syndrome (FXS) is the foremost monogenic cause of autism spectrum disorder and intellectual disability, caused by FMR1 gene silencing. Here, we report that common marmosets carrying FMR1 mutation, a non-human primate model for FXS, share common features in behavioral and molecular phenotypes with patients with FXS. Founder mutants with markedly reduced fragile X messenger ribonucleoprotein expression display hyperactivity, spontaneous seizures, and transcriptome changes in synapse-related genes that overlap with those reported in patients with FXS. Although spontaneous seizures in these mutants lead to postnatal lethality, the lethality is rescued by introducing mutations into the GRM5 gene, suggesting that elevated mGluR5 signaling contributes to the phenotype. F1 heterozygous females carrying a uniform mutation exhibit phenotypes associated with FXS, including alterations in vocal development and social preferences, electroencephalographic abnormalities, and impaired motor skills. Thus, female marmosets heterozygous for the FMR1 mutation represent a valuable translational model for investigating FXS mechanisms and potential therapeutic strategies.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Maria", "last_name": "Harbers", "name": null }, { "creator_type": "author", "first_name": "Zefeng", "last_name": "Wei", "name": null }, { "creator_type": "author", "first_name": "Harumi", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Motoki", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Moe", "last_name": "Tamano", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Kimiko", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugaya", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Atsu", "last_name": "Aiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2025.116208" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40912249" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Callithrix", "descriptor_ui": "D002144", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fragile X Messenger Ribonucleoprotein 1", "descriptor_ui": "D051860", "major_topic": true }, { "descriptor": "Fragile X Syndrome", "descriptor_ui": "D005600", "major_topic": true }, { "descriptor": "Heterozygote", "descriptor_ui": "D006579", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Receptor, Metabotropic Glutamate 5", "descriptor_ui": "D064529", "major_topic": false }, { "descriptor": "Seizures", "descriptor_ui": "D012640", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Aug 27", "date_precision": "day", "issue": "", "normalized_date": "2025-08-27", "pages": "116208", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "FMR1 mutant marmosets show fragile X syndrome phenotypes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Synaptic transmission has long been thought to regulate neuronal wiring during postnatal development, but this assumption remains largely untested. Selective strengthening of a single \"winner\" climbing fiber (CF) afferent to each Purkinje cell (PC) and elimination of the other \"loser\" CF axons in the cerebellum has been a representative model of neural circuit refinement. Here, we examined the role of neurotransmission at CF-PC synapses in their postnatal development. We labeled a subset of CFs in neonatal mice with fluorescent markers and the tetanus toxin light chain to ablate neurotransmitter release from these CFs. Surprisingly, we found that such neurotransmitter release-deficient CFs were able to become the winners. However, synaptic transmission was crucial for the winning CF to extend its synaptic territory along the PC dendritic arbor and eliminate the loser CFs. These findings reveal how synaptic transmission governs multiple steps of synapse elimination but not the selection of the winner input that persists throughout life.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tzu-Huei", "last_name": "Kao", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Okuno", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Matsuyama", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2416797122" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40838889" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": true }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": true }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Aug 26", "date_precision": "day", "issue": "34", "normalized_date": "2025-08-26", "pages": "e2416797122", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "122", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Synaptic transmission is dispensable for selecting the winner input but is crucial for the subsequent events of synapse elimination.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Anti-pituitary-specific transcription factor (PIT)-1 hypophysitis is an autoimmune disease characterized by hormone secretion impairment from PIT-1-expressing pituitary cells, accompanied by malignancies with ectopic PIT-1 expression. Cytotoxic T cells (CTL) targeting PIT-1-positive cells have been implicated in disease development, yet direct evidence is lacking. As human leukocyte antigen (HLA)-matching is required for modeling T cell-mediated autoimmune diseases, we employ induced pluripotent stem cells (iPSC) to generate pituitary organoids harboring the patients' HLA haplotype and coculture the organoids with PIT-1-reactive CTLs isolated from the patients' peripheral blood mononuclear cells. The coculture demonstrates specific CTL-mediated cytotoxicity against PIT-1-positive cells exclusively in autologous conditions, with this cytotoxicity inhibited by immunosuppressive agents such as dexamethasone and cyclosporin A. Multiple combinations of epitopes, CTLs, and HLA molecules are responsible for pathogenesis. These data demonstrate CTL-mediated autoimmunity in anti-PIT-1 hypophysitis and highlight the potential application of this strategy for other T cell-mediated autoimmune diseases.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Keitaro", "last_name": "Kanie", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Genzo", "last_name": "Iguchi", "name": null }, { "creator_type": "author", "first_name": "Ryusaku", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Urai", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Kitayama", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Fukuoka", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-63183-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40855071" } }, "mesh": [ { "descriptor": "Autoimmune Diseases", "descriptor_ui": "D001327", "major_topic": true }, { "descriptor": "Autoimmune Hypophysitis", "descriptor_ui": "D000069281", "major_topic": true }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "HLA Antigens", "descriptor_ui": "D006680", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunosuppressive Agents", "descriptor_ui": "D007166", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Octamer Transcription Factor-3", "descriptor_ui": "D050814", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": true }, { "descriptor": "Pituitary Gland", "descriptor_ui": "D010902", "major_topic": false }, { "descriptor": "T-Lymphocytes, Cytotoxic", "descriptor_ui": "D013602", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Aug 25", "date_precision": "day", "issue": "1", "normalized_date": "2025-08-25", "pages": "7900", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Modeling of T cell-mediated autoimmune pituitary disease using human induced pluripotent stem cell-originated organoid.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescence microscopy enables the visualization of cellular morphology, molecular distribution, ion distribution, and their dynamic behaviors during biological processes. Enhancing the signal-to-noise ratio (SNR) in fluorescence imaging improves the quantification accuracy and spatial resolution; however, achieving high SNR at fast image acquisition rates, which is often required to observe cellular dynamics, still remains a challenge. In this study, we developed a technique to rapidly freeze biological cells in milliseconds during optical microscopy observation. Compared to chemical fixation, rapid freezing provides rapid immobilization of samples while more effectively preserving the morphology and conditions of cells. This technique combines the advantages of both live-cell and cryofixation microscopy, i.e., temporal dynamics and high SNR snapshots of selected moments, and is demonstrated by fluorescence and Raman microscopy with high spatial resolution and quantification under low temperature conditions. Furthermore, we also demonstrated that intracellular calcium dynamics can be frozen rapidly and visualized using fluorescent ion indicators, suggesting that ion distribution and conformation of the probe molecules can be fixed both spatially and temporally. These results confirmed that our technique can time-deterministically suspend and visualize cellular dynamics while preserving molecular and ionic states, indicating the potential to provide detailed insights into sample dynamics with improved spatial resolution and temporal accuracy in observations.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Wakana", "last_name": "Miyamura", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Mizushima", "name": null }, { "creator_type": "author", "first_name": "Kakeru", "last_name": "Kono", "name": null }, { "creator_type": "author", "first_name": "Hanae", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Momoko", "last_name": "Shiozaki", "name": null }, { "creator_type": "author", "first_name": "Xiaowei", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Heqi", "last_name": "Xi", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Kunimoto", "name": null }, { "creator_type": "author", "first_name": "Yoshino", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Rainer", "last_name": "Heintzmann", "name": null }, { "creator_type": "author", "first_name": "Zhiheng", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Meng C.", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41377-025-01941-8" }, "pmcid": { "normalized": "PMC12373960" }, "pmid": { "normalized": "40846863" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Aug 23", "date_precision": "day", "issue": "1", "normalized_date": "2025-08-23", "pages": "275", "proceedings_title": null, "publisher": "", "title": "Light, science & applications", "volume": "14", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Time-deterministic cryo-optical microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herpesviruses replicate their genomes and package them into capsids within the host cell nucleus. These capsids must then translocate from the nucleus to the cytoplasm through a process designated nuclear egress. The virus-encoded nuclear egress complex (NEC), consisting of a nuclear matrix protein and a nuclear membrane protein, plays a crucial role in this process. Although the role of NEC for nucleo-cytoplasmic transport of capsids is conserved in Herpesviridae, some of the binding partners of the NEC components are specific for individual viruses. The NECs of alpha- and gammaherpesviruses recruit the Endosomal Sorting Complex Required for Transport III (ESCRT-III) to the inner nuclear membrane for efficient nuclear egress of capsids. In contrast, the role of ESCRT-III for nuclear egress of betaherpesviruses, including human cytomegalovirus (HCMV) and human herpesvirus 6A (HHV-6A), has not been elucidated. Here, we show that ESCRT-III is recruited to the nuclear rim in cells expressing the NEC of HCMV or of HHV-6A. Inhibition of ESCRT-III impaired HHV-6A replication and nuclear egress of the capsids. Mechanistically, ESCRT-III adaptor ALIX interacts with HHV-6A NEC membrane protein U34 and thus contributes to HHV-6A replication. From these observations, we conclude that, like at least some alpha- and gammaherpesviruses, HHV-6A NEC recruits ESCRT-III through ALIX to promote viral capsid nuclear egress.IMPORTANCEESCRT-III performs reverse-topology scission involved in many diverse cellular processes, including cytokinesis, endosome maturation, autophagy, membrane repair, and viral budding. Nucleo-cytoplasmic transport of herpesvirus capsids requires scission at the inner nuclear membrane. In alpha- and gammaherpesviruses, this process requires ESCRT-III, but it is not known whether this is also the case for betaherpesviruses. Here, we show that ESCRT-III is also important for nuclear egress of capsids of the betaherpesvirus human herpesvirus 6A. These results imply that ESCRT-III-mediated inner nuclear membrane scission is a conserved feature in the virion maturation process of Herpesviridae. Our findings thus suggest that ESCRT-III is a potential therapeutic target also for betaherpesvirus infections.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Aila", "last_name": "Gulijiahani", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Vuk", "last_name": "Isakovic", "name": null }, { "creator_type": "author", "first_name": "Jing Rin", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00844-25" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40827914" } }, "mesh": [ { "descriptor": "Capsid", "descriptor_ui": "D002213", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": true }, { "descriptor": "Cytomegalovirus", "descriptor_ui": "D003587", "major_topic": false }, { "descriptor": "Endosomal Sorting Complexes Required for Transport", "descriptor_ui": "D056827", "major_topic": true }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Herpesvirus 6, Human", "descriptor_ui": "D015654", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nuclear Envelope", "descriptor_ui": "D009685", "major_topic": false }, { "descriptor": "Nucleocapsid", "descriptor_ui": "D019251", "major_topic": true }, { "descriptor": "Virus Release", "descriptor_ui": "D057074", "major_topic": true }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Aug 19", "date_precision": "day", "issue": "", "normalized_date": "2025-08-19", "pages": "e0084425", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "ESCRT-III is recruited by human herpesvirus 6A nuclear egress complex to promote nuclear egress of the nucleocapsid.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent advances in computing technology and the development of data utilization environments have rapidly accelerated the application of artificial intelligence in clinical research and healthcare. This review provides a comprehensive overview of current machine learning techniques for analyzing clinical data, with illustrative examples from the field of allergic diseases. In addition to conventional methods for clinical data analysis, we discuss emerging approaches including medical image analysis and time-series modeling of electronic health record data. Recent developments such as large language models and foundation models trained on massive datasets are also discussed. Looking ahead, we explore future directions in analytical methodology, including mathematical modeling, interpretable artificial intelligence, and multimodal learning that integrates various data types. We also introduce the concept of the digital twin-a virtual representation of an individual patient that simulates disease progression and treatment response-as a promising concept for advancing precision medicine. Finally, we discuss the essential role of physicians in the development and implementation of machine learning tools and discuss emerging ethical issues such as fairness, privacy, and patient autonomy. By synthesizing recent technical advances with clinical relevance, this review aims to provide clinicians and researchers with a practical and forward-looking guide to machine learning in clinical medicine, including its growing application in the field of allergy.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yutaro", "last_name": "Fuse", "name": null }, { "creator_type": "author", "first_name": "Shawn N.", "last_name": "Murphy", "name": null }, { "creator_type": "author", "first_name": "Hisahiro", "last_name": "Ikari", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Kenshiro", "last_name": "Fuse", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.alit.2025.06.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40835529" } }, "mesh": [ { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": true }, { "descriptor": "Data Analysis", "descriptor_ui": "D000078332", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypersensitivity", "descriptor_ui": "D006967", "major_topic": true }, { "descriptor": "Language", "descriptor_ui": "D007802", "major_topic": false }, { "descriptor": "Large Language Models", "descriptor_ui": "D000098342", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Precision Medicine", "descriptor_ui": "D057285", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Aug 19", "date_precision": "day", "issue": "", "normalized_date": "2025-08-19", "pages": "S1323-8930(25)00080-2", "proceedings_title": null, "publisher": "", "title": "Allergology international : official journal of the Japanese Society of Allergology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Artificial intelligence in clinical data analysis: A review of large language models, foundation models, digital twins, and allergy applications.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Differentiated muscle cells contain myofibrils and well-organized organelles, enabling powerful contractions. Muscle cell reorganization occurs in response to various physiological stimuli; however, the mechanisms behind this remodeling remain enigmatic due to the lack of a genetically trackable system. Previously, we reported that a subset of larval muscle cells is remodeled into adult abdominal muscle through an autophagy-dependent mechanism in Drosophila. To unveil the underlying mechanisms of this remodeling, we performed a comparative time-course RNA-seq analysis of isolated muscle cells with or without autophagy. It revealed both transcriptional dynamics independent of autophagy and highlighted the significance of BNIP3-mediated mitophagy in muscle remodeling. Mechanistically, we found that BNIP3 recruits autophagic machinery to mitochondria through its LC3-interacting motif and minimal essential region, which interact with Atg8a and Atg18a, respectively. Loss of BNIP3 leads to a substantial accumulation of larval mitochondria, ultimately impairing muscle remodeling. In summary, this study demonstrates that BNIP3-dependent mitophagy is critical for orchestrating the dynamic process of muscle remodeling.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Taoka", "name": null }, { "creator_type": "author", "first_name": "Tadayoshi", "last_name": "Murakawa", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Kaminishi", "name": null }, { "creator_type": "author", "first_name": "Yuriko", "last_name": "Sakamaki", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Tomotake", "last_name": "Kanki", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Naonobu", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.105834" }, "pmcid": { "normalized": "PMC12349898" }, "pmid": { "normalized": "40801807" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autophagy-Related Proteins", "descriptor_ui": "D000071183", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": true }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": true }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": true }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Mitochondrial Proteins", "descriptor_ui": "D024101", "major_topic": true }, { "descriptor": "Mitophagy", "descriptor_ui": "D063306", "major_topic": true }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Aug 13", "date_precision": "day", "issue": "", "normalized_date": "2025-08-13", "pages": "", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "14", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Transcriptional dynamics uncover the role of BNIP3 in mitophagy during muscle remodeling in Drosophila.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The conversion of CO(2) into methanol through hydrogenation represents a promising approach for the utilization of CO(2) and sustainable chemical production. However, current industrial methods rely on copper-based catalysts, which exhibit low CO(2) conversion and limited methanol yields and require high temperatures and pressures. In this study, we utilized a machine-learning (ML) approach to develop low-temperature CO(2) hydrogenation catalysts. By employing iterative ML model predictions and experimental validation in batch reactors, we screened 580 distinct catalysts and identified 33 catalysts that outperformed the previously reported highly active catalyst (Pt(3)/Mo(20)/TiO(2)). The best catalyst, Pt(5)/Mo(8)-Re(1)-W(0.7)/TiO(2), exhibited a methanol production rate of 1.46 mmol g(-1) h(-1) in a batch reactor and a high production rate of 1.8 mmol g(-1) h(-1) in a flow reactor at 150 degrees C under 4 MPa (H(2)/CO(2) = 3). In situ/operando spectroscopic analysis was conducted to elucidate the function of each catalyst component in the methanol synthesis. Detailed analysis revealed that in the best catalyst, Pt primarily facilitated H(2) dissociation, partially reduced Mo oxides were crucial in generating oxygenated species, and the presence of acidic W promoted methanol desorption from the catalyst surface. Re promoted the formate conversion to methanol, thus accelerating the overall methanol formation.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shirun", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Mine", "name": null }, { "creator_type": "author", "first_name": "Gang", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Weiyang", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Abdellah Ait", "last_name": "El Fakir", "name": null }, { "creator_type": "author", "first_name": "Bin", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Zengwei", "last_name": "Qin", "name": null }, { "creator_type": "author", "first_name": "Nazmul Hasan Md", "last_name": "Dostagir", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Toyao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.5c09727" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40794468" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Aug 12", "date_precision": "day", "issue": "", "normalized_date": "2025-08-12", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of Highly Active Catalysts for Low-Temperature CO(2) Hydrogenation to Methanol Using a Machine Learning Approach.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescence imaging is a powerful technique for visualizing biological events in living samples, and new fluorescence-control mechanisms are still needed to extend the scope of biomolecule-targeting fluorogenic probes. Twisted intramolecular charge transfer (TICT) is a unique fluorescence quenching mechanism that depends upon a twisted conformation to promote intramolecular charge separation. Probes utilizing TICT can detect biological molecules/phenomena, such as viscosity, polarity and extended protein structures, that cannot readily be accessed by probes employing other fluorescence-control mechanisms, such as photoinduced electron transfer or spirocyclization. In this review, we summarize recent work on molecular design strategies for TICT-based fluorogenic probes, focusing on structural-modification approaches to control the ease of TICT state formation.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hisashi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Sumitani", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d5cc01802a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40779645" } }, "mesh": [ { "descriptor": "Electron Transport", "descriptor_ui": "D004579", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Aug 8", "date_precision": "day", "issue": "", "normalized_date": "2025-08-08", "pages": "", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Recent advances in fluorogenic probes based on twisted intramolecular charge transfer (TICT) for live-cell imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Patients' clinical status often evolves rapidly after an initial diagnosis, with each patient exhibiting a distinct disease trajectory. As a result, static risk scores fall short in supporting timely interventions-an issue highlighted by COVID-19, where deaths have stemmed from heterogeneous pathways such as pneumonia, multiorgan failure, or exacerbation of preexisting conditions. OBJECTIVE: This study aims to propose a dynamic prognostic risk assessment framework based on longitudinal data collected during hospitalization, using COVID-19 as an example. Our aim was to develop and validate an interpretable framework that (1) screens prognosis at admission and (2) dynamically updates mortality risk throughout hospitalization, thereby providing clinicians with early, explainable warnings while minimizing additional cognitive load. METHODS: In this retrospective study, we extracted electronic medical records of 382 COVID-19 cases treated at Tokyo Shinagawa Hospital between January 27 and September 30, 2020. At admission, gradient boosting decision trees (Light Gradient Boosting Machine) were used to predict the maximum clinical deterioration, including death, based on data available at initial diagnosis. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). For in-hospital monitoring, random survival forests (RSF) were trained on a longitudinal dataset that combined static demographic characteristics with serially measured vital signs and laboratory results. The model dynamically assessed daily mortality risk by calculating a 7-day cumulative hazard function, with risk scores recalculated each day during hospitalization. RSF accuracy was evaluated in an independent one-third test set using the concordance index (C-index), an integrated Brier score (1-50 days), and mean time-dependent AUC. SurvSHAP(t), an extension of Shapley Additive Explanations, was applied to provide time-dependent explanations of each variable's contribution to the prediction. RESULTS: The prediction at initial diagnosis showed good agreement with the actual severity outcomes (AUC of 0.717 for predicting hospitalization/severity >/=2; 0.878 for severity >/=3; 0.951 for severity >/=4; 0.952 for severity >/=5; and 0.970 for death/severity=6), although some cases exhibited discrepancies between the predicted and actual prognoses. The dynamic mortality risk assessment during hospitalization using the RSF achieved a test-set C-index of 0.941, an integrated Brier score of 0.315, and a mean time-dependent AUC of 0.936. This dynamic assessment was able to distinguish between dead and surviving patients as early as 1-2 weeks before the outcome. Early in hospitalization, C-reactive protein was an important risk factor for mortality; during the middle period, peripheral oxygen saturation (SpO2) gained importance; and immediately before death, platelets and beta-D-glucan were the primary risk factors. CONCLUSIONS: Integrating static admission triage with daily, explainable RSF predictions enables early identification of patients with COVID-19 at high risk of deterioration. By surfacing phase-specific, actionable predictors, the framework supports timely interventions and more efficient resource allocation. Prospective, multicenter studies are warranted to validate its generalizability and clinical impact.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Shinoda", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Oya", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ashizaki", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Kamachi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Sakurada", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Shinkai", "name": null } ], "identifiers": { "doi": { "normalized": "10.2196/65585" }, "pmcid": { "normalized": "PMC12501906" }, "pmid": { "normalized": "41084807" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hospitalization", "descriptor_ui": "D006760", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Risk Assessment", "descriptor_ui": "D018570", "major_topic": false }, { "descriptor": "ROC Curve", "descriptor_ui": "D012372", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Aug 7", "date_precision": "day", "issue": "", "normalized_date": "2025-08-07", "pages": "e65585", "proceedings_title": null, "publisher": "", "title": "JMIR formative research", "volume": "9", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Explainable Machine Learning Framework for Dynamic Monitoring of Disease Prognostic Risk: Retrospective Cohort Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nuclear receptors (NRs) play pivotal roles in functionally diverse cell signaling cascades, regulating metabolism and homeostasis. This study introduces a broadly applicable molecular imaging platform for NR activities based on four rationally designed single-chain bioluminescent probes named P1-P4. As all the ligand binding domains (LBDs) of NRs are highly conserved, the probe portfolio was exemplified using the LBD of peroxisome proliferator-activated receptor gamma (PPARgamma-LBD), i.e., the LBD was centrally positioned and fused with luciferases and/or fluorescent proteins based on the schemes of the protein-fragment complementation assay (PCA), molecular strain (MS) probe, circular permutation (CP) probe, and bioluminescence resonance energy transfer (BRET) system. In the developing process, we identified the optimal dissection sites for the marine luciferase RLuc for PCA systems and validated them in in vitro and in vivo studies in response to various ligands. Among the probes, P3 and P4 series probes exhibited strong BL intensities in response to a PPARgamma agonist with signal-to-background ratios of maximally 14-fold. The animal study using furimazine (FMZ) substrate analogs such as Ad-FMZ showed that the probes can sustain agonist-dependent BL signals for up to 24 h in animal models. Considering the biological importance of NRs, the molecular imaging platform with the portfolio of probes developed in this study can contribute to interrogate many NR-related cell signaling pathways by replacing the PPARgamma-LBD with LBDs from other NRs in the probes.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sung-Bae", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Tadaomi", "last_name": "Furuta", "name": null }, { "creator_type": "author", "first_name": "Genta", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Shojiro A.", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Orioka", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Suresh", "last_name": "Thangudu", "name": null }, { "creator_type": "author", "first_name": "Arutselvan", "last_name": "Natarajan", "name": null }, { "creator_type": "author", "first_name": "Ramasamy", "last_name": "Paulmurugan", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsomega.5c04665" }, "pmcid": { "normalized": "PMC12332630" }, "pmid": { "normalized": "40787404" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Aug 5", "date_precision": "day", "issue": "30", "normalized_date": "2025-08-05", "pages": "33850-33861", "proceedings_title": null, "publisher": "", "title": "ACS omega", "volume": "10", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Imaging Ligand-Driven PPAR Activities Using Single-Chain Bioluminescent Probes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Aging is a risk factor for severe COVID-19, characterized by vascular endothelial dysfunction. Although possible susceptibility of vascular endothelial cells (ECs) to SARS-CoV-2 infection has been suggested, the details of entry into cells have not been clarified. Previously, we reported that in an aged mouse model of severe COVID-19, ECs show a massive viral uptake and inflammatory response. Here, we focused on the endocytic capacity of senescent ECs. We found that the senescent ECs showed high endocytic capacity and SARS-CoV-2 virus uptake. This triggers an nuclear factor-kappa B (NF-kappaB) pathway-mediated inflammatory response. Further, Basigin enhanced endocytosis in the senescent ECs by activating the intracellular vascular endothelial growth factor signaling. Thus, EC senescence is associated with enhanced SARS-CoV-2 endocytosis and subsequent vascular endothelial dysfunction. This could prove a potential target for treating severe COVID-19 in older adults.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuya", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Nako", "last_name": "Maishi", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Michihito", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Takahito", "last_name": "Teshirogi", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Hida", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Kanta", "last_name": "Kido", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Orba", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Hida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2502724122" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40720650" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basigin", "descriptor_ui": "D051926", "major_topic": true }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": true }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": true }, { "descriptor": "Human Umbilical Vein Endothelial Cells", "descriptor_ui": "D061307", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor Receptor-2", "descriptor_ui": "D040301", "major_topic": true }, { "descriptor": "Virus Internalization", "descriptor_ui": "D053586", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Aug 5", "date_precision": "day", "issue": "31", "normalized_date": "2025-08-05", "pages": "e2502724122", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "122", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "SARS-CoV-2 uptake and inflammatory response in senescent endothelial cells are regulated by the BSG/VEGFR2 pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Near-infrared photoimmunotherapy (NIR-PIT) employing an antibody labeled with a silicon phthalocyanine dye, IR700, was approved as a minimally invasive treatment for unresectable recurrent head and neck cancer in Japan in 2020. However, further derivatization of IR700 is needed to increase the efficiency of cancer treatment. Here, we developed SiPc-1 as an IR700 analog, in which the linker was constructed using click chemistry to simplify the synthetic scheme and its position was switched from alpha to beta on the benzene ring of phthalocyanine to eliminate intramolecular steric repulsion. We evaluated the cleavage rate of the water-soluble axial moieties of SiPc-1 upon photoirradiation, the cytotoxicity, and the morphological change (blebbing) of treated cells upon photoirradiation. We performed gene expression and protein expression analyses to find a target antigen selectively expressed on cells infected with human T-cell lymphotropic virus type 1 (HTLV-1), the causative virus of adult T-cell leukemia/lymphoma (ATL), and identified CD25 as a suitable target antigen. An anti-CD25 antibody, basiliximab, labeled with SiPc-1 (bas-SiPc-1) showed selective toxicity towards HTLV-1-infected cultured cells and ATL patients' peripheral blood mononuclear cells upon photoirradiation.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Fuse", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Tamaki", "name": null }, { "creator_type": "author", "first_name": "Shunto", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yasunaga", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Hisataka", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Nakasone", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d5cb00150a" }, "pmcid": { "normalized": "PMC12360215" }, "pmid": { "normalized": "40837968" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Aug 5", "date_precision": "day", "issue": "", "normalized_date": "2025-08-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "RSC chemical biology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a silicon phthalocyanine analogue for near-infrared photoimmunotherapy and its application to HTLV-1-infected leukemic cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Influenza A viruses (IAVs) initially infect a few host cells before spreading to neighboring cells. However, the molecular mechanisms underlying this dissemination remain unclear. We have previously demonstrated that intracellular Ca(2+) plays a crucial role in facilitating IAV infection. This study aims to clarify the connections between intracellular Ca(2+) dynamics and spread of IAV infection. METHODS: Madin-Darby canine kidney (MDCK) cells stably expressing a Ca(2+) indicator for optical imaging were established. Cells were cultured in Matrigel to form monolayers, and cell-to-cell Ca(2+) dynamics within IAV-infected cells were analyzed using fluorescence microscopy. RESULTS: IAV infection upregulated the frequency of intercellular calcium wave propagations (iCWPs), facilitating viral spread. ADP released from initially infected cells mediated iCWPs via the P2Y(1) receptor. P2Y(1) antagonist suppressed both the generation of iCWPs and spread of viral infection. Enhanced endocytosis by the surrounding cells that received ADP signaling upregulated viral entry. Expression of IAV matrix protein 2 (M2) in initially infected cells triggered iCWPs through ADP diffusion, thereby increasing infection. Conversely, an ion permeability-deficient mutation of M2 or inhibition of its ion channel activity suppressed iCWPs. CONCLUSIONS: Intercellular calcium signaling plays a crucial role in the early expansion and establishment of IAV infection, presenting a potential target for IAV prophylaxis.", "classifications": [ { "id": "19H05411", "label": "19H05411", "researcher": "Yusuke Ohba", "type": "grant" }, { "id": "21H00413", "label": "21H00413", "researcher": "Yoichiro Fujioka", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Fumiya", "last_name": "Kozawa", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Taishi", "last_name": "Kakizuka", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Rumi", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hironoshin", "last_name": "Onizuska", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Kamasaki", "name": null }, { "creator_type": "author", "first_name": "Maho", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Takasuke", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12964-025-02357-y" }, "pmcid": { "normalized": "PMC12317542" }, "pmid": { "normalized": "40753252" } }, "mesh": [ { "descriptor": "Adenosine Diphosphate", "descriptor_ui": "D000244", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Influenza A virus", "descriptor_ui": "D009980", "major_topic": true }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "Receptors, Purinergic P2Y1", "descriptor_ui": "D058472", "major_topic": false }, { "descriptor": "Viral Matrix Proteins", "descriptor_ui": "D014763", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Aug 2", "date_precision": "day", "issue": "1", "normalized_date": "2025-08-02", "pages": "361", "proceedings_title": null, "publisher": "", "title": "Cell communication and signaling : CCS", "volume": "23", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The crucial role of intercellular calcium wave propagation triggered by influenza A virus in promoting infection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cell cycle is a highly coordinated process governed by cyclin-bound cyclin-dependent kinases (CDKs). While the interaction between cyclin and CDK are well-documented, the dissociation constants (Kd) between specific cyclin-CDK pairs within living cells remain poorly understood. Fluorescence cross-correlation spectroscopy (FCCS) enables the quantification of the Kd, but challenges remain in selecting an optimal pair of fluorescent molecules for FCCS in a living cell. In this study, we demonstrate that mNeonGreen and phycocyanobilin-bound miRFP670 represent a suitable pair for FCCS in living cells from the viewpoint of high photostability and low bleed-through. This fluorescent protein pair enables us to measure the Kd values of the cyclin-dependent kinase Cdc2 and B-type cyclin Cdc13 in fission yeast cells. Moreover, we roughly estimated the Kd values for 36 cyclin-CDK complexes, formed by 9 distinct cyclins and 4 CDKs, in mammalian cells, including unconventional cyclin-CDK pairs. These measurements suggest potential versatility of cyclin-CDK binding in cell cycle progression, with implications for understanding cell cycle regulation in both fission yeast and higher eukaryotes.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Aika", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/jcs.263921" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40741734" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinases", "descriptor_ui": "D018844", "major_topic": true }, { "descriptor": "Cyclins", "descriptor_ui": "D016213", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": true }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Schizosaccharomyces", "descriptor_ui": "D012568", "major_topic": false }, { "descriptor": "Schizosaccharomyces pombe Proteins", "descriptor_ui": "D029702", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul 31", "date_precision": "day", "issue": "", "normalized_date": "2025-07-31", "pages": "jcs.263921", "proceedings_title": null, "publisher": "", "title": "Journal of cell science", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000455" ] }, "title": "Quantification of Cyclin-CDK dissociation constants using FCCS with green and near-infrared fluorescent proteins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herpesvirus nucleocapsids are transported from the nucleus to the cytoplasm via a conserved process known as nuclear egress, which is mediated by the nuclear egress complex (NEC) consisting of two core viral proteins. Although the NEC structure is conserved among herpesviruses, functional divergence may exist. Human herpesvirus 6A (HHV-6A) and HHV-6B are genetically similar members of the Roseolovirus genus within the Betaherpesvirinae subfamily, yet they differ in their pathogenic profiles. In this study, we examined and compared the functions of NEC components U37 and U34 from HHV-6A and HHV-6B. We demonstrated that HHV-6A U34 localizes to the nuclear envelope via its C-terminal transmembrane domain and is essential for viral replication. Moreover, NEC components from HHV-6A and HHV-6B colocalize at the nuclear rim and share a high degree of sequence similarity. These findings suggest that the nuclear egress mechanism is highly conserved within roseoloviruses, despite their distinct biological properties.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Aila", "last_name": "Gulijiahani", "name": null }, { "creator_type": "author", "first_name": "Vuk", "last_name": "Isakovic", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/1348-0421.70004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40715028" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": true }, { "descriptor": "Herpesvirus 6, Human", "descriptor_ui": "D015654", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nuclear Envelope", "descriptor_ui": "D009685", "major_topic": false }, { "descriptor": "Nucleocapsid", "descriptor_ui": "D019251", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": true }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul 27", "date_precision": "day", "issue": "", "normalized_date": "2025-07-27", "pages": "", "proceedings_title": null, "publisher": "", "title": "Microbiology and immunology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparative Analysis of the Nuclear Egress Complex in Human Herpesvirus 6A and 6B.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vasculitis and vascular injury are induced in coronavirus disease 2019 (COVID-19) patients, suggesting an association between multi-organ failure and sequelae. Vascular endothelial dysfunction induced by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) disrupts vascular barrier function, activates coagulation pathways, and induces extravasation of inflammatory cells. In addition to employing standard anti-inflammatory and antiviral agents, using treatments that stabilize and protect blood vessels following SARS-CoV-2 infection is a potentially effective strategy to relieve COVID-19 severity. Here, we focused on the vasoprotective effects of lysophosphatidic acid (LPA), a lipid mediator with diverse activities, and investigated whether it could be a novel therapeutic for COVID-19. Three-dimensional cultures of various human vascular endothelial cells that form luminal structures showed increased expression of LPA4 and entry receptors for SARS-CoV-2 infection, mimicking blood vessels in vivo. Validation using this culture system showed that LPA attenuated SARS-CoV-2 infection-induced vascular destruction and the activation of inflammatory signaling. In experiments with infected animals, LPA administration protected blood vessels and suppressed inflammation and vascular damage in lung tissue. The activation of LPA signaling in vascular endothelial cells may be an effective therapeutic approach for mitigating vascular injury in COVID-19.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Naoi", "last_name": "Hosoe", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Teppei", "last_name": "Shimamura", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takara", "name": null }, { "creator_type": "author", "first_name": "Lamri", "last_name": "Lynda", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Weizhen", "last_name": "Jia", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-06569-7" }, "pmcid": { "normalized": "PMC12297521" }, "pmid": { "normalized": "40715151" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "COVID-19 Drug Treatment", "descriptor_ui": "D000093485", "major_topic": true }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lysophospholipids", "descriptor_ui": "D008246", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Vascular System Injuries", "descriptor_ui": "D057772", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jul 25", "date_precision": "day", "issue": "1", "normalized_date": "2025-07-25", "pages": "24622", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Vasoprotective effects of lysophosphatidic acid inhibit vascular injury caused by SARS-CoV-2 infection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: We previously reported that TRIO pY2681, a novel prognostic biomarker for CRC, can be detected by polyclonal antibodies (pAb). We have now developed a novel monoclonal antibody (mAb) that recognizes TRIO pY2681. This study aims to assess the utility of immunohistochemical (IHC) staining using the TRIO pY2681 mAb as a prognostic marker for CRC in clinical practice. METHODS: IHC using TRIO pY2681 mAb was performed on surgical specimens from 357 CRC patients at Kyoto Medical Center and 320 at Kyoto University Hospital. Based on the results, we conducted a retrospective outcome analysis. RESULTS: TRIO pY2681 mAb exhibited significantly higher titers than pAb. In both cohorts of all stages, TRIO pY2681 IHC positivity correlated with shorter disease-specific survival (DSS) (HR, 1.67; 95% CI, 1.00-2.79; P = 0.046, and HR, 5.84; 95% CI, 2.26-15.1; P < 0.001) and relapse-free survival (RFS) (HR, 1.92; 95% CI, 1.15-3.22; P = 0.011, and HR, 4.36; 95% CI, 2.17-8.76; P < 0.001). The trend persisted in stage III. Multivariate analysis confirmed TRIO pY2681 IHC positivity as an independent prognostic factor for RFS. CONCLUSIONS: The novel TRIO pY2681 mAb identifies CRC patient subsets with poorer prognoses, enhancing prognostic precision in clinical settings.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Taro", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Kakizaki", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Miyoshi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null }, { "creator_type": "author", "first_name": "Hisatsugu", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Yoshiro", "last_name": "Itatani", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Matsusue", "name": null }, { "creator_type": "author", "first_name": "Iwao", "last_name": "Ikai", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Moriyoshi", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Obama", "name": null }, { "creator_type": "author", "first_name": "Tosiya Shun", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yoshiharu", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Makoto Mark", "last_name": "Taketo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s44276-025-00163-0" }, "pmcid": { "normalized": "PMC12297228" }, "pmid": { "normalized": "40715467" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jul 25", "date_precision": "day", "issue": "1", "normalized_date": "2025-07-25", "pages": "53", "proceedings_title": null, "publisher": "", "title": "BJC reports", "volume": "3", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Monoclonal antibody for phosphorylated TRIO Y2681 that helps predict prognosis of post-operative colorectal cancer patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent advances in fish freshness evaluation rely on a combination of optical imaging and artificial intelligence due to their applicability to non-invasive and non-destructive measurements. Using trout salmon, red sea bream, and Japanese amberjack, we investigated the feasibility of using autofluorescence spectroscopy, influenced by biochemical reactions, to assess the freshness of fish filets. Spectral analyses using principal component analysis and curve-fitting revealed considerable differences among species. No common spectral changes were associated with the production of inosine monophosphate (IMP), a known freshness indicator. However, fluorescence attributed to flavin adenine dinucleotide oxidation emerged as a potential universal indicator of oxidative state across species, with the largest increase observed in Japanese amberjack, which lacks astaxanthin. These findings suggest that change in autofluorescence spectra reflects oxidative progression during storage but does not correlate with IMP production. Therefore, autofluorescence can reflect the oxidative status but is not suitable for regressive prediction of IMP production.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kaho", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Kyota", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Saiki", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.foodchem.2025.145577" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40729997" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fishes", "descriptor_ui": "D005399", "major_topic": true }, { "descriptor": "Food Storage", "descriptor_ui": "D061353", "major_topic": false }, { "descriptor": "Sea Bream", "descriptor_ui": "D021541", "major_topic": false }, { "descriptor": "Seafood", "descriptor_ui": "D017747", "major_topic": true }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul 16", "date_precision": "day", "issue": "Pt 1", "normalized_date": "2025-07-16", "pages": "145577", "proceedings_title": null, "publisher": "", "title": "Food chemistry", "volume": "493", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparative analysis of autofluorescence spectra in a filet of three fish species during chilled storage for raw consumption.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Microglia, resident immune cells of the central nervous system, play an essential role in responding to pathological conditions by adopting diverse activation states and morphologies. Recent single-cell RNA sequencing have revealed that microglial subtypes were heterogeneous based on their gene expression profiles. However, the mechanism on how morphological changes in microglia are correlated with their gene expression profiles remains unclear. The current study aimed to identify a distinct population of rod-shaped microglia, characterized by an elongated morphology, in glutamyl cysteine ligase (GCLC)-deficient mice, a model of glutathione deficiency-induced oxidative stress. In the process of brain atrophy accompanied by neuronal cell death, which was observed in GCLC-KO mice, the rod-shaped microglia emerged in early stages of neurodegeneration and subsequently decreased in number over time. C1q-mediated synaptic pruning has been implicated in microglial activation under pathological conditions. Thus, whether C1q contributes to the formation of rod-shaped microglia was investigated. Notably, the genetic deletion of C1q did not affect the number or distribution of rod-shaped microglia in GCLC-KO mice. These findings suggest that their formation occurs via a C1q-independent mechanism. According to morphological and molecular analyses, the gene expression profile of the rod-shaped microglia was similar to that of the disease-associated microglia (DAM). To investigate the mechanisms underlying their formation, single-nucleus RNA sequencing was performed on cortical tissues collected from GCLC-KO mice. DAM-like microglial clusters were consistently identified. Further, pathway enrichment analysis suggested the potential involvement of the urokinase-type plasminogen activator (uPA, encoded by Plau) signaling. Considering the role of uPA in extracellular matrix degradation and cell migration, it may contribute to the morphological changes in rod-shaped microglia. In addition, the phosphorylation of growth-associated protein 43 (GAP43), a modification linked to structural plasticity, increased in rod-shaped microglia. Based on these findings, uPA signaling and phosphorylated GAP43 may be involved in microglial elongation and alignment along neuronal fibers, which potentially facilitate their migration during early neurodegenerative responses. Taken together, the rod-shaped microglia are a previously unrecognized activated population that emerges early in neurodegeneration and may be involved in disease-related processes. Understanding their molecular regulation can provide insights into early microglial responses and potential therapeutic targets.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yukio", "last_name": "Matsuba", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Kadota", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Takaomi C.", "last_name": "Saido", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12974-025-03504-5" }, "pmcid": { "normalized": "PMC12269120" }, "pmid": { "normalized": "40671004" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Complement C1q", "descriptor_ui": "D015922", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Microglia", "descriptor_ui": "D017628", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jul 16", "date_precision": "day", "issue": "1", "normalized_date": "2025-07-16", "pages": "184", "proceedings_title": null, "publisher": "", "title": "Journal of neuroinflammation", "volume": "22", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Rod-shaped microglia represent a morphologically distinct subpopulation of disease-associated microglia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Innovative identification technologies for hematopoietic stem cells (HSCs) have expanded the scope of stem cell biology. Clinically, the functional quality of HSCs critically influences the safety and therapeutic efficacy of stem cell therapies. However, most analytical techniques capture only a single snapshot, disregarding the temporal context. A comprehensive understanding of the temporal heterogeneity of HSCs necessitates live-cell, real-time and non-invasive analysis. Here, we developed a prediction system for HSC diversity by integrating single-HSC ex vivo expansion technology with quantitative phase imaging (QPI)-driven machine learning. By analyzing the cellular kinetics of individual HSCs, we discovered previously undetectable diversity that snapshot analysis cannot resolve. The QPI-driven algorithm quantitatively evaluates stemness at the single-cell level and leverages temporal information to significantly improve prediction accuracy. This platform advances the field from snapshot-based identification of HSCs to dynamic, time-resolved prediction of their functional quality based on past cellular kinetics.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takao", "last_name": "Yogo", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Hans Jiro", "last_name": "Becker", "name": null }, { "creator_type": "author", "first_name": "Takaharu", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Sugiyama-Finnis", "name": null }, { "creator_type": "author", "first_name": "Tomomasa", "last_name": "Yokomizo", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yamazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-61846-3" }, "pmcid": { "normalized": "PMC12260078" }, "pmid": { "normalized": "40659629" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Quantitative Phase Imaging", "descriptor_ui": "D000097913", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul 14", "date_precision": "day", "issue": "1", "normalized_date": "2025-07-14", "pages": "6496", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative phase imaging with temporal kinetics predicts hematopoietic stem cell diversity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Inkjet printing of pi-conjugated organic compounds enabled rapid, low-cost generation of training images for the image-based machine learning (ML) prediction of mixing ratios. ML models with mean absolute errors below 4% were achieved within hours, even for dyes with subtle color differences. Changing the printing surface from filter paper to a polypropylene film extended the method to colorless compounds, including isomeric and macrocyclic systems. This approach also enabled spatial mapping of sub-microgram levels of Zn(2+) ions using a weakly responsive colorimetric sensor, without the need for a spectrometer. This work demonstrates a simple, versatile strategy for integrating pi-conjugated materials with ML in colorimetric sensing and mixture analysis.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taichi", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Terauchi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Yasuhide", "last_name": "Inokuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.orglett.5c02270" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40651000" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jul 12", "date_precision": "day", "issue": "", "normalized_date": "2025-07-12", "pages": "", "proceedings_title": null, "publisher": "", "title": "Organic letters", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Image-Based Machine Learning Using Inkjet-Printed Chemicals: Mixing Ratio Prediction and Metal Ion Detection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Advancements in cytometry technologies have led to a remarkable increase in the number of markers that can be analyzed simultaneously, presenting significant challenges in data analysis. Traditional approaches, such as dimensional reduction techniques and computational clustering, although popular, often face reproducibility challenges due to their heavy reliance on inherent data structures. This reliance prevents the direct translation of their outputs into gating strategies for downstream experiments. Here, we propose the novel Gating Tree methodology, a pathfinding approach that investigates the multidimensional data landscape to unravel group-specific features without the use of dimensional reduction. This method employs novel measures, including enrichment scores and gating entropy, to effectively identify group-specific features within high-dimensional cytometric data sets. Our analysis, applied to both simulated and real cytometric data sets, demonstrates that the Gating Tree not only identifies group-specific features comprehensively but also produces outputs that are immediately usable as gating strategies for pinpointing key cell populations. Furthermore, by integrating machine learning methods, including Random Forest, we have benchmarked Gating Tree against existing methods, demonstrating its superior performance. A range of supervised and unsupervised methods implemented in Gating Tree thus provides effective visualization and output data, which can be immediately used as successive gating strategies for downstream study.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cyto.a.24948" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40616426" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul 5", "date_precision": "day", "issue": "", "normalized_date": "2025-07-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cytometry. Part A : the journal of the International Society for Analytical Cytology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "GatingTree: Pathfinding Analysis of Group-Specific Effects in Cytometry Data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The crustacean Daphnia magna produces genetically identical females and males by parthenogenesis. Males are produced in response to environmental cues including crowding and lack of food. For male development, the DM-domain containing transcription factor Doublesex1 (DSX1) is expressed spatiotemporally in male-specific traits and orchestrates male trait formation in both somatic and gonadal tissues. However, it remains unknown how the dsx1 gene is silenced in females to avoid male trait development. Heterochromatin Protein 1 (HP1) plays a crucial role in epigenetic gene silencing during developmental processes. Here we report the identification of four HP1 orthologs in D. magna. None of these orthologs exhibited sexually dimorphic expression, and among them, HP1-1 was most abundantly expressed during embryogenesis. The knock-down of HP1-1 in female embryos led to the derepression of dsx1 in the male-specific traits, resulting in the development of male characteristics, such as the elongation of the first antennae. These results suggest that HP1-1 silences dsx1 for female development while environmental cues unlock this silencing to induce male production. We infer the HP1-dependent formation of a sex-specific chromatin structure on the dsx1 locus is a key process in the environmental sex determination of D. magna.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Junya", "last_name": "Leim", "name": null }, { "creator_type": "author", "first_name": "Nikko", "last_name": "Adhitama", "name": null }, { "creator_type": "author", "first_name": "Quang Dang", "last_name": "Nong", "name": null }, { "creator_type": "author", "first_name": "Pijar", "last_name": "Religia", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/jdb13030023" }, "pmcid": { "normalized": "PMC12286036" }, "pmid": { "normalized": "40700141" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jul 3", "date_precision": "day", "issue": "3", "normalized_date": "2025-07-03", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of developmental biology", "volume": "13", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "HP1-Mediated Silencing of the Doublesex1 Gene for Female Determination in the Crustacean Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Anti-epileptics and diuretics, used for unapproved purposes, have been reported to ameliorate social deficits in individuals with autism spectrum disorder. However, the underlying neural mechanisms remain unclear. Here, we explored the effects of bumetanide, clonazepam, and phenytoin, all with clinically reported properties for improving social deficits, in a prenatal valproic acid exposure male mouse model. By combining comprehensive behavioral analysis with brain-wide mapping of Arc, an immediate early gene, we found a correlation between social behaviors and Arc-positive cell counts across brain areas. Network analysis identified the medial prefrontal and sensory-related cortices as critical nodes with high centrality, playing critical roles in connecting other brain regions. These metrics are associated with both the decreased social behaviors and their recovery following drug treatment. Our findings suggest that restoring the centralities of the medial prefrontal and sensory-related cortices serve as a potential biomarker for evaluating drug efficacy in autism spectrum disorder.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Iyanaga", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Kunida", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Tanuma", "name": null }, { "creator_type": "author", "first_name": "Misuzu", "last_name": "Hayashida", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Jin", "last_name": "Ohkubo", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Tomoka", "last_name": "Ao", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Shiho", "last_name": "Kitaoka", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Furuyashiki", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Junichiro", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-05996-w" }, "pmcid": { "normalized": "PMC12218910" }, "pmid": { "normalized": "40594719" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anticonvulsants", "descriptor_ui": "D000927", "major_topic": false }, { "descriptor": "Autism Spectrum Disorder", "descriptor_ui": "D000067877", "major_topic": true }, { "descriptor": "Autistic Disorder", "descriptor_ui": "D001321", "major_topic": true }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Bumetanide", "descriptor_ui": "D002034", "major_topic": false }, { "descriptor": "Clonazepam", "descriptor_ui": "D002998", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": true }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": true }, { "descriptor": "Valproic Acid", "descriptor_ui": "D014635", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul 2", "date_precision": "day", "issue": "1", "normalized_date": "2025-07-02", "pages": "22895", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Recovery of centralities in medial prefrontal and sensory-related cortices associated with social behavior improvements in an autism mouse model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The impact on prognosis of neutrophil infiltration in the microenvironment of ovarian cancer remains to be elucidated. In this study, we analyzed the association between neutrophil infiltration in peritoneal metastasis and prognosis. Furthermore, we analyzed the correlation between neutrophil infiltration in peritoneal metastasis and the number of peripheral blood neutrophils, the degree of neutropenia, vascular endothelial area, and the number of stromal cells. Thirty-four specimens each of primary and metastatic advanced ovarian cancer with high-grade serous carcinoma histology were taken. Staining for MPO, CD31, and alphaSMA was performed on all specimens. We investigated the correlation among tissue neutrophil infiltration, prognosis, and neutrophil indicators from blood tests. Survival analysis showed that neutrophil infiltration in the primary tumor had no impact on prognosis, whereas high neutrophil infiltration in the disseminated tumor significantly shortened progression-free survival and overall survival. No correlation was found between neutrophil infiltration and the number of peripheral blood neutrophils, the degree of neutropenia, area of vascular endothelial cells, and number of stromal cells. Neutrophil infiltration into disseminated lesions of the omentum has a significant impact on prognosis. The results of the present study may provide insights for refining clinical approaches.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Emiri", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Iyoshi", "name": null }, { "creator_type": "author", "first_name": "Kazumasa", "last_name": "Mogi", "name": null }, { "creator_type": "author", "first_name": "Kaname", "last_name": "Uno", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Koya", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Kitami", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Tamauchi", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Yokoi", "name": null }, { "creator_type": "author", "first_name": "Nobuhisa", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Niimi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Shiraki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kajiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-05010-3" }, "pmcid": { "normalized": "PMC12223313" }, "pmid": { "normalized": "40603365" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neutrophil Infiltration", "descriptor_ui": "D020556", "major_topic": true }, { "descriptor": "Neutrophils", "descriptor_ui": "D009504", "major_topic": false }, { "descriptor": "Ovarian Neoplasms", "descriptor_ui": "D010051", "major_topic": true }, { "descriptor": "Peritoneal Neoplasms", "descriptor_ui": "D010534", "major_topic": true }, { "descriptor": "Platelet Endothelial Cell Adhesion Molecule-1", "descriptor_ui": "D019408", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul 2", "date_precision": "day", "issue": "1", "normalized_date": "2025-07-02", "pages": "23196", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Neutrophil infiltration in peritoneal metastasis affects prognosis in patients with ovarian cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Rotator cuff tears are a leading cause of shoulder pain and dysfunction, yet the molecular mechanisms that link tendon injury to inflammation and nociceptive signaling remain poorly understood. Netrin-1, a classical axon guidance cue signaling through dependence receptors UNC5B and Neogenin-1, has been implicated in both neuronal plasticity and inflammatory processes, but its role in tendon pathology has not been explored. A rat supraspinatus tear model was employed to assess, in vivo, the expression of genes encoding netrin-1 (Ntn1) and its receptors (Unc5b and Neo1) at 0, 7, 14, 28, and 56 days post-injury (n = 10 per time point). Primary rat tenocytes isolated from rotator cuff tissue were treated in vitro with recombinant netrin-1, and transcriptional changes in genes encoding TNF-alpha (Tnfa), IL-6 (Il6), MMP-1 (Mmp1), and MMP-3 (Mmp3) were quantified by qRT-PCR. Separately, human iPSC-derived sensory neurons were exposed to netrin-1, and dose- and time-dependent effects on neurite outgrowth were measured at 4 and 14 days in culture. In injured tendons, Ntn1 mRNA increased significantly at day 14 (p = 0.010) and 28 (p = 0.042), Unc5b at day 7 (p = 0.002) and 14 (p < 0.001), and Neo1 at day 14 (p < 0.001) versus intact controls. Tenocyte exposure to 500 ng/mL netrin-1 induced transient upregulation of Tnfa (3 h, p = 0.023; 6 h, p = 0.009) and Il6 (3 h-24 h, all p < 0.013), as well as Mmp3 (3-24 h, p < 0.043) and Mmp1 (6 h-24 h, p < 0.024); no induction was observed at 50 ng/mL. In sensory neurons, 50 ng/mL of netrin-1 enhanced neurite extension at day 4 (p = 0.006) but not at 500 ng/mL or at day 14 for either dose. Netrin-1 and its receptors are upregulated in a rat rotator cuff tear model, and netrin-1 elicits distinct pro-inflammatory and matrix-remodeling responses in tenocytes while promoting early neurite growth in sensory neurons. These findings suggest netrin-1 as a key modulator of tendon inflammation, matrix turnover, and peripheral nerve plasticity following injury.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Mitsuyoshi", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Tazawa", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Kenmoku", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Uekusa", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Takaso", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cimb47070511" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40728980" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jul 2", "date_precision": "day", "issue": "7", "normalized_date": "2025-07-02", "pages": "511", "proceedings_title": null, "publisher": "", "title": "Current issues in molecular biology", "volume": "47", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Characterization of Netrin-1 and Its Receptors UNC5B and Neogenin-1 in a Rat Rotator Cuff Tear Model: Associations with Inflammatory Mediators and Neurite Extension.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Coinciding with the global outbreak of clade IIb mpox virus (MPXV), the Democratic Republic of the Congo (DRC) recently experienced a rapid surge in mpox cases with clade I MPXV. On 14 August 2024, the World Health Organization declared the continued cross-border spread of this clade in Africa a public health emergency of international concern (PHEIC). Clade I MPXV is known to be more fatal than clade IIb, but its clinical characteristics and prognosis differ between patients. Here, we used mathematical modeling to quantify temporal changes in total lesion counts during clade I MPXV infections, using data from a large cohort of patients with mpox in the DRC from 2007 to 2011. We further analyzed individuals' clinical data to explore predictive biomarkers of high lesion counts. Our analysis indicates that patients with clade I mpox can be stratified into two groups according to lesion severity and that viral load in peripheral blood at symptom onset may serve as a predictor for this classification [area under the curve (AUC) = 0.70]. Our estimates also suggest substantial individual heterogeneity in the time period during which patients have lesions, ranging from 20 to 65 days. Understanding the severity and duration of lesions in different patients, as characterized by our approach, may contribute to more tailored treatment strategies and control measures in ongoing clade I mpox outbreaks.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takara", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Fuminari", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Yong Dam", "last_name": "Jeong", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hyeongki", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ishikane", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Michiyo", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Ayana", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Watashi", "name": null }, { "creator_type": "author", "first_name": "William S.", "last_name": "Hart", "name": null }, { "creator_type": "author", "first_name": "Robin N.", "last_name": "Thompson", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yasutomi", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Ohmagari", "name": null }, { "creator_type": "author", "first_name": "Placide Mbala", "last_name": "Kingebeni", "name": null }, { "creator_type": "author", "first_name": "John W.", "last_name": "Huggins", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Iwami", "name": null }, { "creator_type": "author", "first_name": "Phillip R.", "last_name": "Pittman", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/scitranslmed.ads4773" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40601777" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Democratic Republic of the Congo", "descriptor_ui": "D015023", "major_topic": false }, { "descriptor": "Disease Outbreaks", "descriptor_ui": "D004196", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": true }, { "descriptor": "Mpox, Monkeypox", "descriptor_ui": "D045908", "major_topic": true }, { "descriptor": "Viral Load", "descriptor_ui": "D019562", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul 2", "date_precision": "day", "issue": "805", "normalized_date": "2025-07-02", "pages": "eads4773", "proceedings_title": null, "publisher": "", "title": "Science translational medicine", "volume": "17", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Modeling lesion transition dynamics to clinically characterize patients with clade I mpox in the Democratic Republic of the Congo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Investigating the temporal dynamics of gene expression is crucial for understanding gene regulation across various biological processes. Using the Fluorescent Timer protein, the Timer-of-cell-kinetics-and-activity system enables analysis of transcriptional dynamics at the single-cell level. However, the complexity of Timer fluorescence data has limited its broader application. Here, we introduce an integrative approach combining molecular biology and machine learning to elucidate Foxp3 transcriptional dynamics through flow cytometric Timer analysis. We have developed a convolutional neural network-based method that incorporates image conversion and class-specific feature visualisation for class-specific feature identification at the single-cell level. Biologically, we developed a novel CRISPR mutant of Foxp3 fluorescent Timer reporter mice lacking the enhancer Conserved Non-coding Sequence 2, which revealed new roles of this enhancer in regulating Foxp3 transcription frequency under specific conditions. Furthermore, analysis of wild-type Foxp3 fluorescent Timer reporter mice at different ages uncovered distinct patterns of Foxp3 expression from neonatal to aged mice, highlighting prominent thymus-like features of neonatal splenic Foxp3(+) T cells. In conclusion, our study uncovers previously unrecognised Foxp3 transcriptional dynamics, establishing a proof-of-concept for integrating CRISPR, single-cell dynamics analysis, and machine learning methods as advanced techniques to understand transcriptional dynamics in vivo.", "classifications": [ { "id": "21H00433", "label": "21H00433", "researcher": "Masahiro Ono", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Nobuko", "last_name": "Irie", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Yorifumi", "last_name": "Satou", "name": null }, { "creator_type": "author", "first_name": "Kimi", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-61279-y" }, "pmcid": { "normalized": "PMC12219120" }, "pmid": { "normalized": "40595611" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Enhancer Elements, Genetic", "descriptor_ui": "D004742", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": true }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neural Networks, Computer", "descriptor_ui": "D016571", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Spleen", "descriptor_ui": "D013154", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jul 1", "date_precision": "day", "issue": "1", "normalized_date": "2025-07-01", "pages": "5720", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Machine learning-assisted decoding of temporal transcriptional dynamics via fluorescent timer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Macrophages play essential roles in immune defense and tissue homeostasis, but the mechanisms underlying their colonization in the gut mucosa remain incompletely understood. Here, we identify CSF1, primarily derived from fibroblasts, as the dominant factor maintaining mucosal macrophage colonization, whereas IL-34 deficiency alone has a minimal impact. We reveal that CSF1R ligands originate from distinct cellular sources: macrophages at the upper villus region depend on fibroblast-derived CSF1 and IL-34, while macrophages in the lower villus and the submucosal (lower villus + SM) region are regulated by CSF1 from both fibroblasts and endothelial cells. Additionally, within the lower villus + SM region, CSF1-producing CD81(+) LepR(+) fibroblasts directly interact with CD163(+) macrophages, forming a localized niche. The loss of CSF1 in fibroblasts results in accelerated systemic dissemination of Salmonella Typhimurium, highlighting fibroblast-derived CSF1 as a key regulator of gut macrophage function in host defense. Collectively, our findings uncover a previously unrecognized fibroblast-macrophage crosstalk that governs gut macrophage homeostasis and immunity.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daichi", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Xiaojun", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Umemoto", "name": null }, { "creator_type": "author", "first_name": "Taisho", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Miyuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Shozo", "last_name": "Jinno", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Jean X.", "last_name": "Jiang", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Sumiya", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.mucimm.2025.06.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40609641" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": true }, { "descriptor": "Interleukins", "descriptor_ui": "D007378", "major_topic": false }, { "descriptor": "Intestinal Mucosa", "descriptor_ui": "D007413", "major_topic": true }, { "descriptor": "Macrophage Colony-Stimulating Factor", "descriptor_ui": "D016173", "major_topic": true }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Salmonella Infections", "descriptor_ui": "D012480", "major_topic": true }, { "descriptor": "Salmonella typhimurium", "descriptor_ui": "D012486", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jul 1", "date_precision": "day", "issue": "", "normalized_date": "2025-07-01", "pages": "S1933-0219(25)00071-6", "proceedings_title": null, "publisher": "", "title": "Mucosal immunology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Fibroblast-derived CSF1 maintains colonization of gut mucosal macrophage to resist bacterial infection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Collective behaviors in groups emerge from complex webs of direct and indirect interactions among individuals. While pairwise interactions are fundamental to understanding group dynamics, each agent's historical trajectory confounds causal inference, making it challenging to disentangle direct interactions from those mediated by hidden intermediaries. Here, we address the question: given observational tracking data from only a single pair of agents, can we determine whether their interaction is direct or mediated by an unseen third agent? We propose a framework based on modified transfer entropy analysis across delay times to detect the presence of a hidden intermediary. Our approach reveals a distinct signature: direct interactions exhibit a consistently decreasing modified transfer entropy with increasing delay time, whereas indirect interactions deviate from this trend. This method provides a simple yet versatile tool for uncovering hidden structures in complex systems, with broad implications for networked dynamics in biological, social, and artificial systems.", "classifications": [ { "id": "18H05413", "label": "18H05413", "researcher": "Tamiki Komatsuzaki", "type": "grant" }, { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "M.", "last_name": "Mohiuddin", "name": null }, { "creator_type": "author", "first_name": "Udoy S.", "last_name": "Basak", "name": null }, { "creator_type": "author", "first_name": "Md Motaleb", "last_name": "Hossain", "name": null }, { "creator_type": "author", "first_name": "Sulimon", "last_name": "Sattari", "name": null }, { "creator_type": "author", "first_name": "Mikito", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-04436-z" }, "pmcid": { "normalized": "PMC12217958" }, "pmid": { "normalized": "40593927" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jul 1", "date_precision": "day", "issue": "1", "normalized_date": "2025-07-01", "pages": "21610", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Detecting existence of a hidden mediator between a pair of individual time series.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A serine-threonine protein kinase (PK), Us3, encoded by herpes simplex virus 1 (HSV-1), shares substrate specificity with host cellular PKs, protein kinase A (PKA), and AKT. Many Us3 substrates have been identified, and it is thought that during HSV-1 infection, Us3 fine-tunes the phosphorylation levels of individual substrates within their repertoire. However, the significance of this regulatory fine-tuning by Us3 during HSV-1 infection is poorly understood. Here, we found alanine at position 326 (Ala-326) in Us3 was required for the proper fine-tuning of Us3-mediated phosphorylation across the target repertoire in HSV-1-infected cells. Using recombinant viruses in which Us3 Ala-326 was replaced with valine (A326V) or isoleucine (A326I), we showed these mutations selectively altered the phosphorylation of only a subset of at least 14 Us3 target proteins tested in HSV-1-infected cells, with each mutation generally affecting different targets. Of note, (i) both mutations significantly reduced plaque sizes without affecting viral replication in cell cultures; (ii) the Us3 A326I mutation impaired viral replication in the brains of mice and improved survival following intracranial infection, whereas the Us3 A326V mutation had little effect; and (iii) the Us3 A326V mutation reduced ocular pathogenic manifestations and viral replication in the trigeminal ganglia and brains of mice, thereby improving survival following ocular infection. Taken together, these results suggest that the proper fine-tuning of Us3-mediated phosphorylation across its target repertoire is required for efficient cell-to-cell spread of HSV-1 in vitro, and its replication and pathogenicity in vivo.IMPORTANCEThe activation loop (A-loop) is a conformationally flexible loop that critically regulates cellular protein kinases (PKs), but its role in viral PKs during infection remains unclear. We demonstrated alanine at position 326 (Ala-326) in the A-loop of herpes simplex virus 1 (HSV-1) PK Us3 was important for the proper fine-tuning of Us3-mediated phosphorylation across the target repertoire in HSV-1-infected cells. This fine-tuning was necessary for efficient HSV-1 cell-cell spread in cell cultures, and replication and pathogenicity in mice. Taken together, fine-tuning phosphorylation levels of individual Us3 targets within its repertoire is important for HSV-1 infection in vitro and in vivo. Different amino acid substitutions at Us3 Ala-326 selectively affected the phosphorylation of most distinct Us3 targets, leading to varied phenotypic outcomes in viral replication and pathogenicity in mice. These results provide important clues to elucidate the mechanisms by which Us3 regulates HSV-1 infection in vivo.", "classifications": [ { "id": "21H00417", "label": "21H00417", "researcher": "Yuhei Maruzuru", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Saori", "last_name": "Shio", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Jurika", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Kousuke", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Harima", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00400-25" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40586577" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": true }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": true }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": true }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jun 30", "date_precision": "day", "issue": "", "normalized_date": "2025-06-30", "pages": "e0040025", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Impact of the changes in substrate specificity of herpes simplex virus 1 protein kinase Us3 on viral infection in vitro and in vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: PD-L1 inhibitors combined etoposide-platinum (EP) are standard first-line treatments for extensive-stage small-cell lung cancer (ES-SCLC). However, their efficacy remains suboptimal. Irinotecan-cisplatin (IP) is optional regimen for ES-SCLC, and irinotecan has shown potential immunostimulatory activity. This study evaluated the efficacy and safety of IP plus durvalumab in untreated ES-SCLC. METHODS: Eligible patients (aged 20-74 years; PS 0-1 received four cycles of IP (irinotecan 60 mg/m(2), days 1,8,15 and cisplatin 60 mg/m(2), day 1) with durvalumab 1500 mg, followed by durvalumab 1500 mg every 4 weeks. Primary endpoint was the 12-month progression-free survival (PFS) rate, assessed by an independent central review (ICR). RESULTS: Between May 2021 and Nov 2022, 42 patients (median age, 66 years; 76.2 % were male; 31.0 % had PS 0) were enrolled. The 12-month PFS rate by ICR was 18.8 % (90 % CI, 9.3-30.8 %), with a median PFS of 5.7 months (95 % CI, 4.9-7.6 months). Median overall survival (OS) was 16.9 months (95 % CI, 11.8-NE), and the 12-month OS rate was 65.8 % (95 % CI, 49.1-78.1). Confirmed overall response rate (ORR) was 65.9 %, and disease control rate (DCR) was 85.4 %. Grade >/=3 adverse events (AEs) occurred in 73.8 %, including two grade 5 (2.4 %; pneumonitis and hepatitis). Pneumonitis occurred in 4.8 % (grade 1 and 5), while diarrhea of grade 3 or more occurred in 7.1 % patients. CONCLUSION: The REBORN study did not demonstrate the expected efficacy of IP plus durvalumab in untreated ES-SCLC, with its efficacy and safety generally comparable to those of EP plus durvalumab.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Motoko", "last_name": "Tachihara", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Shoda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Akazawa", "name": null }, { "creator_type": "author", "first_name": "Takayo", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kaneda", "name": null }, { "creator_type": "author", "first_name": "Shoichi", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Bessho", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Katakami", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Isamu", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.lungcan.2025.108637" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40602202" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": true }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": true }, { "descriptor": "Cisplatin", "descriptor_ui": "D002945", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Irinotecan", "descriptor_ui": "D000077146", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Small Cell Lung Carcinoma", "descriptor_ui": "D055752", "major_topic": true }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jun 29", "date_precision": "day", "issue": "", "normalized_date": "2025-06-29", "pages": "108637", "proceedings_title": null, "publisher": "", "title": "Lung cancer (Amsterdam, Netherlands)", "volume": "206", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Durvalumab plus irinotecan + cisplatin for untreated extensive-stage small cell lung cancer: REBORN, phase II study (WJOG13520L).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hirabayashi", "last_name": "Yusuke", "name": null }, { "creator_type": "author", "first_name": "Onami", "last_name": "Shuichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jmicro/dfaf026" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40576096" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jun 26", "date_precision": "day", "issue": "3", "normalized_date": "2025-06-26", "pages": "145", "proceedings_title": null, "publisher": "", "title": "Microscopy (Oxford, England)", "volume": "74", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Bioimaging and image analysis at scale.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Shitara", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Mukai", "name": null }, { "creator_type": "author", "first_name": "Goh", "last_name": "Kimoto", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kakiuchi", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Tomo", "last_name": "Kakihara", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nagamatsu", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Fujishiro", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Ohara", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Eiichiro", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-61278-z" }, "pmcid": { "normalized": "PMC12198388" }, "pmid": { "normalized": "40562747" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jun 25", "date_precision": "day", "issue": "1", "normalized_date": "2025-06-25", "pages": "5398", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Author Correction: Host-derived protein profiles of human neonatal meconium across gestational ages.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Rapid eye movement (REM) sleep is primarily regulated by the brainstem pons. In particular, the sublaterodorsal tegmentum (SubLDT) in the dorsal pons contains neurons whose activity is selective to REM sleep. Elucidation of the precise identities of these neurons and their roles in REM sleep regulation is challenging, however, due to the functional and molecular heterogeneity of the SubLDT. A recent study revealed that corticotropin-releasing hormone-binding protein (Crhbp)-positive neurons in the SubLDT projecting to the medulla play a crucial role in REM sleep regulation and that loss of these Crhbp-positive neurons underlies sleep deficits observed in Parkinson's disease. The firing patterns of these neurons during sleep/wake, however, remained unknown. Here, we used an opto-tagging method and conducted cell-type-specific recordings from Crhbp-positive neurons using a glass pipette microelectrode in unanesthetized male mice. We recorded 58 Crhbp-positive neurons and found that many of these neurons are REM sleep-active neurons (41.4%) and that the remaining neurons are mostly either wake-active, wake/REM sleep-active, or NREM sleep-active. In addition, projection-specific recordings revealed that the medulla-projecting Crhbp-positive neurons are mostly REM sleep-active neurons (75.0%). Based on clustering analysis and spike waveform analysis, REM sleep-active Crhbp-positive neurons can be further divided into different subtypes according to their electrophysiological properties, suggesting that Crhbp-positive neurons play diverse roles in REM sleep regulation.Significance statement Reduced REM sleep is a risk for dementia and mortality, suggesting it has critical roles in health. The mechanisms and functions of REM sleep, however, remain largely elusive. Classical electrophysiological studies identified neurons in the pons that are active during REM sleep, and a recent study revealed that Crhbp-positive neurons within the same area contribute to REM sleep regulation. The relationship between the neurons identified in each study, however, remained unknown. Loss of Crhbp-positive neurons underlies sleep deficits in Parkinson's disease, underscoring the importance of characterizing these neurons. Our study revealed that many of the Crhbp-positive neurons are REM sleep-active and comprise distinct subtypes in regard to firing patterns, suggesting their diverse roles in REM sleep regulation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Mitsuaki", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Iyo", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Yoshimasa", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.2365-24.2025" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40550695" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Pons", "descriptor_ui": "D011149", "major_topic": true }, { "descriptor": "Sleep, REM", "descriptor_ui": "D012895", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jun 23", "date_precision": "day", "issue": "", "normalized_date": "2025-06-23", "pages": "e2365242025", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Diverse firing profiles of Crhbp-positive neurons in the dorsal pons suggestive of their pleiotropic roles in REM sleep regulation in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer develops through the transformation of normal epithelial cells, followed by the expansion of hyperplastic cells within epithelial tissues and the subsequent generation of invasive cells capable of breaching the basement membrane. Basal delamination represents a pivotal early step that primes transformed cells for invasion and accounts for a large part of the lethality associated with carcinomas. Emerging evidence indicates that, upon the appearance of transformed cells, an intricate interplay between these cells and the surrounding epithelial neighbors acts as a potential driver of cancer cell invasion. Notably, certain transformed cells exploit cell competition for their own benefit to guide basal delamination. In this review, we delineate the physiological roles of cell competition in cancer cell dissemination and discuss the molecular cues underlying heterotypic cell interaction-induced basal extrusion.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Eilma", "last_name": "Akter", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kon", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.70120" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40542711" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basement Membrane", "descriptor_ui": "D001485", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": true }, { "descriptor": "Cell Competition", "descriptor_ui": "D000084502", "major_topic": true }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jun 21", "date_precision": "day", "issue": "", "normalized_date": "2025-06-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Basal Invasion of Cancer Cells Driven by Cell-Cell Interactions: An Affirmative Role of Cell Competition in Cancer Progression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Eliminating redundant synapses formed around birth is essential for shaping functionally mature neural circuits during postnatal development. Each Purkinje cell (PC) in the neonatal mouse cerebellum receives synaptic inputs from multiple climbing fibers (CFs). Only one CF is strengthened and extends its innervation over PC dendrites, whereas the other CFs are eventually pruned during postnatal development. These events are believed to require proper gene expression, but the underlying mechanisms are not yet understood. Here, we report that the transcription factor ZFP64 in PCs mediates part of CF synapse elimination events presumably downstream of P/Q-type voltage-dependent Ca(2+) channels (P/Q-VDCCs). PC-specific knockdown (KD) of ZFP64 during postnatal development delayed the elimination of redundant CF synapses and the dendritic extension of CF innervation. The KD of semaphorin 3A (Sema3A) in PCs partially restored the effects of ZFP64 or P/Q-VDCC KD. We propose that ZFP64 promotes developmental CF synapse elimination by regulating Sema3A expression.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jianling", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Miwako", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Kohtarou", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Okuno", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Matsuyama", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Noro", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2025.112746" }, "pmcid": { "normalized": "PMC12178792" }, "pmid": { "normalized": "40546958" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jun 20", "date_precision": "day", "issue": "6", "normalized_date": "2025-06-20", "pages": "112746", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "28", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The transcription factor ZFP64 promotes activity-dependent synapse elimination during postnatal cerebellar development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cytological diagnosis of follicular thyroid carcinoma (FTC) is one of the main challenges in the field of endocrine oncology due to the absence of evident morphological indicators. Morphological abnormalities in the nucleus are typically key indicators of cancer cytopathology and are attributed to a range of biochemical alterations in nuclear components. Consequently, Raman spectroscopy has been widely used to detect cancer in various cytological samples, often identifying biochemical changes prior to observable morphological alterations. However, in the case of FTC, cytoplasmic features, such as carotenoids, cytochromes, and lipid droplets, have shown greater diagnostic relevance compared to nuclear features. This study leverages single-cell Raman imaging to explore the spatial origin of diagnostic signals in FTC and normal thyroid (NT) cells, assessing the contributions of the nucleus and cytoplasm independently. Our results demonstrate that Raman spectra from the cytoplasmic region can distinguish between FTC and NT cells with an accuracy of 84% under coculture conditions, consistently across two cell lines originated from two donors and maintaining robustness across multiple devices. In contrast, classification based on nuclear spectra achieved only 53% accuracy, suggesting that biochemical alterations in the cytoplasm play a more significant role in FTC detection than those in the nucleus. Our work elevates the promise of Raman-based cytopathology by providing complementary organelle-dependent information to traditional diagnostic methods and demonstrating transferability across different devices.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Aurelien", "last_name": "Pelissier", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "J. Nicholas", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Jean-Emmanuel", "last_name": "Clement", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.4c06544" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40536131" } }, "mesh": [ { "descriptor": "Adenocarcinoma, Follicular", "descriptor_ui": "D018263", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": true }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Thyroid Neoplasms", "descriptor_ui": "D013964", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jun 19", "date_precision": "day", "issue": "", "normalized_date": "2025-06-19", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Beyond the Nucleus: Cytoplasmic Dominance in Follicular Thyroid Carcinoma Detection Using Single-Cell Raman Imaging across Multiple Devices.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Larvae of the ascidian Ciona initiate metamorphosis tens of minutes after adhesion to a substratum via their adhesive organ. The gap between adhesion and metamorphosis initiation is suggested to ensure the rigidity of adhesion, allowing Ciona to maintain settlement after losing locomotive activity through metamorphosis. The mechanism producing the gap is unknown. Here, by combining gene functional analyses, pharmacological analyses, and live imaging, we propose that the gap represents the time required for sufficient cyclic adenosine monophosphate (cAMP) accumulation to trigger metamorphosis. Not only the Gs pathway but also the Gi and Gq pathways are involved in the initiation of metamorphosis in the downstream signaling cascade of the neurotransmitter GABA, the known initiator of Ciona metamorphosis. The mutual crosstalk of stimulatory and inhibitory G-proteins functions as the accelerator and brake for cAMP production, ensuring the faithful initiation of metamorphosis at an appropriate time and in the right situation.", "classifications": [ { "id": "21H00440", "label": "21H00440", "researcher": "Kohji Hotta", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akiko", "last_name": "Hozumi", "name": null }, { "creator_type": "author", "first_name": "Nozomu M.", "last_name": "Totsuka", "name": null }, { "creator_type": "author", "first_name": "Arata", "last_name": "Onodera", "name": null }, { "creator_type": "author", "first_name": "Yanbin", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Honoo", "last_name": "Satake", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Sasakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.99825" }, "pmcid": { "normalized": "PMC12176390" }, "pmid": { "normalized": "40531176" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ciona", "descriptor_ui": "D000077262", "major_topic": true }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": true }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": true }, { "descriptor": "GTP-Binding Proteins", "descriptor_ui": "D019204", "major_topic": true }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": false }, { "descriptor": "Metamorphosis, Biological", "descriptor_ui": "D008675", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jun 18", "date_precision": "day", "issue": "", "normalized_date": "2025-06-18", "pages": "", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "13", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Stimulatory and inhibitory G-protein signaling relays drive cAMP accumulation for timely metamorphosis in the chordate Ciona.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tissue growth and deformation result from the combined effects of various cellular events, including cell shape change, cell rearrangement, cell division, and cell death. Resolving and integrating these cellular events is essential for understanding the coordination of tissue-scale growth and deformation by individual cellular behaviors that are critical for morphogenesis, wound healing, and other collective cellular phenomena. For epithelial tissues composed of tightly connected cells, the texture tensor method provides a unified framework for quantifying tissue and cell strains by tracking individual cells in live imaging data. The corresponding kinematic relationships have been introduced in a hydrodynamic model that we previously reported. In this study, we quantitatively evaluated the kinematic equations proposed in the hydrodynamic model using experimental data from a growing Drosophila wing. To accomplish this, we introduced modified definitions of the texture tensor and confirmed that one of these modifications more accurately represents approximated cellular shapes without relying on ad hoc scaling factors. By utilizing the modified tensor, we demonstrated the compatibility of the strain rate tensors and the accuracy of both the kinematic and cell number density equations. These results cross-validate the modified texture analysis and the hydrodynamic model. Furthermore, the precision of the kinematic relationships achieved in this study provides a robust foundation for more advanced integration of modeling and experiment.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Toshinori", "last_name": "Namba", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Sugimura", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1140/epje/s10189-025-00495-2" }, "pmcid": { "normalized": "PMC12167722" }, "pmid": { "normalized": "40517354" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": true }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Hydrodynamics", "descriptor_ui": "D057446", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": true }, { "descriptor": "Wings, Animal", "descriptor_ui": "D014921", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jun 15", "date_precision": "day", "issue": "6-7", "normalized_date": "2025-06-15", "pages": "31", "proceedings_title": null, "publisher": "", "title": "The European physical journal. E, Soft matter", "volume": "48", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "In vivo assessment of kinematic relationships for epithelial morphogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Near-infrared (NIR) fluorescence probes for hypochlorous acid (HClO) are powerful tools for investigating various biological phenomena because of their low autofluorescence, high tissue penetration and usefulness for multicolour imaging. Here we present a rational probe design strategy based on the phenyl-induced twisted intramolecular charge transfer (p-TICT) mechanism and apply it to develop a NIR fluorescence probe for HClO, N-Phenol SiR1. This probe was applied for multicolor (4 colors) live-cell fluorescence imaging, occupying the NIR color window.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hisashi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Sumitani", "name": null }, { "creator_type": "author", "first_name": "Ariunbold", "last_name": "Chuluun-Erdene", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d5cc02212f" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40497359" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jun 11", "date_precision": "day", "issue": "", "normalized_date": "2025-06-11", "pages": "", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a near-infrared fluorescence probe for hypochlorous acid based on the phenyl-induced twisted intramolecular charge transfer (p-TICT) mechanism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fibroblastic reticular cells (FRCs) are specialized fibroblasts that construct secondary lymphoid organs where they provide crucial signals for immune cell homeostasis and migration. While splenic FRCs are thought to support antiviral T cell responses, their role remains unclear. Here, we found that ablation of splenic FRCs impaired virus-specific CD8(+) T cell responses during lymphocytic choriomeningitis virus (LCMV) infection. Immunofluorescence imaging revealed that FRCs promote CD8(+) T cell clustering with type 1 conventional dendritic cells (cDC1) in the T cell zone before migration to the infected marginal zone. Without FRCs, T cells instead clustered with cDC1 and virus-infected cells in the marginal zone, leading to suboptimal priming. Mechanistically, FRCs coordinated early viral replication and the inflammatory milieu for optimal DC activation, and an intact FRC network was crucial for generating effector T cells and maintaining protective memory T cells. Thus, splenic FRCs provide essential lymphoid niches for antiviral T cell responses.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yannick O.", "last_name": "Alexandre", "name": null }, { "creator_type": "author", "first_name": "Nikita", "last_name": "Potemkin", "name": null }, { "creator_type": "author", "first_name": "Dominik", "last_name": "Schienstock", "name": null }, { "creator_type": "author", "first_name": "Baptiste", "last_name": "Duchamp", "name": null }, { "creator_type": "author", "first_name": "Annika", "last_name": "Poch", "name": null }, { "creator_type": "author", "first_name": "Susan N.", "last_name": "Christo", "name": null }, { "creator_type": "author", "first_name": "Shihan", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Qin", "name": null }, { "creator_type": "author", "first_name": "Lynette", "last_name": "Beattie", "name": null }, { "creator_type": "author", "first_name": "Daniel T.", "last_name": "Utzschneider", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Jan", "last_name": "Schroder", "name": null }, { "creator_type": "author", "first_name": "Laura K.", "last_name": "Mackay", "name": null }, { "creator_type": "author", "first_name": "Scott N.", "last_name": "Mueller", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adt5939" }, "pmcid": { "normalized": "PMC12136048" }, "pmid": { "normalized": "40465738" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": true }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": true }, { "descriptor": "Immunologic Memory", "descriptor_ui": "D007156", "major_topic": true }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Lymphocytic Choriomeningitis", "descriptor_ui": "D008216", "major_topic": false }, { "descriptor": "Lymphocytic choriomeningitis virus", "descriptor_ui": "D008217", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Spleen", "descriptor_ui": "D013154", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jun 6", "date_precision": "day", "issue": "23", "normalized_date": "2025-06-06", "pages": "eadt5939", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "11", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Splenic fibroblastic reticular cells orchestrate dendritic cell maturation and facilitate CD8(+) T cell priming and protective memory.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herpes simplex virus 1 (HSV-1) is the most common cause of viral encephalitis, which can be lethal or result in severe neurological defects despite antiviral therapy. The apolipoprotein B messenger-RNA editing enzyme, catalytic polypeptide-like (APOBEC) group of proteins can act as viral restriction factors. How HSV-1 evades this intrinsic immune mechanism is unclear. Here, using human carcinoma HEp-2 cells, we find that phosphorylation and therefore activation of HSV-1 uracil-DNA glycosylase counteracts mouse APOBEC1 DNA-editing activity on HSV-1 genomes. This protects viral genomes, promotes viral replication and encephalitis in the central nervous system of mice. Presence of Apobec1 improved encephalitis outcomes in mice challenged with HSV-1 carrying a mutation in the phosphorylation site of uracil-DNA glycosylase. Treatment with an UNG inhibitor, adeno-associated virus vector expressing UGI, protected wild-type HSV-1-infected mice from lethal encephalitis. These findings identify uracil-DNA glycosylase as a viral factor enabling evasion from intrinsic antiviral immunity mediated by APOBEC1 in the central nervous system and suggests a potential therapeutic approach to treat HSV-1 encephalitis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Harima", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Tsunekawa", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Kousho", "last_name": "Wakae", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kozuka-Hata", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Motooka", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kousuke", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Toshifumi", "last_name": "Inada", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41564-025-02026-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40461648" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "APOBEC-1 Deaminase", "descriptor_ui": "D000071479", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Encephalitis, Herpes Simplex", "descriptor_ui": "D020803", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Evasion", "descriptor_ui": "D057131", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Uracil-DNA Glycosidase", "descriptor_ui": "D051981", "major_topic": true }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jun 3", "date_precision": "day", "issue": "", "normalized_date": "2025-06-03", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature microbiology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Herpes simplex virus 1 evades APOBEC1-mediated immunity via its uracil-DNA glycosylase in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Atopic dermatitis (AD) is a skin disease exhibiting clinical and molecular heterogeneity, thereby jeopardizing the development of personalized treatments. Here we pursue a cross-sectional and longitudinal cohort analysis of 951 whole-skin samples, employing an unsupervised decomposition analysis to link gene expression profiles to disease severity, six distinct skin phenotypes, and blood cytokines representative of given endotypes. Specifically, type 2 and type 17 responses are associated with major skin phenotypes such as erythema and induration, while type 1 response is upregulated in lichen amyloidosis of AD patients. Longitudinal analysis of patients treated with dupilumab finds sustained gene signatures related to type 17 response in lesional skin and upregulated transcription factors in non-lesional skin of patients with poor treatment outcomes. Lastly, several extracellular matrix organization-associated genes are correlated with clinical severity and treatment response to dupilumab. Our findings thus provide potential skin and blood biomarkers for assessing endotypes and therapeutic responses in AD to pave the way for personalized medicine.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ayano", "last_name": "Fukushima-Nomura", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Yashiro", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Obata", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Tanese", "name": null }, { "creator_type": "author", "first_name": "Tamotsu", "last_name": "Ebihara", "name": null }, { "creator_type": "author", "first_name": "Hidehisa", "last_name": "Saeki", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Etoh", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Junshi", "last_name": "Yazaki", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Seita", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Ohara", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Sekita", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Miyai", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ashizaki", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Koseki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Sakurada", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Amagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-59340-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40456762" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal, Humanized", "descriptor_ui": "D061067", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Dermatitis, Atopic", "descriptor_ui": "D003876", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Longitudinal Studies", "descriptor_ui": "D008137", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Precision Medicine", "descriptor_ui": "D057285", "major_topic": false }, { "descriptor": "Severity of Illness Index", "descriptor_ui": "D012720", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": true }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jun 2", "date_precision": "day", "issue": "1", "normalized_date": "2025-06-02", "pages": "4981", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "An unbiased tissue transcriptome analysis identifies potential markers for skin phenotypes and therapeutic responses in atopic dermatitis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pancreatic ductal adenocarcinoma (PDAC) ranks among the most lethal malignancies, highlighting the critical need for innovative therapeutic strategies. In this study, we examined the roles of nicotinamide adenine dinucleotide (NAD) synthesis pathway in PDAC. Targeting the nicotinamide adenine dinucleotide (NAD) synthesis pathway significantly mitigated lethality in a Drosophila model that recapitulated the PDAC genotype. Within this pathway, we identified Glutathione peroxidase 4 (GPx4) as a critical effector responsible for scavenging reactive oxygen species (ROS). The combined application of GPx4 and Mitogen-activated protein kinase kinase (MEK) inhibitors, namely ML210 and trametinib, respectively, reduced lethality and tumor-like phenotypes in these flies. Notably, this combination treatment synergistically suppressed the proliferation of human PDAC cells and their corresponding xenografts in mice by inducing ROS accumulation, which triggered ferroptosis. These results suggest that inducing ferroptosis could represent a promising therapeutic strategy for PDAC.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hui", "last_name": "Jiang", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Ryodai", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Ooshio", "name": null }, { "creator_type": "author", "first_name": "Yang", "last_name": "Luo", "name": null }, { "creator_type": "author", "first_name": "Han", "last_name": "Hai", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Otsuka", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Reo", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Taiga", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Osawa", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Goda", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ymthe.2025.05.037" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40450524" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinoma, Pancreatic Ductal", "descriptor_ui": "D021441", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Ferroptosis", "descriptor_ui": "D000079403", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase Kinases", "descriptor_ui": "D020929", "major_topic": true }, { "descriptor": "NAD", "descriptor_ui": "D009243", "major_topic": true }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": true }, { "descriptor": "Phospholipid Hydroperoxide Glutathione Peroxidase", "descriptor_ui": "D000080662", "major_topic": true }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Pyridones", "descriptor_ui": "D011728", "major_topic": false }, { "descriptor": "Pyrimidinones", "descriptor_ui": "D011744", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 30", "date_precision": "day", "issue": "", "normalized_date": "2025-05-30", "pages": "S1525-0016(25)00407-1", "proceedings_title": null, "publisher": "", "title": "Molecular therapy : the journal of the American Society of Gene Therapy", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Inhibition of NAD-GPx4 axis and MEK triggers ferroptosis to suppress pancreatic ductal adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The global circulation of SARS-CoV-2 in human populations has driven the emergence of Omicron subvariants, which have become highly diversified through recombination. In late 2024, SARS-CoV-2 Omicron XEC variant emerged from the recombination of two JN.1 progeny, KS.1.1 and KP.3.3, and became predominant worldwide. Here, we investigated virological features of the XEC variant. Epidemic dynamics modeling suggested that spike substitutions in XEC mainly contribute to its increased viral fitness. Additionally, four licensed antivirals were effective against XEC. Although the fusogenicity of XEC spike is comparable to that of the JN.1 spike, the intrinsic pathogenicity of XEC in hamsters was significantly higher than that of JN.1. Notably, we found that the nucleocapsid R204P mutation of XEC enhanced inflammation through NF-kappaB activation. Recent studies suggest that the evolutionary potential of spike protein is reaching its limit. Indeed, our findings highlight the critical role of non-spike mutations in the future evolution of SARS-CoV-2.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shuhei", "last_name": "Tsujino", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Deguchi", "name": null }, { "creator_type": "author", "first_name": "Taha Y.", "last_name": "Taha", "name": null }, { "creator_type": "author", "first_name": "Hesham", "last_name": "Nasser", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Julia", "last_name": "Rosecrans", "name": null }, { "creator_type": "author", "first_name": "Rigel", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Yoshimatsu", "name": null }, { "creator_type": "author", "first_name": "Melanie", "last_name": "Ott", "name": null }, { "creator_type": "author", "first_name": "Terumasa", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Takasuke", "last_name": "Fukuhara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/2025.05.28.656516" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 May 30", "date_precision": "day", "issue": null, "normalized_date": "2025-05-30", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "A non-spike nucleocapsid R204P mutation in SARS-CoV-2 Omicron XEC enhances inflammation and pathogenicity.", "url": "", "zotero": { "item_type": "preprint" } }, { "abstract": "Metal naphthalocyanine (MNc) is one of the most promising near-infrared (NIR) dyes as a photosensitizer for phototheranostics, combining photoacoustic imaging (PAI) and photothermal therapy (PTT). However, the extremely low solubility of MNc has limited its practical application as a theranostic agent. In this research, we synthesized NiNc precursors (ox-NiNc) having two alkoxy groups on the alpha-carbons of the diagonal pyrroles with significantly improved solubility. We also prepared an amphiphilic derivative, ox-NiNc-PEG, and investigated its conversion to NiNc through reductive aromatization. We demonstrated that ox-NiNc-PEG was efficiently converted to NiNc in cancer cells with elevated glutathione levels, resulting in enhanced photoacoustic signals and increased phototoxicity based on photothermal conversion under NIR light irradiation. The target-oriented reductive aromatization in response to the reducing environment in cancer cells offers a critical strategy for developing PAI/PTT theranostic agents.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kohei", "last_name": "Nogita", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Sugahara", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Huiying", "last_name": "Mu", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/chem.202501346" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40442961" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Indoles", "descriptor_ui": "D007211", "major_topic": true }, { "descriptor": "Infrared Rays", "descriptor_ui": "D007259", "major_topic": false }, { "descriptor": "Nickel", "descriptor_ui": "D009532", "major_topic": true }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Photoacoustic Techniques", "descriptor_ui": "D061088", "major_topic": false }, { "descriptor": "Photosensitizing Agents", "descriptor_ui": "D017319", "major_topic": true }, { "descriptor": "Photothermal Therapy", "descriptor_ui": "D000082703", "major_topic": false }, { "descriptor": "Solubility", "descriptor_ui": "D012995", "major_topic": false }, { "descriptor": "Theranostic Nanomedicine", "descriptor_ui": "D000068936", "major_topic": false }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 29", "date_precision": "day", "issue": "", "normalized_date": "2025-05-29", "pages": "e202501346", "proceedings_title": null, "publisher": "", "title": "Chemistry (Weinheim an der Bergstrasse, Germany)", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "A Reductively Activatable Phototheranostic Agent Based on a Water-Soluble Nickel Naphthalocyanine Precursor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "RNA polymerase II (RNAPII) is a central transcription enzyme that exists as multiple forms with or without accessory factors, and transcribes the genomic DNA packaged in chromatin. To understand how RNAPII functions in the human genome, we isolate transcribing RNAPII complexes from human nuclei by chromatin immunopurification, and determine the cryo-electron microscopy structures of RNAPII elongation complexes (ECs) associated with genomic DNA in distinct forms, without or with the elongation factors SPT4/5, ELOF1, and SPT6. This ChIP-cryoEM method also reveals the two EC-nucleosome complexes corresponding nucleosome disassembly/reassembly processes. In the structure of EC-downstream nucleosome, EC paused at superhelical location (SHL) -5 in the nucleosome, suggesting that SHL(-5) pausing occurs in a sequence-independent manner during nucleosome disassembly. In the structure of the EC-upstream nucleosome, EC directly contacts the nucleosome through the nucleosomal DNA-RPB4/7 stalk and the H2A-H2B dimer-RPB2 wall interactions, suggesting that EC may be paused during nucleosome reassembly. These representative EC structures transcribing the human genome provide mechanistic insights into understanding RNAPII transcription on chromatin.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuma", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Hosoi", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Kujirai", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kyoka", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Takeru", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Lumi", "last_name": "Negishi", "name": null }, { "creator_type": "author", "first_name": "Mitsuo", "last_name": "Ogasawara", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Yoshimasa", "last_name": "Takizawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurumizaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-59580-x" }, "pmcid": { "normalized": "PMC12119854" }, "pmid": { "normalized": "40436841" } }, "mesh": [ { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": true }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Chromatin Immunoprecipitation", "descriptor_ui": "D047369", "major_topic": false }, { "descriptor": "Cryoelectron Microscopy", "descriptor_ui": "D020285", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nucleosomes", "descriptor_ui": "D009707", "major_topic": false }, { "descriptor": "RNA Polymerase II", "descriptor_ui": "D012319", "major_topic": true }, { "descriptor": "Transcriptional Elongation Factors", "descriptor_ui": "D035602", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 28", "date_precision": "day", "issue": "1", "normalized_date": "2025-05-28", "pages": "4724", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Multiple structures of RNA polymerase II isolated from human nuclei by ChIP-CryoEM analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Modeling the 3D structures of cells and tissues is crucial in biology. Sequential cross-sectional images from electron microscopy provide high-resolution intracellular structure information. The segmentation of complex cell structures remains a laborious manual task for experts, demanding time and effort. This bottleneck in analyzing biological images requires efficient and automated solutions. In this study, the deep learning-based automated segmentation of biological images was explored to enable accurate reconstruction of the 3D structures of cells and organelles. An analysis system for the cell images of Cyanidioschyzon merolae, a primitive unicellular red algae, was constructed. This system utilizes sequential cross-sectional images captured by a focused ion beam scanning electron microscope (FIB-SEM). A U-Net was adopted and training was performed to identify and segment cell organelles from single-cell images. In addition, the segment anything model (SAM) and 3D watershed algorithm were employed to extract individual 3D images of each cell from large-scale microscope images containing numerous cells. Finally, the trained U-Net was applied to segment each structure within these 3D images. Through this procedure, the creation of 3D cell models could be fully automated. The adoption of other deep learning techniques and combinations of image processing methods will also be explored to enhance the segmentation accuracy further.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Jin", "last_name": "Kousaka", "name": null }, { "creator_type": "author", "first_name": "Atsuko H.", "last_name": "Iwane", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Togashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-01763-z" }, "pmcid": { "normalized": "PMC12092829" }, "pmid": { "normalized": "40394179" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": true }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": true }, { "descriptor": "Microscopy, Electron", "descriptor_ui": "D008854", "major_topic": true }, { "descriptor": "Microscopy, Electron, Scanning", "descriptor_ui": "D008855", "major_topic": false }, { "descriptor": "Rhodophyta", "descriptor_ui": "D000461", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 May 20", "date_precision": "day", "issue": "1", "normalized_date": "2025-05-20", "pages": "17481", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Automated cell structure extraction for 3D electron microscopy by deep learning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Chida", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Hanai", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Hananoe", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Hatakeyama", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Mizui", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Nagasu", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Shinzawa", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.compbiomed.2025.110360" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40375428" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 May 14", "date_precision": "day", "issue": "Pt B", "normalized_date": "2025-05-14", "pages": "110360", "proceedings_title": null, "publisher": "", "title": "Computers in biology and medicine", "volume": "192", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Rigorous multiple statistical test unveils combinations of preceding diseases at risk for the development of adult nephrotic syndrome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Histones bind directly to DNA and play a role in regulating gene expression in part by influencing chromatin structure. The DNA sequences of these histone genes are quite similar, which has hindered individual analyses. The exact function of the 13 different isoforms of histone H2B remains unclear. In this study, we performed a comprehensive gene expression analysis of the H2B isoforms, focusing on tissue specificity. Our results revealed that the H2bc27 gene exhibited brain-specific expression in mice at E14.5. We generated mice lacking the H2bc27 gene using the CRISPR /Cas9 system. While the phenotype of H2bc27 knockout mouse brains was not different from that of wild-type mouse brains, transcriptome analysis indicated that H2bc27 is associated with regulating the expression of several functional genes involved in mouse brain development. The methods used in this study may serve to facilitate comprehensive H2B isoform analysis.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" }, { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Saki", "last_name": "Egashira", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jb/mvaf026" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40367935" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 14", "date_precision": "day", "issue": "", "normalized_date": "2025-05-14", "pages": "mvaf026", "proceedings_title": null, "publisher": "", "title": "Journal of biochemistry", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Histone H2B isoform H2bc27 is expressed in the developing brain of mouse embryos.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND/OBJECTIVE: Ulcerative colitis (UC) is significantly linked with gut microbiota, which is essential for maintaining gut health. Their metabolites mitigate gut inflammation and bolster barrier function. Among these metabolites, we focused on vitamin B3, which has been reported to improve the pathogenesis of UC in mice. This study aimed to compare fecal vitamin B3 and gut microbiota between non-UC and UC patients. METHODS: We assessed fecal metabolites and gut microbiota in 71 UC patients (UC group) and 72 non-UC patients (non-UC group) matched by sex and age in 10-year intervals. Fecal samples were collected and metabolites were analyzed using capillary electrophoresis time-of-flight mass spectrometry. Bacterial DNA was extracted for 16S rRNA gene sequencing. We analyzed fecal nicotinamide levels and gut microbiota composition, employing statistical adjustments for confounding factors. RESULTS: We found that the UC group exhibited significantly lower fecal nicotinamide levels and alpha-diversity (Shannon index) compared to the non-UC group. The relative abundance of bacterial genera such as Treponema, UCG-002, and Fusicatenibacter was decreased, while Sellimonas, Fournierella, and Oscillospira were increased in the UC group. Moreover, a negative correlation was observed between Sellimonas abundance and fecal nicotinamide levels in the UC group. Additionally, the UC group showed higher expression of a bacterial gene encoding nicotinamidase compared to the non-UC group. CONCLUSIONS: These findings suggest that gut microbiota dysbiosis contributes to reduced vitamin B3 metabolism in UC patients. The study highlights the potential of replenishing vitamin B3 metabolic pathways as a novel therapeutic approach for UC treatment.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Keiya", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Ryodai", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Katsurada", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Norimasa", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Tamakoshi", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/ibd/izaf092" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40357746" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": true }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Colitis, Ulcerative", "descriptor_ui": "D003093", "major_topic": true }, { "descriptor": "Feces", "descriptor_ui": "D005243", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gastrointestinal Microbiome", "descriptor_ui": "D000069196", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Niacinamide", "descriptor_ui": "D009536", "major_topic": true }, { "descriptor": "RNA, Ribosomal, 16S", "descriptor_ui": "D012336", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 13", "date_precision": "day", "issue": "", "normalized_date": "2025-05-13", "pages": "izaf092", "proceedings_title": null, "publisher": "", "title": "Inflammatory bowel diseases", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Decreased Fecal Nicotinamide and Increased Bacterial Nicotinamidase Gene Expression in Ulcerative Colitis Patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Retroviruses integrate their genetic material into the host genome, enabling persistent infection. Human T cell leukaemia virus type 1 (HTLV-1) and human immunodeficiency virus type 1 (HIV-1) share similarities in genome structure and target cells, yet their infection dynamics differ drastically. While HIV-1 leads to high viral replication and immune system collapse, HTLV-1 establishes latency, promoting the survival of infected cells and, in some cases, leading to leukaemia. The mechanisms underlying this latency preference remain unclear. Here we analyse blood samples from people with HTLV-1 and identify an open chromatin region within the HTLV-1 provirus that functions as a transcriptional silencer and regulates transcriptional burst. The host transcription factor RUNX1 binds to this open chromatin region, repressing viral expression. Mutation of this silencer enhances HTLV-1 replication and immunogenicity, while its insertion into HIV-1 suppresses viral production. These findings reveal a strategy by which HTLV-1 ensures long-term persistence, offering potential insights into retroviral evolution and therapeutic targets.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Sugata", "name": null }, { "creator_type": "author", "first_name": "Akhinur", "last_name": "Rahman", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Niimura", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Monde", "name": null }, { "creator_type": "author", "first_name": "Takaharu", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Samiul Alam", "last_name": "Rajib", "name": null }, { "creator_type": "author", "first_name": "Mitsuyoshi", "last_name": "Takatori", "name": null }, { "creator_type": "author", "first_name": "Wajihah", "last_name": "Sakhor", "name": null }, { "creator_type": "author", "first_name": "Md Belal", "last_name": "Hossain", "name": null }, { "creator_type": "author", "first_name": "Sharmin Nahar", "last_name": "Sithi", "name": null }, { "creator_type": "author", "first_name": "M. Ishrat", "last_name": "Jahan", "name": null }, { "creator_type": "author", "first_name": "Kouki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Mitsuharu", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Yamano", "name": null }, { "creator_type": "author", "first_name": "Terumasa", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kiyoto", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Yuetsu", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Atae", "last_name": "Utsunomiya", "name": null }, { "creator_type": "author", "first_name": "Kazu", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yorifumi", "last_name": "Satou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41564-025-02006-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40360701" } }, "mesh": [ { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Core Binding Factor Alpha 2 Subunit", "descriptor_ui": "D050676", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Viral", "descriptor_ui": "D015967", "major_topic": false }, { "descriptor": "HIV-1", "descriptor_ui": "D015497", "major_topic": false }, { "descriptor": "HTLV-I Infections", "descriptor_ui": "D015490", "major_topic": true }, { "descriptor": "Human T-lymphotropic virus 1", "descriptor_ui": "D015368", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Proviruses", "descriptor_ui": "D011533", "major_topic": false }, { "descriptor": "Silencer Elements, Transcriptional", "descriptor_ui": "D037941", "major_topic": true }, { "descriptor": "Virus Latency", "descriptor_ui": "D017735", "major_topic": true }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 13", "date_precision": "day", "issue": "", "normalized_date": "2025-05-13", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature microbiology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Intragenic viral silencer element regulates HTLV-1 latency via RUNX complex recruitment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dormancy is a physiological state that enables cells to survive under adverse conditions by halting their proliferation while retaining the capacity to resume growth when conditions become favorable. This remarkable transition between dormant and proliferative states occurs across a wide range of species, including bacteria, fungi, plants, and tardigrades. Among these organisms, yeast cells have emerged as powerful model systems for elucidating the molecular and biophysical principles governing dormancy and dormancy breaking. In this review, we provide a comprehensive summary of current knowledge on the molecular mechanisms underlying cellular dormancy, with particular focus on the two major model yeasts: Saccharomyces cerevisiae and Schizosaccharomyces pombe. Recent advances in multifaceted approaches-such as single-cell RNA-seq, proteomic analysis, and live-cell imaging-have revealed dynamic changes in gene expression, proteome composition, and viability. Furthermore, insights into the biophysical properties of the cytoplasm have offered new understanding of dormant cell regulation through changes in cytoplasmic fluidity. These properties contribute to both the remarkable stability of dormant cells and their capacity to exit dormancy upon environmental cues, deepening our understanding of fundamental cellular survival strategies across diverse species.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Goto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biom15050701" }, "pmcid": { "normalized": "PMC12109108" }, "pmid": { "normalized": "40427594" } }, "mesh": [ { "descriptor": "Gene Expression Regulation, Fungal", "descriptor_ui": "D015966", "major_topic": false }, { "descriptor": "Proteome", "descriptor_ui": "D020543", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae", "descriptor_ui": "D012441", "major_topic": true }, { "descriptor": "Schizosaccharomyces", "descriptor_ui": "D012568", "major_topic": true }, { "descriptor": "Spores, Fungal", "descriptor_ui": "D013172", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 May 11", "date_precision": "day", "issue": "5", "normalized_date": "2025-05-11", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biomolecules", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular and Biophysical Perspectives on Dormancy Breaking: Lessons from Yeast Spore.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The gsr-1 gene encodes the only glutathione reductase in Caenorhabditis elegans and gsr-1 loss-of-function alleles have a fully penetrant embryonic lethal phenotype. Therefore, maintenance of glutathione redox homeostasis is essential for nematode survival. We report here that impairment of the nonsense-mediated mRNA decay (NMD) pathway suppresses the embryonic lethality of gsr-1 mutants, allowing their normal development and growth. This NMD pathway dependent suppression requires cth-1 and cth-2 that encode two isoforms of cystathionine-gamma-lyase that catalyze the conversion of cystathionine to cysteine through the transsulfuration pathway. In contrast, the thioredoxin system that can also provide cysteine through the cystine reduction pathway appears to be dispensable for the suppression of the lethal phenotype of gsr-1 embryos when the NMD pathway is inactivated. Together, our data indicate that increasing the activity of the reverse transsulfuration pathway can compensate the detrimental effect of the gsr-1 mutation, raising the interesting question of why C. elegans has not preserved such compensatory mechanism to avoid the embryonic lethality of these mutants.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Marina", "last_name": "Valenzuela-Villatoro", "name": null }, { "creator_type": "author", "first_name": "Eva", "last_name": "Gomez-Orte", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Guerrero-Gomez", "name": null }, { "creator_type": "author", "first_name": "Qing", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Angelina", "last_name": "Zheleva", "name": null }, { "creator_type": "author", "first_name": "Jose Antonio", "last_name": "Mora-Lorca", "name": null }, { "creator_type": "author", "first_name": "Dunja", "last_name": "Petrovic", "name": null }, { "creator_type": "author", "first_name": "Nigel J.", "last_name": "O Neil", "name": null }, { "creator_type": "author", "first_name": "Julian", "last_name": "Ceron Madrigal", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Hatakeyama", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Alexandra", "last_name": "Ordonez-Luque", "name": null }, { "creator_type": "author", "first_name": "Cristina", "last_name": "Ayuso", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Askjaer", "name": null }, { "creator_type": "author", "first_name": "Milos", "last_name": "Filipovic", "name": null }, { "creator_type": "author", "first_name": "Elias S. J.", "last_name": "Arner", "name": null }, { "creator_type": "author", "first_name": "Juan", "last_name": "Cabello", "name": null }, { "creator_type": "author", "first_name": "Antonio", "last_name": "Miranda-Vizuete", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/g3journal/jkaf102" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40333285" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": true }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": true }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Genes, Lethal", "descriptor_ui": "D005804", "major_topic": false }, { "descriptor": "Glutathione Reductase", "descriptor_ui": "D005980", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Nonsense Mediated mRNA Decay", "descriptor_ui": "D059365", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 7", "date_precision": "day", "issue": "", "normalized_date": "2025-05-07", "pages": "jkaf102", "proceedings_title": null, "publisher": "", "title": "G3 (Bethesda, Md.)", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The transsulfuration pathway suppresses the embryonic lethal phenotype of glutathione reductase mutants in Caenorhabditis elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Newly generated plasma cells in secondary lymphoid organs migrate to niches in the bone marrow, wherein they survive as long-lived plasma cells (LLPCs). Although LLPCs have been extensively characterized, it is still unclear what the key determinant(s) are for plasma cell longevity. One model postulates that plasma cell heterogeneity is established at the induction site, thereby instructing their longevity. Here, we found that, among newly generated IgG plasma cells, integrin beta7hi marks plasma cells predisposed to home to the bone marrow, whereas integrin beta7lo cells remain in secondary lymphoid organs. Mechanistically, this egress-prone fraction had a higher expression of the KLF2 transcription factor, the loss of which resulted in defective egress by downregulating S1PR1 and CD11b. Disruption of plasma cell egress results in defective antibody durability, thereby making mice more susceptible to influenza reinfection. Thus, the migration program of plasma cells established at the induction site plays a critical role in determining antibody durability.", "classifications": [ { "id": "18H05411", "label": "18H05411", "researcher": "Katsuyuki Shiroguchi", "type": "grant" }, { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Wataru", "last_name": "Ise", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Tai", "name": null }, { "creator_type": "author", "first_name": "Taiichiro", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Ryoji", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Shida", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Hojo", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Ichiyama", "name": null }, { "creator_type": "author", "first_name": "Shimon", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kurosaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1084/jem.20241019" }, "pmcid": { "normalized": "PMC11841683" }, "pmid": { "normalized": "39976598" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Marrow", "descriptor_ui": "D001853", "major_topic": false }, { "descriptor": "CD11b Antigen", "descriptor_ui": "D039481", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Immunoglobulin G", "descriptor_ui": "D007074", "major_topic": true }, { "descriptor": "Integrin beta Chains", "descriptor_ui": "D039641", "major_topic": false }, { "descriptor": "Kruppel-Like Transcription Factors", "descriptor_ui": "D051741", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Orthomyxoviridae Infections", "descriptor_ui": "D009976", "major_topic": false }, { "descriptor": "Plasma Cells", "descriptor_ui": "D010950", "major_topic": true }, { "descriptor": "Sphingosine-1-Phosphate Receptors", "descriptor_ui": "D000081025", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 5", "date_precision": "day", "issue": "5", "normalized_date": "2025-05-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "The Journal of experimental medicine", "volume": "222", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "KLF2 expression in IgG plasma cells at their induction site regulates the migration program.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although viral protein expression and progeny virus production were independently shown to be highly heterogeneous in individual cells, their direct relationship, analyzed by considering their heterogeneities, has not been investigated to date. To elucidate the direct relationship between viral protein expression and progeny virus production, we constructed a reporter herpes simplex virus 1 (HSV-1) by tagging Venus to the late protein Us11. We then separated the HSV-1-infected cell population into multiple subpopulations according to the fluorescence intensity of Venus-which reflected the expression of L proteins, largely constituting virion structural proteins-and titrated virus yields and performed electron microscopic analysis in each subpopulation. Our results revealed that infectious progeny virus production, as well as nucleocapsid maturation, was triggered only when L protein expression exceeded a specific threshold. This suggested the existence of a rate-limiting step in progeny virus production, with nucleocapsid maturation potentially being one such step.IMPORTANCEEarlier single-cell studies of virus-infected cells have revealed high heterogeneity in the state of viral gene expression and progeny virus yield. Notably, these two aspects have been shown independently, and therefore, the direct relationship between progeny virus production and viral gene expression has been unclear. This study, for the first time, demonstrated the direct and quantitative relationship between viral protein expression and progeny virus production by taking into account their heterogeneities and revealed a threshold for the levels of herpes simplex virus 1 protein expression for progeny virus production, thereby suggesting the existence of a rate-limiting step in progeny virus production.", "classifications": [ { "id": "21H00417", "label": "21H00417", "researcher": "Yuhei Maruzuru", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Moeka", "last_name": "Nobe", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Kusano", "name": null }, { "creator_type": "author", "first_name": "Raiki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Takara", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Hyeongki", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Kozaki", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Iwami", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Natsume", "name": null }, { "creator_type": "author", "first_name": "Shungo", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/mbio.00280-25" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40323094" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Viral", "descriptor_ui": "D015967", "major_topic": true }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nucleocapsid", "descriptor_ui": "D019251", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": true }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 May 5", "date_precision": "day", "issue": "", "normalized_date": "2025-05-05", "pages": "e0028025", "proceedings_title": null, "publisher": "", "title": "mBio", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Direct relationship between protein expression and progeny yield of herpes simplex virus 1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "DNA damage repair is a critical physiological process closely linked to aging. The accumulation of DNA damage in renal proximal tubular epithelial cells (PTEC) is related to a decline in kidney function. Here, we report that DNA double-strand breaks in PTECs lead to systemic metabolic dysfunction, including weight loss, reduced fat mass, impaired glucose tolerance with mitochondrial dysfunction, and increased inflammation in adipose tissues and the liver. Single-cell RNA sequencing analysis reveals expansion of CD11c+ Ccr2+ macrophages in the kidney cortex, liver, and adipose tissues and Ly6C(hi) monocytes in peripheral blood. DNA damage in PTECs is associated with hypomethylation of macrophage activation genes, including Gasdermin D, in peripheral blood cells, which is linked to reduced DNA methylation at KLF9-binding motifs. Macrophage depletion ameliorates metabolic abnormalities. These findings highlight the impact of kidney DNA damage on systemic metabolic homeostasis, revealing a kidney-blood-metabolism axis mediated by epigenetic changes in macrophages.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Erina Sugita", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Hishikawa", "name": null }, { "creator_type": "author", "first_name": "Ran", "last_name": "Nakamichi", "name": null }, { "creator_type": "author", "first_name": "Riki", "last_name": "Akashio", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Hashiguchi", "name": null }, { "creator_type": "author", "first_name": "Norifumi", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Eriko Yoshida", "last_name": "Hama", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Maruki", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Yoshino", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-59297-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40295524" } }, "mesh": [ { "descriptor": "Adipose Tissue", "descriptor_ui": "D000273", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DNA Breaks, Double-Stranded", "descriptor_ui": "D053903", "major_topic": false }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": true }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": true }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Gasdermins", "descriptor_ui": "D000094524", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Kidney Tubules, Proximal", "descriptor_ui": "D007687", "major_topic": true }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Macrophage Activation", "descriptor_ui": "D008262", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Phosphate-Binding Proteins", "descriptor_ui": "D028044", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Apr 28", "date_precision": "day", "issue": "1", "normalized_date": "2025-04-28", "pages": "3958", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "DNA damage in proximal tubules triggers systemic metabolic dysfunction through epigenetically altered macrophages.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herpesviruses encode conserved protein kinases (CHPKs) that target cellular cyclin-dependent kinase (CDK) phosphorylation sites; thus, they are termed viral CDK-like kinases. Tyrosine 15 in the GxGxxG motifs of CDK1 and CDK2, whose phosphorylation down-regulates their catalytic activities, is conserved in the corresponding motifs of CHPKs. We found that CHPK UL13, the corresponding Tyr-162 in herpes simplex virus 2 (HSV-2), was phosphorylated in HSV-2-infected cells. Mutational analyses of HSV-2 UL13 Tyr-162 suggested that phosphorylation of UL13 Tyr-162 reduced the phosphorylation of all UL13 substrates tested in HSV-2-infected cells. These findings suggested that HSV-2 UL13 mimicked the regulatory mechanism of CDKs and that this CHPK has regulatory and functional mimicry with CDKs. Furthermore, phosphorylation of HSV-2 UL13 Tyr-162 was suggested to be required for the downregulation of viral replication and pathogenicity, specifically in the brains of mice, and for efficient viral recurrence in guinea pigs. These findings highlight the dual impact of the regulatory mimicry of CDKs by CHPK on the fine-tuned regulation of lytic and latent HSV-2 infections in vivo.", "classifications": [ { "id": "21H00417", "label": "21H00417", "researcher": "Yuhei Maruzuru", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Kowit", "last_name": "Hengphasatporn", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Moeka", "last_name": "Nobe", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Maenaka", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Shigeta", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2500264122" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40238458" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinases", "descriptor_ui": "D018844", "major_topic": true }, { "descriptor": "Guinea Pigs", "descriptor_ui": "D006168", "major_topic": false }, { "descriptor": "Herpesvirus 2, Human", "descriptor_ui": "D018258", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Mimicry", "descriptor_ui": "D018716", "major_topic": true }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Kinases", "descriptor_ui": "D011494", "major_topic": true }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": true }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Apr 22", "date_precision": "day", "issue": "16", "normalized_date": "2025-04-22", "pages": "e2500264122", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "122", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Regulatory mimicry of cyclin-dependent kinases by a conserved herpesvirus protein kinase.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Here, we present a protocol for describing the generation of a proximal tubule-on-chip model using human induced pluripotent stem cell (hiPSC)-derived kidney organoids for renal transporter analysis. We describe steps for hiPSC differentiation into kidney organoids, proximal tubule cell isolation, and microfluidic chip seeding. The hiPSC-derived model enhances transporter expression and polarization, with improved uptake and efflux functions compared to conventional immortalized cell-based models. This protocol serves as a platform to assess renal transporter function, nephrotoxicity, and drug-drug interactions. For complete details on the use and execution of this protocol, please refer to Ma et al.(1).", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Cheng", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Ramin", "last_name": "Banan Sadeghian", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Negoro", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Toshikazu", "last_name": "Araoka", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Yokokawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xpro.2025.103777" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40266846" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Kidney Tubules, Proximal", "descriptor_ui": "D007687", "major_topic": true }, { "descriptor": "Lab-On-A-Chip Devices", "descriptor_ui": "D056656", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Apr 22", "date_precision": "day", "issue": "2", "normalized_date": "2025-04-22", "pages": "103777", "proceedings_title": null, "publisher": "", "title": "STAR protocols", "volume": "6", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Protocol to develop a proximal tubule-on-chip model based on hiPSC-derived kidney organoids for functional analysis of renal transporters.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Age-associated B cells (ABCs) with autoreactive properties accumulate with age and expand prematurely in autoimmune diseases. However, the mechanisms behind ABC generation and maintenance remain poorly understood. We show that continuous B cell receptor (BCR) signaling is essential for ABC development from anergic B cells in aged and autoimmune mice. ABCs exhibit constitutive BCR activation, with surface BCRs being internalized. Notably, anergic B cells, but not nonautoreactive B cells, contributed to ABC formation in these models. Anergic B cells also showed a greater propensity for in vitro differentiation into ABCs, which was inhibited by the expression of the transcription factor Nr4a1. Bruton's tyrosine kinase (Btk), a key BCR signaling component, was constitutively activated in ABCs from aged and autoimmune mice as well as patients with lupus. Inhibiting Btk reduced ABC numbers and ameliorated the pathogenicity of lupus mice. Our findings reveal critical mechanisms underlying ABC development and offer previously unrecognized therapeutic insights for autoimmune diseases.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Imabayashi", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Yada", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Motoki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Akemi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Niiro", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adt8199" }, "pmcid": { "normalized": "PMC12007576" }, "pmid": { "normalized": "40249819" } }, "mesh": [ { "descriptor": "Agammaglobulinaemia Tyrosine Kinase", "descriptor_ui": "D000077329", "major_topic": false }, { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autoimmunity", "descriptor_ui": "D015551", "major_topic": true }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Clonal Anergy", "descriptor_ui": "D017635", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lupus Erythematosus, Systemic", "descriptor_ui": "D008180", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Receptors, Antigen, B-Cell", "descriptor_ui": "D011947", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Apr 18", "date_precision": "day", "issue": "16", "normalized_date": "2025-04-18", "pages": "eadt8199", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "11", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Critical roles of chronic BCR signaling in the differentiation of anergic B cells into age-associated B cells in aging and autoimmunity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: To our knowledge, the ACHILLES/TORG1834 trial is the first randomized study comparing afatinib and chemotherapy in patients with non-small cell lung cancer (NSCLC) harboring sensitizing uncommon epidermal growth factor receptor (EGFR) mutations. METHODS: This randomized, open-label study was performed at 51 Japanese institutions and recruited treatment-naive patients with nonsquamous NSCLC with uncommon EGFR mutations, excluding exon 20 insertions and T790M mutations. Patients were randomly assigned 2:1 to receive afatinib (30 or 40 mg orally, at the treating physician's discretion) or a combination of platinum (cisplatin or carboplatin) and pemetrexed, followed by pemetrexed maintenance. The primary end point was progression-free survival (PFS). Secondary end points included objective response rate (ORR), overall survival, and safety. A prespecified interim analysis was planned to provide clinically meaningful information promptly, along with a crossover recommendation if necessary. RESULTS: A total of 109 patients were enrolled between March 2019 and February 2023. In the interim analysis, the Data and Safety Monitoring Committee recommended early study termination. The median PFS was significantly longer in patients receiving afatinib than in those undergoing chemotherapy (10.6 v 5.7 months; hazard ratio, 0.421 [95% CI, 0.251 to 0.706]; P = .0010). ORRs to afatinib were similar across the overall population and among participants with major uncommon (G719X, L861Q, and S768I), compound, and other mutations (61.7%, 55.8%, 72.7%, and 60.0%, respectively). The most common grade 3 or higher adverse events were diarrhea, paronychia, and rash for afatinib, and appetite loss and nausea for chemotherapy. CONCLUSION: Afatinib should be considered the standard initial therapy for patients with NSCLC with sensitizing uncommon EGFR mutations.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Misumi", "name": null }, { "creator_type": "author", "first_name": "Hiroshige", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Tokito", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yoshimasa", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Naoki", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Akamatsu", "name": null }, { "creator_type": "author", "first_name": "Ou", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Shoichi", "last_name": "Kuyama", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Furuya", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kurata", "name": null }, { "creator_type": "author", "first_name": "Terufumi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Eiki", "last_name": "Ichihara", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Takiguchi", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Okamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1200/jco-24-02007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40239133" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Afatinib", "descriptor_ui": "D000077716", "major_topic": true }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": true }, { "descriptor": "Carboplatin", "descriptor_ui": "D016190", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Cisplatin", "descriptor_ui": "D002945", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Pemetrexed", "descriptor_ui": "D000068437", "major_topic": false }, { "descriptor": "Progression-Free Survival", "descriptor_ui": "D000077982", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Apr 16", "date_precision": "day", "issue": "", "normalized_date": "2025-04-16", "pages": "JCO2402007", "proceedings_title": null, "publisher": "", "title": "Journal of clinical oncology : official journal of the American Society of Clinical Oncology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Pragmatic Randomized Study of Afatinib Versus Chemotherapy for Patients With Non-Small Cell Lung Cancer With Uncommon Epidermal Growth Factor Receptor Mutations: ACHILLES/TORG1834.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We developed CaliAli, a comprehensive suite designed to extract neuronal signals from one-photon calcium imaging data collected across multiple sessions in free-moving conditions in mice. CaliAli incorporates information from blood vessels and neurons to correct inter-session misalignments, making it robust against non-rigid brain deformations even after substantial changes in the field of view across sessions. This also makes CaliAli robust against high neuron overlap and changes in active neuron population across sessions. CaliAli performs computationally efficient signal extraction from concatenated video sessions that enhances the detectability of weak calcium signals. Notably, CaliAli enhanced the spatial coding accuracy of extracted hippocampal CA1 neuron activity across sessions. An optogenetic tagging experiment showed that CaliAli enhanced neuronal trackability in the dentate gyrus across a time scale of weeks. Finally, dentate gyrus neurons tracked using CaliAli exhibited stable population activity for 99 days. Overall, CaliAli advances our capacity to understand the activity dynamics of neuronal ensembles over time, which is crucial for deciphering the complex neuronal substrates of natural animal behaviors.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Pablo", "last_name": "Vergara", "name": null }, { "creator_type": "author", "first_name": "Yuteng", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Sakthivel", "last_name": "Srinivasan", "name": null }, { "creator_type": "author", "first_name": "Zhe", "last_name": "Dong", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Feng", "name": null }, { "creator_type": "author", "first_name": "Iyo", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Deependra", "last_name": "Kumar", "name": null }, { "creator_type": "author", "first_name": "Yoan", "last_name": "Cherasse", "name": null }, { "creator_type": "author", "first_name": "Toshie", "last_name": "Naoi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugaya", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Tristan", "last_name": "Shuman", "name": null }, { "creator_type": "author", "first_name": "Denise", "last_name": "Cai", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Sakaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-58817-z" }, "pmcid": { "normalized": "PMC11992088" }, "pmid": { "normalized": "40216771" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CA1 Region, Hippocampal", "descriptor_ui": "D056547", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": true }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Dentate Gyrus", "descriptor_ui": "D018891", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Photons", "descriptor_ui": "D017785", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Apr 11", "date_precision": "day", "issue": "1", "normalized_date": "2025-04-11", "pages": "3443", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "A comprehensive suite for extracting neuron signals across multiple sessions in one-photon calcium imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Selection of appropriate food is an ability that allows animals to make optimal foraging choices. However, the neural mechanisms that control this food selection remain unclear. The purpose of this study was to investigate the connection between memory and the feeding behavior of Drosophila melanogaster when two sucrose solutions with different concentrations are available. We placed flies into plates with 150 mM and 100 mM sucrose solutions and measured the preference for the 150 mM one. Flies preferred the 150 mM solution over the 100 mM when all 60 wells of the plate were filled with both solutions; this preference decreased when there were only 8 wells with food. Remarkably, prior exposure to a plate with all 60 wells filled with both solutions enhanced the preference for the 150 mM, even when there were only 8 wells with food. We found that the memory-related gene rut and the dopamine D1 receptor on the mushroom body were required to enhance the preference after the prior exposure. These findings show that memory acquired through experiencing both solutions is stored in the mushroom body optimizing the food selection process.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Maximiliano", "last_name": "Martinez-Cordera", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Saitoe", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Ueno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13041-025-01202-0" }, "pmcid": { "normalized": "PMC11983738" }, "pmid": { "normalized": "40211246" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Choice Behavior", "descriptor_ui": "D002755", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": true }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Feeding Behavior", "descriptor_ui": "D005247", "major_topic": false }, { "descriptor": "Food Preferences", "descriptor_ui": "D005518", "major_topic": true }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": true }, { "descriptor": "Mushroom Bodies", "descriptor_ui": "D024521", "major_topic": false }, { "descriptor": "Receptors, Dopamine D1", "descriptor_ui": "D017447", "major_topic": false }, { "descriptor": "Sucrose", "descriptor_ui": "D013395", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Apr 10", "date_precision": "day", "issue": "1", "normalized_date": "2025-04-10", "pages": "32", "proceedings_title": null, "publisher": "", "title": "Molecular brain", "volume": "18", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparative experience shapes sucrose preference through memory in Drosophila.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND PURPOSE: Several G protein-coupled receptors (GPCRs) are known to homodimerise. Dimeric GPCRs may have different properties from their monomers, but the molecular basis and functional significance of GPCR dimerisation remain largely unknown. We recently found that signalling by the vasoactive intestinal peptide receptor, VIPR2, regulates breast cancer cell migration and proliferation. However, it is unclear whether VIPR2 monomers directly interact with each other and what function the dimeric receptor has. Here, we showed that VIPR2 dimerises and investigated their role in breast cancer progression. EXPERIMENTAL APPROACH: Dimerisation of VIPR2 was assessed by fluorescence resonance energy transfer (FRET) analysis and a pull-down assay. Breast cancer progression was analysed by orthotopic growth and metastasis of human breast cancers into proper axillary and subiliac lymph-nodes in mice. KEY RESULTS: VIPR2 monomers directly interacted with each other through transmembrane domains (TM)3-4. FRET analysis revealed that VIPR2 moved further apart in cells expressing TM3-4-peptides, suggesting that TM3-4 prevents VIPR2 dimerisation. Breast cancer cells stably expressing TM3-4 region exhibited suppressed tumour growth and lymph-node metastasis. Furthermore, ligand-receptor binding assays revealed that VIP-FITC bound to cells dose-dependently, and VIPR2 de-dimerisation by TM3-4 expression decreased VIP's affinity to cells. Additionally, TM3-4 expression decreased Galpha(i)-VIPR2 interactions. CONCLUSION AND IMPLICATIONS: Dimeric VIPR2 forms the minimal functional unit that effectively promotes growth and metastasis of breast cancer. Therefore, dimeric VIPR2 is a potential therapeutic target for breast cancer, and TM3-4-peptides are potential anti-cancer drug candidates to suppress cancer progression.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Kairi", "last_name": "Ozasa", "name": null }, { "creator_type": "author", "first_name": "Teru", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Souichi", "last_name": "Yanamoto", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/bph.70039" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40203889" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "GTP-Binding Protein alpha Subunits, Gi-Go", "descriptor_ui": "D019206", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Multimerization", "descriptor_ui": "D055503", "major_topic": false }, { "descriptor": "Receptors, Vasoactive Intestinal Peptide, Type II", "descriptor_ui": "D051239", "major_topic": true }, { "descriptor": "Vasoactive Intestinal Peptide", "descriptor_ui": "D014660", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Apr 9", "date_precision": "day", "issue": "", "normalized_date": "2025-04-09", "pages": "", "proceedings_title": null, "publisher": "", "title": "British journal of pharmacology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Dimerisation of the VIP receptor VIPR2 is essential to its binding VIP and Galpha(i) proteins, and to its functions in breast cancer cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: In recent years, computer-aided diagnosis (CAD) using deep learning methods for medical images has been studied. Although studies have been conducted to classify ultrasound images of tumors of the liver into four categories (liver cysts (Cyst), liver hemangiomas (Hemangioma), hepatocellular carcinoma (HCC), and metastatic liver cancer (Meta)), no studies with additional information for deep learning have been reported. Therefore, we attempted to improve the classification accuracy of ultrasound images of hepatic tumors by adding hepatitis virus infection information to deep learning. METHODS: Four combinations of hepatitis virus infection information were assigned to each image, plus or minus HBs antigen and plus or minus HCV antibody, and the classification accuracy was compared before and after the information was input and weighted to fully connected layers. RESULTS: With the addition of hepatitis virus infection information, accuracy changed from 0.574 to 0.643. The F1-Score for Cyst, Hemangioma, HCC, and Meta changed from 0.87 to 0.88, 0.55 to 0.57, 0.46 to 0.59, and 0.54 to 0.62, respectively, remaining the same for Hemangioma but increasing for the rest. CONCLUSION: Learning hepatitis virus infection information showed the highest increase in the F1-Score for HCC, resulting in improved classification accuracy of ultrasound images of hepatic tumors.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hatamoto", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10396-025-01528-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40205118" } }, "mesh": [ { "descriptor": "Carcinoma, Hepatocellular", "descriptor_ui": "D006528", "major_topic": false }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Hemangioma", "descriptor_ui": "D006391", "major_topic": false }, { "descriptor": "Hepatitis, Viral, Human", "descriptor_ui": "D006525", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Interpretation, Computer-Assisted", "descriptor_ui": "D007090", "major_topic": true }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Ultrasonography", "descriptor_ui": "D014463", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Apr 9", "date_precision": "day", "issue": "", "normalized_date": "2025-04-09", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of medical ultrasonics (2001)", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Improving ultrasound image classification accuracy of liver tumors using deep learning model with hepatitis virus infection information.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The early identification of developmental concerns requires understanding individual differences that may represent early signs of neurodevelopmental conditions. However, few studies have longitudinally examined how child and maternal factors interact to shape these early developmental characteristics. OBJECTIVE: We aim to identify factors from the perinatal to infant periods associated with early developmental characteristics that may precede formal diagnoses and propose a method for evaluating individual differences in neurodevelopmental trajectories. METHODS: A prospective longitudinal observational study of 147 mother-child pairs was conducted from gestation to 12 months post partum. Assessments included prenatal questionnaires and blood collection, cord blood at delivery, and postpartum questionnaires at 1, 6, and 12 months. The Modified Checklist for Autism in Toddlers (M-CHAT) was used to evaluate developmental characteristics that might indicate early signs of atypical neurodevelopment. Polychoric or polyserial correlation coefficients assessed relationships between M-CHAT scores and longitudinal variables. L2-regularized logistic regression and Shapley Additive Explanations predicted M-CHAT scores and determined feature contributions. RESULTS: Twenty-one factors (4 prenatal, 3 at birth, and 14 postnatal) showed significant associations with M-CHAT scores (adjusted P values<.05). The predictive accuracy for M-CHAT scores demonstrated reasonable predictive accuracy (area under the receiver operating characteristic curve=0.79). Key predictors included infant sleep status after 6 months (nighttime sleep duration, bedtime, and difficulties falling asleep), maternal Kessler Psychological Distress Scale scores, and Mother-to-Infant Bonding Scale scores after late gestation. CONCLUSIONS: Maternal psychological distress, mother-infant bonding, and infant sleep patterns were identified as significant predictors of early developmental characteristics that may indicate emerging developmental concerns. This study advances our understanding of early developmental assessment by providing a novel approach to identifying and evaluating early indicators of atypical neurodevelopment.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Daigo", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Okuno", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Itakura", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Oguchi", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Kasahara", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kanenishi", "name": null }, { "creator_type": "author", "first_name": "Yuzo", "last_name": "Kitadai", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Shimojo", "name": null }, { "creator_type": "author", "first_name": "Kazushige", "last_name": "Nakahara", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Hanai", "name": null }, { "creator_type": "author", "first_name": "Hiromichi", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Haruta", "last_name": "Mogami", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Morokuma", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Sakurada", "name": null }, { "creator_type": "author", "first_name": "Yukuo", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.2196/58337" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40190042" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Apr 4", "date_precision": "day", "issue": "", "normalized_date": "2025-04-04", "pages": "e58337", "proceedings_title": null, "publisher": "", "title": "JMIR pediatrics and parenting", "volume": "8", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Multilevel Factors and Indicators of Atypical Neurodevelopment During Early Infancy in Japan: Prospective, Longitudinal, Observational Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cannabinoid receptor type 1 (CB1R) is the key modulator of neuronal viability. CB1R antagonists provide neuroprotective effects on neurotoxicity caused by e.g. neuronal injury. However, the underlying mechanisms and potential limitations of CB1R antagonism remain unclear. Here we investigated the impact of environmental conditions on CB1R antagonist effects. We have found that cell-permeable CB1R antagonists, rimonabant and AM251, induced cell death in human neuroblastoma SH-SY5Y cells under serum-free conditions. Mitochondrial morphological analysis revealed mitochondrial swelling characterized by their network fragmentation and cristae reduction. Phosphoproteomics analysis showed the ER stress signaling pathway PERK/eIF2alpha/ATF4/CHOP, leading to caspase-dependent apoptosis. These results suggest that CB1R antagonists promote apoptosis via mitochondrial damage and ER stress under serum-free conditions in SH-SY5Y cells. Our findings indicate that while CB1R antagonists may be neuroprotective in certain conditions, they may also pose a neurotoxic risk in environments characterized by cellular stress or nutrient deprivation.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Akinobu", "last_name": "Togo", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Sakuragi", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null }, { "creator_type": "author", "first_name": "Taishi", "last_name": "Umezawa", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Asahi", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Nozaki", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Kataoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuropharm.2025.110440" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40185361" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": true }, { "descriptor": "Cannabinoid Receptor Antagonists", "descriptor_ui": "D063387", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum Stress", "descriptor_ui": "D059865", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": true }, { "descriptor": "Neuroblastoma", "descriptor_ui": "D009447", "major_topic": false }, { "descriptor": "Piperidines", "descriptor_ui": "D010880", "major_topic": false }, { "descriptor": "Pyrazoles", "descriptor_ui": "D011720", "major_topic": false }, { "descriptor": "Receptor, Cannabinoid, CB1", "descriptor_ui": "D043884", "major_topic": true }, { "descriptor": "Rimonabant", "descriptor_ui": "D000077285", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Apr 2", "date_precision": "day", "issue": "", "normalized_date": "2025-04-02", "pages": "110440", "proceedings_title": null, "publisher": "", "title": "Neuropharmacology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Mitochondrial Damage and ER Stress in CB1 Receptor Antagonist-Induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Despite the importance of imaging in biological and medical research, a large body of informative and precious image data never sees the light of day. To ensure scientific rigor as well as the reuse of data for scientific discovery, image data need to be made FAIR (findable, accessible, interoperable and reusable). Image data experts are working together globally to agree on common data formats, metadata, ontologies and supporting tools toward image data FAIRification. With this Perspective, we call on public funders to join these efforts to support their national scientists. What researchers most urgently need are openly accessible resources for image data storage that are operated under long-term commitments by their funders. Although existing resources in Australia, Japan and Europe are already collaborating to enable global image data sharing, these efforts will fall short unless more countries invest in operating and federating their own open data resources. This will allow us to harvest the enormous potential of existing image data, preventing substantial loss of unrealized value from past investments in imaging acquisition infrastructure.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Peter", "last_name": "Bajcsy", "name": null }, { "creator_type": "author", "first_name": "Sreenivas", "last_name": "Bhattiprolu", "name": null }, { "creator_type": "author", "first_name": "Katy", "last_name": "Borner", "name": null }, { "creator_type": "author", "first_name": "Beth A.", "last_name": "Cimini", "name": null }, { "creator_type": "author", "first_name": "Lucy", "last_name": "Collinson", "name": null }, { "creator_type": "author", "first_name": "Jan", "last_name": "Ellenberg", "name": null }, { "creator_type": "author", "first_name": "Reto", "last_name": "Fiolka", "name": null }, { "creator_type": "author", "first_name": "Maryellen", "last_name": "Giger", "name": null }, { "creator_type": "author", "first_name": "Wojtek", "last_name": "Goscinski", "name": null }, { "creator_type": "author", "first_name": "Matthew", "last_name": "Hartley", "name": null }, { "creator_type": "author", "first_name": "Nathan", "last_name": "Hotaling", "name": null }, { "creator_type": "author", "first_name": "Rick", "last_name": "Horwitz", "name": null }, { "creator_type": "author", "first_name": "Florian", "last_name": "Jug", "name": null }, { "creator_type": "author", "first_name": "Isabel", "last_name": "Kemmer", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Kreshuk", "name": null }, { "creator_type": "author", "first_name": "Emma", "last_name": "Lundberg", "name": null }, { "creator_type": "author", "first_name": "Aastha", "last_name": "Mathur", "name": null }, { "creator_type": "author", "first_name": "Kedar", "last_name": "Narayan", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Anne L.", "last_name": "Plant", "name": null }, { "creator_type": "author", "first_name": "Fred", "last_name": "Prior", "name": null }, { "creator_type": "author", "first_name": "Jason R.", "last_name": "Swedlow", "name": null }, { "creator_type": "author", "first_name": "Adam", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Antje", "last_name": "Keppler", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41592-024-02585-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40155720" } }, "mesh": [ { "descriptor": "Biological Science Disciplines", "descriptor_ui": "D001690", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Information Dissemination", "descriptor_ui": "D033181", "major_topic": true }, { "descriptor": "Information Storage and Retrieval", "descriptor_ui": "D016247", "major_topic": false }, { "descriptor": "Metadata", "descriptor_ui": "D000071253", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Mar 28", "date_precision": "day", "issue": "", "normalized_date": "2025-03-28", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature methods", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Enabling global image data sharing in the life sciences.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Wolffian duct is a pair of epithelial ductal structures along the body axis that induces nephron development by interaction with the metanephric mesenchyme. The interaction between the mesenchyme and the ureteric bud derived from the Wolffian duct is mediated by Wnt ligands, the loss of which results in kidney agenesis. Nonetheless, the early contribution of Wnt signaling to Wolffian duct formation remains unclear. We therefore examined these dynamics in knockout and transgenic mouse embryos. The Wnt signal reporter was active in the extending Wolffian duct, and Wnt3a-knockout embryos exhibited a fragmented and misdirectional Wolffian duct. Apicobasal polarity was disrupted under Wnt3a-deficiency. These findings suggest that Wnt3a plays an important role in Wolffian duct development by regulating apicobasal polarity.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shinichi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2025.03.015" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40154784" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": true }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": false }, { "descriptor": "Wnt3A Protein", "descriptor_ui": "D060509", "major_topic": true }, { "descriptor": "Wolffian Ducts", "descriptor_ui": "D014928", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Mar 27", "date_precision": "day", "issue": "", "normalized_date": "2025-03-27", "pages": "136-142", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "522", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Wnt3a is an early regulator of the Wolffian duct directionality via the regulation of apicobasal cell polarity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: To identify key molecules involved in the disease pathophysiology of systemic vasculitis through trans-omics analysis, with a specific focus on demonstrating MMP12 as a potential biomarker in rheumatic entities. METHODS: Patients with newly diagnosed or relapsed rheumatic and musculoskeletal diseases from June 2013 until September 2022 were enrolled. We screened vasculitis-specific molecules by combining findings from serum proteome analysis and whole-blood RNA sequencing. We further validated the identified molecules using immunohistochemical staining and spatial transcriptome analysis. RESULTS: Serum proteome and RNA sequencing identified matrix metalloproteinase (MMP) 12 as a significant molecule for systemic vasculitis; it distinguished vasculitis from other rheumatic and musculoskeletal diseases, reflected disease activity along with longitudinal change, and predicted relapse in patients with large-vessel vasculitis. MMP12 could also be used to detect insidious disease activity even under treatment with interleukin-6 inhibition. Immunohistochemical staining of the affected tissues demonstrated that MMP12 was specifically expressed in tissue-infiltrating CD206-positive macrophages. Spatial transcriptome analysis revealed the characteristic phenotype of MMP12-positive macrophages and its association with macrophage maturation and formation of multinucleated giant cells. CONCLUSION: MMP12 is a disease-specific molecule that is associated with macrophage maturation and the formation of multinucleated giant cells and reflects disease activity independently of the interleukin-6 pathway in systemic vasculitis.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kotaro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Mayu", "last_name": "Magi", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Onishi", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Takeshita", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Kuramoto", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Yazawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Noguchi-Sasaki", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Kaneko", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/rheumatology/keaf175" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40139687" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Matrix Metalloproteinase 12", "descriptor_ui": "D053508", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Proteome", "descriptor_ui": "D020543", "major_topic": true }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "Systemic Vasculitis", "descriptor_ui": "D056647", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Mar 26", "date_precision": "day", "issue": "", "normalized_date": "2025-03-26", "pages": "keaf175", "proceedings_title": null, "publisher": "", "title": "Rheumatology (Oxford, England)", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Trans-omics landscape of systemic vasculitis identified matrix metalloproteinase 12 as a novel signature molecule.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Monoclonal antibodies (mAbs) have become essential in modern therapeutics, offering high specificity and efficacy in treating diseases such as cancer, autoimmune disorders, and infectious diseases. With the increasing demand for mAbs, robust analytical and purification technologies are critical to ensuring their safety, efficacy, and consistency. This review highlights recent advances in the application of HPLC for both mAb analysis and purification. In the analytical domain, techniques such as size exclusion chromatography (SEC), hydrophobic interaction chromatography (HIC), ion exchange chromatography (IEX), and reversed-phase chromatography (RPLC) are explored for their role in evaluating mAb structural attributes and post-translational modifications (PTMs). These methods are indispensable for ensuring stability and functionality while meeting stringent regulatory requirements. In the context of purification, Protein A affinity chromatography remains the gold standard for initial capture of mAb; however, challenges such as high cost and harsh elution conditions have prompted the development of alternative purification technologies. IEX, HIC, multimodal, and membrane chromatography are also critical in achieving high-purity mAb products through multistep workflows, including intermediate purification and polishing stages. This review emphasizes the central role of HPLC in addressing the complex challenges of mAb manufacturing and characterization. By integrating established and emerging chromatographic techniques, it provides insights into the future directions of therapeutic antibody development.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Suprit", "last_name": "Deol", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s44211-025-00748-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40126861" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": true }, { "descriptor": "Chromatography, High Pressure Liquid", "descriptor_ui": "D002851", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Mar 24", "date_precision": "day", "issue": "", "normalized_date": "2025-03-24", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical sciences : the international journal of the Japan Society for Analytical Chemistry", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Current advances in separation chemistry for antibody purification and analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Anti-vascular endothelial growth factor (VEGF) agents in combination with immunotherapies have improved outcomes for cancer patients, but predictive biomarkers have not been elucidated. We report here a preplanned analysis in the previously reported APPLE study, a phase 3 trial evaluating the efficacy of the bevacizumab in combination with atezolizumab, plus platinum chemotherapy in metastatic, nonsquamous non-small cell lung cancer (NSCLC). We investigated the correlation of serum VEGF-A and its isoforms at baseline with treatment response by using an enzyme-linked immunosorbent assay. We reveal that the addition of bevacizumab significantly improves the progression-free survival in patients with the low VEGF-A level. Our results demonstrate that measuring serum VEGF-A or its isoforms may identify NSCLC patients who are likely to benefit from the addition of bevacizumab to immunotherapy. These assays are easy to measure and have significant potential for further clinical development.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kentaro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Sugisaka", "name": null }, { "creator_type": "author", "first_name": "Yoshimasa", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Yasutaka", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Daga", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Takayo", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Haruhiro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kozuki", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Akamatsu", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Motoko", "last_name": "Tachihara", "name": null }, { "creator_type": "author", "first_name": "Kazushige", "last_name": "Wakuda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Tsuchiya-Kawano", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Isamu", "last_name": "Okamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-58186-7" }, "pmcid": { "normalized": "PMC11929838" }, "pmid": { "normalized": "40121197" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal, Humanized", "descriptor_ui": "D061067", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": true }, { "descriptor": "Bevacizumab", "descriptor_ui": "D000068258", "major_topic": true }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunotherapy", "descriptor_ui": "D007167", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false }, { "descriptor": "Progression-Free Survival", "descriptor_ui": "D000077982", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor A", "descriptor_ui": "D042461", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Mar 22", "date_precision": "day", "issue": "1", "normalized_date": "2025-03-22", "pages": "2825", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Serum VEGF-A as a biomarker for the addition of bevacizumab to chemo-immunotherapy in metastatic NSCLC.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Liquid-liquid phase separation leads to the formation of liquid droplets (LqDs) such as P granules in Caenorhabditis elegans (C. elegans). In this study, we demonstrate the label-free visualization of LqDs using multimodal nonlinear optical imaging both in vitro and in vivo. In vitro measurements with polymerized adenine [poly(A)], we found significantly higher poly(A) concentrations in LqDs compared to surrounding solutions, with the limit of detection (LoD) of 32 mg/mL. In vivo measurements, we performed label-free imaging of C. elegans. Despite efforts to detect P granules within P lineage cells in both wild-type C. elegans and green fluorescent protein (GFP)-tagged strains, no clear RNA-specific signals were observed. This indicates that the RNA concentration in P granules is lower than anticipated and falls below our in vitro LoD. These results underscore the challenges of label-free RNA detection in P granules.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Mia", "last_name": "Obuchi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kamizawa", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Kishimura", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Oketani", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Hiramatsu", "name": null }, { "creator_type": "author", "first_name": "Philippe", "last_name": "Leproux", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Shiraki", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s44211-025-00747-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40113733" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": true }, { "descriptor": "Nonlinear Dynamics", "descriptor_ui": "D017711", "major_topic": true }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": true }, { "descriptor": "Phase Separation", "descriptor_ui": "D000095496", "major_topic": false }, { "descriptor": "Poly A", "descriptor_ui": "D011061", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Mar 20", "date_precision": "day", "issue": "", "normalized_date": "2025-03-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical sciences : the international journal of the Japan Society for Analytical Chemistry", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Exploring liquid-liquid phase separation in vitro and in vivo using multimodal nonlinear optical imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The identification of kinetically feasible reaction pathways that connect a reactant to its product, including numerous intermediates and transition states, is crucial for predicting chemical reactions and elucidating reaction mechanisms. However, as molecular systems become increasingly complex or larger, the number of local minimum structures and transition states grows, which makes this task challenging, even with advanced computational approaches. We introduced a reinforcement learning algorithm to efficiently identify a kinetically feasible reaction pathway between a given local minimum structure for the reactant and a given one for the product, starting from the reactant. The performance of the algorithm was validated using a benchmark data set of large-scale chemical reaction path networks. Several search policies were proposed, using metrics based on energetic or structural similarity to the product's goal structure, for each local minimum structure candidate found during the search. The performances of baseline greedy, random, and uniform search policies varied substantially depending on the system. In contrast, exploration-exploitation balanced policies such as Thompson sampling, probability of improvement, and expected improvement consistently demonstrated stable and high performance. Furthermore, we characterized the search mechanisms that depend on different policies in detail. This study also addressed potential avenues for further research, such as hierarchical reinforcement learning and multiobjective optimization, which could deepen the problem setting explored in this study.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jctc.4c01780" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40105681" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Mar 19", "date_precision": "day", "issue": "", "normalized_date": "2025-03-19", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of chemical theory and computation", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparative Analysis of Reinforcement Learning Algorithms for Finding Reaction Pathways: Insights from a Large Benchmark Data Set.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although the cerebellum is typically associated with supervised learning algorithms, it also exhibits extensive involvement in reward processing. In this study, we investigated the cerebellum's role in executing reinforcement learning algorithms, with a particular emphasis on essential reward-prediction errors. We employed the Q-learning model to accurately reproduce the licking responses of mice in a Go/No-go auditory-discrimination task. This method enabled the calculation of reinforcement learning variables, such as reward, predicted reward, and reward-prediction errors in each learning trial. Through tensor component analysis of two-photon Ca2+ imaging data from more than 6,000 Purkinje cells, we found that climbing fiber inputs of the two distinct components, which were specifically activated during Go and No-go cues in the learning process, showed an inverse relationship with predictive reward-prediction errors. Assuming bidirectional parallel-fiber Purkinje-cell synaptic plasticity, we constructed a cerebellar neural-network model with 5,000 spiking neurons of granule cells, Purkinje cells, cerebellar nuclei neurons, and inferior olive neurons. The network model qualitatively reproduced distinct changes in licking behaviors, climbing-fiber firing rates, and their synchronization during discrimination learning separately for Go/No-go conditions. We found that Purkinje cells in the two components could develop specific motor commands for their respective auditory cues, guided by the predictive reward-prediction errors from their climbing fiber inputs. These results indicate a possible role of context-specific actors in modular reinforcement learning, integrating with cerebellar supervised learning capabilities.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Huu", "last_name": "Hoang", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Matsuzaki", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Mitsuo", "last_name": "Kawato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1012899" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40096178" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": true }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Models, Neurological", "descriptor_ui": "D008959", "major_topic": true }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Reinforcement, Psychology", "descriptor_ui": "D012054", "major_topic": true }, { "descriptor": "Reward", "descriptor_ui": "D012201", "major_topic": true }, { "descriptor": "Supervised Machine Learning", "descriptor_ui": "D000069553", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Mar 17", "date_precision": "day", "issue": "3", "normalized_date": "2025-03-17", "pages": "e1012899", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "21", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Predictive reward-prediction errors of climbing fiber inputs integrate modular reinforcement learning with supervised learning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Multiple signal detection methods are known for lateral flow immunoassays (LFIAs), with colorimetric approaches dominating the field. However, their limited sensitivity is a remaining challenge. Fluorescence-based signaling is regarded as a more sensitive method, but it comes at the cost of partial sacrifice of the user-friendliness of LFIAs due to the requirement of an excitation light source. In this context, bioluminescence providing an inherently high signal to noise ratio without the need of excitation light could be an attractive alternative. But only a few studies have demonstrated the application of bioluminescence signaling in LFIAs. This work aimed at the development of a simple bioluminescence-based LFIA for the detection of aflatoxin B1 (AFB1), used as a model target in a competitive LFIA format. Signal transduction was achieved by nanobody-nanoluciferase (Nluc) fusion proteins. These small-sized recombinant heavy-chain-only antibodies derived from the camelidae family directly linked with the Nluc enzyme produce high intensity glow-type bioluminescence in combination with the furimazine substrate. LFIA devices consisting of a sample pad, nitrocellulose membrane and absorbent pad with AFB1-BSA conjugate deposited at the test line on the nitrocellulose membrane, achieved an LOD of 0.26 ng mL(-1) for aqueous AFB1 solutions pre-mixed with Nanobody-Nluc and bioluminescence emission observed on an imaging system. More user-friendly LFIA devices with integrated conjugate pad and pre-deposited Nanobody-Nluc provided clear AFB1 concentration-dependent bioluminescence signals with low background and enabled readout with a standard digital camera, resulting in an LOD of 1.12 ng mL(-1). Finally, the LFIA strips have been applied in AFB1-spiked oat milk samples. The LOD of 4.09 ng mL(-1) achieved in the real sample matrix is well below the maximum allowable residual concentration of AFB1 in the U.S. (20 ng mL(-1)).", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shun", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d5an00030k" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40094173" } }, "mesh": [ { "descriptor": "Aflatoxin B1", "descriptor_ui": "D016604", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Food Contamination", "descriptor_ui": "D005506", "major_topic": false }, { "descriptor": "Immunoassay", "descriptor_ui": "D007118", "major_topic": false }, { "descriptor": "Limit of Detection", "descriptor_ui": "D057230", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": true }, { "descriptor": "Milk", "descriptor_ui": "D008892", "major_topic": false }, { "descriptor": "Single-Domain Antibodies", "descriptor_ui": "D061905", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Mar 17", "date_precision": "day", "issue": "", "normalized_date": "2025-03-17", "pages": "", "proceedings_title": null, "publisher": "", "title": "The Analyst", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Bioluminescence readout lateral flow immunoassay using nanobody targeting aflatoxin B1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In clinical diagnosis, the determination of target proteins at low concentration levels is generally performed by immunoassays, such as the enzyme-linked immunosorbent assay (ELISA), which is a time-consuming process. To date, paper-based ELISA platforms enabling faster and less expensive analysis have been developed, but their important issue for clinical applications is the limited sensitivity compared to conventional ELISA. To address this challenge, this paper introduces a simple, rapid, and highly sensitive detection method for non-nucleic acid targets achieved by integrating the CRISPR/Cas12a system into paper-based ELISA. An origami-type paper-based device enabling simple assay operation has been designed, and the detection of targets on the paper substrates is based on observing the fluorescence signal induced by the CRISPR/Cas12a enzyme cleaving a probe single-stranded DNA (ssDNA) labeled with fluorophore and quencher (FQ reporter). To enhance sensitivity, antibodies labeled with a network of multiple DNA activating the CRISPR/Cas12a enzyme have been utilized as detection antibodies. As a result, the developed device successfully boosted the detection sensitivity for both human IgG and the hepatitis B virus surface antigen (HBsAg). In particular, the limit of detection (LOD) for HBsAg was estimated to be 12 pg/mL, representing over 10-fold higher sensitivity compared with commercially available HBsAg ELISA kits (LOD: 200 pg/mL). In addition, the fluorescence response toward porcine whole blood samples containing different HBsAg concentrations was also confirmed by capturing images with a smartphone, followed by quantitative data analysis. These results demonstrate the potential applicability of the proposed platform for clinical tests at the point of care.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hikaru", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Guodong", "last_name": "Tong", "name": null }, { "creator_type": "author", "first_name": "Pabitra", "last_name": "Nath", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acssensors.4c02733" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40059372" } }, "mesh": [ { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "CRISPR-Associated Proteins", "descriptor_ui": "D064130", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": true }, { "descriptor": "DNA, Single-Stranded", "descriptor_ui": "D004277", "major_topic": false }, { "descriptor": "Endodeoxyribonucleases", "descriptor_ui": "D004706", "major_topic": true }, { "descriptor": "Enzyme-Linked Immunosorbent Assay", "descriptor_ui": "D004797", "major_topic": false }, { "descriptor": "Hepatitis B Surface Antigens", "descriptor_ui": "D006514", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoassay", "descriptor_ui": "D007118", "major_topic": false }, { "descriptor": "Immunoglobulin G", "descriptor_ui": "D007074", "major_topic": true }, { "descriptor": "Limit of Detection", "descriptor_ui": "D057230", "major_topic": false }, { "descriptor": "Paper", "descriptor_ui": "D010209", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Mar 9", "date_precision": "day", "issue": "", "normalized_date": "2025-03-09", "pages": "", "proceedings_title": null, "publisher": "", "title": "ACS sensors", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Origami Paper-Based Immunoassay Device with CRISPR/Cas12a Signal Amplification.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Osteoarthritis (OA) is a chronic joint disease marked by synovial inflammation, cartilage degradation, and persistent pain. Although Netrin-4 (NTN4) has been implicated in pain modulation in rheumatoid arthritis (RA), its role in OA pain remains less understood. Previous research has documented that NTN4 promotes axonal growth in rodent-derived neurons; however, its effects on human sensory neurons are yet to be fully explored. NTN4 also plays a multifactorial role in various non-neuronal cells, such as endothelial cells, tumor cells, and stromal cells. Nevertheless, its specific impact on synovial fibroblasts, which are key components of the synovium and have been linked to OA pain, is still unclear. This study examined the correlation between NTN4 expression levels and pain severity in OA, specifically investigating its effects on human iPSC-derived sensory neurons (iPSC-SNs) and synovial fibroblasts from OA patients. Our findings indicate a positive correlation between synovial NTN4 expression and pain severity. Recombinant human Netrin-4 (rh-NTN4) was also shown to enhance neurite outgrowth in human iPSC-SNs, suggesting a potential role in neuronal sensitization. Additionally, rh-NTN4 stimulated the production of pro-inflammatory cytokines (IL-6, IL-8) and chemokines (CXCL1, CXCL6, CXCL8) in synovium-derived fibroblastic cells, implicating it in synovial inflammation. Collectively, these results suggest that NTN4 may contribute to KOA pathology by promoting synovial inflammation and potentially sensitizing sensory neurons, thereby influencing the mechanisms of underlying pain.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ayumi", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Uekusa", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Mukai", "name": null }, { "creator_type": "author", "first_name": "Dai", "last_name": "Iwase", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Aikawa", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Takaso", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Uchida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cells14060395" }, "pmcid": { "normalized": "PMC11941210" }, "pmid": { "normalized": "40136644" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Netrins", "descriptor_ui": "D000075385", "major_topic": true }, { "descriptor": "Osteoarthritis, Knee", "descriptor_ui": "D020370", "major_topic": true }, { "descriptor": "Pain", "descriptor_ui": "D010146", "major_topic": true }, { "descriptor": "Sensory Receptor Cells", "descriptor_ui": "D011984", "major_topic": true }, { "descriptor": "Synovial Membrane", "descriptor_ui": "D013583", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Mar 8", "date_precision": "day", "issue": "6", "normalized_date": "2025-03-08", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cells", "volume": "14", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Association Between Synovial NTN4 Expression and Pain Scores, and Its Effects on Fibroblasts and Sensory Neurons in End-Stage Knee Osteoarthritis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Near-infrared I (NIR-I: 650-950 nm) fluorescence imaging is a powerful tool for deep-tissue biological imaging, addressing the limitations of photon penetration depth in the visible-light region. Over the past decade, NIR imaging has extended to the near-infrared II (NIR-II: 1000-1700 nm) region, offering high-resolution and low background imaging by suppressing light scattering, and autofluorescence of tissues. Near-infrared fluorescent probes from NIR-I to NIR-II, with diverse functionalities, are increasingly utilized across biological fields to meet various detection needs and to explore physiological events in real time and spatial dimensions. This review discusses recent advancements in small-molecule NIR fluorescent dyes and probes, particularly those based on cyanine and rhodamine scaffolds, highlighting examples of their applications in bioimaging.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuzuka", "last_name": "Kuronuma", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s44211-025-00735-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40019707" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infrared Rays", "descriptor_ui": "D007259", "major_topic": true }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": true }, { "descriptor": "Spectroscopy, Near-Infrared", "descriptor_ui": "D019265", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Feb 28", "date_precision": "day", "issue": "", "normalized_date": "2025-02-28", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical sciences : the international journal of the Japan Society for Analytical Chemistry", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The latest developments of near-infrared fluorescent probes from NIR-I to NIR-II for bioimaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Type I collagen is a major component of the dermis and is formed by dermal fibroblasts. The development of dermal collagen structures has not been fully elucidated despite the major presence and importance of the dermis. This lack of understanding is due in part to the opacity of mammalian skin and it has been an obstacle to cosmetic and medical developments. We reveal the process of dermal collagen formation using the highly transparent skin of the axolotl and fluorescent collagen probes. We clarify that epidermal cells, not dermal fibroblasts, contribute to dermal collagen formation. Mesenchymal cells (fibroblasts) play a role in modifying the collagen fibers already built by keratinocytes. We confirm that collagen production by keratinocytes is a widely conserved mechanism in other model organisms. Our findings warrant a change in the current consensus about dermal collagen formation and could lead to innovations in cosmetology and skin medication.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ayaka", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Junpei", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kamei", "name": null }, { "creator_type": "author", "first_name": "Shigenori", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Saya", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Sakiya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Satoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-57055-7" }, "pmcid": { "normalized": "PMC11850728" }, "pmid": { "normalized": "39994199" } }, "mesh": [ { "descriptor": "Ambystoma mexicanum", "descriptor_ui": "D000558", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Collagen", "descriptor_ui": "D003094", "major_topic": true }, { "descriptor": "Collagen Type I", "descriptor_ui": "D024042", "major_topic": true }, { "descriptor": "Dermis", "descriptor_ui": "D020405", "major_topic": true }, { "descriptor": "Epidermal Cells", "descriptor_ui": "D000078404", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": true }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Feb 24", "date_precision": "day", "issue": "1", "normalized_date": "2025-02-24", "pages": "1757", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Keratinocyte-driven dermal collagen formation in the axolotl skin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human herpesvirus 6B (HHV-6B) belongs to the genus Roseolovirus of the betaherpesvirus subfamily, causing exanthema subitum and encephalitis. Although viral ribonucleotide reductase (RNR) is conserved in betaherpesviruses, it has lost its enzymatic activity. Human cytomegalovirus (HCMV) belongs to the other betaherpesvirus genus, Cytomegalovirus; its RNR inhibits nuclear factor-kappa B (NF-kappaB) signaling via interaction with the adaptor molecule RIPK1. However, the significance of enzymatically inactive RNR in roseoviruses is unclear. Here, we show that the RNRs from all three human roseoloviruses inhibit NF-kappaB activation. HHV-6B RNR sequesters NF-kappaB subunit p65 in the cytoplasm and inhibits its translocation into the nucleus. Silencing HHV-6B RNR increased the expression of inflammatory molecules in infected cells. This study reveals that inhibiting NF-kappaB is a conserved role of the RNR in betaherpesviruses but that the precise mechanisms responsible for these effects are different.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mansaku", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Khoir", "last_name": "Amaliin", "name": null }, { "creator_type": "author", "first_name": "Jing Rin", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Salma", "last_name": "Aktar", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2024.111710" }, "pmcid": { "normalized": "PMC11772975" }, "pmid": { "normalized": "39877902" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Feb 21", "date_precision": "day", "issue": "2", "normalized_date": "2025-02-21", "pages": "111710", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "28", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "HHV-6B ribonucleotide reductase sequesters NF-kappaB subunit p65 to inhibit innate immune responses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Inactivation of most light-sensitive G protein-coupled receptor (GPCR) opsins involves arrestin binding to terminate cell responses. In the zebrafish pineal organ, UV sensitive parapinopsin 1 (PP1)-expressing cells exhibit color opponency through photoequilibria between two photo-interconvertible states of PP1. The amount of visible light-sensitive active states (photoproducts) is crucial for generating color opponency, raising questions about how and what arrestins are involved in PP1 inactivation. Here, we found two arrestins, Arr3a and Sagb competitively bind to PP1. Photoresponse analyses of the PP1 cells using gene-knockdown larvae revealed Arr3a-involved quick inactivation was switched to Sagb-involved moderate inactivation depending on increased light intensity. Furthermore, we found photoregeneration of PP1 facilitates the dissociation of the PP1-arrestin complex, allowing for continuous arrestin supply in the photoequilibria under strong light. These regulations for the active photoproduct amounts of PP1 may help maintain appropriate color opponency. The current findings provide insight into the dynamics of GPCR inactivation involving multiple arrestins.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Baoguo", "last_name": "Shen", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sugihara", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Nishioka", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Kawano-Yamashita", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2024.111706" }, "pmcid": { "normalized": "PMC11803233" }, "pmid": { "normalized": "39925416" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Feb 21", "date_precision": "day", "issue": "2", "normalized_date": "2025-02-21", "pages": "111706", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "28", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Light intensity-dependent arrestin switching for inactivation of a light-sensitive GPCR, bistable opsin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The large-scale multiparametric analysis of individual nanoparticles is increasingly vital in the diverse fields of biology, medicine, and materials science. However, the current methods struggle with the tradeoff between measurement scalability and sensitivity, especially when identifying rare nanoparticles in heterogeneous mixtures. By developing and combining an unsupervised deep learning-based denoising method and an optofluidic device tuned for nanoparticle detection, we realize a nanoparticle analyzer that simultaneously achieves high scalability, throughput, and sensitivity levels; we name this approach \"Deep Nanometry\" (DNM). DNM detects polystyrene beads with a detection of limit of 30 nm at a throughput of over 100,000 events/second. The sensitive and scalable DNM directly detects rare target extracellular vesicles (EVs) in non-purified serum, making up as little as 0.002% of the 1,214,392 total particles. Moreover, DNM accurately and sufficiently counts diagnostic marker EVs present in only 0.93% and 0.17% of particle detections in sera of colorectal cancer patients and healthy controls, demonstrating its potential application to the early detection of colorectal cancer.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Benjamin", "last_name": "Salmon", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Krull", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-56812-y" }, "pmcid": { "normalized": "PMC11842628" }, "pmid": { "normalized": "39979247" } }, "mesh": [ { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": true }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": false }, { "descriptor": "Extracellular Vesicles", "descriptor_ui": "D000067128", "major_topic": false }, { "descriptor": "High-Throughput Screening Assays", "descriptor_ui": "D057166", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": true }, { "descriptor": "Polystyrenes", "descriptor_ui": "D011137", "major_topic": false }, { "descriptor": "Unsupervised Machine Learning", "descriptor_ui": "D000069558", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Feb 20", "date_precision": "day", "issue": "1", "normalized_date": "2025-02-20", "pages": "1728", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "High throughput analysis of rare nanoparticles with deep-enhanced sensitivity via unsupervised denoising.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "For the safe use of chemicals widely used in human activities, it is crucial to assess their ecological impacts when released into the environment. Daphnia, a well-established environmental indicator species, is commonly used to evaluate the biological effects of chemicals and testing methods have been established. Among various indicators, the growth rate is one of the important parameters, but it requires significant time and effort to measure. In this study, we applied deep learning-based image recognition techniques to extract images of Daphnia from live imaging and assess their size. The estimated size of Daphnia, derived from images processed through deep learning, showed a high correlation with measured values, demonstrating the capability to measure Daphnia size from the images while they are swimming. This approach enables non-invasive measurements of Daphnia size without complicated procedures, which not only streamlines ecological impact assessments but also presents a valuable technique for ecological studies, such as analyzing the size distribution of zooplankton.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Pijar", "last_name": "Religia", "name": null }, { "creator_type": "author", "first_name": "Nikko", "last_name": "Adhitama", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbiosc.2025.01.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39955201" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": true }, { "descriptor": "Daphnia magna", "descriptor_ui": "D000096602", "major_topic": false }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Feb 14", "date_precision": "day", "issue": "", "normalized_date": "2025-02-14", "pages": "S1389-1723(25)00024-6", "proceedings_title": null, "publisher": "", "title": "Journal of bioscience and bioengineering", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Application of deep learning for evaluation of the growth rate of Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Positive-type reversibly photoswitching fluorescent proteins (p-rsFPs) transition to a bright on-state upon light exposure for fluorescence excitation and to a dark off-state under a different wavelength. p-rsFPs are widely used in superresolution (SR) imaging techniques, offering simplified observation procedure and enhanced biocompatibility. Although some green p-rsFPs possess adequate photoproperties for SR imaging, all red p-rsFPs (p-rsRFPs) to date exhibit suboptimal properties, limiting the color palette for multiplexed SR imaging. Here, we present a p-rsRFP, rsZACRO, with 3.0-fold brighter fluorescence, 5.3-fold faster off-switching, and 1.5-fold higher on/off contrast than rsCherry, a conventional representative p-rsRFP. Using rsZACRO with superresolution polarization demodulation/on-state polarization angle narrowing (SPoD-OnSPAN), we successfully demonstrated SR imaging in the red spectrum and dual-color SR imaging with a single light for off-switching, visualizing vimentin intermediate filaments and actin filaments at higher spatial resolution than the diffraction limit of light in a living mammalian cell.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryohei", "last_name": "Ozaki-Noma", "name": null }, { "creator_type": "author", "first_name": "Tetsuichi", "last_name": "Wazawa", "name": null }, { "creator_type": "author", "first_name": "Taishi", "last_name": "Kakizuka", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Shidara", "name": null }, { "creator_type": "author", "first_name": "Kiwamu", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsnano.4c16847" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39937184" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Color", "descriptor_ui": "D003116", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": true }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": true }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": true }, { "descriptor": "Red Fluorescent Protein", "descriptor_ui": "D000097573", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Feb 12", "date_precision": "day", "issue": "", "normalized_date": "2025-02-12", "pages": "", "proceedings_title": null, "publisher": "", "title": "ACS nano", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Positive-Type Reversibly Photoswitching Red Fluorescent Protein for Dual-Color Superresolution Imaging with Single Light Exposure for Off-Switching.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Fluorescent Timer proteins, which display time-dependent changes in their emission spectra, are invaluable for analyzing the temporal dynamics of cellular events at the single-cell level. We previously developed the Timer-of-cell-kinetics-and-activity (Tocky) tools, utilizing a specific Timer protein, Fast-FT, to monitor temporal changes in cellular activities. Despite their potential, the analysis of Timer fluorescence in flow cytometry is frequently compromised by variability in instrument settings and the absence of standardized preprocessing methods. The development and implementation of effective data preprocessing methods remain to be achieved. RESULTS: In this study, we introduce the R package that automates the data preprocessing of Timer fluorescence data from flow cytometry experiments for quantitative analysis at single-cell level. Our aim is to standardize Timer data analysis to enhance reproducibility and accuracy across different experimental setups. The package includes a trigonometric transformation method to elucidate the dynamics of Fluorescent Timer proteins. We have identified the normalization of immature and mature Timer fluorescence data as essential for robust analysis, clarifying how this normalization affects the analysis of Timer maturation. These preprocessing methods are all encapsulated within the TockyPrep package. CONCLUSIONS: TockyPrep is available for distribution via GitHub at https://github.com/MonoTockyLab/TockyPrep , providing tools for data preprocessing and basic visualization of Timer fluorescence data. This toolkit is expected to enhance the utility of experimental systems utilizing Fluorescent Timer proteins, including the Tocky tools.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12859-025-06058-8" }, "pmcid": { "normalized": "PMC11807314" }, "pmid": { "normalized": "39923022" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": true }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Feb 8", "date_precision": "day", "issue": "1", "normalized_date": "2025-02-08", "pages": "44", "proceedings_title": null, "publisher": "", "title": "BMC bioinformatics", "volume": "26", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "TockyPrep: data preprocessing methods for flow cytometric fluorescent timer analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Severely hypoxic environments with oxygen concentrations around 1% are often found in serious diseases such as ischemia and cancer. However, existing near-infrared (NIR) fluorescent probes that can visualize hypoxia are also activated in mildly hypoxic environments (around 5% oxygen). Here, in order to selectively detect severe hypoxia, we used julolidine-based SiR (JSiR) as a NIR fluorophore and developed T-azoJSiR640 as a fluorescent probe. T-azoJSiR640 was able to detect severe hypoxia (around 1% oxygen concentration or less) in live cell imaging. Furthermore, the ischemic liver in a portal-vein-ligated mouse model was successfully visualized in vivo.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takafumi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Kyohhei", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d4cb00243a" }, "pmcid": { "normalized": "PMC11791654" }, "pmid": { "normalized": "39911856" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Feb 4", "date_precision": "day", "issue": "", "normalized_date": "2025-02-04", "pages": "", "proceedings_title": null, "publisher": "", "title": "RSC chemical biology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a near-infrared fluorescent probe for the selective detection of severe hypoxia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We established a volumetric trans-scale imaging system with an ultra-large field-of-view (FOV) that enables simultaneous observation of millions of cellular dynamics in centimeter-wide three-dimensional (3D) tissues and embryos. Using a custom-made giant lens system with a magnification of x2 and a numerical aperture (NA) of 0.25, and a CMOS camera with more than 100 megapixels, we built a trans-scale scope AMATERAS-2, and realized fluorescence imaging with a transverse spatial resolution of approximately 1.1 microm across an FOV of approximately 1.5x1.0 cm(2). The 3D resolving capability was realized through a combination of optical and computational sectioning techniques tailored for our low-power imaging system. We applied the imaging technique to 1.2 cm-wide section of mouse brain, and successfully observed various regions of the brain with sub-cellular resolution in a single FOV. We also performed time-lapse imaging of a 1-cm-wide vascular network during quail embryo development for over 24 hr, visualizing the movement of over 4.0x10(5) vascular endothelial cells and quantitatively analyzing their dynamics. Our results demonstrate the potential of this technique in accelerating production of comprehensive reference maps of all cells in organisms and tissues, which contributes to understanding developmental processes, brain functions, and pathogenesis of disease, as well as high-throughput quality check of tissues used for transplantation medicine.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "18H05412", "label": "18H05412", "researcher": "Shuichi Onami", "type": "grant" }, { "id": "18H05416", "label": "18H05416", "researcher": "Hitoshi Hashimoto", "type": "grant" }, { "id": "21H00431", "label": "21H00431", "researcher": "Yuki Sato", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" }, { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Taishi", "last_name": "Kakizuka", "name": null }, { "creator_type": "author", "first_name": "Yoshitsugu", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ejima", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Itano", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Itoga", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.93633" }, "pmcid": { "normalized": "PMC11790249" }, "pmid": { "normalized": "39899352" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": true }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": true }, { "descriptor": "Quail", "descriptor_ui": "D011784", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Feb 3", "date_precision": "day", "issue": "", "normalized_date": "2025-02-03", "pages": "", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "13", "year": 2025 }, "ssbd": { "database": [ "ssbd-database-000409" ], "repository": [ "ssbd-repos-000409" ] }, "title": "Volumetric trans-scale imaging of massive quantity of heterogeneous cell populations in centimeter-wide tissue and embryo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chemical reactions are regarded as transformations of chemical structures, and the question of which atoms in the reactants correspond to which atoms in the products has attracted chemists for a long time. Atom-to-atom mapping (AAM) is a procedure that establishes such correspondence(s) between the atoms of reactants and products in a chemical reaction. Currently, automatic AAM tools play a pivotal role in various chemoinformatics tasks. However, achieving accurate automatic AAM for complex or unknown reactions within a reasonable computation time remains a significant challenge due to the combinatorial nature of the problem and the difficulty in applying appropriate reaction rules. In this study, we propose a rule-free AAM algorithm, which enumerates all atom-to-atom correspondences that minimize the number of bond cleavages and formations during the reaction. To reduce the computational burden associated with the combinatorial optimization (i.e., minimizing bond changes), we introduce Ising computing, a computing paradigm that has gained significant attention for its efficiency in solving hard combinatorial optimization problems. We found that our Ising computing framework outperforms conventional combinatorial optimization algorithms in terms of computation times, making it feasible to solve the AAM problem without reaction rules in an acceptable time. Furthermore, our AAM algorithm successfully found the correct AAM solution for all problems in a benchmark data set. In contrast, conventional AAM algorithms based on chemical heuristics failed for several problems. Specifically, these algorithms either failed to find the optimal solution in terms of bond changes, or they identified only one optimal solution, which was incorrect when multiple optimal solutions exist. These results emphasize the importance of enumerating all optimal correspondences that minimize bond changes, which is effectively achieved by our Ising-computing framework.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mohammad", "last_name": "Ali", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Yuuya", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jcim.4c01871" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39893651" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": true }, { "descriptor": "Cheminformatics", "descriptor_ui": "D000080911", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Feb 2", "date_precision": "day", "issue": "", "normalized_date": "2025-02-02", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of chemical information and modeling", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Enumeration Approach to Atom-to-Atom Mapping Accelerated by Ising Computing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The availability of various calcium ion (Ca(2+)) fluorescent probes has contributed to revealing physiological events related to intracellular Ca(2+). However, conventional probes face challenges for quantitatively and selectively visualizing high Ca(2+) concentrations in cells induced by any stimuli, including biomolecules or electrical signal that disrupt Ca(2+) homeostasis. In this report, we designed and synthesized a low-affinity ratiometric Ca(2+) probe, KLCA-Fura, utilizing o-aminophenol-N,N-diacetate-O-methylene-methylphosphinate (APDAP) as a ligand, for which we recently demonstrated the suitability as a new low-affinity ligand for Ca(2+). KLCA-Fura showed a blue shift in excitation wavelength with increasing Ca(2+) concentration based on the intramolecular charge transfer (ICT). Its affinity for Ca(2+) is lower than commercially available conventional Ca(2+) probes. Furthermore, the selectivity for Ca(2+) and the fluorescence intensity were considered sufficient to accurately detect Ca(2+). The corresponding acetoxymethyl ester, KLCA-FuraAM, was synthesized for intracellular imaging and applied to Ca(2+) quantification in neurons. KLCA-FuraAM enabled quantitative ratiometric monitoring of the two-step Ca(2+) concentration increase induced by glutamate stimulation. While this two-step response was not clearly observed with a commercially available low-affinity ratiometric Ca(2+) probe, Fura-FF, KLCA-FuraAM has demonstrated the potential to quantitatively visualize the behavior of high Ca(2+) concentrations. The ratiometric low-affinity Ca(2+) probe, KLCA-Fura, is expected to be a powerful tool for discovering new functions of Ca(2+) in neurons.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuzuka", "last_name": "Kuronuma", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Kumada", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Sakama", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acschemneuro.4c00668" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39886901" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": true }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jan 31", "date_precision": "day", "issue": "", "normalized_date": "2025-01-31", "pages": "", "proceedings_title": null, "publisher": "", "title": "ACS chemical neuroscience", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Ratiometric Imaging for Quantification of Elevated Ca(2+) in Neurons Using Synthetic Low-Affinity Fluorescent Probe.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cysteine is an essential amino acid for sustaining life, including protein synthesis, and serves as a precursor for antioxidant glutathione. Pathogenic bacteria synthesize cysteine via a two-step enzymatic process using serine as the starting material. The first step is catalyzed by serine acetyltransferase, also known as CysE, and the second by O-acetylserine sulfhydrylase (OASS), referred to as CysK or CysM. This cysteine biosynthetic pathway in bacteria differs significantly from that in mammals, making it an attractive target for the development of novel antibacterial agents. In this study, we aimed to identify OASS inhibitors. To achieve this, a high-throughput screening system was developed to analyze compounds capable of inhibiting CysK/CysM activity. Screening 168,640 compounds from a chemical library revealed that gliotoxin, a fungal metabolite, strongly inhibits both CysK and CysM. Furthermore, gliotoxin significantly suppressed the growth of Salmonella enterica serovar Typhimurium, a Gram-negative bacterium, under cystine-deficient conditions. Gliotoxin possesses a unique disulfide structure classified as epipolythiodioxopiperazine. To date, no studies have reported OASS inhibition by compounds with this structural motif, highlighting its potential for future structural optimization. The screening system developed in this study is expected to accelerate the discovery of functional CysK/CysM inhibitors, providing a foundation for novel antibacterial strategies.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Azizur", "last_name": "Rahman", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Touya", "last_name": "Toyomoto", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms26031106" }, "pmcid": { "normalized": "PMC11818871" }, "pmid": { "normalized": "39940875" } }, "mesh": [ { "descriptor": "Anti-Bacterial Agents", "descriptor_ui": "D000900", "major_topic": true }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": true }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Cysteine Synthase", "descriptor_ui": "D003547", "major_topic": true }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": true }, { "descriptor": "Fungi", "descriptor_ui": "D005658", "major_topic": true }, { "descriptor": "Gliotoxin", "descriptor_ui": "D005912", "major_topic": true }, { "descriptor": "High-Throughput Screening Assays", "descriptor_ui": "D057166", "major_topic": false }, { "descriptor": "Salmonella typhimurium", "descriptor_ui": "D012486", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jan 27", "date_precision": "day", "issue": "3", "normalized_date": "2025-01-27", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "26", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of Fungal Metabolite Gliotoxin as a Potent Inhibitor Against Bacterial O-Acetylserine Sulfhydrylase CysK and CysM.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ayami", "last_name": "Okuzumi", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Shuko", "last_name": "Nojiri", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Imamichi-Tatano", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Kakuta", "name": null }, { "creator_type": "author", "first_name": "Akihide", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Yuanzhe", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Funayama", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Saiki", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Tsunemi", "name": null }, { "creator_type": "author", "first_name": "Deborah", "last_name": "McIntyre", "name": null }, { "creator_type": "author", "first_name": "Jean-Jacques", "last_name": "Gerardy", "name": null }, { "creator_type": "author", "first_name": "Michel", "last_name": "Mittelbronn", "name": null }, { "creator_type": "author", "first_name": "Rejko", "last_name": "Kruger", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Nukina", "name": null }, { "creator_type": "author", "first_name": "Nobutaka", "last_name": "Hattori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41591-025-03521-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39856337" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jan 24", "date_precision": "day", "issue": "", "normalized_date": "2025-01-24", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature medicine", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Author Correction: Propagative alpha-synuclein seeds as serum biomarkers for synucleinopathies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bioluminescence, an optical marker that does not require excitation by light, allows researchers to simultaneously observe multiple targets, each exhibiting a different color. Notably, the colors of the bioluminescent proteins must sufficiently vary to enable simultaneous detection. Here, we aimed to introduce a method that can be used to expand the color variation by tuning dual-acceptor bioluminescence resonance energy transfer. Using this approach, we could visualize multiple targets with up to 20 colors through single-shot acquisition using a color complementary metal-oxide semiconductor camera. Overall, this method enables simple and simultaneous observation of multiple biological targets and phenomena.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "21H00437", "label": "21H00437", "researcher": "Yuki Hiruta", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Tetsuichi", "last_name": "Wazawa", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Orioka", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adp4750" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39841832" } }, "mesh": [ { "descriptor": "Color", "descriptor_ui": "D003116", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescence", "descriptor_ui": "D049449", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": true }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": true }, { "descriptor": "Semiconductors", "descriptor_ui": "D012666", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jan 24", "date_precision": "day", "issue": "4", "normalized_date": "2025-01-24", "pages": "", "proceedings_title": null, "publisher": "", "title": "Science Advances", "volume": "11", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Creating coveted bioluminescence colors for simultaneous multi-color bioimaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lateral flow immunoassays (LFIAs) are widely used for the simple and rapid detection of various targets at the point of need. However, LFIAs enabling the simultaneous detection of multiple analytes and the possibility for naked-eye semi-quantitative analysis are facing various challenges, including the requirement of large sample volumes, low efficiency, and accuracy. This is particularly the case for the competitive immunoassay format targeting the detection of low molecular weight compounds, such as, for example, drugs. Due to limited space for multiple reaction zones on a single planar nitrocellulose membrane, conducting multiplexed tests requires the addition of more test strips, which consequently increases the size of the whole device. To overcome these spatial constraints, two 3D-printed devices fitting eight assay lanes of both backed and unbacked nitrocellulose membranes have been designed. For proof of concept, 8-OHdG, caffeine, and acetaminophen were used as model analytes. Inkjet printing was applied to deposit capture reagents in the form of text symbols while controlling the concentration thresholds for text readability to achieve an intuitive result expression. A comparably small sample volume of 350 muL was sufficient to simultaneously visually distinguish 4 concentration levels of caffeine (0, 4, 10, 175 ng mL(-1)) and acetaminophen (0, 4, 8, 12 ng mL(-1)) in mixed solutions without crosstalk. This study demonstrates the potential of 3D-printed LFIA devices for multiplex and semi-quantitative analyte detection.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Guodong", "last_name": "Tong", "name": null }, { "creator_type": "author", "first_name": "Kazushi", "last_name": "Misawa", "name": null }, { "creator_type": "author", "first_name": "Purim", "last_name": "Jarujamrus", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d4ay02009j" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39834243" } }, "mesh": [ { "descriptor": "Acetaminophen", "descriptor_ui": "D000082", "major_topic": false }, { "descriptor": "Collodion", "descriptor_ui": "D003101", "major_topic": false }, { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoassay", "descriptor_ui": "D007118", "major_topic": false }, { "descriptor": "Printing, Three-Dimensional", "descriptor_ui": "D066330", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jan 21", "date_precision": "day", "issue": "", "normalized_date": "2025-01-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical methods : advancing methods and applications", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "3D-printed devices for multiplexed semi-quantitative competitive lateral flow immunoassays.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The efficacy and safety of sotorasib plus platinum-doublet chemotherapy in KRAS G12C-mutated non-squamous non-small cell lung cancer (non-Sq NSCLC) were previously reported with limited follow-up period. METHOD: SCARLET was a single-arm phase II study of chemotherapy-naive patients with KRAS G12C-mutated non-Sq NSCLC. Participants received sotorasib 960 mg daily plus four cycles of carboplatin (area under the curve, 5)/pemetrexed 500 mg/m(2), followed by sotorasib/pemetrexed until disease progression. The primary endpoint was the overall response rate (ORR); secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Using plasma samples, next-generation sequencing was performed at baseline, 3 weeks, and disease progression (jRCT2051210086). RESULTS: Thirty patients were enrolled between Oct 2021 and Jul 2022, with a median follow-up of 14.8 months. ORR was 88.9% (80% confidence interval [CI], 78.5-94.8%; 95% CI, 70.8-97.6%), median PFS was 6.6 months (95% CI, 5.3-16.7 months), and median OS was 20.6 months (95% CI, 8.1 months-not estimated). Among patients with programmed death ligand 1 expression levels >/= 1% and < 1%, ORRs were 82.3 and 100% and median PFS was 7.6 and 9.7 months, respectively. Using plasma samples, patients without KRAS G12C at baseline, without KRAS-related pathway co-alterations, or who cleared KRAS G12C at 3 weeks had better median PFS (16.7, 13.9, 8.7 months, respectively). TP53 mutation and epidermal growth factor receptor (EGFR) and MET amplification were detected acquired resistances. CONCLUSION: In patients with KRAS G12C-mutated non-Sq NSCLC, sotorasib plus carboplatin/pemetrexed demonstrated favorable efficacy especially in PD-L1 <1%, with manageable toxicity.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Akamatsu", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Sakata", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Hiroshige", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Tsuchiya-Kawano", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Esumi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kurosaki", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Kiichiro", "last_name": "Ninomiya", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Toyozawa", "name": null }, { "creator_type": "author", "first_name": "Yasuto", "last_name": "Yoneshima", "name": null }, { "creator_type": "author", "first_name": "Takehito", "last_name": "Shukuya", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kozuki", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Daga", "name": null }, { "creator_type": "author", "first_name": "Terufumi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Mitsuo", "last_name": "Osuga", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Koh", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2025.01.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39828218" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": true }, { "descriptor": "Carboplatin", "descriptor_ui": "D016190", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Pemetrexed", "descriptor_ui": "D000068437", "major_topic": false }, { "descriptor": "Piperazines", "descriptor_ui": "D010879", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": true }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": false }, { "descriptor": "Sulfonamides", "descriptor_ui": "D013449", "major_topic": true }, { "descriptor": "Survival Rate", "descriptor_ui": "D015996", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jan 17", "date_precision": "day", "issue": "", "normalized_date": "2025-01-17", "pages": "S1556-0864(25)00007-3", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "A single-arm, phase II study of sotorasib plus carboplatin/pemetrexed in advanced non-squamous non-small cell lung cancer patients with KRAS G12C mutation (WJOG14821L, SCARLET).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We develop a data harmonization approach for C. elegans volumetric microscopy data, consisting of a standardized format, pre-processing techniques, and human-in-the-loop machine-learning-based analysis tools. Using this approach, we unify a diverse collection of 118 whole-brain neural activity imaging datasets from five labs, storing these and accompanying tools in an online repository WormID (wormid.org). With this repository, we train three existing automated cell-identification algorithms, CPD, StatAtlas, and CRF_ID, to enable accuracy that generalizes across labs, recovering all human-labeled neurons in some cases. We mine this repository to identify factors that influence the developmental positioning of neurons. This growing resource of data, code, apps, and tutorials enables users to (1) study neuroanatomical organization and neural activity across diverse experimental paradigms, (2) develop and benchmark algorithms for automated neuron detection, segmentation, cell identification, tracking, and activity extraction, and (3) share data with the community and comply with data-sharing policies.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Daniel Y.", "last_name": "Sprague", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Rusch", "name": null }, { "creator_type": "author", "first_name": "Raymond L.", "last_name": "Dunn", "name": null }, { "creator_type": "author", "first_name": "Jackson M.", "last_name": "Borchardt", "name": null }, { "creator_type": "author", "first_name": "Steven", "last_name": "Ban", "name": null }, { "creator_type": "author", "first_name": "Greg", "last_name": "Bubnis", "name": null }, { "creator_type": "author", "first_name": "Grace C.", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Chentao", "last_name": "Wen", "name": null }, { "creator_type": "author", "first_name": "Ryoga", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shivesh", "last_name": "Chaudhary", "name": null }, { "creator_type": "author", "first_name": "Hyun Jee", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Zikai", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Benjamin", "last_name": "Dichter", "name": null }, { "creator_type": "author", "first_name": "Ryan", "last_name": "Ly", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Hang", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Koutarou D.", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Eviatar", "last_name": "Yemini", "name": null }, { "creator_type": "author", "first_name": "Saul", "last_name": "Kato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.crmeth.2024.100964" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39826553" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Neuroimaging", "descriptor_ui": "D059906", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jan 15", "date_precision": "day", "issue": "", "normalized_date": "2025-01-15", "pages": "100964", "proceedings_title": null, "publisher": "", "title": "Cell reports methods", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Unifying community whole-brain imaging datasets enables robust neuron identification and reveals determinants of neuron position in C. elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Heavy metal contamination in water bodies has raised global concerns due to its significant threats to both public health and ecosystem. Copper (Cu), one of the most widely used metals, is also an essential trace element in physiological systems. Excessive intake of Cu from water can cause toxicity, potentially resulting in serious health risks. Ensuring water safety necessitates the critical detection of copper ion (Cu(2+)). Here, we report a ratiometric bioluminescent detection method for Cu(2+), DERK-Cu(II), which is based on the Distinct Enzymatic Reaction Kinetics of two luciferase variants. In DERK-Cu(II), the blue luminescent luciferase exhibits lower catalytic efficiency than the green luminescent luciferase, thus it is less inhibited by Cu(2+). Consequently, the luminescence color of their mixture is dependent on the Cu(2+) concentrations, enabling us to find an optimal mixing ratio at which luminescence color changes evidently from green to blue. Building on this, we established a quantitative detection method for Cu(2+) using a smartphone and successfully measured the Cu(2+) concentrations in several water samples. The method we developed, using the difference in reaction kinetics of two enzymes with the same substrate specificity, would become a versatile approach applicable to the development of other enzyme-based indicators.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ti", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Md Nadim", "last_name": "Hossain", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.talanta.2025.127576" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39818047" } }, "mesh": [ { "descriptor": "Copper", "descriptor_ui": "D003300", "major_topic": true }, { "descriptor": "Ions", "descriptor_ui": "D007477", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": true }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": true }, { "descriptor": "Metals, Heavy", "descriptor_ui": "D019216", "major_topic": true }, { "descriptor": "Point-of-Care Systems", "descriptor_ui": "D019095", "major_topic": false }, { "descriptor": "Smartphone", "descriptor_ui": "D000068997", "major_topic": false }, { "descriptor": "Water Pollutants, Chemical", "descriptor_ui": "D014874", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jan 15", "date_precision": "day", "issue": "", "normalized_date": "2025-01-15", "pages": "127576", "proceedings_title": null, "publisher": "", "title": "Talanta", "volume": "287", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Ratiometric bioluminescent detection of Cu(II) ion based on differences in enzymatic reaction kinetics of two luciferase variants.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.31662/jmaj.2024-0355" }, "pmcid": { "normalized": "PMC11799609" }, "pmid": { "normalized": "39926070" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jan 15", "date_precision": "day", "issue": "1", "normalized_date": "2025-01-15", "pages": "38-39", "proceedings_title": null, "publisher": "", "title": "JMA journal", "volume": "8", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Medical AI and AI for Medical Sciences: An Editorial.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yumiko", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Shiota", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Takao", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Jo", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Shinozaki", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Fukuyama", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hiroo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Tsukita", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Isamu", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kan-O", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.alit.2024.12.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39809629" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jan 13", "date_precision": "day", "issue": "", "normalized_date": "2025-01-13", "pages": "S1323-8930(24)00158-8", "proceedings_title": null, "publisher": "", "title": "Allergology international : official journal of the Japanese Society of Allergology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Claudin-3 deficiency inhibits allergic responses in an ovalbumin-induced asthma mouse model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The root of asthma can be linked to early life, with prenatal environments influencing risk. We investigate the effects of maternal asthma on the offspring's lungs during fetal and adult life. Adult offspring of asthmatic mothers show an increase in lung group 2 innate lymphoid cell (ILC2) number and function with allergen-induced lung inflammation. Offspring of asthmatic mothers show phenotypic alteration of their lung ILC2s during fetal life, with increased expression of genes related to activation and glucocorticoid signaling. Furthermore, these offspring carry overlapping chromatin-accessible altered regions, including glucocorticoid receptor-binding regions in their lung ILC2s both at the fetal stage and adulthood, suggesting persistent prenatal epigenetic changes. Moreover, maternal exposure to glucocorticoids has similar effects on fetal lung ILC2s and contributes to allergen-induced lung inflammation during adulthood. Thus, asthma during pregnancy may have long-term effects on lung ILC2s in the offspring from the embryonic period, contributing to an increased risk of developing asthma.", "classifications": [ { "id": "21H00432", "label": "21H00432", "researcher": "Minako Ito", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Takao", "name": null }, { "creator_type": "author", "first_name": "Ako", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Kikutake", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kan-O", "name": null }, { "creator_type": "author", "first_name": "Azusa", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Mikita", "last_name": "Suyama", "name": null }, { "creator_type": "author", "first_name": "Isamu", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-55941-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39805834" } }, "mesh": [ { "descriptor": "Allergens", "descriptor_ui": "D000485", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Asthma", "descriptor_ui": "D001249", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fetus", "descriptor_ui": "D005333", "major_topic": false }, { "descriptor": "Glucocorticoids", "descriptor_ui": "D005938", "major_topic": true }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": true }, { "descriptor": "Lymphocytes", "descriptor_ui": "D008214", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Maternal Exposure", "descriptor_ui": "D018811", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Prenatal Exposure Delayed Effects", "descriptor_ui": "D011297", "major_topic": true }, { "descriptor": "Receptors, Glucocorticoid", "descriptor_ui": "D011965", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jan 13", "date_precision": "day", "issue": "1", "normalized_date": "2025-01-13", "pages": "631", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Maternal asthma imprints fetal lung ILC2s via glucocorticoid signaling leading to worsened allergic airway inflammation in murine adult offspring.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Microthrombus formation is associated with COVID-19 severity; however, the detailed mechanism remains unclear. In this study, we investigated mouse models with severe pneumonia caused by SARS-CoV-2 infection by using our in vivo two-photon imaging system. In the lungs of SARS-CoV-2-infected mice, increased expression of adhesion molecules in intravascular neutrophils prolonged adhesion time to the vessel wall, resulting in platelet aggregation and impaired lung perfusion. Re-analysis of scRNA-seq data from peripheral blood mononuclear cells from COVID-19 cases revealed increased expression levels of CD44 and SELL in neutrophils in severe COVID-19 cases compared to a healthy group, consistent with our observations in the mouse model. These findings suggest that pulmonary perfusion defects caused by neutrophil adhesion to pulmonary vessels contribute to COVID-19 severity.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ueki", "name": null }, { "creator_type": "author", "first_name": "I.-Hsuan", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Kiso", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Sohtaro", "last_name": "Mine", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Ujie", "name": null }, { "creator_type": "author", "first_name": "Hung-Wei", "last_name": "Hsu", "name": null }, { "creator_type": "author", "first_name": "Chen-Hui Henry", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Tadaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Kamitani", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kawaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-55272-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39805823" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hyaluronan Receptors", "descriptor_ui": "D018960", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neutrophils", "descriptor_ui": "D009504", "major_topic": true }, { "descriptor": "Platelet Aggregation", "descriptor_ui": "D010974", "major_topic": false }, { "descriptor": "Pulmonary Circulation", "descriptor_ui": "D011652", "major_topic": true }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jan 13", "date_precision": "day", "issue": "1", "normalized_date": "2025-01-13", "pages": "455", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Neutrophil adhesion to vessel walls impairs pulmonary circulation in COVID-19 pathology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kanno", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Hiramatsu", "name": null }, { "creator_type": "author", "first_name": "Hideharu", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Nakayashiki", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Arata", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Kohki", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Fan", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Fei", "last_name": "Yin", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Tominaga", "name": null }, { "creator_type": "author", "first_name": "Omer Faruk", "last_name": "Bicer", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Noma", "name": null }, { "creator_type": "author", "first_name": "Bahareh", "last_name": "Kiani", "name": null }, { "creator_type": "author", "first_name": "Olga", "last_name": "Efa", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Buscher", "name": null }, { "creator_type": "author", "first_name": "Tetsuichi", "last_name": "Wazawa", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shintaku", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Sigurd", "last_name": "Braun", "name": null }, { "creator_type": "author", "first_name": "Jessica P.", "last_name": "Houston", "name": null }, { "creator_type": "author", "first_name": "Sherif", "last_name": "Rashad", "name": null }, { "creator_type": "author", "first_name": "Kuniyasu", "last_name": "Niizuma", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Goda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-55961-4" }, "pmcid": { "normalized": "PMC11724113" }, "pmid": { "normalized": "39794325" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jan 10", "date_precision": "day", "issue": "1", "normalized_date": "2025-01-10", "pages": "582", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Publisher Correction: High-throughput fluorescence lifetime imaging flow cytometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The integration of barcode technology with smartphones on paper-based analytical devices (PADs) presents a promising approach to bridging manual detection with digital interpretation and data storage. However, previous studies of 1D barcode approaches have been limited to providing only a \"yes/no\" response for analyte detection. Herein, a method of using barcode readout for semiquantitative signal detection on PADs has been achieved through the integration of barcode technology with a distance-based measurement concept on PADs. To demonstrate the feasibility of this concept, a PAD fabrication strategy incorporating barcodes was explored, using the enzymatic reaction between horseradish peroxidase (HRP), 3,3'-diaminobenzidine (DAB), and H(2)O(2) as a model system. The enzyme-catalyzed polymerization of DAB to polyDAB in the presence of hydrogen peroxide results in the appearance of color observable by the naked eye inside a paperfluidic channel, with the color-changed length depending on the H(2)O(2) concentration. At the same time, the barcode pattern displayed as a result of this distance-based color evolution overlaid with a paper-based barcode layer can be read using a smartphone application. Parameters affecting the signal readout performance were studied. The developed device can be used to detect H(2)O(2) concentrations in the range of 0.25 to 10 mM within 90 min with 79.6% of barcode signals correctly readable. Additionally, results from different smartphone models showed a consistent reading performance (78.4-79.6%). Finally, the quantification of glucose levels in artificial urine samples was demonstrated. This developed PAD signaling strategy offers end-users more simplicity and can be used as a standalone device or in conjunction with other digital devices.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yanawut", "last_name": "Manmana", "name": null }, { "creator_type": "author", "first_name": "Shuma", "last_name": "Kinugasa", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.4c04113" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39791888" } }, "mesh": [ { "descriptor": "3,3'-Diaminobenzidine", "descriptor_ui": "D015100", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": true }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": true }, { "descriptor": "Horseradish Peroxidase", "descriptor_ui": "D006735", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": true }, { "descriptor": "Paper", "descriptor_ui": "D010209", "major_topic": true }, { "descriptor": "Smartphone", "descriptor_ui": "D000068997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jan 10", "date_precision": "day", "issue": "", "normalized_date": "2025-01-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a Semiquantitative Barcode Readout Approach for Paper-Based Analytical Devices (PADs) for Enzymatic H(2)O(2) and Glucose Detection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Brain damage caused by subarachnoid hemorrhage (SAH) currently lacks effective treatment, leading to stagnation in the improvement of functional outcomes for decades. Recent studies have demonstrated the therapeutic potential of exosomes released from mesenchymal stem cells (MSC), which effectively attenuate neuronal apoptosis and inflammation in neurological diseases. Due to the challenge of systemic dilution associated with intravenous administration, intranasal delivery has emerged as a novel approach for targeting the brain. In this study, we investigate the effects of intranasally administered MSC-derived exosomes in a SAH animal model and elucidate their mode of action. METHODS: Exosomes were isolated from the cell supernatants of amnion-derived MSC. SAH was induced in 8-week-old Sprague-Dawley rats using an autologous blood prechiasmatic cistern injection model. A total of 1.2 x 10(10) particles of exosomes in 200 muL of PBS or PBS alone were intranasally administered immediately and 24 h post-injury. Neurological function was assessed up to 7 days after injury, and histological analysis was performed to evaluate their anti-apoptotic and anti-inflammatory effects. The biodistribution of exosomes was assessed using PET/CT imaging of (64)Cu labeled exosome. In vitro analyses were performed using primary glial cells and cell lines to evaluate the anti-inflammatory effects of the exosomes. RESULTS: Animals treated with exosomes exhibited significant improvement in cognitive function compared with PBS treated animal. Apoptotic cells and inflammation were reduced for the exosome group in the hippocampal CA1 area and in cortex, resulting in better neuronal cell survival. Blood brain barrier permeability was also preserved in the exosome group. Nuclear imaging revealed that exosomes were primarily transferred to the olfactory nerve and cerebrum; furthermore, exosomes were also observed in the trigeminal nerve and brainstem, where exosomes were co-localized with microglia and with endothelial cells. In vitro assessment showed that exosome administration ameliorated inflammation and prevented the death of glial cells. CONCLUSIONS: MSC-derived exosomes were successfully transferred into the brain through intranasal administration and alleviated brain damage following SAH.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shuho", "last_name": "Gotoh", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Kawabori", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Yo", "last_name": "Nakahara", "name": null }, { "creator_type": "author", "first_name": "Erika", "last_name": "Yoshie", "name": null }, { "creator_type": "author", "first_name": "Kohtarou", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kuge", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Fujimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.expneurol.2025.115143" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39800250" } }, "mesh": [ { "descriptor": "Administration, Intranasal", "descriptor_ui": "D000281", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cognitive Dysfunction", "descriptor_ui": "D060825", "major_topic": true }, { "descriptor": "Exosomes", "descriptor_ui": "D055354", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mesenchymal Stem Cells", "descriptor_ui": "D059630", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Subarachnoid Hemorrhage", "descriptor_ui": "D013345", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jan 10", "date_precision": "day", "issue": "", "normalized_date": "2025-01-10", "pages": "115143", "proceedings_title": null, "publisher": "", "title": "Experimental neurology", "volume": "386", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Intranasal administration of stem cell-derived exosome alleviates cognitive impairment against subarachnoid hemorrhage.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Quantification of intrahepatic covalently closed circular DNA (cccDNA) is a key for evaluating an elimination of hepatitis B virus (HBV) in infected patients. However, quantifying cccDNA requires invasive methods such as a liver biopsy, which makes it impractical to access the dynamics of cccDNA in patients. Although HBV RNA and HBV core-related antigens (HBcrAg) have been proposed as surrogate markers for evaluating cccDNA activity, they do not necessarily estimate the amount of cccDNA. Here, we employed a recently developed multiscale mathematical model describing intra- and intercellular viral propagation and applied it in HBV-infected patients under treatment. We developed a model that can predict intracellular HBV dynamics by use of extracellular viral markers, including HBsAg, HBV DNA, and HBcrAg in peripheral blood. Importantly, the model prediction of the amount of cccDNA in patients over time was confirmed to be well correlated with the data for quantified cccDNA by paired liver biopsy. Thus, our method combining classic and emerging surrogate markers enables us to predict the decay dynamics of cccDNA in patients undergoing treatment.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kwang Su", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Kosaku", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Hyeongki", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Sanae", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Senko", "last_name": "Tsukuda", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Atsukawa", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Natthaya", "last_name": "Chuaypen", "name": null }, { "creator_type": "author", "first_name": "Pisit", "last_name": "Tangkijvanich", "name": null }, { "creator_type": "author", "first_name": "Lena", "last_name": "Allweiss", "name": null }, { "creator_type": "author", "first_name": "Takara", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Nakaoka", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Takaji", "last_name": "Wakita", "name": null }, { "creator_type": "author", "first_name": "Alan S.", "last_name": "Perelson", "name": null }, { "creator_type": "author", "first_name": "Maura", "last_name": "Dandri", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Watashi", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Iwami", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1012615" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39787253" } }, "mesh": [ { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "DNA, Circular", "descriptor_ui": "D004270", "major_topic": true }, { "descriptor": "DNA, Viral", "descriptor_ui": "D004279", "major_topic": true }, { "descriptor": "Hepatitis B", "descriptor_ui": "D006509", "major_topic": true }, { "descriptor": "Hepatitis B Core Antigens", "descriptor_ui": "D006512", "major_topic": false }, { "descriptor": "Hepatitis B Surface Antigens", "descriptor_ui": "D006514", "major_topic": false }, { "descriptor": "Hepatitis B virus", "descriptor_ui": "D006515", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jan 9", "date_precision": "day", "issue": "1", "normalized_date": "2025-01-09", "pages": "e1012615", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "21", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Prediction of cccDNA dynamics in hepatitis B patients by a combination of serum surrogate markers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epoxide hydrolases (EHs) play pivotal roles in detoxification, catabolism, and signaling by converting epoxides into diols and have been implicated in several diseases, such as cancers and diabetes. EH homologs in insects are designated as Juvenile hormone epoxide hydrolases (JHEHs) due to their catalytic activity toward Juvenile hormone (JH). However, the biological function of JHEHs has been controversial in the fruit fly Drosophila melanogaster. In this study, we generated and characterized flies deficient in Jheh1 and Jheh2 genes. We found that Jheh1/2 deficiency caused a developmental delay and enhanced the growth retardation effects of caffeine and paraquat. Additionally, we observed that the deficiency reduced tolerance to cold stress. These results indicate that JHEHs are required for growth promotion and stress tolerance. Metabolomic and transcriptomic analyses revealed that Jheh1/2 deficiency impaired glucose metabolism and downregulated genes involved in glycolysis and the TCA cycle. Furthermore, transgenic overexpression of Jheh1 increased glycolytic metabolites and restored the Jheh1/2 deficiency-associated phenotype. These results demonstrate that JHEHs play a crucial role in glucose metabolism in Drosophila, providing a valuable model to study the mechanisms underlying the function of EHs in energy metabolism.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Felipe", "last_name": "Rogalski", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Takeo", "name": null }, { "creator_type": "author", "first_name": "Tsunaki", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Aigaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2025.151313" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39809137" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Caffeine", "descriptor_ui": "D002110", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": true }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": true }, { "descriptor": "Epoxide Hydrolases", "descriptor_ui": "D004851", "major_topic": true }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": true }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jan 9", "date_precision": "day", "issue": "", "normalized_date": "2025-01-09", "pages": "151313", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "748", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Epoxide hydrolases JHEH1 and JHEH2 deficiency impairs glucose metabolism in Drosophila.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell type-specific reporter transgenic chicken lines are invaluable tools in developmental biology, allowing the visualization of dynamics and differentiation states of target cell types in living embryos. Here, we report the establishment of a new transgenic chicken line in which limb mesenchyme and apical ectodermal ridge (AER) cells are labeled with different fluorescent proteins in the embryos. The processes for generating the reporter line involved using tissue-specific promoters, the Tol2 transposon-mediated genomic integration, and clonal culture system of primordial germ cells. Employing the transgenic chickens would facilitate the detailed characterization of limb mesenchyme and AER cells. Thus, this reporter chicken line will be a powerful tool for advancing the study of vertebrate limb development.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Atsuta", "name": null }, { "creator_type": "author", "first_name": "Yi-Chen", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yuna", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2025.01.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39788366" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": true }, { "descriptor": "Chick Embryo", "descriptor_ui": "D002642", "major_topic": false }, { "descriptor": "Chickens", "descriptor_ui": "D002645", "major_topic": true }, { "descriptor": "Ectoderm", "descriptor_ui": "D004475", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Limb Buds", "descriptor_ui": "D018878", "major_topic": true }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jan 8", "date_precision": "day", "issue": "", "normalized_date": "2025-01-08", "pages": "53-61", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "520", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of a transgenic chicken line with reporters for limb bud mesenchyme and apical ectodermal ridge cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nucleic acid testing (NAT) is widely considered the gold standard in analytical fields, with applications spanning environmental monitoring, forensic science and clinical diagnostics, among others. However, its widespread use is often constrained by complicated assay procedures, the need for specialized equipment, and the complexity of reagent handling. In this study, we demonstrate a fully integrated 3D-printed biosensensing device employing a CRISPR/Cas12a-based dual-enzymatic mechanism for highly sensitive and user-friendly nucleic acid detection. A plastic probe stick was designed to host small-sized gold nanoparticles, enhancing enzyme labeling density. Alkaline phosphatase (ALP) was then conjugated via single-stranded DNA, requiring only a single enzyme substrate addition to generate a simple visual signal change. This approach eliminates the need for amplification or centrifugation steps, achieving a limit of detection (LOD) as low as 10 pM - among the highest sensitivities reported for amplification-free colorimetric nucleic acid detection. Furthermore, we developed a device that incorporates this probe stick, integrates all necessary reagents, and features a smartphone-compatible accessory for quantitative analysis. This allows end-users to perform visual or quantitative DNA analysis with simple operations, achieving a visual detection limit of approximately 100 pM, comparable to other CRISPR-based non-amplified nucleic acid detection methods. Additionally, the system successfully distinguished perfectly matched from mismatched nucleic acid sequences, demonstrating its specificity and versatility. Although certain design limitations affected the sensitivity of the integrated device compared to the probe stick alone, the simplicity and portability of this device make it a promising tool for rapid nucleic acid screening in clinical diagnostics, environmental monitoring, and food safety control. This study paves the way for the development of practical biosensors for point-of-care testing (POCT) applications.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Guodong", "last_name": "Tong", "name": null }, { "creator_type": "author", "first_name": "Pabitra", "last_name": "Nath", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d4lc01039f" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39775780" } }, "mesh": [ { "descriptor": "Alkaline Phosphatase", "descriptor_ui": "D000469", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": true }, { "descriptor": "Colorimetry", "descriptor_ui": "D003124", "major_topic": true }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": true }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": true }, { "descriptor": "Gold", "descriptor_ui": "D006046", "major_topic": false }, { "descriptor": "Limit of Detection", "descriptor_ui": "D057230", "major_topic": false }, { "descriptor": "Metal Nanoparticles", "descriptor_ui": "D053768", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jan 8", "date_precision": "day", "issue": "", "normalized_date": "2025-01-08", "pages": "", "proceedings_title": null, "publisher": "", "title": "Lab on a chip", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Amplification-free CRISPR/Cas based dual-enzymatic colorimetric nucleic acid biosensing device.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "From September 16 to 19, 2024, an international symposium to celebrate the centennial of the discovery of the gastrula organizer by Hans Spemann and Hilde Mangold, was held at the University of Freiburg, Germany, where they studied embryology. There were 41 plenary lectures, 11 short talks, and 182 poster presentations, with more than 300 participants from 23 countries. The symposium covered research topics broadly related to developmental, cell, genome, and evolutionary biology, mainly focused on early animal development. In addition to in vivo studies on topics such as gastrulation, embryonic patterning, cell polarity, and morphogenesis, recent studies using gastruloids and organoids, which recapitulate embryogenesis and organogenesis in in vitro cell culture, were also presented at this symposium, entitled Self-Organization in Biology. Most of the reported studies used vertebrate models such as mice, frogs, and zebrafish; however, evolutionary studies involving invertebrate and plant models were also presented. Presentations employing traditional methods such as cell transplantation and phenotype screening, and state-of-the-art technologies such as single-cell omics, high-resolution imaging, and computational analysis showed that experimental embryology has a long history, to which studies of the organizer have contributed significantly. Here we discuss memorable aspects of the symposium in the hope that this report will encourage young scientists to actively participate in face-to-face international conferences.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kuwana", "name": null }, { "creator_type": "author", "first_name": "Yuuri", "last_name": "Yasuoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12954" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39777708" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Developmental Biology", "descriptor_ui": "D015509", "major_topic": true }, { "descriptor": "Embryology", "descriptor_ui": "D004626", "major_topic": true }, { "descriptor": "Gastrula", "descriptor_ui": "D005775", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jan 8", "date_precision": "day", "issue": "", "normalized_date": "2025-01-08", "pages": "", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Meeting report about self-organization in biology: Freiburg Spemann-Mangold Centennial Symposium.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Detecting biothiols like glutathione (GSH), homocysteine (Hcy), and cysteine (Cys) is key to understanding their roles in health and disease. We developed BT-DNBS, a cyanine-based turn-on fluorescent probe with a dinitrobenzenesulfonyl (DNBS) quencher group. Upon biothiol interaction, the quencher is cleaved, restoring fluorescence. The resulting probe BT-NH shows a maximum emission wavelength at 630 nm and a large Stokes shift ( approximately 200 nm), enhancing detection accuracy. Low cytotoxicity and high time resolution make BT-DNBS suitable for live-cell imaging. Imaging of A431 cells confirmed intracellular biothiol detection, with NEM pre-treatment reducing fluorescence, verifying specificity. BT-DNBS holds promise for biomedical research, particularly in disease diagnostics.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shuai", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d4ra07109c" }, "pmcid": { "normalized": "PMC11694346" }, "pmid": { "normalized": "39758906" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jan 2", "date_precision": "day", "issue": "1", "normalized_date": "2025-01-02", "pages": "135-141", "proceedings_title": null, "publisher": "", "title": "RSC advances", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "BT-DNBS: a novel cyanine-based turn-on fluorescent probe with large Stokes shift for sensitive and selective detection of biothiols in live-cell imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Heterogeneity is a critical determinant for multicellular pattern formation. Although the importance of microscale and macroscale heterogeneity at the single-cell and whole-system levels, respectively, has been well accepted, the presence and functions of mesoscale heterogeneity, such as cell clusters with distinct properties, have been poorly recognized. We investigated the biological importance of mesoscale heterogeneity in signal-relaying abilities (excitability) in the self-organization of spiral waves of intercellular communications by studying the self-organized pattern formation in a population of Dictyostelium discoideum cells, a classical signal-relaying system model. By utilizing pulse-count analysis to evaluate cellular excitability, we successfully visualized the development of mesoscale heterogeneity in excitability, whose spatial scale was comparably large to that of the traveling waves of intercellular communication. Together with perturbation experiments, our detailed analysis of the structural change in mesoscale heterogeneity and associated wave dynamics demonstrated the functional importance of mesoscale heterogeneity in generating the spiral wave pattern, whose experimental observations were first realized. We propose that mesoscale heterogeneity, in addition to microscale and macroscale heterogeneities, is a critical determinant of diverse multicellular pattern formations.", "classifications": [ { "id": "18H05412", "label": "18H05412", "researcher": "Shuichi Onami", "type": "grant" }, { "id": "18H05415", "label": "18H05415", "researcher": "Kazuki Horikawa", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" }, { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taishi", "last_name": "Kakizuka", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Nakaoka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Ichiraku", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Itoga", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-85759-9" }, "pmcid": { "normalized": "PMC11717926" }, "pmid": { "normalized": "39789232" } }, "mesh": [ { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025-01", "date_precision": "month", "issue": "1", "normalized_date": "2025-01", "pages": "1422", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000173" ] }, "title": "Mesoscale heterogeneity is a critical determinant for spiral pattern formation in developing social amoeba", "url": "https://www.nature.com/articles/s41598-025-85759-9", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Functionally mature neural circuits are shaped during postnatal development by eliminating redundant synapses formed around birth. This process is known as synapse elimination and requires a proper balance of excitation and inhibition. Neuroligin-2 (NL2) is a postsynaptic cell adhesion molecule required for the formation, maintenance, and function of inhibitory synapses. However, how NL2 regulates synapse elimination during postnatal development is largely unknown. Here we report that the deletion of NL2 from Purkinje cells (PCs) in the cerebellum impairs the developmental elimination of redundant climbing fiber (CF) to PC synapses. In global NL2-knockout (KO) mice, GABAergic inhibition to PCs was attenuated and CF synapse elimination was impaired after postnatal day 10 (P10). These phenotypes were restored by the expression of NL2 into PCs of NL2-KO mice. Moreover, microRNA-mediated knockdown of NL2 specifically from PCs during development caused attenuated inhibition and impaired CF synapse elimination. In PCs innervated by \"strong\" and \"weak\" CFs, calcium transients elicited by \"weak\" CFs were enhanced in NL2-deficient PCs, suggesting that excess calcium signaling permits the survival of redundant \"weak\" CF synapses. We conclude that NL2 is crucial for maintaining inhibitory synaptic function and properly eliminating redundant CF synapses during postnatal development.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Esther Suk King", "last_name": "Lai", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fncir.2025.1530141" }, "pmcid": { "normalized": "PMC11949940" }, "pmid": { "normalized": "40160866" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Cell Adhesion Molecules, Neuronal", "descriptor_ui": "D015816", "major_topic": true }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": true }, { "descriptor": "Inhibitory Postsynaptic Potentials", "descriptor_ui": "D053444", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": true }, { "descriptor": "Neural Inhibition", "descriptor_ui": "D009433", "major_topic": true }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": true }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "1530141", "proceedings_title": null, "publisher": "", "title": "Frontiers in neural circuits", "volume": "19", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Reduced GABAergic inhibition and impaired synapse elimination by neuroligin-2 deletion from Purkinje cells of the developing cerebellum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Finding early trigger genes involved in cell-fate-determining processes is important for understanding molecular mechanisms of, e.g., differentiation and disease progression. One of the powerful tools for the finding is hypothesis-free omics measurements, e.g., gene expression analysis (transcriptome analysis) by RNA sequencing (RNA-seq). However, because whole single-cell RNA-seq requires cell disruption and the fate of the disrupted cell is generally unknown, it is difficult to find fate-related genes by single-cell RNA-seq profiles, especially in the early stages of cell-fate determination. Meanwhile, deep learning has successfully predicted cell fates using individual cell images. Here, we developed an approach by integrating image-based cell-fate prediction using deep learning and single-cell whole-transcriptome analysis to find differentially expressed genes (DEGs) between different predicted fates. As a proof of principle, we applied this approach to cells fated to die and survive. First, we applied temporary heat stress to a mammalian cell line to induce a certain fraction of cells to die, and performed time-lapse imaging to observe this process. Second, we made image-based deep learning models trained with our dataset for the cell fate prediction (survival and death). Third, we picked the cells after another time-lapse imaging and performed single-cell RNA-seq. Finally, we compared the transcriptomes between cells predicted to die and survive. We successfully detected the DEGs when the transcriptomic profiles did not show clear multiple clusters that may correspond to the heat-induced different fates in a dimension-reduced plane. Our approach may contribute to a deeper understanding of cell-fate regulation and new molecular marker detection.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Okaniwa", "name": null }, { "creator_type": "author", "first_name": "Kirill", "last_name": "Kryukov", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v22.0022" }, "pmcid": { "normalized": "PMC12582640" }, "pmid": { "normalized": "41189733" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "4", "normalized_date": "2025", "pages": "e220022", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "22", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Finding differentially expressed genes between cell fates predicted by image-based deep learning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Drastic changes in chromosome number and cellular contents upon ploidy alterations profoundly affect the stability of mitotic regulation in different biological and pathological processes. Isogenic ploidy series of somatic cell lines are useful for studying the effects of ploidy differences on mitotic regulation at cellular and molecular levels. This chapter describes experimental procedures using isogenic human HAP1 cell lines that cover haploid, diploid, and tetraploid states. We first describe methods to establish and maintain these isogenic HAP1 ploidy series using a flow cytometer. We then describe a procedure of comparative pharmacological assay for analyzing ploidy-dependent changes in the functionality of the mitotic spindle components.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Koya", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-4224-5_14" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39616578" } }, "mesh": [ { "descriptor": "Antimitotic Agents", "descriptor_ui": "D050256", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": true }, { "descriptor": "Ploidies", "descriptor_ui": "D011003", "major_topic": true }, { "descriptor": "Spindle Apparatus", "descriptor_ui": "D008941", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "207-219", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2872", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparative Pharmacological Analysis of Mitotic Inhibitors Using Isogenic Ploidy Series of HAP1 Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Sleep disorders are common in individuals with kidney failure. Whether kidney impairment is the direct cause of sleep abnormalities is unclear, however, partly due to confounding factors including comorbidities, dialysis, and drugs. METHODS: Here, we used a mouse model of acute kidney injury (AKI) transitioning to chronic kidney disease (CKD) induced by aristolochic acid to examine the effects of kidney impairment on sleep architecture. Each group, comprising 8~10 male mice, underwent cortical electroencephalogram (EEG) and electroencephalogram (EMG) recordings to measure sleep and cortical oscillations. RESULTS: During the acute phase, which models AKI, mice exhibited an approximately 20% increase in non-rapid eye movement sleep (NREMS) amount but reduced NREMS delta power in the EEG, which might be a consequence of systemic inflammation. Notably, in the chronic phase, which models CDK, the NREMS abnormalities were resolved, but rapid eye movement sleep (REMS) amount was largely reduced by approximately 20%. In addition, EEG theta power during both wakefulness and REMS was decreased. EEG slowing during wake and REMS was observed during both AKI and CKD. REMS disturbances in CKD mice correlated with serum levels of creatinine, urea nitrogen, and calcium. DISCUSSION: Together, these findings provide direct evidence that kidney impairment has dynamic effects on sleep architecture and EEG power spectra, and provide insight into the mechanisms underlying sleep abnormalities in individuals with AKI or CKD. Regarding sleep management in individuals with kidney failure, it is thus crucial to be aware of the possibility that kidney impairment directly causes sleep disturbances independent of treatment, comorbidities, or patient background.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naoko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Kaeko", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Mina", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Motoko", "last_name": "Yanagita", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2025.1581494" }, "pmcid": { "normalized": "PMC12267241" }, "pmid": { "normalized": "40678758" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "1581494", "proceedings_title": null, "publisher": "", "title": "Frontiers in neuroscience", "volume": "19", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic changes in sleep architecture in a mouse model of acute kidney injury transitioning to chronic kidney disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: The development of non-invasive clinical diagnostics is paramount for the early detection of Alzheimer's disease (AD). Neurofibrillary tangles in AD originate from the entorhinal cortex, a cortical memory area that mediates navigation via path integration (PI). Here, we studied correlations between PI errors and levels of a range of AD biomarkers using a 3D virtual reality navigation system to explore PI as a non-invasive surrogate marker for early detection. METHODS: We examined 111 healthy adults for PI using a head-mounted 3D VR system, AD-related plasma biomarkers (GFAP, NfL, Abeta40, Abeta42, and p-tau181), Apolipoprotein E (ApoE) genotype, and demographic and cognitive assessments. Covariance of PI and AD biomarkers was assessed statistically, including tests for multivariate linear regression, logistic regression, and predictor importance ranking using machine learning, to identify predictive relationships for PI errors. RESULTS: We found significant positive correlations between PI errors with age and plasma GFAP, p-tau181, and NfL levels. Multivariate analysis identified significant correlations of plasma GFAP (t-value = 2.16, p = 0.0332) and p-tau181 (t-value = 2.53, p = 0.0128) with PI errors. Predictor importance ranking using machine learning and receiver operating characteristic curves identified plasma p-tau181 as the most significant predictor of PI. ApoE genotype and plasma p-tau181 showed positive and negative PI associations (ApoE: coefficient = 0.650, p = 0.037; p-tau181: coefficient = -0.899, p = 0.041). EC thickness exhibited negative correlations with age, mean PI errors, and GFAP, NfL, and p-tau181; however, none of these associations remained significant after adjusting for age in linear regression analyses. CONCLUSION: These findings suggest that PI quantified by 3D VR navigation systems may be useful as a surrogate diagnostic tool for the detection of early AD pathophysiology. The hierarchical application of 3D VR PI and plasma p-tau181, in particular, may be an effective combinatorial biomarker for early AD neurodegeneration. These findings advance the application of non-invasive diagnostic tools for early testing and monitoring of AD, paving the way for timely therapeutic interventions and improved epidemiological patient outcomes.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Sayuri", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Ohdake", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Harutsugu", "last_name": "Tatebe", "name": null }, { "creator_type": "author", "first_name": "Riki", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Epifanio", "last_name": "Bagarinao", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Kawabata", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Ishigaki", "name": null }, { "creator_type": "author", "first_name": "Junichiro", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Tokuda", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Hirohisa", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnagi.2025.1571429" }, "pmcid": { "normalized": "PMC12405256" }, "pmid": { "normalized": "40908958" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "1571429", "proceedings_title": null, "publisher": "", "title": "Frontiers in aging neuroscience", "volume": "17", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Virtual reality navigation for the early detection of Alzheimer's disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In adult mammals and other highly developed animals, incomplete wound healing, scar formation, and fibrosis occur. No treatment for complete tissue regeneration is currently available. However, in mice, at up to 13 days of gestation, early embryonic wounds regenerate without visible scarring. In mouse fetuses, actin cable formation at the epidermal wound margin contributes to regeneration after wounding; however, the relationship between actin behavior and dermal regeneration or scar formation by myofibroblasts is unknown. In the present study, we observed actin dynamics in the wound dermis of mouse fetuses and investigated fibroblast and alpha-smooth muscle actin (alpha-SMA) properties involved in the switch between regeneration and scar formation in the dermis. In the wound healing process of mouse fetuses, actomyosin bundles develop and contract in a mesh-like pattern in different parts depending on the developmental stage, i.e., in the dermis of E13 (regeneration) and in the fascia of E15 and later (scar formation). Furthermore, in E13 dermal fibroblasts, alpha-SMA is present in the cytoplasm independently of actin, but in E15 and later myofibroblasts, TGFbeta-1 stimulation causes the distribution of alpha-SMA and actin to coincide, and in E17, when dermal scarring occurs, alpha-SMA is expressed particularly in the nucleus. The results indicate that reticular contraction by actomyosin is involved in dermal regeneration, and that the discrepancy in the localization of actin and alpha-SMA in fibroblasts is necessary. The findings may contribute to effective wound regeneration therapy.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kento", "last_name": "Takaya", "name": null }, { "creator_type": "author", "first_name": "Qi", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Imbe", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nobusue", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Aramaki-Hattori", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Saya", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kishi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0331006" }, "pmcid": { "normalized": "PMC12416743" }, "pmid": { "normalized": "40920843" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": true }, { "descriptor": "Actomyosin", "descriptor_ui": "D000205", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cicatrix", "descriptor_ui": "D002921", "major_topic": true }, { "descriptor": "Dermis", "descriptor_ui": "D020405", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fetus", "descriptor_ui": "D005333", "major_topic": true }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Primary Cell Culture", "descriptor_ui": "D061251", "major_topic": false }, { "descriptor": "Wound Healing", "descriptor_ui": "D014945", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "9", "normalized_date": "2025", "pages": "e0331006", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "20", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Formation of actin mesh structures and alpha-smooth muscle actin dynamics in fibroblasts contribute to dermal regeneration in mouse fetus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Solitary ascidians, such as Ciona robusta, have been used for over a century as model systems for embryological studies. These species are oviparous, producing many relatively small and transparent eggs, which are released and fertilized outside the parent body. Embryos develop rapidly in a stereotyped manner and reach the larva stage in less than 1 day (at 20 degrees C). The larvae then settle and metamorphose into sessile juveniles in approximately 2 days. On the other hand, colonial ascidians are ovoviviparous, with heavily yolked eggs that develop inside the parent body. In the colonial Botryllus schlosseri, embryos are connected to the parental body via a cup-like placenta and develop into larvae within a week (at 20 degrees C). These larvae, which possess both typical larval organs and prospective juvenile organs, are released into seawater, where they settle very rapidly, sometimes after only 15 minutes of free swimming. Then, they metamorphose into juvenile oozooids. The ability to study embryo development in colonial ascidians within the parent body is limited. To address this, we developed a method for in vitro culturing B. schlosseri embryos outside the parental body and combined it with time-lapse and confocal microscopy to describe the embryonic developmental stages. Moreover, we used histological analysis based on serial sections to investigate late-stage development, when embryo opacity made other techniques ineffective. We identified 19 stages of development, from the fertilized egg to the swimming larva, and described the stage of organ appearance and differentiation. Comparing the embryonic development timeline of B. schlosseri with that of C. robusta, we found heterochrony in development, particularly in the timing of organ appearance and growth rate. We hypothesize that this difference in maturation timing between solitary and colonial ascidians reflects a shift in the regulation of key developmental pathways that contributed to ascidian diversification. This heterochronic evolution likely facilitated a significant (approximately four-fold) shortening of the metamorphosis time in B. schlosseri by allowing embryos to remain in a safe ovoviviparous environment five times longer than those in C. robusta before hatching.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Chiara", "last_name": "Anselmi", "name": null }, { "creator_type": "author", "first_name": "Katherine J.", "last_name": "Ishizuka", "name": null }, { "creator_type": "author", "first_name": "Karla J.", "last_name": "Palmeri", "name": null }, { "creator_type": "author", "first_name": "Paolo", "last_name": "Burighel", "name": null }, { "creator_type": "author", "first_name": "Ayelet", "last_name": "Voskoboynik", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Lucia", "last_name": "Manni", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2025.1540212" }, "pmcid": { "normalized": "PMC11933078" }, "pmid": { "normalized": "40134577" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "1540212", "proceedings_title": null, "publisher": "", "title": "Frontiers in cell and developmental biology", "volume": "13", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Speed vs completeness: a comparative study of solitary and colonial tunicate embryogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Complications in neuroendovascular therapy for cerebral aneurysm (AN) affect the clinical course of patients. Patient conditions, operating procedures, and operator expertise were highlighted as risk factors for complications. These risk factors often combine and constitute particularly strong risks, resulting in a worsened clinical course. In this study, we performed a multifactorial assessment of complication risks in neuroendovascular therapy. METHODS: We analyzed patient data from the Japanese Registry of NeuroEndovascular Therapy 3, which is a nationwide retrospective cohort study of neuroendovascular procedures conducted between 2010 and 2014. Patients who underwent coil embolization for a ruptured anterior communicating artery (Acom) AN, an internal carotid artery-posterior communicating artery (IC-PC) AN, or basilar artery bifurcation (BA-bif) AN were included in this analysis. Information on 16 explanatory variables and 1 objective variable for each patient was obtained from the dataset as nominal variables. The explanatory variables consisted of patient factors, procedural factors, and an operator factor. The objective variable was whether the following complications occurred: intraprocedural bleeding, postprocedural bleeding, and procedure-related infarction. The specific situations involving multiple risk factors associated with high complication rates were identified using a programmed method. The impact of the absence of a supervising physician was also assessed. RESULTS: A total of 2971 patients were analyzed. The complication rates for patients with Acom ANs, IC-PC ANs, and BA-bif ANs were 12.9%, 10.2%, and 13.7%, respectively. A total of 15 specific situations were identified as follows: 3 related to an Acom AN, with complication rates ranging from 19.3% to 20.3%; 4 related to an IC-PC AN, with complication rates ranging from 15.6% to 17.9%; and 8 related to a BA-bif AN, with complication rates ranging from 20.6% to 33.3%. In 4 of these situations, the absence of a supervising physician significantly impacted complication rates. For instance, the complication rate for patients with IC-PC AN treated under local anesthesia was 16.0% overall, but it was 23.8% without supervising physicians. CONCLUSION: Multifactorial assessment based on patient, procedural, and operator factors provides more reliable risk estimations and will help improve the clinical course.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Arata", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Sonobe", "name": null }, { "creator_type": "author", "first_name": "Kuniyasu", "last_name": "Niizuma", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Hirotoshi", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Tetsu", "last_name": "Satow", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Iihara", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Teiji", "last_name": "Tominaga", "name": null } ], "identifiers": { "doi": { "normalized": "10.5797/jnet.oa.2024-0095" }, "pmcid": { "normalized": "PMC11830954" }, "pmid": { "normalized": "39963173" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "1", "normalized_date": "2025", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of neuroendovascular therapy", "volume": "19", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Multifactorial Assessment of Complication Risks in Embolization for Ruptured Cerebral Aneurysm.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The clinical impact of hypomagnesemia induced by necitumumab plus gemcitabine and cisplatin (GCN) as a second-line or later therapy is unclear. OBJECTIVE: We aimed to evaluate the clinical characteristics and survival impact of hypomagnesemia induced by this therapy. DESIGN: This was a sub-analysis of the retrospective multicenter NINJA study. METHODS: Among the 93 patients enrolled in the NINJA study, this subanalysis included 75 patients with baseline serum magnesium concentrations. RESULTS: The incidence of grade ⩾2 hypomagnesemia was 18.0% in the patients with normal baseline serum magnesium concentrations and 42.8% in those with low concentrations (p = 0.073). The discontinuation rates of GCN treatment owing to hypomagnesemia in each group were 0% and 7.1%, respectively (p = 0.187). The number of necitumumab doses and severity of hypomagnesemia were positively correlated (r = 0.389, p < 0.001). Patients who developed hypomagnesemia in fewer than 21 days after the first dose of GCN (n = 12) had significantly poorer progression-free survival (PFS) than those without the condition (n = 63; median: 4.1 vs 4.4 months, p = 0.048). A similar trend was observed for OS (median: 9.7 vs 15.7 months, p = 0.062). These results were maintained after multivariate analyses (PFS: hazard ratio (HR) 2.46, p = 0.014; OS: HR 2.78, p = 0.021). CONCLUSION: GCN as a second-line or later therapy may be tolerable regardless of the patient's baseline serum magnesium concentration. On the other hand, early serum magnesium reduction with this therapy is associated with a poor prognosis. However, caution should be needed because our results lacked sufficient information for confounding variables other than those analyzed here that may influence the correlation between hypomagnesemia and survival.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shigeru", "last_name": "Tanzawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshige", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Misumi", "name": null }, { "creator_type": "author", "first_name": "Eisaku", "last_name": "Miyauchi", "name": null }, { "creator_type": "author", "first_name": "Kiichiro", "last_name": "Ninomiya", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Takeshita", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Takatoshi", "last_name": "Fujishita", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Miyanaga", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Nojiri", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Nobuhisa", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kozuki", "name": null }, { "creator_type": "author", "first_name": "Takahisa", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Teppei", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Tetsumoto", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Kakuhiro", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Nishii", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Tsuruno", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Misumi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kuraishi", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Seki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1177/17588359251318850" }, "pmcid": { "normalized": "PMC11829289" }, "pmid": { "normalized": "39957806" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "17588359251318850", "proceedings_title": null, "publisher": "", "title": "Therapeutic advances in medical oncology", "volume": "17", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical impact of hypomagnesemia induced by necitumumab plus cisplatin and gemcitabine treatment in patients with advanced lung squamous cell carcinoma: a subanalysis of the NINJA study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Photoswitchable compounds are potent tools for elucidating molecular functions in dynamic cellular processes. Photoswitchable inhibitors targeting various mitotic spindle factors have been developed. In this chapter, we describe experimental methods for photo-controlling mitotic chromosome dynamics using a recently developed photoswitchable inhibitor of mitotic kinesin, CENP-E. This inhibitor undergoes reversible photoisomerization to a more inhibitory trans or less inhibitory cis state by visible or UV light irradiation, respectively, enabling photoswitching of CENP-E function both in vitro and in vivo. First, we explain the procedures used to optimize the experimental condition for efficient photoswitching of CENP-E functionality in cultured cells. We then describe how to conduct de novo photo-control of mitotic chromosome motion using the inhibitor under a microscope.", "classifications": [ { "id": "19H05413", "label": "19H05413", "researcher": "Ryota Uehara", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akira", "last_name": "Matsura", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Hiruma", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Tamaoki", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-4224-5_7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39616571" } }, "mesh": [ { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Chromosomal Proteins, Non-Histone", "descriptor_ui": "D002868", "major_topic": true }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false }, { "descriptor": "Photochemical Processes", "descriptor_ui": "D055668", "major_topic": false }, { "descriptor": "Ultraviolet Rays", "descriptor_ui": "D014466", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "101-113", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2872", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Photochemical Control of Cell Division Using a Photoswitchable CENP-E Inhibitor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Because of its good spectral separation from green (GFP) and red (RFP) fluorescent proteins, blue fluorescent protein (BFP) is essential for multicolor live cell imaging. However, the commonly used bright mTagBFP2 strongly perturbs the cellular localization of Lifeact, an F-actin marker. As an alternative, we tested the expression of Electra2 in Dictyostelium . Both standalone and as a fusion tag to Lifeact, HistoneH1, or the Akt/PKB PH domain, Electra2 showed brightness comparable to that of mTagBFP2, with intracellular localization patterns consistent with those of GFP and RFP. Electra2 is a promising BFP of choice for studying actin and other targets.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hidenori", "last_name": "Hashimura", "name": null }, { "creator_type": "author", "first_name": "Hibiki", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.17912/micropub.biology.001774" }, "pmcid": { "normalized": "PMC12413638" }, "pmid": { "normalized": "40918425" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "", "proceedings_title": null, "publisher": "", "title": "microPublication biology", "volume": "2025", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Use of blue fluorescent protein Electra2 for live-cell imaging in Dictyostelium discoideum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A bioluminescence-based RNA monitoring method in living cells was developed using a split NanoLuc (NLuc) reconstitution technique. For specific recognition of a target RNA sequence, a mutant PUM-HD (mPUM) was used. The method was applied to beta-actin mRNA in various cells, including primary cultures of rat hippocampal neurons. It allowed for continuous observation of intracellular localization distribution of the target mRNA in living cells, providing insights into various biological phenomena involving intracellular RNA localization and dynamics.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-4248-1_2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39535636" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "9-20", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2875", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "A Method for Bioluminescence-Based RNA Monitoring Using Split-Luciferase Reconstitution Techniques.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Temperature crucially affects molecular processes in living organisms and thus it is one of the vital physical parameters for life. To investigate how temperature is biologically maintained and regulated and its biological impact on organisms, it is essential to measure the spatial distribution and/or temporal changes of temperature across different biological scales, from whole organism to subcellular structures. Fluorescent nanothermometers have been developed as probes for temperature measurement by fluorescence microscopy for applications in microscopic scales where macroscopic temperature sensors are inaccessible, such as embryos, tissues, cells, and organelles. Although fluorescent nanothermometers have been developed from various materials, fluorescent protein-based ones are especially of interest because they can be introduced into cells as the transgenes for expression with or without specific localization, making them suitable for less-invasive temperature observation in living biological samples. In this article, we review protein-based fluorescent nanothermometers also known as genetically-encoded temperature indicators (GETIs), covering most published GETIs, for developers, users, and researchers in thermal biology as well as interested readers. We provide overviews of the temperature sensing mechanisms and measurement methods of these protein-based fluorescent nanothermometers. We then outline key information for GETI development, focusing on unique protein engineering techniques and building blocks distinct to GETIs, unlike other fluorescent nanothermometers. Furthermore, we propose several standards for the characterization of GETIs. Additionally, we explore various issues and offer perspectives in the field of thermal biology.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuichi", "last_name": "Wazawa", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Ozaki-Noma", "name": null }, { "creator_type": "author", "first_name": "Lu", "last_name": "Kai", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v22.0008" }, "pmcid": { "normalized": "PMC12040488" }, "pmid": { "normalized": "40309302" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "2", "normalized_date": "2025", "pages": "e220008", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "22", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetically-encoded temperature indicators for thermal biology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescent Timer proteins undergo a time-dependent shift from blue to red fluorescence after translation, providing a temporal record of transcriptional activity in Timer reporter systems. While Timer proteins are well suited for studying dynamic cellular processes such as T cell activation using the Timer-of-Cell-Kinetics-and-Activity (Tocky) framework, quantitative analysis of Timer-based flow cytometry data has yet to be fully standardized. In this study, we optimize quantitative analysis methods for the key parameter within the Tocky framework, Timer Angle, and introduce TockyLocus, an open-source R package that implements a five-category scheme based on biologically grounded angular intervals (designated as Tocky Loci). This approach is validated using both simulated and experimental datasets and enables downstream statistical testing and visualization of transcriptional dynamics in flow cytometry data. Using computational modelling of Timer protein kinetics, we define transcriptional dynamics in relation to key anchoring points in Timer Angle values at 0 degrees , 45 degrees , and 90 degrees . Comprehensive simulations with synthetic spike-in datasets further demonstrate the robustness of the five-locus approach, which captures the three key points and the intermediate regions between these points. Building on the TockyPrep preprocessing framework, we systematically evaluated categorization schemes ranging from three to seven loci on real-world datasets from Nr4a3-Tocky and Foxp3-Tocky mice. The five-locus model emerged as optimal, showing significant advantages in balancing biological interpretability and statistical robustness. Optimized algorithms implemented in the TockyLocus package now standardize quantitative analysis of Timer Angle data, enabling reproducible interpretation without reliance on arbitrary gating or complex assumptions. In summary, the five-locus categorization of Timer Angle data effectively links underlying biological dynamics to the percentage of cells in each Tocky Locus, providing a robust and interpretable framework for investigating transcriptional dynamics in immunology and related fields.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/biomethods/bpaf060" }, "pmcid": { "normalized": "PMC12464679" }, "pmid": { "normalized": "41018847" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "1", "normalized_date": "2025", "pages": "bpaf060", "proceedings_title": null, "publisher": "", "title": "Biology methods & protocols", "volume": "10", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "TockyLocus: quantitative analysis of flow cytometric fluorescent timer data in Nr4a3-Tocky and Foxp3-Tocky mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Skin disorders are major adverse events associated with necitumumab plus gemcitabine and cisplatin (Neci + GC) administration. However, the prognostic effect of skin disorders in patients with lung squamous cell carcinoma (LSCC) administered Neci + GC is unclear. OBJECTIVES: We examined this prognostic effect in patients with LSCC, and the usefulness of minocycline administration. DESIGN: This was a sub-analysis of the retrospective multicenter NINJA study. METHODS: We performed a landmark survival analysis according to the presence of skin disorders at Day 30 of treatment and examined the usefulness of minocycline for treating skin disorders. RESULTS: Among the 93 patients, 62 (66.7%) had a skin disorder at Day 30. Nineteen, 30, and 13 patients experienced Grade 1, 2, and 3 skin disorders, respectively. The overall survival (OS) and progression-free survival (PFS) of patients with skin disorders at Day 30 were longer than those of patients without skin disorders (median OS: 434 vs 278 days, p = 0.0201; median PFS: 148 vs 82 days, p = 0.0835). Multivariable analysis showed that a skin disorder at Day 30 was an independent prognostic factor for both OS (p = 0.0044) and PFS (p = 0.0514). Of the 62 patients with skin disorders at Day 30, 38 (61.3%) were taking minocycline, and their time to treatment failure (TTF) was better than that in patients not taking minocycline (median TTF: 148 vs 101 days, p = 0.0495). CONCLUSION: A skin disorder within 30 days was a favorable prognostic factor for patients with LSCC administered Neci + GC. Additionally, minocycline administration may be beneficial in patients who develop skin disorders within 30 days.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Tanzawa", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Misumi", "name": null }, { "creator_type": "author", "first_name": "Hiroshige", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Eisaku", "last_name": "Miyauchi", "name": null }, { "creator_type": "author", "first_name": "Kiichiro", "last_name": "Ninomiya", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Takeshita", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Miyanaga", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Nojiri", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kozuki", "name": null }, { "creator_type": "author", "first_name": "Takahisa", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Teppei", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Tetsumoto", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Kakuhiro", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Shoichi", "last_name": "Kuyama", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Tsuruno", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Misumi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kuraishi", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Seki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1177/17588359241312503" }, "pmcid": { "normalized": "PMC11909677" }, "pmid": { "normalized": "40093977" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "17588359241312503", "proceedings_title": null, "publisher": "", "title": "Therapeutic advances in medical oncology", "volume": "17", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Skin disorder within 30 days is a favorable prognostic factor in patients with lung squamous cell carcinoma treated with necitumumab plus gemcitabine and cisplatin: a sub-analysis of the NINJA study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hi-C methods reveal 3D genome features but lack correspondence to dynamic chromatin behavior. PHi-C2, Python software, addresses this gap by transforming Hi-C data into polymer models. After the optimization algorithm, it enables us to calculate 3D conformations and conduct dynamic simulations, providing insights into chromatin dynamics, including the mean-squared displacement and rheological properties. This chapter introduces PHi-C2 usage, offering a tutorial for comprehensive 4D genome analysis.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-4136-1_16" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39283458" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": true }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": true }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "271-279", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2856", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "4D Genome Analysis Using PHi-C2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Most animals capture light through opsins, which are light-sensitive G protein-coupled receptors (GPCRs). Recent genome analyses of anthozoans, including corals and sea anemones, have identified novel opsins that are phylogenetically classified into two groups distinct from previously known opsin groups. Despite their significance in clarifying biological functions, the specific molecular properties of these opsins remain largely unknown. In this study, we investigated the G protein activations and biochemical responses light-dependently induced by two anthozoan opsins, Antho2a and Antho2d, obtained from the reef-building coral Acropora tenuis, in mammalian cultured cells. Using jumping spider Rh1 (SpiRh1), which belongs to a known Gq-type G protein (Gq)-coupled opsin group as a control, we observed that Antho2a and Antho2d elicited light-dependent increases in Ca(2)+ levels in cultured cells. This response was inhibited by a Gq inhibitor, indicating that these opsins activated Gq in a light-dependent manner. Interestingly, Antho2d also activated the Gi-type G protein (Gi), similar to SpiRh1, while Antho2a showed limited or negligible Gi activation. We also found that Gi activation additionally contributed to the Ca(2)(+) elevation, suggesting it enhances Gq-dependent Ca(2)(+) elevation in Antho2d- and SpiRh1-expressing cells. In contrast, Antho2a demonstrated a higher specificity for Gq activation compared to SpiRh1 and was nearly equivalent to hM3Dq, a GPCR known for its strong Gq specificity and widely used as a chemogenetic tool for manipulating Gq activation. Our results suggest that this new anthozoan opsin group consists of Gq-coupled opsins with varying levels of Gi activation, demonstrating their potential for optogenetic applications.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Taishi", "last_name": "Shirata", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sugihara", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.2108/zs240085" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40184198" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anthozoa", "descriptor_ui": "D037421", "major_topic": true }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "GTP-Binding Protein alpha Subunits, Gq-G11", "descriptor_ui": "D043802", "major_topic": true }, { "descriptor": "Opsins", "descriptor_ui": "D055355", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "196-205", "proceedings_title": null, "publisher": "", "title": "Zoological science", "volume": "42", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Characterization of Anthozoan-Specific Opsins from a Reef-Building Coral, Acropora tenuis, as Gq-Coupled Opsins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Data-driven methodologies have transformed the discovery and prediction of hard materials with well-defined atomic structures by leveraging standardized datasets, enabling accurate property predictions and facilitating efficient exploration of design spaces(1-3). However, their application to soft materials remains challenging because of complex, multiscale structure-property relationships(4-6). Here we present a data-driven approach that integrates data mining, experimentation and machine learning to design high-performance adhesive hydrogels from scratch, tailored for demanding underwater environments. By leveraging protein databases, we developed a descriptor strategy to statistically replicate protein sequence patterns in polymer strands by ideal random copolymerization, enabling targeted hydrogel design and dataset construction. Using machine learning, we optimized hydrogel formulations from an initial dataset of 180 bioinspired hydrogels, achieving remarkable improvements in adhesive strength, with a maximum value exceeding 1 MPa. These super-adhesive hydrogels hold immense potential across diverse applications, from biomedical engineering to deep-sea exploration, marking a notable advancement in data-driven innovation for soft materials.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hongguang", "last_name": "Liao", "name": null }, { "creator_type": "author", "first_name": "Sheng", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Hu", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Hailong", "last_name": "Fan", "name": null }, { "creator_type": "author", "first_name": "Jian Ping", "last_name": "Gong", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41586-025-09269-4" }, "pmcid": { "normalized": "PMC12328221" }, "pmid": { "normalized": "40770436" } }, "mesh": [ { "descriptor": "Adhesiveness", "descriptor_ui": "D000268", "major_topic": false }, { "descriptor": "Adhesives", "descriptor_ui": "D000269", "major_topic": true }, { "descriptor": "Data Mining", "descriptor_ui": "D057225", "major_topic": true }, { "descriptor": "Databases, Protein", "descriptor_ui": "D030562", "major_topic": false }, { "descriptor": "Hydrogels", "descriptor_ui": "D020100", "major_topic": true }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Polymerization", "descriptor_ui": "D058105", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Aug", "date_precision": "unknown", "issue": "8075", "normalized_date": null, "pages": "89-95", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "644", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Data-driven de novo design of super-adhesive hydrogels.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinichi", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s41105-025-00585-w" }, "pmcid": { "normalized": "PMC12173990" }, "pmid": { "normalized": "40538391" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jul", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "257-258", "proceedings_title": null, "publisher": "", "title": "Sleep and biological rhythms", "volume": "23", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Circular RNA as a potential biomarker for obstructive sleep apnea.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Radiation therapy is an indispensable treatment for head and neck cancer; however, the development of radiation-induced oral mucositis causes erythema and ulcers in the patient's oral cavity, resulting in severe pain. The purpose of this study was to investigate the efficacy of Episil® in the treatment of radiation-induced oral mucositis. STUDY DESIGN: Seventy-six F344 rats were randomly divided into an Episil® group (n=38) and a control group (n=38). After irradiation, the rats were evaluated based on body weight measurements, the oral mucositis index (OMI), tissue myeloperoxidase (MPO) activity, and intraoral bacteria counts. RESULTS: The mean ratio of body weight change in the Episil®group was significantly lower than that in the control group. The maximum mean OMI and maximum mean MPO activity did not differ to a statistically significant extent between the Episil®​​​​​​​ and control groups. The mean bacterial count in the Episil®​​​​​​​ group was significantly lower than that in the control group on days 8-12. CONCLUSIONS:  It is hypothesised that Episil®​​​​​​​ prevents bacterial infections and body weight loss, potentially suppressing the aggravation of oral mucositis. It is necessary to investigate the bacterial count, the bacterial environments, oral management and the severity of oral mucositis in clinical trials in future to verify the bacterial prevention effect of Episil®​​​​​​​.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Naka", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Ohara", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Shibuya", "name": null } ], "identifiers": { "doi": { "normalized": "10.7759/cureus.88479" }, "pmcid": { "normalized": "PMC12372579" }, "pmid": { "normalized": "40861560" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "e88479", "proceedings_title": null, "publisher": "", "title": "Cureus", "volume": "17", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The Efficacy of Episil® for Radiation-induced Oral Mucositis in Rats.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "General anesthesia produces a rapid and reversible loss of consciousness, yet the neural circuits through which chemically unrelated agents achieve this state remain largely unknown. Here, we combined Targeted Recombination in Active Populations (TRAP), Clear, Unobstructed Brain/Body Imaging Cocktails and Computational analysis (CUBIC) tissue clearing, and light-sheet microscopy to generate a hemisphere-wide, single-cell atlas of neurons activated by three mechanistically distinct anesthetics in adult Fos(2A-iCreER/+); R26(Ai14/+) (TRAP2; Ai14) female mice. Automated alignment to the Atlas and unbiased effect-size analysis across 252 regions revealed a striking convergence. Vermal cerebellar lobules and their deep nuclei ranked at the top for every drug, whereas neocortical and thalamic areas showed mixed or drug-specific patterns. Within the cerebellum, the major population of tdTomato-labeled cells was the Purkinje cells, as confirmed by manual counting. Two additional subcortical hubs, the lateral paragigantocellular nucleus and external globus pallidus, were activated by all three agents, suggesting a broader cerebello-autonomic network. These results position Purkinje cells as a commonly activated population by chemically divergent anesthetics, raising the possibility that general anesthesia produces a state of loss of consciousness through the activation of Purkinje cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Nozomi", "last_name": "Utsumi", "name": null }, { "creator_type": "author", "first_name": "Daisuke H.", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Shizuki", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Shigenori", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/jnc.70331" }, "pmcid": { "normalized": "PMC12742451" }, "pmid": { "normalized": "41452264" } }, "mesh": [ { "descriptor": "Anesthetics, General", "descriptor_ui": "D018681", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "e70331", "proceedings_title": null, "publisher": "", "title": "Journal of neurochemistry", "volume": "169", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Convergent Recruitment of Cerebellar Purkinje Cells by Mechanistically Diverse General Anesthetics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Patients undergoing long-term peritoneal dialysis (PD) frequently develop peritoneal fibrosis and angiogenesis, leading to membrane dysfunction. Transglutaminase 2 (TG2) stabilizes the extracellular matrix against proteases. In an animal model, inhibition of TG2 reduced peritoneal fibrosis, angiogenesis, and inflammation. We investigated the expression of TG2 in 163 human peritoneal membrane tissue samples, including controls, tissues exposed to conventional acidic or low-glucose degradation product (GDP) pH-neutral solutions, and those with peritonitis or encapsulating peritoneal sclerosis (EPS), and explored the role of TG2 in high-glucose-induced pathophysiology in mesothelial cells. TG2 expression was upregulated in association with peritoneal membrane injury and was the highest in peritonitis. TG2 expression was correlated with peritoneal membrane thickness, CD68-positive macrophages, and myofibroblast expression. TG2 was expressed in mesothelial cells, alpha-smooth muscle actin-positive myofibroblast expression, macrophages, and endothelial cells in the diseased state. In cultured mesothelial cells, high-glucose-induced upregulation of collagen 1, TGF-beta1, and TG2 was suppressed by a TG2 inhibitor or by TGF-beta1 small interfering RNA. TG2 is involved in the development of peritoneal injury during PD. High-glucose dialysate is involved in the induction of peritoneal fibrosis through the interactive regulation of TGF-beta and TG2. Targeting TG2 may offer therapeutic potential for managing PD complications and EPS.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shunnosuke", "last_name": "Kunoki", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Ikeno", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Tatsukawa", "name": null }, { "creator_type": "author", "first_name": "Yukinao", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kinashi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Sasakura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Morioka", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Banshodani", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Tawada", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Iwabu", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Ishimoto", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Kiyotaka", "last_name": "Hitomi", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Kawanishi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.14814/phy2.70567" }, "pmcid": { "normalized": "PMC12451402" }, "pmid": { "normalized": "40977502" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Dialysis Solutions", "descriptor_ui": "D015314", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "GTP-Binding Proteins", "descriptor_ui": "D019204", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Peritoneal Dialysis", "descriptor_ui": "D010530", "major_topic": true }, { "descriptor": "Peritoneal Fibrosis", "descriptor_ui": "D056627", "major_topic": true }, { "descriptor": "Peritoneum", "descriptor_ui": "D010537", "major_topic": true }, { "descriptor": "Peritonitis", "descriptor_ui": "D010538", "major_topic": false }, { "descriptor": "Protein Glutamine gamma Glutamyltransferase 2", "descriptor_ui": "D000091345", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta1", "descriptor_ui": "D053773", "major_topic": false }, { "descriptor": "Transglutaminases", "descriptor_ui": "D011503", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Sep", "date_precision": "unknown", "issue": "18", "normalized_date": null, "pages": "e70567", "proceedings_title": null, "publisher": "", "title": "Physiological reports", "volume": "13", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Transglutaminase 2 in human peritoneal dialysis-related peritoneal injury.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Orexin neurons regulate physiological functions, including not only energy homeostasis and wakefulness but also motivated behaviors. These neurons play important roles in linking metabolic requirements to such behaviors. However, it is unknown whether these neurons are involved in reward-based choice behavior. We recently developed a transgenic rat line that expresses Cre recombinase exclusively in orexin neurons. Here, we examined the roles of orexin neurons in reward choice behavior under conditions of uncertainty in a gambling test in rats and analyzed the changes in choice behavior when orexin neurons were manipulated using chemogenetic approaches. In the gambling test, chemogenetic activation of orexin neurons resulted in risky arm choice. Positive, but not negative, reward-prediction error contributed to reward-based risky choice when orexin neurons were activated. These risky choice behaviors were canceled by suvorexant, an orexin receptor antagonist. In addition, suvorexant administered alone led to conservative choice behavior. The computational approach revealed that orexin/orexin neurons modulate the learning process and motivational value of rewards. Thus, our data suggest that orexin/orexin neurons affect the processing of reward-prediction error and alter strategy in reward-based decision-making.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mizoguchi", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Katahira", "name": null }, { "creator_type": "author", "first_name": "Ayumu", "last_name": "Inutsuka", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Hada", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Yasuike", "name": null }, { "creator_type": "author", "first_name": "Madoka", "last_name": "Isobe", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Kusaba", "name": null }, { "creator_type": "author", "first_name": "Yutao", "last_name": "Dong", "name": null }, { "creator_type": "author", "first_name": "Haruna", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Fukumoto", "name": null }, { "creator_type": "author", "first_name": "Yuchio", "last_name": "Yanagawa", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Kiyofumi", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pnasnexus/pgaf322" }, "pmcid": { "normalized": "PMC12578371" }, "pmid": { "normalized": "41179847" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "pgaf322", "proceedings_title": null, "publisher": "", "title": "PNAS nexus", "volume": "4", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Activation of orexin neurons changes reward-based decision-making strategies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Patients with hematologic diseases have experienced coronavirus disease 2019 (COVID-19) with a prolonged, progressive course. Here, we present clinical, pathological, and virological analyses of three cases of prolonged COVID-19 among patients undergoing treatment for B-cell lymphoma. These patients had all been treated with anti-CD20 antibody and bendamustine. Despite various antiviral treatments, high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) levels persisted for >4 weeks, and two of them succumbed to COVID-19. The autopsy showed bronchopneumonia, interstitial pneumonia, alveolar hemorrhage, and fibrosis. Overlapping cytomegalovirus, fungal and/or bacterial infections were also confirmed. Sequencing of SARS-CoV-2 showed accumulation of mutations and changes in variant allele frequencies over time. NSP12 mutations V792I and M794I appeared independently in two cases as COVID-19 progressed. In vitro drug susceptibility analysis and an animal experiment using recombinant SARS-CoV-2 demonstrated that each mutation, V792 and M794I, was independently responsible for remdesivir resistance and attenuated pathogenicity. E340A, E340D, and F342INS mutations in the spike protein were found in one case, which may account for the sotrovimab resistance. Analysis of autopsy specimens indicated heterogeneous distribution of these mutations. In summary, we demonstrated temporal and spatial diversity in SARS-CoV-2 that evolved resistance to various antiviral agents in malignant lymphoma patients under immunodeficient conditions caused by certain types of immunochemotherapies. Strategies may be necessary to prevent the acquisition of drug resistance and improve outcomes, such as the selection of appropriate treatment strategies for lymphoma considering patients' immune status and the institution of early intensive antiviral therapy.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Chisako", "last_name": "Iriyama", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Mutsumi", "last_name": "Takahata", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ishio", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ibata", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Mitsunaga", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Naganori", "last_name": "Nao", "name": null }, { "creator_type": "author", "first_name": "Hikoyu", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Kamiyama", "name": null }, { "creator_type": "author", "first_name": "Tadaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Harutaka", "last_name": "Katano", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Nanase", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Shimpei", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Doi", "name": null }, { "creator_type": "author", "first_name": "Takasuke", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pnasnexus/pgaf085" }, "pmcid": { "normalized": "PMC11950820" }, "pmid": { "normalized": "40160532" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "pgaf085", "proceedings_title": null, "publisher": "", "title": "PNAS nexus", "volume": "4", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical and molecular landscape of prolonged SARS-CoV-2 infection with resistance to remdesivir in immunocompromised patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Peyer's patches (PPs) are sites of antigen entry and immunoinduction in the small intestine. In PPs, pathogens are transferred through microfold (M) cells; however, the mechanisms of antigen capture by mononuclear phagocytes beneath M cells remain unclear. Here, we demonstrate that bacterial metabolite pyruvate acted on lysozyme-expressing dendritic cells (LysoDCs), a monocyte-derived phagocyte subset, and induced protrusion of dendrites particularly with \"balloon\" shapes into basolateral M-cell pockets via its receptor, G-protein coupled receptor 31 (GPR31). Pyruvate administration in wild-type but not Gpr31b-deficient mice increased LysoDC uptake of orally infected Listeria monocytogenes. GPR31 signaling boosted antigen processing and altered gene expression. It also increased LysoDC migration to the interfollicular region, thereby promoting production of pathogen-specific Th1 cells as well as cytotoxic T cells, and effector T cell migration to the lamina propria. Furthermore, oral pyruvate administration conferred high resistance to a virulent L. monocytogenes strain in a GPR31-dependent manner. Collectively, the pyruvate - GPR31 axis plays critical roles in orchestrating intestinal protective immunity.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Katsuhiro", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ajiro", "name": null }, { "creator_type": "author", "first_name": "Kaito", "last_name": "Yukishima", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Kikuta", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Tomura", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Shimanuki", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Maeshima", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Ichisawa", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Hayasaka", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Umemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/19490976.2025.2536089" }, "pmcid": { "normalized": "PMC12320816" }, "pmid": { "normalized": "40745869" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigen Presentation", "descriptor_ui": "D017951", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": true }, { "descriptor": "Listeria monocytogenes", "descriptor_ui": "D008089", "major_topic": false }, { "descriptor": "Listeriosis", "descriptor_ui": "D008088", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Muramidase", "descriptor_ui": "D009113", "major_topic": false }, { "descriptor": "Peyer's Patches", "descriptor_ui": "D010581", "major_topic": true }, { "descriptor": "Pyruvic Acid", "descriptor_ui": "D019289", "major_topic": true }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Dec", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "2536089", "proceedings_title": null, "publisher": "", "title": "Gut microbes", "volume": "17", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Pyruvate-GPR31 axis induces LysoDC dendrite protrusion to M-cell pockets for effective immune responses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Adipose-derived stem cells (ADSCs) can be obtained from adipose tissue, which is considered clinically dispensable. ADSCs have the ability to differentiate not only into adipocytes and osteoblasts but also into various other cell types, such as nerve cells and cardiomyocytes. However, the clinical application of ADSCs in stem cell therapy is hampered by the risk of transplant rejection and the need for facilities for their storage and transportation. In comparison, cell extracts (CEs) obtained from stem cells by freeze-thawing and lysis are less tumorigenic and immunogenic. However, there are currently no studies on the application of ADSC-derived CEs (ADSC-CEs) in peripheral nerve regeneration. Therefore, in this study, we investigated the effects of ADSC-CEs on proliferation and neurite extension in peripheral nerve cells. ADSCs were harvested from the inguinal region of mice, and ADSC-CEs were obtained following repeated freeze-thawing of ADSCs. We examined the effects of the ADSC-CEs, added to the culture medium, on glial fibrillary acidic protein (GFAP) expression and proliferation in Schwann cells. Moreover, we examined the effects of the ADSC-CEs on neurite length in DRG neurons and PC12D cells. ADSC-CEs stimulated the proliferation of Schwann cells, elevated GFAP expression in these cells, and promoted the elongation of DRG neuron and PC12D cell projections. Notably, heat treatment of the ADSC-CEs abolished these effects. Together, these findings suggest that ADSC-CEs may have therapeutic application in peripheral nerve regeneration.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuzo", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Naotaka", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sango", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Jun-Ichi", "last_name": "Tanuma", "name": null }, { "creator_type": "author", "first_name": "Simon D.", "last_name": "Tran", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Seo", "name": null } ], "identifiers": { "doi": { "normalized": "10.7759/cureus.94180" }, "pmcid": { "normalized": "PMC12595584" }, "pmid": { "normalized": "41209978" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "e94180", "proceedings_title": null, "publisher": "", "title": "Cureus", "volume": "17", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Effects of Adipose-Derived Stem Cell Extract on Peripheral Nerve Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIM: Neurodevelopmental disorders (NDDs) are the most common diagnosis among pediatric and adolescent psychiatric inpatients in Japan. However, there is limited evidence regarding nursing care for hospitalized children with NDDs. This study aimed to establish nursing care guidelines for children with NDDs hospitalized for aggressive behaviors. METHODS: The draft of the guidelines was based on qualitative content analysis of interviews with nurses. It was revised to ensure content validity through discussions with multidisciplinary experts in child and adolescent psychiatry. A three-round Delphi survey was conducted among nurses from child and adolescent psychiatric wards across Japan to reach consensus on the guidelines. RESULTS: Sixty-two nurses participated in the final survey. The agreement criterion was set to 80% to improve the content validity of the items. The survey identified 19 guideline items across five domains: \"Giving children a sense of security and safety regarding nurses and hospital life,\" \"Helping children reflect on and verbalize the situation and feelings they experience when engaging in aggressive behavior based on a sense of safety and security,\" \"Supporting children's motivation to change their behavior by helping them understand the inappropriateness and disadvantages of aggressive behavior,\" \"After motivating children, assisting them in setting specific behavioral goals to drive change,\" and \"Supporting children in establishing appropriate behavior to achieve their behavioral goals.\" CONCLUSION: These guidelines achieved a strong consensus and demonstrated content validity and value for inpatient treatment of children with NDDs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuka", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Tae", "last_name": "Kawahara", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Azusa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Akemi", "last_name": "Yamazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/pcn5.70144" }, "pmcid": { "normalized": "PMC12206547" }, "pmid": { "normalized": "40590034" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Sep", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "e70144", "proceedings_title": null, "publisher": "", "title": "PCN reports : psychiatry and clinical neurosciences", "volume": "4", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Validity of nursing interventions for aggressive behavior in neurodevelopmental disorders in child and adolescent psychiatry: A modified e-Delphi study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Tau protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD) and in regulating neuronal excitability. Among tau-coding microtubule associated protein tau (MAPT) gene mutations, the A152T mutation is reported to increase the risk of AD and neuronal excitability in mouse models. METHODS: To investigate the effects of MAPT gene expression and its mutations on neuronal activity in human neurons, we employed genome editing technology to introduce the A152T or P301S mutations into induced pluripotent stem cells (iPSCs). We then differentiated them into excitatory and inhibitory neurons. As a control, iPSCs in which the MAPT gene was replaced with a fluorescent protein were also created. RESULTS: In excitatory neuronal cultures, the A152T mutation was found to enhance spontaneous neuronal activity and the association of tau and Fyn. However, in inhibitory neuron-enriched cultures, the A152T mutation did not affect neuronal activity. Inhibition of NMDA receptors (NMDAR) and the reduction of tau protein levels decreased neuronal excitability in both A152T/A152T and healthy control (WT/WT) excitatory neurons. In addition, the A152T mutation increased the interaction between tau and Fyn. These findings suggest that the tau-Fyn interaction plays a critical role in regulating neuronal activity under physiological conditions, while the A152T mutation enhances neuronal activity by strengthening this endogenous interaction between tau and Fyn. In addition, transcriptomic analysis revealed structural changes specific to excitatory neurons with the A152T mutation. Common changes observed in both A152T and P301S lines recapitulated a dedifferentiation phenotype, consistent with previous reports. CONCLUSIONS: These data demonstrate that the A152T mutation in the MAPT gene increases neuronal excitability through the tau-Fyn-NMDAR pathway in excitatory neurons, shedding light on its role in AD pathogenesis.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Maika", "last_name": "Itsuno", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Chisato", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Setsu", "last_name": "Endoh-Yamagami", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Sumihiro", "last_name": "Maeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.reth.2024.12.009" }, "pmcid": { "normalized": "PMC11730958" }, "pmid": { "normalized": "39811068" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Mar", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "201-213", "proceedings_title": null, "publisher": "", "title": "Regenerative therapy", "volume": "28", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "MAPT-A152T mutation drives neuronal hyperactivity through Fyn-NMDAR signaling in human iPSC-Derived neurons: Insights into Alzheimer's pathogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During mouse embryonic development, the embryonic day (E) 5.5 stage represents a crucial period for the formation of the primitive body axis, where the symmetry breaking of cellular states influences the multicellular system. Elucidating the detailed mechanisms of this process necessitates a trans-layered dynamic observation of the embryo and all internal cells. In this report, we present our success in achieving in-toto single-cell observation in a whole hemisphere of an E5.5 embryo for 12 h, using a newly developed incubator-type biaxial light-sheet microscope. To achieve the success, we optimized our microscope system, including an incubator for culture stability, and refining the observation protocol to reduce phototoxicity. Our key discovery is that the scan speed during light-sheet formation plays a critical role in reducing phototoxicity, rather than the irradiation intensity or the interval time between frames. This innovative system not only enabled in-toto single-cell tracking but also led to the discovery of the abrupt shrinking of embryos whose contractile center was located at the extraembryonic ectoderm during monotonous growth up to the E6.5 stage.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" }, { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Go", "last_name": "Shioi", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Kaneshiro", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.26508/lsa.202402839" }, "pmcid": { "normalized": "PMC11735545" }, "pmid": { "normalized": "39814551" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": true }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Incubators", "descriptor_ui": "D007185", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": true }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Life science alliance", "volume": "8", "year": 2025 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000243" ] }, "title": "Trans-scale live-imaging of an E5.5 mouse embryo using incubator-type biaxial light-sheet microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIM: Renal fibrosis is a final common pathway for progressive chronic kidney diseases. Immune cell infiltration and production of tumour growth factor-beta (TGF-beta) are essential factors for fibrosis development. We examined the role of chondroitin sulfate (CS) proteoglycan, which is one of the main extracellular matrix components induced by TGF-beta signalling. We also examined CS N-acetylgalactosaminyltransferase 1 (T1), an enzyme that catalyses the first step of CS-specific synthesis. METHODS: T1(-/-) mice, genetically lacking T1, and T1(+/+) mice underwent 5/6 nephrectomy (Nx) or sham operation. Kidney function, urine marker, mRNA expression, and TGF-beta signalling were evaluated 1 month after Nx or sham operation. Renal fibrotic area was quantified 3 months later. RESULTS: Both T1(+/+) and T1(-/-) mice with Nx showed equivalent loss of kidney function; however, a tubular damage marker, upregulation of TGF-beta and collagen expression, and renal fibrosis were suppressed in T1(-/-) mice with Nx. Versican, one of the core proteins of CS proteoglycan, was exclusively upregulated in T1(+/+) mice with Nx. Among the versican splicing variants, versican 1 (V1) was expressed in the medullary interstitium of the remnant kidney in T1(+/+) mice. V1 was produced in the interstitial macrophages, fibroblasts/myofibroblasts, and endothelial cells, whereas TGF-beta was expressed in fibroblasts/myofibroblasts. Phosphorylation of the TGF-beta signalling molecules Smad2/3 was not induced in T1(-/-) mice with Nx. In vivo administration of TGF-beta inhibitor into Nx mice reduced V1 and Tgfb expression. CONCLUSION: T1 was essential for effective TGF-beta signalling, V1 upregulation, and subsequent renal fibrosis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kaho", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Ichiei", "last_name": "Narita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/nep.70109" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40826886" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Fibrosis", "descriptor_ui": "D005355", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "N-Acetylgalactosaminyltransferases", "descriptor_ui": "D017350", "major_topic": true }, { "descriptor": "Nephrectomy", "descriptor_ui": "D009392", "major_topic": false }, { "descriptor": "Renal Insufficiency, Chronic", "descriptor_ui": "D051436", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false }, { "descriptor": "Versicans", "descriptor_ui": "D053675", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "e70109", "proceedings_title": null, "publisher": "", "title": "Nephrology (Carlton, Vic.)", "volume": "30", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Chondroitin Sulfate N-Acetylgalactosaminyltransferase 1 Promotes the Progression of Renal Fibrosis Mediated by Versican 1 in Mouse Remnant Kidney.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Acute liver failure (ALF) is a serious disease that progresses from acute liver injury (ALI) and that often leads to multiorgan failure and ultimately death. Currently, effective treatment strategies for ALF, aside from transplantation, remain elusive, partly because ALI is highly heterogeneous. Furthermore, clinicians lack a quantitative indicator that they can use to predict which patients hospitalized with ALI will progress to ALF and the need for liver transplantation. In our study, we retrospectively analyzed data from 319 patients admitted to the hospital with ALI. By applying a machine-learning approach and by using the SHapley Additive exPlanations (SHAP) algorithm to analyze time-course blood test data, we identified prothrombin time activity percentage (PT%) as a biomarker reflecting individual ALI status. Unlike previous studies predicting the need for liver transplantation in patients with ALF, our study focused on PT% dynamics. Use of this variable allowed us to stratify the patients with highly heterogeneous ALI into six groups with distinct clinical courses and prognoses, i.e. self-limited, intensive care-responsive, or intensive care-refractory patterns. Notably, these groups were well predicted by clinical data collected at the time of admission. Additionally, utilizing mathematical modeling and machine learning, we assessed the predictability of individual PT% dynamics during the early phase of ALI. Our findings may allow for optimizing medical resource allocation and early introduction of tailored individualized treatment, which may result in improving ALF prognosis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Raiki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Masatake", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Kurokawa", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Goya", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Motoyuki", "last_name": "Kohjima", "name": null }, { "creator_type": "author", "first_name": "Katsuhito", "last_name": "Fujiu", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Iwami", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Ogawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pnasnexus/pgaf004" }, "pmcid": { "normalized": "PMC11801268" }, "pmid": { "normalized": "39917257" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "pgaf004", "proceedings_title": null, "publisher": "", "title": "PNAS nexus", "volume": "4", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Stratifying and predicting progression to acute liver failure during the early phase of acute liver injury.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Serotonin neurons are central to the pathophysiology and therapeutics of mental disorders, including major depressive disorder, anxiety, and schizophrenia. Genetically modified mice make it possible to target serotonin neurons by selective expression of the Cre and Flp genes; however, orthogonal methods that can be used in combination with Cre and Flp are of high importance, considering the highly complicated neural networks in the brain. Here, we improved serotonin neuron-specific viral vectors with higher specificity and sufficient potency for optogenetic manipulation and recording.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takuma", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Harune", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Shirakawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphs.2025.05.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40543995" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": true }, { "descriptor": "Integrases", "descriptor_ui": "D019426", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": true }, { "descriptor": "Serotonergic Neurons", "descriptor_ui": "D059326", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "331-335", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "158", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Improved serotonin neuron-specific viral vectors applicable for optogenetic manipulation and recording.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.alit.2025.09.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41067803" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Oct", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "497-498", "proceedings_title": null, "publisher": "", "title": "Allergology international : official journal of the Japanese Society of Allergology", "volume": "74", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Artificial intelligence and big data: Reshaping allergy research and patient care.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Schwann cells are essential for supporting the metabolic activity of neurons and myelination in the peripheral nervous system. While hypoxia is known to influence development in aerobic organisms and has recently been shown to regulate oligodendrocyte differentiation in the central nervous system, its role in Schwann cell function remains less understood. Here we demonstrate that hypoxia-inducible factor 1α (HIF1α) in Schwann cells promotes peripheral nerve myelination. HIF1α protein expression is post-transcriptionally regulated and highly induced in myelinating Schwann cells during development and after injury. We also demonstrated that peripheral nerve tissue experiences hypoxic conditions during physiological development and during regeneration following injury. Stabilization or overexpression of HIF1α in Schwann cells promotes myelination in culture. Analysis of HIF1α targets revealed that HIF1α upregulates genes associated with Schwann cell myelination and repair. Furthermore, conditional deletion of HIF1α in Schwann cells results in delayed morphological and functional recovery from peripheral nerve injury. Together, these findings identify HIF1α as a novel regulator of Schwann cell myelination and nerve repair.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuka", "last_name": "Kobayashi-Ujiie", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Wakatsuki", "name": null }, { "creator_type": "author", "first_name": "Yurika", "last_name": "Numata-Uematsu", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Nobuhito", "last_name": "Goda", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Araki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbc.2025.110433" }, "pmcid": { "normalized": "PMC12309608" }, "pmid": { "normalized": "40609787" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Hypoxia-Inducible Factor 1, alpha Subunit", "descriptor_ui": "D051795", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myelin Sheath", "descriptor_ui": "D009186", "major_topic": true }, { "descriptor": "Nerve Regeneration", "descriptor_ui": "D009416", "major_topic": false }, { "descriptor": "Peripheral Nerve Injuries", "descriptor_ui": "D059348", "major_topic": false }, { "descriptor": "Peripheral Nerves", "descriptor_ui": "D010525", "major_topic": true }, { "descriptor": "Schwann Cells", "descriptor_ui": "D012583", "major_topic": true }, { "descriptor": "Sciatic Nerve", "descriptor_ui": "D012584", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "110433", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "301", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Hypoxia-inducible factor 1α in Schwann cells promotes peripheral nerve myelination.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Self-tolerance in T cells is a vital self-defense strategy for mammals to specifically respond to invading pathogens. During T cell development in the thymus, thymocytes migrate from the cortex to the medulla to sequentially acquire non-self-reactivity and self-tolerance. This cortex-to-medulla migration is regulated by CCR7-mediated chemokine signaling. Previous studies have identified CCL21 but not CCL19 as a functional ligand for this CCR7-dependent migration. CCL21 in the mouse is encoded by multiple genes, including CCL21Ser-encoding Ccl21a and several CCL21Leu-encoding genes, including Ccl21b. The importance of Ccl21a in thymocyte migration has been demonstrated, whereas the role of CCL21Leu-encoding genes remains unclear. By producing mice specifically deficient in Ccl21b, we show that Ccl21b plays little to no role in the cortex-to-medulla migration of developing thymocytes. CCL21Leu-encoding gene transcripts remain detectable even in the absence of Ccl21b, suggesting that Ccl21b is not a major source of CCL21Leu. We further show that the copy number of CCL21Leu-encoding genes is smaller than the currently estimated copy number in a public database. These findings underscore the predominant role of Ccl21a over Ccl21b in the mouse thymus.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Izumi", "last_name": "Ohigashi", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Kyuma", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Otsu", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Yousuke", "last_name": "Takahama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/eji.70114" }, "pmcid": { "normalized": "PMC12717634" }, "pmid": { "normalized": "41420491" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Chemokine CCL21", "descriptor_ui": "D054421", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Receptors, CCR7", "descriptor_ui": "D054400", "major_topic": false }, { "descriptor": "Self Tolerance", "descriptor_ui": "D017634", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Thymocytes", "descriptor_ui": "D060168", "major_topic": true }, { "descriptor": "Thymus Gland", "descriptor_ui": "D013950", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "e70114", "proceedings_title": null, "publisher": "", "title": "European journal of immunology", "volume": "55", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Ccl21a, Rather Than Ccl21b, is Essential for Thymocyte Migration in Mouse.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Chemoradiotherapy (CRT) followed by durvalumab is the standard of care for unresectable locally advanced NSCLC. Limited prospective data have been reported on intensity-modulated radiotherapy (IMRT)-adapted CRT in the immunotherapy era. METHODS: In this multicenter prospective observational study, patients underwent IMRT-adapted CRT (platinum-doublet chemotherapy plus 60 Gy IMRT in 30 fractions under a prespecified radiation protocol), followed by consolidative durvalumab. The primary outcome was the durvalumab introduction rate within 42 days post-CRT. RESULTS: Thirty-two patients with unresectable locally advanced NSCLC were enrolled between November 2019 and February 2021. Among the 28 evaluable cases, durvalumab was introduced in 24 (85.7%, 90% confidence interval: 70.2%-95.0%) of 28 patients after CRT, achieving the primary end point. All 29 patients who received IMRT completed the scheduled 60 Gy radiotherapy dose. One year of durvalumab treatment was completed in 12 of 24 patients (50%). In the 24 patients who were durvalumab-introduced, the median progression-free survival and overall survival were 20.9 (95% confidence interval: 6.9-not evaluable) months and not reached, respectively. Two-year progression-free survival and overall survival rates were 44% and 73%, respectively. Among the 29 patients in the safety analysis set, there were no treatment-related deaths or grade 4 nonhematological adverse events. Pneumonitis grade 1 was observed in 13 patients (45%), grade 2 in seven (24%), and grade 3 in one (3%). CONCLUSIONS: High durvalumab introduction rate was reported after the completion of IMRT-adapted CRT under a prespecified radiation protocol. Its efficacy has been suggested, with favorable safety profiles, including a low incidence of severe pneumonitis. TRIAL REGISTRATION: University Hospital Medical Information Network database ID: UMIN000038366.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Nobuaki", "last_name": "Mamesaya", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Nakamatsu", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Haratani", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Mayahara", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Kokubo", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Nobuki", "last_name": "Imano", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Haruyuki", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Toshikatsu", "last_name": "Sado", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Isamu", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtocrr.2025.100828" }, "pmcid": { "normalized": "PMC12053000" }, "pmid": { "normalized": "40336674" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "100828", "proceedings_title": null, "publisher": "", "title": "JTO clinical and research reports", "volume": "6", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Intensity-Modulated Radiotherapy for Locally Advanced Lung Cancer in the Immunotherapy Era: A Prospective Study WJOG12019L.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The trigeminal spinal tract nucleus receives primary afferent input from the orofacial region, serving as a relay between peripheral terminals and secondary neurons. The trigeminal nerve is divided into ophthalmic, maxillary, and mandibular. While it is known that primary afferent terminals synapse with secondary neurons, the interaction between different primary terminals remains unclear. Recent studies have shown that trigeminal neurons with lost input can be activated through electrical stimulation of other afferent terminals. Therefore, we examined the possibility of inducing neural activity using synaptic organizers to promote circuit reorganization. To assess the regeneration of the injured inferior alveolar nerve (third division of the trigeminal nerve), the potential involvement of input from the infraorbital nerve (second division of the trigeminal nerve) in the regeneration of the injured inferior alveolar nerve (third division of the trigeminal nerve) was investigated. Intact and injured groups were created for the second and third divisions to facilitate comparative analysis. A synapse organizer was applied to establish input between the primary afferent terminals of these divisions. This study aimed to determine if central connections between different terminals can activate trigeminal neurons with lost input, ultimately promoting peripheral nerve regeneration. In this research, male C57BL/6J mice (seven to nine weeks old) (total n=40) underwent transection of the inferior alveolar nerve. They were divided into three groups: intact (n=10), injured (saline control) (n=10), and synapse organizer (n=10). In addition, the mice were divided into two groups: one group underwent inferior alveolar nerve transection only (II, intact; III, injured, n=5), and the other group underwent transection of both the infraorbital and inferior alveolar nerves (II, injured; III, injured, n=5), followed by local administration of a synapse organizer. Regeneration was assessed using immunostaining, sensory tests, and retrograde tracing. Regeneration was confirmed by retrograde tracing and functional recovery of sensory thresholds in the skin of the mental region. These findings align with previous observations that infraorbital nerve transection reduced regeneration activity, suggesting that infraorbital input triggered regeneration in the mandibular nerve. Thus, the results propose a novel therapeutic approach where mandibular nerve injury can be treated by stimulating the infraorbital nerve immediately after injury, enhancing peripheral nerve regeneration.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Emi", "last_name": "Sawada", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Naotaka", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Dai", "last_name": "Ooishi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Sasakura", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Seo", "name": null } ], "identifiers": { "doi": { "normalized": "10.7759/cureus.78708" }, "pmcid": { "normalized": "PMC11805595" }, "pmid": { "normalized": "39926623" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "e78708", "proceedings_title": null, "publisher": "", "title": "Cureus", "volume": "17", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Creating Alternative Afferent Input to Facilitate the Regeneration of Injured Primary Afferent Neurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mechanisms underlying sexual differentiation in viviparous chondrichthyans remain poorly understood, particularly regarding the impact of the maternal environment on early gonadal differentiation. In this study, we examined gonadal and reproductive duct differentiation in red stingray (Hemitrygon akajei) embryos before and after clasper formation through detailed histological analyses. Histological observations revealed that early embryos (stage 3, before clasper formation) exhibited undifferentiated gonads with scattered primordial germ cells, whereas later embryos (stage 4, during clasper development) exhibited clear sexual dimorphism. Female gonads contained numerous germ cells localized in the dorsal region, whereas male gonads contained fewer scattered germ cells. Both the Mullerian and Wolffian ducts were present in both sexes, with the Wolffian ducts emerging from the Mullerian ducts in a segmental pattern. Stage 4 female embryos exhibited a selective enlargement of the right Mullerian duct, establishing reproductive tract asymmetry. The sex ratio of red stingray embryos was 1:1. These findings provide the first detailed histological characterization of gonadal differentiation and reproductive duct development in a viviparous chondrichthyan and establish an essential foundation for future studies on sexual development in these evolutionarily significant vertebrates.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Naoaki", "last_name": "Tsutsui", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.2108/zs250013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41065487" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gonads", "descriptor_ui": "D006066", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Sex Characteristics", "descriptor_ui": "D012727", "major_topic": true }, { "descriptor": "Sex Differentiation", "descriptor_ui": "D012733", "major_topic": true }, { "descriptor": "Skates, Fish", "descriptor_ui": "D012860", "major_topic": true }, { "descriptor": "Viviparity, Nonmammalian", "descriptor_ui": "D052286", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Oct", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "446-452", "proceedings_title": null, "publisher": "", "title": "Zoological science", "volume": "42", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Early Gonadal Differentiation in the Viviparous Red Stingray: Histological Characterization of Sexual Dimorphism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The question of how changes in chemoattractant concentration translate into the chemotactic response of immune cells serves as a paradigm for the quantitative understanding of how cells perceive and process temporal and spatial information. Here, using a microfluidic approach, we analyzed the migration of neutrophil-like HL-60 cells to a traveling wave of the chemoattractants fMLP and leukotriene B4 (LTB4). We found that under a pulsatile wave that travels at a speed of 95 and 170 microm/min, cells move forward in the front of the wave but slow down and randomly orient at the back due to temporal decrease in the attractant concentration. Under a slower wave, cells re-orient and migrate at the back of the wave; thus, cell displacement is canceled out or even becomes negative as cells chase the receding wave. FRET-based analysis indicated that these patterns of movement correlated well with spatiotemporal changes in Cdc42 activity. Furthermore, pharmacological perturbations showed that (re-)orientation in front and back of the wave had different susceptibility to Cdc42 and ROCK inhibition. These results suggest that pulsatile attractant waves may recruit or disperse neutrophils, depending on their speed and degree of cell polarization.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Motohiko", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Uwamichi", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1091/mbc.e24-06-0245" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39718770" } }, "mesh": [ { "descriptor": "cdc42 GTP-Binding Protein", "descriptor_ui": "D020764", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Chemotactic Factors", "descriptor_ui": "D002630", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": true }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "HL-60 Cells", "descriptor_ui": "D018922", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukotriene B4", "descriptor_ui": "D007975", "major_topic": false }, { "descriptor": "N-Formylmethionine Leucyl-Phenylalanine", "descriptor_ui": "D009240", "major_topic": false }, { "descriptor": "Neutrophils", "descriptor_ui": "D009504", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Dec 24", "date_precision": "day", "issue": "", "normalized_date": "2024-12-24", "pages": "mbcE24060245", "proceedings_title": null, "publisher": "", "title": "Molecular biology of the cell", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Traveling wave chemotaxis of neutrophil-like HL-60 cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "MID1-COMPLEMENTING ACTIVITY (MCA) is a land plant-specific, plasma membrane protein, and Ca2+ signaling component that responds to exogenous mechanical stimuli, such as touch, gravity, and hypotonic-osmotic stress, in various plant species. MCA is essential for cell proliferation and differentiation during growth and development in rice (Oryza sativa) and maize (Zea mays). However, the mechanism by which MCA mediates cell proliferation and differentiation via Ca2+ signaling remains unknown. Here, we address this question using the liverwort Marchantia polymorpha. We show that the M. polymorpha MCA ortholog, MpMCA, is highly expressed in actively dividing regions, such as apical notches in the thalli and developing gametangiophores, and that MpMCA is a plasma membrane protein. In vivo, Ca2+ imaging using a Ca2+ sensor (yellow cameleon) revealed that MpMCA is required for maintaining proper [Ca2+]cyt levels in the apical notch region, egg cells, and antheridium cells. Mpmca mutant plants showed severe cell proliferation and differentiation defects in the thalli, gametangiophores, and gametangia, resulting in abnormal development and unsuccessful fertilization. Furthermore, expression of the Arabidopsis MCA1 gene complemented most of the defects in the growth and development of the Mpmca mutant plants. Our findings indicate that MpMCA is an evolutionarily conserved Ca2+-signaling component that regulates cell proliferation and development across the life cycle of land plants.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Megumi", "last_name": "Iwano", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Suetsugu", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Nishihama", "name": null }, { "creator_type": "author", "first_name": "Sakiko", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Alex", "last_name": "Costa", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Katsuno", "name": null }, { "creator_type": "author", "first_name": "Midori", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Kohchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/plphys/kiae613" }, "pmcid": { "normalized": "PMC11663713" }, "pmid": { "normalized": "39535860" } }, "mesh": [ { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": true }, { "descriptor": "Marchantia", "descriptor_ui": "D047008", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Plant Proteins", "descriptor_ui": "D010940", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Dec 23", "date_precision": "day", "issue": "1", "normalized_date": "2024-12-23", "pages": "", "proceedings_title": null, "publisher": "", "title": "Plant physiology", "volume": "197", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "MID1-COMPLEMENTING ACTIVITY regulates cell proliferation and development via Ca2+ signaling in Marchantia polymorpha.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Radiation induces various changes in biological specimens; however, the evaluation of these changes is usually complicated and can be achieved only through investment in time and labor. Optical methods reduce the cost of such evaluations as they require less pretreatment of the sample, are adaptable to high-throughput screening and are easy to automate. Optical methods are also advantageous, owing to their real-time and onsite evaluation capabilities. Here, we discuss three optical technologies to evaluate the effects of radiation on biological samples: single-molecule tracking microscopy to evaluate the changes in the physical properties of DNA, Raman spectral microscopy for dosimetry using human hair and second-harmonic generation microscopy to evaluate the effect of radiation on the differentiation of stem cells. These technologies can also be combined for more detailed information and are applicable to other biological samples. Although optical methods are not commonly used to evaluate the effects of radiation, advances in this technology may facilitate the easy and rapid assessment of radiation effects on biological samples.", "classifications": [ { "id": "18H05409", "label": "18H05409", "researcher": "Tomonobu M Watanabe", "type": "grant" }, { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jrr/rrae016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39679890" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Hair", "descriptor_ui": "D006197", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Radiation, Ionizing", "descriptor_ui": "D011839", "major_topic": true }, { "descriptor": "Radiometry", "descriptor_ui": "D011874", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Dec 16", "date_precision": "day", "issue": "Supplement_1", "normalized_date": "2024-12-16", "pages": "i117-i125", "proceedings_title": null, "publisher": "", "title": "Journal of radiation research", "volume": "65", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Use of optical techniques to evaluate the ionizing radiation effects on biological specimens.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Imaging flow cytometry is a technology that performs microscopy image analysis of cells within flow cytometry and allows high-throughput, high-content cell analysis based on their intracellular molecular distribution and/or cellular morphology. While the technology has been available for a couple of decades, it has recently gained significant attention as technical limitations for higher throughput, sorting capability, and additional imaging dimensions have been overcome with various approaches. These evolutions have enabled imaging flow cytometry to offer a variety of solutions for life science and medicine that are not possible with conventional flow cytometry or microscopy-based screening. It is anticipated that the extent of applications will expand in the upcoming years as the technology becomes more accessible through dissemination. In this review, we will cover the technical advances that have led to this new generation of imaging flow cytometry, focusing on the advantages and limitations of each technique.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Ugawa", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cells13242073" }, "pmcid": { "normalized": "PMC11674929" }, "pmid": { "normalized": "39768164" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Cytometry", "descriptor_ui": "D019044", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Dec 16", "date_precision": "day", "issue": "24", "normalized_date": "2024-12-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cells", "volume": "13", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Recent Technologies on 2D and 3D Imaging Flow Cytometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Using our recently developed laser speckle contrast imaging (LSCI) to visualize blood vessels and monitor blood flow, we test the utility of the developing chick heart as a functional model for drug screening. To this end, we examined the effects of antihypertensive agents Nifedipine and Amlodipine, belonging to the L-type calcium channel antagonist family, on blood flow visualized noninvasively through the intact shell. Guided by the live view mode, the drugs were injected through the shell and ventral to HH16-19 chick embryos. Our results show a significant reduction in the chick's heart rate, blood flow, and vascular size within 5-20 minutes after Nifedipine or Amlodipine injection. For moderate Nifedipine concentrations, these parameters returned to initial values within 2-3 hours. Nifedipine showed a rapid reduction in heart rate and blood flow dynamics at a concentration ten times lower than Amlodipine. These findings show that our LSCI system can monitor and distinguish the chick heart's response to injected drugs from the same family. This serves as proof-of-concept, paving the way for a rapid, cost-effective, and quantitative test system for screening drugs that affect the cardiovascular system of live chick embryos. Live noninvasive imaging may also provide insights into the development and functioning of the vertebrate heart.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Carol", "last_name": "Readhead", "name": null }, { "creator_type": "author", "first_name": "Simon", "last_name": "Mahler", "name": null }, { "creator_type": "author", "first_name": "Zhenyu", "last_name": "Dong", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Changhuei", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Marianne E.", "last_name": "Bronner", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2024.12.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39675502" } }, "mesh": [ { "descriptor": "Amlodipine", "descriptor_ui": "D017311", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antihypertensive Agents", "descriptor_ui": "D000959", "major_topic": false }, { "descriptor": "Blood Vessels", "descriptor_ui": "D001808", "major_topic": true }, { "descriptor": "Calcium Channel Blockers", "descriptor_ui": "D002121", "major_topic": false }, { "descriptor": "Chick Embryo", "descriptor_ui": "D002642", "major_topic": false }, { "descriptor": "Heart", "descriptor_ui": "D006321", "major_topic": true }, { "descriptor": "Heart Rate", "descriptor_ui": "D006339", "major_topic": true }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": false }, { "descriptor": "Nifedipine", "descriptor_ui": "D009543", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Dec 13", "date_precision": "day", "issue": "", "normalized_date": "2024-12-13", "pages": "S0012-1606(24)00277-X", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Automated non-invasive laser speckle imaging of the chick heart rate and extraembryonic blood vessels and their response to nifedipine and amlodipine drugs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The BCR::ABL1 oncogene plays a crucial role in the development of chronic myeloid leukemia (CML). Previous studies have investigated the involvement of mitochondrial dynamics in various cancers, revealing potential therapeutic strategies. However, the impact of BCR::ABL1 on mitochondrial dynamics remains unclear. In this study, we demonstrated that BCR::ABL1 is sufficient to induce excessive mitochondrial fragmentation by activating dynamin-related protein (DRP)1 through the mitogen-activated protein kinase (MAPK) pathway. Leukocytes obtained from patients with CML and the BCR::ABL1-positive cell lines exhibited increased mitochondrial fragmentation compared to leukocytes obtained from healthy donors and BCR::ABL1-negative cells. Furthermore, the analysis of BCR::ABL1-transduced cells showed increased phosphorylation of DRP1 at serine 616 and extracellular signal-regulated kinase (ERK) 1/2. Moreover, the inhibition of DRP1 and upstream mitogen-activated extracellular signal-regulated kinase (MEK) 1/2 suppressed mitochondrial fragmentation. Strikingly, DRP1 inhibition effectively reduced the viability of BCR::ABL1-positive cells and induced necrotic cell death. Additionally, a label-free artificial intelligence-driven flow cytometry successfully identified not only the BCR::ABL1-transduced cells but also peripheral leukocytes from CML patients by assessing mitochondrial morphological alterations. These findings suggested the crucial role of BCR::ABL1-induced mitochondrial fragmentation in driving BCR::ABL1-positive cell proliferation, and the potential use of mitochondrial morphological alterations as a clinical biomarker for the label-free detection of CML cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kohjin", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Torii", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Arakawa", "name": null }, { "creator_type": "author", "first_name": "Kiyosumi", "last_name": "Ochi", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Shigeomi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Tomoiku", "last_name": "Takaku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.16424" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39652455" } }, "mesh": [ { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Dynamins", "descriptor_ui": "D034281", "major_topic": false }, { "descriptor": "Fusion Proteins, bcr-abl", "descriptor_ui": "D016044", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia, Myelogenous, Chronic, BCR-ABL Positive", "descriptor_ui": "D015464", "major_topic": true }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": true }, { "descriptor": "Mitochondrial Dynamics", "descriptor_ui": "D063154", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Dec 9", "date_precision": "day", "issue": "", "normalized_date": "2024-12-09", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "BCR::ABL1-induced mitochondrial morphological alterations as a potential clinical biomarker in chronic myeloid leukemia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The opioid system plays crucial roles in modulating social behaviors in both humans and animals. However, the pharmacological profiles of opioids regarding social behavior and their therapeutic potential remain unclear. Multiple pharmacological, behavioral, and immunohistological c-Fos mapping approaches were used to characterize the effects of mu-opioid receptor agonists on social behavior and investigate the mechanisms in naive mice and autism spectrum disorder-like (ASD-like) mouse models, such as prenatally valproic acid-treated mice and Fmr1-KO mice. Here, we report that low-dose morphine, a mu-opioid receptor agonist, promoted social behavior by selectively activating neurons in prosocial brain regions, including the nucleus accumbens, but not those in the dorsomedial periaqueductal gray (dmPAG), which are only activated by analgesic high-dose morphine. Critically, intra-dmPAG morphine injection counteracted the prosocial effect of low-dose morphine, suggesting that dmPAG neural activation suppresses social behavior. Moreover, buprenorphine, a mu-opioid receptor partial agonist with less abuse liability and a well-established safety profile, ameliorated social behavior deficits in two mouse models recapitulating ASD symptoms by selectively activating prosocial brain regions without dmPAG neural activation. Our findings highlight the therapeutic potential of brain region-specific neural activation induced by low-dose opioids for social behavior deficits in ASD.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Soichiro", "last_name": "Ohnami", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Haruki", "last_name": "Kawase", "name": null }, { "creator_type": "author", "first_name": "Momoko", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Takasu", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Kanemaru", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kochi", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Imado", "name": null }, { "creator_type": "author", "first_name": "Takeru", "last_name": "Tahara", "name": null }, { "creator_type": "author", "first_name": "Yaichiro", "last_name": "Kotake", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hidekuni", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci.insight.182060" }, "pmcid": { "normalized": "PMC11623950" }, "pmid": { "normalized": "39641273" } }, "mesh": [ { "descriptor": "Analgesics, Opioid", "descriptor_ui": "D000701", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autism Spectrum Disorder", "descriptor_ui": "D000067877", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Buprenorphine", "descriptor_ui": "D002047", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fragile X Messenger Ribonucleoprotein 1", "descriptor_ui": "D051860", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": true }, { "descriptor": "Morphine", "descriptor_ui": "D009020", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Nucleus Accumbens", "descriptor_ui": "D009714", "major_topic": false }, { "descriptor": "Periaqueductal Gray", "descriptor_ui": "D010487", "major_topic": true }, { "descriptor": "Receptors, Opioid, mu", "descriptor_ui": "D017450", "major_topic": true }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": true }, { "descriptor": "Valproic Acid", "descriptor_ui": "D014635", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Dec 6", "date_precision": "day", "issue": "23", "normalized_date": "2024-12-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "JCI insight", "volume": "9", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Brain region-specific neural activation by low-dose opioid promotes social behavior.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The orchestration of our genes heavily relies on coordinated communication between enhancers and promoters, yet the mechanisms behind this dynamic interplay during active transcription remain unclear. Here, we investigated enhancer-promoter (E-P) interactions in relation to transcriptional bursting in mouse embryonic stem cells using sequential DNA/RNA/immunofluorescence–fluorescence in situ hybridization analyses. Our data reveal that the active state of specific genes is characterized by specific proximities between different genomic regions and the accumulation of transcriptional regulatory factors. Mathematical simulations suggest that an increase in local viscosity could potentially contribute to stabilizing the duration of these E-P proximities. Our study provides insights into the association among E-P proximity, protein accumulation, and transcriptional dynamics, paving the way for a more nuanced understanding of gene-specific regulatory mechanisms.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Ohishi", "name": null }, { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Owada", "name": null }, { "creator_type": "author", "first_name": "Takeru", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Kazufumi", "last_name": "Hosoda", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ochiai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adn0020" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39642226" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Enhancer Elements, Genetic", "descriptor_ui": "D004742", "major_topic": true }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "In Situ Hybridization, Fluorescence", "descriptor_ui": "D017404", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mouse Embryonic Stem Cells", "descriptor_ui": "D000066450", "major_topic": true }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Dec 06", "date_precision": "day", "issue": "49", "normalized_date": "2024-12-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "Science Advances", "volume": "10", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Transcription-coupled changes in genomic region proximities during transcriptional bursting.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Oscillatory phenomena play widespread roles in the control of biological systems. In D. discoideum, oscillatory cyclic adenosine monophosphate (cAMP) signaling drives collective behavior and induces a temporal developmental gene expression program. How collective cAMP oscillations emerge or how they encode temporal transcriptional information is still poorly understood. To address this, we identified a transcription factor required for the initiation of collective behavior. Hbx5 activity is cAMP dependent and provides a sensitive single-cell readout for cAMP signaling. Extensive stochastic pulsatile cAMP signaling is found to precede collective oscillations. Stochastic signaling induces Hbx5-dependent transcriptional feedback, which enhances signal sensitivity and cell-cell coupling. This results in the emergence of synchronized collective oscillations, which subsequently activates the GtaC transcription factor and triggers shifts in developmental gene expression. Our results suggest this temporal coordination is encoded by changes in the amplitude of cAMP oscillations and differential sensitivity of these transcription factors to the cAMP-regulated kinase ErkB.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Christopher A.", "last_name": "Brimson", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Baines", "name": null }, { "creator_type": "author", "first_name": "Elisabeth", "last_name": "Sams-Dodd", "name": null }, { "creator_type": "author", "first_name": "Ioanina", "last_name": "Stefanescu", "name": null }, { "creator_type": "author", "first_name": "Bethany", "last_name": "Evans", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kuwana", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Hashimura", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Christopher R. L.", "last_name": "Thompson", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2024.11.016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39672161" } }, "mesh": [ { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": true }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Protozoan Proteins", "descriptor_ui": "D015800", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Dec 5", "date_precision": "day", "issue": "", "normalized_date": "2024-12-05", "pages": "S1534-5807(24)00698-1", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Collective oscillatory signaling in Dictyosteliumdiscoideum acts as a developmental timer initiated by weak coupling of a noisy pulsatile signal.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cellular slime mold Dictyostelium discoideum, a member of the Amoebozoa, has been extensively studied in cell and developmental biology. D. discoideum is unique in that they are genetically tractable, with a wealth of data accumulated over half a century of research. Fluorescence live-cell imaging of D. discoideum has greatly facilitated studies on fundamental topics, including cytokinesis, phagocytosis, and cell migration. Additionally, its unique life cycle places Dictyostelium at the forefront of understanding aggregative multicellularity, a recurring evolutionary trait found across the Opisthokonta and Amoebozoa clades. The use of multiple fluorescent proteins (FP) and labels with separable spectral properties is critical for tracking cells in aggregates and identifying co-occurring biomolecular events and factors that underlie the dynamics of the cytoskeleton, membrane lipids, second messengers, and gene expression. However, in D. discoideum, the number of frequently used FP species is limited to two or three. In this study, we explored the use of new-generation FP for practical 4- to 5-color fluorescence imaging of D. discoideum. We showed that the yellow fluorescent protein Achilles and the red fluorescent protein mScarlet-I both yield high signals and allow sensitive detection of rapid gene induction. The color palette was further expanded to include blue (mTagBFP2 and mTurquosie2), large Stoke-shift LSSmGFP, and near-infrared (miRFP670nano3) FPs, in addition to the HaloTag ligand SaraFluor 650T. Thus, we demonstrated the feasibility of deploying 4- and 5- color imaging of D. discoideum using conventional confocal microscopy.Key words: fluorescence imaging, organelle, cytoskeleton, small GTPase, Dictyostelium.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hidenori", "last_name": "Hashimura", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kuwana", "name": null }, { "creator_type": "author", "first_name": "Hibiki", "last_name": "Nakagwa", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Toyoko", "last_name": "Sugita", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Fujishiro", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1247/csf.24065" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39631875" } }, "mesh": [ { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": true }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": true }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Red Fluorescent Protein", "descriptor_ui": "D000097573", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Dec 4", "date_precision": "day", "issue": "", "normalized_date": "2024-12-04", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cell structure and function", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Multi-color fluorescence live-cell imaging in Dictyostelium discoideum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Targeted drug delivery in response to external stimuli is therapeutically desirable, but long-term drug retention at the target site after stimulation is turned off remains a challenge. Herein, we present a targeted-delivery strategy via irreversible aggregation of drug carriers in response to mild external heating. We constructed two types of polymeric micelles, DBCO-TRM and Az-TRM, having a thermo-responsive polymer shell based on N-isopropylacrylamide (NIPAAm) and incorporating alkyne and azide moieties, respectively. Upon heating at 42 degrees C, the micelles aggregated through hydrophobic interaction between their dehydrated shells. Further, the azide moieties of Az-TRM become exposed on the surface due to the thermally shrinkage of the shells, thereby enabling crosslinking between the two types of micelles via azide-alkyne click chemistry to form irreversible aggregates. These aggregates were efficiently accumulated at tumor sites in mice by local heating after intravenous administration of a mixture of the micelles, and were well retained after cessation of heating due to their increased size. As proof of concept, we show that delivery of doxorubicin in this heat-guided drug delivery system dramatically improved the anti-tumor effect in a mouse model after a single treatment. Our results suggest that this platform could be an efficient tool for on-demand drug delivery.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Sota", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42004-024-01383-0" }, "pmcid": { "normalized": "PMC11615195" }, "pmid": { "normalized": "39627351" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Dec 3", "date_precision": "day", "issue": "1", "normalized_date": "2024-12-03", "pages": "287", "proceedings_title": null, "publisher": "", "title": "Communications chemistry", "volume": "7", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Heat-guided drug delivery via thermally induced crosslinking of polymeric micelles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Abnormalities in spermatogenesis, a fundamental component of male reproductive function, can cause male infertility. Somatic cells constituting the testis microenvironment are essential for controlling normal spermatogenesis. Although testicular somatic cells are thought to sense and respond to germ cells to ensure proper spermatogenesis, the details of this signaling mechanism are unknown. Here, we investigated somatic cell dynamics in testicular tissue lacking spermatogenesis using the mice with deletion of the testis-specific histone H3 variant gene H3t. Testicular tissue sections of H3t(Delta/Delta) mice exhibited an increased interstitial area compared with those of wild-type mice, which was primarily attributed to an increase in Leydig cell numbers. Furthermore, this increase in Leydig cells led to increased testosterone synthesis, which occurred alongside cellular senescence-associated beta-galactosidase activity. These findings suggest that Leydig cells monitor the progress of spermatogenesis and possess a mechanism to promote functional germ cell formation.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" }, { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Qianmei", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takeru", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kohta", "last_name": "Nakatani", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Bamba", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Tomimatsu", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.13182" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39624989" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": true }, { "descriptor": "Infertility, Male", "descriptor_ui": "D007248", "major_topic": false }, { "descriptor": "Leydig Cells", "descriptor_ui": "D007985", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Spermatogenesis", "descriptor_ui": "D013091", "major_topic": true }, { "descriptor": "Testis", "descriptor_ui": "D013737", "major_topic": false }, { "descriptor": "Testosterone", "descriptor_ui": "D013739", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Dec 3", "date_precision": "day", "issue": "", "normalized_date": "2024-12-03", "pages": "e13182", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Defects in the H3t Gene Cause an Increase in Leydig Cells With Impaired Spermatogenesis in Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In mammals, the central circadian clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus, which transmits circadian information to other brain regions and regulates the timing of sleep and wakefulness. Neurons in the lateral hypothalamus (LH), particularly those producing melanin-concentrating hormone (MCH)- and orexin are key regulators of sleep and wakefulness. Although the SCN receives non-photic input from other brain regions, the mechanisms of functional input from the LH to the SCN remain poorly understood. Here, we show that orexin and MCH peptides influence the circadian period within the SCN of both sexes. When these neurons are ablated, the circadian behavioral rhythms are lengthened under constant darkness. Using anterograde and retrograde tracing, we found that orexin and MCH neurons project to the SCN. Furthermore, the application of these peptides to cultured SCN slices shortened circadian rhythms and reduced intracellular cAMP levels. Additionally, pharmacological reduction of intracellular cAMP levels similarly shortened the circadian period in SCN slices. These findings suggest that orexin and MCH peptides from the LH contribute to the modulation of the circadian period in the SCN.Significance statement In mammals, the central circadian clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus, where it regulates circadian rhythms, including sleep and wakefulness. The SCN receives both neuronal and humoral input signals from external brain regions, which can modify circadian rhythms within the SCN. While several brain regions that project to the SCN have been anatomically identified, the specific regions, neuronal cell types, and neurotransmitters that influence SCN circadian rhythms remain largely uncharacterized. This study identifies two neuronal populations within the lateral hypothalamus that project to the SCN and modulate the circadian period.", "classifications": [ { "id": "21H00422", "label": "21H00422", "researcher": "Daisuke Ono", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Chi", "last_name": "Jung Hung", "name": null }, { "creator_type": "author", "first_name": "Chang-Ting", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "Sheikh Mizanur", "last_name": "Rahaman", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Wooseok", "last_name": "Seo", "name": null }, { "creator_type": "author", "first_name": "Tatsushi", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.0351-24.2024" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39622648" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": true }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hypothalamic Area, Lateral", "descriptor_ui": "D007026", "major_topic": true }, { "descriptor": "Hypothalamic Hormones", "descriptor_ui": "D007028", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Melanins", "descriptor_ui": "D008543", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": true }, { "descriptor": "Orexins", "descriptor_ui": "D000068797", "major_topic": false }, { "descriptor": "Pituitary Hormones", "descriptor_ui": "D010907", "major_topic": false }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Dec 2", "date_precision": "day", "issue": "", "normalized_date": "2024-12-02", "pages": "e0351242024", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Neuropeptidergic input from the lateral hypothalamus to the suprachiasmatic nucleus alters the circadian period in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "With advancements in human induced pluripotent stem cell (hiPSC) technology, there is an increasing demand for quality control techniques to manage the long-term process of target cell production effectively. While monitoring systems designed for use within incubators are promising for assessing culture quality, existing systems still face challenges in terms of compactness, throughput, and available metrics. To address these limitations, we have developed a compact and high-throughput lens-free imaging device named INSPCTOR. The device is as small as a standard culture plate, which allows for the installation of multiple units within an incubator. INSPCTOR utilises a large thin-film transistor image sensor, enabling simultaneous observation of six independent culture environments, each approximately 1 cm2. With this device, we successfully monitored the confluency of hiPSC cultures and identified the onset timing of epithelial-to-mesenchymal transition during mesodermal induction. Additionally, we quantified the beating frequency and conduction of hiPSC-derived cardiomyocytes by using high-speed imaging modes. This enabled us to identify the onset of spontaneous beating during differentiation and assess chronotropic responses in drug evaluations. Moreover, by tracking beating frequency over 10 days of cardiomyocyte maturation, we identified week-scale and daily-scale fluctuations, the latter of which correlated with cellular metabolic activity. The metrics derived from this device would enhance the reproducibility and quality of target cell production.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taishi", "last_name": "Kakizuka", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Natsume", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d4lc00528g" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39436381" } }, "mesh": [ { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": true }, { "descriptor": "Transistors, Electronic", "descriptor_ui": "D014173", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024-12", "date_precision": "month", "issue": "24", "normalized_date": "2024-12", "pages": "5290-5303", "proceedings_title": null, "publisher": "", "title": "Lab on a Chip", "volume": "24", "year": 2024 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000364" ] }, "title": "Compact lens-free imager using a thin-film transistor for long-term quantitative monitoring of stem cell culture and cardiomyocyte production", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chondroitin extends lifespan and healthspan in C. elegans, but the relationship between extracellular chondroitin and intracellular anti-aging mechanisms is unknown. The basement membrane (BM) that contains chondroitin proteoglycans is anchored to cells via hemidesmosomes (HDs), and it accumulates damage with aging. In this study, we found that chondroitin regulates aging through the formation of HDs and inhibition of tubular lysosomes (TLs). Reduction of chondroitin due to a mutation in sqv-5/Chondroitin synthase (ChSy) causes the earlier and excessive formation of TLs and leakage of the lysosomal nuclease in a manner dependent on VHA-7, the a-subunit of V-type ATPase. VHA-7, whose mutation suppresses the short lifespan of the sqv-5 mutant, is initially localized to the basal side of the hypodermal cells and transported to lysosomes with aging. These results demonstrate that endogenous chondroitin suppresses aging by inhibiting the earlier excessive formation of TLs. This is a novel anti-aging mechanism that is controlled by the BM.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yukimasa", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Kaito", "last_name": "Mitsuzumi", "name": null }, { "creator_type": "author", "first_name": "Shion", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Sasakura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Morioka", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sugioka", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Kiyoji", "last_name": "Nishiwaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-024-80242-3" }, "pmcid": { "normalized": "PMC11605119" }, "pmid": { "normalized": "39609482" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basement Membrane", "descriptor_ui": "D001485", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": true }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": true }, { "descriptor": "Chondroitin", "descriptor_ui": "D002807", "major_topic": true }, { "descriptor": "Longevity", "descriptor_ui": "D008136", "major_topic": true }, { "descriptor": "Lysosomes", "descriptor_ui": "D008247", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Nov 29", "date_precision": "day", "issue": "1", "normalized_date": "2024-11-29", "pages": "29651", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "14", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Endogenous chondroitin extends lifespan by inhibiting VHA-7-mediated tubular lysosome formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Progenitor cells initiate development upon receiving key signals, dynamically altering gene and protein expression to diverge into various lineages and fates. Despite the use of several experimental approaches, including the Fluorescent Timer-based method Timer-of-cell-kinetics-and-activity (Tocky), analysing time-dependent processes at the single-cell level in vivo remains challenging. This study introduces a novel integrated experimental and computational approach, using an advanced multidimensional toolkit. This toolkit facilitates the simultaneous examination of temporal progression and T-cell profiles using high-dimensional flow cytometric data. Employing novel algorithms based on Canonical Correspondence Analysis (CCA) and network analysis, our toolkit identifies developmental trajectories and analyses dynamic changes in developing cells. The efficacy of this approach is demonstrated through analysing thymic T-cells from Nr4a3-Tocky mice, which monitor activities downstream of the T-cell receptor (TCR) signal. Further validation was achieved by deleting the proapoptotic gene Bcl2l11 (Bim) in Nr4a3-Tocky mice. This revealed dynamic changes in thymic T-cells during cellular development and negative selection following TCR signalling. Overall, this study establishes a new method for analysing the temporal dynamics of individual developing cells in response to in vivo signalling cues.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Tessa", "last_name": "Crompton", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.204255" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39611743" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": true }, { "descriptor": "Thymus Gland", "descriptor_ui": "D013950", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Nov 29", "date_precision": "day", "issue": "", "normalized_date": "2024-11-29", "pages": "dev.204255", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "A multidimensional toolkit for elucidating temporal trajectories in cell development in vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human pluripotent stem cell-derived kidney organoids are expected to be a useful tool for new drug discoveries, however, the immaturation of kidney organoids causes difficulties in recapitulating renal pharmacokinetics using organoids. Here, we performed time-course single-cell RNA sequencing of kidney organoids and revealed cell heterogeneity in the maturation rate of the proximal tubule. An unbiased analysis to identify upstream targets of genes that are expressed differentially between cells with low and high maturation rates revealed a higher activation of PPARalpha signaling in rapidly maturing cells. Treatment with a combination of a PPARalpha agonist and an RXRalpha agonist induced genes related to proximal tubule maturation and increased the capacity for protein uptake as well as the sensitivity to nephrotoxicity by cisplatin. This method to promote the maturation rate of proximal tubule cells has the potential to be utilized in microphysiological systems to recapitulate proximal tubule functions and to screen nephrotoxic drugs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kuniyoshi", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-024-07069-6" }, "pmcid": { "normalized": "PMC11603349" }, "pmid": { "normalized": "39604738" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kidney Tubules, Proximal", "descriptor_ui": "D007687", "major_topic": true }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": true }, { "descriptor": "PPAR alpha", "descriptor_ui": "D047493", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Nov 27", "date_precision": "day", "issue": "1", "normalized_date": "2024-11-27", "pages": "1532", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "7", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Proximal tubule cell maturation rate and function are controlled by PPARalpha signaling in kidney organoids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The process of antibody purification using Fc affinity ligands such as protein A, G, and L faces several challenges including high cost, low stability, and loss of antibody activity due to harsh elution conditions. Here, we describe a chromatographic purification of antibodies utilizing a pH-responsive mixed-charge polymer that mimics the IgG-binding peptide (Z34C) derived from the B domain of protein A. The protein A mimetic resins were prepared by modifying the surface of a TOYOPEARL, methacrylate resin with a polymer that mimics the amino acid sequence of Z34C and the functions of histidine and acidic and neutral amino acids using histamine methacrylamide (HisMA), methacrylic acid, and neutral monomers. The therapeutic monoclonal antibody (mAb), rituximab, was retained on the column at pH 7 and eluted under mildly acidic conditions at pH 5 using a protein A mimetic resin (HisMA20-EEMA) optimized for antibody interaction. The injected antibodies were selectively captured on the column by hydrophobic and electrostatic interactions with the protein A mimetic polymer under neutral conditions and eluted by electrostatic repulsion under acidic conditions. The HisMA20-EEMA column successfully purified mAbs from mixtures with BSA, mouse ascites fluid, and hybridoma cell culture supernatant. In addition, the HisMA20-EEMA column consistently achieved 90% antibody recovery in 100 consecutive purifications from cell culture supernatant. The antibody purification method presented in this study is low cost, highly durable, easy to synthesize, and allows for mild elution conditions. The results demonstrate that the approach of mimicking IgG-binding peptides with mixed-charge polymers is useful for the development of column packing materials for antibody purification.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koichi", "last_name": "Deura", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Sakama", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Moriwaki", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsami.4c16861" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39588642" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Immunoglobulin G", "descriptor_ui": "D007074", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Peptidomimetics", "descriptor_ui": "D057786", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Rituximab", "descriptor_ui": "D000069283", "major_topic": false }, { "descriptor": "Staphylococcal Protein A", "descriptor_ui": "D013205", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Nov 26", "date_precision": "day", "issue": "", "normalized_date": "2024-11-26", "pages": "", "proceedings_title": null, "publisher": "", "title": "ACS applied materials & interfaces", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "IgG-Binding Peptidomimetic Mixed-Charge Polymer-Modified Resins for Chromatographic Purification of Antibodies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: For biochemical recurrence following radical prostatectomy for prostate cancer, treatments such as radiation therapy and androgen deprivation therapy are administered. To diagnose postoperative recurrence as early as possible and to intervene with treatment at the appropriate time, it is essential to accurately predict recurrence after radical prostatectomy. However, postoperative recurrence involves numerous patient-related factors, making its prediction challenging. The purpose of this study is to accurately predict the timing of biochemical recurrence after radical prostatectomy and to analyze the risk factors for follow-up of high-risk patients and early detection of recurrence. METHODS: We utilized the machine learning survival analysis model called the Random Survival Forest utilizing the 58 clinical factors from 548 patients who underwent radical prostatectomy at Chiba University Hospital. To visualize prognostic factors and assess accuracy of the time course probability, we employed SurvSHAP(t) and time-dependent Area Under Cureve(AUC). RESULTS: The time-dependent AUC of RSF was 0.785, which outperformed the Cox proportional hazards model (0.704), the Cancer of the Prostate Risk Assessment (CAPRA) score (0.710), and the D'Amico score (0.658). The key prognostic factors for early recurrence were Gleason score(GS), Seminal vesicle invasion(SV), and PSA. The contribution of PSA to recurrence decreases after the first year, while SV and GS increase over time. CONCLUSION: Our prognostic model analyzed the time-dependent relationship between the timing of recurrence and prognostic factors. Our study achieved personalized prognosis analysis and its rationale after radical prostatectomy by employing machine learning prognostic model. This prognostic model contributes to the early detection of recurrence by enabling clinicians to conduct appropriate follow-ups for high-risk patients.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kodai", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yasutaka", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Nobuyoshi", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Sazuka", "last_name": "Tomokazu", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12885-024-13203-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39587521" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Grading", "descriptor_ui": "D060787", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": true }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Prostate-Specific Antigen", "descriptor_ui": "D017430", "major_topic": true }, { "descriptor": "Prostatectomy", "descriptor_ui": "D011468", "major_topic": true }, { "descriptor": "Prostatic Neoplasms", "descriptor_ui": "D011471", "major_topic": true }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Nov 25", "date_precision": "day", "issue": "1", "normalized_date": "2024-11-25", "pages": "1446", "proceedings_title": null, "publisher": "", "title": "BMC cancer", "volume": "24", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Time-dependent personalized prognostic analysis by machine learning in biochemical recurrence after radical prostatectomy: a retrospective cohort study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although Green Fluorescent Protein (GFP) is useful and most widely used, steric hindrance due to its size and the time required for chromophore formation are complications. However, it is difficult to form chromophores with peptides to reduce the molecular weight. Therefore, we focused on peptides that can become fluorescent by binding to dyes. In this study, a novel dye-fluorescence-enhancing peptide aptamer was selected by the cDNA display method, which was confirmed by the yeast surface display method. This peptide aptamer binds to the non-fluorescent dye QSY(R)9 and enhances its fluorescence by preventing rotation of its benzene sulfone group. The method described in this paper should enable the development of new cell imaging methods using non-fluorescent dyes and peptides.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Ouchi", "name": null }, { "creator_type": "author", "first_name": "Nayab", "last_name": "Khaliq", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Mitsuyoshi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Nemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ab.2024.115722" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39581337" } }, "mesh": [ { "descriptor": "Aptamers, Peptide", "descriptor_ui": "D052158", "major_topic": true }, { "descriptor": "DNA, Complementary", "descriptor_ui": "D018076", "major_topic": true }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Nov 22", "date_precision": "day", "issue": "", "normalized_date": "2024-11-22", "pages": "115722", "proceedings_title": null, "publisher": "", "title": "Analytical biochemistry", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "In vitro selection of dye-fluorescence-enhancing peptide aptamer by cDNA display.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent advances in RNA analysis have deepened our understanding of cellular states in biological tissues. However, a substantial gap remains in integrating RNA expression data with spatial context across organs, primarily owing to the challenges associated with RNA detection within intact tissue volumes. Here, we developed Tris buffer-mediated retention of in situ hybridization chain reaction signal in cleared organs (TRISCO), an effective tissue-clearing method designed for whole-brain spatial three-dimensional (3D) RNA imaging. TRISCO resolved several crucial issues, including the preservation of RNA integrity, achieving uniform RNA labeling, and enhancing tissue transparency. We tested TRISCO using a broad range of cell-identity markers, noncoding and activity-dependent RNAs, within diverse organs of varying sizes and species. TRISCO thus emerges as a powerful tool for single-cell, whole-brain, 3D imaging that enables comprehensive transcriptional spatial analysis across the entire brain.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shigeaki", "last_name": "Kanatani", "name": null }, { "creator_type": "author", "first_name": "Judith C.", "last_name": "Kreutzmann", "name": null }, { "creator_type": "author", "first_name": "Yue", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Zoe", "last_name": "West", "name": null }, { "creator_type": "author", "first_name": "Lea Lydolph", "last_name": "Larsen", "name": null }, { "creator_type": "author", "first_name": "Danai Vougesi", "last_name": "Nikou", "name": null }, { "creator_type": "author", "first_name": "Ilse", "last_name": "Eidhof", "name": null }, { "creator_type": "author", "first_name": "Abigail", "last_name": "Walton", "name": null }, { "creator_type": "author", "first_name": "Songbai", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Leslie Rubio", "last_name": "Rodriguez-Kirby", "name": null }, { "creator_type": "author", "first_name": "Jacob Lercke", "last_name": "Skytte", "name": null }, { "creator_type": "author", "first_name": "Casper Gravesen", "last_name": "Salinas", "name": null }, { "creator_type": "author", "first_name": "Kimiharu", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Xiaofei", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Daisuke H.", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Dagmara", "last_name": "Kaczynska", "name": null }, { "creator_type": "author", "first_name": "Keishiro", "last_name": "Fukumoto", "name": null }, { "creator_type": "author", "first_name": "Razieh", "last_name": "Karamzadeh", "name": null }, { "creator_type": "author", "first_name": "Yujiao", "last_name": "Xiang", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Mikael", "last_name": "Adner", "name": null }, { "creator_type": "author", "first_name": "Johan", "last_name": "Hartman", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Miyakawa", "name": null }, { "creator_type": "author", "first_name": "Erik", "last_name": "Sundstrom", "name": null }, { "creator_type": "author", "first_name": "Goncalo", "last_name": "Castelo-Branco", "name": null }, { "creator_type": "author", "first_name": "Urmas", "last_name": "Roostalu", "name": null }, { "creator_type": "author", "first_name": "Jacob", "last_name": "Hecksher-Sorensen", "name": null }, { "creator_type": "author", "first_name": "Per", "last_name": "Uhlen", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.adn9947" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39571016" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": true }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": true }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": true }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Nov 22", "date_precision": "day", "issue": "6724", "normalized_date": "2024-11-22", "pages": "907-915", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "386", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Whole-brain spatial transcriptional analysis at cellular resolution.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "T follicular helper (Tfh) cells abundantly express the immunoreceptor programmed cell death protein 1 (PD-1), and the impact of PD-1 deficiency on antibody (Ab)-mediated immunity in mice is associated with compromised Tfh cell functions. Here, we revisited the role of the PD-1-PD-L1 axis on Ab-mediated immunity. Individuals with inherited PD-1 or PD-L1 deficiency had fewer memory B cells and impaired Ab responses, similar to Pdcd1(-/-) and Cd274(-/-)Pdcd1lg2(-/-) mice. PD-1, PD-L1, or both could be detected on the surface of human naive B cells following in vitro activation. PD-1- or PD-L1-deficient B cells had reduced expression of the transcriptional regulator c-Myc and c-Myc-target genes in vivo, and PD-1 deficiency or neutralization of PD-1 or PD-L1 impeded c-Myc expression and Ab production in human B cells isolated in vitro. Furthermore, B cell-specific deletion of Pdcd1 prevented the physiological accumulation of memory B cells in mice. Thus, PD-1 shapes optimal B cell memory and Ab-mediated immunity through B cell-intrinsic and B cell-extrinsic mechanisms, suggesting that B cell dysregulation contributes to infectious and autoimmune complications following anti-PD-1-PD-L1 immunotherapy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masato", "last_name": "Ogishi", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kitaoka", "name": null }, { "creator_type": "author", "first_name": "Kim L.", "last_name": "Good-Jacobson", "name": null }, { "creator_type": "author", "first_name": "Darawan", "last_name": "Rinchai", "name": null }, { "creator_type": "author", "first_name": "Baihao", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Vincent", "last_name": "Gies", "name": null }, { "creator_type": "author", "first_name": "Geetha", "last_name": "Rao", "name": null }, { "creator_type": "author", "first_name": "Tina", "last_name": "Nguyen", "name": null }, { "creator_type": "author", "first_name": "Danielle T.", "last_name": "Avery", "name": null }, { "creator_type": "author", "first_name": "Taushif", "last_name": "Khan", "name": null }, { "creator_type": "author", "first_name": "Megan E.", "last_name": "Smithmyer", "name": null }, { "creator_type": "author", "first_name": "Joseph", "last_name": "Mackie", "name": null }, { "creator_type": "author", "first_name": "Rui", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Andres Augusto", "last_name": "Arias", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Khoren", "last_name": "Ponsin", "name": null }, { "creator_type": "author", "first_name": "Matthieu", "last_name": "Chaldebas", "name": null }, { "creator_type": "author", "first_name": "Peng", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Jessica N.", "last_name": "Peel", "name": null }, { "creator_type": "author", "first_name": "Jonathan", "last_name": "Bohlen", "name": null }, { "creator_type": "author", "first_name": "Romain", "last_name": "Levy", "name": null }, { "creator_type": "author", "first_name": "Simon J.", "last_name": "Pelham", "name": null }, { "creator_type": "author", "first_name": "Wei-Te", "last_name": "Lei", "name": null }, { "creator_type": "author", "first_name": "Ji Eun", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Iris", "last_name": "Fagniez", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Chrabieh", "name": null }, { "creator_type": "author", "first_name": "Candice", "last_name": "Laine", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Langlais", "name": null }, { "creator_type": "author", "first_name": "Conor", "last_name": "Gruber", "name": null }, { "creator_type": "author", "first_name": "Fatima", "last_name": "Al Ali", "name": null }, { "creator_type": "author", "first_name": "Mahbuba", "last_name": "Rahman", "name": null }, { "creator_type": "author", "first_name": "Caner", "last_name": "Aytekin", "name": null }, { "creator_type": "author", "first_name": "Basilin", "last_name": "Benson", "name": null }, { "creator_type": "author", "first_name": "Matthew J.", "last_name": "Dufort", "name": null }, { "creator_type": "author", "first_name": "Clara", "last_name": "Domingo-Vila", "name": null }, { "creator_type": "author", "first_name": "Kunihiko", "last_name": "Moriya", "name": null }, { "creator_type": "author", "first_name": "Mark", "last_name": "Shlomchik", "name": null }, { "creator_type": "author", "first_name": "Gulbu", "last_name": "Uzel", "name": null }, { "creator_type": "author", "first_name": "Paul E.", "last_name": "Gray", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Suan", "name": null }, { "creator_type": "author", "first_name": "Kahn", "last_name": "Preece", "name": null }, { "creator_type": "author", "first_name": "Ignatius", "last_name": "Chua", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyonari", "name": null }, { "creator_type": "author", "first_name": "Timothy I.", "last_name": "Tree", "name": null }, { "creator_type": "author", "first_name": "Dusan", "last_name": "Bogunovic", "name": null }, { "creator_type": "author", "first_name": "Philippe", "last_name": "Gros", "name": null }, { "creator_type": "author", "first_name": "Nico", "last_name": "Marr", "name": null }, { "creator_type": "author", "first_name": "Cate", "last_name": "Speake", "name": null }, { "creator_type": "author", "first_name": "Richard A.", "last_name": "Oram", "name": null }, { "creator_type": "author", "first_name": "Vivien", "last_name": "Beziat", "name": null }, { "creator_type": "author", "first_name": "Jacinta", "last_name": "Bustamante", "name": null }, { "creator_type": "author", "first_name": "Laurent", "last_name": "Abel", "name": null }, { "creator_type": "author", "first_name": "Bertrand", "last_name": "Boisson", "name": null }, { "creator_type": "author", "first_name": "Anne-Sophie", "last_name": "Korganow", "name": null }, { "creator_type": "author", "first_name": "Cindy S.", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Matthew B.", "last_name": "Johnson", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Chamoto", "name": null }, { "creator_type": "author", "first_name": "Stephanie", "last_name": "Boisson-Dupuis", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Honjo", "name": null }, { "creator_type": "author", "first_name": "Jean-Laurent", "last_name": "Casanova", "name": null }, { "creator_type": "author", "first_name": "Stuart G.", "last_name": "Tangye", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.immuni.2024.10.014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39603236" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibody Formation", "descriptor_ui": "D000917", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Memory B Cells", "descriptor_ui": "D000091245", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": true }, { "descriptor": "Programmed Cell Death 1 Ligand 2 Protein", "descriptor_ui": "D061027", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": true }, { "descriptor": "Proto-Oncogene Proteins c-myc", "descriptor_ui": "D016271", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "T Follicular Helper Cells", "descriptor_ui": "D000084522", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Nov 22", "date_precision": "day", "issue": "", "normalized_date": "2024-11-22", "pages": "S1074-7613(24)00495-3", "proceedings_title": null, "publisher": "", "title": "Immunity", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Impaired development of memory B cells and antibody responses in humans and mice deficient in PD-1 signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Neutropenia can easily progress to febrile neutropenia and is a risk factor for life-threatening infections. Predicting and preventing severe neutropenia can help avoid such infections. AIM: This study aimed to develop an optimal model using advanced statistical methods to predict neutropenia after 5-fluorouracil/cisplatin chemotherapy for esophageal cancer and to create a nomogram for clinical application. METHOD: Patients who received 5-fluorouracil/cisplatin chemotherapy at Chiba University Hospital, Japan, between January 2011 and March 2021 were included. Clinical parameters were measured before the first, second, and third chemotherapy cycles and were randomly divided by patient into a training cohort (60%) and test cohort (40%). The predictive performance of Logistic, Stepwise, Lasso, and GLMMLasso models was evaluated by the area under the receiver-operating characteristic curve (AUC). A nomogram based on GLMMLasso was developed, and the accuracy of probabilistic predictions was evaluated by the Brier score. RESULTS: The AUC for the first cycle of chemotherapy was 0.781 for GLMMLasso, 0.751 for Lasso, 0.697 for Stepwise, and 0.669 for Logistic. The respective AUCs for GLMMLasso in the second and third cycles were 0.704 and 0.900. The variables selected by GLMMLasso were cisplatin dose, 5-fluorouracil dose, use of leucovorin, sex, cholinesterase, and platelets. A nomogram predicting neutropenia was created based on each regression coefficient. The Brier score for the nomogram was 0.139. CONCLUSION: We have developed a predictive model with high performance using GLMMLasso. Our nomogram can represent risk visually and may facilitate the assessment of the probability of chemotherapy-induced severe neutropenia in clinical practice.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shuhei", "last_name": "Sugaya", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Itsuko", "last_name": "Ishii", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s11096-024-01836-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39570570" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": true }, { "descriptor": "Cisplatin", "descriptor_ui": "D002945", "major_topic": false }, { "descriptor": "Esophageal Neoplasms", "descriptor_ui": "D004938", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorouracil", "descriptor_ui": "D005472", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neutropenia", "descriptor_ui": "D009503", "major_topic": true }, { "descriptor": "Nomograms", "descriptor_ui": "D049451", "major_topic": true }, { "descriptor": "Predictive Value of Tests", "descriptor_ui": "D011237", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Nov 21", "date_precision": "day", "issue": "", "normalized_date": "2024-11-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of clinical pharmacy", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a robust predictive model for neutropenia after esophageal cancer chemotherapy using GLMMLasso.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND HYPOTHESIS: Activated macrophages, pivotal for driving the immune response in sepsis, express high levels of CD38. Although the circulating levels of its ligand, CD31, increase in sepsis, the functions of CD38 and its ligation remain elusive. This study aimed to elucidate the impact of CD38 ligation on sepsis using single-cell and single-nucleus RNA sequencing (scRNA-seq and snRNA-seq, respectively) to identify a novel therapeutic target for severe sepsis. METHODS: We performed scRNA-seq analysis of mouse peritoneal immune cells to precisely identify cell types exhibiting increased CD38 expression upon exposure to lipopolysaccharide (LPS). Subsequently, we induced CD38 ligation using a well-established agonistic anti-CD38 antibody in a mouse model of LPS-induced sepsis. We analyzed its pathophysiological effects using kidney snRNA-seq. Finally, we performed histological analysis of septic tissues collected from patients to ensure consistency of our findings between mice and humans. RESULTS: LPS stimulation upregulated CD38 expression in peritoneal macrophages. CD38 ligation significantly exacerbated LPS-induced inflammation in vivo, particularly in the kidneys. Kidney snRNA-seq analysis revealed that CD38 ligation induced interleukin (IL)-6 production in renal stromal cells via nicotinamide phosphoribosyltransferase (NAMPT) signaling originating from CD38-positive macrophages. NAMPT inhibition significantly ameliorated LPS-induced IL-6 production and kidney injury. Histological analysis of human septic tissues demonstrated upregulation of IL6 mRNA and NAMPT in renal stromal cells and CD38-positive macrophages, respectively. CONCLUSION: Our findings elucidate the implications of CD38 ligation in an LPS-induced sepsis model and uncover shared signaling pathways between mice and human sepsis. NAMPT signaling identified in this study may be a novel therapeutic target for mitigating systemic inflammation and kidney injury associated with severe sepsis.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuya", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Otsuka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Alexey", "last_name": "Annenkov", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Riuko", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Ichiei", "last_name": "Narita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/ndt/gfae269" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39568061" } }, "mesh": [ { "descriptor": "ADP-ribosyl Cyclase 1", "descriptor_ui": "D051997", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interleukin-6", "descriptor_ui": "D015850", "major_topic": true }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": true }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Glycoproteins", "descriptor_ui": "D008562", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Nicotinamide Phosphoribosyltransferase", "descriptor_ui": "D054409", "major_topic": true }, { "descriptor": "Sepsis", "descriptor_ui": "D018805", "major_topic": true }, { "descriptor": "Stromal Cells", "descriptor_ui": "D017154", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Nov 20", "date_precision": "day", "issue": "", "normalized_date": "2024-11-20", "pages": "gfae269", "proceedings_title": null, "publisher": "", "title": "Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "CD38 ligation in sepsis promotes nicotinamide phosphoribosyltransferase-mediated IL-6 production in kidney stromal cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Small extracellular vesicles (sEVs) are important intercellular information transmitters in various biological contexts, but their release processes remain poorly understood. Herein, we describe a high-throughput assay platform, CRISPR-assisted individually barcoded sEV-based release regulator (CIBER) screening, for identifying key players in sEV release. CIBER screening employs sEVs barcoded with CRISPR-gRNA through the interaction of gRNA and dead Cas9 fused with an sEV marker. Barcode quantification enables the estimation of the sEV amount released from each cell in a massively parallel manner. Barcoding sEVs with different sEV markers in a CRISPR pooled-screening format allows genome-wide exploration of sEV release regulators in a subpopulation-specific manner, successfully identifying previously unknown sEV release regulators and uncovering the exosomal/ectosomal nature of CD63(+)/CD9(+) sEVs, respectively, as well as the synchronization of CD9(+) sEV release with the cell cycle. CIBER should be a valuable tool for detailed studies on the biogenesis, release, and heterogeneity of sEVs.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koki", "last_name": "Kunitake", "name": null }, { "creator_type": "author", "first_name": "Tadahaya", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Chitose", "last_name": "Oneyama", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kojima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-53736-x" }, "pmcid": { "normalized": "PMC11577021" }, "pmid": { "normalized": "39562573" } }, "mesh": [ { "descriptor": "Clustered Regularly Interspaced Short Palindromic Repeats", "descriptor_ui": "D064112", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": true }, { "descriptor": "Exosomes", "descriptor_ui": "D055354", "major_topic": false }, { "descriptor": "Extracellular Vesicles", "descriptor_ui": "D000067128", "major_topic": true }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "RNA, Guide, CRISPR-Cas Systems", "descriptor_ui": "D000094704", "major_topic": true }, { "descriptor": "Tetraspanin 29", "descriptor_ui": "D060245", "major_topic": true }, { "descriptor": "Tetraspanin 30", "descriptor_ui": "D060149", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Nov 19", "date_precision": "day", "issue": "1", "normalized_date": "2024-11-19", "pages": "9777", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Barcoding of small extracellular vesicles with CRISPR-gRNA enables comprehensive, subpopulation-specific analysis of their biogenesis and release regulators.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bacterial cancer therapy (BCT) is a promising therapeutic for solid tumours. Salmonella enterica Typhimurium (STm) is well-studied amongst bacterial vectors due to advantages in genetic modification and metabolic adaptation. A longstanding paradox is the redundancy of T cells for treatment efficacy; instead, STm BCT depends on innate phagocytes for tumour control. Here, we used distal T cell receptor (TCR) and IFNgamma reporter mice (Nr4a3-Tocky-Ifngamma-YFP) and a colorectal cancer (CRC) model to interrogate T cell activity during BCT with attenuated STm. We found that colonic tumour infiltrating lymphocytes (TILs) exhibited a variety of activation defects, including IFN-gamma production decoupled from TCR signalling, decreased polyfunctionality and reduced central memory (T(CM)) formation. Modelling of T-cell-tumour interactions with a tumour organoid platform revealed an intact TCR signalosome, but paralysed metabolic reprogramming due to inhibition of the master metabolic controller, c-Myc. Restoration of c-Myc by deletion of the bacterial asparaginase ansB reinvigorated T cell activation, but at the cost of decreased metabolic control of the tumour by STm. This work shows for the first time that T cells are metabolically defective during BCT, but also that this same phenomenon is inexorably tied to intrinsic tumour suppression by the bacterial vector.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Alastair", "last_name": "Copland", "name": null }, { "creator_type": "author", "first_name": "Gillian M.", "last_name": "Mackie", "name": null }, { "creator_type": "author", "first_name": "Lisa", "last_name": "Scarfe", "name": null }, { "creator_type": "author", "first_name": "Elizabeth", "last_name": "Jinks", "name": null }, { "creator_type": "author", "first_name": "David A. J.", "last_name": "Lecky", "name": null }, { "creator_type": "author", "first_name": "Nancy", "last_name": "Gudgeon", "name": null }, { "creator_type": "author", "first_name": "Riahne", "last_name": "McQuade", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Manja", "last_name": "Barthel", "name": null }, { "creator_type": "author", "first_name": "Wolf-Dietrich", "last_name": "Hardt", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Wilma H. M.", "last_name": "Hoevenaar", "name": null }, { "creator_type": "author", "first_name": "Sarah", "last_name": "Dimeloe", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Bending", "name": null }, { "creator_type": "author", "first_name": "Kendle M.", "last_name": "Maslowski", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s44321-024-00159-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39558103" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Interferon-gamma", "descriptor_ui": "D007371", "major_topic": false }, { "descriptor": "Lymphocytes, Tumor-Infiltrating", "descriptor_ui": "D016246", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false }, { "descriptor": "Salmonella typhimurium", "descriptor_ui": "D012486", "major_topic": true }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Nov 18", "date_precision": "day", "issue": "", "normalized_date": "2024-11-18", "pages": "", "proceedings_title": null, "publisher": "", "title": "EMBO molecular medicine", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Salmonella cancer therapy metabolically disrupts tumours at the collateral cost of T cell immunity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Atopic dermatitis (AD) is characterized by chronic inflammation, barrier dysfunction, and pruritus, exacerbated by external stimuli, such as scratching. This study investigates the role of extracellular adenosine triphosphate (ATP) in the pathophysiology of AD and assesses the therapeutic potential of clodronate, an ATP release inhibitor. Our research demonstrates that extracellular ATP impairs skin barrier function by reducing the filaggrin expression in the keratinocytes, a critical protein for barrier integrity. Furthermore, ATP release, triggered by IL-4 and mechanical stimuli, amplifies inflammation by promoting cytokine and chemokine production by the immune cells. Clodronate, by inhibiting ATP release, restores the filaggrin levels in the keratinocytes, reduces TARC production in the dendritic cells, and alleviates AD symptoms in a mouse model. These findings suggest that targeting extracellular ATP could offer a novel therapeutic approach to improving skin barrier function and reducing inflammation in AD. Future studies should explore the long-term efficacy and safety of ATP-targeted therapies in clinical settings.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Shu", "last_name": "Yotsumoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Nanae", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Kiichiro", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Ichiki", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Kuba-Fuyuno", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Fujishima", "name": null }, { "creator_type": "author", "first_name": "Takamichi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Kido-Nakahara", "name": null }, { "creator_type": "author", "first_name": "Gaku", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nakahara", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms252212294" }, "pmcid": { "normalized": "PMC11595171" }, "pmid": { "normalized": "39596359" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": true }, { "descriptor": "Administration, Topical", "descriptor_ui": "D000287", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Dermatitis, Atopic", "descriptor_ui": "D003876", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Filaggrin Proteins", "descriptor_ui": "D000091344", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": true }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Nov 15", "date_precision": "day", "issue": "22", "normalized_date": "2024-11-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "25", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Extracellular ATP Contributes to Barrier Function and Inflammation in Atopic Dermatitis: Potential for Topical Treatment of Atopic Dermatitis by Targeting Extracellular ATP.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Myofibers are broadly classified as slow-twitch (Type I) and fast-twitch (Type II) fibers. These two types of myofibers coexist within the same skeletal muscle tissue, determining the contractile and metabolic properties of skeletal muscle tissue by fiber type distribution. METHODS AND RESULTS: By examining each fiber type separately, we confirmed that brain-derived neurotrophic factor (BDNF) gene is highly expressed in Type I fibers. When exposed to BDNF, primary myotubes exhibited reduced expression of Myosin Heavy Chain (MyHC) II, a marker protein characteristic of Type II fibers. BDNF overexpression in regenerating muscle tissue led to a decrease in the distribution of Type IIA fibers. CONCLUSIONS: We suggest that BDNF highly expressed in Type I fibers downregulates MyHC II expression in myotubes, eventually inhibiting Type IIA fiber generation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Teng", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Yasuro", "last_name": "Furuichi", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Manabe", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Katakura", "name": null }, { "creator_type": "author", "first_name": "Yuna", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Kun", "last_name": "Tang", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Nobuharu L.", "last_name": "Fujii", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s11033-024-10044-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39531063" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain-Derived Neurotrophic Factor", "descriptor_ui": "D019208", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle Fibers, Fast-Twitch", "descriptor_ui": "D018656", "major_topic": true }, { "descriptor": "Muscle Fibers, Skeletal", "descriptor_ui": "D018485", "major_topic": false }, { "descriptor": "Muscle Fibers, Slow-Twitch", "descriptor_ui": "D018657", "major_topic": true }, { "descriptor": "Myokines", "descriptor_ui": "D000097724", "major_topic": false }, { "descriptor": "Myosin Heavy Chains", "descriptor_ui": "D018995", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Nov 12", "date_precision": "day", "issue": "1", "normalized_date": "2024-11-12", "pages": "1143", "proceedings_title": null, "publisher": "", "title": "Molecular biology reports", "volume": "51", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Myokine BDNF highly expressed in Type I fibers inhibits the differentiation of myotubes into Type II fibers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Anionic lipid molecules, including phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)), are implicated in the regulation of epidermal growth factor receptor (EGFR). However, the role of the spatiotemporal dynamics of PI(4,5)P(2) in the regulation of EGFR activity in living cells is not fully understood, as it is difficult to visualize the local lipid domains around EGFR. Here, we visualized both EGFR and PI(4,5)P(2) nanodomains in the plasma membrane of HeLa cells using super-resolution single-molecule microscopy. The EGFR and PI(4,5)P(2) nanodomains aggregated before stimulation with epidermal growth factor (EGF) through transient visits of EGFR to the PI(4,5)P(2) nanodomains. The degree of coaggregation decreased after EGF stimulation and depended on phospholipase Cgamma, the EGFR effector hydrolyzing PI(4,5)P(2). Artificial reduction in the PI(4,5)P(2) content of the plasma membrane reduced both the dimerization and autophosphorylation of EGFR after stimulation with EGF. Inhibition of PI(4,5)P(2) hydrolysis after EGF stimulation decreased phosphorylation of EGFR-Thr654. Thus, EGFR kinase activity and the density of PI(4,5)P(2) around EGFR molecules were found to be mutually regulated.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Yanagawa", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.101652" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39513999" } }, "mesh": [ { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": true }, { "descriptor": "Epidermal Growth Factor", "descriptor_ui": "D004815", "major_topic": true }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": true }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Phosphatidylinositol 4,5-Diphosphate", "descriptor_ui": "D019269", "major_topic": true }, { "descriptor": "Phospholipase C gamma", "descriptor_ui": "D051966", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Single Molecule Imaging", "descriptor_ui": "D000072760", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Nov 8", "date_precision": "day", "issue": "", "normalized_date": "2024-11-08", "pages": "e101652", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "13", "year": 2024 }, "ssbd": { "database": [ "ssbd-database-000459" ], "repository": [ "ssbd-repos-000459" ] }, "title": "Bilateral regulation of EGFR activity and local PI(4,5)P(2) dynamics in mammalian cells observed with superresolution microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ecological surveys of living things based on DNAs from environmental samples are attractive. However, despite simplicity of water sampling from the target environment, it is still necessary to transport the samples to the laboratory for DNA analysis based on skillful next-generation sequencers. To perform DNA-oriented surveys based on a simple protocol without any special training, we demonstrated, in this study, the detection of genes from cell-containing environmental waters using gene sensor arrays that require no DNA labeling and no external indicators. Cell-suspended PBS or river water were used as models of environmental waters containing living things, and DNA samples were prepared by PCR amplification. Ferrocene-terminated probes were synthesized and immobilized on an electrode array to develop a sensor array. The sensor array showed a large response to a target DNA complementary to the probe and no response to a mismatched DNA, indicating sequence-specific detection. For DNA samples prepared from the cells in PBS, they showed good responses similar to those for the target DNA. They also significantly detected DNA samples from the cells in river water at a general environmental concentration (38 cells mL(-1)) with 28-fold larger responses than those for 0 cells mL(-1).", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Kumakura", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kamo", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Siro", "last_name": "Simizu", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/s24227182" }, "pmcid": { "normalized": "PMC11598411" }, "pmid": { "normalized": "39598959" } }, "mesh": [ { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Electrochemical Techniques", "descriptor_ui": "D055664", "major_topic": true }, { "descriptor": "Electrodes", "descriptor_ui": "D004566", "major_topic": false }, { "descriptor": "Polymerase Chain Reaction", "descriptor_ui": "D016133", "major_topic": true }, { "descriptor": "Rivers", "descriptor_ui": "D045483", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Nov 8", "date_precision": "day", "issue": "22", "normalized_date": "2024-11-08", "pages": "", "proceedings_title": null, "publisher": "", "title": "Sensors (Basel, Switzerland)", "volume": "24", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Sensor Arrays for Electrochemical Detection of PCR-Amplified Genes Extracted from Cells Suspended in Environmental Waters.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The SPRED family proteins act as negative regulators of the Ras-ERK pathway: the N-terminal EVH1 domain interacts with the Ras-GAP domain (GRD) of the NF1 protein, while the C-terminal Sprouty-related (SPR) domain promotes membrane localization of SPRED, thereby recruiting NF-1 to Ras. Loss-of-function mutations in the hSPRED1 cause Legius syndrome in an autosomal dominant manner. In this study, we investigated the effects of missense mutations in the SPR domain identified in patients with Legius syndrome. Among 18 mutations we examined, six (C368S, M369L, V408E, P415A, P415L and P422R) have defects in the palmitoylation of the SPRED1 protein, losing plasma membrane localization and forming cytoplasmic granular aggregates. To evaluate the in vivo effects of SPR mutations, knock-in (KI) mice with P415A and P415V substitutions or M417Afs*4, a C-terminal 28 amino acid deletion, were generated. All these KI mice exhibited cranial malformations, a characteristic feature of Legius syndrome. However, both P415A and P415V mutants formed granular aggregates, whereas M417Afs*4 showed a diffuse cytoplasmic distribution, and Spred1(P415A) and Spred1(P415V) mice, but not Spred1(M417Afs *4) mice, developed cerebellar ataxia and Purkinje cell loss with age. These data suggest that in addition to loss of palmitoylation, the C-terminal region is required for the granular aggregate formation and Purkinje cell loss. The autophagy inducer spermidine rescued the ataxia phenotypes and Purkinje cell loss in Spred1(P415A) mice. These results suggest that some, but not all, SPR mutations that lose lipid modification induce abnormal cytoplasmic aggregation, which could be a target for autophagic clearance, and potentially cause neurodegenerative diseases.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuko", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Hilde", "last_name": "Brems", "name": null }, { "creator_type": "author", "first_name": "Seppe", "last_name": "Van der Auweraer", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Ohyagi", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Iizuka", "name": null }, { "creator_type": "author", "first_name": "Setsuko", "last_name": "Mise-Omata", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Ludwine", "last_name": "Messiaen", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Eric", "last_name": "Legius", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbc.2024.107969" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39510187" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cafe-au-Lait Spots", "descriptor_ui": "D019080", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": true }, { "descriptor": "Cerebellar Ataxia", "descriptor_ui": "D002524", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lipoylation", "descriptor_ui": "D054878", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutation, Missense", "descriptor_ui": "D020125", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Nov 5", "date_precision": "day", "issue": "", "normalized_date": "2024-11-05", "pages": "107969", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Legius Syndrome mutations in the Ras-regulator SPRED1 abolish its membrane localization and potentially cause neurodegeneration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "While epidemiological and experimental studies have demonstrated kidney-protective effects of estrogen and female sex in adulthood, some epidemiological data showed deterioration of kidney function during puberty when estrogen production increases. However, molecular mechanisms explaining these conflicting phenomena remain unknown. Here, we showed that the pubertal sex hormone surge in female mice increases susceptibility to kidney ischemia reperfusion injury partly via downregulation of insulin-like growth factor 1 receptor (IGF-1R) expression in proximal tubules. Adult mice ovariectomized pre-pubertally (at postnatal day 21) showed strong tolerance to kidney ischemia, which was partly reversed by the administration of 17beta-estradiol, while adult mice ovariectomized post-pubertally (at 8 weeks of age) were vulnerable to kidney ischemia. Kidney tubular IGF-1R protein expression decreased during postnatal growth but was highly expressed in adult mice ovariectomized pre-pubertally and in infant mice, which might be partly explained by different expression of an E3 ligase (MDM2) of IGF-1R. Mice deficient of Igf-1r in proximal tubules (iIGF-1RKO mice) during postnatal kidney growth showed increased susceptibility to ischemic injury. RNA-seq and western blotting analysis using proximal tubular cells from pre-pubertally ovariectomized iIGF-1RKO and control mice revealed altered expression of cell cycle-associated molecules such as cyclin D1. These results suggest that Igf-1r deletion during postnatal growth renders proximal tubular cells susceptible to ischemia possibly via altered cell cycle regulation. Thus, our findings provide evidence that exposure to pubertal sex hormones leads to increased susceptibility to kidney ischemia, which is partly mediated by modulation of IGF-1R signaling.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Kitai", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Toriu", "name": null }, { "creator_type": "author", "first_name": "Takahisa", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Sonoko", "last_name": "Kinjo", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Oguchi", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Eiichiro", "last_name": "Uchino", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Sasako", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Haga", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Fukuma", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kadowaki", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Murakawa", "name": null }, { "creator_type": "author", "first_name": "Motoko", "last_name": "Yanagita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.kint.2024.08.034" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39503698" } }, "mesh": [ { "descriptor": "Acute Kidney Injury", "descriptor_ui": "D058186", "major_topic": true }, { "descriptor": "Age Factors", "descriptor_ui": "D000367", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cyclin D1", "descriptor_ui": "D019938", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Disease Susceptibility", "descriptor_ui": "D004198", "major_topic": false }, { "descriptor": "Estradiol", "descriptor_ui": "D004958", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Kidney Tubules, Proximal", "descriptor_ui": "D007687", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": true }, { "descriptor": "Ovariectomy", "descriptor_ui": "D010052", "major_topic": false }, { "descriptor": "Receptor, IGF Type 1", "descriptor_ui": "D017526", "major_topic": true }, { "descriptor": "Reperfusion Injury", "descriptor_ui": "D015427", "major_topic": true }, { "descriptor": "Sex Factors", "descriptor_ui": "D012737", "major_topic": false }, { "descriptor": "Sexual Maturation", "descriptor_ui": "D012741", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Nov 1", "date_precision": "day", "issue": "", "normalized_date": "2024-11-01", "pages": "S0085-2538(24)00712-9", "proceedings_title": null, "publisher": "", "title": "Kidney international", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Female sex hormones inversely regulate acute kidney disease susceptibility throughout life.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "SSBD (https://ssbd.riken.jp) is a platform for the sharing and reuse of bioimaging data. As part of efforts to build a bioimaging data ecosystem, SSBD has recently been updated to a two-tiered data resource comprising SSBD:repository, a public repository for the sharing of all types of bioimaging data reported in journals, and SSBD:database, an added-value database for the sharing of curated, highly reusable, metadata-rich data. This update addresses the conflicting demands of rapid data publication and sharing of richly annotated data, thereby promoting bioimaging data sharing and reuse. With this update, SSBD is now positioned as a core repository and database within the foundingGIDE, an international consortium working to establish a global image data ecosystem. Harmonizing metadata between data resources enables cross-searching and data exchange with data resources from other countries and regions.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Itoga", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Fujisawa", "name": null }, { "creator_type": "author", "first_name": "Fangfang", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Miguel", "last_name": "Miranda-Miranda", "name": null }, { "creator_type": "author", "first_name": "Haruna", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasue", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Tohsato", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nar/gkae860" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39479781" } }, "mesh": [ { "descriptor": "Databases, Factual", "descriptor_ui": "D016208", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Information Dissemination", "descriptor_ui": "D033181", "major_topic": true }, { "descriptor": "Metadata", "descriptor_ui": "D000071253", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Oct 31", "date_precision": "day", "issue": "", "normalized_date": "2024-10-31", "pages": "gkae860", "proceedings_title": null, "publisher": "", "title": "Nucleic acids research", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "SSBD: an ecosystem for enhanced sharing and reuse of bioimaging data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The crustacean Daphnia magna is an emerging model for ecological and toxicological genomics. However, the lack of methods for spatial and temporal control of gene expression has impaired the elucidation of molecular mechanisms underlying responses to environments in vivo. Here we report local activation of the hsp70 promoter-driven gene cassette in D. magna by the infrared laser-evoked gene operator (IR-LEGO), a method for heating the target cells with infrared irradiation. We identified the heat-inducible promoter upstream of the D. magna hsp70-A gene. Using this promoter, we generated a transgenic Daphnia harboring the heat-shock responsive GFP reporter gene and confirmed that the GFP gene responds to heat treatment not only in juveniles and adults but also in embryos. We collected embryos from the reporter line and irradiated four different regions of interest in the embryos: a proximal region of the third thoracic segment, a part of the midline, a second maxilla, and a distal region of the endopodite of the second antenna, all of which increased GFP fluorescence with an infrared laser. Our results suggest that the IR-LEGO method is useful for spatial and temporal control of gene expression and would advance the functional genomics in D. magna.", "classifications": [ { "id": "19H05423", "label": "19H05423", "researcher": "Yasuhiko Kato", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Rina", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Joe", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Nikko", "last_name": "Adhitama", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Fujikawa", "name": null }, { "creator_type": "author", "first_name": "Pijar", "last_name": "Religia", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kamei", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-024-77458-8" }, "pmcid": { "normalized": "PMC11514169" }, "pmid": { "normalized": "39465323" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": true }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": true }, { "descriptor": "Daphnia magna", "descriptor_ui": "D000096602", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": true }, { "descriptor": "HSP70 Heat-Shock Proteins", "descriptor_ui": "D018840", "major_topic": true }, { "descriptor": "Infrared Rays", "descriptor_ui": "D007259", "major_topic": true }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": true }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": true }, { "descriptor": "Spatio-Temporal Analysis", "descriptor_ui": "D062211", "major_topic": false }, { "descriptor": "Transgenes", "descriptor_ui": "D019076", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Oct 28", "date_precision": "day", "issue": "1", "normalized_date": "2024-10-28", "pages": "25696", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "14", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatiotemporal control of transgene expression using an infrared laser in the crustacean Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alport syndrome (AS) is a hereditary disease caused by mutations in the COL4A5 gene and leads to chronic kidney disease. Currently, no specific treatment has been developed. However, a recent study using AS-model mice demonstrated that the exon skipping method could partially rescue the symptoms. In this study, we evaluated the effects of the exon skipping method using kidney organoids generated from AS-patient-derived induced pluripotent stem cells (AS-iPSCs). We generated kidney organoids from AS-iPSCs, which exhibited nephron structures. As expected, the C-terminus of COL4A5 was not expressed in AS-organoids. Interestingly, anti-sense oligonucleotides restored the expression of the C-terminus of COL4A5 in vitro. Next, we transplanted AS-organoids into mice and evaluated glomerular basement membrane formation in vivo. We found that AS-organoids formed a lower slit diaphragm ratio compared to control organoids. Finally, we assessed the effects of exon skipping on transplanted organoids but observed minimum effects. These studies suggest that AS-iPSCs can generate kidney organoids lacking the C-terminus of COL4A5, and that exon skipping can induce its expression in vitro.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kensuke", "last_name": "Yabuuchi", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Kandai", "last_name": "Nozu", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.13170" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39435529" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Collagen Type IV", "descriptor_ui": "D024141", "major_topic": true }, { "descriptor": "Exons", "descriptor_ui": "D005091", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nephritis, Hereditary", "descriptor_ui": "D009394", "major_topic": true }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Oct 22", "date_precision": "day", "issue": "", "normalized_date": "2024-10-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Investigation of exon skipping therapy in kidney organoids from Alport syndrome patients derived iPSCs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transition state theory (TST) provides a framework to estimate the rate of chemical reactions. Despite its great success with many reaction systems, the underlying assumptions such as local equilibrium and nonrecrossing do not necessarily hold in all cases. Although dynamical systems theory can provide the mathematical foundation of reaction tubes existing in phase space that enables us to predict the fate of reactions free from the assumptions of TST, numerical demonstrations for large systems have been yet one of the challenges. Here, we propose a dimensionality reduction algorithm to demonstrate structures in phase space (called reactive islands) that predict reactivity in systems with many degrees of freedom. The core of this method is the application of supervised principal component analysis, where a coordinate transformation is performed to preserve the dynamical information on reactivity (i.e., to which potential basin the system moves from a region of interest) as much as possible. The reactive island structures are expected to be reflected in the transformed, low-dimensional phase space. As an illustrative example, the algorithm is scrutinized using a modified Henon-Heiles Hamiltonian system extended to many degrees of freedom, which has three channels leading to three different products from one stable potential basin. It is shown that our algorithm can predict the reactivity in the transformed, low-dimensional coordinate system better than a naive coordinate system and that the reactivity distribution in the transformed low-dimensional space is considered to reflect the underlying reactive islands.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Mikito", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Taketsugu", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/5.0230618" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39404205" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Oct 21", "date_precision": "day", "issue": "15", "normalized_date": "2024-10-21", "pages": "154103", "proceedings_title": null, "publisher": "", "title": "The Journal of chemical physics", "volume": "161", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Low-dimensional projection of reactivity classes in chemical reaction dynamics using supervised dimensionality reduction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mammalian somatic cells are generally unstable in the haploid state, resulting in haploid-to-diploid conversion within a short time frame. However, cellular and molecular principles that limit the sustainability of somatic haploidy remain unknown. In this study, we found the haploidy-linked vulnerability to ER stress as a critical cause of haploid intolerance in human somatic cells. Pharmacological induction of ER stress selectively induced apoptosis in haploid cells, facilitating the replacement of haploids by co-existing diploidized cells in a caspase-dependent manner. Biochemical analyses revealed that unfolded protein response (UPR) was activated with similar dynamics between haploids and diploids upon ER stress induction. However, haploids were less efficient in solving proteotoxic stress, resulting in a bias toward a proapoptotic mode of UPR signaling. Artificial replenishment of chaperone function substantially alleviated the haploidy-linked upregulation of proapoptotic signaling and improved haploid cell retention under tunicamycin-induced ER stress. These data demonstrate that the ER stress-driven haploid instability stems from inefficient proteostatic control that alters the functionality of UPR to cause apoptosis selectively in haploids. Interestingly, haploids suffered a higher level of protein aggregation even in unperturbed conditions, and the long-term stability of the haploid state was significantly improved by alleviating their natural proteotoxicity. Based on these results, we propose that the haploidy-specific vulnerability to ER stress creates a fundamental cause of haploid intolerance in mammalian somatic cells. Our findings provide new insight into the principle that places a stringent restriction on the evolution of animal life cycles.", "classifications": [ { "id": "19H05413", "label": "19H05413", "researcher": "Ryota Uehara", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Sumire", "last_name": "Ishida-Ishihara", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Yaguchi", "name": null }, { "creator_type": "author", "first_name": "Sena", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Ryoto", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "QiJiao", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Koya", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Kimino", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Guang", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Krisztina", "last_name": "Veszelyi", "name": null }, { "creator_type": "author", "first_name": "Gabor", "last_name": "Banhegyi", "name": null }, { "creator_type": "author", "first_name": "Eva", "last_name": "Margittai", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbc.2024.107909" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39433129" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": true }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": true }, { "descriptor": "Endoplasmic Reticulum Stress", "descriptor_ui": "D059865", "major_topic": true }, { "descriptor": "Haploidy", "descriptor_ui": "D006238", "major_topic": true }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Unfolded Protein Response", "descriptor_ui": "D056811", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Oct 19", "date_precision": "day", "issue": "", "normalized_date": "2024-10-19", "pages": "107909", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Fragility of ER homeostatic regulation underlies haploid instability in human somatic cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Peptides play essential roles in biological phenomena, and, thus, there is a growing interest in detecting in vivo dynamics of peptide metabolisms. Dissolution-dynamic nuclear polarization (d-DNP) is a state-of-the-art technology that can markedly enhance the sensitivity of nuclear magnetic resonance (NMR), providing metabolic and physiological information in vivo. However, the hyperpolarized state exponentially decays back to the thermal equilibrium, depending on the spin-lattice relaxation time (T(1)). Because of the limitation in T(1), peptide-based DNP NMR molecular probes applicable in vivo have been limited to amino acids or dipeptides. Here, we report the direct detection of in vivo metabolic conversions of hyperpolarized (13)C-oligopeptides. Structure-based T(1) relaxation analysis suggests that the C-terminal [1-(13)C]Gly-d(2) residue affords sufficient T(1) for biological uses, even in relatively large oligopeptides, and allowed us to develop (13)C-β-casomorphin-5 and (13)C-glutathione. It was found that the metabolic response and perfusion of the hyperpolarized (13)C-glutathione in the mouse kidney were significantly altered in a model of cisplatin-induced acute kidney injury.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Takakusagi", "name": null }, { "creator_type": "author", "first_name": "Norikazu", "last_name": "Koyasu", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Miyanishi", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Mizukami", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Negoro", "name": null }, { "creator_type": "author", "first_name": "Abdelazim E.", "last_name": "Elhelaly", "name": null }, { "creator_type": "author", "first_name": "Fuminori", "last_name": "Hyodo", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Natarajan", "last_name": "Raju", "name": null }, { "creator_type": "author", "first_name": "Rolf E.", "last_name": "Swenson", "name": null }, { "creator_type": "author", "first_name": "Murali C.", "last_name": "Krishna", "name": null }, { "creator_type": "author", "first_name": "Kazutoshi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Sando", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adp2533" }, "pmcid": { "normalized": "PMC11482307" }, "pmid": { "normalized": "39413185" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carbon Isotopes", "descriptor_ui": "D002247", "major_topic": true }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Magnetic Resonance Spectroscopy", "descriptor_ui": "D009682", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Oligopeptides", "descriptor_ui": "D009842", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Oct 18", "date_precision": "day", "issue": "42", "normalized_date": "2024-10-18", "pages": "eadp2533", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "10", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Directly monitoring the dynamic in vivo metabolisms of hyperpolarized (13)C-oligopeptides.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The single-molecule tracking of transmembrane receptors in living cells has provided significant insights into signaling mechanisms, such as mobility and clustering upon their activation/inactivation, making it a potential screening method for drug discovery. Here we show that single-molecule tracking-based screening can be used to explore compounds both detectable and undetectable by conventional methods for disease-related receptors. Using an automated system for a fast large-scale single-molecule analysis, we screen for epidermal growth factor receptor (EGFR) from 1134 of FDA approved drugs. The 18 hit compounds include all EGFR-targeted tyrosine kinase inhibitors (TKIs) in the library that suppress any phosphorylation-dependent mobility shift of EGFR, proving the concept of this approach. The remaining hit compounds are not reported as EGFR-targeted drugs and do not inhibit EGF-induced EGFR phosphorylation. These non-TKI compounds affect the mobility and/or clustering of EGFR without EGF and induce EGFR internalization, to impede EGFR-dependent cell growth. Thus, single-molecule tracking provides an alternative modality for discovering therapeutics on various receptor functions with previously untargeted mechanisms.", "classifications": [ { "id": "18H05414", "label": "18H05414", "researcher": "Hiroko Bannai", "type": "grant" }, { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-53432-w" }, "pmcid": { "normalized": "PMC11486946" }, "pmid": { "normalized": "39420015" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Drug Discovery", "descriptor_ui": "D055808", "major_topic": false }, { "descriptor": "Drug Evaluation, Preclinical", "descriptor_ui": "D004353", "major_topic": false }, { "descriptor": "Epidermal Growth Factor", "descriptor_ui": "D004815", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Single Molecule Imaging", "descriptor_ui": "D000072760", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Oct 17", "date_precision": "day", "issue": "1", "normalized_date": "2024-10-17", "pages": "8975", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Single molecule tracking based drug screening.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Opsins are G protein-coupled receptors (GPCRs) that have evolved to detect light stimuli and initiate intracellular signaling cascades. Their role as signal transducers is critical to light perception across the animal kingdom. Opsins covalently bind to the chromophore 11-cis retinal, which isomerizes to the all-trans isomer upon photon absorption, causing conformational changes that result in receptor activation. Monostable opsins, responsible for vision in vertebrates, release the chromophore after activation and must bind another retinal molecule to remain functional. In contrast, bistable opsins, responsible for non-visual light perception in vertebrates and for vision in invertebrates, absorb a second photon in the active state to return the chromophore and protein to the inactive state. Structures of bistable opsins in the activated state have proven elusive, limiting our understanding of how they function as bidirectional photoswitches. Here we present active state structures of a bistable opsin, jumping spider rhodopsin isoform-1 (JSR1), in complex with its downstream signaling partners, the G(i) and G(q) heterotrimers. These structures elucidate key differences in the activation mechanisms between monostable and bistable opsins, offering essential insights for the rational engineering of bistable opsins into diverse optogenetic tools to control G protein signaling pathways.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Oliver", "last_name": "Tejero", "name": null }, { "creator_type": "author", "first_name": "Filip", "last_name": "Pamula", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Pavel", "last_name": "Afanasyev", "name": null }, { "creator_type": "author", "first_name": "Ishita", "last_name": "Das", "name": null }, { "creator_type": "author", "first_name": "Xavier", "last_name": "Deupi", "name": null }, { "creator_type": "author", "first_name": "Mordechai", "last_name": "Sheves", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null }, { "creator_type": "author", "first_name": "Gebhard F. X.", "last_name": "Schertler", "name": null }, { "creator_type": "author", "first_name": "Matthew J.", "last_name": "Rodrigues", "name": null }, { "creator_type": "author", "first_name": "Ching-Ju", "last_name": "Tsai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-53208-2" }, "pmcid": { "normalized": "PMC11484933" }, "pmid": { "normalized": "39414813" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Crystallography, X-Ray", "descriptor_ui": "D018360", "major_topic": false }, { "descriptor": "GTP-Binding Protein alpha Subunits, Gq-G11", "descriptor_ui": "D043802", "major_topic": false }, { "descriptor": "GTP-Binding Proteins", "descriptor_ui": "D019204", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Opsins", "descriptor_ui": "D055355", "major_topic": true }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Rhodopsin", "descriptor_ui": "D012243", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Spiders", "descriptor_ui": "D013112", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Oct 16", "date_precision": "day", "issue": "1", "normalized_date": "2024-10-16", "pages": "8928", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Active state structures of a bistable visual opsin bound to G proteins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nonalcoholic steatohepatitis (NASH) is a chronic progressive liver disease and highly prevalent worldwide. NASH is characterized by hepatic steatosis, inflammation, fibrosis and liver damage, which eventually results in liver dysfunction due to cirrhosis or hepatocellular carcinoma. However, the cellular and molecular mechanisms underlying NASH progression remain largely unknown. Here, we found an increase of Nr4a family of orphan nuclear receptors expression in intrahepatic T cells from mice with diet-induced NASH. Loss of Nr4a1 and Nr4a2 in T cell (dKO) ameliorated liver cell death and fibrosis, thereby mitigating liver dysfunction in NASH mice. dKO resulted in reduction of infiltrated macrophages and Th1/Th17 cells, whereas massive accumulation of T regulatory (Treg) cells in the liver of NASH mice. Combined single-cell RNA transcriptomic and TCR sequencing analysis revealed that intrahepatic dKO Tregs exhibited enhanced TIGIT and IL10 expression and were clonally expanded during NASH progression. Mechanistically, we found that dKO Tregs expressed high levels of Batf which promotes Treg cell proliferation and function upon TCR stimulation. Collectively, our findings not only provide an insight into the impact of intrahepatic Treg cells on NASH pathogenesis, but also suggest a therapeutic potential of targeting of Nr4a family to treat the disease.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Aki", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Tanakorn", "last_name": "Srirat", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Shichino", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiroh", "last_name": "Saitoh", "name": null }, { "creator_type": "author", "first_name": "Setsuko", "last_name": "Mise-Omata", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci175305" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39405120" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Fatty Liver", "descriptor_ui": "D005234", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Liver Cirrhosis", "descriptor_ui": "D008103", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": true }, { "descriptor": "Nuclear Receptor Subfamily 4, Group A, Member 1", "descriptor_ui": "D057105", "major_topic": true }, { "descriptor": "Nuclear Receptor Subfamily 4, Group A, Member 2", "descriptor_ui": "D057126", "major_topic": true }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Oct 15", "date_precision": "day", "issue": "", "normalized_date": "2024-10-15", "pages": "e175305", "proceedings_title": null, "publisher": "", "title": "The Journal of clinical investigation", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "The Nr4a family regulates intrahepatic Treg proliferation and liver fibrosis in MASLD models.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To establish protection against harmful foreign antigens, the small intestine harbors guardian sites called Peyer's patches (PPs). PPs take up antigens through microfold (M) cells and transfer them to the sub-epithelial dome (SED), which contains a high density of mononuclear phagocytes (MPs), for T cell-priming. Accumulating evidence indicates that SED-MPs have unique functions other than T cell-priming to facilitate mucosal immune responses; however, the crucial factors regulating the functions of SED-MPs have not been determined. Here we performed transcriptome analysis, and identified the gene signatures of SED-MPs. Further data interpretation with transcription factor (TF) enrichment analysis estimated TFs responsible for the functions of SED-MPs. Among them, we found that RelB and C/EBPalpha were preferentially activated in SED-MPs. RelB-deficiency silenced the expression of IL-22BP and S100A4 by SED-MPs. On the other hand, C/EBPalpha-deficiency decreased the expression of lysozyme by SED-MPs, resulting the increased invasion of orally administered pathogenic bacteria into PPs and mesenteric lymph nodes. Our findings thus demonstrate that RelB and C/EBPalpha are essential to regulate the functions of SED-MPs.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Kanaya", "name": null }, { "creator_type": "author", "first_name": "Toshi", "last_name": "Jinnohara", "name": null }, { "creator_type": "author", "first_name": "Sayuri", "last_name": "Sakakibara", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Takaharu", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Tamotsu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Marc", "last_name": "Riemann", "name": null }, { "creator_type": "author", "first_name": "Jianshi", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.mucimm.2024.10.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39413971" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CCAAT-Enhancer-Binding Protein-alpha", "descriptor_ui": "D022763", "major_topic": true }, { "descriptor": "CCAAT-Enhancer-Binding Proteins", "descriptor_ui": "D022762", "major_topic": true }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Immunity, Mucosal", "descriptor_ui": "D018928", "major_topic": false }, { "descriptor": "Intestinal Mucosa", "descriptor_ui": "D007413", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Peyer's Patches", "descriptor_ui": "D010581", "major_topic": true }, { "descriptor": "Phagocytes", "descriptor_ui": "D010586", "major_topic": true }, { "descriptor": "Transcription Factor RelB", "descriptor_ui": "D051841", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Oct 14", "date_precision": "day", "issue": "", "normalized_date": "2024-10-14", "pages": "S1933-0219(24)00108-9", "proceedings_title": null, "publisher": "", "title": "Mucosal immunology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000507" ] }, "title": "RelB and C/EBPalpha critically regulate the development of Peyer's patch mononuclear phagocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bioluminescence imaging has become a valuable tool in biological research, offering several advantages over fluorescence-based techniques, including the absence of phototoxicity and photobleaching, along with a higher signal-to-noise ratio. Common bioluminescence imaging methods often require the addition of an external chemical substrate (luciferin), which can result in a decrease in luminescence intensity over time and limit prolonged observations. Since the bacterial bioluminescence system is genetically encoded for luciferase-luciferin production, it enables autonomous bioluminescence (auto-bioluminescence) imaging. However, its application to multiple reporters is restricted due to a limited range of color variants. Here, we report five-color auto-bioluminescence system named Nano-lanternX (NLX), which can be expressed in bacterial, mammalian, and plant hosts, thereby enabling auto-bioluminescence in various living organisms. Utilizing spectral unmixing, we achieved the successful observation of multicolor auto-bioluminescence, enabling detailed single-cell imaging across both bacterial and mammalian cells. We have also expanded the applications of the NLX system, such as multiplexed auto-bioluminescence imaging for gene expression, protein localization, and dynamics of biomolecules within living mammalian cells.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Subhan Hadi", "last_name": "Kusuma", "name": null }, { "creator_type": "author", "first_name": "Taishi", "last_name": "Kakizuka", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2406358121" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39356665" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Luminescence", "descriptor_ui": "D049449", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Oct 8", "date_precision": "day", "issue": "41", "normalized_date": "2024-10-08", "pages": "e2406358121", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "121", "year": 2024 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000407" ] }, "title": "Autonomous multicolor bioluminescence imaging in bacteria, mammalian, and plant hosts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Patients with germline pathogenic variants of BRCA1/2 genes have a particular predisposition to develop breast cancer. No clinical test has been developed to accurately and quantitatively evaluate their risk of developing breast cancer. We hypothesized that aberrant cell clonal expansion may be initiated in normal breast tissues without manifesting pathologic changes. To assess the prevalence of clonal expansion in the normal breast, we collected normal breast tissue from 24 breast cancer patients who had undergone surgical resection and 5 carriers of pathogenic BRCA1/2 variant who had undergone prophylactic mastectomy. Whole-exome sequencing (WES) was conducted in 97 specimens from 14 individuals, and TOP panel, a gene panel targeting 464 genes, was conducted in 321 specimens from 26 individuals, including 8 individuals with germline pathogenic variants of BRCA1/2 genes. Recurrent oncogenic mutations within PIK3CA, ARHGAP35, HRAS, and NF1 were identified in normal breast tissue at considerable variant allelic frequencies (VAF), suggesting clonal expansion. In addition, 937 normal breast tissues were evaluated using the Breast Cancer Panel (BCP) targeting 25 genes to determine the exact prevalence and distribution of clonal expansion. To assess the clonal expansion, we developed the clonality score, which is the mean value of clonal cell fractions for samples obtained from a given breast. The average clonality score in macroscopically normal breast tissue was 0.95 (0-2.46), with a significant difference between cases with and without a history of breast cancer of stage 2 or more advanced stage (p = 0.01). Additional WES on 42 samples with relatively large clone size (VAF > 3%) confirmed that these cell clones harbored multiple mutations (10.7 mutations/sample), and the number of existing mutations was consistent with the clone size (R = 0.50). The results suggest that clonal changes occur in normal breast tissue of women at high risk for breast cancer even before cancer is detected pathologically and/or radiologically, and the clonality score shows the potential to be a valid method of evaluating clonal expansion for cancer-risk assessment that provides appropriate preventive options for patients at high risk for breast cancer.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Masachika", "last_name": "Ikegami", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Kida", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Kitada", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Yasuharu", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kanomata", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Hideko", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kohsaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41523-024-00693-9" }, "pmcid": { "normalized": "PMC11452615" }, "pmid": { "normalized": "39366967" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Oct 4", "date_precision": "day", "issue": "1", "normalized_date": "2024-10-04", "pages": "87", "proceedings_title": null, "publisher": "", "title": "NPJ breast cancer", "volume": "10", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Cancer risk assessment of premalignant breast tissues from patients with BRCA mutations by genome profiling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: Early diagnosis of a precursor lesion in the uterine cervix is an essential factor in uterine cervical cancer prevention. Although colposcopy is an established procedure for detecting high-risk patients, its accuracy and reproducibility are relatively low. Some supportive or alternative techniques to improve the early diagnosis of a precursor lesion have been studied, and correct diagnosis with high reliability using a minimally invasive, cost-effective technique has been pursued. This study aimed to examine the possibility of using photoacoustic (PA) imaging as a supportive technique to improve the accuracy of early diagnosis of cervical precursor lesions. METHODS: A PA imaging system for microvessels was used to detect angiogenesis in severe lesions. A total of 21 patients who underwent surgical treatment and 114 outpatients who visited our colposcopy clinic were examined. A retrospective evaluation of PA images was performed as follows: (i) pathological assessment of the specific PA findings and (ii) retrospective evaluation of the severe lesion detection rate through PA. RESULTS: PA image evaluation and pathological findings showed dense angiogenesis in a severe precursor lesion appearing as a \"hot spot\" in the PA image. A comparison with colposcopy findings was performed for accuracy evaluation, and the detection rate of severe lesions using PA was relatively high (positive predictive value, 84.5%; negative predictive value, 82.1%). CONCLUSION: Our results indicate the possibility of using PA imaging for early diagnosis of severe cervical precursor lesions. With its ability to yield quantitative information, PA imaging can improve ultrasound diagnosis.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kiguna Sei", "last_name": "Okawa", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Okawa", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Sasa", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10396-024-01501-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39361106" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Cervix Uteri", "descriptor_ui": "D002584", "major_topic": false }, { "descriptor": "Colposcopy", "descriptor_ui": "D003127", "major_topic": false }, { "descriptor": "Early Detection of Cancer", "descriptor_ui": "D055088", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Photoacoustic Techniques", "descriptor_ui": "D061088", "major_topic": true }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Uterine Cervical Neoplasms", "descriptor_ui": "D002583", "major_topic": true }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Oct 3", "date_precision": "day", "issue": "", "normalized_date": "2024-10-03", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of medical ultrasonics (2001)", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical application of photoacoustic imaging for cervical precursor lesion detection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Collagen is the most abundant protein in the extracellular matrix of animals, and 28 types of collagen have been reported in humans. We previously analyzed the endoplasmic reticulum (ER)-to-Golgi transport of fibril-forming type III collagen (Hirata et al., 2022) and network-forming type IV collagen (Matsui et al., 2020), both of which have long collagenous triple-helical regions. To understand the ER-to-Golgi trafficking of various types of collagens, we analyzed the transport of short-chain type X collagen in this study. We fused cysteine-free GFP to the N-telopeptide region of procollagen X (GFP-COL10A1), as employed in our previous analysis of procollagens III and IV, and analyzed its transport by live-cell imaging. Procollagen X was transported to the Golgi apparatus via vesicular and tubular carriers containing ERGIC53 and RAB1B, similar to those used for procollagen III. Carriers containing procollagen X probably used the same transport processes as those containing conventional cargoes such as α(1)-antitrypsin. SAR1, TANGO1, SLY1/SCFD1, and BET3/TRAPPC3 were required for trafficking of procollagen X, which are different from the factors required for trafficking of procollagens III (SAR1, TANGO1, and CUL3) and IV (SAR1 and SLY1/SCFD1). These findings reveal that accommodation of various types of collagens with different shapes into carriers may require fine-tuning of the ER-to-Golgi transport machinery.Key words: collagen, GFP-procollagen X, ER-to-Golgi trafficking, export from ER, TANGO1.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuan", "last_name": "Ximin", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Ikuo", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Nobuko", "last_name": "Hosokawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1247/csf.24024" }, "pmcid": { "normalized": "PMC11930776" }, "pmid": { "normalized": "39245571" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aryl Hydrocarbon Receptor Nuclear Translocator", "descriptor_ui": "D051784", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": true }, { "descriptor": "Golgi Apparatus", "descriptor_ui": "D006056", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Procollagen", "descriptor_ui": "D011347", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Oct 2", "date_precision": "day", "issue": "2", "normalized_date": "2024-10-02", "pages": "67-81", "proceedings_title": null, "publisher": "", "title": "Cell structure and function", "volume": "49", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualization of ER-to-Golgi trafficking of procollagen X.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The oral mucosa is the first line of defense against pathogenic bacteria and plays a vital role in maintaining tolerance to food antigens and commensal bacteria. We used CD11c reporter mice to visualize dendritic cells (DCs), a key immune cell population, in the oral cavity. We identified differences in DC density in each oral tissue region. Sublingual immune cell clusters (SLICs) extended from the lamina propria to the epithelium, where DCs and T cells resided in close contact with each other and innate lymphoid cells (ILCs). Targeted in situ photolabeling revealed that the SLICs comprised mostly of CD11c+CD11b+ DCs and were enriched for cDC1s and Langerhans cells. Although the frequency of T cell subsets was similar within and outside the SLICs, tissue resident memory T cells were significantly enriched within the clusters and cluster size increased in response to inflammation. Collectively, we found that SLICs form a unique microenvironment that facilitates T cell-DC interactions in the steady state and during inflammation. Since the oral mucosa is an important target for needle-free vaccination and sublingual immunotherapy to induce tolerogenic responses, the novel insight into the localized immunoregulation provided in this study may accelerate the development of these approaches.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yutaka", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Nishii", "name": null }, { "creator_type": "author", "first_name": "Atsuki", "last_name": "Fujino", "name": null }, { "creator_type": "author", "first_name": "Akiho", "last_name": "Kurahashi", "name": null }, { "creator_type": "author", "first_name": "Momoka", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Iwasa", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Karin", "last_name": "Obazaki", "name": null }, { "creator_type": "author", "first_name": "Ryoto", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Naruya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yukika", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Tetsushi", "last_name": "Hoshida", "name": null }, { "creator_type": "author", "first_name": "Tsuneyasu", "last_name": "Kaisho", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Hemmi", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Kikuta", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Ryoyo", "last_name": "Ikebuchi", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Moriya", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kabashima", "name": null }, { "creator_type": "author", "first_name": "Tatyana", "last_name": "Chtanova", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Tomura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci.insight.167373" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39352752" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CD11c Antigen", "descriptor_ui": "D039521", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Langerhans Cells", "descriptor_ui": "D007801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mouth", "descriptor_ui": "D009055", "major_topic": false }, { "descriptor": "Mouth Mucosa", "descriptor_ui": "D009061", "major_topic": true }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Oct 1", "date_precision": "day", "issue": "", "normalized_date": "2024-10-01", "pages": "e167373", "proceedings_title": null, "publisher": "", "title": "JCI insight", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Sublingual immune cell clusters and dendritic cell distribution in the oral cavity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Renal transporters play critical roles in predicting potential drug-drug interactions. However, current in vitro models often fail to adequately express these transporters, particularly solute carrier proteins, including organic anion transporters (OAT1/3), and organic cation transporter 2 (OCT2). Here, we developed a hiPSC-derived kidney organoids-based proximal tubule-on-chip (OPTC) model that emulates in vivo renal physiology to assess transporter function. Compared to chips based on immortalized cells, OPTC derived from the two most commonly used differentiation protocols exhibited significant improvement in expression level and polarity of OAT1/3 and OCT2. Hence, the OPTC demonstrates enhanced functionality in efflux and uptake assessments, and nephrotoxicity. Furthermore, these functionalities are diminished upon adding inhibitors during substrate-inhibitor interactions, which were closer to in vivo observations. Overall, these results support that OPTC can reliably assess the role of renal transporters in drug transport and nephrotoxicity, paving the way for personalized models to assess renal transport and disease modeling.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Cheng", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Ramin", "last_name": "Banan Sadeghian", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Negoro", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Toshikazu", "last_name": "Araoka", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Yokokawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2024.110760" }, "pmcid": { "normalized": "PMC11403423" }, "pmid": { "normalized": "39286490" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Sep 20", "date_precision": "day", "issue": "9", "normalized_date": "2024-09-20", "pages": "110760", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "27", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Efficient proximal tubule-on-chip model from hiPSC-derived kidney organoids for functional analysis of renal transporters.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Automation and quality control (QC) are critical in manufacturing safe and effective cell and gene therapy products. However, current QC methods, reliant on molecular staining, pose difficulty in in-line testing and can increase manufacturing costs. Here we demonstrate the potential of using label-free ghost cytometry (LF-GC), a machine learning-driven, multidimensional, high-content, and high-throughput flow cytometry approach, in various stages of the cell therapy manufacturing processes. LF-GC accurately quantified cell count and viability of human peripheral blood mononuclear cells (PBMCs) and identified non-apoptotic live cells and early apoptotic/dead cells in PBMCs (ROC-AUC: area under receiver operating characteristic curve = 0.975), T cells and non-T cells in white blood cells (ROC-AUC = 0.969), activated T cells and quiescent T cells in PBMCs (ROC-AUC = 0.990), and particulate impurities in PBMCs (ROC-AUC >== 0.998). The results support that LF-GC is a non-destructive label-free cell analytical method that can be used to monitor cell numbers, assess viability, identify specific cell subsets or phenotypic states, and remove impurities during cell therapy manufacturing. Thus, LF-GC holds the potential to enable full automation in the manufacturing of cell therapy products with reduced cost and increased efficiency.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuki", "last_name": "Teranishi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Wagatsuma", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Nomaru", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Yanagihashi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ochiai", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Akai", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Yuuki", "last_name": "Onda", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Keiki", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hideto", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-024-72016-8" }, "pmcid": { "normalized": "PMC11413197" }, "pmid": { "normalized": "39300150" } }, "mesh": [ { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Cell- and Tissue-Based Therapy", "descriptor_ui": "D064987", "major_topic": true }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukocytes, Mononuclear", "descriptor_ui": "D007963", "major_topic": true }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Quality Control", "descriptor_ui": "D011786", "major_topic": true }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Sep 19", "date_precision": "day", "issue": "1", "normalized_date": "2024-09-19", "pages": "21848", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "14", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-free ghost cytometry for manufacturing of cell therapy products.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Gravity has profoundly influenced life on Earth, yet how organisms adapt to changes in gravity remains largely unknown. This study examines vestibular plasticity, specifically how the vestibular system responds to altered gravity. We subjected male C57BL/6J mice to hypergravity (2 G) followed by normal gravity (1 G) to analyze changes in vestibular function and gene expression. Mice showed significant vestibular dysfunction, assessed by righting reflex tests, which persisted for days but reversed at 1 G after exposure to 2 G. Gene expression analysis in the vestibular ganglion identified significant changes in 212 genes out of 49,585 due to gravitational changes. Specifically, 25 genes were upregulated under 2 G and recovered at 1 G after 2 G exposure, while one gene showed the opposite trend. Key neural function genes like Shisa3, Slc25a37, Ntn4, and Snca were involved. Our results reveal that hypergravity-induced vestibular dysfunction is reversible and highlight genes critical for adaptation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Murat", "last_name": "Bazek", "name": null }, { "creator_type": "author", "first_name": "Motoya", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Horii", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Iwami", "name": null }, { "creator_type": "author", "first_name": "Chia-Hsien", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Nin", "name": null }, { "creator_type": "author", "first_name": "Chikara", "last_name": "Abe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12576-024-00939-y" }, "pmcid": { "normalized": "PMC11409750" }, "pmid": { "normalized": "39294564" } }, "mesh": [ { "descriptor": "Adaptation, Physiological", "descriptor_ui": "D000222", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Gravitation", "descriptor_ui": "D006112", "major_topic": false }, { "descriptor": "Hypergravity", "descriptor_ui": "D018471", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": true }, { "descriptor": "Vestibule, Labyrinth", "descriptor_ui": "D014722", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Sep 18", "date_precision": "day", "issue": "1", "normalized_date": "2024-09-18", "pages": "44", "proceedings_title": null, "publisher": "", "title": "The journal of physiological sciences : JPS", "volume": "74", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Gravitational change-induced alteration of the vestibular function and gene expression in the vestibular ganglion of mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Identifying the properties of the rapid eye movement (REM) sleep circuitry and its relation to diseases has been challenging due to the neuronal heterogeneity of the brainstem. Here, we show in mice that neurons in the pontine sublaterodorsal tegmentum (SubLDT) that express corticotropin-releasing hormone-binding protein (Crhbp(+) neurons) and project to the medulla promote REM sleep. Within the medullary area receiving projections from Crhbp(+) neurons, neurons expressing nitric oxide synthase 1 (Nos1(+) neurons) project to the SubLDT and promote REM sleep, suggesting a positively interacting loop between the pons and the medulla operating as a core REM sleep circuit. Nos1(+) neurons also project to areas that control wide forebrain activity. Ablating Crhbp(+) neurons reduces sleep and impairs REM sleep atonia. In Parkinson's disease patients with REM sleep behavior disorders, CRHBP-immunoreactive neurons are largely reduced and contain pathologic alpha-synuclein, providing insight into the mechanisms underlying the sleep deficits characterizing this disease.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuaki", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Goichi", "last_name": "Beck", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Kanuka", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Kaeko", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Tatsuzawa", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Yuki C.", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Marina", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Yo", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Kousuke", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Ikuno", "name": null }, { "creator_type": "author", "first_name": "Hodaka", "last_name": "Yamakado", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cell.2024.08.046" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39303715" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "alpha-Synuclein", "descriptor_ui": "D051844", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Medulla Oblongata", "descriptor_ui": "D008526", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Nitric Oxide Synthase Type I", "descriptor_ui": "D052248", "major_topic": false }, { "descriptor": "Parkinson Disease", "descriptor_ui": "D010300", "major_topic": true }, { "descriptor": "Pons", "descriptor_ui": "D011149", "major_topic": false }, { "descriptor": "REM Sleep Behavior Disorder", "descriptor_ui": "D020187", "major_topic": false }, { "descriptor": "Sleep, REM", "descriptor_ui": "D012895", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Sep 17", "date_precision": "day", "issue": "", "normalized_date": "2024-09-17", "pages": "S0092-8674(24)00975-9", "proceedings_title": null, "publisher": "", "title": "Cell", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "A pontine-medullary loop crucial for REM sleep and its deficit in Parkinson's disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We surveyed the status of the secondary finding (SF) disclosure in comprehensive genome profiling (CGP) in 2020. The situation has changed: increase in the number of hospitals that provide CGP, an update to the Comprehensive Tumor Genomic Profiling: Materials for Review of Secondary Findings (CTGPMRSF), and the addition of a liquid biopsy test, FoundationOne((R)) Liquid CDx (F1L). Moreover, the actual situation was unclear because the 2020 survey did not include all designated and cooperative hospitals. Herein, we conducted a questionnaire survey of all designated-core, designated, and cooperative hospitals to identify the current status and challenges concerning SF in the CGP in 2022. A total of 82.1% of the hospitals responded and 77.7% of the response was from cooperative hospitals. Approximately 80% of the hospitals used CTGPMRSF. SF disclosure, confirmatory test implementation, and SF confirmation rates were 12.4%, 31.6%, and 46.6% for FoundationOne((R)) CDx (F1CDx), respectively, and 6.8%, 31.8%, and 70.7% for F1L, respectively. The implementation rate of the confirmatory test was substantially higher in hospitals with genetic experts and in hospitals that could conduct confirmatory tests on the same day. Our survey provides insight into how SF is handled in Japan. The percentage of cases leading to confirmatory tests has gradually increased, although challenges such as insurance coverage limitations and varied understanding of SF among patients and healthcare providers persist. With the increasing use of whole-genome analysis, our findings will provide valuable insights into establishing an effective SF disclosure system.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Saki", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Akari", "last_name": "Minamoto", "name": null }, { "creator_type": "author", "first_name": "Manami", "last_name": "Matsukawa", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Yabe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Katsutoshi", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Arisa", "last_name": "Ueki", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Higashigawa", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Morikawa", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Muto", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kosugi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s10038-024-01294-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39289525" } }, "mesh": [ { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Genetic Testing", "descriptor_ui": "D005820", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": true }, { "descriptor": "Hospitals", "descriptor_ui": "D006761", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liquid Biopsy", "descriptor_ui": "D000073890", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Sep 17", "date_precision": "day", "issue": "", "normalized_date": "2024-09-17", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of human genetics", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Nationwide survey of the secondary findings in cancer genomic profiling: survey including liquid biopsy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Volvocales in green algae have evolved by multicellularity of Chlamydomonas-like unicellular ancestor. Those with various cell numbers exist, such as unicellular Chlamydomonas, four-celled Tetrabaena, and Volvox species with different cell numbers (~1,000, ~5,000, and ~10,000). Each cell of these organisms shares two cilia and an eyespot, which are used for swimming and photosensing. They are all freshwater microalgae but inhabit different fluid environments: unicellular species live in low Reynolds-number (Re) environments where viscous forces dominate, whereas multicellular species live in relatively higher Re where inertial forces become non-negligible. Despite significant changes in the physical environment, during the evolution of multicellularity, they maintained photobehaviors (i.e., photoshock and phototactic responses), which allows them to survive under changing light conditions. RESULTS: In this study, we utilized high-speed imaging to observe flash-induced changes in the ciliary beating manner of 27 Volvocales strains. We classified flash-induced ciliary responses in Volvocales into four patterns: \"1: temporal waveform conversion\", \"2: no obvious response\", \"3: pause in ciliary beating\", and \"4: temporal changes in ciliary beating directions\". We found that which species exhibit which pattern depends on Re, which is associated with the individual size of each species rather than phylogenetic relationships. CONCLUSIONS: These results suggest that only organisms that acquired different patterns of ciliary responses survived the evolutionary transition to multicellularity with a greater number of cells while maintaining photobehaviors. This study highlights the significance of the Re as a selection pressure in evolution and offers insights for designing propulsion systems in biomimetic micromachines.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Noriko", "last_name": "Ueki", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12862-024-02307-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39277710" } }, "mesh": [ { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": true }, { "descriptor": "Chlorophyta", "descriptor_ui": "D000460", "major_topic": false }, { "descriptor": "Cilia", "descriptor_ui": "D002923", "major_topic": true }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Volvox", "descriptor_ui": "D044446", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Sep 14", "date_precision": "day", "issue": "1", "normalized_date": "2024-09-14", "pages": "119", "proceedings_title": null, "publisher": "", "title": "BMC ecology and evolution", "volume": "24", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Multicellularity and increasing Reynolds number impact on the evolutionary shift in flash-induced ciliary response in Volvocales.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Staphylococcal enterotoxin B (SEB), a potent enterotoxin produced by Staphylococcus aureus, has been implicated in incidences of Staphylococcal food poisoning in the Philippines. The use of lateral flow immunoassay devices to detect this toxin in solid food samples, like durian candy, at the point of sampling is constrained by the requirement for sample purification (e.g. centrifugation). This problem is also true with the other applications of LFIA devices on food samples. To overcome this challenge, a lateral flow immunoassay (LFIA) device capable of detecting SEB in unpurified durian candy sample was developed in this study. A modified LFIA device was assembled with three layers of glass fiber pads functioning as sample pads instead of a conventional cellulose fiber pad. Unlike with the cellulose fiber pad, the glass fiber sample pads acted as filter and allowed the flow of a 1:5 dilution of durian candy. The LFIA device applied to spiked 1:5 diluted durian candy samples achieved a visual limit of detection of 5 ng/mL for SEB, which is twofold lower than reported for previous LFIA devices designed to detect SEB in food samples.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Paquito E. Jr", "last_name": "Relox", "name": null }, { "creator_type": "author", "first_name": "Katherine Ann C.", "last_name": "Israel", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s44211-024-00665-w" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39271599" } }, "mesh": [ { "descriptor": "Enterotoxins", "descriptor_ui": "D004768", "major_topic": true }, { "descriptor": "Food Analysis", "descriptor_ui": "D005504", "major_topic": false }, { "descriptor": "Food Contamination", "descriptor_ui": "D005506", "major_topic": false }, { "descriptor": "Immunoassay", "descriptor_ui": "D007118", "major_topic": false }, { "descriptor": "Limit of Detection", "descriptor_ui": "D057230", "major_topic": false }, { "descriptor": "Staphylococcus aureus", "descriptor_ui": "D013211", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Sep 13", "date_precision": "day", "issue": "", "normalized_date": "2024-09-13", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical sciences : the international journal of the Japan Society for Analytical Chemistry", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Lateral flow immunoassay device to detect staphylococcal enterotoxin B (SEB) in durian candy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Flow cytometry is a vital tool in biomedical research and laboratory medicine. However, its accuracy is often compromised by undesired fluctuations in fluorescence intensity. While fluorescence lifetime imaging microscopy (FLIM) bypasses this challenge as fluorescence lifetime remains unaffected by such fluctuations, the full integration of FLIM into flow cytometry has yet to be demonstrated due to speed limitations. Here we overcome the speed limitations in FLIM, thereby enabling high-throughput FLIM flow cytometry at a high rate of over 10,000 cells per second. This is made possible by using dual intensity-modulated continuous-wave beam arrays with complementary modulation frequency pairs for fluorophore excitation and acquiring fluorescence lifetime images of rapidly flowing cells. Moreover, our FLIM system distinguishes subpopulations in male rat glioma and captures dynamic changes in the cell nucleus induced by an anti-cancer drug. FLIM flow cytometry significantly enhances cellular analysis capabilities, providing detailed insights into cellular functions, interactions, and environments.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kanno", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Hiramatsu", "name": null }, { "creator_type": "author", "first_name": "Hideharu", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Nakayashiki", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Arata", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Kohki", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Fan", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Fei", "last_name": "Yin", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Tominaga", "name": null }, { "creator_type": "author", "first_name": "Omer Faruk", "last_name": "Bicer", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Noma", "name": null }, { "creator_type": "author", "first_name": "Bahareh", "last_name": "Kiani", "name": null }, { "creator_type": "author", "first_name": "Olga", "last_name": "Efa", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Buscher", "name": null }, { "creator_type": "author", "first_name": "Tetsuichi", "last_name": "Wazawa", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shintaku", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Sigurd", "last_name": "Braun", "name": null }, { "creator_type": "author", "first_name": "Jessica P.", "last_name": "Houston", "name": null }, { "creator_type": "author", "first_name": "Sherif", "last_name": "Rashad", "name": null }, { "creator_type": "author", "first_name": "Kuniyasu", "last_name": "Niizuma", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Goda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-51125-y" }, "pmcid": { "normalized": "PMC11375057" }, "pmid": { "normalized": "39231964" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": true }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Glioma", "descriptor_ui": "D005910", "major_topic": true }, { "descriptor": "High-Throughput Screening Assays", "descriptor_ui": "D057166", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Sep 4", "date_precision": "day", "issue": "1", "normalized_date": "2024-09-04", "pages": "7376", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "High-throughput fluorescence lifetime imaging flow cytometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Tagai", "name": null }, { "creator_type": "author", "first_name": "Harutsugu", "last_name": "Tatebe", "name": null }, { "creator_type": "author", "first_name": "Sayo", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Zhang", "last_name": "Hong", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Kokubo", "name": null }, { "creator_type": "author", "first_name": "Kiwamu", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Asaka", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shinotoh", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Oya", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Kurose", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Takahata", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Ichihashi", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Takado", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Ming-Rong", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Soeda", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Tokuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s40035-024-00439-4" }, "pmcid": { "normalized": "PMC11375937" }, "pmid": { "normalized": "39238067" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": true }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Sep 3", "date_precision": "day", "issue": "1", "normalized_date": "2024-09-03", "pages": "44", "proceedings_title": null, "publisher": "", "title": "Translational neurodegeneration", "volume": "13", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "A novel plasma p-tau181 assay as a specific biomarker of tau pathology in Alzheimer's disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The entorhinal cortex is the very earliest involvement of Alzheimer's disease (AD). Grid cells in the medial entorhinal cortex form part of the spatial navigation system. OBJECTIVE: We aimed to determine whether path integration performance can be used to detect patients with mild cognitive impairment (MCI) at high risk of developing AD, and whether it can predict cognitive decline. METHODS: Path integration performance was assessed in 71 patients with early MCI (EMCI) and late MCI (LMCI) using a recently developed 3D virtual reality navigation task. Patients with LMCI were further divided into those displaying characteristic brain imaging features of AD, including medial temporal lobe atrophy on magnetic resonance imaging and posterior hypoperfusion on single-photon emission tomography (LMCI+), and those not displaying such features (LMCI-). RESULTS: Path integration performance was significantly lower in patients with LMCI+than in those with EMCI and LMCI-. A significantly lower performance was observed in patients who showed progression of MCI during 12 months, than in those with stable MCI. Path integration performance distinguished patients with progressive MCI from those with stable MCI, with a high classification accuracy (a sensitivity of 0.88 and a specificity of 0.70). CONCLUSIONS: Our results suggest that the 3D virtual reality navigation task detects prodromal AD patients and predicts cognitive decline after 12 months. Our navigation task, which is simple, short (12-15 minutes), noninvasive, and inexpensive, may be a screening tool for therapeutic choice of disease-modifiers in individuals with prodromal AD.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Haruo", "last_name": "Hanyu", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Umekida", "name": null }, { "creator_type": "author", "first_name": "Sadayoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Riki", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.3233/jad-240347" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39240637" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": true }, { "descriptor": "Cognitive Dysfunction", "descriptor_ui": "D060825", "major_topic": true }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Entorhinal Cortex", "descriptor_ui": "D018728", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neuropsychological Tests", "descriptor_ui": "D009483", "major_topic": false }, { "descriptor": "Prodromal Symptoms", "descriptor_ui": "D062706", "major_topic": true }, { "descriptor": "Spatial Navigation", "descriptor_ui": "D065854", "major_topic": false }, { "descriptor": "Tomography, Emission-Computed, Single-Photon", "descriptor_ui": "D015899", "major_topic": false }, { "descriptor": "Virtual Reality", "descriptor_ui": "D000076142", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Aug 30", "date_precision": "day", "issue": "", "normalized_date": "2024-08-30", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of Alzheimer's disease : JAD", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Path Integration Detects Prodromal Alzheimer's Disease and Predicts Cognitive Decline.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Three thienopyrrole-fused thiadiazole (TPT) fluorescent dyes featuring a common amide linker and different alkoxy substituents on peripheral trialkoxybenzene moieties were synthesized, and their self-assembly behavior in solution was investigated. The obtained results revealed a substantial steric effect of the alkoxy substituents on the supramolecular polymerization mechanism, which results from a combination of pi-stacking and hydrogen (H)-bonding interactions. Detailed spectroscopic measurements revealed that with increasing steric demand of the substituents, the supramolecular polymerization processes in pure methylcyclohexane (MCH) or a mixture of MCH and toluene become temperature-sensitive and enthalpically favorable, resulting in a change from the isodesmic assembly mechanism to the cooperative mechanism. Theoretical calculations suggested that in TPTs with bulky substituents, steric hindrance causes the H-bonding array of the amide moieties to be aligned along the stacking axis of the pi-systems; thus, the H-bonding interactions are strengthened compared to those in TPTs with less bulky substituents, compensating for the weakened pi-stacking interactions. A chiral TPT derivative with (S) stereogenic centers was found to form homochiral helical supramolecular assemblies that generate discernible circularly polarized luminescence. Achiral TPTs also generate helical assemblies to which preferential helicity can be imparted through the external chiral bias of the solvents (R)- and (S)-limonene.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Chitoshi", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Takeshita", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Ishi-I", "name": null }, { "creator_type": "author", "first_name": "Kazumasa", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yoshihito", "last_name": "Shiota", "name": null }, { "creator_type": "author", "first_name": "Daiya", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoshitane", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Ikeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/asia.202400829" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39177426" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Aug 23", "date_precision": "day", "issue": "", "normalized_date": "2024-08-23", "pages": "e202400829", "proceedings_title": null, "publisher": "", "title": "Chemistry, an Asian journal", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Self-Assembly of Thienopyrrole-Fused Thiadiazoles Containing an Amide Linker: Control of Supramolecular Polymerization Mechanism and Chiroptical Properties by Trialkoxy Side Chains.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular temperature is a fundamental parameter in biochemical reactions. Genetically encoded fluorescent temperature indicators (GETIs) have been developed to visualize intracellular thermogenesis; however, the temperature sensitivity or localization capability in specific organelles should have been further improved to clearly capture when and where intracellular temperature changes at the subcellular level occur. Here, we developed a new GETI, gMELT, composed of donor and acceptor subunits, in which cyan and yellow fluorescent proteins, respectively, as a Förster resonance energy transfer (FRET) pair were fused with temperature-sensitive domains. The donor and acceptor subunits associated and dissociated in response to temperature changes, altering the FRET efficiency. Consequently, gMELT functioned as a fluorescence ratiometric indicator. Untagged gMELT was expressed in the cytoplasm, whereas versions fused with specific localization signals were targeted to the endoplasmic reticulum (ER) or mitochondria. All gMELT variations enabled more sensitive temperature measurements in cellular compartments than those in previous GETIs. The gMELTs, tagged with ER or mitochondrial targeting sequences, were used to detect thermogenesis in organelles stimulated chemically, a method previously known to induce thermogenesis. The observed temperature changes were comparable to previous reports, assuming that the fluorescence readout changes were exclusively due to temperature variations. Furthermore, we demonstrated how macromolecular crowding influences gMELT fluorescence given that this factor can subtly affect the fluorescence readout. Investigating thermogenesis with gMELT, accounting for factors such as macromolecular crowding, will enhance our understanding of intracellular thermogenesis phenomena.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shun-ichi", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Tetsuichi", "last_name": "Wazawa", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acssensors.3c02658" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39042704" } }, "mesh": [ { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": true }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Organelles", "descriptor_ui": "D015388", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Aug 23", "date_precision": "day", "issue": "8", "normalized_date": "2024-08-23", "pages": "3889-3897", "proceedings_title": null, "publisher": "", "title": "ACS Sensors", "volume": "9", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Extremely Sensitive Genetically Encoded Temperature Indicator Enabling Measurement at the Organelle Level.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although CRISPR-based nucleic acid detection has great potential in point-of-care testing due to its simplicity, it has been rarely integrated into paper-based analytical devices (PADs), which are attractive platforms to simplify assays. This work introduces a CRISPR-assisted nucleic acid quantification approach integrated into a PAD with signal readout by a personal glucose meter (PGM). Retention of magnetic beads by filter paper and pre-deposition of all required reagents by freeze-drying stabilized with trehalose enabled the indirect quantification of human papilloma virus (HPV) DNA through a PGM readout without complicated user intervention and complex reagent handling. The calculated limit of detection was 57 pM, which is comparable with other amplification-free CRISPR-based assays detecting nucleic acids. The fully integrated device exhibited good storage stability for up to 4 weeks, suggesting its applicability toward practical point-of-care nucleic acid quantification.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Tanifuji", "name": null }, { "creator_type": "author", "first_name": "Guodong", "last_name": "Tong", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d4an00905c" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39171545" } }, "mesh": [ { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Blood Glucose Self-Monitoring", "descriptor_ui": "D015190", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": true }, { "descriptor": "DNA, Viral", "descriptor_ui": "D004279", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Limit of Detection", "descriptor_ui": "D057230", "major_topic": true }, { "descriptor": "Paper", "descriptor_ui": "D010209", "major_topic": true }, { "descriptor": "Point-of-Care Systems", "descriptor_ui": "D019095", "major_topic": false }, { "descriptor": "Point-of-Care Testing", "descriptor_ui": "D000067716", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Aug 22", "date_precision": "day", "issue": "", "normalized_date": "2024-08-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "The Analyst", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Paper-based analytical device for point-of-care nucleic acid quantification combining CRISPR/Cas12a and a personal glucose meter.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIMS/HYPOTHESIS: Clustering-based subclassification of type 2 diabetes, which reflects pathophysiology and genetic predisposition, is a promising approach for providing personalised and effective therapeutic strategies. Ahlqvist's classification is currently the most vigorously validated method because of its superior ability to predict diabetes complications but it does not have strong consistency over time and requires HOMA2 indices, which are not routinely available in clinical practice and standard cohort studies. We developed a machine learning (ML) model to classify individuals with type 2 diabetes into Ahlqvist's subtypes consistently over time. METHODS: Cohort 1 dataset comprised 619 Japanese individuals with type 2 diabetes who were divided into training and test sets for ML models in a 7:3 ratio. Cohort 2 dataset, comprising 597 individuals with type 2 diabetes, was used for external validation. Participants were pre-labelled (T2D(kmeans)) by unsupervised k-means clustering based on Ahlqvist's variables (age at diagnosis, BMI, HbA(1c), HOMA2-B and HOMA2-IR) to four subtypes: severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD) and mild age-related diabetes (MARD). We adopted 15 variables for a multiclass classification random forest (RF) algorithm to predict type 2 diabetes subtypes (T2D(RF15)). The proximity matrix computed by RF was visualised using a uniform manifold approximation and projection. Finally, we used a putative subset with missing insulin-related variables to test the predictive performance of the validation cohort, consistency of subtypes over time and prediction ability of diabetes complications. RESULTS: T2D(RF15) demonstrated a 94% accuracy for predicting T2D(kmeans) type 2 diabetes subtypes (AUCs >/=0.99 and F1 score [an indicator calculated by harmonic mean from precision and recall] >/=0.9) and retained the predictive performance in the external validation cohort (86.3%). T2D(RF15) showed an accuracy of 82.9% for detecting T2D(kmeans), also in a putative subset with missing insulin-related variables, when used with an imputation algorithm. In Kaplan-Meier analysis, the diabetes clusters of T2D(RF15) demonstrated distinct accumulation risks of diabetic retinopathy in SIDD and that of chronic kidney disease in SIRD during a median observation period of 11.6 (4.5-18.3) years, similarly to the subtypes using T2D(kmeans). The predictive accuracy was improved after excluding individuals with low predictive probability, who were categorised as an 'undecidable' cluster. T2D(RF15), after excluding undecidable individuals, showed higher consistency (100% for SIDD, 68.6% for SIRD, 94.4% for MOD and 97.9% for MARD) than T2D(kmeans). CONCLUSIONS/INTERPRETATION: The new ML model for predicting Ahlqvist's subtypes of type 2 diabetes has great potential for application in clinical practice and cohort studies because it can classify individuals with missing HOMA2 indices and predict glycaemic control, diabetic complications and treatment outcomes with long-term consistency by using readily available variables. Future studies are needed to assess whether our approach is applicable to research and/or clinical practice in multiethnic populations.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hayato", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Akimitsu", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Shimajiri", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Ojima", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Masuzaki", "name": null }, { "creator_type": "author", "first_name": "Junichiro J.", "last_name": "Kazama", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Katagiri", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Tamiya", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Shimabukuro", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00125-024-06248-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39168869" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 2", "descriptor_ui": "D003924", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glycated Hemoglobin", "descriptor_ui": "D006442", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin Resistance", "descriptor_ui": "D007333", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Aug 21", "date_precision": "day", "issue": "", "normalized_date": "2024-08-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "Diabetologia", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Machine learning-based reproducible prediction of type 2 diabetes subtypes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Salinization poses an increasing problem worldwide, threatening freshwater organisms and raising questions about their ability to adapt. We explored the mechanisms enabling a planktonic crustacean to tolerate elevated salinity. By gradually raising water salinity in clonal cultures from 185 Daphnia magna populations, we showed that salt tolerance strongly correlates with native habitat salinity, indicating local adaptation. A genome-wide association study (GWAS) further revealed a major effect of the Alpha,alpha-trehalose-phosphate synthase (TPS) gene, suggesting that trehalose production facilitates salinity tolerance. Salinity-tolerant animals showed a positive correlation between water salinity and trehalose concentrations, while intolerant animals failed to produce trehalose. Animals with a non-functional TPS gene, generated through CRISPR-Cas9, supported the trehalose role in salinity stress. Our study highlights how a keystone freshwater animal adapts to salinity stress using an evolutionary mechanism known in bacteria, plants, and arthropods.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Joana L.", "last_name": "Santos", "name": null }, { "creator_type": "author", "first_name": "Fabienne", "last_name": "Nick", "name": null }, { "creator_type": "author", "first_name": "Nikko", "last_name": "Adhitama", "name": null }, { "creator_type": "author", "first_name": "Peter D.", "last_name": "Fields", "name": null }, { "creator_type": "author", "first_name": "Jonathon H.", "last_name": "Stillman", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Dieter", "last_name": "Ebert", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2024.07.082" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39168123" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": true }, { "descriptor": "Fresh Water", "descriptor_ui": "D005618", "major_topic": true }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": false }, { "descriptor": "Glucosyltransferases", "descriptor_ui": "D005964", "major_topic": false }, { "descriptor": "Salinity", "descriptor_ui": "D054712", "major_topic": false }, { "descriptor": "Salt Stress", "descriptor_ui": "D000077323", "major_topic": false }, { "descriptor": "Salt Tolerance", "descriptor_ui": "D055049", "major_topic": false }, { "descriptor": "Trehalose", "descriptor_ui": "D014199", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Aug 20", "date_precision": "day", "issue": "", "normalized_date": "2024-08-20", "pages": "S0960-9822(24)01021-2", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Trehalose mediates salinity-stress tolerance in natural populations of a freshwater crustacean.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: To investigate transcriptomic and immunophenotypic features of muscle specimens from patients with idiopathic inflammatory myopathy (IIM). METHODS: Bulk RNA-sequencing was performed on muscle biopsy samples from 16 patients with dermatomyositis (DM) and 9 patients with polymyositis (PM). Seven tested positive for anti-aminoacyl t-RNA synthetase antibodies in the DM patients (ARS-DM). We conducted weighted gene coexpression network analysis (WGCNA), differentially expressed gene (DEG) analysis, and gene set variation analysis (GSVA) to assess contributions of specific pathways. Cell proportions in muscle specimens were estimated using a deconvolution approach. RESULTS: WGCNA revealed significant positive correlations between serum creatine kinase (CK) levels and gene modules involved in cellular respiration, phagocytosis, and oxidative phosphorylation (OXPHOS). Significant positive correlations were also observed between CK levels and proportions of CD16-positive and -negative monocytes and myeloid dendritic cells. Notably, DM patients demonstrated enrichment of complement and interferon-alpha and -gamma pathway genes compared to those with PM. Furthermore, ARS-DM demonstrated a higher proportion of Th1 cells and DEGs related to OXPHOS. Additionally, serum Krebs von den Lungen-6 levels correlated with gene modules associated with extracellular matrix and transforming growth factor-beta signaling pathway. CONCLUSION: Our study highlights a significant involvement of monocytes in muscle damage and delineates pathological differences among IIM subtypes. DM was characterized by complement, interferon-alpha and -gamma signaling, whilst ARS-DM was associated with OXPHOS. Distinctive gene expression variations in muscle specimens suggest that different pathologic mechanisms underlie muscle damage in each IIM phenotype.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shinji", "last_name": "Izuka", "name": null }, { "creator_type": "author", "first_name": "Natsuka", "last_name": "Umezawa", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Komai", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sugimori", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Mizoguchi", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Fujieda", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Ninagawa", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Ohmura", "name": null }, { "creator_type": "author", "first_name": "Tsuneyo", "last_name": "Mimori", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Atsumi", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Akari", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Kochi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Tomohisa", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Mineto", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Keishi", "last_name": "Fujio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/art.42972" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39162115" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biopsy", "descriptor_ui": "D001706", "major_topic": false }, { "descriptor": "Creatine Kinase", "descriptor_ui": "D003402", "major_topic": false }, { "descriptor": "Dermatomyositis", "descriptor_ui": "D003882", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Monocytes", "descriptor_ui": "D009000", "major_topic": true }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": true }, { "descriptor": "Myositis", "descriptor_ui": "D009220", "major_topic": false }, { "descriptor": "Oxidative Phosphorylation", "descriptor_ui": "D010085", "major_topic": false }, { "descriptor": "Polymyositis", "descriptor_ui": "D017285", "major_topic": true }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Aug 20", "date_precision": "day", "issue": "", "normalized_date": "2024-08-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "Arthritis & rheumatology (Hoboken, N.J.)", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "The muscle tissue transcriptome of idiopathic inflammatory myopathy reflects the muscle damage process by monocytes and presence of skin lesions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dragon fruit oligosaccharide (DFO) is an indigestible prebiotic that enhances the growth and reproduction of Daphnia magna, increases the expression of genes involved in immunity, and reduces oxidative stress. This study investigated the effects of DFO on the expression of innate immunity- (Toll, Pelle, proPO, A2M, and CTL), oxidative stress- (Mn-SOD), and nitric oxide (NO) synthesis-related genes (NOS1, NOS2, and arginase) as well as NO localization and number of hemocytes in D. magna. For this ten-day-old D. magna were treated with 0 or 9 mg l(-1) of DFO for 24 and 85 h. Gene expression levels, NO intensity and localization, and total hemocytes were evaluated. After 24 h, the expression of Toll and proPO increased significantly (p < 0.05), while that of C-type lectins (CTL) was reduced (p < 0.05). At 85 h, Mn-SOD and CTL expressions were markedly suppressed (p < 0.05). NO was mostly localized in the foregut, midgut, hindgut, and carapace. The expression of NOS1 was reduced after 24 h (p < 0.05). In addition, NO intensity at 24 h was insignificantly lower than the control (p > 0.05). At 85 h, the expression of NOS1, NOS2, and arginase was higher than control, but, NO intensity did not differ significantly (p > 0.05). Furthermore, the total hemocyte count elevated remarkably at 85 h (p < 0.05). Our study suggested that 9 mg l(-1) of DFO could alter the expression of the genes related to innate immunity, oxidative stress, and NO synthesis in D. magna and significantly stimulate hemocyte production.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Thanwarat", "last_name": "Sangkuanun", "name": null }, { "creator_type": "author", "first_name": "Chittipong", "last_name": "Tipbunjong", "name": null }, { "creator_type": "author", "first_name": "Kato", "last_name": "Yasuhiko", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Saranya", "last_name": "Peerakietkhajorn", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.dci.2024.105251" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39168396" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arthropod Proteins", "descriptor_ui": "D060829", "major_topic": false }, { "descriptor": "Cactaceae", "descriptor_ui": "D029421", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": true }, { "descriptor": "Daphnia magna", "descriptor_ui": "D000096602", "major_topic": false }, { "descriptor": "Fruit", "descriptor_ui": "D005638", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Hemocytes", "descriptor_ui": "D006434", "major_topic": true }, { "descriptor": "Immunity, Cellular", "descriptor_ui": "D007111", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": true }, { "descriptor": "Lectins, C-Type", "descriptor_ui": "D037181", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": true }, { "descriptor": "Oligosaccharides", "descriptor_ui": "D009844", "major_topic": true }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": true }, { "descriptor": "Prebiotics", "descriptor_ui": "D056692", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Aug 19", "date_precision": "day", "issue": "", "normalized_date": "2024-08-19", "pages": "105251", "proceedings_title": null, "publisher": "", "title": "Developmental and comparative immunology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Dragon fruit-derived oligosaccharides alter hemocyte-mediated immunity and expression of genes related to innate immunity and oxidative stress in Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Antitumor effect of chimeric antigen receptor (CAR)-T cells against solid tumors is limited due to various factors, such as low infiltration rate, poor expansion capacity, and exhaustion of T cells within the tumor. NR4A transcription factors have been shown to play important roles in T-cell exhaustion in mice. However, the precise contribution of each NR4a factor to human T-cell differentiation remains to be clarified. METHODS: In this study, we deleted NR4A family factors, NR4A1, NR4A2, and NR4A3, in human CAR-T cells recognizing human epidermal growth factor receptor type 2 (HER2) by using the CRISPR/Cas9 system. We induced T-cell exhaustion in these cells in vitro through repeated co-culturing of CAR-T cells with Her2(+)A549 lung adenocarcinoma cells and evaluated cell surface markers such as memory and exhaustion phenotypes, proliferative capacity, cytokine production and metabolic activity. We validated the antitumor toxicity of NR4A1/2/3 triple knockout (TKO) CAR-T cells in vivo by transferring CAR-T cells into A549 tumor-bearing immunodeficient mice. RESULTS: Human NR4A-TKO CAR-T cells were resistant against exhaustion induced by repeated antigen stimulation in vitro, and maintained higher tumor-killing activity both in vitro and in vivo compared with control CAR-T cells. A comparison of the effectiveness of NR4A single, double, and TKOs demonstrated that triple KO was the most effective in avoiding exhaustion. Furthermore, a strong enhancement of antitumor effects by NR4A TKO was also observed in T cells from various donors including aged persons. Mechanistically, NR4A TKO CAR-T cells showed enhanced mitochondrial oxidative phosphorylation, therefore could persist for longer periods within the tumors. CONCLUSIONS: NR4A factors regulate CAR-T cell persistence and stemness through mitochondrial gene expression, therefore NR4A is a highly promising target for the generation of superior CAR-T cells against solid tumors.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kensuke", "last_name": "Nakagawara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Tanakorn", "last_name": "Srirat", "name": null }, { "creator_type": "author", "first_name": "Setsuko", "last_name": "Mise-Omata", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fukunaga", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1136/jitc-2023-008665" }, "pmcid": { "normalized": "PMC11331892" }, "pmid": { "normalized": "39151930" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunotherapy, Adoptive", "descriptor_ui": "D016219", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": true }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Nuclear Receptor Subfamily 4, Group A, Member 1", "descriptor_ui": "D057105", "major_topic": false }, { "descriptor": "Nuclear Receptor Subfamily 4, Group A, Member 2", "descriptor_ui": "D057126", "major_topic": false }, { "descriptor": "Receptors, Chimeric Antigen", "descriptor_ui": "D000076962", "major_topic": true }, { "descriptor": "Receptors, Steroid", "descriptor_ui": "D011987", "major_topic": false }, { "descriptor": "Receptors, Thyroid Hormone", "descriptor_ui": "D011988", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Aug 16", "date_precision": "day", "issue": "8", "normalized_date": "2024-08-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal for immunotherapy of cancer", "volume": "12", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "NR4A ablation improves mitochondrial fitness for long persistence in human CAR-T cells against solid tumors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The combination of radiotherapy/chemoradiotherapy and immune checkpoint blockade can result in poor outcomes in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Here, we show that combining ATR inhibition (ATRi) with radiotherapy (RT) increases the frequency of activated NKG2A(+)PD-1(+) T cells in animal models of HNSCC. Compared with the ATRi/RT treatment regimen alone, the addition of simultaneous NKG2A and PD-L1 blockade to ATRi/RT, in the adjuvant, post-radiotherapy setting induces a robust antitumour response driven by higher infiltration and activation of cytotoxic T cells in the tumour microenvironment. The efficacy of this combination relies on CD40/CD40L costimulation and infiltration of activated, proliferating memory CD8(+) and CD4(+) T cells with persistent or new T cell receptor (TCR) signalling, respectively. We also observe increased richness in the TCR repertoire and emergence of numerous and large TCR clonotypes that cluster based on antigen specificity in response to NKG2A/PD-L1/ATRi/RT. Collectively, our data point towards potential combination approaches for the treatment of HNSCC.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Emmanuel C.", "last_name": "Patin", "name": null }, { "creator_type": "author", "first_name": "Pablo", "last_name": "Nenclares", "name": null }, { "creator_type": "author", "first_name": "Charleen", "last_name": "Chan Wah Hak", "name": null }, { "creator_type": "author", "first_name": "Magnus T.", "last_name": "Dillon", "name": null }, { "creator_type": "author", "first_name": "Anton", "last_name": "Patrikeev", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "McLaughlin", "name": null }, { "creator_type": "author", "first_name": "Lorna", "last_name": "Grove", "name": null }, { "creator_type": "author", "first_name": "Shane", "last_name": "Foo", "name": null }, { "creator_type": "author", "first_name": "Heba", "last_name": "Soliman", "name": null }, { "creator_type": "author", "first_name": "Joao P.", "last_name": "Barata", "name": null }, { "creator_type": "author", "first_name": "Joanna", "last_name": "Marsden", "name": null }, { "creator_type": "author", "first_name": "Holly", "last_name": "Baldock", "name": null }, { "creator_type": "author", "first_name": "Jim", "last_name": "Gkantalis", "name": null }, { "creator_type": "author", "first_name": "Victoria", "last_name": "Roulstone", "name": null }, { "creator_type": "author", "first_name": "Joan", "last_name": "Kyula", "name": null }, { "creator_type": "author", "first_name": "Amy", "last_name": "Burley", "name": null }, { "creator_type": "author", "first_name": "Lisa", "last_name": "Hubbard", "name": null }, { "creator_type": "author", "first_name": "Malin", "last_name": "Pedersen", "name": null }, { "creator_type": "author", "first_name": "Simon A.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Eleanor", "last_name": "Clancy-Thompson", "name": null }, { "creator_type": "author", "first_name": "Alan A.", "last_name": "Melcher", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Antonio", "last_name": "Rullan", "name": null }, { "creator_type": "author", "first_name": "Kevin J.", "last_name": "Harrington", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-51236-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39134540" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ataxia Telangiectasia Mutated Proteins", "descriptor_ui": "D064007", "major_topic": true }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": true }, { "descriptor": "CD4-Positive T-Lymphocytes", "descriptor_ui": "D015496", "major_topic": false }, { "descriptor": "CD40 Antigens", "descriptor_ui": "D019013", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Head and Neck Neoplasms", "descriptor_ui": "D006258", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Checkpoint Inhibitors", "descriptor_ui": "D000082082", "major_topic": false }, { "descriptor": "Immunotherapy", "descriptor_ui": "D007167", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "NK Cell Lectin-Like Receptor Subfamily C", "descriptor_ui": "D055654", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false }, { "descriptor": "Squamous Cell Carcinoma of Head and Neck", "descriptor_ui": "D000077195", "major_topic": true }, { "descriptor": "T-Lymphocytes, Cytotoxic", "descriptor_ui": "D013602", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Aug 13", "date_precision": "day", "issue": "1", "normalized_date": "2024-08-13", "pages": "6923", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Sculpting the tumour microenvironment by combining radiotherapy and ATR inhibition for curative-intent adjuvant immunotherapy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Highly transmissible viruses including SARS-CoV-2 frequently accumulate novel mutations that are detected via high-throughput sequencing. However, there is a need to develop an alternative rapid and non-expensive approach. Here we developed a novel multiplex DNA detection method Intelli-OVI for analysing existing and novel mutations of SARS-CoV-2. METHODS: We have developed Intelli-OVI that includes the micro-disc-based method IntelliPlex and computational algorithms of objective variant identification (OVI). More than 250 SARS-CoV-2 positive samples including wastewater ones were analysed to verify the efficiency of the method. RESULTS: IntelliPlex uses micro-discs printed with a unique pictorial pattern as a labelling conjugate for DNA probes, and OVI allows simultaneous identification of several variants using multidimensional data obtained by the IntelliPlex method. Importantly, de novo mutations can be identified by decreased signals, which indicates that there is an emergence of de novo variant virus as well as prompts the need to design additional primers and probes. We have upgraded probe panel according to the emergence of new variants and demonstrated that Intelli-OVI efficiently identified more than 20 different SARS-CoV-2 variants by using 35 different probes simultaneously. CONCLUSIONS: Intelli-OVI can be upgraded to keep up with rapidly evolving viruses as we showed in this study using SARS-CoV-2 as an example and may be suitable for other viruses but would need to be validated.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Md Belal", "last_name": "Hossain", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Samiul Alam", "last_name": "Rajib", "name": null }, { "creator_type": "author", "first_name": "Akhinur", "last_name": "Rahman", "name": null }, { "creator_type": "author", "first_name": "Mitsuyoshi", "last_name": "Takatori", "name": null }, { "creator_type": "author", "first_name": "Benjy Jek Yang", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sugata", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Mamiyo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sadamasu", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Ogi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Takasuke", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Yorifumi", "last_name": "Satou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s43856-024-00582-z" }, "pmcid": { "normalized": "PMC11316138" }, "pmid": { "normalized": "39122992" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Aug 9", "date_precision": "day", "issue": "1", "normalized_date": "2024-08-09", "pages": "161", "proceedings_title": null, "publisher": "", "title": "Communications medicine", "volume": "4", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "A micro-disc-based multiplex method for monitoring emerging SARS-CoV-2 variants using the molecular diagnostic tool Intelli-OVI.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chloroplast ATP synthase (CF(o)CF(1)) synthesizes ATP by using a proton electrochemical gradient across the thylakoid membrane, termed DeltamuH(+), as an energy source. This gradient is necessary not only for ATP synthesis but also for reductive activation of CF(o)CF(1) by thioredoxin, using reducing equivalents produced by the photosynthetic electron transport chain. DeltamuH(+) comprises two thermodynamic components: pH differences across the membrane (DeltapH) and the transmembrane electrical potential (DeltaPsi). In chloroplasts, the ratio of these two components in DeltamuH(+) is crucial for efficient solar energy utilization. However, the specific contribution of each component to the reductive activation of CF(o)CF(1) remains unclear. In this study, an in vitro assay system for evaluating thioredoxin-mediated CF(o)CF(1) reduction is established, allowing manipulation of DeltamuH(+) components in isolated thylakoid membranes using specific chemicals. Our biochemical analyses revealed that DeltapH formation is essential for thioredoxin-mediated CF(o)CF(1) reduction on the thylakoid membrane, whereas DeltaPsi formation is nonessential.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takatoshi", "last_name": "Sekiguchi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbc.2024.107659" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39128728" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Chloroplast Proton-Translocating ATPases", "descriptor_ui": "D025222", "major_topic": true }, { "descriptor": "Chloroplasts", "descriptor_ui": "D002736", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Membrane Potentials", "descriptor_ui": "D008564", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": true }, { "descriptor": "Proton-Motive Force", "descriptor_ui": "D018892", "major_topic": false }, { "descriptor": "Protons", "descriptor_ui": "D011522", "major_topic": false }, { "descriptor": "Thioredoxins", "descriptor_ui": "D013879", "major_topic": false }, { "descriptor": "Thylakoids", "descriptor_ui": "D020524", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Aug 9", "date_precision": "day", "issue": "", "normalized_date": "2024-08-09", "pages": "107659", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Proton gradient across the chloroplast thylakoid membrane governs the redox regulatory function of ATP synthase.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Photosensitizing fluorescence protein is a promising tool for chromophore-assisted light inactivation (CALI) that enables specific oxidation and inactivation of intracellular molecules. However, a commonly used monomeric photosensitizing fluorescent protein, SuperNova, shows a low CALI efficiency due to its insufficient maturation at 37 degrees C, thereby limiting the application of CALI to various molecules, especially in mammalian cells. Here, we present a photosensitizing fluorescence protein, HyperNova, with markedly improved maturation at 37 degrees C, leading to greatly enhanced CALI efficiency. Exploiting this quality, HyperNova enables the application of CALI to variety of molecules such as a mitotic kinase and transcriptional factors that were highly challenging with conventional SuperNova. To further demonstrate the utility of HyperNova, we have also succeeded in developing novel CALI techniques for MAP kinases by HyperNova. Our findings suggest that HyperNova has the potential to expand the molecular toolbox for manipulating biological events in living cells, providing new avenues for investigating cellular signaling pathways.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "21H00423", "label": "21H00423", "researcher": "Kiwamu Takemoto", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hisashi", "last_name": "Shidara", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Ozaki-Noma", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Jitsuki", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Kiwamu", "last_name": "Takemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-024-06583-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39107369" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromophore-Assisted Light Inactivation", "descriptor_ui": "D061885", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": true }, { "descriptor": "Photosensitizing Agents", "descriptor_ui": "D017319", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Aug 6", "date_precision": "day", "issue": "1", "normalized_date": "2024-08-06", "pages": "945", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "7", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Optical inactivation of intracellular molecules by fast-maturating photosensitizing fluorescence protein, HyperNova.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The adaptive biasing force (ABF) technique allows sampling to proceed in a flat free energy surface when performing molecular dynamics (MD) simulations. Here, we present a protocol to perform MD simulations using the ABF technique and apply it to calculate the binding free energy of an RNA:RNA interaction. We describe steps for server setup, test running software, and building molecular models. We then detail procedures for running and configuring ABF-MD simulations and analyzing binding free energy and structural change. For complete details on the use and execution of this protocol, please refer to Fujita et al.(1) and Kameda et al.(2).", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takeru", "last_name": "Kameda", "name": null }, { "creator_type": "author", "first_name": "Daniel K.", "last_name": "Saha", "name": null }, { "creator_type": "author", "first_name": "Sourav", "last_name": "Ray", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Togashi", "name": null }, { "creator_type": "author", "first_name": "Katsura", "last_name": "Asano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xpro.2024.103223" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39083381" } }, "mesh": [ { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": true }, { "descriptor": "Nucleic Acid Conformation", "descriptor_ui": "D009690", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": true }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false }, { "descriptor": "Thermodynamics", "descriptor_ui": "D013816", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jul 30", "date_precision": "day", "issue": "3", "normalized_date": "2024-07-30", "pages": "103223", "proceedings_title": null, "publisher": "", "title": "STAR protocols", "volume": "5", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Protocol for calculating binding free energy of RNA:RNA interactions through molecular dynamics simulations using adaptive biasing force technique.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Prior to the formation of amyloid fibrils, the pathological hallmark in tau-related neurodegenerative disease, tau monomers aggregate into a diverse range of oligomers. Granular tau oligomers, consisting of approximately 40 tau protein molecules, are present in the prefrontal cortex of patients at Braak stages I-II, preclinical stages of Alzheimer's disease (AD). Antibodies to granular tau oligomers as antigens have not been reported. Therefore, we generated new rat monoclonal antibodies by immunization with granular tau oligomers. Three antibodies from different hybridoma clones showed stronger immunoreactivity to granular tau oligomers and tau fibrils compared with monomeric tau. Of the three antibodies, 2D6-2C6 showed 3000-fold greater immunoreactivity in P301L-tau transgenic (rTg4510) mice than in non-transgenic mice, while MC1 antibody, which detects pathological conformations of tau, showed a 5.5-fold increase. These results suggest that 2D6-2C6 recognizes aggregates more specifically than MC1. In AD subjects, 2D6-2C6 recognized neurofibrillary tangles and pretangles, and co-localized within AT8-positive cells containing phosphorylated tau aggregates. The epitope of 2D6-2C6 is the 423-430 amino acid (AA) sequence of C-terminal regions. Taken together, a novel monoclonal antibody, 2D6-2C6, generated by immunization with granular tau oligomers binds to tau aggregates at the 423-430 AA sequence.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Soeda", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Nakatani", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Ishigaki", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Takaichi", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Riku", "name": null }, { "creator_type": "author", "first_name": "James K.", "last_name": "Chambers", "name": null }, { "creator_type": "author", "first_name": "Riki", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Moniruzzaman", "last_name": "Mohammad", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-024-65949-7" }, "pmcid": { "normalized": "PMC11282240" }, "pmid": { "normalized": "39060263" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": true }, { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": true }, { "descriptor": "Epitopes", "descriptor_ui": "D000939", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunization", "descriptor_ui": "D007114", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": true }, { "descriptor": "Neurofibrillary Tangles", "descriptor_ui": "D016874", "major_topic": false }, { "descriptor": "Protein Aggregates", "descriptor_ui": "D066329", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jul 26", "date_precision": "day", "issue": "1", "normalized_date": "2024-07-26", "pages": "16391", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "14", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "A novel monoclonal antibody generated by immunization with granular tau oligomers binds to tau aggregates at 423-430 amino acid sequence.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Over the past decade, cancer immunotherapies have revolutionized the treatment of melanoma; however, responses vary across patient populations. Recently, baseline tumor size has been identified as an independent prognostic factor for overall survival in patients with melanoma receiving immune checkpoint inhibitors. MG1 is a novel oncolytic agent with broad tumor tropism that has recently entered early-phase clinical trials. The aim of this study was to characterize T-cell responses in human and mouse melanoma models following MG1 treatment and to establish if features of the tumor immune microenvironment (TIME) at two distinct tumor burdens would impact the efficacy of oncolytic virotherapy. METHODS: Human three-dimensional in vitro priming assays were performed to measure antitumor and antiviral T-cell responses following MG1 infection. T-cell receptor (TCR) sequencing, T2 killing assay, and peptide recall assays were used to assess the evolution of the TCR repertoire, and measure specific T-cell responses, respectively. In vivo, subcutaneous 4434 melanomas were characterized using RNA sequencing, immunohistochemistry, and flow cytometry. The effectiveness of intratumoral MG1 was assessed in advancing 4434 tumors and the generation of antitumor and antiviral T cells measured by splenocyte recall assays. Finally, combination MG1 and programmed cell death protein-1 antibody (alphaPD-1) therapy was investigated in advanced 4434 tumors. RESULTS: MG1 effectively supported priming of functional cytotoxic T cells (CTLs) against tumor-associated antigens as well as virus-derived peptides, as assessed using peptide recall and T2 killing assays, respectively. TCR sequencing revealed that MG1-primed CTL comprised larger clusters of similar CDR3 amino acid sequences compared with controls. In vivo testing of MG1 demonstrated that MG1 monotherapy was highly effective at treating early disease, resulting in 90% cures; however, the efficacy of MG1 reduced as the disease burden (local tumor size) increased, and the addition of alphaPD-1 was required to overcome resistance in more advanced disease. Differential gene expression profiles revealed that increased tumor burden was associated with an immunologically colder TIME. Furthermore, analysis of TCR signaling in advancing tumors demonstrated a different dynamic of TCR engagement compared with smaller tumors, in particular a shift in antigen recognition by CD4+ cells, from conventional to regulatory subsets. CONCLUSION: Addition of alphaPD-1 to MG1 is required to overcome viral therapy resistance in immunologically 'colder' more advanced melanoma, highlighting the importance of tumor burden to different types of immunotherapy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Edward", "last_name": "Armstrong", "name": null }, { "creator_type": "author", "first_name": "Matthew K. L.", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Shane", "last_name": "Foo", "name": null }, { "creator_type": "author", "first_name": "Lizzie", "last_name": "Appleton", "name": null }, { "creator_type": "author", "first_name": "Pablo", "last_name": "Nenclares", "name": null }, { "creator_type": "author", "first_name": "Anton", "last_name": "Patrikeev", "name": null }, { "creator_type": "author", "first_name": "Nitya", "last_name": "Mohan", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Mclaughlin", "name": null }, { "creator_type": "author", "first_name": "Galabina", "last_name": "Bozhanova", "name": null }, { "creator_type": "author", "first_name": "Julia", "last_name": "Hoebart", "name": null }, { "creator_type": "author", "first_name": "Victoria", "last_name": "Roulstone", "name": null }, { "creator_type": "author", "first_name": "Emmanuel", "last_name": "Patin", "name": null }, { "creator_type": "author", "first_name": "Malin", "last_name": "Pedersen", "name": null }, { "creator_type": "author", "first_name": "Joan", "last_name": "Kyula", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Fiona", "last_name": "Errington-Mais", "name": null }, { "creator_type": "author", "first_name": "John", "last_name": "Bell", "name": null }, { "creator_type": "author", "first_name": "Kevin J.", "last_name": "Harrington", "name": null }, { "creator_type": "author", "first_name": "Alan", "last_name": "Melcher", "name": null }, { "creator_type": "author", "first_name": "Victoria", "last_name": "Jennings", "name": null } ], "identifiers": { "doi": { "normalized": "10.1136/jitc-2024-009443" }, "pmcid": { "normalized": "PMC11284828" }, "pmid": { "normalized": "39060020" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Checkpoint Inhibitors", "descriptor_ui": "D000082082", "major_topic": true }, { "descriptor": "Melanoma", "descriptor_ui": "D008545", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Oncolytic Virotherapy", "descriptor_ui": "D050130", "major_topic": true }, { "descriptor": "Oncolytic Viruses", "descriptor_ui": "D050504", "major_topic": true }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jul 25", "date_precision": "day", "issue": "7", "normalized_date": "2024-07-25", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal for immunotherapy of cancer", "volume": "12", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Combination of oncolytic Maraba virus with immune checkpoint blockade overcomes therapy resistance in an immunologically cold model of advanced melanoma with dysfunctional T-cell receptor signalling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The auxin-inducible degron (AID) system degrades target proteins rapidly in a controllable manner. Although this is a highly versatile technique for studying protein functionality, protein degradation with spatiotemporal resolution is not currently possible. Herein we describe a photoswitchable AID using a light-active auxin derivative for reversible and site-specific protein degradation with temporal resolution.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Saugata", "last_name": "Sahu", "name": null }, { "creator_type": "author", "first_name": "Koya", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Tamaoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.4c05135" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39047232" } }, "mesh": [ { "descriptor": "Degrons", "descriptor_ui": "D000097791", "major_topic": true }, { "descriptor": "Indoleacetic Acids", "descriptor_ui": "D007210", "major_topic": true }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Photochemical Processes", "descriptor_ui": "D055668", "major_topic": false }, { "descriptor": "Proteolysis", "descriptor_ui": "D059748", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jul 24", "date_precision": "day", "issue": "", "normalized_date": "2024-07-24", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Photoswitchable Auxin-Inducible Degron System for Conditional Protein Degradation with Spatiotemporal Resolution.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: Predicting the prognosis of lung cancer is crucial for providing optimal medical care. However, a method to accurately predict the overall prognosis in patients with stage IV lung cancer, even with the use of machine learning, has not been established. Moreover, the inter-institutional generalizability of such algorithms remains unexplored. This study aimed to establish machine learning-based algorithms with inter-institutional generalizability to predict prognosis. MATERIALS AND METHODS: This multicenter, retrospective, hospital-based cohort study included consecutive patients with stage IV lung cancer who were randomly categorized into the training and independent test cohorts with a 2:1 ratio, respectively. The primary metric to assess algorithm performance was the area under the receiver operating characteristic curve in the independent test cohort. To assess the inter-institutional generalizability of the algorithms, we investigated their ability to predict patient outcomes in the remaining facility after being trained using data from 15 other facilities. RESULTS: Overall, 6,751 patients (median age, 70 years) were enrolled, and 1,515 (22 %) showed mutated epidermal growth factor receptor expression. The median overall survival was 16.6 (95 % confidence interval, 15.9-17.5) months. Algorithm performance metrics in the test cohort showed that the areas under the curves were 0.90 (95 % confidence interval, 0.88-0.91), 0.85 (0.84-0.87), 0.83 (0.81-0.85), and 0.85 (0.82-0.87) at 180, 360, 720, and 1,080 predicted survival days, respectively. The performance test of 16 algorithms for investigating inter-institutional generalizability showed median areas under the curves of 0.87 (range, 0.84-0.92), 0.84 (0.78-0.88), 0.84 (0.76-0.89), and 0.84 (0.75-0.90) at 180, 360, 720, and 1,080 days, respectively. CONCLUSION: This study developed machine learning algorithms that could accurately predict the prognosis in patients with stage IV lung cancer with high inter-institutional generalizability. This can enhance the accuracy of prognosis prediction and support informed and shared decision-making in clinical settings.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Murotani", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Toi", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Terufumi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Teppei", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Tamiya", "name": null }, { "creator_type": "author", "first_name": "Motoko", "last_name": "Tachihara", "name": null }, { "creator_type": "author", "first_name": "Takehito", "last_name": "Shukuya", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Tsuchiya-Kawano", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Sakata", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Otsubo", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Shibaki", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Makino", "name": null }, { "creator_type": "author", "first_name": "Isamu", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.lungcan.2024.107896" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39043076" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "ROC Curve", "descriptor_ui": "D012372", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jul 18", "date_precision": "day", "issue": "", "normalized_date": "2024-07-18", "pages": "107896", "proceedings_title": null, "publisher": "", "title": "Lung cancer (Amsterdam, Netherlands)", "volume": "194", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Prediction of prognosis in lung cancer using machine learning with inter-institutional generalizability: A multicenter cohort study (WJOG15121L: REAL-WIND).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Facilitates chromatin transcription (FACT) interacts with nucleosomes to promote gene transcription by regulating the dissociation and reassembly of nucleosomes downstream and upstream of RNA polymerase II (Pol II). A previous study reported that herpes simplex virus 1 (HSV-1) regulatory protein ICP22 interacted with FACT and was required for its recruitment to the viral DNA genome in HSV-1-infected cells. However, the biological importance of interactions between ICP22 and FACT in relation to HSV-1 infection is unclear. Here, we mapped the minimal domain of ICP22 required for its efficient interaction with FACT to a cluster of five basic amino acids in ICP22. A recombinant virus harboring alanine substitutions in this identified cluster led to the decreased accumulation of viral mRNAs from UL54, UL38, and UL44 genes, reduced Pol II occupancy of these genes in MRC-5 cells, and impaired HSV-1 virulence in mice following ocular or intracranial infection. Furthermore, the treatment of mice infected with wild-type HSV-1 with CBL0137, a FACT inhibitor currently being investigated in clinical trials, significantly improved the survival rate of mice. These results suggested that the interaction between ICP22 and FACT was required for efficient HSV-1 gene expression and pathogenicity. Therefore, FACT might be a potential therapeutic target for HSV-1 infection.IMPORTANCEICP22 is a well-known regulatory factor of HSV-1 gene expression, but its mechanism(s) are poorly understood. Although the interaction of FACT with ICP22 was reported previously, its significance in HSV-1 infection is unknown. Given that FACT is involved in gene transcription, it is of interest to investigate this interaction as it relates to HSV-1 gene expression. To determine a direct link between the interaction and HSV-1 infection, we mapped a minimal domain of ICP22 required for its efficient interaction with FACT and generated a recombinant virus carrying mutations in the identified domain. Using the recombinant virus, we obtained evidence suggesting that the interaction between ICP22 and FACT promoted Pol II transcription from HSV-1 genes and viral virulence in mice. In addition, CBL0137, an inhibitor of FACT, effectively protected mice from lethal HSV-1 infection, suggesting FACT might be a potential target for the development of novel anti-HSV drugs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shaocong", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00737-24" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39016551" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Viral", "descriptor_ui": "D015967", "major_topic": true }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": true }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immediate-Early Proteins", "descriptor_ui": "D017874", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Multigene Family", "descriptor_ui": "D005810", "major_topic": false }, { "descriptor": "Nucleosomes", "descriptor_ui": "D009707", "major_topic": true }, { "descriptor": "Recombination, Genetic", "descriptor_ui": "D011995", "major_topic": false }, { "descriptor": "RNA Polymerase II", "descriptor_ui": "D012319", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": true }, { "descriptor": "Virulence", "descriptor_ui": "D014774", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jul 17", "date_precision": "day", "issue": "", "normalized_date": "2024-07-17", "pages": "e0073724", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Impact of the interaction between herpes simplex virus 1 ICP22 and FACT on viral gene expression and pathogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Meconium, a non-invasive biomaterial reflecting prenatal substance accumulation, could provide valuable insights into neonatal health. However, the comprehensive protein profile of meconium across gestational ages remains unclear. Here, we conducted an extensive proteomic analysis of first meconium from 259 newborns across varied gestational ages to delineate protein composition and elucidate its relevance to neonatal diseases. The first meconium samples were collected, with the majority obtained before feeding, and the mean time for the first meconium passage from the anus was 11.9 +/- 9.47 h. Our analysis revealed 5370 host-derived meconium proteins, which varied depending on sex and gestational age. Specifically, meconium from preterm infants exhibited elevated concentrations of proteins associated with the extracellular matrix. Additionally, the protein profiles of meconium also exhibited unique variations depending on both specific diseases, including gastrointestinal diseases, congenital heart diseases, and maternal conditions. Furthermore, we developed a machine learning model to predict gestational ages using meconium proteins. Our model suggests that newborns with gastrointestinal diseases and congenital heart diseases may have immature gastrointestinal systems. These findings highlight the intricate relationship between clinical parameters and meconium protein composition, offering potential for a novel approach to assess neonatal gastrointestinal health.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Shitara", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Mukai", "name": null }, { "creator_type": "author", "first_name": "Goh", "last_name": "Kimoto", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kakiuchi", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Tomo", "last_name": "Kakihara", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nagamatsu", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Fujishiro", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Ohara", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Eiichiro", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-49805-w" }, "pmcid": { "normalized": "PMC11255260" }, "pmid": { "normalized": "39019879" } }, "mesh": [ { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gastrointestinal Diseases", "descriptor_ui": "D005767", "major_topic": false }, { "descriptor": "Gestational Age", "descriptor_ui": "D005865", "major_topic": true }, { "descriptor": "Heart Defects, Congenital", "descriptor_ui": "D006330", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infant, Newborn", "descriptor_ui": "D007231", "major_topic": false }, { "descriptor": "Infant, Premature", "descriptor_ui": "D007234", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Meconium", "descriptor_ui": "D008470", "major_topic": true }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Proteome", "descriptor_ui": "D020543", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jul 17", "date_precision": "day", "issue": "1", "normalized_date": "2024-07-17", "pages": "5543", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Host-derived protein profiles of human neonatal meconium across gestational ages.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular tau aggregation requires a local protein concentration increase, referred to as \"droplets\". However, the cellular mechanism for droplet formation is poorly understood. Here, we expressed OptoTau, a P301L mutant tau fused with CRY2olig, a light-sensitive protein that can form homo-oligomers. Under blue light exposure, OptoTau increased tau phosphorylation and was sequestered in aggresomes. Suppressing aggresome formation by nocodazole formed tau granular clusters in the cytoplasm. The granular clusters disappeared by discontinuing blue light exposure or 1,6-hexanediol treatment suggesting that intracellular tau droplet formation requires microtubule collapse. Expressing OptoTau-DeltaN, a species of N-terminal cleaved tau observed in the Alzheimer's disease brain, formed 1,6-hexanediol and detergent-resistant tau clusters in the cytoplasm with blue light stimulation. These intracellular stable tau clusters acted as a seed for tau fibrils in vitro. These results suggest that tau droplet formation and N-terminal cleavage are necessary for neurofibrillary tangles formation in neurodegenerative diseases.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Soeda", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null }, { "creator_type": "author", "first_name": "Riki", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Isshin", "last_name": "Shiiba", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.str.2024.06.018" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39032487" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Neurofibrillary Tangles", "descriptor_ui": "D016874", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Aggregation, Pathological", "descriptor_ui": "D066263", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jul 12", "date_precision": "day", "issue": "", "normalized_date": "2024-07-12", "pages": "S0969-2126(24)00236-3", "proceedings_title": null, "publisher": "", "title": "Structure (London, England : 1993)", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Intracellular tau fragment droplets serve as seeds for tau fibrils.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dietary intake of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA) exerts antiarrhythmic effects, although the mechanisms are poorly understood. Here, we investigated the possible beneficial actions of EPA on saturated fatty acid-induced changes in the L-type Ca(2+) channel in cardiomyocytes. Cardiomyocytes were cultured with an oleic acid/palmitic acid mixture (OAPA) in the presence or absence of EPA. Beating rate reduction in cardiomyocytes caused by OAPA were reversed by EPA. EPA also retrieved a reduction in Cav1.2 L-type Ca(2+) current, mRNA, and protein caused by OAPA. Immunocytochemical analysis revealed a distinct downregulation of the Cav1.2 channel caused by OAPA with a concomitant decrease in the phosphorylated component of a transcription factor adenosine-3',5'-cyclic monophosphate (cAMP) response element binding protein (CREB) in the nucleus, which were rescued by EPA. A free fatty acid receptor 4 (FFAR4) agonist TUG-891 reversed expression of Cav1.2 and CREB mRNA caused by OAPA, whereas an FFAR4 antagonist AH-7614 abolished the effects of EPA. Excessive reactive oxygen species (ROS) accumulation caused by OAPA decreased Cav1.2 and CREB mRNA expressions, which was reversed by an ROS scavenger. Our data suggest that EPA rescues cellular Cav1.2-Ca(2+) channel decline caused by OAPA lipotoxicity and oxidative stresses via both free fatty acid receptor 4-dependent and -independent pathways.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masaki", "last_name": "Morishima", "name": null }, { "creator_type": "author", "first_name": "Pu", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Horii", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Katsushige", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms25147570" }, "pmcid": { "normalized": "PMC11276759" }, "pmid": { "normalized": "39062812" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Channels, L-Type", "descriptor_ui": "D020746", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cyclic AMP Response Element-Binding Protein", "descriptor_ui": "D017362", "major_topic": false }, { "descriptor": "Eicosapentaenoic Acid", "descriptor_ui": "D015118", "major_topic": true }, { "descriptor": "Fatty Acids", "descriptor_ui": "D005227", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jul 10", "date_precision": "day", "issue": "14", "normalized_date": "2024-07-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "25", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Eicosapentaenoic Acid Rescues Cav1.2-L-Type Ca(2+) Channel Decline Caused by Saturated Fatty Acids via Both Free Fatty Acid Receptor 4-Dependent and -Independent Pathways in Cardiomyocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sequential optimization is one of the promising approaches in identifying the optimal candidate(s) (molecules, reactants, drugs, etc.) with desired properties (reaction yield, selectivity, efficacy, etc.) from a large set of potential candidates, while minimizing the number of experiments required. However, the high dimensionality of the feature space (e.g., molecular descriptors) makes it often difficult to utilize the relevant features during the process of updating the set of candidates to be examined. In this article, we developed a new sequential optimization algorithm for molecular problems based on reinforcement learning, multi-armed linear bandit framework, and online, dynamic feature selections in which relevant molecular descriptors are updated along with the experiments. We also designed a stopping condition aimed to guarantee the reliability of the chosen candidate from the dataset pool. The developed algorithm was examined by comparing with Bayesian optimization (BO), using two synthetic datasets and two real datasets in which one dataset includes hydration free energy of molecules and another one includes a free energy difference between enantiomer products in chemical reaction. We found that the dynamic feature selection in representing the desired properties along the experiments provides a better performance (e.g., time required to find the best candidate and stop the experiment) as the overall trend and that our multi-armed linear bandit approach with a dynamic feature selection scheme outperforms the standard BO with fixed feature variables. The comparison of our algorithm to BO with dynamic feature selection is also addressed.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Md Menhazul", "last_name": "Abedin", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/5.0206042" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38958158" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Jul 7", "date_precision": "day", "issue": "1", "normalized_date": "2024-07-07", "pages": "014115", "proceedings_title": null, "publisher": "", "title": "The Journal of chemical physics", "volume": "161", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Multi-armed bandit algorithm for sequential experiments of molecular properties with dynamic feature selection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures and experimental animals, and the use of human sera and antiviral compounds, to reveal the virological features of the newly emerging EG.5.1 variant. Our phylogenetic analysis and epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T are critical to its increased viral fitness. Experimental investigations on the growth kinetics, sensitivity to clinically available antivirals, fusogenicity, and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 are comparable to those of XBB.1.5. However, cryo-electron microscopy revealed structural differences between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible in our experimental setup. Our multiscale investigations provide knowledge for understanding the evolutionary traits of newly emerging pathogenic viruses, including EG.5.1, in the human population.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shuhei", "last_name": "Tsujino", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Deguchi", "name": null }, { "creator_type": "author", "first_name": "Tomo", "last_name": "Nomai", "name": null }, { "creator_type": "author", "first_name": "Miguel", "last_name": "Padilla-Blanco", "name": null }, { "creator_type": "author", "first_name": "Arnon", "last_name": "Plianchaisuk", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Mst Monira", "last_name": "Begum", "name": null }, { "creator_type": "author", "first_name": "Keiya", "last_name": "Uriu", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Mizuma", "name": null }, { "creator_type": "author", "first_name": "Naganori", "last_name": "Nao", "name": null }, { "creator_type": "author", "first_name": "Isshu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Tsubo", "name": null }, { "creator_type": "author", "first_name": "Jingshu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Anraku", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Hisano", "last_name": "Yajima", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Sasaki-Tabata", "name": null }, { "creator_type": "author", "first_name": "Ziyi", "last_name": "Guo", "name": null }, { "creator_type": "author", "first_name": "Alfredo A. Jr", "last_name": "Hinay", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Yoshimatsu", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tetsuharu", "last_name": "Nagamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Asakura", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sadamasu", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Hesham", "last_name": "Nasser", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Jonathan", "name": null }, { "creator_type": "author", "first_name": "Olivia", "last_name": "Putri", "name": null }, { "creator_type": "author", "first_name": "Yoonjin", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Luo", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Rigel", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Maenaka", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Irie", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Matsuno", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Terumasa", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Jiri", "last_name": "Zahradnik", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Hashiguchi", "name": null }, { "creator_type": "author", "first_name": "Takasuke", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/1348-0421.13165" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38961765" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antiviral Agents", "descriptor_ui": "D000998", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Cryoelectron Microscopy", "descriptor_ui": "D020285", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": true }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true }, { "descriptor": "Spike Glycoprotein, Coronavirus", "descriptor_ui": "D064370", "major_topic": true }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jul 4", "date_precision": "day", "issue": "", "normalized_date": "2024-07-04", "pages": "", "proceedings_title": null, "publisher": "", "title": "Microbiology and immunology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Virological characteristics of the SARS-CoV-2 Omicron EG.5.1 variant.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Developmental synapse elimination is crucial for shaping mature neural circuits. In the neonatal mouse cerebellum, Purkinje cells (PCs) receive excitatory synaptic inputs from multiple climbing fibers (CFs) and synapses from all but one CF are eliminated by around postnatal day 20. Heterosynaptic interaction between CFs and parallel fibers (PFs), the axons of cerebellar granule cells (GCs) forming excitatory synapses onto PCs and molecular layer interneurons (MLIs), is crucial for CF synapse elimination. However, mechanisms for this heterosynaptic interaction are largely unknown. Here we show that deletion of AMPA-type glutamate receptor functions in GCs impairs CF synapse elimination mediated by metabotropic glutamate receptor 1 (mGlu1) signaling in PCs. Furthermore, CF synapse elimination is impaired by deleting NMDA-type glutamate receptors from MLIs. We propose that PF activity is crucial for CF synapse elimination by directly activating mGlu1 in PCs and indirectly enhancing the inhibition of PCs through activating NMDA receptors in MLIs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hisako", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Myeongjeong", "last_name": "Choo", "name": null }, { "creator_type": "author", "first_name": "Kohtarou", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-024-06447-4" }, "pmcid": { "normalized": "PMC11222442" }, "pmid": { "normalized": "38961250" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": true }, { "descriptor": "Interneurons", "descriptor_ui": "D007395", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Receptors, AMPA", "descriptor_ui": "D018091", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": true }, { "descriptor": "Receptors, N-Methyl-D-Aspartate", "descriptor_ui": "D016194", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jul 3", "date_precision": "day", "issue": "1", "normalized_date": "2024-07-03", "pages": "806", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "7", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Direct and indirect pathways for heterosynaptic interaction underlying developmental synapse elimination in the mouse cerebellum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The fluorinated thymidine analog trifluridine (FTD) is a chemotherapeutic drug commonly used to treat cancer; however, the mechanism by which FTD induces cytotoxicity is not fully understood. In addition, the effect of gain-of-function (GOF) missense mutations of the TP53 gene (encoding p53), which promote cancer progression and chemotherapeutic drug resistance, on the chemotherapeutic efficacy of FTD is unclear. Here, we revealed the mechanisms by which FTD-induced aberrant mitosis and contributed to cytotoxicity in both p53-null and p53-GOF missense mutant cells. In p53-null mutant cells, FTD-induced DNA double-stranded breaks, single-stranded DNA accumulation, and the associated DNA damage responses during the G2 phase. Nevertheless, FTD-induced DNA damage and the related responses were not sufficient to trigger strict G2/M checkpoint arrest. Thus, these features were carried over into mitosis, resulting in chromosome breaks and bridges, and subsequent cytokinesis failure. Improper mitotic exit eventually led to cell apoptosis, caused by the accumulation of extensive DNA damage and the presence of micronuclei encapsulated in the disrupted nuclear envelope. Upon FTD treatment, the behavior of the p53-GOF-missense mutant, isogenic cell lines, generated by CRISPR/Cas9 genome editing, was similar to that of p53-null mutant cells. Thus, our data suggest that FTD treatment overrode the effect on gene expression induced by p53-GOF mutants and exerted its anti-tumor activity in a manner that was independent of the p53 function.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Wakasa", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Kikutake", "name": null }, { "creator_type": "author", "first_name": "Mikita", "last_name": "Suyama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kobunai", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Tsunekuni", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Ochiiwa", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Miyadera", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Sagara", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Ohdo", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Iimori", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kitao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41420-024-02083-3" }, "pmcid": { "normalized": "PMC11219725" }, "pmid": { "normalized": "38956056" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Jul 2", "date_precision": "day", "issue": "1", "normalized_date": "2024-07-02", "pages": "307", "proceedings_title": null, "publisher": "", "title": "Cell death discovery", "volume": "10", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "The anti-tumor effect of trifluridine via induction of aberrant mitosis is unaffected by mutations modulating p53 activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We develop a data harmonization approach for C. elegans volumetric microscopy data, still or video, consisting of a standardized format, data pre-processing techniques, and a set of human-in-the-loop machine learning based analysis software tools. We unify a diverse collection of 118 whole-brain neural activity imaging datasets from 5 labs, storing these and accompanying tools in an online repository called WormID (wormid.org). We use this repository to train three existing automated cell identification algorithms to, for the first time, enable accuracy in neural identification that generalizes across labs, approaching human performance in some cases. We mine this repository to identify factors that influence the developmental positioning of neurons. To facilitate communal use of this repository, we created open-source software, code, web-based tools, and tutorials to explore and curate datasets for contribution to the scientific community. This repository provides a growing resource for experimentalists, theorists, and toolmakers to (a) study neuroanatomical organization and neural activity across diverse experimental paradigms, (b) develop and benchmark algorithms for automated neuron detection, segmentation, cell identification, tracking, and activity extraction, and (c) inform models of neurobiological development and function.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Daniel Y.", "last_name": "Sprague", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Rusch", "name": null }, { "creator_type": "author", "first_name": "Raymond L.", "last_name": "Dunn", "name": null }, { "creator_type": "author", "first_name": "Jackson M.", "last_name": "Borchardt", "name": null }, { "creator_type": "author", "first_name": "Steven", "last_name": "Ban", "name": null }, { "creator_type": "author", "first_name": "Greg", "last_name": "Bubnis", "name": null }, { "creator_type": "author", "first_name": "Grace C.", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Chentao", "last_name": "Wen", "name": null }, { "creator_type": "author", "first_name": "Ryoga", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shivesh", "last_name": "Chaudhary", "name": null }, { "creator_type": "author", "first_name": "Hyun Jee", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Zikai", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Benjamin", "last_name": "Dichter", "name": null }, { "creator_type": "author", "first_name": "Ryan", "last_name": "Ly", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Hang", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Koutarou D.", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Eviatar", "last_name": "Yemini", "name": null }, { "creator_type": "author", "first_name": "Saul", "last_name": "Kato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/2024.04.28.591397" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Jun 29", "date_precision": "day", "issue": null, "normalized_date": "2024-06-29", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Unifying community-wide whole-brain imaging datasets enables robust automated neuron identification and reveals determinants of neuron positioning in C. elegans.", "url": "", "zotero": { "item_type": "preprint" } }, { "abstract": "Bow-tie architecture is a layered network structure that has a narrow middle layer with multiple inputs and outputs. Such structures are widely seen in the molecular networks in cells, suggesting that a universal evolutionary mechanism underlies the emergence of bow-tie architecture. The previous theoretical studies have implemented evolutionary simulations of the feedforward network to satisfy a given input-output goal and proposed that the bow-tie architecture emerges when the ideal input-output relation is given as a rank-deficient matrix with mutations in network link intensities in a multiplicative manner. Here, we report that the bow-tie network inevitably appears when the link intensities representing molecular interactions are small at the initial condition of the evolutionary simulation, regardless of the rank of the goal matrix. Our dynamical system analysis clarifies the mechanisms underlying the emergence of the bow-tie structure. Further, we demonstrate that the increase in the input-output matrix reduces the width of the middle layer, resulting in the emergence of bow-tie architecture, even when evolution starts from large link intensities. Our data suggest that bow-tie architecture emerges as a side effect of evolution rather than as a result of evolutionary adaptation.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Thoma", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Nen", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41540-024-00396-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38951549" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Systems Biology", "descriptor_ui": "D049490", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jun 29", "date_precision": "day", "issue": "1", "normalized_date": "2024-06-29", "pages": "70", "proceedings_title": null, "publisher": "", "title": "NPJ systems biology and applications", "volume": "10", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Revisiting the evolution of bow-tie architecture in signaling networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cytoplasm is a complex, crowded environment that influences myriad cellular processes including protein folding and metabolic reactions. Recent studies have suggested that changes in the biophysical properties of the cytoplasm play a key role in cellular homeostasis and adaptation. However, it still remains unclear how cells control their cytoplasmic properties in response to environmental cues. Here, we used fission yeast spores as a model system of dormant cells to elucidate the mechanisms underlying regulation of the cytoplasmic properties. By tracking fluorescent tracer particles, we found that particle mobility decreased in spores compared to vegetative cells and rapidly increased at the onset of dormancy breaking upon glucose addition. This cytoplasmic fluidization depended on glucose-sensing via the cyclic adenosine monophosphate-protein kinase A pathway. PKA activation led to trehalose degradation through trehalase Ntp1, thereby increasing particle mobility as the amount of trehalose decreased. In contrast, the rapid cytoplasmic fluidization did not require de novo protein synthesis, cytoskeletal dynamics, or cell volume increase. Furthermore, the measurement of diffusion coefficients with tracer particles of different sizes suggests that the spore cytoplasm impedes the movement of larger protein complexes (40 to 150 nm) such as ribosomes, while allowing free diffusion of smaller molecules (~3 nm) such as second messengers and signaling proteins. Our experiments have thus uncovered a series of signaling events that enable cells to quickly fluidize the cytoplasm at the onset of dormancy breaking.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2405553121" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38889144" } }, "mesh": [ { "descriptor": "Cyclic AMP-Dependent Protein Kinases", "descriptor_ui": "D017868", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": true }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Schizosaccharomyces", "descriptor_ui": "D012568", "major_topic": true }, { "descriptor": "Schizosaccharomyces pombe Proteins", "descriptor_ui": "D029702", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Spores, Fungal", "descriptor_ui": "D013172", "major_topic": true }, { "descriptor": "Trehalose", "descriptor_ui": "D014199", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jun 25", "date_precision": "day", "issue": "26", "normalized_date": "2024-06-25", "pages": "e2405553121", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "121", "year": 2024 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000360" ] }, "title": "Cytoplasmic fluidization contributes to breaking spore dormancy in fission yeast.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Aldehyde dehydrogenase 1A1 (ALDH1A1) stands out as one of the most reliable intracellular biomarkers for stem cells because it is expressed in both cancer stem cells (CSCs) and normal somatic stem cells (NSCs). Although several turn-on fluorescent probes for ALDH1A1 have been developed to visualize CSCs in cancer cells, the discrimination of CSCs from NSCs is difficult. We here report an AND-type dual-responsive fluorescent probe, CHO_betagal, the near-infrared fluorescence of which can be turned on after responding to both ALDH1A1 and beta-galactosidase. The AND-type dual responsiveness enables CSCs to be clearly visualized, whereas NSCs are non-emissive in microscopy. CSC-positive metastasis model lungs were successfully discriminated from normal lungs in ex vivo staining experiments using CHO_betagal, whereas the single-input ALDH1A1-responsive probe failed to achieve this discrimination owing to pronounced false-positive fluorescence output from lung NSCs. In tissue slice staining experiments, even in the presence of adjacent normal tissues, the peripheral region-specific localization of CSCs was clear. The versatility of CHO_betagal holds promise not only as a fundamental in vitro research tool for visualizing CSCs but also as a valuable asset in practical tissue staining diagnosis, significantly contributing to the assessment of cancer malignancy.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Oe", "name": null }, { "creator_type": "author", "first_name": "Kanae", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Huiying", "last_name": "Mu", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Iwatake", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yukawa", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d4tb00897a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38913327" } }, "mesh": [ { "descriptor": "Aldehyde Dehydrogenase 1 Family", "descriptor_ui": "D000080924", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infrared Rays", "descriptor_ui": "D007259", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": true }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Retinal Dehydrogenase", "descriptor_ui": "D050697", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jun 24", "date_precision": "day", "issue": "", "normalized_date": "2024-06-24", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of materials chemistry. B", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Dual-responsive near-infrared turn-on fluorescent probe for cancer stem cell-specific visualization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Adeno-associated virus (AAV) vectors are potential tools for cell-type-selective gene delivery to the central nervous system. Although cell-type-specific enhancers and promoters have been identified for AAV systems, there is limited information regarding the effects of AAV genomic components on the selectivity and efficiency of gene expression. Here, we offer an alternative strategy to provide specific and efficient gene delivery to a targeted neuronal population by optimizing recombinant AAV genomic components, named TAREGET (TransActivator-Regulated Enhanced Gene Expression within Targeted neuronal populations). We established this strategy in oxytocinergic neurons and showed that the TAREGET enabled sufficient gene expression to label long-projecting axons in wild-type mice. Its application to other cell types, including serotonergic and dopaminergic neurons, was also demonstrated. These results demonstrate that optimization of AAV expression cassettes can improve the specificity and efficiency of cell-type-specific gene expression and that TAREGET can renew previously established cell-type-specific promoters with improved performance.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Leo", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Rokujo", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2024.109878" }, "pmcid": { "normalized": "PMC11126825" }, "pmid": { "normalized": "38799556" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Jun 21", "date_precision": "day", "issue": "6", "normalized_date": "2024-06-21", "pages": "109878", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "27", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Optimization of AAV vectors for transactivator-regulated enhanced gene expression within targeted neuronal populations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Plasticity during the critical period is important for the functional maturation of cortical neurons. While characteristics of plasticity are diverse among cortical layers, it is unknown whether critical period timing is controlled by a common or unique molecular mechanism among them. We here clarified layer-specific regulation of the critical period timing of ocular dominance plasticity in the primary visual cortex. Mice lacking the endocannabinoid synthesis enzyme diacylglycerol lipase-alpha exhibited precocious critical period timing, earlier maturation of inhibitory synaptic function in layers 2/3 and 4, and impaired development of the binocular matching of orientation selectivity exclusively in layer 2/3. Activation of cannabinoid receptor restored ocular dominance plasticity at the normal critical period in layer 2/3. Suppression of GABA(A) receptor rescued precocious ocular dominance plasticity in layer 4. Therefore, endocannabinoids regulate critical period timing and maturation of visual function partly through the development of inhibitory synaptic functions in a layer-dependent manner.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Taisuke", "last_name": "Yoneda", "name": null }, { "creator_type": "author", "first_name": "Katsuro", "last_name": "Kameyama", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Gotou", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Terata", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Hata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2024.110145" }, "pmcid": { "normalized": "PMC11215304" }, "pmid": { "normalized": "38952682" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Jun 21", "date_precision": "day", "issue": "6", "normalized_date": "2024-06-21", "pages": "110145", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "27", "year": 2024 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000418" ] }, "title": "Layer specific regulation of critical period timing and maturation of mouse visual cortex by endocannabinoids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The differentiation of B cells into plasma cells is associated with substantial transcriptional and epigenetic remodeling. H3.3 histone variant marks active chromatin via replication-independent nucleosome assembly. However, its role in plasma cell development remains elusive. Herein, we show that during plasma cell differentiation, H3.3 is downregulated, and the deposition of H3.3 and chromatin accessibility are dynamically changed. Blockade of H3.3 downregulation by enforced H3.3 expression impairs plasma cell differentiation in an H3.3-specific sequence-dependent manner. Mechanistically, enforced H3.3 expression inhibits the upregulation of plasma cell-associated genes such as Irf4, Prdm1, and Xbp1 and maintains the expression of B cell-associated genes, Pax5, Bach2, and Bcl6. Concomitantly, sustained H3.3 expression prevents the structure of chromatin accessibility characteristic for plasma cells. Our findings suggest that appropriate H3.3 expression and deposition control plasma cell differentiation.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuichi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Ushijima", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Akemi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Stephen L.", "last_name": "Nutt", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-49375-x" }, "pmcid": { "normalized": "PMC11190180" }, "pmid": { "normalized": "38902223" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interferon Regulatory Factor-4", "descriptor_ui": "D000099218", "major_topic": false }, { "descriptor": "Interferon Regulatory Factors", "descriptor_ui": "D050835", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Plasma Cells", "descriptor_ui": "D010950", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jun 20", "date_precision": "day", "issue": "1", "normalized_date": "2024-06-20", "pages": "5004", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Plasma cell differentiation is regulated by the expression of histone variant H3.3.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Social behavior, defined as any mode of communication between conspecifics is regulated by a widespread network comprising multiple brain structures. The anterior cingulate cortex (ACC) serves as a hub region interconnected with several brain regions involved in social behavior. Because the ACC coordinates various behaviors, it is important to focus on a subpopulation of neurons that are potentially involved in social behavior to clarify the precise role of the ACC in social behavior. In this study, we aimed to analyze the roles of a social stimulus-responsive subpopulation of neurons in the ACC in social behavior in mice. We demonstrated that a subpopulation of neurons in the ACC was activated by social stimuli and that silencing the social stimulus-responsive subpopulation of neurons in the ACC significantly impaired social interaction without affecting locomotor activity or anxiety-like behavior. Our current findings highlight the importance of the social stimulus-responsive subpopulation of neurons in the ACC for social behavior and the association between ACC dysfunction and impaired social behavior, which sheds light on therapeutic interventions for psychiatric conditions.", "classifications": [ { "id": "18H05416", "label": "18H05416", "researcher": "Hitoshi Hashimoto", "type": "grant" }, { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kohei", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2024.150251" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38936249" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anxiety", "descriptor_ui": "D001007", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Gyrus Cinguli", "descriptor_ui": "D006179", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jun 19", "date_precision": "day", "issue": "", "normalized_date": "2024-06-19", "pages": "150251", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "726", "year": 2024 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000423" ] }, "title": "Socially activated neurons in the anterior cingulate cortex are essential for social behavior in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Despite the promising features of the CRISPR/Cas system for application to point-of-care nucleic acid tests, there are only a few reports on its integration into paper-based analytical devices (PADs) for the purpose of assay simplification. In most cases, paper platforms have only been used for the final signal readout in an assay otherwise performed in a test tube. Therefore, there is very limited information on the suitability of the CRISPR/Cas system for on-device reagent storage. To fill this gap, the current work primarily investigated the influence of various factors, including the type of paper, reagent drying method, effect of stabilizers, and storage condition on the storage stability of reagents necessary for CRISPR-based assays on paper substrates, by comparing the fluorescence signal emitted by the trans-cleavage of the dsDNA-activated Cas12a complex. The results obtained in the form of fluorescence signals emitted after trans-cleavage of a ssDNA probe through a dsDNA-activated Cas12a complex on paper substrates showed that CRISPR-related reagents spontaneously dried at room temperature on BSA blocked paper retained over 70% of their initial activity when stored at -20 degrees C for 28 days, independent of the type of paper substrates, which was improved by the addition of sucrose as a stabilizer. In addition, reagents dried on paper substrates under the optimized conditions exhibited stronger heat tolerance at temperatures above 65 degrees C compared to their corresponding solutions. This work is expected to contribute to the future development of fully integrated PADs relying on CRISPR/Cas systems for point-of-care applications requiring no additional reagent handling.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Tanifuji", "name": null }, { "creator_type": "author", "first_name": "Hikaru", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Guodong", "last_name": "Tong", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d4ay00848k" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38864392" } }, "mesh": [ { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": true }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Paper", "descriptor_ui": "D010209", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jun 12", "date_precision": "day", "issue": "", "normalized_date": "2024-06-12", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical methods : advancing methods and applications", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Basic evaluation of the CRISPR/Cas system stability for application to paper-based analytical devices.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genetically encoded Ca(2+) indicators (GECIs) are versatile for live imaging of cellular activities. Besides the brightness and dynamic range of signal change of GECIs, Ca(2+) affinity is another critical parameter for successful Ca(2+) imaging, as the concentration range of Ca(2+) dynamics differs from low nanomolar to sub-millimolar depending on the celltype and organism. However, ultrahigh-affinity GECIs, particularly the single fluorescent protein (1FP)-type, are lacking. Here, we report a simple strategy that increases Ca(2+) affinity through the linker length optimization in topology mutants of existing 1FP-type GECIs. The resulting ultrahigh-affinity GECIs, CaMPARI-nano, BGECO-nano, and RCaMP-nano (K(d) = 17-25 nM), enable unique biological applications, including the detection of low nanomolar Ca(2+) dynamics, highlighting active signaling cells, and multi-functional imaging with other second messengers. The linker length optimization in topology mutants could be applied to other 1FP-type indicators of glutamate and potassium, rendering it a widely applicable technique for modulating indicator affinity.", "classifications": [ { "id": "18H05415", "label": "18H05415", "researcher": "Kazuki Horikawa", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Ichiraku", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Ayuko", "last_name": "Sakane", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-024-06394-0" }, "pmcid": { "normalized": "PMC11162441" }, "pmid": { "normalized": "38851844" } }, "mesh": [ { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": true }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jun 8", "date_precision": "day", "issue": "1", "normalized_date": "2024-06-08", "pages": "705", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "7", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "High-affinity tuning of single fluorescent protein-type indicators by flexible linker length optimization in topology mutant.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "T cells play an important role in the acquired immune response, with regulatory T cells (Tregs) serving as key players in immune tolerance. Tregs are found in nonlymphoid and damaged tissues and are referred to as \"tissue Tregs\". They have tissue-specific characteristics and contribute to immunomodulation, homeostasis, and tissue repair through interactions with tissue cells. However, important determinants of Treg tissue specificity, such as antigen specificity, tissue environment, and pathology, remain unclear. In this study, we analyzed Tregs in the central nervous system of mice with ischemic stroke and experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. The gene expression pattern of brain Tregs in the EAE model was more similar to that of ischemic stroke Tregs in the brain than to that of spinal cord Tregs. In addition, most T-cell receptors (TCRs) with high clonality were present in both the brain and spinal cord. Furthermore, Gata3(+) and Rorc(+) Tregs expressed TCRs recognizing MOG in the spinal cord, suggesting a tissue environment conducive to Rorc expression. Tissue-specific chemokine/chemokine receptor interactions in the spinal cord and brain influenced Treg localization. Finally, spinal cord- or brain-derived Tregs had greater anti-inflammatory capacities in EAE mice, respectively. Taken together, these findings suggest that the tissue environment, rather than pathogenesis or antigen specificity, is the primary determinant of the tissue-specific properties of Tregs. These findings may contribute to the development of novel therapies to suppress inflammation through tissue-specific Treg regulation.", "classifications": [ { "id": "21H00432", "label": "21H00432", "researcher": "Minako Ito", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mahiro", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Ako", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Awata", "name": null }, { "creator_type": "author", "first_name": "Ayame", "last_name": "Nagafuchi", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kawazoe", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12974-024-03144-1" }, "pmcid": { "normalized": "PMC11143704" }, "pmid": { "normalized": "38824594" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Encephalomyelitis, Autoimmune, Experimental", "descriptor_ui": "D004681", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": true }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": true }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jun 1", "date_precision": "day", "issue": "1", "normalized_date": "2024-06-01", "pages": "146", "proceedings_title": null, "publisher": "", "title": "Journal of neuroinflammation", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Differences in the characteristics and functions of brain and spinal cord regulatory T cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We developed a centromere-associated protein E (CENP-E) inhibitor employing trans to cis photoisomerization with 405 nm visible light illumination and fast thermal relaxation. This photoswitching characteristic of the inhibitor enabled selective blockage or release of the motion of particular chromosomes within a single mitotic cell. Using this technique, we successfully demonstrated targeted chromosome gain and loss in daughter cells by introducing asymmetric chromosome segregation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuya", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kikukawa", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Waku", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Kobori", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Tamaoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d4cc01922a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38845591" } }, "mesh": [ { "descriptor": "Azo Compounds", "descriptor_ui": "D001391", "major_topic": false }, { "descriptor": "Chromosomal Proteins, Non-Histone", "descriptor_ui": "D002868", "major_topic": true }, { "descriptor": "Chromosome Segregation", "descriptor_ui": "D020090", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": true }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Photochemical Processes", "descriptor_ui": "D055668", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024-06", "date_precision": "month", "issue": "52", "normalized_date": "2024-06", "pages": "6611-6614", "proceedings_title": null, "publisher": "", "title": "Chemical Communications", "volume": "60", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatiotemporal regulation of CENP-E-guided chromosomes using a fast-relaxing arylazopyrazole photoswitch", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although the herpes simplex virus type 1 (HSV-1) genome was thought to contain approximately 80 different protein coding sequences (CDSs), recent multi-omics analyses reported HSV-1 encodes more than 200 potential CDSs. However, few of the newly identified CDSs were confirmed to be expressed at the peptide or protein level in HSV-1-infected cells. Furthermore, the impact of the proteins they encode on HSV-1 infection is largely unknown. This study focused on a newly identified CDS, UL31.6. Re-analyzation of our previous chemical proteomics data verified that UL31.6 was expressed at the peptide level in HSV-1-infected cells. Antisera raised against a viral protein encoded by UL31.6 (pUL31.6) reacted with a protein with an approximate molecular mass of 37 kDa in lysates of Vero cells infected with each of three HSV-1 strains. pUL31.6 was efficiently dissociated from virions in high-salt solution. A UL31.6-null mutation had a minimal effect on HSV-1 gene expression, replication, cell-to-cell spread, and morphogenesis in Vero cells; in contrast, it significantly reduced HSV-1 cell-to-cell spread in three neural cells but not in four non-neural cells including Vero cells. The UL31.6-null mutation also significantly reduced the mortality and viral replication in the brains of mice after intracranial infection, but had minimal effects on pathogenic manifestations in and around the eyes, and viral replication detected in the tear films of mice after ocular infection. These results indicated that pUL31.6 was a tegument protein and specifically acted as a neurovirulence factor by potentially promoting viral transmission between neuronal cells in the central nervous system.IMPORTANCERecent multi-omics analyses reported the herpes simplex virus type 1 (HSV-1) genome encodes an additional number of potential coding sequences (CDSs). However, the expressions of these CDSs at the peptide or protein levels and the biological effects of these CDSs on HSV-1 infection remain largely unknown. This study annotated a cryptic orphan CDS, termed UL31.6, an HSV-1 gene that encodes a tegument protein with an approximate molecular mass of 37 kDa, which specifically acts as a neurovirulence factor. Our study indicates that HSV-1 proteins important for viral pathogenesis remain to be identified and a comprehensive understanding of the pathogenesis of HSV-1 will require not only the identification of cryptic orphan CDSs using emerging technologies but also step-by-step and in-depth analyses of each of the cryptic orphan CDSs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Ryoji", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Kousuke", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Natsume", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Kusano", "name": null }, { "creator_type": "author", "first_name": "Shungo", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00747-24" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38819171" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": true }, { "descriptor": "Virulence", "descriptor_ui": "D014774", "major_topic": false }, { "descriptor": "Virulence Factors", "descriptor_ui": "D037521", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 May 31", "date_precision": "day", "issue": "", "normalized_date": "2024-05-31", "pages": "e0074724", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of a novel neurovirulence factor encoded by the cryptic orphan gene UL31.6 of herpes simplex virus 1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mechanisms by which the number of memory CD8 T cells is stably maintained remains incompletely understood. It has been postulated that maintaining them requires help from CD4 T cells, because adoptively transferred memory CD8 T cells persist poorly in MHC class II (MHCII)-deficient mice. Here we show that chronic interferon-gamma signals, not CD4 T cell-deficiency, are responsible for their attrition in MHCII-deficient environments. Excess IFN-gamma is produced primarily by endogenous colonic CD8 T cells in MHCII-deficient mice. IFN-gamma neutralization restores the number of memory CD8 T cells in MHCII-deficient mice, whereas repeated IFN-gamma administration or transduction of a gain-of-function STAT1 mutant reduces their number in wild-type mice. CD127(high) memory cells proliferate actively in response to IFN-gamma signals, but are more susceptible to attrition than CD127(low) terminally differentiated effector memory cells. Furthermore, single-cell RNA-sequencing of memory CD8 T cells reveals proliferating cells that resemble short-lived, terminal effector cells and documents global downregulation of gene signatures of long-lived memory cells in MHCII-deficient environments. We propose that chronic IFN-gamma signals deplete memory CD8 T cells by compromising their long-term survival and by diverting self-renewing CD127(high) cells toward terminal differentiation.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ruka", "last_name": "Setoguchi", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Sengiku", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kono", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Hori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-48704-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38806459" } }, "mesh": [ { "descriptor": "Adoptive Transfer", "descriptor_ui": "D019264", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CD4-Positive T-Lymphocytes", "descriptor_ui": "D015496", "major_topic": true }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Histocompatibility Antigens Class II", "descriptor_ui": "D000949", "major_topic": false }, { "descriptor": "Immunologic Memory", "descriptor_ui": "D007156", "major_topic": true }, { "descriptor": "Interferon-gamma", "descriptor_ui": "D007371", "major_topic": true }, { "descriptor": "Interleukin-7 Receptor alpha Subunit", "descriptor_ui": "D053699", "major_topic": false }, { "descriptor": "Memory T Cells", "descriptor_ui": "D000091246", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "STAT1 Transcription Factor", "descriptor_ui": "D050794", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 May 28", "date_precision": "day", "issue": "1", "normalized_date": "2024-05-28", "pages": "4418", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Memory CD8 T cells are vulnerable to chronic IFN-gamma signals but not to CD4 T cell deficiency in MHCII-deficient mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Excited-state intramolecular proton transfer (ESIPT) molecules, which feature large Stokes shifts to avoid self-absorption, play an essential role in photoluminescent bioimaging probes. Herein, we report the development of an ESIPT molecule 3-(3-hydroxypyridin-2-yl)isoquinolin-4-ol (PiQ). PiQ not only undergoes a distinct ESIPT process unlike the symmetrical 2,2'-bipyridyl-3,3'-diol but also exhibits aggregation-induced emission (AIE) characteristics. PiQ self-assembles into aggregates with an average size of 241.0 +/- 51.9 nm in aqueous solutions, leading to significantly enhanced photoluminescence. On the basis of the ESIPT and AIE characteristics of PiQ, the latter is functionalized with a hydrogen peroxide-responsive 4-pinacoratoborylbenzyl group (B) and a carboxylesterase-responsive acetyl group (A) to produce a photoluminescent probe B-PiQ-A. The potential of PiQ for applications in bioimaging and chemical sensing is underscored by its efficient detection of both endogenous and exogenous hydrogen peroxide in living cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Wenting", "last_name": "Huo", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Nogita", "name": null }, { "creator_type": "author", "first_name": "Shuai", "last_name": "Shao", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Huiying", "last_name": "Mu", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/chem.202401451" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38803241" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 May 27", "date_precision": "day", "issue": "", "normalized_date": "2024-05-27", "pages": "e202401451", "proceedings_title": null, "publisher": "", "title": "Chemistry (Weinheim an der Bergstrasse, Germany)", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "AIE-ESIPT Photoluminescent Probe Based on 3-(3-Hydroxypyridin-2-yl)isoquinolin-4-ol for the Detection of Intracellular Hydrogen Peroxide.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Hair beauty treatments glorify human life. As a side effect, there is a risk of deteriorating the health of the hair. Optically polarized microscopy has been used for many decades to evaluate hair conditions owing to its ease of use and low operating costs. However, the low biopermeability of light hinders the observation of detailed structures inside hair. The aim of this study is to establish an evaluation technique of internal damages in a hair by utilizing a near-infrared (NIR) light with a wavelength of 1000-1600 nm, called \"second NIR window\". METHODS: We built a laser scanning transmission microscope system with an indium gallium arsenide detector, a 1064 nm laser source, and optical circular polarization to visualize the anisotropy characterization of keratin fibres in hair. Samples of Asian black hair before and after bleaching, after permanent-waving, after lithium bromide (LiBr) treatment, and after heating was observed. Some parameters reflecting intra-hair damage were quantitatively compared with the parameters in digitally recorded images with analytical developments. RESULTS: The light transmittance of black hair was dramatically improved by utilizing the second NIR window. Numerical analysis of circular polarization in hair quantified the internal damage in chemically or thermally treated hair and found two different types of damage. The present method enabled quantitative evaluation of the condition changes in the cortex; for example, a decrease in circular polarizability by LiBr treatment and restoration by replacing the LiBr solution with water. In addition, black speckles were observed after the heat treatment. Longer heating and wetting times increased the appearance probability and size of the speckles. According to quantitative analyses, the emergence of black spots was independent of polarizability changes, indicating that they were not pores. CONCLUSION: Circular polarization microscopy based on near-infrared optics in the second NIR window provides an effective evaluation method for quantifying intra-hair damage caused by cosmetic treatments. The present method provides noninvasive, easy, and inexpensive hair evaluation and has potential as a gold standard in hair care research/medical fields.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Seiko", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Saki", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Shioi", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Kaneshiro", "name": null }, { "creator_type": "author", "first_name": "Michi", "last_name": "Magari", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/ics.12970" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38802700" } }, "mesh": [ { "descriptor": "Hair", "descriptor_ui": "D006197", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infrared Rays", "descriptor_ui": "D007259", "major_topic": false }, { "descriptor": "Microscopy, Polarization", "descriptor_ui": "D008859", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 May 27", "date_precision": "day", "issue": "", "normalized_date": "2024-05-27", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of cosmetic science", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Optical evaluation of internal damage to human hair based on second near-infrared window polarization microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Patients with heart failure (HF) often experience repeated acute decompensation and develop comorbidities such as chronic kidney disease and frailty syndrome. Although this suggests pathological interaction among comorbidities, the mechanisms linking them are poorly understood. Here, we identified alterations in hematopoietic stem cells (HSCs) as a critical driver of recurrent HF and associated comorbidities. Bone marrow transplantation from HF-experienced mice resulted in spontaneous cardiac dysfunction and fibrosis in recipient mice, as well as increased vulnerability to kidney and skeletal muscle insults. HF enhanced the capacity of HSCs to generate proinflammatory macrophages. In HF mice, global chromatin accessibility analysis and single-cell RNA-seq showed that transforming growth factor-beta (TGF-beta) signaling was suppressed in HSCs, which corresponded with repressed sympathetic nervous activity in bone marrow. Transplantation of bone marrow from mice in which TGF-beta signaling was inhibited similarly exacerbated cardiac dysfunction. Collectively, these results suggest that cardiac stress modulates the epigenome of HSCs, which in turn alters their capacity to generate cardiac macrophage subpopulations. This change in HSCs may be a common driver of repeated HF events and comorbidity by serving as a key carrier of \"stress memory.\"", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yukiteru", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Katsuhito", "last_name": "Fujiu", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Sugita", "name": null }, { "creator_type": "author", "first_name": "Takumi James", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Yuxiang", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Kohsaku", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Kunihiro", "last_name": "Kani", "name": null }, { "creator_type": "author", "first_name": "Ryoko", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Norifumi", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Yingda", "last_name": "Xiao", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yujin", "last_name": "Maru", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Hasumi", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Soh", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kijima", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Yachie", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Fujimi", "last_name": "Kudo", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Iwama", "name": null }, { "creator_type": "author", "first_name": "Ryoji", "last_name": "Fujiki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kaneda", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Ohara", "name": null }, { "creator_type": "author", "first_name": "Ryozo", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Manabe", "name": null }, { "creator_type": "author", "first_name": "Issei", "last_name": "Komuro", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciimmunol.ade3814" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38787963" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": true }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": true }, { "descriptor": "Immunologic Memory", "descriptor_ui": "D007156", "major_topic": true }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": true }, { "descriptor": "Multimorbidity", "descriptor_ui": "D000076322", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Trained Immunity", "descriptor_ui": "D000094384", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 May 24", "date_precision": "day", "issue": "95", "normalized_date": "2024-05-24", "pages": "eade3814", "proceedings_title": null, "publisher": "", "title": "Science immunology", "volume": "9", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Heart failure promotes multimorbidity through innate immune memory.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Caffeoylquinic acid (CQA), which is abundant in coffee beans and Centella asiatica, reportedly improves cognitive function in Alzheimer's disease (AD) model mice, but its effects on neuroinflammation, neuronal loss, and the amyloid-beta (Abeta) plaque burden have remained unclear. OBJECTIVE: To assess the effects of a 16-week treatment with CQA on recognition memory, working memory, Abeta levels, neuronal loss, neuroinflammation, and gene expression in the brains of 5XFAD mice, a commonly used mouse model of familial AD. METHODS: 5XFAD mice at 7 weeks of age were fed a 0.8% CQA-containing diet for 4 months and then underwent novel object recognition (NOR) and Y-maze tests. The Abeta levels and plaque burden were analyzed by enzyme-linked immunosorbent assay and immunofluorescent staining, respectively. Immunostaining of markers of mature neurons, synapses, and glial cells was analyzed. AmpliSeq transcriptome analysis and quantitative reverse-transcription-polymerase chain reaction were performed to assess the effect of CQA on gene expression levels in the cerebral cortex of the 5XFAD mice. RESULTS: CQA treatment for 4 months improved recognition memory and ameliorated the reduction of mature neurons and synaptic function-related gene mRNAs. The Abeta levels, plaque burden, and glial markers of neuroinflammation seemed unaffected. CONCLUSIONS: These findings suggest that CQA treatment mitigates neuronal loss and improves cognitive function without reducing Abeta levels or neuroinflammation. Thus, CQA is a potential therapeutic compound for AD, improving cognitive function via as-yet unknown mechanisms independent of reductions in Abeta or neuroinflammation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takaya", "last_name": "Suganuma", "name": null }, { "creator_type": "author", "first_name": "Sena", "last_name": "Hatori", "name": null }, { "creator_type": "author", "first_name": "Chung-Kuan", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Kanuka", "name": null }, { "creator_type": "author", "first_name": "Chih-Yao", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Tatsuzawa", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3233/jad-240033" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38788074" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Amyloid beta-Peptides", "descriptor_ui": "D016229", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cognitive Dysfunction", "descriptor_ui": "D060825", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Maze Learning", "descriptor_ui": "D018782", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Plaque, Amyloid", "descriptor_ui": "D058225", "major_topic": true }, { "descriptor": "Quinic Acid", "descriptor_ui": "D011801", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 May 23", "date_precision": "day", "issue": "", "normalized_date": "2024-05-23", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of Alzheimer's disease : JAD", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Caffeoylquinic Acid Mitigates Neuronal Loss and Cognitive Decline in 5XFAD Mice Without Reducing the Amyloid-beta Plaque Burden.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: One significant challenge in addressing the coronavirus disease 2019 (COVID-19) pandemic is to grasp a comprehensive picture of its infectious mechanisms. We urgently need a consistent framework to capture the intricacies of its complicated viral infectious processes and diverse symptoms. RESULTS: We systematized COVID-19 infectious processes through an ontological approach and provided a unified description framework of causal relationships from the early infectious stage to severe clinical manifestations based on the homeostasis imbalance process ontology (HoIP). HoIP covers a broad range of processes in the body, ranging from normal to abnormal. Moreover, our imbalance model enabled us to distinguish viral functional demands from immune defense processes, thereby supporting the development of new drugs, and our research demonstrates how ontological reasoning contributes to the identification of patients at severe risk. CONCLUSIONS: The HoIP organises knowledge of COVID-19 infectious processes and related entities, such as molecules, drugs, and symptoms, with a consistent descriptive framework. HoIP is expected to harmonise the description of various heterogeneous processes and improve the interoperability of COVID-19 knowledge through the COVID-19 ontology harmonisation working group.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Kushida", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Masuya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12911-024-02516-0" }, "pmcid": { "normalized": "PMC11110177" }, "pmid": { "normalized": "38778394" } }, "mesh": [ { "descriptor": "Biological Ontologies", "descriptor_ui": "D064229", "major_topic": true }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 May 22", "date_precision": "day", "issue": "Suppl 4", "normalized_date": "2024-05-22", "pages": "301", "proceedings_title": null, "publisher": "", "title": "BMC medical informatics and decision making", "volume": "23", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Homeostasis imbalance process ontology: a study on COVID-19 infectious processes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "pH-responsive spirocyclic cyanine dyes were designed and synthesized. The equilibrium constant for cyclization (pK(cycl)) could be rationally controlled by changing the nucleophilic moiety and the side chains. Encapsulation in polymeric micelles inhibited the H-aggregation of the dye, and the pK(cycl) could be shifted according to the amphiphilic polymer employed.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akihiro", "last_name": "Sakama", "name": null }, { "creator_type": "author", "first_name": "Hyemin", "last_name": "Seo", "name": null }, { "creator_type": "author", "first_name": "Joji", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Yuma", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d4cc01484g" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38770871" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 May 21", "date_precision": "day", "issue": "", "normalized_date": "2024-05-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Rational design of pH-responsive near-infrared spirocyclic cyanines: the effects of substituents and the external environment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Complex networks are pervasive in various fields such as chemistry, biology, and sociology. In chemistry, first-order reaction networks are represented by a set of first-order differential equations, which can be constructed from the underlying energy landscape. However, as the number of nodes increases, it becomes more challenging to understand complex kinetics across different timescales. Hence, how to construct an interpretable, coarse-graining scheme that preserves the underlying timescales of overall reactions is of crucial importance. Here, we develop a scheme to capture the underlying hierarchical subsets of nodes, and a series of coarse-grained (reduced-dimensional) rate equations between the subsets as a function of time resolution from the original reaction network. Each of the coarse-grained representations guarantees to preserve the underlying slow characteristic timescales in the original network. The crux is the construction of a lumping scheme incorporating a similarity measure in deciphering the underlying timescale hierarchy, which does not rely on the assumption of equilibrium. As an illustrative example, we apply the scheme to four-state Markovian models and Claisen rearrangement of allyl vinyl ether (AVE), and demonstrate that the reduced-dimensional representation accurately reproduces not only the slowest but also the faster timescales of overall reactions although other reduction schemes based on equilibrium assumption well reproduce the slowest timescale but fail to reproduce the second-to-fourth slowest timescales with the same accuracy. Our scheme can be applied not only to the reaction networks but also to networks in other fields, which helps us encompass their hierarchical structures of the complex kinetics over timescales.", "classifications": [ { "id": "18H05413", "label": "18H05413", "researcher": "Tamiki Komatsuzaki", "type": "grant" }, { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yutaka", "last_name": "Nagahata", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Mikito", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Taketsugu", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2317781121" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38758700" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 May 21", "date_precision": "day", "issue": "21", "normalized_date": "2024-05-21", "pages": "e2317781121", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "121", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "An encompassed representation of timescale hierarchies in first-order reaction network.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lymphocytes such as CD4(+) T cells and B cells mainly infiltrate the salivary glands; however, the precise roles and targets of autoreactive T cells and autoantibodies in the pathogenesis of Sjogren's Syndrome (SS) remain unclear. This study was designed to clarify the role of autoreactive T cells and autoantibodies at the single-cell level involved in the development of sialadenitis. Infiltrated CD4(+) T and B cells in the salivary glands of a mouse model resembling SS were single-cell-sorted, and their T cell receptor (TCR) and B cell receptor (BCR) sequences were analyzed. The predominant TCR and BCR clonotypes were reconstituted in vitro, and their pathogenicity was evaluated by transferring reconstituted TCR-expressing CD4(+) T cells into Rag2(-/-) mice and administering recombinant IgG in vivo. The reconstitution of Th17 cells expressing TCR (#G) in Rag2(-/-) mice resulted in the infiltration of T cells into the salivary glands and development of sialadenitis, while an autoantibody (IgGr22) was observed to promote the proliferation of pathogenic T cells. IgGr22 specifically recognizes double-stranded RNA (dsRNA) and induces the activation of dendritic cells, thereby enhancing the expression of IFN signature and inflammatory genes. TCR#G recognizes antigens related to the gut microbiota. Antibiotic treatment severely reduces the activation of TCR#G-expressing Th17 cells and suppresses sialadenitis development. These data suggest that the anti-dsRNA antibodies and, TCR recognizing the gut microbiota involved in the development of sialadenitis like SS. Thus, our model provides a novel strategy for defining the roles of autoreactive TCR and autoantibodies in the development and pathogenesis of SS.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mana", "last_name": "Iizuka-Koga", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Yumoto", "name": null }, { "creator_type": "author", "first_name": "Setsuko", "last_name": "Mise-Omata", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Komai", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Sumida", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.clim.2024.110258" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38762063" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autoantibodies", "descriptor_ui": "D001323", "major_topic": true }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "CD4-Positive T-Lymphocytes", "descriptor_ui": "D015496", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Receptors, Antigen, B-Cell", "descriptor_ui": "D011947", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": true }, { "descriptor": "Salivary Glands", "descriptor_ui": "D012469", "major_topic": false }, { "descriptor": "Sialadenitis", "descriptor_ui": "D012793", "major_topic": true }, { "descriptor": "Sjogren's Syndrome", "descriptor_ui": "D012859", "major_topic": true }, { "descriptor": "Th17 Cells", "descriptor_ui": "D058504", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 May 16", "date_precision": "day", "issue": "", "normalized_date": "2024-05-16", "pages": "110258", "proceedings_title": null, "publisher": "", "title": "Clinical immunology (Orlando, Fla.)", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Reconstruction of Sjogren's syndrome-like sialadenitis by a defined disease specific gut-reactive single TCR and an autoantibody.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent single-cell RNA-sequencing analysis of rheumatoid arthritis (RA) synovial tissues revealed the heterogeneity of RA synovial fibroblasts (SFs) with distinct functions such as high IL-6 production. The molecular mechanisms responsible for high IL-6 production will become a promising drug target of RASFs to treat RA. In this study, we performed siRNA screening of 65 transcription factors (TFs) differentially expressed among RASF subsets to identify TFs involved in IL-6 production. The siRNA screening identified 7 TFs including ARID5B, a RA risk gene, that affected IL-6 production. Both long and short isoforms of ARID5B were expressed and negatively regulated by TNF-alpha in RASFs. The siRNA knockdown and lentiviral overexpression of long and short isoforms of ARID5B revealed that the long isoform suppressed IL-6 production stimulated with TNF-alpha. eQTL analysis using 58 SFs demonstrated that RA risk allele, rs10821944, in intron 4 of the ARID5B gene had a trend of eQTL effects to the expression of long isoform of ARID5B in SFs treated with TNF-alpha. ARID5B was found to be a negative modulator of IL-6 production in RASFs. The RA risk allele of ARID5B intron may cause high IL-6 production, suggesting that ARID5B will become a promising drug target to treat RA.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Tagawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Iwai", "name": null }, { "creator_type": "author", "first_name": "Motohiko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Mineto", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Takahara", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Keishi", "last_name": "Fujio", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Mizoguchi", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Yasuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/25785826.2024.2346956" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38747454" } }, "mesh": [ { "descriptor": "Arthritis, Rheumatoid", "descriptor_ui": "D001172", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": true }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": true }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interleukin-6", "descriptor_ui": "D015850", "major_topic": true }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false }, { "descriptor": "Quantitative Trait Loci", "descriptor_ui": "D040641", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Synovial Membrane", "descriptor_ui": "D013583", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": true }, { "descriptor": "Tumor Necrosis Factor-alpha", "descriptor_ui": "D014409", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 May 15", "date_precision": "day", "issue": "", "normalized_date": "2024-05-15", "pages": "1-10", "proceedings_title": null, "publisher": "", "title": "Immunological medicine", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "ARID5B is a negative modulator of IL-6 production in rheumatoid arthritis synovial fibroblasts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "B cell initial activity is regulated through a balance of activation and suppression mediated by regulatory molecules expressed in B cells; however, the molecular mechanisms underlying this process remain incompletely understood. In this study, we investigated the function of the Fc receptor-like (Fcrl) family molecule Fcrl5, which is constitutively expressed on naive B cells, in humoral immune responses. Our study demonstrated that B cell-specific overexpression of Fcrl5 enhanced antibody (Ab) production in both T cell-independent type 1 (TI1) and T cell-dependent (TD) responses. Additionally, it promoted effector B cell formation under competitive conditions in TD responses. Mechanistically, in vitro ligation of Fcrl5 by agonistic Abs reduced cell death and enhanced proliferation in lipopolysaccharide (LPS)-stimulated B cells. In the presence of anti-CD40 Abs and IL-5, the Fcrl5 ligation not only suppressed cell death but also enhanced differentiation into plasma cells. These findings reveal a novel role of Fcrl5 in promoting humoral immune responses by enhancing B cell viability and plasma cell differentiation.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Chisato", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Kochi", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/intimm/dxae028" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38738271" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": true }, { "descriptor": "Histocompatibility Antigens Class I", "descriptor_ui": "D015395", "major_topic": false }, { "descriptor": "Immunity, Humoral", "descriptor_ui": "D056724", "major_topic": true }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Receptors, Fc", "descriptor_ui": "D011961", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 May 13", "date_precision": "day", "issue": "", "normalized_date": "2024-05-13", "pages": "dxae028", "proceedings_title": null, "publisher": "", "title": "International immunology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Humoral responses are enhanced by facilitating B cell viability by Fcrl5 overexpression in B cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The gramicidin-perforated patch-clamp technique is indispensable for recording neuronal activities without changing the intracellular Cl(-) concentration. Conventionally, gramicidin contained in the pipette fluid is delivered to the cell membrane by passive diffusion. Gramicidin deposited on the pipette orifice sometimes hampers giga-seal formation, and perforation progresses only slowly. These problems may be circumvented by delivering a high concentration of gramicidin from an intra-pipette capillary after a giga-seal is formed. We herein describe the detailed protocol of this improved method. This protocol would greatly facilitate the investigation of Cl(-) gradient-dependent neuronal activities.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Kazashi", "name": null }, { "creator_type": "author", "first_name": "Kakeru", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Kazuhito", "last_name": "Utsunomiya", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Kiriyama", "name": null }, { "creator_type": "author", "first_name": "Motoki", "last_name": "Yagisawa", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Tabata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2024.05.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38740268" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Gramicidin", "descriptor_ui": "D006096", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 May 11", "date_precision": "day", "issue": "", "normalized_date": "2024-05-11", "pages": "S0168-0102(24)00064-6", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Delayed gramicidin delivery through an intra-pipette capillary facilitates perforated patch recordings.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although cellular senescence is a key factor in organismal aging, with both positive and negative effects on individuals, its mechanisms remain largely unknown. Thus, integrating knowledge is essential to explain how cellular senescence manifests in tissue damage and age-related diseases. Here, we propose an ontological model that organizes knowledge of cellular senescence in a computer-readable form. We manually annotated and defined cellular senescence processes, molecules, anatomical structures, phenotypes, and other entities based on the Homeostasis Imbalance Process ontology (HOIP). We described the mechanisms as causal relationships of processes and modelled a homeostatic imbalance between stress and stress response in cellular senescence for a unified framework. HOIP was assessed formally, and the relationships between cellular senescence and diseases were inferred for higher-order knowledge processing. We visualized cellular senescence processes to support knowledge utilization. Our study provides a knowledge base to help elucidate mechanisms linking cellular and organismal aging.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Tsubasa", "last_name": "Fukuyama", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Masuya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41597-024-03331-y" }, "pmcid": { "normalized": "PMC11087592" }, "pmid": { "normalized": "38729991" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": true }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 May 10", "date_precision": "day", "issue": "1", "normalized_date": "2024-05-10", "pages": "485", "proceedings_title": null, "publisher": "", "title": "Scientific data", "volume": "11", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Prototyping an Ontological Framework for Cellular Senescence Mechanisms: A Homeostasis Imbalance Perspective.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell deformability is an essential determinant for tissue-scale mechanical nature, such as fluidity and rigidity, and is thus crucial for tissue homeostasis and stable developmental processes. However, large-scale simulations of deformable cells have been restricted to those of polygonal-shaped cells, limiting our understanding of populations of arbitrarily deformable cells, such as mesenchymal, amoeboid cells, and nonconfluent epithelial cells. Here, we present an efficient approach for simulating large populations of nonpolygonally deformable cells with considerably higher computational efficiency than existing methods. Using the method, we demonstrate that the densely packed active cell population interacting via excluded volume interactions exhibits a fluid-to-fluid transition. An experimentally measurable index of topological defects, defined using the number of neighboring cells, is also proposed to characterize this transition. This study provides a flexible approach to tissue-scale cell population and a broader perspective on the biological fluid phases.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Nen", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adi8433" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38718115" } }, "mesh": [ { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Phase Transition", "descriptor_ui": "D044367", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 May 10", "date_precision": "day", "issue": "19", "normalized_date": "2024-05-10", "pages": "eadi8433", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "10", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell deformability drives fluid-to-fluid phase transition in active cell monolayers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Retinal pigment epithelium (RPE) cells show heterogeneous levels of pigmentation when cultured in vitro. To know whether their color in appearance is correlated with the function of the RPE, we analyzed the color intensities of human-induced pluripotent stem cell-derived RPE cells (iPSC-RPE) together with the gene expression profile at the single-cell level. For this purpose, we utilized our recent invention, Automated Live imaging and cell Picking System (ALPS), which enabled photographing each cell before RNA-sequencing analysis to profile the gene expression of each cell. While our iPSC-RPE were categorized into four clusters by gene expression, the color intensity of iPSC-RPE did not project any specific gene expression profiles. We reasoned this by less correlation between the actual color and the gene expressions that directly define the level of pigmentation, from which we hypothesized the color of RPE cells may be a temporal condition not strongly indicating the functional characteristics of the RPE.", "classifications": [ { "id": "18H05411", "label": "18H05411", "researcher": "Katsuyuki Shiroguchi", "type": "grant" }, { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoko", "last_name": "Nakai-Futatsugi", "name": null }, { "creator_type": "author", "first_name": "Jianshi", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Taisaku", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Danno", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null }, { "creator_type": "author", "first_name": "Masayo", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.92510" }, "pmcid": { "normalized": "PMC11081631" }, "pmid": { "normalized": "38722314" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Pigmentation", "descriptor_ui": "D010858", "major_topic": true }, { "descriptor": "Retinal Pigment Epithelium", "descriptor_ui": "D055213", "major_topic": true }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 May 9", "date_precision": "day", "issue": "", "normalized_date": "2024-05-09", "pages": "", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "12", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Pigmentation level of human iPSC-derived RPE does not indicate a specific gene expression profile.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell states are regulated by the response of signaling pathways to receptor ligand-binding and intercellular interactions. High-resolution imaging has been attempted to explore the dynamics of these processes and, recently, multiplexed imaging has profiled cell states by achieving a comprehensive acquisition of spatial protein information from cells. However, the specificity of antibodies is still compromised when visualizing activated signals. Here, we develop Precise Emission Canceling Antibodies (PECAbs) that have cleavable fluorescent labeling. PECAbs enable high-specificity sequential imaging using hundreds of antibodies, allowing for reconstruction of the spatiotemporal dynamics of signaling pathways. Additionally, combining this approach with seq-smFISH can effectively classify cells and identify their signal activation states in human tissue. Overall, the PECAb system can serve as a comprehensive platform for analyzing complex cell processes.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Tomimatsu", "name": null }, { "creator_type": "author", "first_name": "Takeru", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Ryoma", "last_name": "Bise", "name": null }, { "creator_type": "author", "first_name": "Kazufumi", "last_name": "Hosoda", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ochiai", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Ohishi", "name": null }, { "creator_type": "author", "first_name": "Kanta", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Ryoma", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Nagasaki", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-47989-9" }, "pmcid": { "normalized": "PMC11078938" }, "pmid": { "normalized": "38719795" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies", "descriptor_ui": "D000906", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": true }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "In Situ Hybridization, Fluorescence", "descriptor_ui": "D017404", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Single Molecule Imaging", "descriptor_ui": "D000072760", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 May 8", "date_precision": "day", "issue": "1", "normalized_date": "2024-05-08", "pages": "3657", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Precise immunofluorescence canceling for highly multiplexed imaging to capture specific cell states.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In animals, three main RNA interference mechanisms have been described so far, which respectively maturate three types of small noncoding RNAs (sncRNAs): miRNAs, piRNAs and endo-siRNAs. The diversification of these mechanisms is deeply linked with the evolution of the Argonaute gene superfamily since each type of sncRNA is typically loaded by a specific Argonaute homolog. Moreover, other protein families play pivotal roles in the maturation of sncRNAs, like the DICER ribonuclease family, whose DICER1 and DICER2 paralogs maturate respectively miRNAs and endo-siRNAs. Within Metazoa, the distribution of these families has been only studied in major groups, and there are very few data for clades like Lophotrochozoa. Thus, we here inferred the evolutionary history of the animal Argonaute and DICER families including 43 lophotrochozoan species. Phylogenetic analyses along with newly sequenced sncRNA libraries suggested that in all Trochozoa the proteins related to the endo-siRNA pathway have been lost, a part of them in some phyla (i.e., Nemertea, Bryozoa, Entoprocta), while all of them in all the others. On the contrary, early diverging phyla, Platyhelminthes and Syndermata, showed a complete endo-siRNA pathway. On the other hand, miRNAs were revealed the most conserved and ubiquitous mechanism of the metazoan RNA interference machinery, confirming their pivotal role in animal cell regulation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Alessandro", "last_name": "Formaggioni", "name": null }, { "creator_type": "author", "first_name": "Gianmarco", "last_name": "Cavalli", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Federico", "last_name": "Plazzi", "name": null }, { "creator_type": "author", "first_name": "Marco", "last_name": "Passamonti", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/gbe/evae098" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38713108" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Argonaute Proteins", "descriptor_ui": "D060565", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": true }, { "descriptor": "Invertebrates", "descriptor_ui": "D007448", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": true }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": true }, { "descriptor": "Ribonuclease III", "descriptor_ui": "D043244", "major_topic": true }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": true }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 May 7", "date_precision": "day", "issue": "", "normalized_date": "2024-05-07", "pages": "evae098", "proceedings_title": null, "publisher": "", "title": "Genome biology and evolution", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "The evolution and characterization of the RNA interference pathways in Lophotrochozoa.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cladoceran crustacean Daphnia exhibits phenotypic plasticity, a phenomenon that leads to diverse phenotypes from one genome. Alternative usage of gene isoforms has been considered a key gene regulation mechanism for controlling different phenotypes. However, to understand the phenotypic plasticity of Daphnia, gene isoforms have not been comprehensively analyzed. Here we identified 25,654 transcripts derived from the 9710 genes expressed during environmental sex determination of Daphnia magna using the long-read RNA-Seq with PacBio Iso-Seq. We found that 14,924 transcripts were previously unidentified and 5713 genes produced two or more isoforms. By a combination of Illumina short-read RNA-Seq, we detected 824 genes that implemented switching of the highest expressed isoform between females and males. Among the 824 genes, we found isoform switching of an ortholog of CREB-regulated transcription coactivator, a major regulator of carbohydrate metabolism in animals, and a correlation of this switching event with the sexually dimorphic expression of carbohydrate metabolic genes. These results suggest that a comprehensive catalog of isoforms may lead to understanding the molecular basis for environmental sex determination of Daphnia. We also infer the applicability of the full-length isoform analyses to the elucidation of phenotypic plasticity in Daphnia.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Joel H.", "last_name": "Nitta", "name": null }, { "creator_type": "author", "first_name": "Christelle Alexa Garcia", "last_name": "Perez", "name": null }, { "creator_type": "author", "first_name": "Nikko", "last_name": "Adhitama", "name": null }, { "creator_type": "author", "first_name": "Pijar", "last_name": "Religia", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-024-59774-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38688940" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Daphnia magna", "descriptor_ui": "D000096602", "major_topic": true }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Parthenogenesis", "descriptor_ui": "D010312", "major_topic": false }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": true }, { "descriptor": "Sex Determination Processes", "descriptor_ui": "D019849", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Apr 30", "date_precision": "day", "issue": "1", "normalized_date": "2024-04-30", "pages": "9407", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "14", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of gene isoforms and their switching events between male and female embryos of the parthenogenetic crustacean Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Inherited retinal dystrophies (IRDs) are progressive diseases leading to vision loss. Mutation in the eyes shut homolog (EYS) gene is one of the most frequent causes of IRD. However, the mechanism of photoreceptor cell degeneration by mutant EYS has not been fully elucidated. Here, we generated retinal organoids from induced pluripotent stem cells (iPSCs) derived from patients with EYS-associated retinal dystrophy (EYS-RD). In photoreceptor cells of RD organoids, both EYS and G protein-coupled receptor kinase 7 (GRK7), one of the proteins handling phototoxicity, were not in the outer segment, where they are physiologically present. Furthermore, photoreceptor cells in RD organoids were vulnerable to light stimuli, and especially to blue light. Mislocalization of GRK7, which was also observed in eys-knockout zebrafish, was reversed by delivering control EYS into photoreceptor cells of RD organoids. These findings suggest that avoiding phototoxicity would be a potential therapeutic approach for EYS-RD.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Otsuka", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Kazuhide", "last_name": "Asakawa", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Risako", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Suga", "name": null }, { "creator_type": "author", "first_name": "Ikuyo", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Sagara", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Tsukita", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Teranaka", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Umeyama", "name": null }, { "creator_type": "author", "first_name": "Nanako", "last_name": "Okushima", "name": null }, { "creator_type": "author", "first_name": "Kohnosuke", "last_name": "Mitani", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Akitaka", "last_name": "Tsujikawa", "name": null }, { "creator_type": "author", "first_name": "Haruhisa", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci.insight.174179" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38646933" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Eye Proteins", "descriptor_ui": "D005136", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": true }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Retinal Dystrophies", "descriptor_ui": "D058499", "major_topic": true }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": true }, { "descriptor": "Zebrafish Proteins", "descriptor_ui": "D029961", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Apr 22", "date_precision": "day", "issue": "8", "normalized_date": "2024-04-22", "pages": "e174179", "proceedings_title": null, "publisher": "", "title": "JCI insight", "volume": "9", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Phototoxicity avoidance is a potential therapeutic approach for retinal dystrophy caused by EYS dysfunction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIMS: This study was designed to develop a model for predicting bone mineral density (BMD) loss of the femur after total hip arthroplasty (THA) using artificial intelligence (AI), and to identify factors that influence the prediction. Additionally, we virtually examined the efficacy of administration of bisphosphonate for cases with severe BMD loss based on the predictive model. METHODS: The study included 538 joints that underwent primary THA. The patients were divided into groups using unsupervised time series clustering for five-year BMD loss of Gruen zone 7 postoperatively, and a machine-learning model to predict the BMD loss was developed. Additionally, the predictor for BMD loss was extracted using SHapley Additive exPlanations (SHAP). The patient-specific efficacy of bisphosphonate, which is the most important categorical predictor for BMD loss, was examined by calculating the change in predictive probability when hypothetically switching between the inclusion and exclusion of bisphosphonate. RESULTS: Time series clustering allowed us to divide the patients into two groups, and the predictive factors were identified including patient- and operation-related factors. The area under the receiver operating characteristic (ROC) curve (AUC) for the BMD loss prediction averaged 0.734. Virtual administration of bisphosphonate showed on average 14% efficacy in preventing BMD loss of zone 7. Additionally, stem types and preoperative triglyceride (TG), creatinine (Cr), estimated glomerular filtration rate (eGFR), and creatine kinase (CK) showed significant association with the estimated patient-specific efficacy of bisphosphonate. CONCLUSION: Periprosthetic BMD loss after THA is predictable based on patient- and operation-related factors, and optimal prescription of bisphosphonate based on the prediction may prevent BMD loss.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Akira", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tezuka", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hyonmin", "last_name": "Choe", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Ike", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1302/2046-3758.134.bjr-2023-0188.r1" }, "pmcid": { "normalized": "PMC11023718" }, "pmid": { "normalized": "38631686" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Apr 18", "date_precision": "day", "issue": "4", "normalized_date": "2024-04-18", "pages": "184-192", "proceedings_title": null, "publisher": "", "title": "Bone & joint research", "volume": "13", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Preoperative prediction for periprosthetic bone loss and individual evaluation of bisphosphonate effect after total hip arthroplasty using artificial intelligence.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer stem cells (CSCs), which are critical targets for cancer therapy as they are involved in drug resistance to anticancer drugs, and metastasis, are maintained by angiocrine factors produced by particular niches that form within tumor tissue. Secreted frizzled-related protein 1 (Sfrp1) is an extracellular protein that modulates Wnt signaling. However, the cells that produce Sfrp1 in the tumor environment and its function remain unclear. We aimed to elucidate angiocrine factors related to CSC maintenance, focusing on Sfrp1. Although Sfrp1 is a Wnt pathway-related factor, its impact on tumor tissues remains unknown. We investigated the localization of Sfrp1 in tumors and found that it is expressed in some tumor vessels. Analysis of mice lacking Sfrp1 showed that tumor growth was suppressed in Sfrp1-deficient tumor tissues. Flow cytometry analysis indicated that CSCs were maintained in the early tumor growth phase in the Sfrp1 knockout (KO) mouse model of tumor-bearing cancer. However, tumor growth was inhibited in the late tumor growth phase because of the inability to maintain CSCs. Real-time PCR results from tumors of Sfrp1 KO mice showed that the expression of Wnt signaling target genes significantly decreased in the late stage of tumor growth. This suggests that Sfrp1, an angiocrine factor produced by the tumor vascular niche, is involved in Wnt signaling-mediated mechanisms in tumor tissues.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" }, { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yumiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Katsuyoshi", "last_name": "Takaoka", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s11626-024-00899-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38625488" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": true }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": true }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": true }, { "descriptor": "Secreted Frizzled-Related Proteins", "descriptor_ui": "D000094742", "major_topic": false }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Apr 16", "date_precision": "day", "issue": "", "normalized_date": "2024-04-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "In vitro cellular & developmental biology. Animal", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Tumor endothelial cell-derived Sfrp1 supports the maintenance of cancer stem cells via Wnt signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Separase is a key cysteine protease in the separation of sister chromatids through the digestion of the cohesin ring that inhibits chromosome segregation as a trigger of the metaphase-anaphase transition in eukaryotes. Its activity is highly regulated by binding with securin and cyclinB-CDK1 complex. These bindings prevent the proteolytic activity of separase until the onset of anaphase. Chromosome missegregation and aneuploidy are frequently observed in malignancies. However, there are some difficulties in biochemical examinations due to the instability of separase in vitro and the fact that few spatiotemporal resolution approaches exist for monitoring live separase activity throughout mitotic processes. Here, we have developed FRET-based molecular sensors, including GFP variants, with separase-cleavable sequences as donors and covalently attached fluorescent dyes as acceptor molecules. These are applicable to conventional live cell imaging and flow cytometric analysis because of efficient live cell uptake. We investigated the performance of equivalent molecular sensors, either localized or not localized inside the nucleus under cell cycle control, using flow cytometry. Synchronized cell cycle progression rendered significant separase activity detections in both molecular sensors. We obtained consistent outcomes with localized molecular sensor introduction and cell cycle control by fluorescent microscopic observations. We thus established live cell separase activity monitoring systems that can be used specifically or statistically, which could lead to the elucidation of separase properties in detail.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Md Shazadur", "last_name": "Rahman", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/bios14040192" }, "pmcid": { "normalized": "PMC11048197" }, "pmid": { "normalized": "38667185" } }, "mesh": [ { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": true }, { "descriptor": "Chromosome Segregation", "descriptor_ui": "D020090", "major_topic": true }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": true }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Separase", "descriptor_ui": "D064247", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Apr 15", "date_precision": "day", "issue": "4", "normalized_date": "2024-04-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biosensors", "volume": "14", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Live Cell Monitoring of Separase Activity, a Key Enzymatic Reaction for Chromosome Segregation, with Chimeric FRET-Based Molecular Sensor upon Cell Cycle Progression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: MAPT is a causative gene in frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), a hereditary degenerative disease with various clinical manifestations, including progressive supranuclear palsy, corticobasal syndrome, Parkinson's disease, and frontotemporal dementia. OBJECTIVES: To analyze genetically, biochemically, and pathologically multiple members of two families who exhibited various phenotypes of the disease. METHODS: Genetic analysis included linkage analysis, homozygosity haplotyping, and exome sequencing. We conducted tau protein microtubule polymerization assay, heparin-induced tau aggregation, and western blotting with brain lysate from an autopsy case. We also evaluated abnormal tau aggregation by using anti-tau antibody and PM-PBB3. RESULTS: We identified a variant, c.896_897insACA, p.K298_H299insQ, in the MAPT gene of affected patients. Similar to previous reports, most patients presented with atypical parkinsonism. Biochemical analysis revealed that the mutant tau protein had a reduced ability to polymerize microtubules and formed abnormal fibrous aggregates. Pathological study revealed frontotemporal lobe atrophy, midbrain atrophy, depigmentation of the substantia nigra, and four-repeat tau-positive inclusions in the hippocampus, brainstem, and spinal cord neurons. The inclusion bodies also stained positively with PM-PBB3. CONCLUSIONS: This study confirmed that the insACA mutation caused FTDP-17. The affected patients showed symptoms resembling Parkinson's disease initially and symptoms of progressive supranuclear palsy later. Despite the initial clinical diagnosis of frontotemporal dementia in the autopsy case, the spread of lesions could explain the process of progressive supranuclear palsy. The study of more cases in the future will help clarify the common pathogenesis of MAPT mutations or specific pathogeneses of each mutation.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Morino", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kurashige", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Miyasaka", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Soeda", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yuishin", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Hidefumi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Arihiro", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/mdc3.14042" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38605589" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Chromosomes, Human, Pair 17", "descriptor_ui": "D002886", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Frontotemporal Dementia", "descriptor_ui": "D057180", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Parkinsonian Disorders", "descriptor_ui": "D020734", "major_topic": false }, { "descriptor": "Pedigree", "descriptor_ui": "D010375", "major_topic": false }, { "descriptor": "Supranuclear Palsy, Progressive", "descriptor_ui": "D013494", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Apr 11", "date_precision": "day", "issue": "", "normalized_date": "2024-04-11", "pages": "", "proceedings_title": null, "publisher": "", "title": "Movement disorders clinical practice", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical and Pathological Features of FTDP-17 with MAPT p.K298_H299insQ Mutation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mutations in the SNCA gene, which encodes alpha-synuclein (alpha-syn), play a key role in the development of genetic Parkinson's disease (PD). alpha-Syn is a major component of Lewy bodies in PD and glial cytoplasmic inclusions in multiple system atrophy (MSA). Rapid eye movement sleep behavior disorder (RBD) patients often progress to PD, dementia with Lewy bodies (DLB), or MSA, collectively known as alpha-synucleinopathies. The loss of dopaminergic neurons with Lewy bodies precedes motor dysfunction in these diseases, but the mechanisms of neurodegeneration due to alpha-syn aggregation are poorly understood. Monitoring alpha-syn aggregation in vivo could serve as a diagnostic biomarker and help elucidate the pathogenesis, necessitating a simple and accurate detection method. Seed amplification assays (SAAs), such as real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA), are used to detect small amounts of abnormally structured alpha-syn protofibrils, which are central to aggregation. These methods are promising for the early diagnosis of alpha-synucleinopathy. Differences in alpha-syn filament structures between alpha-synucleinopathies, observed through transmission electron microscopy and cryo-electron microscopy, suggest their role in the pathogenesis of neurodegeneration. SAAs may differentiate between subtypes of alpha-synucleinopathy and other diseases. Efforts are also being made to identify alpha-syn from blood using various methods. This review introduces body fluid alpha-syn biomarkers based on pathogenic alpha-syn seeds, which are expected to redefine alpha-synucleinopathy diagnosis and staging, improving clinical research accuracy and facilitating biomarker development.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taku", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Ayami", "last_name": "Okuzumi", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Tsunemi", "last_name": "Taiji", "name": null }, { "creator_type": "author", "first_name": "Nobutaka", "last_name": "Hattori", "name": null } ], "identifiers": { "doi": { "normalized": "10.14802/jmd.24075" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38589016" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Apr 9", "date_precision": "day", "issue": "", "normalized_date": "2024-04-09", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of movement disorders", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "alpha-Synuclein: A Promising Biomarker for Parkinson's Disease and Related Disorders.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Autoimmune diseases often arise from conditions where the immune system is compromised. While lymphopenia-induced proliferation (LIP) is crucial for immune system development and maturation, it is also caused by environmental insult, such as infection and becomes a risk factor for autoimmunity in adults. We used Dsg3H1 TCR Transgenic mice, whose T cells are designed to recognize desmogrein-3, a skin antigen, to explore the impact of lymphopenia on post-thymic tolerance. Dsg3H1 mice are known to delete the most highly autoreactive T cells in thymus, and develop only subtle immune-mediated pathology in a steady state. However, we found that a transient lymphopenia by total body irradiation or cyclophosphamide, results in massive dermatitis in Dsg3H1 mice. The symptoms included expansion and development of self-reactive T cells, their differentiation into CD44 high IL-17 producing helper T cells, and severe neutrophilic inflammation. Repopulation of FOXP3+ T regulatory cells after lymphopenia normally occurred, suggesting escape of skin-reactive conventional T cells from control by regulatory T cell. Furthermore, we found that a depletion of the intestinal microbiota by antibiotics prevents the cyclophosphamide induced dermatitis, indicating roles of commensal intestinal microbiota in LIP and Th17 development in vivo. The current data suggested that post thymic tolerance of Dsg3H1 mice is established on a fragile balance in lymphoreplete immune environment and broken by interplay between lymphopenia and intestinal microbiota. The dynamic phenotypes observed in Dsg3H1 mice prompts a reevaluation of opportunistic lymphopenia together with microbiota as pivotal environmental factors, impacting individuals with genetic predispositions of autoimmune diseases.", "classifications": [ { "id": "19H05431", "label": "19H05431", "researcher": "Shunsuke Chikuma", "type": "grant" }, { "id": "21H00439", "label": "21H00439", "researcher": "Shunsuke Chikuma", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hodaka", "last_name": "Hayabuchi", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Tokifuji", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Amagai", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/intimm/dxae018" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38576231" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Gastrointestinal Microbiome", "descriptor_ui": "D000069196", "major_topic": true }, { "descriptor": "Immune Tolerance", "descriptor_ui": "D007108", "major_topic": true }, { "descriptor": "Lymphopenia", "descriptor_ui": "D008231", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": true }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Thymus Gland", "descriptor_ui": "D013950", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Apr 5", "date_precision": "day", "issue": "", "normalized_date": "2024-04-05", "pages": "dxae018", "proceedings_title": null, "publisher": "", "title": "International immunology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Disruption of Post-thymic tolerance in Skin-Reactive TCR Transgenic Mice through the Interaction of Lymphopenia and Intestinal Microbiota.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dimension reduction has been used to visualise the distribution of multidimensional microbiome data, but the composite variables calculated by the dimension reduction methods have not been widely used to investigate the relationship of the human gut microbiome with lifestyle and disease. In the present study, we applied several dimension reduction methods, including principal component analysis, principal coordinate analysis (PCoA), non-metric multidimensional scaling (NMDS), and non-negative matrix factorization, to a microbiome dataset from 186 subjects with symptoms of allergic rhinitis (AR) and 106 controls. All the dimension reduction methods supported that the distribution of microbial data points appeared to be continuous rather than discrete. Comparison of the composite variables calculated from the different dimension reduction methods showed that the characteristics of the composite variables differed depending on the distance matrices and the dimension reduction methods. The first composite variables calculated from PCoA and NMDS with the UniFrac distance were strongly associated with AR (FDR adjusted P = 2.4 x 10(-4) for PCoA and P = 2.8 x 10(-4) for NMDS), and also with the relative abundance of Bifidobacterium and Prevotella. The abundance of Bifidobacterium was also linked to intake of several nutrients, including carbohydrate, saturated fat, and alcohol via composite variables. Notably, the association between the composite variables and AR was much stronger than the association between the relative abundance of individual genera and AR. Our results highlight the usefulness of the dimension reduction methods for investigating the association of microbial composition with lifestyle and disease in clinical research.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shohei", "last_name": "Komaki", "name": null }, { "creator_type": "author", "first_name": "Yukari", "last_name": "Sahoyama", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hachiya", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Koseki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Hamazato", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Shiozawa", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Masahira", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-024-57934-x" }, "pmcid": { "normalized": "PMC10995140" }, "pmid": { "normalized": "38575668" } }, "mesh": [ { "descriptor": "Bifidobacterium", "descriptor_ui": "D001644", "major_topic": false }, { "descriptor": "Gastrointestinal Microbiome", "descriptor_ui": "D000069196", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Multidimensional Scaling Analysis", "descriptor_ui": "D000084142", "major_topic": false }, { "descriptor": "Prevotella", "descriptor_ui": "D018720", "major_topic": false }, { "descriptor": "Rhinitis, Allergic", "descriptor_ui": "D065631", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Apr 5", "date_precision": "day", "issue": "1", "normalized_date": "2024-04-05", "pages": "7983", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "14", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Dimension reduction of microbiome data linked Bifidobacterium and Prevotella to allergic rhinitis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The background light from out-of-focus planes hinders resolution enhancement in structured illumination microscopy when observing volumetric samples. Here we used selective plane illumination and reversibly photoswitchable fluorescent proteins to realize structured illumination within the focal plane and eliminate the out-of-focus background. Theoretical investigation of the imaging properties and experimental demonstrations show that selective plane activation is beneficial for imaging dense microstructures in cells and cell spheroids.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kenta", "last_name": "Temma", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Oketani", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Rainer", "last_name": "Heintzmann", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Kaminishi", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Maho", "last_name": "Hamasaki", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41592-024-02236-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38580844" } }, "mesh": [ { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lighting", "descriptor_ui": "D008029", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": true }, { "descriptor": "Spheroids, Cellular", "descriptor_ui": "D018874", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Apr 5", "date_precision": "day", "issue": "", "normalized_date": "2024-04-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature methods", "volume": "", "year": 2024 }, "ssbd": { "database": [ "ssbd-database-000448" ], "repository": [ "ssbd-repos-000448" ] }, "title": "Selective-plane-activation structured illumination microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Objectives The objective of this study was to explore the feature of generative artificial intelligence (AI) in asking sexual health among cancer survivors, which are often challenging for patients to discuss.Methods We employed the Generative Pre-trained Transformer-3.5 (GPT) as the generative AI platform and used DocsBot for citation retrieval (June 2023). A structured prompt was devised to generate 100 questions from the AI, based on epidemiological survey data regarding sexual difficulties among cancer survivors. These questions were submitted to Bot1 (standard GPT) and Bot2 (sourced from two clinical guidelines).Results No censorship of sexual expressions or medical terms occurred. Despite the lack of reflection on guideline recommendations, 'consultation' was significantly more prevalent in both bots' responses compared with pharmacological interventions, with ORs of 47.3 (p<0.001) in Bot1 and 97.2 (p<0.001) in Bot2.Discussion Generative AI can serve to provide health information on sensitive topics such as sexual health, despite the potential for policy-restricted content. Responses were biased towards non-pharmacological interventions, which is probably due to a GPT model designed with the 's prohibition policy on replying to medical topics. This shift warrants attention as it could potentially trigger patients' expectations for non-pharmacological interventions.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Akiko", "last_name": "Hanai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Shoichiro", "last_name": "Kawauchi", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1136/bmjhci-2023-100924" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38575326" } }, "mesh": [ { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": false }, { "descriptor": "Bias", "descriptor_ui": "D015982", "major_topic": false }, { "descriptor": "Health Communication", "descriptor_ui": "D058015", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Sexual Health", "descriptor_ui": "D000074384", "major_topic": true }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Apr 4", "date_precision": "day", "issue": "1", "normalized_date": "2024-04-04", "pages": "e100924", "proceedings_title": null, "publisher": "", "title": "BMJ health & care informatics", "volume": "31", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Generative artificial intelligence and non-pharmacological bias: an experimental study on cancer patient sexual health communications.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Saki", "last_name": "Egashira", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/mab.2024.0005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38563773" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": true }, { "descriptor": "Epitopes", "descriptor_ui": "D000939", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Apr 2", "date_precision": "day", "issue": "", "normalized_date": "2024-04-02", "pages": "", "proceedings_title": null, "publisher": "", "title": "Monoclonal antibodies in immunodiagnosis and immunotherapy", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Monoclonal Antibody Rat 2F11 and Rabbit A3 Against Anti-H2b3b.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "All tumour cells in a patient have shared and non-shared genetic alterations, and the diversity of mutations is described as intratumoural heterogeneity (ITH). Multiregion sequencing is a genome sequencing analytical technique used for multiple, spatially-separated biopsy tissues that may further our understanding of ITH and tumour evolution. Although genetic mutations in extramammary Paget's disease (EMPD) have recently been detected by next-generation sequencing analysis, there have been no reports of ITH based on multiregion sequencing in EMPD. Thus, we clarified the landscape of ITH and tumour evolution in EMPD. We performed whole-exome sequencing on 35 tissues (30 tumour tissues and five normal skin samples as a paired control), collected from five patients with EMPD. The rate of private mutations was significantly higher than that of ubiquitous and shared mutations. Ubiquitous mutations were not present in driver genes, and most driver genes exhibited private and shared mutations. The most frequent base substitution was C>T in almost all lesions, and most mutational signatures corresponded to signature 1, 2, 3, and 8. The types of proposed aetiology in most lesions were based on age and AID/APOBEC family and BRCA1/BRCA2 mutations. Evolutionary trees were characterized by short trunks and long branches due to the extremely high ratio of private mutations. In contrast, pathogenic factors, such as base substitutions, mutational signatures, and proposed aetiology, were shared. Tumour evolution in EMPD appears to be characterized by a high level of genetic ITH with shared background factors.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ikko", "last_name": "Kajihara", "name": null }, { "creator_type": "author", "first_name": "Kazuro", "last_name": "Shimokawa", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yudo", "last_name": "Kusaba", "name": null }, { "creator_type": "author", "first_name": "Ryoko", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Saki", "last_name": "Maeda-Otsuka", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Yamada-Kanazawa", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Sawamura", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Kanemaru", "name": null }, { "creator_type": "author", "first_name": "Katsunari", "last_name": "Makino", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Aoi", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Masuguchi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fukushima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1684/ejd.2024.4609" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38907549" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Clonal Evolution", "descriptor_ui": "D060965", "major_topic": true }, { "descriptor": "Exome Sequencing", "descriptor_ui": "D000073359", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Heterogeneity", "descriptor_ui": "D018740", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Paget Disease, Extramammary", "descriptor_ui": "D010145", "major_topic": true }, { "descriptor": "Skin Neoplasms", "descriptor_ui": "D012878", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Apr 1", "date_precision": "day", "issue": "2", "normalized_date": "2024-04-01", "pages": "182-192", "proceedings_title": null, "publisher": "", "title": "European journal of dermatology : EJD", "volume": "34", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetic intratumour heterogeneity and clonal evolution in extramammary Paget's disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The social amoeba Dictyostelium discoideum switches between solitary growth and social fruitification depending on nutrient availability. Under starvation, cells aggregate and form fruiting bodies consisting of spores and altruistic stalk cells. Once cells socially committed, they complete fruitification, even if a new source of nutrients becomes available. This social commitment is puzzling because it hinders individual cells from resuming solitary growth quickly. One idea posits that traits that facilitate premature de-commitment are hindered from being selected. We studied outcomes of the premature de-commitment through forced refeeding. Our results show that when refed cells interacted with non-refed cells, some of them became solitary, whereas a fraction was redirected to the altruistic stalk, regardless of their original fate. The refed cells exhibited reduced cohesiveness and were sorted out during morphogenesis. Our findings provide an insight into a division of labor of the social amoeba, in which less cohesive individuals become altruists.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuka", "last_name": "Shirokawa", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-024-58277-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38561423" } }, "mesh": [ { "descriptor": "Amoeba", "descriptor_ui": "D000656", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Apr 1", "date_precision": "day", "issue": "1", "normalized_date": "2024-04-01", "pages": "7677", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "14", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Prestalk-like positioning of de-differentiated cells in the social amoeba Dictyostelium discoideum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tissues consist of cells with different molecular and/or mechanical properties. Measuring the forces and stresses in mixed-cell populations is essential for understanding the mechanisms by which tissue development, homeostasis, and disease emerge from the cooperation of distinct cell types. However, many previous studies have primarily focused their mechanical measurements on dissociated cells or aggregates of a single-cell type, leaving the mechanics of mixed-cell populations largely unexplored. In the present study, we aimed to elucidate the influence of interactions between different cell types on cell mechanics by conducting in situ mechanical measurements on a monolayer of mammalian epithelial cells. Our findings revealed that while individual cell types displayed varying magnitudes of traction and intercellular stress before mixing, these mechanical values shifted in the mixed monolayer, becoming nearly indistinguishable between the cell types. Moreover, by analyzing a mixed-phase model of active tissues, we identified physical conditions under which such mechanical convergence is induced. Overall, the present study underscores the importance of in situ mechanical measurements in mixed-cell populations to deepen our understanding of the mechanics of multicellular systems.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Estelle", "last_name": "Gauquelin", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Kuromiya", "name": null }, { "creator_type": "author", "first_name": "Toshinori", "last_name": "Namba", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Sugimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1140/epje/s10189-024-00415-w" }, "pmcid": { "normalized": "PMC10973031" }, "pmid": { "normalized": "38538808" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": true }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": true }, { "descriptor": "Stress, Mechanical", "descriptor_ui": "D013314", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 27", "date_precision": "day", "issue": "3", "normalized_date": "2024-03-27", "pages": "21", "proceedings_title": null, "publisher": "", "title": "The European physical journal. E, Soft matter", "volume": "47", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Mechanical convergence in mixed populations of mammalian epithelial cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2294 animals with genetic and other experimental manipulations relevant to neuropsychiatric disorders. Systematic analysis revealed that decreased brain pH and increased lactate levels were common features observed in multiple models of depression, epilepsy, Alzheimer's disease, and some additional schizophrenia models. While certain autism models also exhibited decreased pH and increased lactate levels, others showed the opposite pattern, potentially reflecting subpopulations within the autism spectrum. Furthermore, utilizing large-scale behavioral test battery, a multivariate cross-validated prediction analysis demonstrated that poor working memory performance was predominantly associated with increased brain lactate levels. Importantly, this association was confirmed in an independent cohort of animal models. Collectively, these findings suggest that altered brain pH and lactate levels, which could be attributed to dysregulated excitation/inhibition balance, may serve as transdiagnostic endophenotypes of debilitating neuropsychiatric disorders characterized by cognitive impairment, irrespective of their beneficial or detrimental nature.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hideo", "last_name": "Hagihara", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Shoji", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Giovanni", "last_name": "Sala", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Takamiya", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Mihiro", "last_name": "Shibutani", "name": null }, { "creator_type": "author", "first_name": "Izuho", "last_name": "Hatada", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Mikio", "last_name": "Hoshino", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Anja", "last_name": "Urbach", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Akinobu", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Keiichi I.", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Katori", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Iwasato", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Goshima", "name": null }, { "creator_type": "author", "first_name": "Matthieu", "last_name": "Raveau", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Tatsukawa", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Johji", "last_name": "Inazawa", "name": null }, { "creator_type": "author", "first_name": "Ikuo", "last_name": "Nobuhisa", "name": null }, { "creator_type": "author", "first_name": "Tetsushi", "last_name": "Kagawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Taga", "name": null }, { "creator_type": "author", "first_name": "Mohamed", "last_name": "Darwish", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Nishizono", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Takao", "name": null }, { "creator_type": "author", "first_name": "Kiran", "last_name": "Sapkota", "name": null }, { "creator_type": "author", "first_name": "Kazutoshi", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Haruki", "last_name": "Fujisawa", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Sugimura", "name": null }, { "creator_type": "author", "first_name": "Kyosuke", "last_name": "Yamanishi", "name": null }, { "creator_type": "author", "first_name": "Lakshmi", "last_name": "Rajagopal", "name": null }, { "creator_type": "author", "first_name": "Nanette Deneen", "last_name": "Hannah", "name": null }, { "creator_type": "author", "first_name": "Herbert Y.", "last_name": "Meltzer", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Wakatsuki", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Tabuchi", "name": null }, { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Numakawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kunugi", "name": null }, { "creator_type": "author", "first_name": "Freesia L.", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Tamada", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takumi", "name": null }, { "creator_type": "author", "first_name": "Takaoki", "last_name": "Kasahara", "name": null }, { "creator_type": "author", "first_name": "Tadafumi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Isabella A.", "last_name": "Graef", "name": null }, { "creator_type": "author", "first_name": "Gerald R.", "last_name": "Crabtree", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Asaoka", "name": null }, { "creator_type": "author", "first_name": "Hikari", "last_name": "Hatakama", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Mitsuharu", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Hoshiba", "name": null }, { "creator_type": "author", "first_name": "Ryuhei", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Kisho", "last_name": "Obi-Nagata", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Hayashi-Takagi", "name": null }, { "creator_type": "author", "first_name": "Lea J.", "last_name": "Becker", "name": null }, { "creator_type": "author", "first_name": "Ipek", "last_name": "Yalcin", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Hagino", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kotajima-Murakami", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Moriya", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Hyopil", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Bong-Kiun", "last_name": "Kaang", "name": null }, { "creator_type": "author", "first_name": "Hikari", "last_name": "Otabi", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Noboru H.", "last_name": "Komiyama", "name": null }, { "creator_type": "author", "first_name": "Seth G. N.", "last_name": "Grant", "name": null }, { "creator_type": "author", "first_name": "Michiru", "last_name": "Ida-Eto", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Emiko", "last_name": "Okuda-Ashitaka", "name": null }, { "creator_type": "author", "first_name": "Iori", "last_name": "Ohmori", "name": null }, { "creator_type": "author", "first_name": "Tadayuki", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Kanato", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ageta", "name": null }, { "creator_type": "author", "first_name": "Kunihiro", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Inokuchi", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Sassa", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Kihara", "name": null }, { "creator_type": "author", "first_name": "Motoaki", "last_name": "Fukasawa", "name": null }, { "creator_type": "author", "first_name": "Nobuteru", "last_name": "Usuda", "name": null }, { "creator_type": "author", "first_name": "Tayo", "last_name": "Katano", "name": null }, { "creator_type": "author", "first_name": "Teruyuki", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Nakada", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Hirotsune", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Egawa", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Higashisaka", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Nishihara", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Sugo", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Kimiko", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Higo-Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Katsutaka", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Tamio", "last_name": "Furuse", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Shirakawa", "name": null }, { "creator_type": "author", "first_name": "Daiki X.", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yukiko U.", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yuriko", "last_name": "Komine", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Yamamori", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Miyakawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.89376" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38529532" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cognitive Dysfunction", "descriptor_ui": "D060825", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Endophenotypes", "descriptor_ui": "D058068", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Lactates", "descriptor_ui": "D007773", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 26", "date_precision": "day", "issue": "", "normalized_date": "2024-03-26", "pages": "RP89376", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "12", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Large-scale animal model study uncovers altered brain pH and lactate levels as a transdiagnostic endophenotype of neuropsychiatric disorders involving cognitive impairment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent advancements in image-based pooled CRISPR screening have facilitated the mapping of diverse genotype-phenotype associations within mammalian cells. However, the rapid enrichment of cells based on morphological information continues to pose a challenge, constraining the capacity for large-scale gene perturbation screening across diverse high-content cellular phenotypes. In this study, we demonstrate the applicability of multimodal ghost cytometry-based cell sorting, including both fluorescent and label-free high-content phenotypes, for rapid pooled CRISPR screening within vast cell populations. Using the high-content cell sorter operating in fluorescence mode, we successfully executed kinase-specific CRISPR screening targeting genes influencing the nuclear translocation of RelA. Furthermore, using the multiparametric, label-free mode, we performed large-scale screening to identify genes involved in macrophage polarization. Notably, the label-free platform can enrich target phenotypes without requiring invasive staining, preserving untouched cells for downstream assays and expanding the potential for screening cellular phenotypes even when suitable markers are absent.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Asako", "last_name": "Tsubouchi", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "An", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Yanagihashi", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Teranishi", "name": null }, { "creator_type": "author", "first_name": "Soh", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Aburatani", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Yachie", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.crmeth.2024.100737" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38531306" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Separation", "descriptor_ui": "D002469", "major_topic": false }, { "descriptor": "Clustered Regularly Interspaced Short Palindromic Repeats", "descriptor_ui": "D064112", "major_topic": true }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Genetic Testing", "descriptor_ui": "D005820", "major_topic": true }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 25", "date_precision": "day", "issue": "3", "normalized_date": "2024-03-25", "pages": "100737", "proceedings_title": null, "publisher": "", "title": "Cell reports methods", "volume": "4", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Pooled CRISPR screening of high-content cellular phenotypes using ghost cytometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cellular temperature affects every biochemical reaction, underscoring its critical role in cellular functions. In neurons, temperature not only modulates neurotransmission but is also a key determinant of neurodegenerative diseases. Considering that the brain consumes a disproportionately high amount of energy relative to its weight, neural circuits likely generate a lot of heat, which can increase cytosolic temperature. However, the changes in temperature within neurons and the mechanisms of heat generation during neural excitation remain unclear. In this study, we achieved simultaneous imaging of Ca(2+) and temperature using the genetically encoded indicators, B-GECO and B-gTEMP. We then compared the spatiotemporal distributions of Ca(2+) responses and temperature. Following neural excitation induced by veratridine, an activator of the voltage-gated Na(+) channel, we observed an approximately 2 degrees C increase in cytosolic temperature occurring 30 s after the Ca(2+) response. The temperature elevation was observed in the non-nuclear region, while Ca(2+) increased throughout the cell body. Moreover, this temperature increase was suppressed under Ca(2+)-free conditions and by inhibitors of ATP synthesis. These results indicate that Ca(2+)-induced upregulation of energy metabolism serves as the heat source during neural excitation.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jiayang", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Cong Quang", "last_name": "Vu", "name": null }, { "creator_type": "author", "first_name": "Kai", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Tetsuichi", "last_name": "Wazawa", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2024.149799" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38522401" } }, "mesh": [ { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": true }, { "descriptor": "Calcium, Dietary", "descriptor_ui": "D002136", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Hot Temperature", "descriptor_ui": "D006358", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 22", "date_precision": "day", "issue": "", "normalized_date": "2024-03-22", "pages": "149799", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "708", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Calcium-induced upregulation of energy metabolism heats neurons during neural activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To monitor the Ca(2+) dynamics in cells, various genetically encoded Ca(2+) indicators (GECIs) based on Forster resonance energy transfer (FRET) between fluorescent proteins are widely used for live imaging. Conventionally, cyan and yellow fluorescent proteins have been often used as FRET pairs. Meanwhile, bathochromically shifted indicators with green and red fluorescent protein pairs have various advantages, such as low toxicity and autofluorescence in cells. However, it remains difficult to develop them with a similar level of dynamic range as cyan and yellow fluorescent protein pairs. To improve this, we used Gamillus, which has a unique trans-configuration chromophore, as a green fluorescent protein. Based on one of the best high-dynamic-range GECIs, Twitch-NR, we developed a GECI with 1.5-times higher dynamic range (253%), Twitch-GmRR, using RRvT as a red fluorescent protein. Twitch-GmRR had high brightness and photostability and was successfully applied for imaging the Ca(2+) dynamics in live cells. Our results suggest that Gamillus with trans-type chromophores contributes to improving the dynamic range of GECIs. Therefore, selection of the cis-trans isomer of the chromophore may be a fundamental approach to improve the dynamic range of green-red FRET indicators, unlimited by GECIs.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Kei-Ichi", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acssensors.3c02398" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38515268" } }, "mesh": [ { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": true }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": true }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": true }, { "descriptor": "Red Fluorescent Protein", "descriptor_ui": "D000097573", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 21", "date_precision": "day", "issue": "", "normalized_date": "2024-03-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "ACS sensors", "volume": "", "year": 2024 }, "ssbd": { "database": [ "ssbd-database-000476" ], "repository": [ "ssbd-repos-000476" ] }, "title": "Improvement of the Green-Red Forster Resonance Energy Transfer-Based Ca(2+) Indicator by Using the Green Fluorescent Protein, Gamillus, with a Trans Chromophore as the Donor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neuromesodermal progenitors (NMPs), serving as the common origin of neural and paraxial mesodermal development in a large part of the trunk, have recently gained significant attention because of their critical importance in the understanding of embryonic organogenesis and the design of in vitro models of organogenesis. However, the nature of NMPs at many essential points remains only vaguely understood or even incorrectly assumed. Here, we discuss the nature of NMPs, focusing on their dynamic migratory behavior during embryogenesis and the mechanisms underlying their neural vs. mesodermal fate choice. The discussion points include the following: (1) How the sinus rhomboidals is organized; the tissue where the neural or mesodermal fate choice of NMPs occurs. (2) NMPs originating from the broad posterior epiblast are associated with Sox2 N1 enhancer activity. (3) Tbx6-dependent Sox2 repression occurs during NMP-derived paraxial mesoderm development. (4) The nephric mesenchyme, a component of the intermediate mesoderm, was newly identified as an NMP derivative. (5) The transition of embryonic tissue development from tissue-specific progenitors in the anterior part to that from NMPs occurs at the forelimb bud axial level. (6) The coexpression of Sox2 and Bra in NMPs is conditional and is not a hallmark of NMPs. (7) The ability of the NMP pool to sustain axial embryo growth depends on Wnt3a signaling in the NMP population. Current in vitro models of NMPs are also critically reviewed.", "classifications": [ { "id": "18H05415", "label": "18H05415", "researcher": "Kazuki Horikawa", "type": "grant" }, { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hisato", "last_name": "Kondoh", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cells13060549" }, "pmcid": { "normalized": "PMC10968745" }, "pmid": { "normalized": "38534393" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Germ Layers", "descriptor_ui": "D005855", "major_topic": false }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": false }, { "descriptor": "Nervous System", "descriptor_ui": "D009420", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 21", "date_precision": "day", "issue": "6", "normalized_date": "2024-03-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cells", "volume": "13", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "The Origin and Regulation of Neuromesodermal Progenitors (NMPs) in Embryos.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Determinants of HIV-1 latency establishment are yet to be elucidated. HIV reservoir comprises a rare fraction of infected cells that can survive host and virus-mediated killing. In vitro reporter models so far offered a feasible means to inspect this population, but with limited capabilities to dissect provirus silencing dynamics. Here, we describe a new HIV reporter model, HIV-Timer of cell kinetics and activity (HIV-Tocky) with dual fluorescence spontaneous shifting to reveal provirus silencing and reactivation dynamics. This unique feature allows, for the first time, identifying two latent populations: a directly latent, and a recently silenced subset, with the latter having integration features suggestive of stable latency. Our proposed model can help address the heterogeneous nature of HIV reservoirs and offers new possibilities for evaluating eradication strategies.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Omnia", "last_name": "Reda", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Monde", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sugata", "name": null }, { "creator_type": "author", "first_name": "Akhinur", "last_name": "Rahman", "name": null }, { "creator_type": "author", "first_name": "Wajihah", "last_name": "Sakhor", "name": null }, { "creator_type": "author", "first_name": "Samiul Alam", "last_name": "Rajib", "name": null }, { "creator_type": "author", "first_name": "Sharmin Nahar", "last_name": "Sithi", "name": null }, { "creator_type": "author", "first_name": "Benjy Jek Yang", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Niimura", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Motozono", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yorifumi", "last_name": "Satou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-024-06025-8" }, "pmcid": { "normalized": "PMC10954732" }, "pmid": { "normalized": "38509308" } }, "mesh": [ { "descriptor": "HIV Infections", "descriptor_ui": "D015658", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Proviruses", "descriptor_ui": "D011533", "major_topic": true }, { "descriptor": "Virus Latency", "descriptor_ui": "D017735", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 20", "date_precision": "day", "issue": "1", "normalized_date": "2024-03-20", "pages": "344", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "7", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "HIV-Tocky system to visualize proviral expression dynamics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Accelerating the measurement for discrimination of samples, such as classification of cell phenotype, is crucial when faced with significant time and cost constraints. Spontaneous Raman microscopy offers label-free, rich chemical information but suffers from long acquisition time due to extremely small scattering cross-sections. One possible approach to accelerate the measurement is by measuring necessary parts with a suitable number of illumination points. However, how to design these points during measurement remains a challenge. To address this, we developed an imaging technique based on a reinforcement learning in machine learning (ML). This ML approach adaptively feeds back \"optimal\" illumination pattern during the measurement to detect the existence of specific characteristics of interest, allowing faster measurements while guaranteeing discrimination accuracy. Using a set of Raman images of human follicular thyroid and follicular thyroid carcinoma cells, we showed that our technique requires 3,333 to 31,683 times smaller number of illuminations for discriminating the phenotypes than raster scanning. To quantitatively evaluate the number of illuminations depending on the requisite discrimination accuracy, we prepared a set of polymer bead mixture samples to model anomalous and normal tissues. We then applied a home-built programmable-illumination microscope equipped with our algorithm, and confirmed that the system can discriminate the sample conditions with 104 to 4,350 times smaller number of illuminations compared to standard point illumination Raman microscopy. The proposed algorithm can be applied to other types of microscopy that can control measurement condition on the fly, offering an approach for the acceleration of accurate measurements in various applications including medical diagnosis.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kawagoe", "name": null }, { "creator_type": "author", "first_name": "J. Nicholas", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Jean-Emmanuel", "last_name": "Clement", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Atsuyoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2304866121" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38483992" } }, "mesh": [ { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": true }, { "descriptor": "Nonlinear Optical Microscopy", "descriptor_ui": "D000073758", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Thyroid Gland", "descriptor_ui": "D013961", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 19", "date_precision": "day", "issue": "12", "normalized_date": "2024-03-19", "pages": "e2304866121", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "121", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "On-the-fly Raman microscopy guaranteeing the accuracy of discrimination.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "H2b3b is one of the histone H2b isoforms that differs from canonical H2b by five to six amino acids. Previously, we identified H3t as the testis-specific histone H3 variant located in histone cluster 3, which is also the site of H2b3b. In this study, we produced monoclonal antibodies against H2b3b, using the iliac rat lymph node method for rat antibody and the immunochamber method for rabbit antibody. Immunoblot analysis confirmed that our antibodies could specifically discriminate between H2b3b and canonical H2b. Moreover, immunostaining revealed colocalization with a testicular stem cell marker, Plzf, but not with a meiotic marker, Sycp. This indicated that H2b3b is expressed in spermatogenic cells before meiosis. Our monoclonal antibodies enable further studies to reveal specific functions of H2b3b during spermatogenesis. We also hope that the established method will lead to the production of antibodies that can identify other H2b isoforms.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Saki", "last_name": "Egashira", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/mab.2023.0025" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38502827" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": true }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Spermatogenesis", "descriptor_ui": "D013091", "major_topic": false }, { "descriptor": "Testis", "descriptor_ui": "D013737", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 19", "date_precision": "day", "issue": "", "normalized_date": "2024-03-19", "pages": "", "proceedings_title": null, "publisher": "", "title": "Monoclonal antibodies in immunodiagnosis and immunotherapy", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Production of a Monoclonal Antibody for Histone H2b Isoform H2b3b.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: Vascular distribution is important information for diagnosing diseases and supporting surgery. Photoacoustic imaging is a technology that can image blood vessels noninvasively and with high resolution. In photoacoustic imaging, a hemispherical array sensor is especially suitable for measuring blood vessels running in various directions. However, as a hemispherical array sensor, a sparse array sensor is often used due to technical and cost issues, which causes artifacts in photoacoustic images. Therefore, in this study, we reduce these artifacts using deep learning technology to generate signals of virtual dense array sensors. METHODS: Generating 2D virtual array sensor signals using a 3D convolutional neural network (CNN) requires huge computational costs and is impractical. Therefore, we installed virtual sensors between the real sensors along the spiral pattern in three different directions and used a 2D CNN to generate signals of the virtual sensors in each direction. Then we reconstructed a photoacoustic image using the signals from both the real sensors and the virtual sensors. RESULTS: We evaluated the proposed method using simulation data and human palm measurement data. We found that these artifacts were significantly reduced in the images reconstructed using the proposed method, while the artifacts were strong in the images obtained only from the real sensor signals. CONCLUSION: Using the proposed method, we were able to significantly reduce artifacts, and as a result, it became possible to recognize deep blood vessels. In addition, the processing time of the proposed method was sufficiently applicable to clinical measurement.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10396-024-01413-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38480548" } }, "mesh": [ { "descriptor": "Artifacts", "descriptor_ui": "D016477", "major_topic": true }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Hand", "descriptor_ui": "D006225", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": true }, { "descriptor": "Photoacoustic Techniques", "descriptor_ui": "D061088", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Mar 14", "date_precision": "day", "issue": "", "normalized_date": "2024-03-14", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of medical ultrasonics (2001)", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Artifact reduction in photoacoustic images by generating virtual dense array sensor from hemispheric sparse array sensor using deep learning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Synaptic plasticity, the process whereby neuronal connections are either strengthened or weakened in response to stereotyped forms of stimulation, is widely believed to represent the molecular mechanism that underlies learning and memory. The holoenzyme CaMKII plays a well-established and critical role in the induction of a variety of forms of synaptic plasticity such as long-term potentiation (LTP), long-term depression (LTD) and depotentiation. Previously, we identified the GTPase Rem2 as a potent, endogenous inhibitor of CaMKII. Here, we report that knock out of Rem2 enhances LTP at the Schaffer collateral to CA1 synapse in hippocampus, consistent with an inhibitory action of Rem2 on CaMKII in vivo. Further, re-expression of WT Rem2 rescues the enhanced LTP observed in slices obtained from Rem2 conditional knock out (cKO) mice, while expression of a mutant Rem2 construct that is unable to inhibit CaMKII in vitro fails to rescue increased LTP. In addition, we demonstrate that CaMKII and Rem2 interact in dendritic spines using a 2pFLIM-FRET approach. Taken together, our data lead us to propose that Rem2 serves as a brake on runaway synaptic potentiation via inhibition of CaMKII activity. Further, the enhanced LTP phenotype we observe in Rem2 cKO slices reveals a previously unknown role for Rem2 in the negative regulation of CaMKII function.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Rabia", "last_name": "Anjum", "name": null }, { "creator_type": "author", "first_name": "Vernon R. J.", "last_name": "Clarke", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Nagasawa", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Suzanne", "last_name": "Paradis", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/2024.03.11.584540" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Mar 12", "date_precision": "day", "issue": null, "normalized_date": "2024-03-12", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Rem2 interacts with CaMKII at synapses and restricts long-term potentiation in hippocampus.", "url": "", "zotero": { "item_type": "preprint" } }, { "abstract": "Chronic infection with hepatitis B virus (HBV) is caused by the persistence of closed circular DNA (cccDNA) in the nucleus of infected hepatocytes. Despite available therapeutic anti-HBV agents, eliminating the cccDNA remains challenging. Thus, quantifying and understanding the dynamics of cccDNA are essential for developing effective treatment strategies and new drugs. However, such study requires repeated liver biopsy to measure the intrahepatic cccDNA, which is basically not accepted because liver biopsy is potentially morbid and not common during hepatitis B treatment. We here aimed to develop a noninvasive method for quantifying cccDNA in the liver using surrogate markers in peripheral blood. We constructed a multiscale mathematical model that explicitly incorporates both intracellular and intercellular HBV infection processes. The model, based on age-structured partial differential equations, integrates experimental data from in vitro and in vivo investigations. By applying this model, we roughly predicted the amount and dynamics of intrahepatic cccDNA within a certain range using specific viral markers in serum samples, including HBV DNA, HBsAg, HBeAg, and HBcrAg. Our study represents a significant step towards advancing the understanding of chronic HBV infection. The noninvasive quantification of cccDNA using our proposed method holds promise for improving clinical analyses and treatment strategies. By comprehensively describing the interactions of all components involved in HBV infection, our multiscale mathematical model provides a valuable framework for further research and the development of targeted interventions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kosaku", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Kwang Su", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Sanae", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Hyeongki", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Takara", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Nakaoka", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Alan S.", "last_name": "Perelson", "name": null }, { "creator_type": "author", "first_name": "Lena", "last_name": "Allweiss", "name": null }, { "creator_type": "author", "first_name": "Maura", "last_name": "Dandri", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Watashi", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Iwami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1011238" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38466770" } }, "mesh": [ { "descriptor": "Antiviral Agents", "descriptor_ui": "D000998", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "DNA, Circular", "descriptor_ui": "D004270", "major_topic": false }, { "descriptor": "DNA, Viral", "descriptor_ui": "D004279", "major_topic": false }, { "descriptor": "Hepatitis B", "descriptor_ui": "D006509", "major_topic": true }, { "descriptor": "Hepatitis B e Antigens", "descriptor_ui": "D006513", "major_topic": false }, { "descriptor": "Hepatitis B Surface Antigens", "descriptor_ui": "D006514", "major_topic": false }, { "descriptor": "Hepatitis B virus", "descriptor_ui": "D006515", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 11", "date_precision": "day", "issue": "3", "normalized_date": "2024-03-11", "pages": "e1011238", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "20", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Multiscale modeling of HBV infection integrating intra- and intercellular viral propagation to analyze extracellular viral markers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Highly polar and charged molecules, such as oligonucleotides, face significant barriers in crossing the cell membrane to access the cytoplasm. To address this problem, we developed a light-triggered twistable tetraphenylethene (TPE) derivative, TPE-C-N, to facilitate the intracellular delivery of charged molecules through an endocytosis-independent pathway. The central double bond of TPE in TPE-C-N is planar in the ground state but becomes twisted in the excited state. Under light irradiation, this planar-to-twisted structural change induces continuous cell membrane disturbances. Such disturbance does not lead to permanent damage to the cell membrane. TPE-C-N significantly enhanced the intracellular delivery of negatively charged molecules under light irradiation when endocytosis was inhibited through low-temperature treatment, confirming the endocytosis-independent nature of this delivery method. We have successfully demonstrated that the TPE-C-N-mediated light-controllable method can efficiently promote the intracellular delivery of charged molecules, such as peptides and oligonucleotides, with molecular weights ranging from 1000 to 5000 Da.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Wenting", "last_name": "Huo", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Huiying", "last_name": "Mu", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Osawa", "name": null }, { "creator_type": "author", "first_name": "Harumi", "last_name": "Yamaguma", "name": null }, { "creator_type": "author", "first_name": "Yuuya", "last_name": "Kasahara", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Obika", "name": null }, { "creator_type": "author", "first_name": "Yoshimasa", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Hisaaki", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Shiroh", "last_name": "Futaki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Shinoda", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Akai", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d3tb02956e" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38456552" } }, "mesh": [ { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": true }, { "descriptor": "Drug Delivery Systems", "descriptor_ui": "D016503", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": true }, { "descriptor": "Oligonucleotides", "descriptor_ui": "D009841", "major_topic": false }, { "descriptor": "Stilbenes", "descriptor_ui": "D013267", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Mar 8", "date_precision": "day", "issue": "", "normalized_date": "2024-03-08", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of materials chemistry. B", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Light-controllable cell-membrane disturbance for intracellular delivery.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Whole genome analysis has identified rare copy number variations (CNV) that are strongly involved in the pathogenesis of psychiatric disorders, and 3q29 deletion has been found to have the largest effect size. The 3q29 deletion mice model (3q29-del mice) has been established as a good pathological model for schizophrenia based on phenotypic analysis; however, circadian rhythm and sleep, which are also closely related to neuropsychiatric disorders, have not been investigated. In this study, our aims were to reevaluate the pathogenesis of 3q29-del by recreating model mice and analyzing their behavior and to identify novel new insights into the temporal activity and temperature fluctuations of the mouse model using a recently developed small implantable accelerometer chip, Nano-tag. We generated 3q29-del mice using genome editing technology and reevaluated common behavioral phenotypes. We next implanted Nano-tag in the abdominal cavity of mice for continuous measurements of long-time activity and body temperature. Our model mice exhibited weight loss similar to that of other mice reported previously. A general behavioral battery test in the model mice revealed phenotypes similar to those observed in mouse models of schizophrenia, including increased rearing frequency. Intraperitoneal implantation of Nano-tag, a miniature acceleration sensor, resulted in hypersensitive and rapid increases in the activity and body temperature of 3q29-del mice upon switching to lights-off condition. Similar to the 3q29-del mice reported previously, these mice are a promising model animals for schizophrenia. Successive quantitative analysis may provide results that could help in treating sleep disorders closely associated with neuropsychiatric disorders.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Sawahata", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Kodama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Hirao", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Arioka", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Inami", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Nawa", "name": null }, { "creator_type": "author", "first_name": "Seiko", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Kushima", "name": null }, { "creator_type": "author", "first_name": "Branko", "last_name": "Aleksic", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mizoguchi", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kozo", "last_name": "Kaibuchi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Kume", "name": null }, { "creator_type": "author", "first_name": "Kiyofumi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Ozaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41398-023-02679-w" }, "pmcid": { "normalized": "PMC10920862" }, "pmid": { "normalized": "38453903" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Temperature", "descriptor_ui": "D001831", "major_topic": false }, { "descriptor": "Child", "descriptor_ui": "D002648", "major_topic": false }, { "descriptor": "Chromosome Deletion", "descriptor_ui": "D002872", "major_topic": false }, { "descriptor": "Developmental Disabilities", "descriptor_ui": "D002658", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "DNA Copy Number Variations", "descriptor_ui": "D056915", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intellectual Disability", "descriptor_ui": "D008607", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 7", "date_precision": "day", "issue": "1", "normalized_date": "2024-03-07", "pages": "138", "proceedings_title": null, "publisher": "", "title": "Translational psychiatry", "volume": "14", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Phenotypes for general behavior, activity, and body temperature in 3q29 deletion model mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescence imaging is a powerful technique for visualizing biological events in living samples with high temporal and spatial resolution. Fluorescent probes emitting far-red to near infrared (NIR) fluorescence are particularly advantageous for in vivo imaging due to their high tissue permeability and low autofluorescence, as well as their suitability for multicolor imaging. Among the far-red to NIR fluorophores, Si-rhodamine is one of the most practical fluorophores for the development of tailor-made NIR fluorescent probes because of the relative ease of synthesis of various derivatives, the unique intramolecular spirocyclization behavior, and the relatively high water solubility and high photostability of the probes. This review summarizes these features of Si-rhodamines and presents recent advances in the synthesis and applications of far-red to NIR fluorescent probes based on Si-rhodamines, focusing on live-cell imaging applications such as fluorogenic probes, super-resolution imaging and dye-protein hybrid-based indicators.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hisashi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d4ob00130c" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38444309" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Mar 6", "date_precision": "day", "issue": "", "normalized_date": "2024-03-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "Organic & biomolecular chemistry", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Recent advances in Si-rhodamine-based fluorescent probes for live-cell imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "T cell exhaustion impairs tumor immunity and contributes to resistance against immune checkpoint inhibitors. The nuclear receptor subfamily 4 group A (NR4a) family of nuclear receptors plays a crucial role in driving T cell exhaustion. In this study, we observe that NR4a1 and NR4a2 deficiency in CD8(+) tumor-infiltrating lymphocytes (TILs) results in potent tumor eradication and exhibits not only reduced exhaustion characteristics but also an increase in the precursors/progenitors of exhausted T (Pre-Tex) cell fraction. Serial transfers of NR4a1(-/-)NR4a2(-/-)CD8(+) TILs into tumor-bearing mice result in the expansion of TCF1(+) (Tcf7(+)) stem-like Pre-Tex cells, whereas wild-type TILs are depleted upon secondary transfer. NR4a1/2-deficient CD8(+) T cells express higher levels of stemness/memory-related genes and illustrate potent mitochondrial oxidative phosphorylation. Collectively, these findings suggest that inhibiting NR4a in tumors represents a potent immuno-oncotherapy strategy by increasing stem-like Pre-Tex cells and reducing exhaustion of CD8(+) T cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tanakorn", "last_name": "Srirat", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Setsuko", "last_name": "Mise-Omata", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Nakagawara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Shichino", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2024.113898" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38451819" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": true }, { "descriptor": "Lymphocytes, Tumor-Infiltrating", "descriptor_ui": "D016246", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Nuclear Receptor Subfamily 4, Group A, Member 1", "descriptor_ui": "D057105", "major_topic": false }, { "descriptor": "Nuclear Receptor Subfamily 4, Group A, Member 2", "descriptor_ui": "D057126", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 5", "date_precision": "day", "issue": "3", "normalized_date": "2024-03-05", "pages": "113898", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "43", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "NR4a1/2 deletion promotes accumulation of TCF1(+) stem-like precursors of exhausted CD8(+) T cells in the tumor microenvironment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Temperature is a critical factor for living organisms. Many microorganisms migrate toward preferable temperatures, and this behavior is called thermotaxis. In this study, the molecular and physiological bases for thermotaxis are examined in Chlamydomonas reinhardtii. A mutant with knockout of a transient receptor potential (TRP) channel, trp2-3, showed defective thermotaxis. The swimming velocity and ciliary beat frequency of wild-type Chlamydomonas increase with temperature; however, this temperature-dependent enhancement of motility was almost absent in the trp2-3 mutant. Wild-type Chlamydomonas showed negative thermotaxis, but mutants deficient in the outer or inner dynein arm showed positive thermotaxis and a defect in temperature-dependent increase in swimming velocity, suggesting involvement of both dynein arms in thermotaxis.", "classifications": [ { "id": "21H00420", "label": "21H00420", "researcher": "Ken-ichi Wakabayashi", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shunta", "last_name": "Fueki", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Matsuki", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Isu", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cm.21840" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38426808" } }, "mesh": [ { "descriptor": "Chlamydomonas reinhardtii", "descriptor_ui": "D016825", "major_topic": true }, { "descriptor": "Cilia", "descriptor_ui": "D002923", "major_topic": true }, { "descriptor": "Taxis Response", "descriptor_ui": "D000071442", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false }, { "descriptor": "Transient Receptor Potential Channels", "descriptor_ui": "D050051", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 1", "date_precision": "day", "issue": "", "normalized_date": "2024-03-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cytoskeleton (Hoboken, N.J.)", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Temperature-dependent augmentation of ciliary motility by the TRP2 channel in Chlamydomonas reinhardtii.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The development of induced pluripotent stem cells (iPSCs) technology has enabled human cellular disease modeling for inaccessible cell types, such as neural cells in the brain. However, many of the iPSC-derived disease models established to date typically involve only a single cell type. These monoculture models are inadequate for accurately simulating the brain environment, where multiple cell types interact. The limited cell type diversity in monoculture models hinders the accurate recapitulation of disease phenotypes resulting from interactions between different cell types. Therefore, our goal was to create cell models that include multiple interacting cell types to better recapitulate disease phenotypes. METHODS: To establish a co-culture model of neurons and astrocytes, we individually induced neurons and astrocytes from the same iPSCs using our novel differentiation methods, and then co-cultured them. We evaluated the effects of co-culture on neurons and astrocytes using immunocytochemistry, immuno-electron microscopy, and Ca(2+) imaging. We also developed a co-culture model using iPSCs from a patient with familial Alzheimer's disease (AD) patient (APP (V717L) mutation) to investigate whether this model would manifest disease phenotypes not seen in the monoculture models. RESULTS: The co-culture of the neurons and astrocytes increased the branching of astrocyte processes, the number of GFAP-positive cells, neuronal activities, the number of synapses, and the density of presynaptic vesicles. In addition, immuno-electron microscopy confirmed the formation of a tripartite synaptic structure in the co-culture model, and inhibition of glutamate transporters increased neuronal activity. Compared to the co-culture model of the control iPSCs, the co-culture model of familial AD developed astrogliosis-like phenotype, which was not observed in the monoculture model of astrocytes. CONCLUSIONS: Co-culture of iPSC-derived neurons and astrocytes enhanced the morphological changes mimicking the in vivo condition of both cell types. The formation of the functional tripartite synaptic structures in the co-culture model suggested the mutual interaction between the cells. Furthermore, the co-culture model with the APP (V717L) mutation expressed in neurons exhibited an astrocytic phenotype reminiscent of AD brain pathology. These results suggest that our co-culture model is a valuable tool for disease modeling of neurodegenerative diseases.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Sopak", "last_name": "Supakul", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Chisato", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hatakeyama", "name": null }, { "creator_type": "author", "first_name": "Maika", "last_name": "Itsuno", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Sumihiro", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s41232-023-00310-5" }, "pmcid": { "normalized": "PMC10900748" }, "pmid": { "normalized": "38419091" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Feb 28", "date_precision": "day", "issue": "1", "normalized_date": "2024-02-28", "pages": "8", "proceedings_title": null, "publisher": "", "title": "Inflammation and regeneration", "volume": "44", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Mutual interaction of neurons and astrocytes derived from iPSCs with APP V717L mutation developed the astrocytic phenotypes of Alzheimer's disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The AP-2 transcription factors are crucial for regulating sleep in both vertebrate and invertebrate animals. In mice, loss of function of the transcription factor AP-2beta (TFAP2B) reduces non-rapid eye movement (NREM) sleep. When and where TFAP2B functions, however, is unclear. Here, we used the Cre-loxP system to generate mice in which Tfap2b was specifically deleted in the nervous system during development and mice in which neuronal Tfap2b was specifically deleted postnatally. Both types of mice exhibited reduced NREM sleep, but the nervous system-specific deletion of Tfap2b resulted in more severe sleep phenotypes accompanied by defective light entrainment of the circadian clock and stereotypic jumping behavior. These findings indicate that TFAP2B in postnatal neurons functions at least partly in sleep regulation and imply that TFAP2B also functions either at earlier stages or in additional cell types within the nervous system.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ayaka", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Mitsuaki", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Fujiyama", "name": null }, { "creator_type": "author", "first_name": "Kanako", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Arisa", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Funato", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13041-024-01084-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38413970" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nervous System", "descriptor_ui": "D009420", "major_topic": false }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": false }, { "descriptor": "Transcription Factor AP-2", "descriptor_ui": "D050656", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Feb 27", "date_precision": "day", "issue": "1", "normalized_date": "2024-02-27", "pages": "13", "proceedings_title": null, "publisher": "", "title": "Molecular brain", "volume": "17", "year": 2024 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000434" ] }, "title": "Crucial role of TFAP2B in the nervous system for regulating NREM sleep.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chondroitin, a class of glycosaminoglycan polysaccharides, is found as proteoglycans in the extracellular matrix, plays a crucial role in tissue morphogenesis during development and axonal regeneration. Ingestion of chondroitin prolongs the lifespan of C. elegans. However, the roles of endogenous chondroitin in regulating lifespan and healthspan mostly remain to be investigated. Here, we demonstrate that a gain-of-function mutation in MIG-22, the chondroitin polymerizing factor (ChPF), results in elevated chondroitin levels and a significant extension of both the lifespan and healthspan in C. elegans. Importantly, the remarkable longevity observed in mig-22(gf) mutants is dependent on SQV-5/chondroitin synthase (ChSy), highlighting the pivotal role of chondroitin in controlling both lifespan and healthspan. Additionally, the mig-22(gf) mutation effectively suppresses the reduced healthspan associated with the loss of MIG-17/ADAMTS metalloprotease, a crucial for factor in basement membrane (BM) remodeling. Our findings suggest that chondroitin functions in the control of healthspan downstream of MIG-17, while regulating lifespan through a pathway independent of MIG-17.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yukimasa", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Sasakura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Morioka", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Sassa", "name": null }, { "creator_type": "author", "first_name": "Shion", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Kaito", "last_name": "Mitsuzumi", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Ikeno", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Hidenao", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Kiyoji", "last_name": "Nishiwaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-024-55417-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38413743" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": true }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": true }, { "descriptor": "Chondroitin", "descriptor_ui": "D002807", "major_topic": false }, { "descriptor": "Disintegrins", "descriptor_ui": "D019483", "major_topic": false }, { "descriptor": "Glycosaminoglycans", "descriptor_ui": "D006025", "major_topic": false }, { "descriptor": "Longevity", "descriptor_ui": "D008136", "major_topic": false }, { "descriptor": "Metalloendopeptidases", "descriptor_ui": "D008666", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Feb 27", "date_precision": "day", "issue": "1", "normalized_date": "2024-02-27", "pages": "4813", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "14", "year": 2024 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000428" ] }, "title": "Endogenous chondroitin extends the lifespan and healthspan in C. elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "More than 100 different herpes simplex virus 1 (HSV-1) genes belong to three major classes, and their expression is coordinately regulated and sequentially ordered in a cascade. This complex HSV-1 gene expression is thought to be regulated by various viral and host cellular proteins. A host cellular protein, Myb-binding protein 1A (MYBBP1A), has been reported to be associated with HSV-1 viral genomes in conjunction with viral and cellular proteins critical for DNA replication, repair, and transcription within infected cells. However, the role(s) of MYBBP1A in HSV-1 infections remains unclear. In this study, we examined the effects of MYBBP1A depletion on HSV-1 infection and found that MYBBP1A depletion significantly reduced HSV-1 replication, as well as the accumulation of several viral proteins. These results suggest that MYBBP1A is an important host cellular factor that contributes to HSV-1 replication, plausibly by promoting viral gene expression.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Moeka", "last_name": "Nobe", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/1348-0421.13120" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38402407" } }, "mesh": [ { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": true }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": true }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": true }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Feb 24", "date_precision": "day", "issue": "", "normalized_date": "2024-02-24", "pages": "", "proceedings_title": null, "publisher": "", "title": "Microbiology and immunology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "MYBBP1A is required for efficient replication and gene expression of herpes simplex virus 1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chronic social isolation increases the risk of mental health problems, including cognitive impairments and depression. While subanesthetic ketamine is considered effective for cognitive impairments in patients with depression, the neural mechanisms underlying its effects are not well understood. Here we identified unique activation of the anterior insular cortex (aIC) as a characteristic feature in brain-wide regions of mice reared in social isolation and treated with (R)-ketamine, a ketamine enantiomer. Using fiber photometry recording on freely moving mice, we found that social isolation attenuates aIC neuronal activation upon social contact and that (R)-ketamine, but not (S)-ketamine, is able to counteracts this reduction. (R)-ketamine facilitated social cognition in social isolation-reared mice during the social memory test. aIC inactivation offset the effect of (R)-ketamine on social memory. Our results suggest that (R)-ketamine has promising potential as an effective intervention for social cognitive deficits by restoring aIC function.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Rei", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Momoko", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Tanuma", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Shimazaki", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Misuzu", "last_name": "Hayashida", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41380-024-02419-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38388704" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": false }, { "descriptor": "Cognition", "descriptor_ui": "D003071", "major_topic": false }, { "descriptor": "Cognition Disorders", "descriptor_ui": "D003072", "major_topic": false }, { "descriptor": "Cognitive Dysfunction", "descriptor_ui": "D060825", "major_topic": true }, { "descriptor": "Insular Cortex", "descriptor_ui": "D000087623", "major_topic": true }, { "descriptor": "Ketamine", "descriptor_ui": "D007649", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": false }, { "descriptor": "Social Isolation", "descriptor_ui": "D012934", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Feb 23", "date_precision": "day", "issue": "", "normalized_date": "2024-02-23", "pages": "", "proceedings_title": null, "publisher": "", "title": "Molecular psychiatry", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "(R)-ketamine restores anterior insular cortex activity and cognitive deficits in social isolation-reared mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Spinal cord injury (SCI) leads to devastating sequelae, demanding effective treatments. Recent advancements have unveiled the role of neutrophil extracellular traps (NETs) produced by infiltrated neutrophils in exacerbating secondary inflammation after SCI, making it a potential target for treatment intervention. Previous research has established that intravenous administration of stem cell-derived exosomes can mitigate injuries. While stem cell-derived exosomes have demonstrated the ability to modulate microglial reactions and enhance blood-brain barrier integrity, their impact on neutrophil deactivation, especially in the context of NETs, remains poorly understood. This study aims to investigate the effects of intravenous administration of MSC-derived exosomes, with a specific focus on NET formation, and to elucidate the associated molecular mechanisms. Exosomes were isolated from the cell supernatants of amnion-derived mesenchymal stem cells using the ultracentrifugation method. Spinal cord injuries were induced in Sprague-Dawley rats (9 weeks old) using a clip injury model, and 100 mug of exosomes in 1 mL of PBS or PBS alone were intravenously administered 24 h post-injury. Motor function was assessed serially for up to 28 days following the injury. On Day 3 and Day 28, spinal cord specimens were analyzed to evaluate the extent of injury and the formation of NETs. Flow cytometry was employed to examine the formation of circulating neutrophil NETs. Exogenous miRNA was electroporated into neutrophil to evaluate the effect of inflammatory NET formation. Finally, the biodistribution of exosomes was assessed using (64)Cu-labeled exosomes in animal positron emission tomography (PET). Rats treated with exosomes exhibited a substantial improvement in motor function recovery and a reduction in injury size. Notably, there was a significant decrease in neutrophil infiltration and NET formation within the spinal cord, as well as a reduction in neutrophils forming NETs in the circulation. In vitro investigations indicated that exosomes accumulated in the vicinity of the nuclei of activated neutrophils, and neutrophils electroporated with the miR-125a-3p mimic exhibited a significantly diminished NET formation, while miR-125a-3p inhibitor reversed the effect. PET studies revealed that, although the majority of the transplanted exosomes were sequestered in the liver and spleen, a notably high quantity of exosomes was detected in the damaged spinal cord when compared to normal rats. MSC-derived exosomes play a pivotal role in alleviating spinal cord injury, in part through the deactivation of NET formation via miR-125a-3p.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yutaka", "last_name": "Morishima", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Kawabori", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Takamiya", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Yo", "last_name": "Nakahara", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Senjo", "name": null }, { "creator_type": "author", "first_name": "Daigo", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Sakiko", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kuge", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Fujimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms25042406" }, "pmcid": { "normalized": "PMC10889446" }, "pmid": { "normalized": "38397083" } }, "mesh": [ { "descriptor": "Administration, Intravenous", "descriptor_ui": "D061605", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Exosomes", "descriptor_ui": "D055354", "major_topic": true }, { "descriptor": "Extracellular Traps", "descriptor_ui": "D065206", "major_topic": true }, { "descriptor": "Mesenchymal Stem Cells", "descriptor_ui": "D059630", "major_topic": true }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Spinal Cord Injuries", "descriptor_ui": "D013119", "major_topic": true }, { "descriptor": "Tissue Distribution", "descriptor_ui": "D014018", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Feb 18", "date_precision": "day", "issue": "4", "normalized_date": "2024-02-18", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "25", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Intravenous Administration of Mesenchymal Stem Cell-Derived Exosome Alleviates Spinal Cord Injury by Regulating Neutrophil Extracellular Trap Formation through Exosomal miR-125a-3p.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Various control strategies are available for building fluorogenic probes to visualize biological events in terms of a fluorescence change. Here, we performed the time-dependent density functional theory (TD-DFT) computational analysis of the twisted intramolecular charge transfer (TICT) process in rhodamine dyes. On the basis of the results, we designed and synthesized a series of rhodamine dyes and established a fluorescence quenching strategy that we call steric repulsion-induced TICT (sr-TICT), in which the fluorescence quenching process is greatly accelerated by simple intramolecular twisting. As proof of concept of this design strategy, we used it to develop a fluorogenic probe, 2-Me PeER (pentyloxyethylrhodamine), for the N-dealkylation activity of CYP3A4. We applied 2-Me PeER for CYP3A4 activity-based fluorescence-activated cell sorting (FACS), providing access to homogeneous, highly functional human-induced pluripotent stem cell (hiPSC)-derived hepatocytes and intestinal epithelial cells. Our results suggest that sr-TICT represents a general fluorescence control method for fluorogenic probes.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ikeno", "name": null }, { "creator_type": "author", "first_name": "Shimpei", "last_name": "Iwaki", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Deguchi", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mizuguchi", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Tao", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kusuhara", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adi8847" }, "pmcid": { "normalized": "PMC10871538" }, "pmid": { "normalized": "38363840" } }, "mesh": [ { "descriptor": "Coloring Agents", "descriptor_ui": "D004396", "major_topic": true }, { "descriptor": "Cytochrome P-450 CYP3A", "descriptor_ui": "D051544", "major_topic": true }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mercaptoethanol", "descriptor_ui": "D008623", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Feb 16", "date_precision": "day", "issue": "7", "normalized_date": "2024-02-16", "pages": "eadi8847", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "10", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "A general fluorescence off/on strategy for fluorogenic probes: Steric repulsion-induced twisted intramolecular charge transfer (sr-TICT).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "It has been 50 years since the suprachiasmatic nucleus (SCN) was first identified as the central circadian clock and 25 years since the last overview of developments in the field was published in the Journal of Biological Rhythms. Here, we explore new mechanisms and concepts that have emerged in the subsequent 25 years. Since 1997, methodological developments, such as luminescent and fluorescent reporter techniques, have revealed intricate relationships between cellular and network-level mechanisms. In particular, specific neuropeptides such as arginine vasopressin, vasoactive intestinal peptide, and gastrin-releasing peptide have been identified as key players in the synchronization of cellular circadian rhythms within the SCN. The discovery of multiple oscillators governing behavioral and physiological rhythms has significantly advanced our understanding of the circadian clock. The interaction between neurons and glial cells has been found to play a crucial role in regulating these circadian rhythms within the SCN. Furthermore, the properties of the SCN network vary across ontogenetic stages. The application of cell type-specific genetic manipulations has revealed components of the functional input-output system of the SCN and their correlation with physiological functions. This review concludes with the high-risk effort of identifying open questions and challenges that lie ahead.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "David R.", "last_name": "Weaver", "name": null }, { "creator_type": "author", "first_name": "Michael H.", "last_name": "Hastings", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Sato", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Rae", "last_name": "Silver", "name": null } ], "identifiers": { "doi": { "normalized": "10.1177/07487304231225706" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38366616" } }, "mesh": [ { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": true }, { "descriptor": "Gastrin-Releasing Peptide", "descriptor_ui": "D019886", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": true }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": false }, { "descriptor": "Vasoactive Intestinal Peptide", "descriptor_ui": "D014660", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Feb 16", "date_precision": "day", "issue": "", "normalized_date": "2024-02-16", "pages": "7487304231225706", "proceedings_title": null, "publisher": "", "title": "Journal of biological rhythms", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "The Suprachiasmatic Nucleus at 50: Looking Back, Then Looking Forward.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Correction for 'Evaluation of separation performance for eggshell-based reversed-phase HPLC columns by controlling particle size and application in quantitative therapeutic drug monitoring' by Tomoka Yoshii et al., Anal. Methods, 2023, 15, 1790-1796, https://doi.org/10.1039/D3AY00219E.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tomoka", "last_name": "Yoshii", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d4ay90022g" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38348702" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Feb 13", "date_precision": "day", "issue": "", "normalized_date": "2024-02-13", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical methods : advancing methods and applications", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Correction: Evaluation of separation performance for eggshell-based reversed-phase HPLC columns by controlling particle size and application in quantitative therapeutic drug monitoring.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epidermal growth factor receptor (EGFR)-mediated signal transduction controls cell growth and proliferation. The signaling pathway is regulated so that it is activated only by external EGF stimuli, but the mechanisms that prevent EGF-independent spontaneous activation of EGFR-mediated signaling are unknown. Here we report cholesterol depletion activates EGFR-mediated signaling without EGF. We applied automated single-molecule imaging to EGFR and characterized the lateral diffusion and cluster formation on cholesterol-depleted and cholesterol-supplemented membranes. In cells in which cholesterol was depleted by methyl-beta-cyclodextrin (MbetaCD) treatment, EGFR exhibited a reduction in lateral diffusion, an acceleration of cluster formation, and autophosphorylation without EGF. Concurrently, extracellular signal-regulated kinase (ERK), which is regulated by EGFR-mediated signaling, exhibited phosphorylation and nuclear translocation without EGF. These cholesterol depletion-induced changes were similar, albeit less efficient, to those that occurred with EGF stimulation in normal cells without MbetaCD, indicating the spontaneous activation of EGFR signaling. The exogenous supplementation of cholesterol suppressed the MbetaCD-induced spontaneous activation of EGFR and ERK nuclear translocation. Single-molecule imaging of EGFR in a large number of cells revealed cell-to-cell heterogeneity, with a sub-population showing a high ability for spontaneous activation. These results provide evidence that EGFR-mediated signaling is properly regulated by cholesterol metabolism to prevent uncontrolled spontaneous activation.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Miri", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Sakura", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kazutoshi", "last_name": "Takebayashi", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2024.149673" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38401305" } }, "mesh": [ { "descriptor": "Cholesterol", "descriptor_ui": "D002784", "major_topic": false }, { "descriptor": "Epidermal Growth Factor", "descriptor_ui": "D004815", "major_topic": true }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Feb 12", "date_precision": "day", "issue": "", "normalized_date": "2024-02-12", "pages": "149673", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "704", "year": 2024 }, "ssbd": { "database": [ "ssbd-database-000439" ], "repository": [ "ssbd-repos-000439" ] }, "title": "Cholesterol suppresses spontaneous activation of EGFR-mediated signal transduction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence of XBB.1.5, a new Variant of Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring the S486P spike (S) mutation, subsequent to the acquisition of a nonsense mutation in ORF8. Neutralization assays showed similar abilities of immune escape between XBB.1.5 and XBB.1. We determine the structural basis for the interaction between human ACE2 and the S protein of XBB.1.5, showing similar overall structures between the S proteins of XBB.1 and XBB.1.5. We provide the intrinsic pathogenicity of XBB.1 and XBB.1.5 in hamsters. Importantly, we find that the ORF8 nonsense mutation of XBB.1.5 resulted in impairment of MHC suppression. In vivo experiments using recombinant viruses reveal that the XBB.1.5 mutations are involved with reduced virulence of XBB.1.5. Together, our study identifies the two viral functions defined the difference between XBB.1 and XBB.1.5.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Irie", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Deguchi", "name": null }, { "creator_type": "author", "first_name": "Hisano", "last_name": "Yajima", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Hesham", "last_name": "Nasser", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Mizuma", "name": null }, { "creator_type": "author", "first_name": "Arnon", "last_name": "Plianchaisuk", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Keiya", "last_name": "Uriu", "name": null }, { "creator_type": "author", "first_name": "Mst Monira", "last_name": "Begum", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Jonathan", "name": null }, { "creator_type": "author", "first_name": "Rigel", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Kamiyama", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Yoshimatsu", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Shofa", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Anraku", "name": null }, { "creator_type": "author", "first_name": "Kanako Terakado", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Jiei", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Sasaki-Tabata", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Maenaka", "name": null }, { "creator_type": "author", "first_name": "Naganori", "last_name": "Nao", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Terumasa", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Akatsuki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Matsuno", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Hashiguchi", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Takasuke", "last_name": "Fukuhara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-45274-3" }, "pmcid": { "normalized": "PMC10853506" }, "pmid": { "normalized": "38332154" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Assay", "descriptor_ui": "D001681", "major_topic": false }, { "descriptor": "Codon, Nonsense", "descriptor_ui": "D018389", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Cricetinae", "descriptor_ui": "D006224", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Feb 8", "date_precision": "day", "issue": "1", "normalized_date": "2024-02-08", "pages": "1176", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Virological characteristics of the SARS-CoV-2 Omicron XBB.1.5 variant.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Together with the molecular knowledge of genes and proteins, biological images promise to significantly enhance the scientific understanding of complex cellular systems and to advance predictive and personalized therapeutic products for human health. For this potential to be realized, quality-assured image data must be shared among labs at a global scale to be compared, pooled, and reanalyzed, thus unleashing untold potential beyond the original purpose for which the data was generated. There are two broad sets of requirements to enable image data sharing in the life sciences. One set of requirements is articulated in the companion White Paper entitled \"Enabling Global Image Data Sharing in the Life Sciences,\" which is published in parallel and addresses the need to build the cyberinfrastructure for sharing the digital array data (arXiv:2401.13023 [q-bio.OT], https://doi.org/10.48550/arXiv.2401.13023). In this White Paper, we detail a broad set of requirements, which involves collecting, managing, presenting, and propagating contextual information essential to assess the quality, understand the content, interpret the scientific implications, and reuse image data in the context of the experimental details. We start by providing an overview of the main lessons learned to date through international community activities, which have recently made considerable progress toward generating community standard practices for imaging Quality Control (QC) and metadata. We then provide a clear set of recommendations for amplifying this work. The driving goal is to address remaining challenges, and democratize access to common practices and tools for a spectrum of biomedical researchers, regardless of their expertise, access to resources, and geographical location.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Nikki", "last_name": "Bialy", "name": null }, { "creator_type": "author", "first_name": "Frank", "last_name": "Alber", "name": null }, { "creator_type": "author", "first_name": "Brenda", "last_name": "Andrews", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Angelo", "name": null }, { "creator_type": "author", "first_name": "Brian", "last_name": "Beliveau", "name": null }, { "creator_type": "author", "first_name": "Lacramioara", "last_name": "Bintu", "name": null }, { "creator_type": "author", "first_name": "Alistair", "last_name": "Boettiger", "name": null }, { "creator_type": "author", "first_name": "Ulrike", "last_name": "Boehm", "name": null }, { "creator_type": "author", "first_name": "Claire M.", "last_name": "Brown", "name": null }, { "creator_type": "author", "first_name": "Mahmoud Bukar", "last_name": "Maina", "name": null }, { "creator_type": "author", "first_name": "James J.", "last_name": "Chambers", "name": null }, { "creator_type": "author", "first_name": "Beth A.", "last_name": "Cimini", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Eliceiri", "name": null }, { "creator_type": "author", "first_name": "Rachel", "last_name": "Errington", "name": null }, { "creator_type": "author", "first_name": "Orestis", "last_name": "Faklaris", "name": null }, { "creator_type": "author", "first_name": "Nathalie", "last_name": "Gaudreault", "name": null }, { "creator_type": "author", "first_name": "Ronald N.", "last_name": "Germain", "name": null }, { "creator_type": "author", "first_name": "Wojtek", "last_name": "Goscinski", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Grunwald", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Halter", "name": null }, { "creator_type": "author", "first_name": "Dorit", "last_name": "Hanein", "name": null }, { "creator_type": "author", "first_name": "John W.", "last_name": "Hickey", "name": null }, { "creator_type": "author", "first_name": "Judith", "last_name": "Lacoste", "name": null }, { "creator_type": "author", "first_name": "Alex", "last_name": "Laude", "name": null }, { "creator_type": "author", "first_name": "Emma", "last_name": "Lundberg", "name": null }, { "creator_type": "author", "first_name": "Jian", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Leonel", "last_name": "Malacrida", "name": null }, { "creator_type": "author", "first_name": "Josh", "last_name": "Moore", "name": null }, { "creator_type": "author", "first_name": "Glyn", "last_name": "Nelson", "name": null }, { "creator_type": "author", "first_name": "Elizabeth Kathleen", "last_name": "Neumann", "name": null }, { "creator_type": "author", "first_name": "Roland", "last_name": "Nitschke", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Jaime A.", "last_name": "Pimentel", "name": null }, { "creator_type": "author", "first_name": "Anne L.", "last_name": "Plant", "name": null }, { "creator_type": "author", "first_name": "Andrea J.", "last_name": "Radtke", "name": null }, { "creator_type": "author", "first_name": "Bikash", "last_name": "Sabata", "name": null }, { "creator_type": "author", "first_name": "Denis", "last_name": "Schapiro", "name": null }, { "creator_type": "author", "first_name": "Johannes", "last_name": "Schoneberg", "name": null }, { "creator_type": "author", "first_name": "Jeffrey M.", "last_name": "Spraggins", "name": null }, { "creator_type": "author", "first_name": "Damir", "last_name": "Sudar", "name": null }, { "creator_type": "author", "first_name": "Wouter-Michiel", "last_name": "Adrien Maria Vierdag", "name": null }, { "creator_type": "author", "first_name": "Niels", "last_name": "Volkmann", "name": null }, { "creator_type": "author", "first_name": "Carolina", "last_name": "Wahlby", "name": null }, { "creator_type": "author", "first_name": "Siyuan Steven", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Ziv", "last_name": "Yaniv", "name": null }, { "creator_type": "author", "first_name": "Caterina", "last_name": "Strambio-De-Castillia", "name": null } ], "identifiers": { "doi": { "normalized": "10.48550/arxiv.2401.13022" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Feb 8", "date_precision": "day", "issue": null, "normalized_date": "2024-02-08", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Harmonizing the Generation and Pre-publication Stewardship of FAIR Image data.", "url": "", "zotero": { "item_type": "preprint" } }, { "abstract": "BACKGROUND: One life event that requires extensive resilience and adaptation is parenting. However, resilience and perceived support in child-rearing vary, making the real-world situation unclear, even with postpartum checkups. OBJECTIVE: This study aimed to explore the psychosocial status of mothers during the child-rearing period from newborn to toddler, with a classifier based on data on the resilience and adaptation characteristics of mothers with newborns. METHODS: A web-based cross-sectional survey was conducted. Mothers with newborns aged approximately 1 month (newborn cohort) were analyzed to construct an explainable machine learning classifier to stratify parenting-related resilience and adaptation characteristics and identify vulnerable populations. Explainable k-means clustering was used because of its high explanatory power and applicability. The classifier was applied to mothers with infants aged 2 months to 1 year (infant cohort) and mothers with toddlers aged >1 year to 2 years (toddler cohort). Psychosocial status, including depressed mood assessed by the Edinburgh Postnatal Depression Scale (EPDS), bonding assessed by the Postpartum Bonding Questionnaire (PBQ), and sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI) between the classified groups, was compared. RESULTS: A total of 1559 participants completed the survey. They were split into 3 cohorts, comprising populations of various characteristics, including parenting difficulties and psychosocial measures. The classifier, which stratified participants into 5 groups, was generated from the self-reported scores of resilience and adaptation in the newborn cohort (n=310). The classifier identified that the group with the greatest difficulties in resilience and adaptation to a child's temperament and perceived support had higher incidences of problems with depressed mood (relative prevalence [RP] 5.87, 95% CI 2.77-12.45), bonding (RP 5.38, 95% CI 2.53-11.45), and sleep quality (RP 1.70, 95% CI 1.20-2.40) compared to the group with no difficulties in perceived support. In the infant cohort (n=619) and toddler cohort (n=461), the stratified group with the greatest difficulties had higher incidences of problems with depressed mood (RP 9.05, 95% CI 4.36-18.80 and RP 4.63, 95% CI 2.38-9.02, respectively), bonding (RP 1.63, 95% CI 1.29-2.06 and RP 3.19, 95% CI 2.03-5.01, respectively), and sleep quality (RP 8.09, 95% CI 4.62-16.37 and RP 1.72, 95% CI 1.23-2.42, respectively) compared to the group with no difficulties. CONCLUSIONS: The classifier, based on a combination of resilience and adaptation to the child's temperament and perceived support, was able identify psychosocial vulnerable groups in the newborn cohort, the start-up stage of childcare. Psychosocially vulnerable groups were also identified in qualitatively different infant and toddler cohorts, depending on their classifier. The vulnerable group identified in the infant cohort showed particularly high RP for depressed mood and poor sleep quality.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Akiko", "last_name": "Hanai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Sugao", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masayo", "last_name": "Matsuzaki", "name": null }, { "creator_type": "author", "first_name": "Goji", "last_name": "Nakamoto", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Yasuji", "last_name": "Kitabatake", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.2196/47372" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38324356" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Feb 7", "date_precision": "day", "issue": "", "normalized_date": "2024-02-07", "pages": "e47372", "proceedings_title": null, "publisher": "", "title": "JMIR formative research", "volume": "8", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Explainable Machine Learning Classification to Identify Vulnerable Groups Among Parenting Mothers: Web-Based Cross-Sectional Questionnaire Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies worldwide. However, drug discovery for PDAC treatment has proven complicated, leading to stagnant therapeutic outcomes. Here, we identify Glycogen synthase kinase 3 (GSK3) as a therapeutic target through a whole-body genetic screening utilizing a '4-hit' Drosophila model mimicking the PDAC genotype. Reducing the gene dosage of GSK3 in a whole-body manner or knocking down GSK3 specifically in transformed cells suppressed 4-hit fly lethality, similar to Mitogen-activated protein kinase kinase (MEK), the therapeutic target in PDAC we have recently reported. Consistently, a combination of the GSK3 inhibitor CHIR99021 and the MEK inhibitor trametinib suppressed the phosphorylation of Polo-like kinase 1 (PLK1) as well as the growth of orthotopic human PDAC xenografts in mice. Additionally, reducing PLK1 genetically in 4-hit flies rescued their lethality. Our results reveal a therapeutic vulnerability in PDAC that offers a treatment opportunity for patients by inhibiting multiple targets.", "classifications": [ { "id": "19H05412", "label": "19H05412", "researcher": "Masahiro Sonoshita", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Junki", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kosuge", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Ryodai", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Ooshio", "name": null }, { "creator_type": "author", "first_name": "Taiga", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Reo", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kanako C.", "last_name": "Hatanaka", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Mitsuhashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Matsuno", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Hatanaka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.16100" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38320747" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinoma, Pancreatic Ductal", "descriptor_ui": "D021441", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Glycogen Synthase Kinase 3", "descriptor_ui": "D038362", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase Kinases", "descriptor_ui": "D020929", "major_topic": false }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Feb 6", "date_precision": "day", "issue": "", "normalized_date": "2024-02-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Concurrent targeting of GSK3 and MEK as a therapeutic strategy to treat pancreatic ductal adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The transplantation of neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) has shown promise in spinal cord injury (SCI) model animals. Establishing a functional synaptic connection between the transplanted and host neurons is crucial for motor function recovery. To boost therapeutic outcomes, we developed an ex vivo gene therapy aimed at promoting synapse formation by expressing the synthetic excitatory synapse organizer CPTX in hiPSC-NS/PCs. Using an immunocompromised transgenic rat model of SCI, we evaluated the effects of transplanting CPTX-expressing hiPSC-NS/PCs using histological and functional analyses. Our findings revealed a significant increase in excitatory synapse formation at the transplantation site. Retrograde monosynaptic tracing indicated extensive integration of transplanted neurons into the surrounding neuronal tracts facilitated by CPTX. Consequently, locomotion and spinal cord conduction significantly improved. Thus, ex vivo gene therapy targeting synapse formation holds promise for future clinical applications and offers potential benefits to individuals with SCI.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Saijo", "name": null }, { "creator_type": "author", "first_name": "Narihito", "last_name": "Nagoshi", "name": null }, { "creator_type": "author", "first_name": "Momotaro", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Suematsu", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Munehisa", "last_name": "Shinozaki", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Kohyama", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Michisuke", "last_name": "Yuzaki", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2024.01.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38366597" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Genetic Therapy", "descriptor_ui": "D015316", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Recovery of Function", "descriptor_ui": "D020127", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false }, { "descriptor": "Spinal Cord Injuries", "descriptor_ui": "D013119", "major_topic": true }, { "descriptor": "Stem Cell Transplantation", "descriptor_ui": "D033581", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Feb 6", "date_precision": "day", "issue": "", "normalized_date": "2024-02-06", "pages": "S2213-6711(24)00010-9", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Human-induced pluripotent stem cell-derived neural stem/progenitor cell ex vivo gene therapy with synaptic organizer CPTX for spinal cord injury.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Acoel flatworms possess epidermal sensory-receptor cells on their body surfaces and exhibit behavioral repertoires such as geotaxis and phototaxis. Acoel epidermal sensory receptors should be mechanical and/or chemical receptors; however, the mechanisms of their sensory reception have not been elucidated. We examined the three-dimensional relationship between epidermal sensory receptors and their innervation in an acoel flatworm, Praesagittifera naikaiensis. The distribution of the sensory receptors was different between the ventral and dorsal sides of worms. The nervous system was mainly composed of a peripheral nerve net, an anterior brain, and three pairs of longitudinal nerve cords. The nerve net was located closer to the body surface than the brain and the nerve cords. The sensory receptors have neural connections with the nerve net in the entire body of worms. We identified five homologs of polycystic kidney disease (PKD): PKD1-1, PKD1-2, PKD1-3, PKD1-4, and, PKD2, from the P. naikaiensis genome. All of these PKD genes were implied to be expressed in the epidermal sensory receptors of P. naikaiensis. PKD1-1 and PKD2 were dispersed across the entire body of worms. PKD1-2, PKD1-3, and PKD1-4 were expressed in the anterior region of worms. PKD1-4 was also expressed around the mouth opening. Our results indicated that P. naikaiensis possessed several types of epidermal sensory receptors to convert various environmental stimuli into electrical signals via the PKD channels and transmit the signals to afferent nerve and/or effector cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tosuke", "last_name": "Sakagami", "name": null }, { "creator_type": "author", "first_name": "Kaho", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Toshimitsu", "last_name": "Hatabu", "name": null }, { "creator_type": "author", "first_name": "Motonori", "last_name": "Ando", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00441-024-03865-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38305882" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Platyhelminths", "descriptor_ui": "D010986", "major_topic": true }, { "descriptor": "Sensory Receptor Cells", "descriptor_ui": "D011984", "major_topic": false }, { "descriptor": "TRPP Cation Channels", "descriptor_ui": "D050396", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Feb 2", "date_precision": "day", "issue": "", "normalized_date": "2024-02-02", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cell and tissue research", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Structure of putative epidermal sensory receptors in an acoel flatworm, Praesagittifera naikaiensis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Elucidation of biological phenomena requires imaging of microenvironments in vivo. Although the seamless visualization of in vivo hypoxia from the level of whole-body to single-cell has great potential to discover unknown phenomena in biological and medical fields, no methodology for achieving it has been established thus far. Here, we report the whole-body and whole-organ imaging of hypoxia, an important microenvironment, at single-cell resolution using activatable covalent fluorescent probes compatible with tissue clearing. We initially focused on overcoming the incompatibility of fluorescent dyes and refractive index matching solutions (RIMSs), which has greatly hindered the development of fluorescent molecular probes in the field of tissue clearing. The fluorescent dyes compatible with RIMS were then incorporated into the development of activatable covalent fluorescent probes for hypoxia. We combined the probes with tissue clearing, achieving comprehensive single-cell-resolution imaging of hypoxia in a whole mouse body and whole organs.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Daichi M.", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Iori", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Bo", "last_name": "Yi", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Takakusagi", "name": null }, { "creator_type": "author", "first_name": "Shimpei I.", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Masayasu", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Masaomi", "last_name": "Nangaku", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Tainaka", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Sando", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsnano.3c12716" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38301048" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Hypoxia", "descriptor_ui": "D000860", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Probes", "descriptor_ui": "D015335", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Feb 1", "date_precision": "day", "issue": "", "normalized_date": "2024-02-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "ACS nano", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Whole-Body and Whole-Organ 3D Imaging of Hypoxia Using an Activatable Covalent Fluorescent Probe Compatible with Tissue Clearing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dopamine neurons play crucial roles in pleasure, reward, memory, learning, and fine motor skills and their dysfunction is associated with various neuropsychiatric diseases. Dopamine receptors are the main target of treatment for neurologic and psychiatric disorders. Antipsychotics that antagonize the dopamine D2 receptor (DRD2) are used to alleviate the symptoms of these disorders, but may also sometimes cause disabling side effects such as parkinsonism (catalepsy in rodents). Here we show that GPR143, a G-protein-coupled receptor for L-3,4-dihydroxyphenylalanine (L-DOPA), expressed in striatal cholinergic interneurons enhances the DRD2-mediated side effects of haloperidol, an antipsychotic agent. Haloperidol-induced catalepsy was attenuated in male Gpr143 gene-deficient (Gpr143(-/y) ) mice compared with wild-type (Wt) mice. Reducing the endogenous release of L-DOPA and preventing interactions between GPR143 and DRD2 suppressed the haloperidol-induced catalepsy in Wt mice but not Gpr143(-/y) mice. The phenotypic defect in Gpr143(-/y) mice was mimicked in cholinergic interneuron-specific Gpr143(-/y) (Chat-cre;Gpr143(flox/y) ) mice. Administration of haloperidol increased the phosphorylation of ribosomal protein S6 at Ser(240/244) in the dorsolateral striatum of Wt mice but not Chat-cre;Gpr143(flox/y) mice. In Chinese hamster ovary cells stably expressing DRD2, co-expression of GPR143 increased cell surface expression level of DRD2, and L-DOPA application further enhanced the DRD2 surface expression. Shorter pauses in cholinergic interneuron firing activity were observed after intrastriatal stimulation in striatal slice preparations from Chat-cre;Gpr143(flox/y) mice compared with those from Wt mice. Together, these findings provide evidence that GPR143 regulates DRD2 function in cholinergic interneurons and may be involved in parkinsonism induced by antipsychotic drugs.Significance Statement Dopamine neuron systems play crucial roles in the control of multiple functions including cognition, fine motor skills and behavioral flexibility, and are involved in neurologic and psychiatric disorders. Antipsychotics are used to alleviate the positive symptoms of schizophrenia and other psychiatric disorders. The therapeutic efficacy of these drugs is related to their antagonistic activities against D2 receptors (DRD2), but disabling side effects may also be caused by DRD2 blockade in multiple dopaminergic pathways. L-DOPA receptor GPR143 when coupled with DRD2 potentiates DRD2-mediated signaling. The neuronal pathways is involved in the GPR143 function, however, have not yet been identified. Here, we identified cholinergic interneurons as the neural circuits in which DRD2 coupled with the L-DOPA receptor GPR143 mediates haloperidol-induced catalepsy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masami", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Momoyo", "last_name": "Otaki", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Miwako", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kambe", "name": null }, { "creator_type": "author", "first_name": "Koshi", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Yuuki", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Tetsu", "last_name": "Arisawa", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Tajika", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Lazarus", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Shigeyoshi", "last_name": "Itohara", "name": null }, { "creator_type": "author", "first_name": "Alban de Kerchove", "last_name": "d'Exaerde", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nawa", "name": null }, { "creator_type": "author", "first_name": "Ryang", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Bito", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Momiyama", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Masukawa", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Goshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.1504-23.2024" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38286627" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antipsychotic Agents", "descriptor_ui": "D014150", "major_topic": true }, { "descriptor": "Catalepsy", "descriptor_ui": "D002375", "major_topic": false }, { "descriptor": "CHO Cells", "descriptor_ui": "D016466", "major_topic": false }, { "descriptor": "Cholinergic Agents", "descriptor_ui": "D018678", "major_topic": false }, { "descriptor": "Cricetinae", "descriptor_ui": "D006224", "major_topic": false }, { "descriptor": "Cricetulus", "descriptor_ui": "D003412", "major_topic": false }, { "descriptor": "Eye Proteins", "descriptor_ui": "D005136", "major_topic": false }, { "descriptor": "Haloperidol", "descriptor_ui": "D006220", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interneurons", "descriptor_ui": "D007395", "major_topic": false }, { "descriptor": "Levodopa", "descriptor_ui": "D007980", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Glycoproteins", "descriptor_ui": "D008562", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Parkinsonian Disorders", "descriptor_ui": "D020734", "major_topic": true }, { "descriptor": "Receptors, Neurotransmitter", "descriptor_ui": "D017981", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jan 29", "date_precision": "day", "issue": "", "normalized_date": "2024-01-29", "pages": "e1504232024", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Enhancement of haloperidol-induced catalepsy by GPR143, an L-DOPA receptor, in striatal cholinergic interneurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have studied a machine learning (ML) technique for refining images acquired during in situ observation using liquid-cell transmission electron microscopy. Our model is constructed using a U-Net architecture and a ResNet encoder. For training our ML model, we prepared an original image dataset that contained pairs of images of samples acquired with and without a solution present. The former images were used as noisy images, and the latter images were used as corresponding ground truth images. The number of pairs of image sets was 1,204, and the image sets included images acquired at several different magnifications and electron doses. The trained model converted a noisy image into a clear image. The time necessary for the conversion was on the order of 10 ms, and we applied the model to in situ observations using the software Gatan DigitalMicrograph (DM). Even if a nanoparticle was not visible in a view window in the DM software because of the low electron dose, it was visible in a successive refined image generated by our ML model.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Katsuno", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/micmic/ozad142" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38285924" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Jan 29", "date_precision": "day", "issue": "", "normalized_date": "2024-01-29", "pages": "ozad142", "proceedings_title": null, "publisher": "", "title": "Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Machine Learning Refinement of In Situ Images Acquired by Low Electron Dose LC-TEM.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The lack of functional vascular system in stem cell-derived cerebral organoids (COs) limits their utility in modeling developmental processes and disease pathologies. Unlike other organs, brain vascularization is poorly understood, which makes it particularly difficult to mimic in vitro. Although several attempts have been made to vascularize COs, complete vascularization leading to functional capillary network development has only been achieved via transplantation into a mouse brain. Understanding the cues governing neurovascular communication is therefore imperative for establishing an efficient in vitro system for vascularized cerebral organoids that can emulate human brain development. Here, we used a multidisciplinary approach combining microfluidics, organoids, and transcriptomics to identify molecular changes in angiogenic programs that impede the successful in vitro vascularization of human induced pluripotent stem cell (iPSC)-derived COs. First, we established a microfluidic cerebral organoid (CO)-vascular bed (VB) co-culture system and conducted transcriptome analysis on the outermost cell layer of COs cultured on the preformed VB. Results revealed coordinated regulation of multiple pro-angiogenic factors and their downstream targets. The VEGF-HIF1A-AKT network was identified as a central pathway involved in the angiogenic response of cerebral organoids to the preformed VB. Among the 324 regulated genes associated with angiogenesis, six transcripts represented significantly regulated growth factors with the capacity to influence angiogenic activity during co-culture. Subsequent on-chip experiments demonstrated the angiogenic and vasculogenic potential of cysteine-rich angiogenic inducer 61 (CYR61) and hepatoma-derived growth factor (HDGF) as potential enhancers of organoid vascularization. Our study provides the first global analysis of cerebral organoid response to three-dimensional microvasculature for in vitro vascularization.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Maneesha", "last_name": "Shaji", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tamada", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Stanislav L.", "last_name": "Karsten", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Yokokawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d3lc00930k" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38284292" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jan 29", "date_precision": "day", "issue": "", "normalized_date": "2024-01-29", "pages": "", "proceedings_title": null, "publisher": "", "title": "Lab on a chip", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Deciphering potential vascularization factors of on-chip co-cultured hiPSC-derived cerebral organoids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "cIPAD is a fluorescent indicator that allows the visualization of trans-interactions of clustered protocadherin (Pcdh), a cell adhesion molecule that mediates neuronal self-recognition. We describe steps for using HEK293T cells to visualize Pcdh trans-interactions across cells as a preliminary experiment before using dissociated mouse neurons. We then detail procedures for visualizing Pcdh trans-interactions between processes originating from the same neurons, which are considered as Pcdh-mediated neuronal self-recognition. For complete details on the use and execution of this protocol, please refer to Kanadome et al.(1).", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Kanadome", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Hoshino", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xpro.2024.102844" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38277267" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": true }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Protocadherins", "descriptor_ui": "D000091363", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jan 25", "date_precision": "day", "issue": "1", "normalized_date": "2024-01-25", "pages": "102844", "proceedings_title": null, "publisher": "", "title": "STAR protocols", "volume": "5", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Protocol to visualize trans-interaction of clustered protocadherin using cIPAD, a fluorescent indicator, in cultured human cells and mouse neurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "IL-17-producing helper T (Th17) cells are long-lived and serve as central effector cells in chronic autoimmune diseases. The underlying mechanisms of Th17 persistence remain unclear. We demonstrated that abatacept, a CD28 antagonist, effectively prevented the development of skin disease in a Th17-dependent experimental autoimmune dermatitis model. Abatacept selectively inhibited the emergence of IL-7R-negative effector-phenotype T cells while allowing the survival and proliferation of IL-7R(+) memory-phenotype cells. The surviving IL-7R(+) Th17 cells expressed genes associated with alcohol/aldehyde detoxification and showed potential to transdifferentiate into IL-7R-negative effector cells. Inhibiting aldehyde dehydrogenase reduced IL-7R(+) Th17 cells in vivo, independently of CD28, and exhibited additive effects when combined with abatacept. Our findings suggest that CD28 blockade prevents inflammation without eliminating persistent memory cells. These remaining memory cells can be targeted by other drugs, such as aldehyde dehydrogenase inhibitors, to limit their survival, thereby facilitating the treatment of chronic autoimmune diseases.", "classifications": [ { "id": "19H05431", "label": "19H05431", "researcher": "Shunsuke Chikuma", "type": "grant" }, { "id": "21H00439", "label": "21H00439", "researcher": "Shunsuke Chikuma", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "By Yukiko", "last_name": "Tokifuji", "name": null }, { "creator_type": "author", "first_name": "Hodaka", "last_name": "Hayabuchi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Hara-Chikuma", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Amagai", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2023.108646" }, "pmcid": { "normalized": "PMC10788227" }, "pmid": { "normalized": "38226171" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Jan 19", "date_precision": "day", "issue": "1", "normalized_date": "2024-01-19", "pages": "108646", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "27", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Targeting abatacept-resistant T-helper-17 cells by aldehyde dehydrogenase inhibition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Calcitonin gene-related peptide (CGRP), a neuropeptide composed of 37 amino acids secreted from the sensory nerve endings, reportedly possesses various physiological effects, such as vasodilation and neurotransmission. Recently, there have been increasing reports of the involvement of CGRP in bone metabolism; however, its specific role in the pathogenesis of periodontitis, particularly in the repair and healing processes, remains to be elucidated. Therefore, this study aimed to investigate dynamic expression patterns of CGRP during the destruction and regeneration processes of periodontal tissues in a mouse model of experimental periodontitis. We also explored the effects of CGRP on periodontal ligament cells, which can differentiate to hard tissue-forming cells (cementoblasts or osteoblasts). Our findings demonstrated that CGRP stimulation promotes the differentiation of periodontal ligament cells into hard tissue-forming cells. Experimental results using a ligature-induced periodontitis mouse model also suggested fluctuations in CGRP expression during periodontal tissue healing, underscoring the vital role of CGRP signaling in alveolar bone recovery. The study results highlight the important role of nerves in the periodontal ligament not only in sensory reception in the periphery, as previously known, but also in periodontal tissue homeostasis and tissue repair processes.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Takeshita", "name": null }, { "creator_type": "author", "first_name": "Motozo", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Murakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-024-52029-z" }, "pmcid": { "normalized": "PMC10791604" }, "pmid": { "normalized": "38228723" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcitonin Gene-Related Peptide", "descriptor_ui": "D015740", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nerve Tissue", "descriptor_ui": "D009417", "major_topic": true }, { "descriptor": "Periodontal Ligament", "descriptor_ui": "D010513", "major_topic": false }, { "descriptor": "Periodontitis", "descriptor_ui": "D010518", "major_topic": true }, { "descriptor": "Periodontium", "descriptor_ui": "D010519", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jan 16", "date_precision": "day", "issue": "1", "normalized_date": "2024-01-16", "pages": "1344", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "14", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Calcitonin gene-related peptide regulates periodontal tissue regeneration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A nickel phthalocyanine precursor bearing poly(ethylene glycol) as a turn-on contrast agent for photoacoustic imaging was prepared. The water-soluble polymeric chains were smoothly eliminated through thiol-mediated reductive aromatization in cancer cells, enabling the detection of endogenous biological thiols in vitro and in vivo.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kohei", "last_name": "Nogita", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Sugahara", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Huiying", "last_name": "Mu", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d3cc05628g" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38224167" } }, "mesh": [ { "descriptor": "Contrast Media", "descriptor_ui": "D003287", "major_topic": true }, { "descriptor": "Indoles", "descriptor_ui": "D007211", "major_topic": false }, { "descriptor": "Isoindoles", "descriptor_ui": "D054833", "major_topic": true }, { "descriptor": "Nickel", "descriptor_ui": "D009532", "major_topic": false }, { "descriptor": "Photoacoustic Techniques", "descriptor_ui": "D061088", "major_topic": true }, { "descriptor": "Polyethylene Glycols", "descriptor_ui": "D011092", "major_topic": false }, { "descriptor": "Sulfhydryl Compounds", "descriptor_ui": "D013438", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jan 15", "date_precision": "day", "issue": "", "normalized_date": "2024-01-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000447" ] }, "title": "A reductively convertible nickel phthalocyanine precursor as a biological thiol-responsive turn-on photoacoustic contrast agent.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Ensuring adequate fetal oxygenation is an essential aim of fetal monitoring. The purpose of this study was to establish a basic technique for real-time measurement of blood oxygen saturation of the placenta by photoacoustic (PA) technique as a new fetal monitoring method. METHODS: The hypoxia model established in our previous study was applied to 7 pregnant rabbits. Three phases were induced: normal phase, hypoxia phase, and recovery phase. Three methods were simultaneously used for real-time fetal monitoring: fetal heat rate (FHR) monitoring, oxygen saturation (SO(2)) measurement by near-infrared spectroscopy (S(N)O(2)), and placenta SO(2) measured by PA technique (S(pl)O(2)). The maternal hypoxia was assessed by skin SO(2) measured by PA technique (SsO(2)), and arterial blood SO(2) by blood gas analysis (SaO(2)). RESULTS: The average of S(pl)O(2) in normal phase was 52.6 +/- 13.9 %. The averages of S(N)O(2), S(S)O(2), and S(pl)O(2) in the seven rabbits changed in parallel from the normal phase to hypoxia phase. In the recovery phase, the S(pl)O(2) rose in parallel with recovery of SaO(2). There was lag in increase of the FHR compared to the change in the other values. In the detailed analysis of PA signals from the labyrinth and decidua, a unique change in oxygen saturation was seen in one case. DISCUSSION: Results of this study showed that sensitivity of our novel PA technique in detecting tissue hypoxia was similar to near-infrared spectroscopy (NIRS). As an advantage, unlike NIRS, monitoring with PA technique was unaffected by ischemia and surface changes in oxygen saturation because of its higher spatial resolution. We conclude that PA technique provides more accurate information about fetal blood placenta than NIRS. Ultrasound imaging, combined with oxygen saturation monitoring by PA technique, would improve fetal monitoring and fetal diagnosis in the future.", "classifications": [ { "id": "21H00445", "label": "21H00445", "researcher": "Miya Ishihara", "type": "grant" }, { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kiguna Sei", "last_name": "Okawa", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Okawa", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.placenta.2024.01.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38241840" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fetal Monitoring", "descriptor_ui": "D005323", "major_topic": false }, { "descriptor": "Hypoxia", "descriptor_ui": "D000860", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": true }, { "descriptor": "Oxygen Saturation", "descriptor_ui": "D000089382", "major_topic": false }, { "descriptor": "Placenta", "descriptor_ui": "D010920", "major_topic": true }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jan 14", "date_precision": "day", "issue": "", "normalized_date": "2024-01-14", "pages": "110-119", "proceedings_title": null, "publisher": "", "title": "Placenta", "volume": "146", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Real-time fetal monitoring using photoacoustic measurement of placental oxygen saturation in a rabbit hypoxia model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intricate branching patterns emerge in internal organs due to the recurrent occurrence of simple deformations in epithelial tissues. During murine lung development, epithelial cells in distal tips of the single tube require fibroblast growth factor (FGF) signals emanating from their surrounding mesenchyme to form repetitive tip bifurcations. However, it remains unknown how the cells employ FGF signaling to convert their behaviors to achieve the recursive branching processes. Here, we show a mechano-chemical regulatory system underlying lung branching morphogenesis, orchestrated by extracellular signal-regulated kinase (ERK) as a downstream driver of FGF signaling. We found that tissue-scale curvature regulated ERK activity in the lung epithelium using two-photon live cell imaging and mechanical perturbations. ERK activation occurs specifically in epithelial tissues exhibiting positive curvature, regardless of whether the change in curvature was attributable to morphogenesis or perturbations. Moreover, ERK activation accelerates actin polymerization preferentially at the apical side of cells, mechanically contributing to the extension of the apical membrane, culminating in a reduction of epithelial tissue curvature. These results indicate the existence of a negative feedback loop between tissue curvature and ERK activity that transcends spatial scales. Our mathematical model confirms that this regulatory mechanism is sufficient to generate the recursive branching processes. Taken together, we propose that ERK orchestrates a curvature feedback loop pivotal to the self-organized patterning of tissues.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2023.12.049" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38228149" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": true }, { "descriptor": "Feedback", "descriptor_ui": "D005246", "major_topic": false }, { "descriptor": "Fibroblast Growth Factors", "descriptor_ui": "D005346", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": true }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jan 9", "date_precision": "day", "issue": "", "normalized_date": "2024-01-09", "pages": "S0960-9822(23)01749-9", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "", "year": 2024 }, "ssbd": { "database": [ "ssbd-database-000398" ], "repository": [ "ssbd-repos-000398" ] }, "title": "ERK-mediated curvature feedback regulates branching morphogenesis in lung epithelial tissue.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: We developed fiducial imaging-guidance markers for the prostate with less imaging artifacts than currently commercially available markers. The aim of this study was to evaluate the imaging artifacts and potential usefulness and safety of these novel fiducial imaging markers in preclinical experiments. METHODS: We selected specific metal materials and a shape that can minimize artifacts in line with a license we obtained for a metal with a gold-platinum (Au-Pt) alloy composition that maximized artifact-free MRI images. Both phantom and canine prostate tests were conducted in order to evaluate the imaging artifacts for three imaging modalities, MRI, CT and ultrasound, and the risk of migration of the markers from the site of insertion to elsewhere, as well as crushing. RESULTS: The newly developed Au-Pt material had less imaging artifacts in the MRI, CT and ultrasound imaging modalities in comparison with current commercially available fiducial markers made from gold materials only. The Au-Pt markers had sufficient strength and durability and were considered to be potentially clinically useful and safe markers. CONCLUSION: The developed Au-Pt markers could be potential tools for accurate lesion-targeted, organ-preserving therapies such as lesion-targeted focal therapy and active surveillance in addition to conventional radiation therapies.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Okihara", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Fujihara", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nomoto", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Masui", "name": null }, { "creator_type": "author", "first_name": "Toshiko", "last_name": "Ito-Ihara", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Ryusuke", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Ukimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/iju.15389" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38193342" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Artifacts", "descriptor_ui": "D016477", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Fiducial Markers", "descriptor_ui": "D057918", "major_topic": true }, { "descriptor": "Gold", "descriptor_ui": "D006046", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Organ Sparing Treatments", "descriptor_ui": "D059351", "major_topic": false }, { "descriptor": "Phantoms, Imaging", "descriptor_ui": "D019047", "major_topic": true }, { "descriptor": "Platinum", "descriptor_ui": "D010984", "major_topic": false }, { "descriptor": "Prostate", "descriptor_ui": "D011467", "major_topic": false }, { "descriptor": "Prostatic Neoplasms", "descriptor_ui": "D011471", "major_topic": true }, { "descriptor": "Tomography, X-Ray Computed", "descriptor_ui": "D014057", "major_topic": false }, { "descriptor": "Ultrasonography", "descriptor_ui": "D014463", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jan 9", "date_precision": "day", "issue": "", "normalized_date": "2024-01-09", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of urology : official journal of the Japanese Urological Association", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Novel image-guided marker aimed at organ-preserving therapies for prostate cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cyclin-dependent kinase (CDK) determines the temporal ordering of the cell cycle phases. However, despite significant progress in studying regulators of CDK and phosphorylation patterns of CDK substrates at the population level, it remains elusive how CDK regulators coordinately affect CDK activity at the single-cell level and how CDK controls the temporal order of cell cycle events. Here, we elucidate the dynamics of CDK activity in fission yeast and mammalian cells by developing a CDK activity biosensor, Eevee-spCDK. We find that although CDK activity does not necessarily correlate with cyclin levels, it converges to the same level around mitotic onset in several mutant backgrounds, including pom1Delta cells and wee1 or cdc25 overexpressing cells. These data provide direct evidence that cells enter the M phase when CDK activity reaches a high threshold, consistent with the quantitative model of cell cycle progression in fission yeast.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hironori", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Damien", "last_name": "Coudreuse", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2023.12.014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38228139" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinases", "descriptor_ui": "D018844", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein-Tyrosine Kinases", "descriptor_ui": "D011505", "major_topic": false }, { "descriptor": "Schizosaccharomyces", "descriptor_ui": "D012568", "major_topic": true }, { "descriptor": "Schizosaccharomyces pombe Proteins", "descriptor_ui": "D029702", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jan 8", "date_precision": "day", "issue": "", "normalized_date": "2024-01-08", "pages": "S1534-5807(23)00695-0", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000325" ] }, "title": "Live-cell imaging defines a threshold in CDK activity at the G2/M transition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Properly patterned cell walls specify cellular functions in plants. Differentiating protoxylem and metaxylem vessel cells exhibit thick secondary cell walls in striped and pitted patterns, respectively. Cortical microtubules are arranged in distinct patterns to direct cell wall deposition. The scaffold protein MIDD1 promotes microtubule depletion by interacting with ROP GTPases and KINESIN-13A in metaxylem vessels. Here we show that the phase separation of MIDD1 fine-tunes cell wall spacing in protoxylem vessels in Arabidopsis thaliana. Compared with wild-type, midd1 mutants exhibited narrower gaps and smaller pits in the secondary cell walls of protoxylem and metaxylem vessel cells, respectively. Live imaging of ectopically induced protoxylem vessels revealed that MIDD1 forms condensations along the depolymerizing microtubules, which in turn caused massive catastrophe of microtubules. The MIDD1 condensates exhibited rapid turnover and were susceptible to 1,6-hexanediol. Loss of ROP abolished the condensation of MIDD1 and resulted in narrow cell wall gaps in protoxylem vessels. These results suggest that the microtubule-associated phase separation of MIDD1 facilitates microtubule arrangement to regulate the size of gaps in secondary cell walls. This study reveals a new biological role of phase separation in the fine-tuning of cell wall patterning.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Higa", "name": null }, { "creator_type": "author", "first_name": "Saku T.", "last_name": "Kijima", "name": null }, { "creator_type": "author", "first_name": "Takema", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Takatani", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Wakazaki", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kiminori", "last_name": "Toyooka", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Demura", "name": null }, { "creator_type": "author", "first_name": "Hiroo", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Oda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41477-023-01593-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38172572" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Cell Wall", "descriptor_ui": "D002473", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Phase Separation", "descriptor_ui": "D000095496", "major_topic": false }, { "descriptor": "Xylem", "descriptor_ui": "D052584", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jan 3", "date_precision": "day", "issue": "", "normalized_date": "2024-01-03", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature plants", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Microtubule-associated phase separation of MIDD1 tunes cell wall spacing in xylem vessels in Arabidopsis thaliana.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Soeda", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.s008" }, "pmcid": { "normalized": "PMC11338678" }, "pmid": { "normalized": "39175863" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "Supplemental", "normalized_date": "2024", "pages": "e211008", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Research on the molecular mechanism of singularity phenomenon in neurological disorders.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell-cell interaction mediated by secreted and adhesive signaling molecules forms the basis of the coordinated cell movements (i.e., collective cell migration) observed in developing embryos, regenerating tissues, immune cells, and metastatic cancer. Decoding the underlying input/output rules at the single-cell level, however, remains a challenge due to the vast complexity in the extracellular environments that support such cellular behaviors. The amoebozoa Dictyostelium discoideum uses GPCR-mediated chemotaxis and cell-cell contact signals mediated by adhesion proteins with immunoglobulin-like folds to form a collectively migrating slug. Coordinated migration and repositioning of the cells in this relatively simple morphogenetic system are driven strictly by regulation of actin cytoskeleton by these signaling factors. Its unique position in the eukaryotic tree of life outside metazoa points to basic logics of tissue self-organization that are common across taxa. Here, we describe a method to reconstitute intercellular contact signals and the resulting cell polarization using purified adhesion proteins. In addition, a protocol using a microfluidic chamber is laid out where one can study how the cell-cell contact signal and chemoattractant signals, when simultaneously presented, are interpreted. Quantitative image analysis for obtaining cell morphology features is also provided. A similar approach should be applicable to study other collectively migrating cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Taihei", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Hashimura", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-4023-4_3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39147967" } }, "mesh": [ { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": true }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": true }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "23-36", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2828", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Imaging-Based Analysis of Cell-Cell Contact-Dependent Migration in Dictyostelium.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Creating a mouse model that recapitulates human tau pathology is essential for developing strategies to intervene in tau-induced neurodegeneration. However, mimicking the pathological features seen in human pathology often involves a trade-off with artificial effects such as unexpected gene insertion and neurotoxicity from the expression system. To overcome these issues, we developed the rTKhomo mouse model by combining a transgenic CaMKII-tTA system with a P301L mutated 1N4R human tau knock-in at the Rosa26 locus with a C57BL/6J background. This model closely mimics human tau pathology, particularly in the hippocampal CA1 region, showing age-dependent tau accumulation, neuronal loss and neuroinflammation. Notably, whole-brain 3D staining and light-sheet microscopy revealed a spatial gradient of tau deposition from the entorhinal cortex to the hippocampus, similar to the spatial distribution of Braak neurofibrillary tangle staging. Furthermore, [(18)F]PM-PBB3 positron emission tomography imaging enabled the quantification and live monitoring of tau deposition. The rTKhomo mouse model shows potential as a promising next-generation preclinical tool for exploring the mechanisms of tauopathy and for developing interventions targeting the spatial progression of tau pathology.", "classifications": [ { "id": "21H00446", "label": "21H00446", "researcher": "Naruhiko Sahara", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Rin", "last_name": "Yanai", "name": null }, { "creator_type": "author", "first_name": "Tomoki T.", "last_name": "Mitani", "name": null }, { "creator_type": "author", "first_name": "Etsuo A.", "last_name": "Susaki", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Minamihisamatsu", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Shimojo", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Mizuma", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Nitta", "name": null }, { "creator_type": "author", "first_name": "Daita", "last_name": "Kaneda", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Tanemura", "name": null }, { "creator_type": "author", "first_name": "Ming-Rong", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Hiroki R.", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/braincomms/fcae326" }, "pmcid": { "normalized": "PMC11483584" }, "pmid": { "normalized": "39420962" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "5", "normalized_date": "2024", "pages": "fcae326", "proceedings_title": null, "publisher": "", "title": "Brain communications", "volume": "6", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "A novel tauopathy model mimicking molecular and spatial aspects of human tau pathology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The medial prefrontal cortex (mPFC) is associated with various behavioral controls via diverse projections to cortical and subcortical areas of the brain. Dysfunctions and modulations of this circuitry are related to the pathophysiology of schizophrenia and its pharmacotherapy, respectively. Clozapine is an atypical antipsychotic drug used for treatment-resistant schizophrenia and is known to modulate neuronal activity in the mPFC. However, it remains unclear which prefrontal cortical projections are activated by clozapine among the various projection targets. To identify the anatomical characteristics of neurons activated by clozapine at the mesoscale level, we investigated the brain-wide projection patterns of neurons with clozapine-induced c-Fos expression in the mPFC. Using a whole-brain imaging and virus-mediated genetic tagging of activated neurons, we found that clozapine-responsive neurons in the mPFC had a wide range of projections to the mesolimbic, amygdala and thalamic areas, especially the mediodorsal thalamus. These results may provide key insights into the neuronal basis of the therapeutic action of clozapine.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yumi", "last_name": "Hirato", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Leo", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Rokujo", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1248/bpb.b23-00898" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38382927" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antipsychotic Agents", "descriptor_ui": "D014150", "major_topic": true }, { "descriptor": "Clozapine", "descriptor_ui": "D003024", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "2", "normalized_date": "2024", "pages": "478-485", "proceedings_title": null, "publisher": "", "title": "Biological & pharmaceutical bulletin", "volume": "47", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Clozapine Induces Neuronal Activation in the Medial Prefrontal Cortex in a Projection Target-Biased Manner.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "STUDY OBJECTIVES: Astrocytes change their intracellular calcium (Ca(2+)) concentration during sleep/wakefulness states in mice. Furthermore, the Ca(2+) dynamics in astrocytes vary depending on the brain region. However, it remains unclear whether alterations in astrocyte activity can affect sleep-wake states and cortical oscillations in a brain region-dependent manner. METHODS: Astrocyte activity was artificially manipulated in mice using chemogenetics. Astrocytes in the hippocampus and pons, which are 2 brain regions previously classified into different clusters based on their Ca(2+) dynamics during sleep-wakefulness, were focused on to compare whether there are differences in the effects of astrocytes from different brain regions. RESULTS: The chemogenetic activation of astrocytes in the hippocampus significantly decreased the total time of wakefulness and increased the total time of sleep. This had little effect on cortical oscillations in all sleep-wakefulness states. On the other hand, the activation of astrocytes in the pons substantially suppressed rapid eye movement (REM) sleep in association with a decreased number of REM episodes, indicating strong inhibition of REM onset. Regarding cortical oscillations, the delta wave component during non-REM sleep was significantly enhanced. CONCLUSIONS: These results suggest that astrocytes modulate sleep-wakefulness states and cortical oscillations. Furthermore, the role of astrocytes in sleep-wakefulness states appears to vary among brain regions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Kurogi", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Sanagi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Tsunematsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/sleepadvances/zpae091" }, "pmcid": { "normalized": "PMC11664484" }, "pmid": { "normalized": "39717113" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "1", "normalized_date": "2024", "pages": "zpae091", "proceedings_title": null, "publisher": "", "title": "Sleep advances : a journal of the Sleep Research Society", "volume": "5", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Chemogenetic activation of astrocytes modulates sleep-wakefulness states in a brain region-dependent manner.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bioluminescence imaging has recently attracted great attention as a highly sensitive and non-invasive analytical method. However, weak signal and low chemical stability of the luciferin are conventional drawbacks of bioluminescence imaging. In this review article, we describe the recent progress on the development and applications of bioluminescent probes for overcoming the aforementioned limitations, thereby enabling spatiotemporal trans-scale imaging. The detailed molecular design for manipulation of their luminescent properties and functions enabled a variety of applications, including in vivo deep tissue imaging, long-term imaging, and chemical sensor.", "classifications": [ { "id": "19H05429", "label": "19H05429", "researcher": "Yuki Hiruta", "type": "grant" }, { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihiro", "last_name": "Sakama", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Orioka", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.s004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39175853" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "Supplemental", "normalized_date": "2024", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biophysics and Physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Current advances in the development of bioluminescent probes toward spatiotemporal trans-scale imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neural circuits are initially created with excessive synapse formation until around birth and undergo massive reorganization until they mature. During postnatal development, necessary synapses strengthen and remain, whereas unnecessary ones are weakened and eventually eliminated. These events, collectively called \"synapse elimination\" or \"synapse pruning\", are thought to be fundamental for creating functionally mature neural circuits in adult animals. In the cerebellum of neonatal rodents, Purkinje cells (PCs) receive synaptic inputs from multiple climbing fibers (CFs). Then, inputs from a single CF are strengthened and those from the other CFs are eliminated, and most PCs become innervated by single CFs by the end of the third postnatal week. These events are regarded as a representative model of synapse elimination. This review examines the molecular and cellular mechanisms of CF synapse elimination in the developing cerebellum and argues how autism spectrum disorder (ASD)-related genes are involved in CF synapse development. We introduce recent studies to update our knowledge, incorporate new data into the known scheme, and discuss the remaining issues and future directions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.2183/pjab.100.034" }, "pmcid": { "normalized": "PMC11635086" }, "pmid": { "normalized": "39522973" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autism Spectrum Disorder", "descriptor_ui": "D000067877", "major_topic": true }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "9", "normalized_date": "2024", "pages": "508-523", "proceedings_title": null, "publisher": "", "title": "Proceedings of the Japan Academy. Series B, Physical and biological sciences", "volume": "100", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular and cellular mechanisms of developmental synapse elimination in the cerebellum: Involvement of autism spectrum disorder-related genes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taku", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.s007" }, "pmcid": { "normalized": "PMC11338679" }, "pmid": { "normalized": "39175858" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "Supplemental", "normalized_date": "2024", "pages": "e211007", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Elucidating molecular and cellular mechanisms of singularity phenomena in immunology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During embryogenesis, human hematopoietic stem cells (HSCs) first emerge in the aorta-gonad-mesonephros (AGM) region via transformation of specialized hemogenic endothelial (HE) cells into premature HSC precursors. This process is termed endothelial-to-hematopoietic transition (EHT), in which the HE cells undergo drastic functional and morphological changes from flat, anchorage-dependent endothelial cells to free-floating round hematopoietic cells. Despite its essential role in human HSC development, molecular mechanisms underlying the EHT are largely unknown. This is due to lack of methods to visualize the emergence of human HSC precursors in real time in contrast to mouse and other model organisms. In this study, by inducing HE from human pluripotent stem cells in feeder-free monolayer cultures, we achieved real-time observation of the human EHT in vitro. By continuous observation and single-cell tracking in the culture, it was possible to visualize a process that a single endothelial cell gives rise to a hematopoietic cell and subsequently form a hematopoietic-cell cluster. The EHT was also confirmed by a drastic HE-to-HSC switching in molecular marker expressions. Notably, HSC precursor emergence was not linked to asymmetric cell division, whereas the hematopoietic cell cluster was formed through proliferation and assembling of the floating cells after the EHT. These results reveal unappreciated dynamics in the human EHT, and we anticipate that our human EHT model in vitro will provide an opportunity to improve our understanding of the human HSC development.", "classifications": [ { "id": "21H00415", "label": "21H00415", "researcher": "Mio Nakanishi", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuriko", "last_name": "Yoneda", "name": null }, { "creator_type": "author", "first_name": "Hisaya", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yoshiro", "last_name": "Maezawa", "name": null }, { "creator_type": "author", "first_name": "Koutaro", "last_name": "Yokote", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Nakanishi", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.s015" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39175869" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "Supplemental", "normalized_date": "2024", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biophysics and Physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Real-time imaging of human endothelial-to-hematopoietic transition in vitro using pluripotent stem cell derived hemogenic endothelium.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.s003" }, "pmcid": { "normalized": "PMC11338687" }, "pmid": { "normalized": "39175865" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "Supplemental", "normalized_date": "2024", "pages": "e211003", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Search for singularity cells at the onset of brain disorders using whole-brain imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Synaptic plasticity, the process whereby neuronal connections are either strengthened or weakened in response to stereotyped forms of stimulation, is widely believed to represent the molecular mechanism that underlies learning and memory. The holoenzyme calcium/calmodulin-dependent protein kinase II (CaMKII) plays a well-established and critical role in the induction of a variety of forms of synaptic plasticity such as long-term potentiation (LTP), long-term depression (LTD) and depotentiation. Previously, we identified the GTPase Rem2 as a potent, endogenous inhibitor of CaMKII. Here, we report that knock out of Rem2 enhances LTP at the Schaffer collateral to CA1 synapse in hippocampus, consistent with an inhibitory action of Rem2 on CaMKII in vivo. Further, re-expression of WT Rem2 rescues the enhanced LTP observed in slices obtained from Rem2 conditional knock out (cKO) mice, while expression of a mutant Rem2 construct that is unable to inhibit CaMKII in vitro fails to rescue increased LTP. In addition, we demonstrate that CaMKII and Rem2 interact in dendritic spines using a 2pFLIM-FRET approach. Taken together, our data lead us to propose that Rem2 serves as a brake on synaptic potentiation via inhibition of CaMKII activity. Further, the enhanced LTP phenotype we observe in Rem2 cKO slices reveals a previously unknown role for Rem2 in the negative regulation of CaMKII function.", "classifications": [ { "id": "19H05434", "label": "19H05434", "researcher": "Hideji Murakoshi", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Rabia", "last_name": "Anjum", "name": null }, { "creator_type": "author", "first_name": "Vernon R. J.", "last_name": "Clarke", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Nagasawa", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Suzanne", "last_name": "Paradis", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0301063" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38995900" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinase Type 2", "descriptor_ui": "D054732", "major_topic": true }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": true }, { "descriptor": "Long-Term Potentiation", "descriptor_ui": "D017774", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Monomeric GTP-Binding Proteins", "descriptor_ui": "D020559", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "7", "normalized_date": "2024", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLOS ONE", "volume": "19", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Rem2 interacts with CaMKII at synapses and restricts long-term potentiation in hippocampus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bacterial phytochromes are attractive molecular templates for engineering fluorescent proteins (FPs) because their near-infrared (NIR) emission significantly extends the spectral coverage of GFP-like FPs. Existing phytochrome-based FPs covalently bind heme-derived tetrapyrrole chromophores and exhibit constitutive fluorescence. Here we introduce Rep-miRFP, an NIR imaging probe derived from bacterial phytochrome, which interacts non-covalently and reversibly with biliverdin chromophore. In Rep-miRFP, the photobleached non-covalent adduct can be replenished with fresh biliverdin, restoring fluorescence. By exploiting this chromophore renewal capability, we demonstrate NIR PAINT nanoscopy in mammalian cells using Rep-miRFP.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kai", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Tetsuichi", "last_name": "Wazawa", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Daria M.", "last_name": "Shcherbakova", "name": null }, { "creator_type": "author", "first_name": "Vladislav V.", "last_name": "Verkhusha", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-024-06169-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38637683" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Biliverdine", "descriptor_ui": "D001664", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": true }, { "descriptor": "Phytochrome", "descriptor_ui": "D010834", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "", "proceedings_title": null, "publisher": "", "title": "Communications Biology", "volume": "7", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Near-infrared PAINT localization microscopy via chromophore replenishment of phytochrome-derived fluorescent tag.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.s013" }, "pmcid": { "normalized": "PMC11338689" }, "pmid": { "normalized": "39175856" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "Supplemental", "normalized_date": "2024", "pages": "e211013", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Editorial: Singularity Biology and Beyond.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.s005" }, "pmcid": { "normalized": "PMC11338686" }, "pmid": { "normalized": "39175857" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "Supplemental", "normalized_date": "2024", "pages": "e211005", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Integration of single-cell manipulation, whole transcriptome analysis, and image-based deep learning for studying \"Singularity Biology\".", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Glucose metabolism is a key factor characterizing the cellular state during multicellular development. In metazoans, the metabolic state of undifferentiated cells correlates with growth/differentiation transition and cell fate determination. Notably, the cell fate of the Amoebozoa species Dictyostelium discoideum is biased by the presence of glucose and is also correlated with early differences in intracellular ATP. However, the relationship between early cell–cell heterogeneity, cell differentiation, and the metabolic state is unclear. To address the link between glucose metabolism and cell differentiation in D. discoideum, we studied the role of phosphoenolpyruvate carboxylase (PEPC), a key enzyme in the PEP-oxaloacetate-pyruvate node, a core junction that dictates the metabolic flux of glycolysis, the TCA cycle, and gluconeogenesis. We demonstrate that there is cell–cell heterogeneity in PEPC promoter activity in vegetative cells, which depends on nutrient conditions, and that cells with high PEPC promoter activity differentiate into spores. The PEPC null mutant exhibited an aberrantly high prestalk/prespore ratio, and the spore mass of the fruiting body was glassy and consisted of immature spores. Furthermore, the PEPC null mutant had high ATP levels and low mitochondrial membrane potential. Our results suggest the importance of cell–cell heterogeneity in the levels of metabolic enzymes during early cell fate priming.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenichi", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Hashimura", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Fujishiro", "name": null }, { "creator_type": "author", "first_name": "Narufumi", "last_name": "Kameya", "name": null }, { "creator_type": "author", "first_name": "Kazuteru", "last_name": "Taoka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kuwana", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fukuzawa", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2024.1526795" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39968235" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Cell and Developmental Biology", "volume": "12", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell–cell heterogeneity in phosphoenolpyruvate carboxylase biases early cell fate priming in Dictyostelium discoideum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Over the last decade, the use of microfabricated substrates has proven pivotal for studying the effect of substrate topography on cell deformation and migration. Microfabrication techniques allow one to construct a transparent substrate with topographic features with high designability and reproducibility and thus well suited to experiments that microscopically address how spatial and directional bias are brought about in the cytoskeletal machineries and hence cell motility. While much of the progress in this avenue of study has so far been made in adhesive cells of epithelial and mesenchymal nature, whether related phenomena exist in less adhesive fast migrating cells is relatively unknown. In this chapter, we describe a method that makes use of micrometer-scale ridges to study fast-migrating Dictyostelium cells where it was recently shown that membrane evagination associated with macropinocytic cup formation plays a pivotal role in the topography sensing. The method requires only basic photolithography, and thus the step-by-step protocol should be a good entry point for cell biologists looking to incorporate similar microfabrication approaches.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Gen", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-3894-1_11" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38954204" } }, "mesh": [ { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": true }, { "descriptor": "Microtechnology", "descriptor_ui": "D055616", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "149-161", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2814", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Analyzing the Micro-topography Guidance of Dictyostelium Cells Using Microfabricated Structures.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In a post-growth multicellular organism, the phenomenon in which a small number of rare cells can be the starting point for inducing a dramatic change in the entire system is considered a “biological singularity.” The immune response and cancer can be regarded as singularity phenomena in mammals, but their nature is fundamentally different. The immune response is considered a “programmed” singularity, whereas cancer is an “unprogrammed” singularity. These two systems perpetually engage in a cycle of attack and defense within the organism. The outcome is depending on the wining system, which determines whether the individual experiences a state resembling light or darkness. However, the overall mechanism of the competition remains unclear and is expected to be elucidated with future innovations in bioimaging technologies. Immune checkpoint blockade therapy is a means by which the two singularity balances can be artificially manipulated; therefore, mechanistic insight is necessary for cancer treatment strategies. Altogether, these findings provide a different perspective crucial for understanding the behavior of dynamic cell populations in multicellular organisms.", "classifications": [ { "id": "18H05417", "label": "18H05417", "researcher": "Taku Okazaki", "type": "grant" }, { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Okazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.s006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39175864" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "Supplemental", "normalized_date": "2024", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biophysics and Physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "A battle between two biological singularities: Immune response vs. cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Considering the fundamental mechanism causing singularity phenomena, we performed the following abduction: Assuming that a multicellular system is driven by spontaneous fluctuation of each cell and dynamic interaction of the cells, state transition of the system would be experimentally predictable from cellular heterogeneity. This study evaluates the abductive hypothesis by analyzing cellular heterogeneity to distinguish pre-state of state transition of differentiating cells with Raman spectroscopy and human induced pluripotent stem cells (hiPSCs) technique. Herein, we investigated the time development of cellular heterogeneity in Raman spectra during cardiomyogenesis of six hiPSC lines and tested two types of analyses for heterogeneity. As expected, some spectral peaks, possibly attributed to glycogen, correctively exhibited higher heterogeneity, prior to intensity changes of the spectrum in the both analyses in the all cell-lines tested. The combination of spectral data and heterogeneity-based analysis will be an approach to the arrival of biology that uses not only signal intensity but also heterogeneity as a biological index.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Haruki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Kuniya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Tomonobu", "last_name": "M Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.s016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39175855" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "Supplemental", "normalized_date": "2024", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biophysics and Physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Yuragi biomarker concept for evaluating human induced pluripotent stem cells using heterogeneity-based Raman finger-printing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During the early development of tetrapods, including humans, the embryonic body elongates caudally once the anterior-posterior axis is established. During this process, region-specific vertebral morphogenesis occurs, with the determination of limb positioning along the anterior-posterior axis. We previously reported that Gdf11 functions as an anatomical integration system that determines the positioning of hindlimbs and sacral vertebrae where Gdf11 is expressed. However, the molecular mechanisms underlying induction of Gdf11 expression remain unclear. In this study, we searched for non-coding regions near the Gdf11 locus that were conserved across species to elucidate the regulatory mechanisms of Gdf11 expression. We identified an enhancer of the Gdf11 gene in intron 1 and named it highly conserved region (HCR). In HCR knockout mice, the expression level of endogenous Gdf11 was decreased, and the position of the sacral-hindlimb unit was shifted posteriorly. We also searched for factors upstream of Gdf11 based on the predicted transcription factor binding sites within the HCR. We found that inhibition of FGF signaling increased endogenous Gdf11 expression, suggesting that FGF signaling negatively regulates Gdf11 expression. However, FGF signaling does not regulate HCR activity. Our results suggest that there are species-specific Gdf11 enhancers other than HCR and that FGF signaling regulates Gdf11 expression independent of HCR.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Seiji", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Utsugi", "last_name": "Kanazawa", "name": null }, { "creator_type": "author", "first_name": "Ayana", "last_name": "Tatsumi", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2024.1302141" }, "pmcid": { "normalized": "PMC10978735" }, "pmid": { "normalized": "38559809" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "1302141", "proceedings_title": null, "publisher": "", "title": "Frontiers in cell and developmental biology", "volume": "12", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Functional analysis of a first hindlimb positioning enhancer via Gdf11 expression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Twisted intramolecular charge transfer (TICT) is a phenomenon involving intramolecular charge transfer together with intramolecular rotation upon photoexcitation, and in general this excited state of fluorescent dyes undergoes non-radiative decay (producing no fluorescence). We recently discovered that the magnitude of TICT in rhodamine derivatives could be regulated by altering the size of the substituents on the xanthene moiety, generating differing degrees of intramolecular steric repulsion. To further illustrate the usefulness and generality of this strategy, we describe here an application of quinone methide chemistry, which is widely used as a fluorescence off/on switching reaction for fluorescence probes detecting enzymatic activity, to construct a steric repulsion-induced (sr)-TICT-based fluorescence probe targeting nitroreductase (NTR) activity. The developed probe was almost non-fluorescent in phosphate-buffered saline (PBS) due to strong induction of the TICT state. On the other hand, when the probe was incubated with NTR and nicotinamide adenine dinucleotide (NADH), a large fluorescence increase was observed over time. We confirmed that the enzymatic reaction proceeded as expected, i.e., the nitro group of the probe was reduced to the corresponding amino group, followed by spontaneous elimination of iminoquinone methide. These results suggest that our simple design strategy based on the sr-TICT mechanism, i.e., controlling intramolecular steric repulsion, would be applicable to the development of fluorescence probes for a variety of enzymes.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mizuki", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ikeno", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1248/cpb.c24-00486" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39313385" } }, "mesh": [ { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Nitroreductases", "descriptor_ui": "D009601", "major_topic": true }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "9", "normalized_date": "2024", "pages": "810-816", "proceedings_title": null, "publisher": "", "title": "Chemical & pharmaceutical bulletin", "volume": "72", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a Fluorescence Probe for Detecting Nitroreductase Activity Based on Steric Repulsion-Induced Twisted Intramolecular Charge Transfer (sr-TICT).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In humans, uric acid is an end-product of purine metabolism. Urate excretion from the human kidney is tightly regulated by reabsorption and secretion. At least eleven genes have been identified as human renal urate transporters. However, it remains unclear whether all renal tubular cells express the same set of urate transporters. Here, we show renal tubular cells are divided into three distinct cell populations for urate handling. Analysis of healthy human kidneys at single-cell resolution revealed that not all tubular cells expressed the same set of urate transporters. Only 32% of tubular cells were related to both reabsorption and secretion, while the remaining tubular cells were related to either reabsorption or secretion at 5% and 63%, respectively. These results provide physiological insight into the molecular function of the transporters and renal urate handling on single-cell units. Our findings suggest that three different cell populations cooperate to regulate urate excretion from the human kidney, and our proposed framework is a step forward in broadening the view from the molecular to the cellular level of transport capacity.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiko M.", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Pattama", "last_name": "Wiriyasermkul", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Matsubayashi", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Miyasaka", "name": null }, { "creator_type": "author", "first_name": "Nau", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Kinugawa", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Sugie", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Eriguchi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Tsuruya", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kuniyasu", "name": null }, { "creator_type": "author", "first_name": "Shushi", "last_name": "Nagamori", "name": null }, { "creator_type": "author", "first_name": "Eiichiro", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12576-023-00894-0" }, "pmcid": { "normalized": "PMC10763458" }, "pmid": { "normalized": "38166558" } }, "mesh": [ { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": true }, { "descriptor": "Uric Acid", "descriptor_ui": "D014527", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "1", "normalized_date": "2024", "pages": "1", "proceedings_title": null, "publisher": "", "title": "The journal of physiological sciences : JPS", "volume": "74", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of three distinct cell populations for urate excretion in human kidneys.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "[This corrects the article DOI: 10.3389/fimmu.2022.1028733.].", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Takunori", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Komai", "name": null }, { "creator_type": "author", "first_name": "Shusaku", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Kitagami", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Serizawa", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Nagaoka", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Yokomizo", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Miyahira", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Kawana", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Kimizuka", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2024.1446711" }, "pmcid": { "normalized": "PMC11237957" }, "pmid": { "normalized": "38994373" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "1446711", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Corrigendum: 1270 nm near-infrared light as a novel vaccine adjuvant acts on mitochondrial photoreception in intradermal vaccines.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alzheimer’s disease is a devastating disease that is accompanied by dementia, and its incidence increases with age. However, no interventions have exhibited clear therapeutic effects. We aimed to develop and characterize behavioural tasks that allow the earlier identification of signs preceding dementia that would facilitate the development of preventative and therapeutic interventions for Alzheimer’s disease. To this end, we developed a 3D virtual reality task sensitive to the activity of grid cells in the entorhinal cortex, which is the region that first exhibits neurofibrillary tangles in Alzheimer’s disease. We investigated path integration (assessed by error distance) in a spatial navigation task sensitive to grid cells in the entorhinal cortex in 177 volunteers, aged 20–89 years, who did not have self-reported dementia. While place memory was intact even in old age, path integration deteriorated with increasing age. To investigate the relationship between neurofibrillary tangles in the entorhinal cortex and path integration deficit, we examined a mouse model of tauopathy (P301S mutant tau-overexpressing mice; PS19 mice). At 6 months of age, PS19 mice showed a significant accumulation of phosphorylated tau only in the entorhinal cortex, associated with impaired path integration without impairments in spatial cognition. These data are consistent with the idea that path integration deficit is caused by the accumulation of phosphorylated tau in the entorhinal cortex. This method may allow the early identification of individuals likely to develop Alzheimer’s disease.", "classifications": [ { "id": "18H05414", "label": "18H05414", "researcher": "Hiroko Bannai", "type": "grant" }, { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Riki", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Soeda", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Ishigaki", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Takaichi", "name": null }, { "creator_type": "author", "first_name": "James K.", "last_name": "Chambers", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Hirohisa", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/braincomms/fcad359" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38347945" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "1", "normalized_date": "2024", "pages": "", "proceedings_title": null, "publisher": "", "title": "Brain Communications", "volume": "6", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Path integration deficits are associated with phosphorylated tau accumulation in the entorhinal cortex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Despite extensive regulatory T cell (Treg) research, fundamental questions on in vivo dynamics remain to be answered. The current study aims to dissect several interwoven concepts in Treg biology, highlighting the 'self-reactivity' of Treg and their counterparts, namely naturally-arising memory-phenotype T-cells, as a key mechanism to be exploited by a human retroviral infection. We propose the novel key concept, Periodic T cell receptor (TCR)-signalled T-cells, capturing self-reactivity in a quantifiable manner using the Nr4a3-Timer-of-cell-kinetics-and-activity (Tocky) technology. Periodic and brief TCR signals in self-reactive T-cells contrast with acute TCR signals during inflammation. Thus, we propose a new two-axis model for T-cell activation by the two types of TCR signals or antigen recognition, elucidating how Foxp3 expression and acute TCR signals actively regulate Periodic TCR-signalled T-cells. Next, we highlight an underappreciated branch of immunological research on Human T-cell Leukemia Virus type 1 (HTLV-1) that precedes Treg studies, illuminating the missing link between the viral infection, CD25, and Foxp3. Based on evidence by single-cell analysis, we show how the viral infection exploits the regulatory mechanisms for T-cell activation and suggests a potential role of periodic TCR signalling in infection and malignant transformation. In conclusion, the new perspectives and models in this study provide a working framework for investigating Treg within the self-reactive T-cell spectrum, expected to advance understanding of HTLV-1 infection, cancer, and immunotherapy strategies for these conditions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yorifumi", "last_name": "Satou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/discim/kyae006" }, "pmcid": { "normalized": "PMC11165433" }, "pmid": { "normalized": "38863793" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "1", "normalized_date": "2024", "pages": "kyae006", "proceedings_title": null, "publisher": "", "title": "Discovery immunology", "volume": "3", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Spectrum of Treg and self-reactive T cells: single cell perspectives from old friend HTLV-1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Identification of the neural circuits in the brain regulating animal behavior and physiology is critical for understanding brain functions and is one of the most challenging goals in neuroscience research. The fruitfly Drosophila melanogaster has often been used to identify the neural circuits involved in the regulation of specific behaviors because of the many neurogenetic tools available to express target genes in particular neurons. Neurons controlling sexual behavior, feeding behavior, and circadian rhythms have been identified, and the number of neurons responsible for controlling these phenomena is small. The search for a few neurons controlling a specific behavior is an important first step to clarify the overall picture of the neural circuits regulating that behavior. We previously found that the clock gene period (per), which is essential for circadian rhythms in Drosophila, is also essential for long-term memory (LTM). We have also found that a very limited number of per-expressing clock neurons in the adult brain are required for the consolidation and maintenance of LTM. In this review, we focus on LTM in Drosophila, introduce the concept of LTM regulation by a few clock neurons that we have recently discovered, and discuss how a few clock neurons regulate Drosophila LTM.", "classifications": [ { "id": "21H00434", "label": "21H00434", "researcher": "Takaomi Sakai", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Rei", "last_name": "Shirakawa", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Kurata", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.s002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39175866" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "Supplemental", "normalized_date": "2024", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biophysics and Physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Regulation of long-term memory by a few clock neurons in Drosophila.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Major depressive disorder (MDD) is a psychiatric disorder that affects more than 300 million people worldwide and has a serious impact on society. Conventional antidepressants targeting monoamines in the brain based on the monoamine hypothesis are known to take a prolonged time to be effective or less effective in 30% of MDD patients. Hence, there is a need to develop antidepressants that are effective against treatment-resistant depression and have a new mechanism different from the monoamine hypothesis. An increasing number of research groups including us have been establishing that pituitary adenylate cyclase-activating polypeptide (PACAP) and one of its receptors, PAC1 receptor, are closely related to the etiology of stress-related diseases such as MDD. Therefore, it is strongly suggested that the PAC1 receptor is a promising target in the treatment of psychiatric disorders. We developed a novel, non-peptidic, small-molecule, high-affinity PAC1 receptor antagonists and conducted behavioral pharmacology experiments in mice to characterize a novel PAC1 receptor antagonist as a new option for MDD therapy. The results show that our novel PAC1 receptor antagonist has the potential to be a new antidepressant with a high safety profile. In this review, we would like to present the background of developing our novel PAC1 receptor antagonist and its effects on mouse models of acute stress.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ichiro", "last_name": "Takasaki", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/fpj.24008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38945904" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antidepressive Agents", "descriptor_ui": "D000928", "major_topic": true }, { "descriptor": "Drug Development", "descriptor_ui": "D000076722", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Major Depressive Disorder", "descriptor_ui": "D003865", "major_topic": false }, { "descriptor": "Molecular Targeted Therapy", "descriptor_ui": "D058990", "major_topic": false }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I", "descriptor_ui": "D051237", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "4", "normalized_date": "2024", "pages": "219-224", "proceedings_title": null, "publisher": "", "title": "Nihon yakurigaku zasshi. Folia pharmacologica Japonica", "volume": "159", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "[Strategy for the development of small-molecule antidepressant targeting PAC1 receptor].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.s001" }, "pmcid": { "normalized": "PMC11338680" }, "pmid": { "normalized": "39175868" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "Supplemental", "normalized_date": "2024", "pages": "e211001", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Analysis of the singularity cells controlling the pattern formation in multi-cellular systems.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Understanding the temporal dynamics of T-cell transcription is crucial for insights into immune cell function and development. In this study, we show the features of the Timer-of-Cell-Kinetics-and-Activity (Tocky) system, which enables analysis of temporal dynamics of cell activities and differentiation, leveraging Fluorescent Timer protein, which spontaneously changes its emission spectrum from blue to red fluorescence in known kinetics, as reporters. The current study examines the properties of the Tocky system, highlighting the Timer-Angle approach, which is a core algorithm of Tocky analysis and converts Timer Blue and Red fluorescence into Timer Angle and Intensity by trigonometric transformation. Importantly, Tocky analyzes time-related events within individual cells by the two phases of measurements, distinguishing between (1) the temporal sequence of cellular activities and differentiation within the time domain, and (2) the transcription frequency within the frequency domain. The transition from time measurement to frequency analysis, particularly at the Persistent locus that bridges these domains, highlights that system's unique property in what is measured and analyzed by Tocky. Intriguingly, the sustained transcriptional activities observed in cells at the Persistent locus may have unique biological features as demonstrated in activated regulatory T-cells (Treg) and pathogenic T-cells, respectively, using Foxp3-Tocky and Nr4a3-Tocky models. In conclusion, the Tocky system can provide crucial data for advancing our understanding of T-cell dynamics and function.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.s010" }, "pmcid": { "normalized": "PMC11338677" }, "pmid": { "normalized": "39175859" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "Supplemental", "normalized_date": "2024", "pages": "e211010", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Unraveling T-cell dynamics using fluorescent timer: Insights from the Tocky system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Aoshi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Nakamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.s012" }, "pmcid": { "normalized": "PMC11338681" }, "pmid": { "normalized": "39175867" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "Supplemental", "normalized_date": "2024", "pages": "e211012", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Model systems for discovering evolutionary singularity of bilaterian physiological regulation: lessons from studies on simple/primitive flatworms.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In collective systems, influence of individuals can permeate an entire group through indirect interactionscom-plicating any scheme to understand individual roles from observations. A typical approach to understand an individuals influence on another involves consideration of confounding factors, for example, by conditioning on other individuals outside of the pair. This becomes unfeasible in many cases as the number of individuals increases. In this article, we review some of the unforeseen problems that arise in understanding individual influence in a collective such as single cells, as well as some of the recent works which address these issues using tools from information theory.", "classifications": [ { "id": "18H05413", "label": "18H05413", "researcher": "Tamiki Komatsuzaki", "type": "grant" }, { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Sulimon", "last_name": "Sattari", "name": null }, { "creator_type": "author", "first_name": "Udoy", "last_name": "S. Basak", "name": null }, { "creator_type": "author", "first_name": "M.", "last_name": "Mohiuddin", "name": null }, { "creator_type": "author", "first_name": "Mikito", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.s014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39175852" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "Supplemental", "normalized_date": "2024", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biophysics and Physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Inferring the roles of individuals in collective systems using information-theoretic measures of influence.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tauopathy is a spectrum of diseases characterized by fibrillary tau aggregate formation in neurons and glial cells in the brain. Tau aggregation originates in the brainstem and entorhinal cortex and then spreads throughout the brain in Alzheimer's disease (AD), which is the most prevalent type of tauopathy. Understanding the mechanism by which locally developed tau pathology propagates throughout the brain is crucial for comprehending AD pathogenesis. Therefore, a novel model of tau pathology that artificially induces tau aggregation in targeted cells at specific times is essential. This study describes a novel optogenetic module, OptoTau, which is a human tau with the P301L mutation fused with a photosensitive protein CRY2olig, inducing various forms of tau according to the temporal pattern of blue light illumination pattern. Continuous blue light illumination for 12 h to Neuro2a cells that stably express OptoTau (OptoTauKI cells) formed clusters along microtubules, many of which eventually accumulated in aggresomes. Conversely, methanol-resistant tau aggregation was formed when alternating light exposure and darkness in 30-min cycles for 8 sets per day were repeated over 8 days. Methanol-resistant tau was induced more rapidly by repeating 5-min illumination followed by 25-min darkness over 24 h. These results indicate that OptoTau induced various tau aggregation stages based on the temporal pattern of blue light exposure. Thus, this technique exhibits potential as a novel approach to developing specific tau aggregation in targeted cells at desired time points.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shigeo", "last_name": "Sakuragi", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Boxiao", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Sakata", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Soeda", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.0023" }, "pmcid": { "normalized": "PMC11832247" }, "pmid": { "normalized": "39963597" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "4", "normalized_date": "2024", "pages": "e210023", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Inducing aggresome and stable tau aggregation in Neuro2a cells with an optogenetic tool.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.s011" }, "pmcid": { "normalized": "PMC11338682" }, "pmid": { "normalized": "39175854" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "Supplemental", "normalized_date": "2024", "pages": "e211011", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualizing Singularity Phenomenon.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Singularity phenomena are rare events that occur only with a probability of one in tens of thousands and yet play an important role in the fate of the entire system. Recently, an ultra-wide-field microscopy imaging systems, AMATERAS, have been developed to reliably capture singularity phenomena. However, to determine whether a rare phenomenon captured by microscopy is a true singularity phenomenon—one with a significant impact on the entire system—, causal analysis is required. In this section, we introduce the CALI method, which uses light to inactivate molecules as one of the techniques enabling causal analysis. In addition, we discuss the technical innovations of the CALI method that are required to contribute to the future development of singularity biology.", "classifications": [ { "id": "21H00423", "label": "21H00423", "researcher": "Kiwamu Takemoto", "type": "grant" }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hisashi", "last_name": "Shidara", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Jitsuki", "name": null }, { "creator_type": "author", "first_name": "Kiwamu", "last_name": "Takemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.s009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39175862" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "Supplemental", "normalized_date": "2024", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biophysics and Physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Chromophore-assisted light inactivation of target proteins for singularity biology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Singularity biology is a scientific field that targets drastic state changes in multicellular systems, aiming to discover the key cells that induce the state change and investigate the mechanisms behind them. To achieve this goal, we developed a trans-scale optical imaging system (trans-scale scope), that is capable of capturing both macroscale changes across the entire system and the micro-scale behavior of individual cells, surpassing the cell observation capabilities of traditional microscopes. We developed two units of the trans-scale scope, named AMATERAS-1 and -2, which demonstrated the ability to observe multicellular systems consisting of over one million cells in a single field of view with sub-cellular resolution. This flagship instrument has been used to observe the dynamics of various cell species, with the advantage of being able to observe a large number of cells, allowing the detection and analysis of rare events and cells such as leader cells in multicellular pattern formation and cells that spontaneously initiate calcium waves. In this paper, we present the design concept of AMATERAS, the optical configuration, and several examples of observations, and demonstrate how the strength-in-numbers works in life sciences.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "18H05415", "label": "18H05415", "researcher": "Kazuki Horikawa", "type": "grant" }, { "id": "19H05411", "label": "19H05411", "researcher": "Yusuke Ohba", "type": "grant" }, { "id": "21H00413", "label": "21H00413", "researcher": "Yoichiro Fujioka", "type": "grant" }, { "id": "21H00431", "label": "21H00431", "researcher": "Yuki Sato", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Taishi", "last_name": "Kakizuka", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.s017" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39175860" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "Supplemental", "normalized_date": "2024", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biophysics and Physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Strength in numbers: Unleashing the potential of trans-scale scope AMATERAS for massive cell quantification.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Single-molecule imaging in living cells is an effective tool for elucidating the mechanisms of cellular phenomena at the molecular level. However, the analysis was not designed for throughput and requires high expertise, preventing it from reaching large scale, which is necessary when searching for rare cells that induce singularity phenomena. To overcome this limitation, we have automated the imaging procedures by combining our own focusing device, artificial intelligence, and robotics. The apparatus, called automated in-cell single-molecule imaging system (AiSIS), achieves a throughput that is a hundred-fold higher than conventional manual imaging operations, enabling the analysis of molecular events by individual cells across a large population. Here, using AiSIS, we demonstrate the single-molecule imaging of molecular behaviors and reactions related to tau protein aggregation, which is considered a singularity phenomenon in neurological disorders. Changes in the dynamics and kinetics of molecular events were observed inside and on the basal membrane of cells after the induction of aggregation. Additionally, to detect rare cells based on the molecular behavior, we developed a method to identify the state of individual cells defined by the quantitative distribution of molecular mobility and clustering. Using this method, cellular variations in receptor behavior were shown to decrease following ligand stimulation. This cell state analysis based on large-scale single-molecule imaging by AiSIS will advance the study of molecular mechanisms causing singularity phenomena.", "classifications": [ { "id": "18H05414", "label": "18H05414", "researcher": "Hiroko Bannai", "type": "grant" }, { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.s018" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39175861" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "Supplemental", "normalized_date": "2024", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biophysics and Physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Application of single-molecule analysis to singularity phenomenon of cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kumiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Gerhard", "last_name": "Hummer", "name": null }, { "creator_type": "author", "first_name": "Jerelle A.", "last_name": "Joseph", "name": null }, { "creator_type": "author", "first_name": "Rong", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Feng", "last_name": "Zhang", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.e2012" }, "pmcid": { "normalized": "PMC11998096" }, "pmid": { "normalized": "40241780" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "Supplemental2", "normalized_date": "2024", "pages": "e212012", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "A round table at IUPAB Congress in Kyoto 2024: Dreaming the next 50 years in our biophysics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "21H00422", "label": "21H00422", "researcher": "Daisuke Ono", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jihwan", "last_name": "Myung", "name": null }, { "creator_type": "author", "first_name": "Rae", "last_name": "Silver", "name": null }, { "creator_type": "author", "first_name": "Jeff R.", "last_name": "Jones", "name": null }, { "creator_type": "author", "first_name": "Takahiro J.", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2024.1453328" }, "pmcid": { "normalized": "PMC11288068" }, "pmid": { "normalized": "39081852" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "1453328", "proceedings_title": null, "publisher": "", "title": "Frontiers in neuroscience", "volume": "18", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Editorial: Development of circadian clock functions, volume II.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Haploid larvae in non-mammalian vertebrates are lethal, with characteristic organ growth retardation collectively called 'haploid syndrome'. In contrast to mammals, whose haploid intolerance is attributed to imprinting misregulation, the cellular principle of haploidy-linked defects in non-mammalian vertebrates remains unknown. Here, we investigated cellular defects that disrupt the ontogeny of gynogenetic haploid zebrafish larvae. Unlike diploid control larvae, haploid larvae manifested unscheduled cell death at the organogenesis stage, attributed to haploidy-linked p53 upregulation. Moreover, we found that haploid larvae specifically suffered the gradual aggravation of mitotic spindle monopolarization during 1-3 days post-fertilization, causing spindle assembly checkpoint-mediated mitotic arrest throughout the entire body. High-resolution imaging revealed that this mitotic defect accompanied the haploidy-linked centrosome loss occurring concomitantly with the gradual decrease in larval cell size. Either resolution of mitotic arrest or depletion of p53 partially improved organ growth in haploid larvae. Based on these results, we propose that haploidy-linked mitotic defects and cell death are parts of critical cellular causes shared among vertebrates that limit the larval growth in the haploid state, contributing to an evolutionary constraint on allowable ploidy status in the vertebrate life cycle.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kan", "last_name": "Yaguchi", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Triveni", "last_name": "Menon", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Matsura", "name": null }, { "creator_type": "author", "first_name": "Miyu", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Takeomi", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Kotani", "name": null }, { "creator_type": "author", "first_name": "Sreelaja", "last_name": "Nair", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1098/rsob.240126" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39378986" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": true }, { "descriptor": "Centrosome", "descriptor_ui": "D018385", "major_topic": false }, { "descriptor": "Haploidy", "descriptor_ui": "D006238", "major_topic": true }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": true }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false }, { "descriptor": "Spindle Apparatus", "descriptor_ui": "D008941", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": true }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": true }, { "descriptor": "Zebrafish Proteins", "descriptor_ui": "D029961", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "240126", "proceedings_title": null, "publisher": "", "title": "Open biology", "volume": "14", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Haploidy-linked cell proliferation defects limit larval growth in zebrafish.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Zebrafish is a useful model organism in neuroscience; however, its gene expression atlas in the adult brain is not well developed. In the present study, we examined the expression of 38 neuropeptides, comparing with GABAergic and glutamatergic neuron marker genes in the adult zebrafish brain by comprehensive in situ hybridization. The results are summarized as an expression atlas in 19 coronal planes of the forebrain. Furthermore, the scanned data of all brain sections were made publicly available in the Adult Zebrafish Brain Gene Expression Database (https://ssbd.riken.jp/azebex/). Based on these data, we performed detailed comparative neuroanatomical analyses of the hypothalamus and found that several regions previously described as one nucleus in the reference zebrafish brain atlas contain two or more subregions with significantly different neuropeptide/neurotransmitter expression profiles. Subsequently, we compared the expression data in zebrafish telencephalon and hypothalamus obtained in this study with those in mice, by performing a cluster analysis. As a result, several nuclei in zebrafish and mice were clustered in close vicinity. The present expression atlas, database, and anatomical findings will contribute to future neuroscience research using zebrafish.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Towako", "last_name": "Hiraki-Kajiyama", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Miyasaka", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Wakisaka", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Itoga", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Yoshihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cne.25619" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38831653" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Atlases as Topic", "descriptor_ui": "D001271", "major_topic": false }, { "descriptor": "Databases, Genetic", "descriptor_ui": "D030541", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": true }, { "descriptor": "Prosencephalon", "descriptor_ui": "D016548", "major_topic": true }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "e25619", "proceedings_title": null, "publisher": "", "title": "The Journal of comparative neurology", "volume": "532", "year": 2024 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000266" ] }, "title": "An atlas and database of neuropeptide gene expression in the adult zebrafish forebrain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Organoids are 3D cultured tissues derived from stem cells that resemble the structure of living organs. Based on the accumulated knowledge of neural development, neural organoids that recapitulate neural tissue have been created by inducing self-organized neural differentiation of stem cells. Neural organoid techniques have been applied to human pluripotent stem cells to differentiate 3D human neural tissues in culture. Various methods have been developed to generate neural tissues of different regions. Currently, neural organoid technology has several significant limitations, which are being overcome in an attempt to create neural organoids that more faithfully recapitulate the living brain. The rapidly advancing neural organoid technology enables the use of living human neural tissue as research material and contributes to our understanding of the development, structure and function of the human nervous system, and is expected to be used to overcome neurological diseases and for regenerative medicine.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tamada", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ibneur.2023.12.006" }, "pmcid": { "normalized": "PMC11240300" }, "pmid": { "normalized": "39007085" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Jun", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "106-117", "proceedings_title": null, "publisher": "", "title": "IBRO neuroscience reports", "volume": "16", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Recapitulation and investigation of human brain development with neural organoids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We derive generalized Langevin equations (GLEs) for single beads in linear elastic networks. In particular, the derivations of the GLEs are conducted without employing normal modes, resulting in two distinct representations in terms of resistance and mobility kernels. The fluctuation-dissipation relations are also confirmed for both GLEs. Subsequently, we demonstrate that these two representations are interconnected via Laplace transforms. Furthermore, another GLE is derived by utilizing a projection operator method, and it is shown that the equation obtained through the projection scheme is consistent with the GLE with the resistance kernel. As simple examples, the general theory is applied to the Rouse model and the ring polymer, where the GLEs with the resistance and mobility kernels are explicitly derived for arbitrary positions of the tagged bead in these models. Finally, the GLE with the mobility kernel is also derived for the elastic network with hydrodynamic interactions under the pre-averaging approximation.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Tomoshige", "last_name": "Miyaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.110.044136" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39562923" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Oct", "date_precision": "unknown", "issue": "4-1", "normalized_date": null, "pages": "044136", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "110", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Generalized Langevin dynamics for single beads in linear elastic networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Although several SARS-CoV-2-related coronaviruses (SC2r-CoVs) were discovered in bats and pangolins, the differences in virological characteristics between SARS-CoV-2 and SC2r-CoVs remain poorly understood. Recently, BANAL-20-236 (B236) was isolated from a rectal swab of Malayan horseshoe bat and was found to lack a furin cleavage site (FCS) in the spike (S) protein. The comparison of its virological characteristics with FCS-deleted SARS-CoV-2 (SC2ΔFCS) has not been conducted yet. METHODS: We prepared human induced pluripotent stem cell (iPSC)-derived airway and lung epithelial cells and colon organoids as human organ-relevant models. B236, SARS-CoV-2, and artificially generated SC2ΔFCS were used for viral experiments. To investigate the pathogenicity of B236 in vivo, we conducted intranasal infection experiments in hamsters. FINDINGS: In human iPSC-derived airway epithelial cells, the growth of B236 was significantly lower than that of the SC2ΔFCS. A fusion assay showed that the B236 and SC2ΔFCS S proteins were less fusogenic than the SARS-CoV-2 S protein. The infection experiment in hamsters showed that B236 was less pathogenic than SARS-CoV-2 and even SC2ΔFCS. Interestingly, in human colon organoids, the growth of B236 was significantly greater than that of SARS-CoV-2. INTERPRETATION: Compared to SARS-CoV-2, we demonstrated that B236 exhibited a tropism toward intestinal cells rather than respiratory cells. Our results are consistent with a previous report showing that B236 is enterotropic in macaques. Altogether, our report strengthens the assumption that SC2r-CoVs in horseshoe bats replicate primarily in the intestinal tissues rather than respiratory tissues. FUNDING: This study was supported in part by AMED ASPIRE (JP23jf0126002, to Keita Matsuno, Kazuo Takayama, and Kei Sato); AMED SCARDA Japan Initiative for World-leading Vaccine Research and Development Centers \"UTOPIA\" (JP223fa627001, to Kei Sato), AMED SCARDA Program on R&D of new generation vaccine including new modality application (JP223fa727002, to Kei Sato); AMED SCARDA Hokkaido University Institute for Vaccine Research and Development (HU-IVReD) (JP223fa627005h0001, to Takasuke Fukuhara, and Keita Matsuno); AMED Research Program on Emerging and Re-emerging Infectious Diseases (JP21fk0108574, to Hesham Nasser; JP21fk0108493, to Takasuke Fukuhara; JP22fk0108617 to Takasuke Fukuhara; JP22fk0108146, to Kei Sato; JP21fk0108494 to G2P-Japan Consortium, Keita Matsuno, Shinya Tanaka, Terumasa Ikeda, Takasuke Fukuhara, and Kei Sato; JP21fk0108425, to Kazuo Takayama and Kei Sato; JP21fk0108432, to Kazuo Takayama, Takasuke Fukuhara and Kei Sato; JP22fk0108534, Terumasa Ikeda, and Kei Sato; JP22fk0108511, to Yuki Yamamoto, Terumasa Ikeda, Keita Matsuno, Shinya Tanaka, Kazuo Takayama, Takasuke Fukuhara, and Kei Sato; JP22fk0108506, to Kazuo Takayama and Kei Sato); AMED Research Program on HIV/AIDS (JP22fk0410055, to Terumasa Ikeda; and JP22fk0410039, to Kei Sato); AMED Japan Program for Infectious Diseases Research and Infrastructure (JP22wm0125008 to Keita Matsuno); AMED CREST (JP21gm1610005, to Kazuo Takayama; JP22gm1610008, to Takasuke Fukuhara; JST PRESTO (JPMJPR22R1, to Jumpei Ito); JST CREST (JPMJCR20H4, to Kei Sato); JSPS KAKENHI Fund for the Promotion of Joint International Research (International Leading Research) (JP23K20041, to G2P-Japan Consortium, Keita Matsuno, Takasuke Fukuhara and Kei Sato); JST SPRING (JPMJSP2108 to Shigeru Fujita); JSPS KAKENHI Grant-in-Aid for Scientific Research C (22K07103, to Terumasa Ikeda); JSPS KAKENHI Grant-in-Aid for Scientific Research B (21H02736, to Takasuke Fukuhara); JSPS KAKENHI Grant-in-Aid for Early-Career Scientists (22K16375, to Hesham Nasser; 20K15767, to Jumpei Ito); JSPS Core-to-Core Program (A. Advanced Research Networks) (JPJSCCA20190008, to Kei Sato); JSPS Research Fellow DC2 (22J11578, to Keiya Uriu); JSPS Research Fellow DC1 (23KJ0710, to Yusuke Kosugi); JSPS Leading Initiative for Excellent Young Researchers (LEADER) (to Terumasa Ikeda); World-leading Innovative and Smart Education (WISE) Program 1801 from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) (to Naganori Nao); Ministry of Health, Labour and Welfare (MHLW) under grant 23HA2010 (to Naganori Nao and Keita Matsuno); The Cooperative Research Program (Joint Usage/Research Center program) of Institute for Life and Medical Sciences, Kyoto University (to Kei Sato); International Joint Research Project of the Institute of Medical Science, the University of Tokyo (to Terumasa Ikeda and Takasuke Fukuhara); The Tokyo Biochemical Research Foundation (to Kei Sato); Takeda Science Foundation (to Terumasa Ikeda and Takasuke Fukuhara); Mochida Memorial Foundation for Medical and Pharmaceutical Research (to Terumasa Ikeda); The Naito Foundation (to Terumasa Ikeda); Hokuto Foundation for Bioscience (to Tomokazu Tamura); Hirose Foundation (to Tomokazu Tamura); and Mitsubishi Foundation (to Kei Sato).", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shigeru", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Arnon", "last_name": "Plianchaisuk", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Deguchi", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Naganori", "last_name": "Nao", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Hesham", "last_name": "Nasser", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yukie", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Rigel", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Kida", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Keiya", "last_name": "Uriu", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Yamasoba", "name": null }, { "creator_type": "author", "first_name": "Ziyi", "last_name": "Guo", "name": null }, { "creator_type": "author", "first_name": "Alfredo A. Jr", "last_name": "Hinay", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kosugi", "name": null }, { "creator_type": "author", "first_name": "Luo", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Lin", "last_name": "Pan", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Kaku", "name": null }, { "creator_type": "author", "first_name": "Hin", "last_name": "Chu", "name": null }, { "creator_type": "author", "first_name": "Flora", "last_name": "Donati", "name": null }, { "creator_type": "author", "first_name": "Sarah", "last_name": "Temmam", "name": null }, { "creator_type": "author", "first_name": "Marc", "last_name": "Eloit", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tetsuharu", "last_name": "Nagamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Asakura", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sadamasu", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Terumasa", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Matsuno", "name": null }, { "creator_type": "author", "first_name": "Takasuke", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ebiom.2024.105181" }, "pmcid": { "normalized": "PMC11215962" }, "pmid": { "normalized": "38838469" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chiroptera", "descriptor_ui": "D002685", "major_topic": true }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Cricetinae", "descriptor_ui": "D006224", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Furin", "descriptor_ui": "D045683", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true }, { "descriptor": "Spike Glycoprotein, Coronavirus", "descriptor_ui": "D064370", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jun", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "105181", "proceedings_title": null, "publisher": "", "title": "EBioMedicine", "volume": "104", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Virological characteristics of a SARS-CoV-2-related bat coronavirus, BANAL-20-236.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alternatives to ketamine without psychotomimetic properties for the treatment of depression have attracted much attention. Here, we examined the anti-despair and anti-anhedonia effects of the ketamine metabolites (S)-norketamine ((S)-NK), (R)-NK, (2S,6S)-hydroxynorketamine, and (2R,6R)-hydroxynorketamine in a mouse model of depression induced by social isolation. All ketamine metabolites examined had acute (30 min after administration) anti-despair-like effects in the forced swim test, but only (S)-NK showed a long-lasting (1 week) effect. Additionally, only (S)-NK improved reduced motivation both 30 min and 24 h after injection in the female encounter test. These results suggest that (S)-NK has potent and long-lasting antidepressant-like effects.", "classifications": [ { "id": "18H05416", "label": "18H05416", "researcher": "Hitoshi Hashimoto", "type": "grant" }, { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Rei", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Momoko", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphs.2023.12.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38246730" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Ketamine", "descriptor_ui": "D007649", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Social Isolation", "descriptor_ui": "D012934", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "72-76", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "154", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Long-lasting anti-despair and anti-anhedonia effects of (S)-norketamine in social isolation-reared mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vasoactive intestinal peptide (VIP) receptor 2 (VIPR2) is a G protein-coupled receptor that binds to Galphas, Galphai, and Galphaq proteins to regulate various downstream signaling molecules, such as protein kinase A (PKA), phosphatidylinositol 3-kinase (PI3K), and phospholipase C. In this study, we examined the role of VIPR2 in cell cycle progression. KS-133, a newly developed VIPR2-selective antagonist peptide, attenuated VIP-induced cell proliferation in MCF-7 cells. The percentage of cells in the S-M phase was decreased in MCF-7 cells treated with KS-133. KS-133 in the presence of VIP decreased the phosphorylation of extracellular signal-regulated kinase (ERK), AKT, and glycogen synthase kinase-3beta (GSK3beta), resulting in a decrease in cyclin D1 levels. In MCF-7 cells stably-expressing VIPR2, KS-133 decreased PI3K activity and cAMP levels. Treatment with the ERK-specific kinase (MEK) inhibitor U0126 and the class I PI3K inhibitor ZSTK474 decreased the percentage of cells in the S phase. KS-133 reduced the percentage of cells in the S phase more than treatment with U0126 or ZSTK474 alone and did not affect the effect of the mixture of these inhibitors. Our findings suggest that VIPR2 signaling regulates cyclin D1 levels through the cAMP/PKA/ERK and PI3K/AKT/GSK3beta pathways, and mediates the G1/S transition to control cell proliferation.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Ami", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Kaede", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Teru", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Souichi", "last_name": "Yanamoto", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Tanimoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphs.2024.01.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38395514" } }, "mesh": [ { "descriptor": "Butadienes", "descriptor_ui": "D002070", "major_topic": true }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cyclin D1", "descriptor_ui": "D019938", "major_topic": true }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Glycogen Synthase Kinase 3 beta", "descriptor_ui": "D000071679", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MCF-7 Cells", "descriptor_ui": "D061986", "major_topic": false }, { "descriptor": "Nitriles", "descriptor_ui": "D009570", "major_topic": true }, { "descriptor": "Peptides, Cyclic", "descriptor_ui": "D010456", "major_topic": true }, { "descriptor": "Phosphatidylinositol 3-Kinase", "descriptor_ui": "D058539", "major_topic": false }, { "descriptor": "Phosphatidylinositol 3-Kinases", "descriptor_ui": "D019869", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": true }, { "descriptor": "Receptors, Vasoactive Intestinal Peptide, Type II", "descriptor_ui": "D051239", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "139-147", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "154", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Blockade of vasoactive intestinal peptide receptor 2 (VIPR2) signaling suppresses cyclin D1-dependent cell-cycle progression in MCF-7 cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Food shortages due to population growth and climate change are expected to occur in the near future as a problem that urgently requires solutions. Conventional breeding techniques, notably crossbreeding and mutation breeding, are known for being inefficient and time-consuming in obtaining seeds and seedlings with desired traits. Thus, there is an urgent need for novel methods for efficient plant breeding. Breeding by genome editing is receiving substantial attention because it can efficiently modify the target gene to obtain desired traits compared with conventional methods. Among the programmable sequence-specific nucleases that have been developed for genome editing, CRISPR-Cas12a and CRISPR-MAD7 nucleases are becoming more broadly adopted for the application of genome editing in grains, vegetables and fruits. Additionally, ST8, an improved variant of MAD7, has been developed to enhance genome editing efficiency and has potential for application to breeding of crops.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shunya", "last_name": "Hozumi", "name": null }, { "creator_type": "author", "first_name": "Yi-Chen", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Sawatsubashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1270/jsbbs.23049" }, "pmcid": { "normalized": "PMC11375424" }, "pmid": { "normalized": "39246434" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Mar", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "22-31", "proceedings_title": null, "publisher": "", "title": "Breeding science", "volume": "74", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Cas12a and MAD7, genome editing tools for breeding.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "It is expected but unknown whether machine-learning models can outperform regression models, such as a logistic regression (LR) model, especially when the number and types of predictor variables increase in electronic health records (EHRs). We aimed to compare the predictive performance of gradient-boosted decision tree (GBDT), random forest (RF), deep neural network (DNN), and LR with the least absolute shrinkage and selection operator (LR-LASSO) for unplanned readmission. We used EHRs of patients discharged alive from 38 hospitals in 2015-2017 for derivation and in 2018 for validation, including basic characteristics, diagnosis, surgery, procedure, and drug codes, and blood-test results. The outcome was 30-day unplanned readmission. We created six patterns of data tables having different numbers of binary variables (that >/=5% or >/=1% of patients or >/=10 patients had) with and without blood-test results. For each pattern of data tables, we used the derivation data to establish the machine-learning and LR models, and used the validation data to evaluate the performance of each model. The incidence of outcome was 6.8% (23,108/339,513 discharges) and 6.4% (7,507/118,074 discharges) in the derivation and validation datasets, respectively. For the first data table with the smallest number of variables (102 variables that >/=5% of patients had, without blood-test results), the c-statistic was highest for GBDT (0.740), followed by RF (0.734), LR-LASSO (0.720), and DNN (0.664). For the last data table with the largest number of variables (1543 variables that >/=10 patients had, including blood-test results), the c-statistic was highest for GBDT (0.764), followed by LR-LASSO (0.755), RF (0.751), and DNN (0.720), suggesting that the difference between GBDT and LR-LASSO was small and their 95% confidence intervals overlapped. In conclusion, GBDT generally outperformed LR-LASSO to predict unplanned readmission, but the difference of c-statistic became smaller as the number of variables was increased and blood-test results were used.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masao", "last_name": "Iwagami", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Inokuchi", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Tomohide", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Kuno", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Nobuaki", "last_name": "Michihata", "name": null }, { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Shinozaki", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Sun", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Komiyama", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Toshikazu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Nanako", "last_name": "Tamiya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pdig.0000578" }, "pmcid": { "normalized": "PMC11335098" }, "pmid": { "normalized": "39163277" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "e0000578", "proceedings_title": null, "publisher": "", "title": "PLOS digital health", "volume": "3", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparison of machine-learning and logistic regression models for prediction of 30-day unplanned readmission in electronic health records: A development and validation study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bacteria often exist and function as a community, known as the bacterial microbiota, which consists of vast numbers of bacteria belonging to many bacterial species (taxa). Characterizing the bacterial microbiota needs high-throughput approaches that enable the identification and quantification of many bacterial cells, and such approaches have been under development for more than 30 years. In this review, we describe the history of high-throughput technologies based on 16S ribosomal RNA (rRNA) gene-amplicon sequencing for the characterization of bacterial microbiotas. Then, we summarize the features and applications of current 16S rRNA gene-amplicon sequencing approaches, including a recent achievement that enables the identification of individual cells with single-base accuracy for 16S rRNA genes and the quantification of many identified cells. Furthermore, we present the prospects for further technical development, including the combined use of high-throughput methods and other informative analyses, such as whole-genome sequencing in the common unit of the cell, which enables bacterial microbiota characterization based on both the number of cells and their functions.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Jianshi", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Xiongduo", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/imo2.9" }, "pmcid": { "normalized": "PMC12806536" }, "pmid": { "normalized": "41675542" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Sep", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "e9", "proceedings_title": null, "publisher": "", "title": "iMetaOmics", "volume": "1", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Long journey of 16S rRNA-amplicon sequencing toward cell-based functional bacterial microbiota characterization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "As we learned during the COVID-19 pandemic, vaccines are one of the most important tools in infectious disease control. To date, an unprecedentedly large volume of high-quality data on COVID-19 vaccinations have been accumulated. For preparedness in future pandemics beyond COVID-19, these valuable datasets should be analyzed to best shape an effective vaccination strategy. We are collecting longitudinal data from a community-based cohort in Fukushima, Japan, that consists of 2,407 individuals who underwent serum sampling two or three times after a two-dose vaccination with either BNT162b2 or mRNA-1273. Using the individually reconstructed time courses of the vaccine-elicited antibody response based on mathematical modeling, we first identified basic demographic and health information that contributed to the main features of the antibody dynamics, i.e., the peak, the duration, and the area under the curve. We showed that these three features of antibody dynamics were partially explained by underlying medical conditions, adverse reactions to vaccinations, and medications, consistent with the findings of previous studies. We then applied to these factors a recently proposed computational method to optimally fit an \"antibody score\", which resulted in an integer-based score that can be used as a basis for identifying individuals with higher or lower antibody titers from basic demographic and health information. The score can be easily calculated by individuals themselves or by medical practitioners. Although the sensitivity of this score is currently not very high, in the future, as more data become available, it has the potential to identify vulnerable populations and encourage them to get booster vaccinations. Our mathematical model can be extended to any kind of vaccination and therefore can form a basis for policy decisions regarding the distribution of booster vaccines to strengthen immunity in future pandemics.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yurie", "last_name": "Kobashi", "name": null }, { "creator_type": "author", "first_name": "Kwang Su", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Hyeongki", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Tani", "name": null }, { "creator_type": "author", "first_name": "Yuzo", "last_name": "Shimazu", "name": null }, { "creator_type": "author", "first_name": "Tianchen", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Omata", "name": null }, { "creator_type": "author", "first_name": "Moe", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Yoshika", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Senoo", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Morihito", "last_name": "Takita", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Yudai", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Yong Dam", "last_name": "Jeong", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Tatematsu", "name": null }, { "creator_type": "author", "first_name": "Marwa", "last_name": "Akao", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shoya", "last_name": "Iwanami", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Wakui", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Kodama", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Shibuya", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Iwami", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Tsubokura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pdig.0000497" }, "pmcid": { "normalized": "PMC11068210" }, "pmid": { "normalized": "38701055" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "e0000497", "proceedings_title": null, "publisher": "", "title": "PLOS digital health", "volume": "3", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Modeling and predicting individual variation in COVID-19 vaccine-elicited antibody response in the general population.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The endosomal-lysosomal system represents a crucial degradation pathway for various extracellular substances, and its dysfunction is linked to cardiovascular and neurodegenerative diseases. This degradation process involves multiple steps: (1) the uptake of extracellular molecules, (2) transport of cargos to lysosomes, and (3) digestion by lysosomal enzymes. While cellular uptake and lysosomal function are reportedly regulated by the mTORC1-TFEB axis, the key regulatory signal for cargo transport remains unclear. Notably, our previous study discovered that isorhamnetin, a dietary flavonoid, enhances endosomal-lysosomal proteolysis in the J774.1 cell line independently of the mTORC1-TFEB axis. This finding suggests the involvement of another signal in the mechanism of isorhamnetin. This study analyzes the molecular mechanism of isorhamnetin using transcriptome analysis and reveals that the transcription factor GATA3 plays a critical role in enhanced endosomal-lysosomal degradation. Our data also demonstrate that mTORC2 regulates GATA3 nuclear translocation, and the mTORC2-GATA3 axis alters endosomal formation and maturation, facilitating the efficient transport of cargos to lysosomes. This study suggests that the mTORC2-GATA3 axis might be a novel target for the degradation of abnormal substances.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Maiko", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Kohta", "last_name": "Ohnishi", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Erika", "last_name": "Harumoto", "name": null }, { "creator_type": "author", "first_name": "Teppei", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Aika", "last_name": "Ohnishi", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Ohminami", "name": null }, { "creator_type": "author", "first_name": "Hisami", "last_name": "Yamanaka-Okumura", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Itakura", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Shigenobu", "last_name": "Yonemura", "name": null }, { "creator_type": "author", "first_name": "Taichi", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Taketani", "name": null } ], "identifiers": { "doi": { "normalized": "10.3164/jcbn.24-22" }, "pmcid": { "normalized": "PMC11273268" }, "pmid": { "normalized": "39070537" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Jul", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "24-32", "proceedings_title": null, "publisher": "", "title": "Journal of clinical biochemistry and nutrition", "volume": "75", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Modulations of the mTORC2-GATA3 axis by an isorhamnetin activated endosomal-lysosomal system of the J774.1 macrophage-like cell line.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The effectiveness of negative-pressure wound therapy (NPWT) in skin graft fixation has been demonstrated in several clinical studies. However, in vitro and in vivo studies on skin graft fixation with NPWT have been scarce. In this in vivo study, we aimed to determine whether NPWT fixation enhances skin graft survival and how it contributes to improving skin graft survival biologically. MATERIALS AND METHODS: We harvested skin from the bilateral abdominal wall of 88 mice after anesthetizing them. Full-thickness skin grafts (FTSGs) were performed on contralateral harvest sites, and grafts were fixed using NPWT (continuous and intermittent modes), conventional compression methods, and wrapping with polyurethane foam as a control group. On days 5 and 10 of grafting, the survival rates of the FTSGs were evaluated. Immunohistopathological analysis and measurement of the expression levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2), and epidermal growth factor (EGF) were performed. RESULTS: The survival rates of FTSG in the continuous NPWT group were significantly higher than those in the other groups. The number of capillaries in the dermis was significantly higher in the continuous NPWT group than in the other groups. In the wound bed, VEGF levels were significantly higher in both NPWT groups than in the other groups. CONCLUSION: Continuous NPWT increases the survival rate of FTSGs and shortens the duration of skin graft survival.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masato", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Toshifumi", "last_name": "Yamashiro", "name": null }, { "creator_type": "author", "first_name": "Yoshine", "last_name": "Mayumi", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Azuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/srt.13865" }, "pmcid": { "normalized": "PMC11259545" }, "pmid": { "normalized": "39031918" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Epidermal Growth Factor", "descriptor_ui": "D004815", "major_topic": false }, { "descriptor": "Fibroblast Growth Factor 2", "descriptor_ui": "D016222", "major_topic": false }, { "descriptor": "Graft Survival", "descriptor_ui": "D006085", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Negative-Pressure Wound Therapy", "descriptor_ui": "D054843", "major_topic": true }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Skin Transplantation", "descriptor_ui": "D016038", "major_topic": true }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor A", "descriptor_ui": "D042461", "major_topic": false }, { "descriptor": "Wound Healing", "descriptor_ui": "D014945", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "e13865", "proceedings_title": null, "publisher": "", "title": "Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI)", "volume": "30", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Continuous negative-pressure wound therapy improves the survival rate of skin grafts and shortens the time required for skin graft survival.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: EGFR tyrosine kinase inhibitors have been the standard treatment for patients with NSCLC who have sensitive EGFR mutations. This study revealed final analysis survival data, biomarkers, and resistance mechanisms of osimertinib plus bevacizumab or osimertinib monotherapy in previously untreated patients with advanced EGFR-positive nonsquamous NSCLC. METHODS: We previously reported the primary results of a randomized, open-label, phase 2 study comparing osimertinib plus bevacizumab with osimertinib monotherapy for this population. In this exploratory analysis using tissue and plasma samples, we evaluated gene profiles at baseline and disease progression or the last dose using targeted deep sequencing. RESULTS: The median progression-free survival (PFS) by the blinded independent central reviewer was 22.1 months for the osimertinib plus bevacizumab arm and 20.2 months for the osimertinib arm (hazard ratio [HR] = 0.864, 95% confidence interval [CI]: 0.549-1.359). The 3-year overall survival was not different between the two arms (osimertinib plus bevacizumab: 57.1%; osimertinib monotherapy: 65.0%; HR 1.271, 95% CI: 0.727-2.223). A total of 94 patients had assessable plasma samples at baseline, and 40 had assessable pretreatment tissue samples. EGFR mutations (76.6%) and TP53 mutations (44.7%) were detected in plasma samples at baseline. In patients with plasma TP53 mutations (n = 42), the median PFS by blinded independent central reviewer was 19.8 months for the osimertinib plus bevacizumab arm and 20.2 months for the osimertinib arm (HR = 1.107, 95% CI: 0.534-2.297). CONCLUSIONS: There was also no significant difference in the PFS between the two arms, even in patients with TP53 mutations.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hirotsugu", "last_name": "Kenmotsu", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Terufumi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Kirita", "name": null }, { "creator_type": "author", "first_name": "Yasuto", "last_name": "Yoneshima", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Teraoka", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Toyozawa", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtocrr.2024.100716" }, "pmcid": { "normalized": "PMC11470244" }, "pmid": { "normalized": "39399795" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "100716", "proceedings_title": null, "publisher": "", "title": "JTO clinical and research reports", "volume": "5", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Final Analysis Data and Exploratory Biomarker Analysis of a Randomized Phase 2 Study of Osimertinib Plus Bevacizumab Versus Osimertinib Monotherapy for Untreated Patients With Nonsquamous NSCLC Harboring EGFR Mutations: The WJOG9717L Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In Kyoto IUPAB Congress, a Japanese bimonthly magazine of biophysics, Seibutsu-Butsuri, organized a round table, with an online English journal of Biophysics and Physicobiology, to discuss the possible future of biophysics by gathering seven prominent researchers who participated in the congress. The content will be published both in Japanese and English in the two journals, which is expected to stimulate our next generation researchers in biophysics over the world.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12551-024-01241-2" }, "pmcid": { "normalized": "PMC11604864" }, "pmid": { "normalized": "39618784" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Oct", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "509-510", "proceedings_title": null, "publisher": "", "title": "Biophysical reviews", "volume": "16", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "An attempt of Seibutsu-Butsuri in Kyoto IUPAB Congress 2024.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Melanin-concentrating hormone-producing neurons (MCH neurons), found mainly in the lateral hypothalamus and surrounding areas, play essential roles in various brain functions, including sleep and wakefulness, reward, metabolism, learning, and memory. These neurons coexpress several neurotransmitters and act as glutamatergic neurons. The contribution of glutamate from MCH neurons to memory- and metabolism-related functions has not been fully investigated. In a mouse model, we conditionally knocked out Slc17a6 gene, which encodes for vesicular glutamate transporter 2 (vGlut2), in the MCH neurons exclusively by using two different methods: the Cre recombinase/loxP system and in vivo genome editing using CRISPR/Cas9. Then, we evaluated several aspects of memory and measured metabolic rates using indirect calorimetry. We found that mice with MCH neuron-exclusive vGlut2 ablation had higher discrimination ratios between novel and familiar stimuli for novel object recognition, object location, and three-chamber tests. In contrast, there was no significant change in body weight, food intake, oxygen consumption, respiratory quotient, or locomotor activity. These findings suggest that glutamatergic signaling from MCH neurons is required to regulate memory, but its role in regulating metabolic rate is negligible.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Xuan Thang", "last_name": "Pham", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Yasutaka", "last_name": "Mukai", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Kenji F.", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Ohmura", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Wake", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pnasnexus/pgae275" }, "pmcid": { "normalized": "PMC11259978" }, "pmid": { "normalized": "39035036" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "pgae275", "proceedings_title": null, "publisher": "", "title": "PNAS nexus", "volume": "3", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Glutamatergic signaling from melanin-concentrating hormone-producing neurons: A requirement for memory regulation, but not for metabolism control.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tau is typically an axonal protein, but in neurons of brains affected by Alzheimer's disease (AD), aggregation of hyperphosphorylated tau in the somatodendritic compartment causes neuronal death. We have previously demonstrated that tau mRNA is transported within dendrites and undergoes immediate translation and hyperphosphorylation of AD epitopes in response to NMDA receptor stimulation. Although this explains the emergence of hyperphosphorylated tau in dendrites, the relationship between tau hyperphosphorylation and aggregation is not well understood. In this study, we found that recombinant highly phosphorylated tau purified from NG108-15 rodent neuroblastoma/glioma cells transfected with both tau and GSK3beta expression vectors bound calcium ions and formed sarkosyl-insoluble aggregates. In addition, thioflavin T analysis revealed that this highly phosphorylated tau tended to aggregate on its own, further facilitated by calcium ions. When NG108-15 cells expressing the highly phosphorylated tau were treated with calcium ionophore, sarkosyl-insoluble tau was generated. Interestingly, these cells exhibited resistance to both calcium ionophore-induced cytotoxicity and glutamate-induced excitotoxicity. We further found that sarkosyl-insoluble phosphorylated tau was increased in cultured hippocampal neurons due to glutamate-induced hyperactivity. Our data suggest that hyperphosphorylated tau synthesized in response to NMDA receptor stimulation contributes to regulation of neuronal activity by binding calcium ions, but that this calcium binding may cause tau to adopt an aggregated form.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Toru", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Sachiyo", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrep.2024.101887" }, "pmcid": { "normalized": "PMC11626071" }, "pmid": { "normalized": "39655264" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Dec", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "101887", "proceedings_title": null, "publisher": "", "title": "Biochemistry and biophysics reports", "volume": "40", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Effect of calcium ions on the aggregation of highly phosphorylated tau.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of lung cancer associated with poor prognosis and resistance to conventional chemotherapy. Immune checkpoint inhibitors (ICIs), alone or in combination with chemotherapy, were found to have clinical benefits in PSC in recent studies. Nevertheless, because these studies included a small number of patients owing to disease rarity, larger studies are needed to evaluate the effectiveness and safety of ICI-based therapy for PSC. METHODS: This multicenter retrospective study evaluated patients with ICI-naive advanced or metastatic PSC who were treated with ICI-based therapy at 25 hospitals in Japan. RESULTS: A total of 124 patients were evaluated. The overall response rate, median progression-free survival (PFS), and median overall survival (OS) were 59.0%, 10.5 months, and 32.8 months, respectively. The PFS and OS rates at 24 months were 35.3% and 51.5%, respectively. Programmed death-ligand 1 expression, concomitant chemotherapy, and the treatment line were not significantly associated with PFS or OS. Immune-related adverse events (irAEs) were observed in 70 patients (56.5%), including 30 (24.2%) with grade 3 to 5 events. Patients with mild irAEs (grades 1-2) had longer PFS and OS than did those with severe (grades 3-5) or no irAEs. In a multivariate analysis, any-grade irAEs and the absence of liver metastases were independently associated with PFS, whereas any-grade irAEs and Eastern Cooperative Oncology Group performance status less than or equal to 1 were independently associated with OS. CONCLUSIONS: ICI-based therapy was found to have promising effectiveness in patients with advanced or metastatic PSC, regardless of programmed death-ligand 1 expression, concomitant chemotherapy, or treatment line.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hazama", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Nakahama", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kodama", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yoshimasa", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Takahama", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Oizumi", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Namba", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Hiroshige", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Tsuya", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Negi", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Michihito", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Motoko", "last_name": "Tachihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtocrr.2023.100613" }, "pmcid": { "normalized": "PMC10788284" }, "pmid": { "normalized": "38229769" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "100613", "proceedings_title": null, "publisher": "", "title": "JTO clinical and research reports", "volume": "5", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Effectiveness and Safety of Immune Checkpoint Inhibitors Alone or in Combination With Chemotherapy in Pulmonary Sarcomatoid Carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Significance: We developed a high-speed optical-resolution photoacoustic microscopy (OR-PAM) system using a high-repetition-rate supercontinuum (SC) light source and a two-axes Galvano scanner. The OR-PAM system enabled real-time imaging of optical absorbers inside biological tissues with excellent excitation wavelength tunability. Aim: In the near-infrared (NIR) wavelength range, high-speed OR-PAM faces limitations due to the lack of wavelength-tunable light sources. Our study aimed to enable high-speed OR-PAM imaging of various optical absorbers, including NIR contrast agents, and validate the performance of high-speed OR-PAM in the detection of circulating tumor cells (CTCs). Approach: A high-repetition nanosecond pulsed SC light source was used for OR-PAM. The excitation wavelength was adjusted by bandpass filtering of broadband light pulses produced by an SC light source. Phantom and in vivo experiments were performed to detect tumor cells stained with an NIR contrast agent within flowing blood samples. Results: The newly developed high-speed OR-PAM successfully detected stained cells both in the phantom and in vivo. The phantom experiment confirmed the correlation between the tumor cell detection rate and tumor cell concentration in the blood sample. Conclusions: The high-speed OR-PAM effectively detected stained tumor cells. Combining high-speed OR-PAM with molecular probes that stain tumor cells in vivo enables in vivo CTC detection.", "classifications": [ { "id": "19H05436", "label": "19H05436", "researcher": "Miya Ishihara", "type": "grant" }, { "id": "21H00445", "label": "21H00445", "researcher": "Miya Ishihara", "type": "grant" }, { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Tachi", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Manami", "last_name": "Miyashita", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1117/1.jbo.29.s1.s11527" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38464883" } }, "mesh": [ { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Optical Devices", "descriptor_ui": "D055096", "major_topic": true }, { "descriptor": "Phantoms, Imaging", "descriptor_ui": "D019047", "major_topic": false }, { "descriptor": "Photoacoustic Techniques", "descriptor_ui": "D061088", "major_topic": true }, { "descriptor": "Spectrum Analysis", "descriptor_ui": "D013057", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jan", "date_precision": "unknown", "issue": "Suppl 1", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of Biomedical Optics", "volume": "29", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Photoacoustic microscopy for real-time monitoring of near-infrared optical absorbers inside biological tissue.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Platyhelminthes are a phylum of simple bilaterian invertebrates with prototypic body systems. Compared with non-bilaterians such as cnidarians, the bilaterians are likely to exhibit integrated free-moving behaviors, which require a concentrated nervous system \"brain\" rather than the distributed nervous system of radiatans. Marine flatworms have an early cephalized 'central' nervous system compared not only with non-bilaterians but also with parasitic flatworms or freshwater planarians. In this study, we used the marine flatworm Stylochoplana pusilla as an excellent model organism in Platyhelminthes because of the early cephalized central nervous system. Here, we investigated the three-dimensional structures of the flatworm central nervous system by the use of X-ray micro-computed tomography (micro-CT) in a synchrotron radiation facility. We found that the obtained tomographic images were sufficient to discriminate some characteristic structures of the nervous system, including nerve cords around the cephalic ganglion, mushroom body-like structures, and putative optic nerves forming an optic commissure-like structure. Through the micro-CT imaging, we could obtain undistorted serial section images, permitting us to visualize precise spatial relationships of neuronal subpopulations and nerve tracts. 3-D micro-CT is very effective in the volume analysis of the nervous system at the cellular level; the methodology is straightforward and could be applied to many other non-model organisms.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takanori", "last_name": "Ikenaga", "name": null }, { "creator_type": "author", "first_name": "Aoshi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Uesugi", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Maezawa", "name": null }, { "creator_type": "author", "first_name": "Norito", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.2108/zs230082" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38809867" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Central Nervous System", "descriptor_ui": "D002490", "major_topic": true }, { "descriptor": "Platyhelminths", "descriptor_ui": "D010986", "major_topic": true }, { "descriptor": "X-Ray Microtomography", "descriptor_ui": "D055114", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jun", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "281-289", "proceedings_title": null, "publisher": "", "title": "Zoological science", "volume": "41", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Volume X-Ray Micro-Computed Tomography Analysis of the Early Cephalized Central Nervous System in a Marine Flatworm, Stylochoplana pusilla.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Endometriosis, a common gynecological disorder characterized by the growth of endometrial gland and stroma outside the uterus, causes several symptoms such as dysmenorrhea, hypermenorrhea, and chronic abdominal pain. 17beta estradiol (E2) stimulates the growth of endometriotic lesions. Although estetrol (E4), produced by human fetal liver, is also a natural estrogen, it may have the opposite effects on endometriotic cells. We investigated different effects of E4 and E2 on the invasion and migration of immortalized human endometrial stromal cells (HESCs) and evaluated whether E4 affects the expression of Wiskott-Aldrich syndrome protein (WASP) family member 1 (WASF-1). We measured the invasion of HESCs by a Matrigel chamber assay. Cell migration was measured by wound healing assay and cell tracking analysis. The expression of WASF-1 was confirmed by independent real-time PCR analysis. Transfection of cells with siRNAs was carried out to knock down the expression of WASF-1 in HESCs. E4 significantly inhibited E2-induced invasion and migration of HESCs. WASF-1 was found to be a potential mediator based on metastasis PCR array. WASF-1 was upregulated by E2 and downregulated by E4. Knockdown of WASF-1 inhibited migration. Our results suggest that E4 may inhibit E2-induced growth of endometriotic lesions. Downregulation of WASF-1 is involved in the inhibitory effects of E4 on migration. The use of E4 combined with progestins as combined oral contraceptives may cause endometriotic lesions to regress in women with endometriosis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihiko", "last_name": "Wakatsuki", "name": null }, { "creator_type": "author", "first_name": "Yinzhi", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Shiori", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Umezawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1507/endocrj.ej23-0397" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38171884" } }, "mesh": [ { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Endometriosis", "descriptor_ui": "D004715", "major_topic": true }, { "descriptor": "Endometrium", "descriptor_ui": "D004717", "major_topic": false }, { "descriptor": "Estetrol", "descriptor_ui": "D004953", "major_topic": true }, { "descriptor": "Estradiol", "descriptor_ui": "D004958", "major_topic": false }, { "descriptor": "Estrogens", "descriptor_ui": "D004967", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Stromal Cells", "descriptor_ui": "D017154", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 28", "date_precision": "day", "issue": "", "normalized_date": "2023-12-28", "pages": "", "proceedings_title": null, "publisher": "", "title": "Endocrine journal", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Inhibitory effects of estetrol on the invasion and migration of immortalized human endometrial stromal cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Infectious virus shedding from individuals infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is used to estimate human-to-human transmission risk. Control of SARS-CoV-2 transmission requires identifying the immune correlates that protect infectious virus shedding. Mucosal immunity prevents infection by SARS-CoV-2, which replicates in the respiratory epithelium and spreads rapidly to other hosts. However, whether mucosal immunity prevents the shedding of the infectious virus in SARS-CoV-2-infected individuals is unknown. We examined the relationship between viral RNA shedding dynamics, duration of infectious virus shedding, and mucosal antibody responses during SARS-CoV-2 infection. Anti-spike secretory IgA antibodies (S-IgA) reduced viral RNA load and infectivity more than anti-spike IgG/IgA antibodies in infected nasopharyngeal samples. Compared with the IgG/IgA response, the anti-spike S-IgA post-infection responses affected the viral RNA shedding dynamics and predicted the duration of infectious virus shedding regardless of the immune history. These findings highlight the importance of anti-spike S-IgA responses in individuals infected with SARS-CoV-2 for preventing infectious virus shedding and SARS-CoV-2 transmission. Developing medical countermeasures to shorten S-IgA response time may help control human-to-human transmission of SARS-CoV-2 infection and prevent future respiratory virus pandemics.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Sho", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Takara", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Hyeongki", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Kanno", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Ozono", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yuuki", "last_name": "Tsuchihashi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ishikane", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Arashiro", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Ainai", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Harutaka", "last_name": "Katano", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Tobiume", "name": null }, { "creator_type": "author", "first_name": "Kenzo", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Tsuguto", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Michiyo", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Igari", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kazutoshi", "last_name": "Hiyama", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Shindou", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Fukumi", "last_name": "Nakamura-Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hase", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Yamato", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Nozaki", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Ohmagari", "name": null }, { "creator_type": "author", "first_name": "Motoi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Iwami", "name": null }, { "creator_type": "author", "first_name": "Tadaki", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2314808120" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38134196" } }, "mesh": [ { "descriptor": "Antibodies, Viral", "descriptor_ui": "D000914", "major_topic": false }, { "descriptor": "Antibody Formation", "descriptor_ui": "D000917", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoglobulin A", "descriptor_ui": "D007070", "major_topic": false }, { "descriptor": "Immunoglobulin A, Secretory", "descriptor_ui": "D007071", "major_topic": false }, { "descriptor": "Immunoglobulin G", "descriptor_ui": "D007074", "major_topic": false }, { "descriptor": "Reaction Time", "descriptor_ui": "D011930", "major_topic": false }, { "descriptor": "RNA, Viral", "descriptor_ui": "D012367", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false }, { "descriptor": "Virus Shedding", "descriptor_ui": "D017201", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 26", "date_precision": "day", "issue": "52", "normalized_date": "2023-12-26", "pages": "e2314808120", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "120", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Infectious virus shedding duration reflects secretory IgA antibody response latency after SARS-CoV-2 infection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To cope with seasonal environmental changes, organisms have evolved approximately 1-y endogenous circannual clocks. These circannual clocks regulate various physiological properties and behaviors such as reproduction, hibernation, migration, and molting, thus providing organisms with adaptive advantages. Although several hypotheses have been proposed, the genes that regulate circannual rhythms and the underlying mechanisms controlling long-term circannual clocks remain unknown in any organism. Here, we show a transcriptional program underlying the circannual clock in medaka fish (Oryzias latipes). We monitored the seasonal reproductive rhythms of medaka kept under natural outdoor conditions for 2 y. Linear regression analysis suggested that seasonal changes in reproductive activity were predominantly determined by an endogenous program. Medaka hypothalamic and pituitary transcriptomes were obtained monthly over 2 y and daily on all equinoxes and solstices. Analysis identified 3,341 seasonally oscillating genes and 1,381 daily oscillating genes. We then examined the existence of circannual rhythms in medaka via maintaining them under constant photoperiodic conditions. Medaka exhibited approximately 6-mo free-running circannual rhythms under constant conditions, and monthly transcriptomes under constant conditions identified 518 circannual genes. Gene ontology analysis of circannual genes highlighted the enrichment of genes related to cell proliferation and differentiation. Altogether, our findings support the \"histogenesis hypothesis\" that postulates the involvement of tissue remodeling in circannual time-keeping.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tomoya", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Tanikawa", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Okushi", "name": null }, { "creator_type": "author", "first_name": "Thoma", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shimmura", "name": null }, { "creator_type": "author", "first_name": "Michiyo", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Matsumiya", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Shinomiya", "name": null }, { "creator_type": "author", "first_name": "Ying-Jey", "last_name": "Guh", "name": null }, { "creator_type": "author", "first_name": "Junfeng", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Naruse", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kudoh", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Honda", "last_name": "Naoki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Atsushi J.", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2313514120" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38109538" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Gonads", "descriptor_ui": "D006066", "major_topic": false }, { "descriptor": "Oryzias", "descriptor_ui": "D009990", "major_topic": true }, { "descriptor": "Photoperiod", "descriptor_ui": "D017440", "major_topic": false }, { "descriptor": "Seasons", "descriptor_ui": "D012621", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 26", "date_precision": "day", "issue": "52", "normalized_date": "2023-12-26", "pages": "e2313514120", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "120", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "A transcriptional program underlying the circannual rhythms of gonadal development in medaka.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "DNA analysis in water samples is attracting attention in various fields. However, conventional methods for DNA analysis require a work-intensive and time-consuming sample pre-treatment. In this study, a simplified pre-treatment method for analyzing DNA in water samples was evaluated. The process consists of filtration, DNA extraction, and amplification, which can be achieved within a short time. In the filtration process, two types of filters, firstly a tissue paper (Kimwipe) and then a glass filter (GF/F), were used in sequence. The first large pore size filter enabled a reduction in filtration time by removing large particulate matter impurities present in river water matrix. Cells spiked into 1 L of river water were recovered at more than 90% within approximately 5 min filtration time. Also, DNA was extracted from the captured cells directly on the surface of the filter in only 5 min. Thus, DNA collection and extraction from a water sample can be completed within about 10 min. Furthermore, PCR amplification was performed directly from DNA-attached filter sections, which greatly reduced the number of required pre-treatment steps. Finally, we succeeded in establishing a simple and fast on-site pre-treatment system by using a hand-driven syringe filtration method. This pre-treatment system is expected to offer the possibility for the future establishment of a rapid and easy DNA analysis method applicable to various types of water samples.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mai", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kamo", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Siro", "last_name": "Simizu", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s44211-023-00482-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38142247" } }, "mesh": [ { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": true }, { "descriptor": "Filtration", "descriptor_ui": "D005374", "major_topic": false }, { "descriptor": "Fresh Water", "descriptor_ui": "D005618", "major_topic": true }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 23", "date_precision": "day", "issue": "", "normalized_date": "2023-12-23", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical sciences : the international journal of the Japan Society for Analytical Chemistry", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Simplified capture, extraction, and amplification of cellular DNA from water samples.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "RNA and DNA delivery technologies using lipid nanoparticles (LNPs) have advanced significantly, as demonstrated by their successful application in mRNA vaccines. To date, commercially available RNA therapeutics include Onpattro, a 21 bp siRNA, and mRNA vaccines comprising 4300 nucleotides for COVID-19. However, a significant challenge remains in achieving efficient transfection, as the size of the delivered RNA and DNA increases. In contrast to RNA transfection, plasmid DNA (pDNA) transfection requires multiple steps, including cellular uptake, endosomal escape, nuclear translocation, transcription, and translation. The low transfection efficiency of large pDNA is a critical limitation in the development of artificial cells and their cellular functionalization. Here, we introduce polymer-lipid hybrid nanoparticles designed for efficient, large-sized pDNA transfection. We demonstrated that LNPs loaded with positively charged pDNA-polycation core nanoparticles exhibited a 4-fold increase in transfection efficiency for 15 kbp pDNA compared with conventional LNPs, which encapsulate a negatively charged pDNA-polycation core. Based on assessments of the size and internal structure of the polymer-lipid nanoparticles as well as hemolysis and cellular uptake analysis, we propose a strategy to enhance large-sized pDNA transfection using LNPs. This approach holds promise for accelerating the in vivo delivery of large-sized pDNA and advancing the development of artificial cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Maeki", "name": null }, { "creator_type": "author", "first_name": "Shuya", "last_name": "Uno", "name": null }, { "creator_type": "author", "first_name": "Kaisei", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Hideyoshi", "last_name": "Harashima", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Tokeshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsami.3c14714" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38141015" } }, "mesh": [ { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Lipids", "descriptor_ui": "D008055", "major_topic": false }, { "descriptor": "Liposomes", "descriptor_ui": "D008081", "major_topic": true }, { "descriptor": "mRNA Vaccines", "descriptor_ui": "D000087503", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": true }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Polyelectrolytes", "descriptor_ui": "D000071228", "major_topic": true }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": true }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 23", "date_precision": "day", "issue": "", "normalized_date": "2023-12-23", "pages": "", "proceedings_title": null, "publisher": "", "title": "ACS applied materials & interfaces", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of Polymer-Lipid Hybrid Nanoparticles for Large-Sized Plasmid DNA Transfection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "3D cell cultures are indispensable in recapitulating in vivo environments. Among the many 3D culture methods, culturing adherent cells on hydrogel beads to form spheroid-like structures is a powerful strategy for maintaining high cell viability and functions in the adherent states. However, high-throughput, scalable technologies for 3D imaging of individual cells cultured on the hydrogel scaffolds are lacking. This study reports the development of a high throughput, scalable 3D imaging flow cytometry platform for analyzing spheroid models. This platform is realized by integrating a single objective fluorescence light-sheet microscopy with a microfluidic device that combines hydrodynamic and acoustofluidic focusing techniques. This integration enabled unprecedentedly high-throughput and scalable optofluidic 3D imaging, processing 1310 spheroids consisting of 28 117 cells min(-1) . The large dataset obtained enables precise quantification and comparison of the nuclear morphology of adhering and suspended cells, revealing that the adhering cells have smaller nuclei with less rounded surfaces. This platform's high throughput, robustness, and precision for analyzing the morphology of subcellular structures in 3D culture models hold promising potential for various biomedical analyses, including image-based phenotypic screening of drugs with spheroids or organoids.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Minato", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Miu", "last_name": "Tamamitsu", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Kirisako", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Goda", "name": null }, { "creator_type": "author", "first_name": "Xiaoyao", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/smtd.202301318" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38133483" } }, "mesh": [ { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Culture Techniques, Three Dimensional", "descriptor_ui": "D000087603", "major_topic": true }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": true }, { "descriptor": "High-Throughput Screening Assays", "descriptor_ui": "D057166", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogels", "descriptor_ui": "D020100", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": true }, { "descriptor": "Lab-On-A-Chip Devices", "descriptor_ui": "D056656", "major_topic": false }, { "descriptor": "Spheroids, Cellular", "descriptor_ui": "D018874", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Dec 22", "date_precision": "day", "issue": "", "normalized_date": "2023-12-22", "pages": "e2301318", "proceedings_title": null, "publisher": "", "title": "Small methods", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "High-Throughput 3D Imaging Flow Cytometry of Suspended Adherent 3D Cell Cultures.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Single-molecule enzyme activity assay is a platform that enables the analysis of enzyme activities at single proteoform level. The limitation of the targetable enzymes is the major drawback of the assay, but the general assay platform is reported to study single-molecule enzyme activities of esterases based on the coupled assay using thioesters as substrate analogues. The coupled assay is realized by developing highly water-soluble thiol-reacting probes based on phosphonate-substituted boron dipyrromethene (BODIPY). The system enables the detection of cholinesterase activities in blood samples at single-molecule level, and it is shown that the dissecting alterations of single-molecule esterase activities can serve as an informative platform for activity-based diagnosis.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Ukegawa", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Mayano", "last_name": "Minoda", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Iwasaka", "name": null }, { "creator_type": "author", "first_name": "Tadahaya", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kusuhara", "name": null }, { "creator_type": "author", "first_name": "Kazufumi", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Rikiya", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/advs.202306559" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38140707" } }, "mesh": [ { "descriptor": "Esterases", "descriptor_ui": "D004950", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Dec 22", "date_precision": "day", "issue": "", "normalized_date": "2023-12-22", "pages": "e2306559", "proceedings_title": null, "publisher": "", "title": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Thioester-Based Coupled Fluorogenic Assays in Microdevice for the Detection of Single-Molecule Enzyme Activities of Esterases with Specified Substrate Recognition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "IMPORTANCE: The combination of an antibody to programmed cell death-1 (PD-1) or to its ligand (PD-L1) with chemotherapy is the standard first-line treatment for metastatic non-small cell lung cancer (NSCLC). Bevacizumab is expected to enhance the efficacy not only of chemotherapy but also of PD-1/PD-L1 antibodies through blockade of vascular endothelial growth factor-mediated immunosuppression, but further data are needed to support this. OBJECTIVE: To evaluate the efficacy and safety of bevacizumab administered with platinum combination therapy and atezolizumab in patients with advanced nonsquamous NSCLC. DESIGN, SETTING, AND PARTICIPANTS: An open-label phase 3 randomized clinical trial was conducted at 37 hospitals in Japan. Patients with advanced nonsquamous NSCLC without genetic driver alterations or those with genetic driver alterations who had received treatment with at least 1 approved tyrosine kinase inhibitor were enrolled between January 20, 2019, and August 12, 2020. INTERVENTIONS: Patients were randomly assigned to receive either atezolizumab plus carboplatin with pemetrexed (APP) or atezolizumab, carboplatin plus pemetrexed, and bevacizumab (APPB). After 4 cycles of induction therapy, maintenance therapy with atezolizumab plus pemetrexed or with atezolizumab, pemetrexed, and bevacizumab was administered until evidence of disease progression, development of unacceptable toxic effects, or the elapse of 2 years from the initiation of protocol treatment. MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival (PFS) as assessed by blinded independent central review (BICR) in the intention-to-treat (ITT) population. RESULTS: A total of 412 patients were enrolled (273 men [66%]; median age, 67.0 [range, 24-89] years) and randomly assigned, with 205 in the APPB group and 206 in the APP group of the ITT population after exclusion of 1 patient for good clinical practice violation. The median BICR-assessed PFS was 9.6 months with APPB vs 7.7 months with APP (stratified hazard ratio [HR], 0.86; 95% CI, 0.70-1.07; 1-sided stratified log-rank test; P = .92). According to prespecified subgroup analysis of BICR-assessed PFS, an improved PFS with APPB vs APP was apparent specifically in driver oncogene-positive patients (median, 9.7 vs 5.8 months; stratified HR, 0.67; 95% CI, 0.46-0.98). Toxic effects related to bevacizumab were increased in the APPB group. CONCLUSIONS AND RELEVANCE: The findings of this trial did not show superiority of APPB over APP for patients with nonsquamous NSCLC; however, this regimen showed a similar tolerability and improved survival relative to APP in patients with driver oncogenes. TRIAL REGISTRATION: Japan Registry of Clinical Trials Identifier: jRCT2080224500.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshimasa", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Junji", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Daga", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Hataji", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Takehito", "last_name": "Shukuya", "name": null }, { "creator_type": "author", "first_name": "Haruhiro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Motoko", "last_name": "Tachihara", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Tsuya", "name": null }, { "creator_type": "author", "first_name": "Kazushige", "last_name": "Wakuda", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Yanagitani", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Morihito", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kozuki", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Taishi", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Isamu", "last_name": "Okamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1001/jamaoncol.2023.5258" }, "pmcid": { "normalized": "PMC10739077" }, "pmid": { "normalized": "38127362" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal, Humanized", "descriptor_ui": "D061067", "major_topic": true }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": false }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Bevacizumab", "descriptor_ui": "D000068258", "major_topic": false }, { "descriptor": "Carboplatin", "descriptor_ui": "D016190", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Pemetrexed", "descriptor_ui": "D000068437", "major_topic": false }, { "descriptor": "Platinum", "descriptor_ui": "D010984", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor A", "descriptor_ui": "D042461", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 21", "date_precision": "day", "issue": "", "normalized_date": "2023-12-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "JAMA oncology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Atezolizumab and Platinum Plus Pemetrexed With or Without Bevacizumab for Metastatic Nonsquamous Non-Small Cell Lung Cancer: A Phase 3 Randomized Clinical Trial.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pluripotent stem cell-based therapy for retinal degenerative diseases is a promising approach to restoring visual function. A clinical study using retinal organoid (RO) sheets was recently conducted in patients with retinitis pigmentosa. However, the graft preparation currently requires advanced skills to identify and excise suitable segments from the transplantable area of the limited number of suitable ROs. This remains a challenge for consistent clinical implementations. Herein, we enabled the enrichment of wild-type (non-reporter) retinal progenitor cells (RPCs) from dissociated ROs using a label-free ghost cytometry (LF-GC)-based sorting system, where a machine-based classifier was trained in advance with another RPC reporter line. The sorted cells reproducibly formed retinal spheroids large enough for transplantation and developed mature photoreceptors in the retinal degeneration rats. This method of enriching early RPCs with no specific surface antigens and without any reporters or chemical labeling is promising for robust preparation of graft tissues during cell-based therapy.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Iwama", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Nomaru", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Michiru", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Teranishi", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Mandai", "name": null }, { "creator_type": "author", "first_name": "Masayo", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2023.12.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38181785" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Retinal Degeneration", "descriptor_ui": "D012162", "major_topic": true }, { "descriptor": "Retinitis Pigmentosa", "descriptor_ui": "D012174", "major_topic": true }, { "descriptor": "Stem Cell Transplantation", "descriptor_ui": "D033581", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 20", "date_precision": "day", "issue": "", "normalized_date": "2023-12-20", "pages": "S2213-6711(23)00463-0", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-free enrichment of human pluripotent stem cell-derived early retinal progenitor cells for cell-based regenerative therapies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Carboxypeptidases (CPs) are a family of hydrolases that cleave one or more amino acids from the C-terminal of peptides or proteins and play indispensable roles in various physiological and pathological processes. However, only a few highly activatable fluorescence probes for CPs have been reported, and there is a need for a flexibly tunable molecular design platform to afford a range of fluorescence probes for CPs for biological and medical research. Here, we focused on the unique activation mechanism of ProTide-based prodrugs and established a modular design platform for CP-targeting florescence probes based on ProTide chemistry. In this design, probe properties such as fluorescence emission wavelength, reactivity/stability, and target CP can be readily tuned and optimized by changing the four probe modules: the fluorophore, the substituent on the phosphorus atom, the linker amino acid at the P1 position, and the substrate amino acid at the P1' position. In particular, switching the linker amino acid at position P1 enabled us to precisely optimize the reactivity for target CPs. As a proof-of-concept, we constructed probes for carboxypeptidase M (CPM) and prostate-specific membrane antigen (also known as glutamate carboxypeptidase II). The developed probes were applicable for the imaging of CP activities in live cells and in clinical specimens from patients. This design strategy should be useful in studying CP-related biological and pathological phenomena.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yugo", "last_name": "Kuriki", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Sogawa", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Kawatani", "name": null }, { "creator_type": "author", "first_name": "Hiroyoshi", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Kyohhei", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Rumi", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Ueo", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Ueo", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.3c10086" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38110248" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Carboxypeptidases", "descriptor_ui": "D002268", "major_topic": true }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrolases", "descriptor_ui": "D006867", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "ProTides", "descriptor_ui": "D000095802", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Dec 18", "date_precision": "day", "issue": "", "normalized_date": "2023-12-18", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Modular Design Platform for Activatable Fluorescence Probes Targeting Carboxypeptidases Based on ProTide Chemistry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Rhabdomeric photoreceptors of eyes in the terrestrial slug Limax are the typical invertebrate-type but unique in that three visual opsins (Gq-coupled rhodopsin, xenopsin, Opn5A) and one retinochrome, all belonging to different groups, are co-expressed. However, molecular properties including spectral sensitivity and G protein selectivity of any of them are not determined, which prevents us from understanding an advantage of multiplicity of opsin properties in a single rhabdomeric photoreceptor. To gain insight into the functional role of the co-expression of multiple opsin species in a photoreceptor, we investigated the molecular properties of the visual opsins in the present study. RESULTS: First, we found that the fourth member of visual opsins, Opn5B, is also co-expressed in the rhabdomere of the photoreceptor together with previously identified three opsins. The photoreceptors were also demonstrated to express Gq and Go alpha subunits. We then determined the spectral sensitivity of the four visual opsins using biochemical and spectroscopic methods. Gq-coupled rhodopsin and xenopsin exhibit maximum sensitivity at ~ 456 and 475 nm, respectively, and Opn5A and Opn5B exhibit maximum sensitivity at ~ 500 and 470 nm, respectively, with significant UV sensitivity. Notably, in vitro experiments revealed that Go alpha was activated by all four visual opsins, in contrast to the specific activation of Gq alpha by Gq-coupled rhodopsin, suggesting that the eye photoreceptor of Limax uses complex G protein signaling pathways. CONCLUSIONS: The eye photoreceptor in Limax expresses as many as four different visual opsin species belonging to three distinct classes. The combination of opsins with different spectral sensitivities and G protein selectivities may underlie physiological properties of the ocular photoreception, such as a shift in spectral sensitivity between dark- and light-adapted states. This may be allowed by adjustment of the relative contribution of the four opsins without neural networks, enabling a simple strategy for fine-tuning of vision.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryota", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sugihara", "name": null }, { "creator_type": "author", "first_name": "Taishi", "last_name": "Shirata", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12915-023-01789-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38110917" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "GTP-Binding Proteins", "descriptor_ui": "D019204", "major_topic": false }, { "descriptor": "Mollusca", "descriptor_ui": "D008974", "major_topic": false }, { "descriptor": "Opsins", "descriptor_ui": "D055355", "major_topic": true }, { "descriptor": "Photoreceptor Cells, Invertebrate", "descriptor_ui": "D017956", "major_topic": true }, { "descriptor": "Rhodopsin", "descriptor_ui": "D012243", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 18", "date_precision": "day", "issue": "1", "normalized_date": "2023-12-18", "pages": "291", "proceedings_title": null, "publisher": "", "title": "BMC biology", "volume": "21", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Functional characterization of four opsins and two G alpha subtypes co-expressed in the molluscan rhabdomeric photoreceptor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "ATP-dependent chromatin remodeling SWI/SNF complexes exist in three subcomplexes: canonical BAF (cBAF), polybromo BAF (PBAF), and a newly described non-canonical BAF (ncBAF). While cBAF and PBAF regulate fates of multiple cell types, roles for ncBAF in hematopoietic stem cells (HSCs) have not been investigated. Motivated by recent discovery of disrupted expression of BRD9, an essential component of ncBAF, in multiple cancers, including clonal hematopoietic disorders, we evaluate here the role of BRD9 in normal and malignant HSCs. BRD9 loss enhances chromatin accessibility, promoting myeloid lineage skewing while impairing B cell development. BRD9 significantly colocalizes with CTCF, whose chromatin recruitment is augmented by BRD9 loss, leading to altered chromatin state and expression of myeloid-related genes within intact topologically associating domains. These data uncover ncBAF as critical for cell fate specification in HSCs via three-dimensional regulation of gene expression and illuminate roles for ncBAF in normal and malignant hematopoiesis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Muran", "last_name": "Xiao", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Koutarou", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Weijia", "last_name": "Zang", "name": null }, { "creator_type": "author", "first_name": "Yifan", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Aaron", "last_name": "Viny", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Shigehiro", "name": null }, { "creator_type": "author", "first_name": "Tomokatsu", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Fukumoto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yasutaka", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hiroyoshi", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Goyama", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Stanley C.", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Kunihiko", "last_name": "Hinohara", "name": null }, { "creator_type": "author", "first_name": "Omar", "last_name": "Abdel-Wahab", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-44081-6" }, "pmcid": { "normalized": "PMC10724271" }, "pmid": { "normalized": "38102116" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": true }, { "descriptor": "Chromatin Assembly and Disassembly", "descriptor_ui": "D042002", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Dec 15", "date_precision": "day", "issue": "1", "normalized_date": "2023-12-15", "pages": "8372", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The aberrant glucose circadian rhythm is associated with the pathogenesis of diabetes. Similar to glucose metabolism in kidney and liver, d-alanine, a rare enantiomer of alanine, shows circadian alteration, although the effect of d-alanine on glucose metabolism has not been explored. Here we show that d-alanine acts on the circadian clock and affects glucose metabolism in the kidney. METHODS: The blood and urinary levels of d-alanine in mice were measured using two-dimensional high performance liquid chromatography system. Metabolic effects of d-alanine were analysed in mice and in primary culture of kidney proximal tubular cells from mice. Behavioural and gene expression analyses of circadian rhythm were performed using mice bred under constant darkness. RESULTS: d-Alanine levels in blood exhibited a clear intrinsic circadian rhythm. Since this rhythm was regulated by the kidney through urinary excretion, we examined the effect of d-alanine on kidney. In kidney, d-alanine induced expressions of genes involved in gluconeogenesis and circadian rhythm. Treatment of d-alanine mediated glucose production in mice. Ex vivo glucose production assay demonstrated that treatment of d-alanine induced glucose production in primary culture of kidney proximal tubular cells, where d-amino acids are known to be reabsorbed, but not in that of liver cells. Gluconeogenetic effect of d-alanine has an intraday variation, and this effect was in part mediated through circadian transcriptional network. Under constant darkness, treatment of d-alanine normalized the circadian cycle of behaviour and kidney gene expressions. CONCLUSIONS: d-Alanine induces gluconeogenesis in the kidney and adjusts the period of the circadian clock. Normalization of circadian cycle by d-alanine may provide the therapeutic options for life style-related diseases and shift workers.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Youichi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Shihoko", "last_name": "Kimura-Ohba", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hesaka", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Hamase", "name": null }, { "creator_type": "author", "first_name": "Chin-Ling", "last_name": "Hsieh", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Hiraku", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Yokote", "name": null }, { "creator_type": "author", "first_name": "Mitsuaki", "last_name": "Yoshino", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Okuzaki", "name": null }, { "creator_type": "author", "first_name": "Hiroyo", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Mita", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Nakane", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Doi", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Isaka", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Kimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.34067/kid.0000000000000345" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38098136" } }, "mesh": [ { "descriptor": "Alanine", "descriptor_ui": "D000409", "major_topic": false }, { "descriptor": "Blood Glucose", "descriptor_ui": "D001786", "major_topic": false }, { "descriptor": "Circadian Clocks", "descriptor_ui": "D057906", "major_topic": true }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 15", "date_precision": "day", "issue": "", "normalized_date": "2023-12-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "Kidney360", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "d-Alanine Affects the Circadian Clock to Regulate Glucose Metabolism in Kidney.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: In clinical research on multifactorial diseases such as atopic dermatitis, data-driven medical research has become more widely used as means to clarify diverse pathological conditions and to realize precision medicine. However, modern clinical data, characterized as large-scale, multimodal, and multi-center, causes difficulties in data integration and management, which limits productivity in clinical data science. METHODS: We designed a generic data management flow to collect, cleanse, and integrate data to handle different types of data generated at multiple institutions by 10 types of clinical studies. We developed MeDIA (Medical Data Integration Assistant), a software to browse the data in an integrated manner and extract subsets for analysis. RESULTS: MeDIA integrates and visualizes data and information on research participants obtained from multiple studies. It then provides a sophisticated interface that supports data management and helps data scientists retrieve the data sets they need. Furthermore, the system promotes the use of unified terms such as identifiers or sampling dates to reduce the cost of pre-processing by data analysts. We also propose best practices in clinical data management flow, which we learned from the development and implementation of MeDIA. CONCLUSIONS: The MeDIA system solves the problem of multimodal clinical data integration, from complex text data such as medical records to big data such as omics data from a large number of patients. The system and the proposed best practices can be applied not only to allergic diseases but also to other diseases to promote data-driven medical research.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tazro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Hananoe", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Fukushima-Nomura", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ashizaki", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Sekita", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Seita", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Sakurada", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Amagai", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Koseki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kawasaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.alit.2023.11.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38102028" } }, "mesh": [ { "descriptor": "Biomedical Research", "descriptor_ui": "D035843", "major_topic": true }, { "descriptor": "Data Management", "descriptor_ui": "D000079803", "major_topic": false }, { "descriptor": "Dermatitis, Atopic", "descriptor_ui": "D003876", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Precision Medicine", "descriptor_ui": "D057285", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 14", "date_precision": "day", "issue": "", "normalized_date": "2023-12-14", "pages": "S1323-8930(23)00118-1", "proceedings_title": null, "publisher": "", "title": "Allergology international : official journal of the Japanese Society of Allergology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Best practices for multimodal clinical data management and integration: An atopic dermatitis research case.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Early diagnosis and prompt initiation of appropriate treatment are critical for improving the prognosis of acute leukemia. Acute leukemia is diagnosed by microscopic morphological examination of bone marrow smears and flow cytometric immunophenotyping of bone marrow cells stained with fluorophore-conjugated antibodies. However, these diagnostic processes require trained professionals and are time and resource-intensive. Here, we present a novel diagnostic approach using ghost cytometry, a recently developed high-content flow cytometric approach, which enables machine vision-based, stain-free, high-speed analysis of cells, leveraging their detailed morphological information. We demonstrate that ghost cytometry can detect leukemic cells from the bone marrow cells of patients diagnosed with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) without relying on biological staining. The approach presented here holds promise as a precise, simple, swift, and cost-effective diagnostic method for acute leukemia in clinical practice. This article is protected by copyright. All rights reserved.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yoko", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Teranishi", "name": null }, { "creator_type": "author", "first_name": "Ryusuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kajiwara", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Hidemasa", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Souichi", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Hidefumi", "last_name": "Hiramatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cyto.a.24821" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38087915" } }, "mesh": [ { "descriptor": "Acute Disease", "descriptor_ui": "D000208", "major_topic": false }, { "descriptor": "Antibodies", "descriptor_ui": "D000906", "major_topic": false }, { "descriptor": "Bone Marrow Cells", "descriptor_ui": "D001854", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunophenotyping", "descriptor_ui": "D016130", "major_topic": false }, { "descriptor": "Leukemia, Myeloid, Acute", "descriptor_ui": "D015470", "major_topic": true }, { "descriptor": "Precursor Cell Lymphoblastic Leukemia-Lymphoma", "descriptor_ui": "D054198", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Dec 13", "date_precision": "day", "issue": "", "normalized_date": "2023-12-13", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cytometry. Part A : the journal of the International Society for Analytical Cytology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-free cell detection of acute leukemia using ghost cytometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Based on studies with a fluorescent reporter dye, Mito Thermo Yellow (MTY), and the genetically encoded gTEMP ratiometric fluorescent temperature indicator targeted to mitochondria, the temperature of active mitochondria in four mammalian and one insect cell line was estimated to be up to 15 degrees C above that of the external environment to which the cells were exposed. High mitochondrial temperature was maintained in the face of a variety of metabolic stresses, including substrate starvation or modification, decreased ATP demand due to inhibition of cytosolic protein synthesis, inhibition of the mitochondrial adenine nucleotide transporter and, if an auxiliary pathway for electron transfer was available via the alternative oxidase, even respiratory poisons acting downstream of oxidative phosphorylation (OXPHOS) complex I. We propose that the high temperature of active mitochondria is an inescapable consequence of the biochemistry of OXPHOS and is homeostatically maintained as a primary feature of mitochondrial metabolism.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mugen", "last_name": "Terzioglu", "name": null }, { "creator_type": "author", "first_name": "Kristo", "last_name": "Veeroja", "name": null }, { "creator_type": "author", "first_name": "Toni", "last_name": "Montonen", "name": null }, { "creator_type": "author", "first_name": "Teemu O.", "last_name": "Ihalainen", "name": null }, { "creator_type": "author", "first_name": "Tiina S.", "last_name": "Salminen", "name": null }, { "creator_type": "author", "first_name": "Paule", "last_name": "Benit", "name": null }, { "creator_type": "author", "first_name": "Pierre", "last_name": "Rustin", "name": null }, { "creator_type": "author", "first_name": "Young-Tae", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Howard T.", "last_name": "Jacobs", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.89232" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38079477" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Temperature Regulation", "descriptor_ui": "D001833", "major_topic": false }, { "descriptor": "Cell Respiration", "descriptor_ui": "D019069", "major_topic": true }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": true }, { "descriptor": "Oxidative Phosphorylation", "descriptor_ui": "D010085", "major_topic": false }, { "descriptor": "Stress, Physiological", "descriptor_ui": "D013312", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 11", "date_precision": "day", "issue": "", "normalized_date": "2023-12-11", "pages": "RP89232", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "12", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Mitochondrial temperature homeostasis resists external metabolic stresses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Many peptide-derived natural products are produced by non-ribosomal peptide synthetases (NRPSs) in an assembly-line fashion. Each amino acid is coupled to a designated peptidyl carrier protein (PCP) through two distinct reactions catalysed sequentially by the single active site of the adenylation domain (A-domain). Accumulating evidence suggests that large-amplitude structural changes occur in different NRPS states; yet how these molecular machines orchestrate such biochemical sequences has remained elusive. Here, using single-molecule Forster resonance energy transfer, we show that the A-domain of gramicidin S synthetase I adopts structurally extended and functionally obligatory conformations for alternating between adenylation and thioester-formation structures during enzymatic cycles. Complementary biochemical, computational and small-angle X-ray scattering studies reveal interconversion among these three conformations as intrinsic and hierarchical where intra-A-domain organizations propagate to remodel inter-A-PCP didomain configurations during catalysis. The tight kinetic coupling between structural transitions and enzymatic transformations is quantified, and how the gramicidin S synthetase I A-domain utilizes its inherent conformational dynamics to drive directional biosynthesis with a flexibly linked PCP domain is revealed.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Xun", "last_name": "Sun", "name": null }, { "creator_type": "author", "first_name": "Jonas", "last_name": "Alfermann", "name": null }, { "creator_type": "author", "first_name": "Hao", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Maxwell B.", "last_name": "Watkins", "name": null }, { "creator_type": "author", "first_name": "Yi-Tsao", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Thomas E.", "last_name": "Morrell", "name": null }, { "creator_type": "author", "first_name": "Florian", "last_name": "Mayerthaler", "name": null }, { "creator_type": "author", "first_name": "Chia-Ying", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null }, { "creator_type": "author", "first_name": "Jhih-Wei", "last_name": "Chu", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Henning D.", "last_name": "Mootz", "name": null }, { "creator_type": "author", "first_name": "Haw", "last_name": "Yang", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41557-023-01361-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38049653" } }, "mesh": [ { "descriptor": "Catalytic Domain", "descriptor_ui": "D020134", "major_topic": false }, { "descriptor": "Gramicidin", "descriptor_ui": "D006096", "major_topic": true }, { "descriptor": "Peptide Synthases", "descriptor_ui": "D010453", "major_topic": true }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 4", "date_precision": "day", "issue": "", "normalized_date": "2023-12-04", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature chemistry", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Subdomain dynamics enable chemical chain reactions in non-ribosomal peptide synthetases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "IMPORTANCE: Biomarker testing for driver mutations is essential for selecting appropriate non-small cell lung cancer (NSCLC) treatment but is insufficient. OBJECTIVE: To investigate the status of biomarker testing and drug therapy for NSCLC in Japan for identifying problems in treatment. DESIGN, SETTING, AND PARTICIPANTS: The REVEAL cohort study included retrospective data collection and prospective follow-up from 29 institutions across Japan. Of 1500 patients diagnosed with advanced or recurrent NSCLC between January 1 and March 18, 2021, 1479 were eligible. Cases recognized at the wrong clinical stage (n = 12), diagnosed outside the study period (n = 6), not treated according to eligibility criteria before recurrence (n = 2), and with deficient consent acquisition procedure (n = 1) were excluded. MAIN OUTCOMES AND MEASURES: The primary end point was the biomarker testing status. Treatment-related factors were examined. RESULTS: Among the 1479 patients included in the analysis, the median age was 72 (range, 30-95) years; 1013 (68.5%) were men; 1161 (78.5%) had an Eastern Cooperative Oncology Group performance status 0 or 1; 1097 (74.2%) were current or past smokers; and 947 (64.0%) had adenocarcinoma. Biomarker status was confirmed in 1273 patients (86.1%). Multigene testing was performed in 705 cases (47.7%); single-gene testing, in 847 (57.3%); and both, in 279 (18.9%). Biomarker testing was performed for EGFR in 1245 cases (84.2%); ALK, in 1165 (78.8%); ROS1, in 1077 (72.8%); BRAF, in 803 (54.3%); and MET, in 805 (54.4%). Positivity rates among 898 adenocarcinoma cases included 305 (34.0%) for EGFR, 29 (3.2%) for ALK, 19 (2.1%) for ROS1, 11 (1.2%) for BRAF, and 14 (1.6%) for MET. Positivity rates among 375 nonadenocarcinoma cases were 14 (3.7%) for EGFR, 6 (1.6%) for ALK, 1 (0.3%) for ROS1, 3 (0.8%) for BRAF, and 8 (2.1%) for MET. Poor physical status, squamous cell carcinoma, and other comorbidities were associated with hampered multigene testing. Targeted therapy was received as first-line treatment by 263 of 278 cases (94.6%) positive for EGFR, 25 of 32 (78.1%) positive for ALK, 15 of 24 (62.5%) positive for ROS1, 9 of 12 (75.0%) positive for BRAF, and 12 of 19 (63.2%) positive for MET. Median overall survival of patients with positive findings for driver gene alteration and who received targeted therapy was 24.3 (95% CI, not reported) months; with positive findings for driver gene alteration and who did not receive targeted therapy, 15.2 (95% CI, 7.7 to not reported) months; and with negative findings for driver gene alteration, 11.0 (95% CI, 10.0-12.5) months. Multigene testing for nonadenocarcinomas and adenocarcinomas accounted for 705 (47.7%) of all NSCLC cases. CONCLUSIONS AND RELEVANCE: These findings suggest that multigene testing has not been sufficiently implemented in Japan and should be considered prospectively, even in nonadenocarcinomas, to avoid missing rare driver gene alterations.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Taichi", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Takahama", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Tokito", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Akamatsu", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Tobino", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Mimura", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Maeno", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kunihiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Hirotsugu", "last_name": "Kenmotsu", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Shimokawa", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Nakagawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1001/jamanetworkopen.2023.47700" }, "pmcid": { "normalized": "PMC10724778" }, "pmid": { "normalized": "38100106" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": true }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Prospective Studies", "descriptor_ui": "D011446", "major_topic": false }, { "descriptor": "Protein-Tyrosine Kinases", "descriptor_ui": "D011505", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins B-raf", "descriptor_ui": "D048493", "major_topic": false }, { "descriptor": "Receptor Protein-Tyrosine Kinases", "descriptor_ui": "D020794", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 1", "date_precision": "day", "issue": "12", "normalized_date": "2023-12-01", "pages": "e2347700", "proceedings_title": null, "publisher": "", "title": "JAMA network open", "volume": "6", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Biomarker Testing in Patients With Unresectable Advanced or Recurrent Non-Small Cell Lung Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A new diradical based on diindenocarbazole or difluorenopyrrole was synthesized and experimentally characterized by optical, electrochemical, and magnetic techniques, as well as quantum chemical calculations. The isomerism of these structures tunes the diradical character and the associated properties, representing a unique case of such important modulation. A full study of the electronic structure was carried out considering the perturbative interactions between different canonical forms as well as the anti-aromatic character of the molecular cores. Such a study reveals how we can tune diradical character simply by reorganizing the bonding patterns at constant chemical costs (composition).", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryotaro", "last_name": "Moriyasu", "name": null }, { "creator_type": "author", "first_name": "Sergio Moles", "last_name": "Quintero", "name": null }, { "creator_type": "author", "first_name": "Carlos J.", "last_name": "Gomez-Garcia", "name": null }, { "creator_type": "author", "first_name": "Kazumasa", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Chitoshi", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Michihisa", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Mercedes", "last_name": "Alonso", "name": null }, { "creator_type": "author", "first_name": "Juan", "last_name": "Casado", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Kato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d3sc03297c" }, "pmcid": { "normalized": "PMC10685319" }, "pmid": { "normalized": "38033889" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Nov 29", "date_precision": "day", "issue": "46", "normalized_date": "2023-11-29", "pages": "13468-13474", "proceedings_title": null, "publisher": "", "title": "Chemical science", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Isomerism tunes the diradical character of difluorenopyrroles at constant Huckel-level anti-aromaticity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Handa", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurumizaka", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41596-023-00940-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38030942" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Nov 29", "date_precision": "day", "issue": "", "normalized_date": "2023-11-29", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature protocols", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Author Correction: Chromatin integration labeling for mapping DNA-binding proteins and modifications with low input.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bacteria often function as a community, called the microbiota, consisting of many different bacterial species. The accurate identification of bacterial types and the simultaneous quantification of the cells of each bacterial type will advance our understanding of microbiota; however, this cannot be performed by conventional 16S rRNA sequencing methods as they only identify and quantify genes, which do not always represent cells. Here, we present a protocol for our developed method, barcoding bacteria for identification and quantification (BarBIQ). In BarBIQ, the 16S rRNA genes of single bacterial cells are amplified and attached to a unique cellular barcode in a droplet. Sequencing the tandemly linked cellular barcodes and 16S rRNA genes from many droplets (representing many cells with unique cellular barcodes) and clustering the sequences using the barcodes determines both the bacterial type for each cell based on 16S rRNA gene and the number of cells for each bacterial type based on the quantity of barcode types sequenced. Single-base accuracy for 16S rRNA sequencing is achieved via the barcodes and by avoiding chimera formation from 16S rRNA genes of different bacteria using droplets. For data processing, an easy-to-use bioinformatic pipeline is available ( https://github.com/Shiroguchi-Lab/BarBIQ_Pipeline_V1_2_0 ). This protocol allows researchers with experience in molecular biology but without bioinformatics experience to perform the process in ~2 weeks. We show the application of BarBIQ in mouse gut microbiota analysis as an example; however, this method is also applicable to other microbiota samples, including those from the mouth and skin, marine environments, soil and plants, as well as those from other terrestrial environments.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Jianshi", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41596-023-00906-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38012397" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": false }, { "descriptor": "DNA, Bacterial", "descriptor_ui": "D004269", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microbiota", "descriptor_ui": "D064307", "major_topic": true }, { "descriptor": "Mouth", "descriptor_ui": "D009055", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "RNA, Ribosomal, 16S", "descriptor_ui": "D012336", "major_topic": false }, { "descriptor": "Sequence Analysis, DNA", "descriptor_ui": "D017422", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Nov 27", "date_precision": "day", "issue": "", "normalized_date": "2023-11-27", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature protocols", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "High-throughput identification and quantification of bacterial cells in the microbiota based on 16S rRNA sequencing with single-base accuracy using BarBIQ.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The 3-dose COVID-19 vaccine (booster vaccination) has been offered worldwide. As booster vaccinations continue, it is important to understand the antibody dynamics elicited by booster vaccination in order to evaluate and develop vaccination needs and strategies. Here, we investigated longitudinal data by monitoring IgG antibodies against the receptor binding domain (RBD) in health care workers. We extended our previously developed mathematical model to booster vaccines and successfully fitted antibody titers over time in the absence and presence of past SARS-CoV-2 infection. Quantitative analysis using our mathematical model indicated that anti-RBD IgG titers increase to a comparable extent after booster vaccination, regardless of the presence or absence of infection, but infection history extends the duration of antibody response by 1.28 times. Such a mathematical modeling approach can be used to inform future vaccination strategies on the basis of an individual's immune history. Our simple quantitative approach can be extended to any kind of vaccination and therefore can form a basis for policy decisions regarding the distribution of booster vaccines to strengthen immunity in future pandemics.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takara", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Miyamatsu", "name": null }, { "creator_type": "author", "first_name": "Hyeongki", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Risa", "last_name": "Yokokawa Shibata", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Iwami", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Nagasaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.vaccine.2023.11.040" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38008663" } }, "mesh": [ { "descriptor": "Antibodies, Viral", "descriptor_ui": "D000914", "major_topic": false }, { "descriptor": "Antibody Formation", "descriptor_ui": "D000917", "major_topic": true }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "COVID-19 Vaccines", "descriptor_ui": "D000086663", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunization, Secondary", "descriptor_ui": "D007117", "major_topic": false }, { "descriptor": "Immunoglobulin G", "descriptor_ui": "D007074", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Nov 25", "date_precision": "day", "issue": "", "normalized_date": "2023-11-25", "pages": "S0264-410X(23)01384-1", "proceedings_title": null, "publisher": "", "title": "Vaccine", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Modeling COVID-19 vaccine booster-elicited antibody response and impact of infection history.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nicotine adenine dinucleotide derivatives NADH and NADPH are intimately involved in energy and electron transport within cells. The fluorescent ubiquinone-rhodol (Q-Rh) probe is used for NADPH activation monitoring. Q-Rh reacts with NADPH yielding its quenched hydroquinone-rhodol (H(2)Q-Rh) form with concurrent NADPH activation (i.e. NADP(+) formation). NADPH activation can be enhanced by the addition of an Ir(III)-complex (i.e. [(eta(5)-C(5)Me(5))Ir(phen)(H(2)O)](2+)) as a promoter. The rate of the Q-Rh fluorescence quenching process is proportional to the NADPH activation rate, which can be used to monitor NADPH. Experiments were performed in phosphate-buffered saline (PBS) solution and on HeLa cell cultures to analyze the kinetics of Q-Rh reduction and the influence of the Ir(III)-complex promoter on the activation of NADPH (in PBS) and of other intracellular reducing agents (in HeLa cells). There is a substantial increase in Q-Rh reduction rate inside HeLa cells especially after the addition of Ir(III)-complex promoter. This increase is partly due to a leakage process (caused by Ir(III)-complex-induced downstream processes which result in cell membrane disintegration) but also involves the nonspecific activation of other intracellular reducing agents, including NADH, FADH(2), FMNH(2) or GSH. In the presence only of Q-Rh, the activation rate of intracellular reducing agents is 2 to 8 times faster in HeLa cells than in PBS solution. When both Q-Rh and Ir(III)-complex are present, the rate of the Ir(III)-complex catalyzed reduction reaction is 7 to 23 times more rapid in HeLa cells. Concentration- and time-dependent fluorescence attenuation of Q-Rh with third-order reaction kinetics (reasonably approximated as pseudo-first-order in Q-Rh) has been observed and modelled. This reaction and its kinetics present an example of \"bioparallel chemistry\", where the activation of a molecule can trigger a unique chemical process. This approach stands in contrast to the conventional concept of \"bioorthogonal chemistry\", which refers to chemical reactions that occur without disrupting native biological processes.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Nadiia", "last_name": "Velychkivska", "name": null }, { "creator_type": "author", "first_name": "Anastasiia B.", "last_name": "Shatan", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ariga", "name": null }, { "creator_type": "author", "first_name": "Jonathan P.", "last_name": "Hill", "name": null }, { "creator_type": "author", "first_name": "Jan", "last_name": "Labuta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d3ra05412h" }, "pmcid": { "normalized": "PMC10658984" }, "pmid": { "normalized": "38020010" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Nov 16", "date_precision": "day", "issue": "48", "normalized_date": "2023-11-16", "pages": "34012-34019", "proceedings_title": null, "publisher": "", "title": "RSC advances", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Kinetic study of NADPH activation using ubiquinone-rhodol fluorescent probe and an Ir(III)-complex promoter at the cell interior.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "IL-31 receptor blockade suppresses pruritus of atopic dermatitis. However, cell-type-specific contributions of IL-31 receptor to itch, its expression mechanism, and the downstream signaling pathway to induce itch remain unknown. Here, using conditional knockout mice, we demonstrate that IL-31-induced itch requires sensory neuronal IL-31 receptor and STAT3. We find that IL-31 receptor expression is dependent on STAT3 in sensory neurons. In addition, pharmacological experiments suggest that STAT3 activation is important for the itch-inducing signaling downstream of the IL-31 receptor. A cutaneous IL-31 injection induces the nuclear accumulation of activated STAT3 first in sensory neurons that abundantly express IL-31 receptor and then in other itch-transmitting neurons. IL-31 enhances itch induced by various pruritogens including even chloroquine. Finally, pruritus associated with dermatitis is partially dependent on sensory neuronal IL-31 receptor and strongly on sensory neuronal STAT3. Thus, sensory neuronal STAT3 is essential for IL-31-induced itch and further contributes to IL-31-independent inflammatory itch.", "classifications": [ { "id": "18H05411", "label": "18H05411", "researcher": "Katsuyuki Shiroguchi", "type": "grant" }, { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Sonoko", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Sotaro", "last_name": "Ochiai", "name": null }, { "creator_type": "author", "first_name": "Jianshi", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Toshima", "name": null }, { "creator_type": "author", "first_name": "Harumichi", "last_name": "Ishigame", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kabashima", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null }, { "creator_type": "author", "first_name": "Takaharu", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2023.113433" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38029739" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dermatitis, Atopic", "descriptor_ui": "D003876", "major_topic": true }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Pruritus", "descriptor_ui": "D011537", "major_topic": true }, { "descriptor": "Sensory Receptor Cells", "descriptor_ui": "D011984", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "STAT3 Transcription Factor", "descriptor_ui": "D050796", "major_topic": false }, { "descriptor": "Ubiquitin-Protein Ligases", "descriptor_ui": "D044767", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Nov 15", "date_precision": "day", "issue": "", "normalized_date": "2023-11-15", "pages": "113433", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000386" ], "repository": [ "ssbd-repos-000386" ] }, "title": "Sensory neuronal STAT3 is critical for IL-31 receptor expression and inflammatory itch.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In vertebrate embryos, the canonical Wnt ligand primes the formation of dorsal organizers that govern dorsal-ventral patterns by secreting BMP antagonists. In contrast, in Drosophila embryos, Toll-like receptor (Tlr)-mediated NFkappaB activation initiates dorsal-ventral patterning, wherein Wnt-mediated negative feedback regulation of Tlr/NFkappaB generates a BMP antagonist-secreting signalling centre to control the dorsal-ventral pattern. Although both Wnt and BMP antagonist are conserved among species, the involvement of Tlr/NFkappaB and feedback regulation in vertebrate organizer formation remains unclear. By imaging and genetic modification, we reveal that a negative feedback loop between canonical and non-canonical Wnts and Tlr4/NFkappaB determines the size of zebrafish organizer, and that Tlr/NFkappaB and Wnts switch initial cue and feedback mediator roles between Drosophila and zebrafish. Here, we show that canonical Wnt signalling stimulates the expression of the non-canonical Wnt5b ligand, activating the Tlr4 receptor to stimulate NFkappaB-mediated transcription of the Wnt antagonist frzb, restricting Wnt-dependent dorsal organizer formation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Juqi", "last_name": "Zou", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Anai", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Shizuka", "last_name": "Ishitani", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Oginuma", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Ishitani", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-42963-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37938219" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Feedback", "descriptor_ui": "D005246", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": true }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Nov 8", "date_precision": "day", "issue": "1", "normalized_date": "2023-11-08", "pages": "7194", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Determining zebrafish dorsal organizer size by a negative feedback loop between canonical/non-canonical Wnts and Tlr4/NFkappaB.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Normal epithelial cells exert their competitive advantage over RasV12-transformed cells and eliminate them into the apical lumen via cell competition. However, the internal or external factors that compromise cell competition and provoke carcinogenesis remain elusive. In this study, we examine the effect of sequential accumulation of gene mutations, mimicking multi-sequential carcinogenesis on RasV12-induced cell competition in intestinal epithelial tissues. Consequently, we find that the directionality of RasV12-cell extrusion in Wnt-activated epithelia is reversed, and transformed cells are delaminated into the basal lamina via non-cell autonomous MMP21 upregulation. Subsequently, diffusively infiltrating, transformed cells develop into highly invasive carcinomas. The elevated production of MMP21 is elicited partly through NF-kappaB signaling, blockage of which restores apical elimination of RasV12 cells. We further demonstrate that the NF-kappaB-MMP21 axis is significantly bolstered in early colorectal carcinoma in humans. Collectively, this study shows that cells with high mutational burdens exploit cell competition for their benefit by behaving as unfit cells, endowing them with an invasion advantage.", "classifications": [ { "id": "21H00441", "label": "21H00441", "researcher": "Shunsuke Kon", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Hancheng", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Yamano", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Kitamoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Saitoh", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Sakuma", "name": null }, { "creator_type": "author", "first_name": "Junpei", "last_name": "Kurauchi", "name": null }, { "creator_type": "author", "first_name": "Eilma", "last_name": "Akter", "name": null }, { "creator_type": "author", "first_name": "Masamitsu", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Kojiro", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Kamata", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Koseki", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Shiraki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Sohei", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Yoku", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ushiku", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Mutoh", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kon", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-42774-6" }, "pmcid": { "normalized": "PMC10624923" }, "pmid": { "normalized": "37923722" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Cell Competition", "descriptor_ui": "D000084502", "major_topic": true }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "Matrix Metalloproteinases, Secreted", "descriptor_ui": "D053505", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Nov 3", "date_precision": "day", "issue": "1", "normalized_date": "2023-11-03", "pages": "7048", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Wnt activation disturbs cell competition and causes diffuse invasion of transformed cells through NF-kappaB-MMP21 pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Divalent metal cations such as calcium ion (Ca(2+)) and magnesium ion (Mg(2+)) are indispensable to the regulation of various cellular activities. In this research, we developed the KLCA series utilizing o-aminophenol-N,N-diacetate-O-methylene-methylphosphinate (APDAP) as a target binding site, which was reported recently as a highly free Mg(2+)-selective ligand. KLCA-301 with orange fluorescence based on a rhodamine fluorophore and KLCA-501 with near-infrared (NIR) fluorescence based on a Si-rhodamine fluorophore were synthesized, intended for application to multicolor imaging. The evaluation of the fluorescence response to Ca(2+) and Mg(2+) of the KLCA series indicated the applicability as low-affinity Ca(2+) probes. While KLCA-301 mainly localized in the cytosol in cultured rat hippocampal neurons, KLCA-501 localized to the cytosol and granular organelles in neurons. Comparison of the fluorescence response of KLCA-301 and the high-affinity Ca(2+) probe Fluo-4 upon stimulation by glutamate in stained neurons revealed that KLCA-301 could reflect the secondary large rise of intracellular Ca(2+), which Fluo-4 could not detect. In addition, KLCA-501 showed a fluorescence response similar to the low-affinity Ca(2+) probe Fluo-5N upon stimulation by glutamate in stained neurons, concluding that KLCA-301 and KLCA-501 could be used as low-affinity Ca(2+) probes. The KLCA series offers new options for low-affinity Ca(2+) probes. Moreover, KLCA-501 achieved simultaneous visualization of the change in Ca(2+) and ATP concentrations and also in mitochondrial inner membrane potential in neurons. KLCA-501 is expected to be a strong tool that enables simultaneous multicolor imaging of multiple targets and elucidation of their relationship in cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Rei", "last_name": "Kumada", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Sakama", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Yuzuka", "last_name": "Kuronuma", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Iwasawa", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.3c03266" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37922450" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Glutamates", "descriptor_ui": "D005971", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Organelles", "descriptor_ui": "D015388", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Nov 3", "date_precision": "day", "issue": "", "normalized_date": "2023-11-03", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of Phosphinate Ligand-Based Low-Affinity Ca(2+) Fluorescent Probes and Application to Intracellular Ca(2+) Imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Allergen immunotherapy (AIT) is the only curative treatment for allergic diseases. However, AIT has many disadvantages related to efficiency, safety, long-term duration, and patient compliance. Dendritic cells (DCs) have an important role in antigen-specific tolerance induction; thus, DC-targeting strategies to treat allergies such as glutaraldehyde crosslinked antigen to mannoprotein (MAN) have been established. However, glutaraldehyde crosslinking may reduce the antigen presentation efficiency of DCs. To overcome this, we developed a MAN-coated ovalbumin (OVA) nanoparticle (MDO), which uses intermolecular disulfide bond to crosslink OVA and MAN. MDO effectively targeted DCs resulting in tolerogenic DCs, and promoted higher antigen presentation efficiency by DCs compared with OVA or glutaraldehyde crosslinked nanoparticles. In vitro and in vivo experiments showed that DCs exposed to MDO induced T(reg) cells. Moreover, MDO had low reactivity with anti-OVA antibodies and did not induce anaphylaxis in allergic mice, demonstrating its high safety profile. In a mouse model of allergic asthma, MDO had significant preventative and therapeutic effects when administered orally or subcutaneously. Therefore, MDO represents a promising new approach for the efficient and safe treatment of allergies.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shunyi", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Toriumi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Kamasaki", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Nagatoishi", "name": null }, { "creator_type": "author", "first_name": "Jinting", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yiwei", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Takanatsu", "last_name": "Hosokawa", "name": null }, { "creator_type": "author", "first_name": "Kouhei", "last_name": "Tsumoto", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Hase", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.biomaterials.2023.122381" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37935073" } }, "mesh": [ { "descriptor": "Allergens", "descriptor_ui": "D000485", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": false }, { "descriptor": "Desensitization, Immunologic", "descriptor_ui": "D003888", "major_topic": false }, { "descriptor": "Glutaral", "descriptor_ui": "D005976", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypersensitivity", "descriptor_ui": "D006967", "major_topic": true }, { "descriptor": "Immunotherapy", "descriptor_ui": "D007167", "major_topic": false }, { "descriptor": "Mannans", "descriptor_ui": "D008351", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": true }, { "descriptor": "Ovalbumin", "descriptor_ui": "D010047", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Oct 31", "date_precision": "day", "issue": "", "normalized_date": "2023-10-31", "pages": "122381", "proceedings_title": null, "publisher": "", "title": "Biomaterials", "volume": "303", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Safe and efficient oral allergy immunotherapy using one-pot-prepared mannan-coated allergen nanoparticles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We present a protocol to induce Cre-dependent transgene expression in specific cell types in the rat brain, suppressing a leak expression in off-target cells, by using a flip-excision switch system with a unilateral spacer sequence. We describe steps for construction of transfer plasmids, preparation of adeno-associated viral vectors, intracranial injection, and detection of transgene expression. Our protocol provides a useful strategy for a better understanding of the structure and function of specific cell types in the complex neural circuit. For complete details on the use and execution of this protocol, please refer to Matsushita et al.(1).", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Natsuki", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kayo", "last_name": "Nishizawa", "name": null }, { "creator_type": "author", "first_name": "Masateru", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Miyasaka", "name": null }, { "creator_type": "author", "first_name": "Tomoji", "last_name": "Mashimo", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xpro.2023.102667" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37906596" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rodentia", "descriptor_ui": "D012377", "major_topic": true }, { "descriptor": "Transgenes", "descriptor_ui": "D019076", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Oct 30", "date_precision": "day", "issue": "4", "normalized_date": "2023-10-30", "pages": "102667", "proceedings_title": null, "publisher": "", "title": "STAR protocols", "volume": "4", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Protocol for highly selective transgene expression through the flip-excision switch system by using a unilateral spacer sequence in rodents.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The intracellular distribution and dynamics of RNAs play pivotal roles in various physiological phenomena. The ability to monitor the amount and localization of endogenous RNAs in living cells allows for elucidating the mechanisms of various intracellular events. Protein-based fluorescent RNA probes are now widely used to visualize and analyze RNAs in living cells. However, continuously monitoring the temporal changes in RNA localization and dynamics in living cells is challenging. In this study, we developed a bioluminescent probe for spatiotemporal monitoring of RNAs in living cells by using a split-luciferase reconstitution technique. The probe consists of split fragments of a bioluminescent protein, NanoLuc, connected with RNA-binding protein domains generated from a custom-made mutation of a PUM-HD. The probe showed rapid luminescence intensity changes in response to an increase or decrease in the amount of a target RNA in vitro. In live-cell imaging, temporal alteration of the intracellular distribution of endogenous beta-actin mRNA was visualized in response to extracellular stimulation. Furthermore, the application of the probe to the visualization of the specific localization of beta-actin mRNA in primary hippocampal neurons was conducted. These results demonstrate the capability of the bioluminescent RNA probe to monitor the changes in localization, dynamics, and the amount of target RNA in living cells.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Yoshibumi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acssensors.3c01080" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37889477" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": true }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": true }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Oct 27", "date_precision": "day", "issue": "", "normalized_date": "2023-10-27", "pages": "", "proceedings_title": null, "publisher": "", "title": "ACS sensors", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Split Luciferase-Fragment Reconstitution for Unveiling RNA Localization and Dynamics in Live Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "One of the fundamental questions in plant developmental biology is how cell proliferation and cell expansion coordinately determine organ growth and morphology. An amenable system to address this question is the Arabidopsis root tip, where cell proliferation and elongation occur in spatially separated domains, and cell morphologies can easily be observed using a confocal microscope. While past studies revealed numerous elements of root growth regulation including gene regulatory networks, hormone transport and signaling, cell mechanics and environmental perception, how cells divide and elongate under possible constraints from cell lineages and neighboring cell files has not been analyzed quantitatively. This is mainly due to the technical difficulties in capturing cell division and elongation dynamics at the tip of growing roots, as well as an extremely labor-intensive task of tracing the lineages of frequently dividing cells. Here, we developed a motion-tracking confocal microscope and an Artificial Intelligence (AI)-assisted image-processing pipeline that enables semi-automated quantification of cell division and elongation dynamics at the tip of vertically growing Arabidopsis roots. We also implemented a data sonification tool that facilitates human recognition of cell division synchrony. Using these tools, we revealed previously unnoted lineage-constrained dynamics of cell division and elongation, and their contribution to the root zonation boundaries.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuaki", "last_name": "Goh", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Yonekura", "name": null }, { "creator_type": "author", "first_name": "Noriyasu", "last_name": "Obushi", "name": null }, { "creator_type": "author", "first_name": "Zeping", "last_name": "Den", "name": null }, { "creator_type": "author", "first_name": "Katsutoshi", "last_name": "Imizu", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Tomizawa", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Miyashima", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Inami", "name": null }, { "creator_type": "author", "first_name": "Yen-Wei", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Nakajima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pcp/pcad105" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37861079" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Meristem", "descriptor_ui": "D018519", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Plant Roots", "descriptor_ui": "D018517", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Oct 20", "date_precision": "day", "issue": "", "normalized_date": "2023-10-20", "pages": "pcad105", "proceedings_title": null, "publisher": "", "title": "Plant & cell physiology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "In-Depth Quantification of Cell Division and Elongation Dynamics at the Tip of Growing Arabidopsis Roots Using 4D Microscopy, AI-Assisted Image Processing and Data Sonification.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cilia are organelles involved in motility and sensory transduction, but how these two functions coexist has not been elucidated in depth. Here, the involvement of the ciliary transient receptor potential (TRP) channel TRP11 in mechanoresponses is studied in Chlamydomonas reinhardtii using a TRP11-knockout mutant. The mutant has defects in the conversion of the bending mode of the cilium from forward to reverse when tapped with a glass rod, the detachment of cilia when shear is applied, the increase in ciliary beat frequency upon application of mechanical agitation by vortex mixing, and the initiation of gliding while both cilia are attached in opposite directions to a glass surface. These observations indicate that TRP11 can perceive mechanical stimuli with distinct intensities and durations and induce various types of ciliary responses.", "classifications": [ { "id": "21H00420", "label": "21H00420", "researcher": "Ken-ichi Wakabayashi", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daichi", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Saga", "name": null }, { "creator_type": "author", "first_name": "Neo", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Miyu", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Isu", "name": null }, { "creator_type": "author", "first_name": "Nobuo", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2023.107926" }, "pmcid": { "normalized": "PMC10543168" }, "pmid": { "normalized": "37790279" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Oct 20", "date_precision": "day", "issue": "10", "normalized_date": "2023-10-20", "pages": "107926", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "26", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Mechanoresponses mediated by the TRP11 channel in cilia of Chlamydomonas reinhardtii.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Narcolepsy is a sleep disorder caused by deficiency of orexin signaling. However, the neural mechanisms by which deficient orexin signaling causes the abnormal rapid eye movement (REM) sleep characteristics of narcolepsy, such as cataplexy and frequent transitions to REM states, are not fully understood. Here, we determined the activity dynamics of orexin neurons during sleep that suppress the abnormal REM sleep architecture of narcolepsy. Orexin neurons were highly active during wakefulness, showed intermittent synchronous activity during non-REM (NREM) sleep, were quiescent prior to the transition from NREM to REM sleep, and a small subpopulation of these cells was active during REM sleep. Orexin neurons that lacked orexin peptides were less active during REM sleep and were mostly silent during cataplexy. Optogenetic inhibition of orexin neurons established that the activity dynamics of these cells during NREM sleep regulate NREM-REM sleep transitions. Inhibition of orexin neurons during REM sleep increased subsequent REM sleep in \"orexin intact\" mice and subsequent cataplexy in mice lacking orexin peptides, indicating that the activity of a subpopulation of orexin neurons during the preceding REM sleep suppresses subsequent REM sleep and cataplexy. Thus, these results identify how deficient orexin signaling during sleep results in the abnormal REM sleep architecture characteristic of narcolepsy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroto", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Fukatsu", "name": null }, { "creator_type": "author", "first_name": "Sheikh Mizanur", "last_name": "Rahaman", "name": null }, { "creator_type": "author", "first_name": "Yasutaka", "last_name": "Mukai", "name": null }, { "creator_type": "author", "first_name": "Shuntaro", "last_name": "Izawa", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Thomas S.", "last_name": "Kilduff", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2301951120" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37796986" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cataplexy", "descriptor_ui": "D002385", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Narcolepsy", "descriptor_ui": "D009290", "major_topic": true }, { "descriptor": "Orexins", "descriptor_ui": "D000068797", "major_topic": true }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": false }, { "descriptor": "Sleep, REM", "descriptor_ui": "D012895", "major_topic": false }, { "descriptor": "Wakefulness", "descriptor_ui": "D014851", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Oct 10", "date_precision": "day", "issue": "41", "normalized_date": "2023-10-10", "pages": "e2301951120", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "120", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Associative learning is crucial for adapting to environmental changes. Interactions among neuronal populations involving the dorso-medial prefrontal cortex (dmPFC) are proposed to regulate associative learning, but how these neuronal populations store and process information about the association remains unclear. Here we developed a pipeline for longitudinal two-photon imaging and computational dissection of neural population activities in male mouse dmPFC during fear-conditioning procedures, enabling us to detect learning-dependent changes in the dmPFC network topology. Using regularized regression methods and graphical modeling, we found that fear conditioning drove dmPFC reorganization to generate a neuronal ensemble encoding conditioned responses (CR) characterized by enhanced internal coactivity, functional connectivity, and association with conditioned stimuli (CS). Importantly, neurons strongly responding to unconditioned stimuli during conditioning subsequently became hubs of this novel associative network for the CS-to-CR transformation. Altogether, we demonstrate learning-dependent dynamic modulation of population coding structured on the activity-dependent formation of the hub network within the dmPFC.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masakazu", "last_name": "Agetsuma", "name": null }, { "creator_type": "author", "first_name": "Issei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro R.", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Luis", "last_name": "Carrillo-Reid", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Noritake", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Yoshitomo", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yukawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Nabekura", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-41547-5" }, "pmcid": { "normalized": "PMC10558457" }, "pmid": { "normalized": "37803014" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Association Learning", "descriptor_ui": "D001245", "major_topic": false }, { "descriptor": "Conditioning, Classical", "descriptor_ui": "D003214", "major_topic": true }, { "descriptor": "Fear", "descriptor_ui": "D005239", "major_topic": false }, { "descriptor": "Learning", "descriptor_ui": "D007858", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Oct 6", "date_precision": "day", "issue": "1", "normalized_date": "2023-10-06", "pages": "5996", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Activity-dependent organization of prefrontal hub-networks for associative learning and signal transformation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The diagnosis of Parkinson's disease (PD) and evaluation of its symptoms require in-person clinical examination. Remote evaluation of PD symptoms is desirable, especially during a pandemic such as the coronavirus disease 2019 pandemic. One potential method to remotely evaluate PD motor impairments is video-based analysis. In this study, we aimed to assess the feasibility of predicting the Unified Parkinson's Disease Rating Scale (UPDRS) score from gait videos using a convolutional neural network (CNN) model. METHODS: We retrospectively obtained 737 consecutive gait videos of 74 patients with PD and their corresponding neurologist-rated UPDRS scores. We utilized a CNN model for predicting the total UPDRS part III score and four subscores of axial symptoms (items 27, 28, 29, and 30), bradykinesia (items 23, 24, 25, 26, and 31), rigidity (item 22) and tremor (items 20 and 21). We trained the model on 80% of the gait videos and used 10% of the videos as a validation dataset. We evaluated the predictive performance of the trained model by comparing the model-predicted score with the neurologist-rated score for the remaining 10% of videos (test dataset). We calculated the coefficient of determination (R(2)) between those scores to evaluate the model's goodness of fit. RESULTS: In the test dataset, the R(2) values between the model-predicted and neurologist-rated values for the total UPDRS part III score and subscores of axial symptoms, bradykinesia, rigidity, and tremor were 0.59, 0.77, 0.56, 0.46, and 0.0, respectively. The performance was relatively low for videos from patients with severe symptoms. CONCLUSIONS: Despite the low predictive performance of the model for the total UPDRS part III score, it demonstrated relatively high performance in predicting subscores of axial symptoms. The model approximately predicted the total UPDRS part III scores of patients with moderate symptoms, but the performance was low for patients with severe symptoms owing to limited data. A larger dataset is needed to improve the model's performance in clinical settings.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Katsuki", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Ikuko", "last_name": "Takahashi-Iwata", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Matsushima", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Yaguchi", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Yabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12883-023-03385-2" }, "pmcid": { "normalized": "PMC10552271" }, "pmid": { "normalized": "37798685" } }, "mesh": [ { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Gait", "descriptor_ui": "D005684", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypokinesia", "descriptor_ui": "D018476", "major_topic": false }, { "descriptor": "Mental Status and Dementia Tests", "descriptor_ui": "D000073216", "major_topic": false }, { "descriptor": "Neurologic Examination", "descriptor_ui": "D009460", "major_topic": false }, { "descriptor": "Parkinson Disease", "descriptor_ui": "D010300", "major_topic": true }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Tremor", "descriptor_ui": "D014202", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Oct 5", "date_precision": "day", "issue": "1", "normalized_date": "2023-10-05", "pages": "358", "proceedings_title": null, "publisher": "", "title": "BMC neurology", "volume": "23", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Gait video-based prediction of unified Parkinson's disease rating scale score: a retrospective study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Characterizing phenotypes is a fundamental aspect of biological sciences, although it can be challenging due to various factors. For instance, the liverwort (Marchantia polymorpha), a model system for plant biology, exhibits morphological variability, making it difficult to identify and quantify distinct phenotypic features using objective measures. To address this issue, we utilized a deep learning-based image classifier that can handle plant images directly without manual extraction of phenotypic features, and analyzed pictures of M. polymorpha. This dioicous plant species exhibits morphological differences between male and female wild accessions at an early stage of gemmaling growth, although it remains elusive whether the differences are attributable to sex chromosomes. To isolate the effects of sex chromosomes from autosomal polymorphisms, we established a male and female set of recombinant inbred lines (RILs) from a set of male and female wild accessions. We then trained deep-learning models to classify the sexes of the RILs and the wild accessions. Our results showed that the trained classifiers accurately classified male and female gemmalings of wild accessions in the first week of growth, confirming the intuition of researchers in a reproducible and objective manner. In contrast, the RILs were less distinguishable, indicating that the differences between the parental wild accessions arose from autosomal variations. Furthermore, we validated our trained models by an \"explainable AI\" technique that highlights image regions relevant to the classification. Our findings demonstrate that the classifier-based approach provides a powerful tool for analyzing plant species that lack standardized phenotyping metrics.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoko", "last_name": "Tomizawa", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Minamino", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Shimokawa", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Aino", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Hiwatashi", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Nishihama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Kohchi", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pcp/pcad117" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37797211" } }, "mesh": [ { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Marchantia", "descriptor_ui": "D047008", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Oct 5", "date_precision": "day", "issue": "", "normalized_date": "2023-10-05", "pages": "pcad117", "proceedings_title": null, "publisher": "", "title": "Plant & cell physiology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Harnessing Deep Learning to Analyze Cryptic Morphological Variability of Marchantia polymorpha.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: To determine, for patients with advanced or recurrent synovial sarcoma not suitable for surgical resection and resistant to anthracycline, the safety and efficacy of the infusion of autologous T lymphocytes expressing NY-ESO-1 antigen-specific T-cell receptor gene and siRNAs to inhibit the expression of endogenous T-cell receptors (product code: TBI-1301). PATIENTS AND METHODS: Eligible Japanese patients (HLA-A*02:01 or *02:06, NY-ESO-1-positive tumor expression) received cyclophosphamide 750 mg/m2 on days -3 and -2 (induction period) followed by a single dose of 5 x 109 (+/-30%) TBI-1301 cells as a divided infusion on days 0 and 1 (treatment period). Primary endpoints were safety-related (phase I part) and efficacy-related (objective response rate [ORR] by RECIST v1.1/irRECIST; phase II part). Safety- and efficacy-related secondary endpoints were considered in both phase I/II parts. RESULTS: For the full analysis set (N=8; phase I, n=3; phase II, n=5), the ORR was 50.0% (95%CI: 15.7-84.3) with best overall partial response in 4 of 8 patients according to RECIST v1.1/irRECIST. All patients experienced adverse events and 7 of 8 patients (87.5%) had adverse drug reactions but no deaths were attributed to adverse events. Cytokine release syndrome occurred in 4 of 8 patients (50.0%) but all cases recovered with prespecified treatment. Immune effector cell-associated neurotoxicity syndrome, replication competent retrovirus, and lymphocyte clonality were absent. CONCLUSIONS: Adoptive immunotherapy with TBI-1301 to selectively target NY-ESO-1 positive tumor cells appears to be a promising strategy for the treatment of advanced or recurrent synovial sarcoma with acceptable toxicity.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akira", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Mikiya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Shigehisa", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Kohichi", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Emori", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Kakunaga", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Miyahara", "name": null }, { "creator_type": "author", "first_name": "Kunihiko", "last_name": "Morino", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Fujio", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Matsumine", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/1078-0432.ccr-23-1456" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37792433" } }, "mesh": [ { "descriptor": "Antigens, Neoplasm", "descriptor_ui": "D000951", "major_topic": false }, { "descriptor": "Genes, T-Cell Receptor", "descriptor_ui": "D019672", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphocytes", "descriptor_ui": "D008214", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false }, { "descriptor": "Sarcoma, Synovial", "descriptor_ui": "D013584", "major_topic": true }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Oct 4", "date_precision": "day", "issue": "", "normalized_date": "2023-10-04", "pages": "", "proceedings_title": null, "publisher": "", "title": "Clinical cancer research : an official journal of the American Association for Cancer Research", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Safety and Efficacy of NY-ESO-1 Antigen-specific T-cell Receptor Gene-Transduced T Lymphocytes in Patients with Synovial Sarcoma: A Phase I/II Clinical Trial.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Atopic dermatitis (AD) is a skin disease that is heterogeneous both in terms of clinical manifestations and molecular profiles. It is increasingly recognized that AD is a systemic rather than a local disease and should be assessed in the context of whole-body pathophysiology. Here we show, via integrated RNA-sequencing of skin tissue and peripheral blood mononuclear cell (PBMC) samples along with clinical data from 115 AD patients and 14 matched healthy controls, that specific clinical presentations associate with matching differential molecular signatures. We establish a regression model based on transcriptome modules identified in weighted gene co-expression network analysis to extract molecular features associated with detailed clinical phenotypes of AD. The two main, qualitatively differential skin manifestations of AD, erythema and papulation are distinguished by differential immunological signatures. We further apply the regression model to a longitudinal dataset of 30 AD patients for personalized monitoring, highlighting patient heterogeneity in disease trajectories. The longitudinal features of blood tests and PBMC transcriptome modules identify three patient clusters which are aligned with clinical severity and reflect treatment history. Our approach thus serves as a framework for effective clinical investigation to gain a holistic view on the pathophysiology of complex human diseases.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Aiko", "last_name": "Sekita", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Fukushima-Nomura", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Yashiro", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Tanese", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Toshima", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ashizaki", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Miyai", "name": null }, { "creator_type": "author", "first_name": "Junshi", "last_name": "Yazaki", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Namba", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Qingbo S.", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Seita", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Ohara", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Sakurada", "name": null }, { "creator_type": "author", "first_name": "Yukinori", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Amagai", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Koseki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-41857-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37783685" } }, "mesh": [ { "descriptor": "Dermatitis, Atopic", "descriptor_ui": "D003876", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukocytes, Mononuclear", "descriptor_ui": "D007963", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Oct 2", "date_precision": "day", "issue": "1", "normalized_date": "2023-10-02", "pages": "6133", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Multifaceted analysis of cross-tissue transcriptomes reveals phenotype-endotype associations in atopic dermatitis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bone marrow-derived cells (BMDCs) infiltrate hypoxic tumors at a pre-angiogenic state and differentiate into mature macrophages, thereby inducing pro-tumorigenic immunity. A critical factor regulating this differentiation is activation of SREBP2-a well-known transcription factor participating in tumorigenesis progression-through unknown cellular mechanisms. Here, we show that hypoxia-induced Golgi disassembly and Golgi-ER fusion in monocytic myeloid cells result in nuclear translocation and activation of SREBP2 in a SCAP-independent manner. Notably, hypoxia-induced SREBP2 activation was only observed in an immature lineage of bone marrow-derived cells. Single-cell RNA-seq analysis revealed that SREBP2-mediated cholesterol biosynthesis was upregulated in HSCs and monocytes but not in macrophages in the hypoxic bone marrow niche. Moreover, inhibition of cholesterol biosynthesis impaired tumor growth through suppression of pro-tumorigenic immunity and angiogenesis. Thus, our findings indicate that Golgi-ER fusion regulates SREBP2-mediated metabolic alteration in lineage-specific BMDCs under hypoxia for tumor progression.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Nakahara", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Aki", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Sugaya", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Daichi M.", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Miyuki", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Ritsuko", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Melvin", "last_name": "Pan", "name": null }, { "creator_type": "author", "first_name": "Rika", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Yanai", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Ryoji", "last_name": "Yao", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Sando", "name": null }, { "creator_type": "author", "first_name": "Masabumi", "last_name": "Shibuya", "name": null }, { "creator_type": "author", "first_name": "Juro", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Kodama", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Teppei", "last_name": "Shimamura", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Osawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.15252/embj.2023114032" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37781951" } }, "mesh": [ { "descriptor": "Bone Marrow", "descriptor_ui": "D001853", "major_topic": false }, { "descriptor": "Cholesterol", "descriptor_ui": "D002784", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypoxia", "descriptor_ui": "D000860", "major_topic": false }, { "descriptor": "Monocytes", "descriptor_ui": "D009000", "major_topic": true }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Sterol Regulatory Element Binding Protein 2", "descriptor_ui": "D051782", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Oct 2", "date_precision": "day", "issue": "", "normalized_date": "2023-10-02", "pages": "e114032", "proceedings_title": null, "publisher": "", "title": "The EMBO journal", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Hypoxia activates SREBP2 through Golgi disassembly in bone marrow-derived monocytes for enhanced tumor growth.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "D,L-Propargylglycine (PAG) has been widely used as a selective inhibitor to investigate the biological functions of cystathionine gamma-lyase (CSE), which catalyzes the formation of reactive sulfur species (RSS). However, PAG also inhibits other PLP (pyridoxal-5'-phosphate)-dependent enzymes such as methionine gamma-lyase (MGL) and L-alanine transaminase (ALT), so highly selective CSE inhibitors are still required. Here, we performed high-throughput screening (HTS) of a large chemical library and identified oxamic hydrazide 1 as a potent inhibitor of CSE (IC(50) = 13 +/- 1 muM (mean +/- S.E.)) with high selectivity over other PLP-dependent enzymes and RSS-generating enzymes. Inhibitor 1 inhibited the enzymatic activity of human CSE in living cells, indicating that it is sufficiently membrane-permeable. X-Ray crystal structure analysis of the complex of rat CSE (rCSE) with 1 revealed that 1 forms a Schiff base linkage with the cofactor PLP in the active site of rCSE. PLP in the active site may be a promising target for development of selective inhibitors of PLP-dependent enzymes, including RSS-generating enzymes such as cystathionine beta-synthase (CBS) and cysteinyl-tRNA synthetase 2 (CARS2), which have unique substrate binding pocket structures.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Honami", "last_name": "Echizen", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Kazuhito", "last_name": "Shimamoto", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hibi", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Toma-Fukai", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Otsuka", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Nagatoishi", "name": null }, { "creator_type": "author", "first_name": "Kouhei", "last_name": "Tsumoto", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-43536-6" }, "pmcid": { "normalized": "PMC10542788" }, "pmid": { "normalized": "37777556" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Catalytic Domain", "descriptor_ui": "D020134", "major_topic": false }, { "descriptor": "Cystathionine beta-Synthase", "descriptor_ui": "D003541", "major_topic": false }, { "descriptor": "Cystathionine gamma-Lyase", "descriptor_ui": "D003542", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Phosphates", "descriptor_ui": "D010710", "major_topic": false }, { "descriptor": "Pyridoxal Phosphate", "descriptor_ui": "D011732", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Schiff Bases", "descriptor_ui": "D012545", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Sep 30", "date_precision": "day", "issue": "1", "normalized_date": "2023-09-30", "pages": "16456", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Discovery of a cystathionine gamma-lyase (CSE) selective inhibitor targeting active-site pyridoxal 5'-phosphate (PLP) via Schiff base formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tauopathies, characterized by fibrillar tau accumulation in neurons and glial cells, constitute a major neuropathological category of neurodegenerative diseases. Neurofibrillary tau lesions are strongly associated with cognitive deficits in these diseases, but the causal mechanisms underlying tau-induced neuronal dysfunction remain unresolved. Recent advances in cryo-electron microscopy examination have revealed various core structures of tau filaments from different tauopathy patients, which can be used to classify tauopathies. In vivo visualization of tau pathology is now available using several tau positron emission tomography tracers. Among these radioprobes, PM-PBB3 allows high-contrast imaging of tau deposits in the brains of patients with diverse disorders and tauopathy mouse models. Selective degradation of pathological tau species by the ubiquitin-proteasome system or autophagy machinery is a potential therapeutic strategy. Alternatively, the non-cell-autonomous clearance of pathological tau species through neuron-glia networks could be reinforced as a disease-modifying treatment. In addition, the development of neuroinflammatory biomarkers is required for understanding the contribution of immunocompetent cells in the brain to preventing neurodegeneration. This review provides an overview of the current research and development of diagnostic and therapeutic agents targeting divergent tau pathologies.", "classifications": [ { "id": "21H00446", "label": "21H00446", "researcher": "Naruhiko Sahara", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/2211-5463.13711" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37746832" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cryoelectron Microscopy", "descriptor_ui": "D020285", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurodegenerative Diseases", "descriptor_ui": "D019636", "major_topic": true }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Sep 25", "date_precision": "day", "issue": "", "normalized_date": "2023-09-25", "pages": "", "proceedings_title": null, "publisher": "", "title": "FEBS open bio", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Diagnostic and therapeutic targeting of pathological tau proteins in neurodegenerative disorders.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A LIM homeodomain transcription factor Apterous (Ap) regulates embryonic and larval neurodevelopment in Drosophila. Although Ap is still expressed in the adult brain, it remains elusive whether Ap is involved in neurodevelopmental events in the adult brain because flies homozygous for ap mutations are usually lethal before they reach the adult stage. In this study, using adult escapers of ap knockout (KO) homozygotes, we examined whether the complete lack of ap expression affects the morphology of the mushroom body (MB) neurons and Pigment-dispersing factor (Pdf)-positive clock neurons in the adult brain. Although ap KO escapers showed severe structural defects of MB neurons, no clear morphological defects were found in Pdf-positive clock neurons. These results suggest that Ap in the adult brain is essential for the neurodevelopment of specific ap-positive neurons, but it is not necessarily involved in the development of all ap-positive neurons.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hikari", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2023.09.071" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37804590" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": true }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": true }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "LIM-Homeodomain Proteins", "descriptor_ui": "D060850", "major_topic": false }, { "descriptor": "Mushroom Bodies", "descriptor_ui": "D024521", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 25", "date_precision": "day", "issue": "", "normalized_date": "2023-09-25", "pages": "77-84", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "682", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Impact of Drosophila LIM homeodomain protein Apterous on the morphology of the adult mushroom body.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neuronal activity is modulated not only by inputs from other neurons but also by various factors, such as bioactive substances. Noradrenergic neurons in the locus coeruleus (LC-NA neurons) are involved in diverse physiological functions, including sleep/wakefulness and stress responses. Previous studies have identified various substances and receptors that modulate LC-NA neuronal activity through techniques including electrophysiology, calcium imaging, and single-cell RNA sequencing. However, many substances with unknown physiological significance have been overlooked. Here, we established an efficient screening method for identifying substances that modulate LC-NA neuronal activity through intracellular calcium ([Ca(2+)](i)) imaging using brain slices. Using both sexes of mice, we screened 53 bioactive substances, and identified 5 novel substances: gastrin-releasing peptide, neuromedin U, and angiotensin II, which increase [Ca(2+)](i), and pancreatic polypeptide and prostaglandin D(2), which decrease [Ca(2+)](i) Among them, neuromedin U induced the greatest response in female mice. In terms of the duration of [Ca(2+)](i) change, we focused on prostaglandin E(2), since it induces a long-lasting decrease in [Ca(2+)](i) via the EP(3) receptor. Conditional knockout of the receptor in LC-NA neurons resulted in increased depression-like behavior, prolonged wakefulness in the dark period, and increased [Ca(2+)](i) after stress exposure. Our results demonstrate the effectiveness of our screening method for identifying substances that modulate a specific neuronal population in an unbiased manner and suggest that stress-induced prostaglandin E(2) can suppress LC-NA neuronal activity to moderate the behavioral response to stressors. Our screening method will contribute to uncovering previously unknown physiological functions of uncharacterized bioactive substances in specific neuronal populations.Significance StatementBioactive substances modulate the activity of specific neuronal populations. However, since only a limited number of substances with predicted effects have been investigated, many substances that may modulate neuronal activity have gone unrecognized. Here, we established an unbiased method for identifying modulatory substances by measuring the intracellular calcium signal, which reflects neuronal activity. We examined noradrenergic neurons in the locus coeruleus (LC-NA neurons), which are involved in diverse physiological functions. We identified 5 novel substances that modulate LC-NA neuronal activity. We also found that stress-induced prostaglandin E(2) may suppress LC-NA neuronal activity and influence behavioral outcomes. Our screening method will help uncover previously overlooked functions of bioactive substances and provide insight into unrecognized roles of specific neuronal populations.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yasutaka", "last_name": "Mukai 向井康敬", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Okubo 大久保達夫", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Lazarus", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono 小野大輔", "name": null }, { "creator_type": "author", "first_name": "Kenji F.", "last_name": "Tanaka 田中謙二", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamanaka 山中章弘", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.0353-23.2023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37734949" } }, "mesh": [ { "descriptor": "Adrenergic Neurons", "descriptor_ui": "D059331", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Locus Coeruleus", "descriptor_ui": "D008125", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Norepinephrine", "descriptor_ui": "D009638", "major_topic": false }, { "descriptor": "Prostaglandins", "descriptor_ui": "D011453", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 21", "date_precision": "day", "issue": "", "normalized_date": "2023-09-21", "pages": "JN-RM-0353-23", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Prostaglandin E(2) induces long-lasting inhibition of noradrenergic neurons in the locus coeruleus and moderates the behavioral response to stressors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Designing novel catalysts is key to solving many energy and environmental challenges. Despite the promise that data science approaches, including machine learning (ML), can accelerate the development of catalysts, truly novel catalysts have rarely been discovered through ML approaches because of one of its most common limitations and criticisms-the assumed inability to extrapolate and identify extraordinary materials. Herein, we demonstrate an extrapolative ML approach to develop new multi-elemental reverse water-gas shift catalysts. Using 45 catalysts as the initial data points and performing 44 cycles of the closed loop discovery system (ML prediction + experiment), we experimentally tested a total of 300 catalysts and identified more than 100 catalysts with superior activity compared to those of the previously reported high-performance catalysts. The composition of the optimal catalyst discovered was Pt(3)/Rb(1)-Ba(1)-Mo(0.6)-Nb(0.2)/TiO(2). Notably, niobium (Nb) was not included in the original dataset, and the catalyst composition identified was not predictable even by human experts.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Gang", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Mine", "name": null }, { "creator_type": "author", "first_name": "Duotian", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yuan", "last_name": "Jing", "name": null }, { "creator_type": "author", "first_name": "Kah Wei", "last_name": "Ting", "name": null }, { "creator_type": "author", "first_name": "Taichi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Motoshi", "last_name": "Takao", "name": null }, { "creator_type": "author", "first_name": "Zen", "last_name": "Maeno", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Toyao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-41341-3" }, "pmcid": { "normalized": "PMC10514199" }, "pmid": { "normalized": "37735169" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Sep 21", "date_precision": "day", "issue": "1", "normalized_date": "2023-09-21", "pages": "5861", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Accelerated discovery of multi-elemental reverse water-gas shift catalysts using extrapolative machine learning approach.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Clustered protocadherin (Pcdh) functions as a cell recognition molecule through the homophilic interaction in the central nervous system. However, its interactions have not yet been visualized in neurons. We previously reported PcdhγB2-Förster resonance energy transfer (FRET) probes to be applicable only to cell lines. Herein, we designed γB2-FRET probes by fusing FRET donor and acceptor fluorescent proteins to a single γB2 molecule and succeeded in visualizing γB2 homophilic interaction in cultured hippocampal neurons. The γB2-FRET probe localized in the soma and neurites, and FRET signals, which were observed at contact sites between neurites, eliminated by ethylene glycol tetraacetic acid (EGTA) addition. Live imaging revealed that the FRET-negative γB2 signals rapidly moved along neurites and soma, whereas the FRET-positive signals remained in place. We observed that the γB2 proteins at synapses rarely interact homophilically. The γB2-FRET probe might allow us to elucidate the function of the homophilic interaction and the cell recognition mechanism.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Natsumi", "last_name": "Hoshino", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kanadome", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Takasugi", "name": null }, { "creator_type": "author", "first_name": "Mizuho", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Yukiko U.", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Hirabayashi", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Tarusawa", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Yagi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2301003120" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-09-19", "date_precision": "day", "issue": "38", "normalized_date": "2023-09-19", "pages": "e2301003120", "proceedings_title": null, "publisher": "Proceedings of the National Academy of Sciences", "title": "Proceedings of the National Academy of Sciences", "volume": "120", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualization of trans homophilic interaction of clustered protocadherin in neurons", "url": "https://www.pnas.org/doi/10.1073/pnas.2301003120", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The aim of this study is to examine the effects of ageing on dermal fibroblast heterogeneity based on samples obtained from the same donor. We used a dermal fibroblast lineage (named ASF-4 cell lines) isolated from the inner side of the upper arm of a healthy male donor over a 35-year period, beginning at 36 years of age. Because clonal analysis of ASF-4 cell lines demonstrated a donor age-dependent loss of proliferative capacity and acquisition of senescent traits at the single-cell level, cultured cells frozen at passage 10 at ages 36 and 72 years were subjected to single-cell RNA sequencing. Transcriptome analysis revealed an increase in senescent fibroblasts and downregulation of genes associated with extracellular matrix remodelling with ageing. In addition, two putative differentiation pathways, with one endpoint consisting of senescent fibroblasts and the other without, were speculated using a pseudo-time analysis. Knockdown of the characteristic gene of the non-senescent fibroblast cluster endpoint, EFEMP2, accelerated cellular senescence. This was also confirmed in two other normal human dermal fibroblast cell lines. The detection of a common cellular senescence-related gene from single-donor analysis is notable. This study provides new insights into the behaviour of dermal fibroblasts during skin ageing.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Eriko", "last_name": "Itai", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Atsugi", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Inomata", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Kaji", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Nanba", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Naru", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/exd.14929" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37727050" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Sep 19", "date_precision": "day", "issue": "", "normalized_date": "2023-09-19", "pages": "", "proceedings_title": null, "publisher": "", "title": "Experimental dermatology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-cell analysis of human dermal fibroblasts isolated from a single male donor over 35 years.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Digestibility is an important characteristic of rice starch. It is affected by the growing environment, such as temperature and soil, so that even in the same genetic cultivar the digestibility of each product will be different. Here, we predicted rice starch digestibility by Raman scattering spectroscopy. A partial least squares (PLS) regression analysis was performed between biochemically quantified digestibility index values and Raman scattering spectra of purified starch from rice samples of different cultivars and growing conditions. The prediction model obtained by analyzing the individual cultivars was able to predict digestibility with a high accuracy, with an R(2) of 0.95 and RMSEP of 0.43, whereas a mixture of all cultivars resulted in more than two times worse accuracy. Our finding suggests that the molecular structures affecting digestibility fluctuate depending on the growing environment while maintaining a unique balance regulated by cultivar-specific starch synthesis mechanisms.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Junya", "last_name": "Ichinose", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Oba", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Arase", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Kaneshiro", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Tate", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.foodchem.2023.137505" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37837895" } }, "mesh": [ { "descriptor": "Amylopectin", "descriptor_ui": "D000687", "major_topic": true }, { "descriptor": "Calibration", "descriptor_ui": "D002138", "major_topic": false }, { "descriptor": "Oryza", "descriptor_ui": "D012275", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "Starch", "descriptor_ui": "D013213", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 16", "date_precision": "day", "issue": "", "normalized_date": "2023-09-16", "pages": "137505", "proceedings_title": null, "publisher": "", "title": "Food chemistry", "volume": "435", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative prediction of rice starch digestibility using Raman spectroscopy and multivariate calibration analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cerebellar climbing fibers convey diverse signals, but how they are organized in the compartmental structure of the cerebellar cortex during learning remains largely unclear. We analyzed a large amount of coordinate-localized two-photon imaging data from cerebellar Crus II in mice undergoing 'Go/No-go' reinforcement learning. Tensor component analysis revealed that a majority of climbing fiber inputs to Purkinje cells were reduced to only four functional components, corresponding to accurate timing control of motor initiation related to a Go cue, cognitive error-based learning, reward processing, and inhibition of erroneous behaviors after a No-go cue. Changes in neural activities during learning of the first two components were correlated with corresponding changes in timing control and error learning across animals, indirectly suggesting causal relationships. Spatial distribution of these components coincided well with boundaries of Aldolase-C/zebrin II expression in Purkinje cells, whereas several components are mixed in single neurons. Synchronization within individual components was bidirectionally regulated according to specific task contexts and learning stages. These findings suggest that, in close collaborations with other brain regions including the inferior olive nucleus, the cerebellum, based on anatomical compartments, reduces dimensions of the learning space by dynamically organizing multiple functional components, a feature that may inspire new-generation AI designs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Huu", "last_name": "Hoang", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Matsuzaki", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Mitsuo", "last_name": "Kawato", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Toyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.86340" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37712651" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Learning", "descriptor_ui": "D007858", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Reinforcement, Psychology", "descriptor_ui": "D012054", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Sep 15", "date_precision": "day", "issue": "", "normalized_date": "2023-09-15", "pages": "e86340", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "12", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic organization of cerebellar climbing fiber response and synchrony in multiple functional components reduces dimensions for reinforcement learning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Periodic boundary conditions are commonly applied in molecular dynamics simulations in the microcanonical (NVE), canonical (NVT), and isothermal-isobaric (NpT) ensembles. In their simplest application, a biological system of interest is placed in the middle of a solvation box, which is chosen 'sufficiently large' to minimize any numerical artifacts associated with the periodic boundary conditions. This practical approach brings limitations to the size of biological systems that can be simulated. Here, we study simulations of effectively infinitely long nucleic acids, which are solvated in the directions perpendicular to the polymer chain, while periodic boundary conditions are also applied along the polymer chain. We study the effects of these asymmetric periodic boundary conditions (APBC) on the simulated results, including the mechanical properties of biopolymers and the properties of the surrounding solvent. To get some further insights into the advantages of using the APBC, a coarse-grained worm-like chain model is first studied, illustrating how the persistence length can be extracted from the local properties of the polymer chain, which are less affected by the APBC than some global averages. This is followed by all-atom molecular dynamics simulations of DNA in ionic solutions, where we use the APBC to investigate sequence-dependent properties of DNA molecules and properties of the surrounding solvent.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Radek", "last_name": "Erban", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Togashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jpcb.3c03887" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37713594" } }, "mesh": [ { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": true }, { "descriptor": "Nucleic Acids", "descriptor_ui": "D009696", "major_topic": true }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Solvents", "descriptor_ui": "D012997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 15", "date_precision": "day", "issue": "", "normalized_date": "2023-09-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "The journal of physical chemistry. B", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Asymmetric Periodic Boundary Conditions for All-Atom Molecular Dynamics and Coarse-Grained Simulations of Nucleic Acids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cyanobacteria are promising photosynthetic organisms owing to their ease of genetic manipulation. Among them, Synechococcus elongatus UTEX 2973 exhibits faster growth, higher biomass production efficiency, and more robust stress tolerance compared with Synechococcus elongatus PCC 7942. This is due to specific genetic differences, including four single nucleotide polymorphisms (SNPs) in three genes. One of these SNPs alters an amino acid at position 252 of the FoF1 ATP synthase alpha subunit from Tyr to Cys (alphaY252C) in S. elongatus 7942. This change has been shown to significantly affect growth rate and stress tolerance, specifically in S. elongatus. Furthermore, experimental substitutions with several other amino acids have been shown to alter ATP synthesis rate in the cell. In the present study, we introduced identical amino acid substitutions into Synechocystis sp. PCC 6803 at position 252 to elucidate the amino acid's significance and generality across cyanobacteria. We investigated the resulting impact on growth, intracellular enzyme complex levels, intracellular ATP levels, and enzyme activity. The results showed that the alphaY252C substitution decreased growth rate and high-light tolerance. This indicates that a specific bulkiness of this amino acid's side chain is important for maintaining cell growth. Additionally, a remarkable decrease in the membrane-bound enzyme complex level was observed. However, the alphaY252C substitution did not affect enzyme activity or intracellular ATP levels. Although the mechanism of growth suppression remains unknown, the amino acid at position 252 is expected to play an important role in the enzyme complex formation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akito", "last_name": "Machida", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pcp/pcad109" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37706547" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Photosynthesis", "descriptor_ui": "D010788", "major_topic": false }, { "descriptor": "Synechococcus", "descriptor_ui": "D046940", "major_topic": true }, { "descriptor": "Synechocystis", "descriptor_ui": "D046939", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Sep 14", "date_precision": "day", "issue": "", "normalized_date": "2023-09-14", "pages": "pcad109", "proceedings_title": null, "publisher": "", "title": "Plant & cell physiology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular bulkiness of a single amino acid in the F1 alpha subunit determines the robustness of cyanobacterial ATP synthase.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Natural killer (NK) cells are innate immune cells critical for protective immune responses against infection and cancer. Although NK cells differentiate in the bone marrow (BM) in an interleukin-15 (IL-15)-dependent manner, the cellular source of IL-15 remains elusive. Using NK cell reporter mice, we show that NK cells are localized in the BM in scattered and clustered manners. NK cell clusters overlap with monocyte and dendritic cell accumulations, whereas scattered NK cells require CXCR4 signaling. Using cell-specific IL-15-deficient mice, we show that hematopoietic cells, but not stromal cells, support NK cell development in the BM through IL-15. In particular, IL-15 produced by monocytes and dendritic cells appears to contribute to NK cell development. These results demonstrate that hematopoietic cells are the IL-15 niche for NK cell development in the BM and that BM NK cells are present in scattered and clustered compartments by different mechanisms, suggesting their distinct functions in the immune response.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shinya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Asahi", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Guangwei", "last_name": "Cui", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Shimba", "name": null }, { "creator_type": "author", "first_name": "Shizue", "last_name": "Tani-Ichi", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Kikuta", "name": null }, { "creator_type": "author", "first_name": "Alexis", "last_name": "Vandenbon", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Ohteki", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Veronika", "last_name": "Sexl", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagasawa", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ikuta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2023.113127" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37729919" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Marrow", "descriptor_ui": "D001853", "major_topic": true }, { "descriptor": "Bone Marrow Cells", "descriptor_ui": "D001854", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Interleukin-15", "descriptor_ui": "D019409", "major_topic": true }, { "descriptor": "Killer Cells, Natural", "descriptor_ui": "D007694", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 10", "date_precision": "day", "issue": "", "normalized_date": "2023-09-10", "pages": "113127", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Hematopoietic cell-derived IL-15 supports NK cell development in scattered and clustered localization within the bone marrow.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Daga", "name": null }, { "creator_type": "author", "first_name": "Isamu", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kasahara", "name": null }, { "creator_type": "author", "first_name": "Tateaki", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Li", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Ravi G.", "last_name": "Gupta", "name": null }, { "creator_type": "author", "first_name": "Judith", "last_name": "Bushong", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Mizutani", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10147-023-02408-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37684530" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Sep 9", "date_precision": "day", "issue": "", "normalized_date": "2023-09-09", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of clinical oncology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Correction to: First-line nivolumab plus ipilimumab in metastatic non-small cell lung cancer: 5-year outcomes in Japanese patients from CheckMate 227 Part 1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cerebellar climbing fibers convey sensorimotor information and their errors, which are used for motor control and learning. Furthermore, they represent reward-related information. Despite such functional diversity of climbing fiber signals, it is still unclear whether each climbing fiber conveys the information of single or multiple modalities and how the climbing fibers conveying different information are distributed over the cerebellar cortex. Here we perform two-photon calcium imaging from cerebellar Purkinje cells in mice engaged in a voluntary forelimb lever-pull task and demonstrate that climbing fiber responses in 68% of Purkinje cells can be explained by the combination of multiple behavioral variables such as lever movement, licking, and reward delivery. Neighboring Purkinje cells exhibit similar climbing fiber response properties, form functional clusters, and share noise fluctuations of responses. Taken together, individual climbing fibers convey behavioral information on multiplex variables and are spatially organized into the functional modules of the cerebellar cortex.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Ikezoe", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Hidaka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Manita", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Isomura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-023-05309-9" }, "pmcid": { "normalized": "PMC10492837" }, "pmid": { "normalized": "37689776" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": true }, { "descriptor": "Reward", "descriptor_ui": "D012201", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 9", "date_precision": "day", "issue": "1", "normalized_date": "2023-09-09", "pages": "924", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "6", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Cerebellar climbing fibers multiplex movement and reward signals during a voluntary movement task in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sleep is a fundamental state of behavioral quiescence and physiological restoration. Sleep is controlled by environmental conditions, indicating a complex regulation of sleep by multiple processes. Our knowledge of the genes and mechanisms that control sleep during various conditions is, however, still incomplete. In Caenorhabditis elegans, sleep is increased when development is arrested upon starvation. Here, we performed a reverse genetic sleep screen in arrested L1 larvae for genes that are associated with metabolism. We found over 100 genes that are associated with a reduced sleep phenotype. Enrichment analysis revealed sphingolipid metabolism as a key pathway that controls sleep. A strong sleep loss was caused by the loss of function of the diacylglycerol kinase 1 gene, dgk-1, a negative regulator of synaptic transmission. Rescue experiments indicated that dgk-1 is required for sleep in cholinergic and tyraminergic neurons. The Ring Interneuron S (RIS) neuron is crucial for sleep in C. elegans and activates to induce sleep. RIS activation transients were abolished in dgk-1 mutant animals. Calcium transients were partially rescued by a reduction-of-function mutation of unc-13, suggesting that dgk-1 might be required for RIS activation by limiting synaptic vesicle release. dgk-1 mutant animals had impaired L1 arrest survival and dampened expression of the protective heat shock factor gene hsp-12.6. These data suggest that dgk-1 impairment causes broad physiological deficits. Microcalorimetry and metabolomic analyses of larvae with impaired RIS showed that RIS is broadly required for energy conservation and metabolic control, including for the presence of sphingolipids. Our data support the notion that metabolism broadly influences sleep and that sleep is associated with profound metabolic changes. We thus provide novel insights into the interplay of lipids and sleep and provide a rich resource of mutants and metabolic pathways for future sleep studies.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Anastasios", "last_name": "Koutsoumparis", "name": null }, { "creator_type": "author", "first_name": "Inka", "last_name": "Busack", "name": null }, { "creator_type": "author", "first_name": "Chung-Kuan", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Bart P.", "last_name": "Braeckman", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Meierhofer", "name": null }, { "creator_type": "author", "first_name": "Henrik", "last_name": "Bringmann", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/genetics/iyad124" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37682641" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": true }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": true }, { "descriptor": "Diacylglycerol Kinase", "descriptor_ui": "D019852", "major_topic": true }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": true }, { "descriptor": "Sphingolipids", "descriptor_ui": "D013107", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Sep 8", "date_precision": "day", "issue": "", "normalized_date": "2023-09-08", "pages": "iyad124", "proceedings_title": null, "publisher": "", "title": "Genetics", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Reverse genetic screening during L1 arrest reveals a role of the diacylglycerol kinase 1 gene dgk-1 and sphingolipid metabolism genes in sleep regulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The sleep state is widely observed in animals. The molecular mechanisms underlying sleep regulation, however, remain largely unclear. In the nematode Caenorhabditis elegans, developmentally timed sleep (DTS) and stress-induced sleep (SIS) are 2 types of quiescent behaviors that fulfill the definition of sleep and share conserved sleep-regulating molecules with mammals. To identify novel sleep-regulating molecules, we conducted an unbiased forward genetic screen based on DTS phenotypes. We isolated 2 mutants, rem8 and rem10, that exhibited significantly disrupted DTS and SIS. The causal gene of the abnormal sleep phenotypes in both mutants was mapped to dgk-1, which encodes diacylglycerol kinase. Perhaps due to the diminished SIS, dgk-1 mutant worms exhibited decreased survival following exposure to a noxious stimulus. Pan-neuronal and/or cholinergic expression of dgk-1 partly rescued the dgk-1 mutant defects in DTS, SIS, and post-stress survival. Moreover, we revealed that pkc-1/nPKC participates in sleep regulation and counteracts the effect of dgk-1; the reduced DTS, SIS, and post-stress survival rate were partly suppressed in the pkc-1; dgk-1 double mutant compared with the dgk-1 single mutant. Excessive sleep observed in the pkc-1 mutant was also suppressed in the pkc-1; dgk-1 double mutant, implying that dgk-1 has a complicated mode of action. Our findings indicate that neuronal DGK-1 is essential for normal sleep and that the counterbalance between DGK-1 and PKC-1 is crucial for regulating sleep and mitigating post-stress damage.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Chung-Kuan", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Taizo", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/genetics/iyad140" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37682636" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": true }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": true }, { "descriptor": "Diacylglycerol Kinase", "descriptor_ui": "D019852", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Kinase C", "descriptor_ui": "D011493", "major_topic": true }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 8", "date_precision": "day", "issue": "", "normalized_date": "2023-09-08", "pages": "iyad140", "proceedings_title": null, "publisher": "", "title": "Genetics", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Forward genetic screen of Caenorhabditis elegans mutants with impaired sleep reveals a crucial role of neuronal diacylglycerol kinase DGK-1 in regulating sleep.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "IMPORTANCE: Administration of durvalumab after concurrent chemoradiotherapy is the standard treatment of unresectable, locally advanced non-small cell lung cancer (NSCLC); however, 20% to 30% of patients do not receive durvalumab because of adverse events (AEs) during concurrent chemoradiotherapy. In addition, radiotherapy and immunotherapy have a synergistic effect. OBJECTIVE: To investigate the efficacy and safety of durvalumab immunotherapy plus concurrent radiotherapy followed by maintenance with durvalumab therapy for treatment of locally advanced NSCLC without chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: The multicenter, single-arm DOLPHIN (Phase II Study of Durvalumab [MEDI4736] Plus Concurrent Radiation Therapy in Advanced Localized NSCLC Patients) nonrandomized controlled trial was performed by 12 institutions in Japan from September 13, 2019, to May 31, 2022. Participants in the primary registration phase included 74 patients with programmed cell death ligand 1 (PD-L1)-positive, unresectable, locally advanced NSCLC. The current analyses were conducted from June 1, 2022, to October 31, 2022. INTERVENTIONS: Patients received radiotherapy (60 Gy) in combination with concurrent and maintenance durvalumab immunotherapy, 10 mg/kg every 2 weeks, for up to 1 year. MAIN OUTCOMES AND MEASURES: The primary end point of the rate of 12-month progression-free survival (PFS), as assessed by an independent central review, was estimated using the Kaplan-Meier method and evaluated with 90% CIs calculated using the Greenwood formula. The key secondary end points were PFS, objective response rate, treatment completion rate, and AEs. RESULTS: Data from 35 patients (median [range] age, 72 [44-83] years; 31 [88.6%] men) were included in the full analysis set of the evaluable population. The 12-month PFS rate was 72.1% (90% CI, 59.1%-85.1%), and the median PFS was 25.6 months (95% CI, 13.1 months to not estimable) at a median follow-up of 22.8 months (range, 4.3-31.8 months). Scheduled radiation therapy was completed in 97.1% of patients. The confirmed objective response rate was 90.9% (95% CI, 75.7%-98.1%), and the treatment completion rate was 57.6% (95% CI, 39.2%-74.5%). Among 34 patients evaluated in the safety analysis set, AEs of grade 3 or 4 occurred in 18 patients (52.9%), and of grade 5 in 2 patients (5.9%). Pneumonitis or radiation pneumonitis of any grade occurred in 23 patients (67.6%), and of grades 3 or 4 in 4 patients (11.8%). CONCLUSIONS AND RELEVANCE: Findings from this phase 2 nonrandomized controlled trial indicate that durvalumab immunotherapy combined with curative radiotherapy for patients with PD-L1-positive, unresectable, locally advanced NSCLC is a promising treatment with tolerable AEs and is appropriate as a study treatment for phase 3 clinical trials. TRIAL REGISTRATION: Japan Registry of Clinical Trials ID: jRCT2080224763.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Motoko", "last_name": "Tachihara", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Tsujino", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kurata", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Yoshimasa", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Teraoka", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Daga", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kodaira", "name": null }, { "creator_type": "author", "first_name": "Miyako", "last_name": "Satouchi", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Shimokawa", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Nakagawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1001/jamaoncol.2023.3309" }, "pmcid": { "normalized": "PMC10485744" }, "pmid": { "normalized": "37676681" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Chemoradiotherapy", "descriptor_ui": "D059248", "major_topic": false }, { "descriptor": "Disease-Free Survival", "descriptor_ui": "D018572", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 7", "date_precision": "day", "issue": "", "normalized_date": "2023-09-07", "pages": "", "proceedings_title": null, "publisher": "", "title": "JAMA oncology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Durvalumab Plus Concurrent Radiotherapy for Treatment of Locally Advanced Non-Small Cell Lung Cancer: The DOLPHIN Phase 2 Nonrandomized Controlled Trial.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Jing Rin", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Mansaku", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00718-23" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-09-06", "date_precision": "day", "issue": "0", "normalized_date": "2023-09-06", "pages": "e00718-23", "proceedings_title": null, "publisher": "American Society for Microbiology", "title": "Journal of Virology", "volume": "0", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Human herpesvirus 6A nuclear matrix protein U37 interacts with heat shock transcription factor 1 and activates the heat shock response", "url": "https://journals.asm.org/doi/10.1128/jvi.00718-23", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Group 2 innate lymphoid cells (ILC2s) are critical for the immune response against parasite infection and tissue homeostasis and involved in the pathogenesis of allergy and inflammatory diseases. Although multiple molecules positively regulating ILC2 development and activation have been extensively investigated, the factors limiting their population size and response remain poorly studied. Here, we found that CD45, a membrane-bound tyrosine phosphatase essential for T cell development, negatively regulated ILC2s in a cell-intrinsic manner. ILC2s in CD45-deficient mice exhibited enhanced proliferation and maturation in the bone marrow and hyperactivated phenotypes in the lung with high glycolytic capacity. Furthermore, CD45 signaling suppressed the type 2 inflammatory response by lung ILC2s and alleviated airway inflammation and pulmonary fibrosis. Finally, the interaction with galectin-9 influenced CD45 signaling in ILC2s. These results demonstrate that CD45 is a cell-intrinsic negative regulator of ILC2s and prevents lung inflammation and fibrosis via ILC2s.", "classifications": [ { "id": "18H05411", "label": "18H05411", "researcher": "Katsuyuki Shiroguchi", "type": "grant" }, { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Guangwei", "last_name": "Cui", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Shimba", "name": null }, { "creator_type": "author", "first_name": "Jianshi", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Hojo", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Asahi", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Aki", "last_name": "Ejima", "name": null }, { "creator_type": "author", "first_name": "Shinri", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Ohira", "name": null }, { "creator_type": "author", "first_name": "Ryoma", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Shizue", "last_name": "Tani-Ichi", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ebihara", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ikuta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2215941120" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37639581" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Lymphocytes", "descriptor_ui": "D008214", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pulmonary Fibrosis", "descriptor_ui": "D011658", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 5", "date_precision": "day", "issue": "36", "normalized_date": "2023-09-05", "pages": "e2215941120", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "120", "year": 2023 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000395" ] }, "title": "CD45 alleviates airway inflammation and lung fibrosis by limiting expansion and activation of ILC2s.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chicken embryos are a powerful and widely used animal model in developmental biology studies. After the development of CRISPR technology, gene-edited chickens have been generated by transferring primordial germ cells (PGCs) after genetic modifications. However, the low inheritance caused by the competition between host germ cells and the transferred ones is the most common complication and largely reduces the production efficiency in this way. Here, we generated a gene-edited chicken, in which germ cells can be ablated in a drug-dependent manner, as recipients for gene-edited PGC transfer. We used the nitroreductase/metronidazole (NTR/Mtz) system for cell ablation, in which NTR produces cytotoxic alkylating agents from administered Mtz, causing cell apoptosis. The chicken Vasa homolog (CVH) gene locus is used to drive the expression of the NTR gene in a germ cell-specific manner. In addition, a fluorescent protein gene, mCherry, was also placed in the CVH locus to visualize the PGCs. We named this system germ cell-Specific AutonoMoUs RemovAl Induction (gSAMURAI). gSAMURAI chickens will be an ideal recipient to produce offspring derived from transplanted exogenous germ cells.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yi-Chen", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.202079" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37665168" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chick Embryo", "descriptor_ui": "D002642", "major_topic": false }, { "descriptor": "Chickens", "descriptor_ui": "D002645", "major_topic": true }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Metronidazole", "descriptor_ui": "D008795", "major_topic": true }, { "descriptor": "Nitroreductases", "descriptor_ui": "D009601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 4", "date_precision": "day", "issue": "", "normalized_date": "2023-09-04", "pages": "dev.202079", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "An inducible germ cell ablation chicken model for high-grade germline chimeras.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The ubiquitin‒proteasome system (UPS) and autophagy are the two primary cellular pathways of misfolded or damaged protein degradation that maintain cellular proteostasis. When the proteasome is dysfunctional, cells compensate for impaired protein clearance by activating aggrephagy, a type of selective autophagy, to eliminate ubiquitinated protein aggregates; however, the molecular mechanisms by which impaired proteasome function activates aggrephagy remain poorly understood. Here, we demonstrate that activation of aggrephagy is transcriptionally induced by the transcription factor NRF1 (NFE2L1) in response to proteasome dysfunction. Although NRF1 has been previously shown to induce the expression of proteasome genes after proteasome inhibition (i.e., the proteasome bounce-back response), our genome-wide transcriptome analyses identified autophagy-related p62/SQSTM1 and GABARAPL1 as genes directly targeted by NRF1. Intriguingly, NRF1 was also found to be indispensable for the formation of p62-positive puncta and their colocalization with ULK1 and TBK1, which play roles in p62 activation via phosphorylation. Consistently, NRF1 knockdown substantially reduced the phosphorylation rate of Ser403 in p62. Finally, NRF1 selectively upregulated the expression of GABARAPL1, an ATG8 family gene, to induce the clearance of ubiquitinated proteins. Our findings highlight the discovery of an activation mechanism underlying NRF1-mediated aggrephagy through gene regulation when proteasome activity is impaired.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hatanaka", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Nakada", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Iori", "last_name": "Aketa", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Hirakawa", "name": null }, { "creator_type": "author", "first_name": "Tadayuki", "last_name": "Tsujita", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Waku", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-41492-9" }, "pmcid": { "normalized": "PMC10474156" }, "pmid": { "normalized": "37658135" } }, "mesh": [ { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Macroautophagy", "descriptor_ui": "D000080550", "major_topic": false }, { "descriptor": "Proteasome Endopeptidase Complex", "descriptor_ui": "D046988", "major_topic": false }, { "descriptor": "Proteostasis", "descriptor_ui": "D000074702", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": true }, { "descriptor": "Ubiquitin", "descriptor_ui": "D025801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 1", "date_precision": "day", "issue": "1", "normalized_date": "2023-09-01", "pages": "14405", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000381" ] }, "title": "The transcription factor NRF1 (NFE2L1) activates aggrephagy by inducing p62 and GABARAPL1 after proteasome inhibition to maintain proteostasis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Purkinje cells are the sole output neurons of the cerebellar cortex and play central roles in the integration of cerebellum-related motor coordination and memory. The loss or dysfunction of Purkinje cells due to cerebellar atrophy leads to severe ataxia. Here we used in vivo transplantation to examine the function of human iPS cell-derived cerebellar progenitors in adult transgenic mice in which Purkinje-specific cell death occurs due to cytotoxicity of polyglutamines. Transplantation using cerebellar organoids (42-48 days in culture), which are rich in neural progenitors, showed a viability of >50% 4 weeks after transplantation. STEM121(+) grafted cells extended their processes toward the deep cerebellar nuclei, superior cerebellar peduncle, and vestibulocerebellar nuclei. The transplanted cells were mostly located in the white matter, and they were not found in the Purkinje cell layer. MAP2-positive fibers seen in the molecular layer of cerebellar cortex received VgluT2 inputs from climbing fibers. Transplanted neural progenitors overgrew in the host cerebellum but were suppressed by pretreatment with the gamma-secretase inhibitor DAPT. Hyperproliferation was also suppressed by transplantation with more differentiated organoids (86 days in culture) or KIRREL2-positive cells purified by FACS sorting. Transplanted cells expressed Purkinje cell markers, GABA, CALB1 and L7, though they did not show fan-shaped morphology. We attempted to improve neuronal integration of stem cell-derived cerebellar progenitors by transplantation into the adult mouse, but this was not successfully achieved. Our findings in the present study contribute to regenerative medical application for cerebellar degeneration and provide new insights into cerebellar development in future.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takamasa", "last_name": "Kamei", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tamada", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kakizuka", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Asai", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.expneurol.2023.114511" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37634697" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebellar Cortex", "descriptor_ui": "D002525", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Aug 25", "date_precision": "day", "issue": "", "normalized_date": "2023-08-25", "pages": "114511", "proceedings_title": null, "publisher": "", "title": "Experimental neurology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Survival and process outgrowth of human iPSC-derived cells expressing Purkinje cell markers in a mouse model for spinocerebellar degenerative disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reactive oxygen species (ROS) are harmful for the human body, and exposure to ultraviolet irradiation triggers ROS generation. Previous studies have demonstrated that ROS decrease mitochondrial membrane potential (MMP) and that Mg(2+) protects mitochondria from oxidative stress. Therefore, we visualized the spatio-temporal dynamics of Mg(2+) in keratinocytes (a skin component) in response to H(2)O(2) (a type of ROS) and found that it increased cytosolic Mg(2+) levels. H(2)O(2)-induced responses in both Mg(2+) and ATP were larger in keratinocytes derived from adults than in keratinocytes derived from newborns, and inhibition of mitochondrial ATP synthesis enhanced the H(2)O(2)-induced Mg(2+) response, indicating that a major source of Mg(2+) was dissociation from ATP. Simultaneous imaging of Mg(2+) and MMP revealed that larger Mg(2+) responses corresponded to lower decreases in MMP in response to H(2)O(2). Moreover, Mg(2+) supplementation attenuated H(2)O(2)-induced cell death. These suggest the potential of Mg(2+) as an active ingredient to protect skin from oxidative stress.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Keigo", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Katsuta", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-023-05247-6" }, "pmcid": { "normalized": "PMC10449934" }, "pmid": { "normalized": "37620401" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": true }, { "descriptor": "Infant, Newborn", "descriptor_ui": "D007231", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": true }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Aug 24", "date_precision": "day", "issue": "1", "normalized_date": "2023-08-24", "pages": "868", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "6", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Intracellular Mg(2+) protects mitochondria from oxidative stress in human keratinocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Abstract Nanog and Oct4 are core transcription factors that form part of a gene regulatory network to regulate hundreds of target genes for pluripotency maintenance in mouse embryonic stem cells (ESCs). To understand their function in the pluripotency maintenance, we visualised and quantified the dynamics of single molecules of Nanog and Oct4 in a mouse ESCs during pluripotency loss. Interestingly, Nanog interacted longer with its target loci upon reduced expression or at the onset of differentiation, suggesting a feedback mechanism to maintain the pluripotent state. The expression level and interaction time of Nanog and Oct4 correlate with their fluctuation and interaction frequency, respectively, which in turn depend on the ESC differentiation status. The DNA viscoelasticity near the Oct4 target locus remained flexible during differentiation, supporting its role either in chromatin opening or a preferred binding to uncondensed chromatin regions. Based on these results, we propose a new negative feedback mechanism for pluripotency maintenance via the DNA condensation state-dependent interplay of Nanog and Oct4.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" }, { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuko", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Kuniya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Shioi", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.15252/embj.2022112305" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-08-23", "date_precision": "day", "issue": "n/a", "normalized_date": "2023-08-23", "pages": "e112305", "proceedings_title": null, "publisher": "John Wiley & Sons, Ltd", "title": "The EMBO Journal", "volume": "n/a", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-molecule tracking of Nanog and Oct4 in living mouse embryonic stem cells uncovers a feedback mechanism of pluripotency maintenance", "url": "https://www.embopress.org/doi/full/10.15252/embj.2022112305", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tetraploidy is a hallmark of broad cancer types, but it remains largely unknown which aspects of cellular processes are influenced by tetraploidization in human cells. Here, we found that tetraploid HCT116 cells manifested severe cell shape instability during cytokinesis, unlike their diploid counterparts. The cell shape instability accompanied the formation of protrusive deformation at the cell poles, indicating ectopic contractile activity of the cell cortex. While cytokinesis regulators such as RhoA and anillin correctly accumulated at the equatorial cortex, myosin II was over-accumulated at the cell poles, specifically in tetraploid cells. Suppression of myosin II activity by Y27632 treatment restored smooth cell shape in tetraploids during cytokinesis, indicating dysregulation of myosin II as a primary cause of the cell shape instability in the tetraploid state. Our results demonstrate a new aspect of the dynamic cellular process profoundly affected by tetraploidization in human cells, which provides a clue to molecular mechanisms of tetraploidy-driven pathogenic processes.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takahiro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2023.08.038" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37619310" } }, "mesh": [ { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": false }, { "descriptor": "Cytokinesis", "descriptor_ui": "D048749", "major_topic": true }, { "descriptor": "Cytoskeletal Proteins", "descriptor_ui": "D003598", "major_topic": false }, { "descriptor": "HCT116 Cells", "descriptor_ui": "D045325", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Tetraploidy", "descriptor_ui": "D057891", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Aug 18", "date_precision": "day", "issue": "", "normalized_date": "2023-08-18", "pages": "39-44", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "678", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell shape instability during cytokinesis in tetraploid HCT116 cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "G-protein-coupled receptors (GPCRs) transmit signals into cells depending on the G protein type. To analyze the functions of GPCR signaling, we assessed the effectiveness of animal G-protein-coupled bistable rhodopsins that can be controlled into active and inactive states by light application using zebrafish. We expressed Gq- and Gi/o-coupled bistable rhodopsins in hindbrain reticulospinal V2a neurons, which are involved in locomotion, or in cardiomyocytes. Light stimulation of the reticulospinal V2a neurons expressing Gq-coupled spider Rh1 resulted in an increase in the intracellular Ca(2+) level and evoked swimming behavior. Light stimulation of cardiomyocytes expressing the Gi/o-coupled mosquito Opn3, pufferfish TMT opsin, or lamprey parapinopsin induced cardiac arrest, and the effect was suppressed by treatment with pertussis toxin or barium, suggesting that Gi/o-dependent regulation of inward-rectifier K(+) channels controls cardiac function. These data indicate that these rhodopsins are useful for optogenetic control of GPCR-mediated signaling in zebrafish neurons and cardiomyocytes.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hanako", "last_name": "Hagio", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Shiori", "last_name": "Hosaka", "name": null }, { "creator_type": "author", "first_name": "Aysenur Deniz", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Janchiv", "last_name": "Narantsatsral", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sugihara", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Hibi", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.83974" }, "pmcid": { "normalized": "PMC10435233" }, "pmid": { "normalized": "37589544" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Potassium Channels, Inwardly Rectifying", "descriptor_ui": "D024661", "major_topic": true }, { "descriptor": "Rhodopsin", "descriptor_ui": "D012243", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Aug 17", "date_precision": "day", "issue": "", "normalized_date": "2023-08-17", "pages": "", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "12", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Optogenetic manipulation of Gq- and Gi/o-coupled receptor signaling in neurons and heart muscle cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The APOE4 genotype is the strongest risk factor for the pathogenesis of sporadic Alzheimer's disease (AD), but the detailed molecular mechanism of APOE4-mediated synaptic impairment remains to be determined. In this study, we generated a human astrocyte model carrying the APOE3 or APOE4 genotype using human induced pluripotent stem cells (iPSCs) in which isogenic APOE4 iPSCs were genome edited from healthy control APOE3 iPSCs. Next, we demonstrated that the astrocytic APOE4 genotype negatively affects dendritic spine dynamics in a co-culture system with primary neurons. Transcriptome analysis revealed an increase of EDIL3, an extracellular matrix glycoprotein, in human APOE4 astrocytes, which could underlie dendritic spine reduction in neuronal cultures. Accordingly, postmortem AD brains carrying the APOE4 allele have elevated levels of EDIL3 protein deposits within amyloid plaques. Together, these results demonstrate the novel deleterious effect of human APOE4 astrocytes on synaptic architecture and may help to elucidate the mechanism of APOE4-linked AD pathogenesis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Tsumagari", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Tadafumi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Iki", "last_name": "Sonn", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Iwatsubo", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2023.08.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37657448" } }, "mesh": [ { "descriptor": "Apolipoprotein E3", "descriptor_ui": "D053318", "major_topic": false }, { "descriptor": "Apolipoprotein E4", "descriptor_ui": "D053327", "major_topic": false }, { "descriptor": "Apolipoproteins E", "descriptor_ui": "D001057", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Calcium-Binding Proteins", "descriptor_ui": "D002135", "major_topic": false }, { "descriptor": "Cell Adhesion Molecules", "descriptor_ui": "D015815", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Aug 14", "date_precision": "day", "issue": "", "normalized_date": "2023-08-14", "pages": "S2213-6711(23)00301-6", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Astrocytic APOE4 genotype-mediated negative impacts on synaptic architecture in human pluripotent stem cell model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "c-Myc, a transcription factor, induces cell proliferation and is often aberrantly or highly expressed in cancers. However, molecular mechanisms underlying this aberrantly high expression remain unclear. Here, we found that intracellular Ca(2+) concentration regulates c-Myc oncoprotein stability. We identified that calcineurin, a Ca(2+)-dependent protein phosphatase, is a positive regulator of c-Myc expression. Calcineurin depletion suppresses c-Myc targeted gene expression and c-Myc degradation. Calcineurin directly dephosphorylates Thr(58) and Ser(62) in c-Myc, which inhibit binding to the ubiquitin ligase Fbxw7. Mutations within the autoinhibitory domain of calcineurin, most frequently observed in cancer, may increase phosphatase activity, increasing c-Myc transcriptional activity in turn. Notably, calcineurin inhibition with FK506 decreased c-Myc expression with enhanced Thr(58) and Ser(62) phosphorylation in a mouse xenograft model. Thus, calcineurin can stabilize c-Myc, promoting tumor progression. Therefore, we propose that Ca(2+) signaling dysfunction affects cancer-cell proliferation via increased c-Myc stability and that calcineurin inhibition could be a new therapeutic target of c-Myc-overexpressing cancers.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takahiro", "last_name": "Masaki", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Habara", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Hanaki", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Haruki", "last_name": "Tomiyasu", "name": null }, { "creator_type": "author", "first_name": "Yosei", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Midori", "last_name": "Shimada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-40412-1" }, "pmcid": { "normalized": "PMC10423207" }, "pmid": { "normalized": "37573463" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcineurin", "descriptor_ui": "D019703", "major_topic": true }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": true }, { "descriptor": "Transcriptional Activation", "descriptor_ui": "D015533", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Aug 12", "date_precision": "day", "issue": "1", "normalized_date": "2023-08-12", "pages": "13116", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Calcineurin-mediated dephosphorylation enhances the stability and transactivation of c-Myc.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Extracellular signal-regulated kinase (ERK) has been recognized as a critical regulator in various physiological and pathological processes. Extensive research has elucidated the signaling mechanisms governing ERK activation via biochemical regulations with upstream molecules, particularly receptor tyrosine kinases (RTKs). However, recent advances have highlighted the role of mechanical forces in activating the RTK-ERK signaling pathways, thereby opening new avenues of research into mechanochemical interplay in multicellular tissues. Here, we review the force-induced ERK activation in cells and propose possible mechanosensing mechanisms underlying the mechanoresponsive ERK activation. We conclude that mechanical forces are not merely passive factors shaping cells and tissues but also active regulators of cellular signaling pathways controlling collective cell behaviors.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ceb.2023.102217" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37574635" } }, "mesh": [ { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": true }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": true }, { "descriptor": "Receptor Protein-Tyrosine Kinases", "descriptor_ui": "D020794", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Aug 11", "date_precision": "day", "issue": "", "normalized_date": "2023-08-11", "pages": "102217", "proceedings_title": null, "publisher": "", "title": "Current opinion in cell biology", "volume": "84", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Stretching the limits of extracellular signal-related kinase (ERK) signaling - Cell mechanosensing to ERK activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Raman hyperspectral microscopy is a valuable tool in biological and biomedical imaging. Because Raman scattering is often weak in comparison to other phenomena, prevalent spectral fluctuations and contaminations have brought advancements in analytical and chemometric methods for Raman spectra. These chemometric advances have been key contributors to the applicability of Raman imaging to biological systems. As studies increase in scale, spectral contamination from extrinsic background, intensity from sources such as the optical components that are extrinsic to the sample of interest, has become an emerging issue. Although existing baseline correction schemes often reduce intrinsic background such as autofluorescence originating from the sample of interest, extrinsic background is not explicitly considered, and these methods often fail to reduce its effects. Here, we show that extrinsic background can significantly affect a classification model using Raman images, yielding misleadingly high accuracies in the distinction of benign and malignant samples of follicular thyroid cell lines. To mitigate its effects, we develop extrinsic background correction (EBC) and demonstrate its use in combination with existing methods on Raman hyperspectral images. EBC isolates regions containing the smallest amounts of sample materials that retain extrinsic contributions that are specific to the device or environment. We perform classification both with and without the use of EBC, and we find that EBC retains biological characteristics in the spectra while significantly reducing extrinsic background. As the methodology used in EBC is not specific to Raman spectra, correction of extrinsic effects in other types of hyperspectral and grayscale images is also possible.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "J. Nicholas", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Aurelien", "last_name": "Pelissier", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Bocklitz", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.3c01406" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37561910" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Aug 10", "date_precision": "day", "issue": "", "normalized_date": "2023-08-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Correction for Extrinsic Background in Raman Hyperspectral Images.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Interleukin (IL)-6 is abundantly expressed in the tumor microenvironment and is associated with poor patient outcomes. Here, we demonstrate that the deletion of the suppressor of cytokine signaling 3 (SOCS3) in T cells potentiates anti-tumor immune responses by conferring the anti-tumorigenic function of IL-6 in mouse and human models. In Socs3-deficient CD8(+) T cells, IL-6 upregulates the expression of type I interferon (IFN)-regulated genes and enhances the anti-tumor effector function of T cells, while also modifying mitochondrial fitness to increase mitochondrial membrane potential and reactive oxygen species (ROS) levels and to promote metabolic glycolysis in the energy state. Furthermore, Socs3 deficiency reduces regulatory T cells and increases T helper 1 (Th1) cells. SOCS3 knockdown in human chimeric antigen receptor T (CAR-T) cells exhibits a strong anti-tumor response in humanized mice. Thus, genetic disruption of SOCS3 offers an avenue to improve the therapeutic efficacy of adoptive T cell therapy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Setsuko", "last_name": "Mise-Omata", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Tanakorn", "last_name": "Srirat", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Nakagawara", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Iizuka-Koga", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nishimasu", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Nureki", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2023.112940" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37582370" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": true }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": true }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interleukin-6", "descriptor_ui": "D015850", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Suppressor of Cytokine Signaling 3 Protein", "descriptor_ui": "D000071223", "major_topic": true }, { "descriptor": "Th1 Cells", "descriptor_ui": "D018417", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Aug 8", "date_precision": "day", "issue": "", "normalized_date": "2023-08-08", "pages": "112940", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "SOCS3 deletion in effector T cells confers an anti-tumorigenic role of IL-6 to the pro-tumorigenic cytokine.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: In CheckMate 227 Part 1 (NCT02477826), first-line nivolumab plus ipilimumab demonstrated long-term durable overall survival (OS) benefit versus chemotherapy in patients with metastatic non-small cell lung cancer (NSCLC), regardless of tumor programmed death ligand 1 (PD-L1) expression. We report results in Japanese patients with >/= 5-year follow-up. METHODS: Adults with stage IV/recurrent NSCLC without EGFR/ALK aberrations were randomized 1:1:1 to nivolumab plus ipilimumab, nivolumab alone, or chemotherapy (patients with tumor PD-L1 >/= 1%), or nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (patients with tumor PD-L1 < 1%). Five-year efficacy and safety were assessed in Japanese patients. RESULTS: At 62.1 months' minimum follow-up, 143 Japanese patients with PD-L1 >/= 1% or < 1% were randomized to nivolumab plus ipilimumab (n = 66) or chemotherapy (n = 77). Five-year OS rates were 46% with nivolumab plus ipilimumab versus 34% with chemotherapy (PD-L1 >/= 1%) and 36% versus 19% (PD-L1 < 1%). Median duration of response was 59.1 versus 7.1 months (PD-L1 >/= 1%) and 17.3 versus 3.0 months (PD-L1 < 1%). Among 5-year survivors treated with nivolumab plus ipilimumab (PD-L1 >/= 1% and < 1%; n = 27), 59% (95% CI, 39%-75%) were off treatment for >/= 3 years without receiving subsequent therapy. No new safety signals were observed. CONCLUSIONS: At 5-year follow-up, nivolumab plus ipilimumab continued to show long-term durable clinical benefit versus chemotherapy, regardless of tumor PD-L1 expression. Consistent with findings for the global population, these data support the use of nivolumab plus ipilimumab as first-line treatment in Japanese patients with metastatic NSCLC.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Daga", "name": null }, { "creator_type": "author", "first_name": "Isamu", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kasahara", "name": null }, { "creator_type": "author", "first_name": "Tateaki", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Li", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Ravi G.", "last_name": "Gupta", "name": null }, { "creator_type": "author", "first_name": "Judith", "last_name": "Bushong", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Mizutani", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10147-023-02390-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37548831" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": false }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "East Asian People", "descriptor_ui": "D000095225", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ipilimumab", "descriptor_ui": "D000074324", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Nivolumab", "descriptor_ui": "D000077594", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Aug 7", "date_precision": "day", "issue": "", "normalized_date": "2023-08-07", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of clinical oncology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "First-line nivolumab plus ipilimumab in metastatic non-small cell lung cancer: 5-year outcomes in Japanese patients from CheckMate 227 Part 1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Endochondral ossification contributes to longitudinal skeletal growth. Osteoblasts, which are bone-forming cells, appear close to terminally differentiated hypertrophic chondrocytes during endochondral ossification. We established mice with conditional knockout (cKO) of Smad4, an essential co-activator for transforming growth factor beta family signaling. The mice showed a marked increase in bone volume in the metaphysis as a result of increased bone formation by osteoblasts, in which beta-catenin, an effector of canonical Wnt signaling, accumulated. We identified Wnt7b as a factor with increased expression in growth plate cartilage in Smad4 cKO mice. Wnt7b mRNA was expressed in differentiated chondrocytes and suppressed by BMP4 stimulation. Ablation of Wnt7b blunted the increase in bone in adult Smad4 cKO mice and reduced skeletal growth in juvenile mice. Overall, we conclude that Wnt7b is a crucial factor secreted from hypertrophic chondrocytes to initiate endochondral ossification. These results suggest that Smad4-dependent BMP signaling regulates the Wnt7b-beta-catenin axis during endochondral ossification.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sho", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Kuratani", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Eijiro", "last_name": "Jimi", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Takenobu", "last_name": "Katagiri", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.201734" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37539462" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "beta Catenin", "descriptor_ui": "D051176", "major_topic": false }, { "descriptor": "Bone and Bones", "descriptor_ui": "D001842", "major_topic": false }, { "descriptor": "Cartilage", "descriptor_ui": "D002356", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Chondrocytes", "descriptor_ui": "D019902", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Osteogenesis", "descriptor_ui": "D010012", "major_topic": true }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "Smad4 Protein", "descriptor_ui": "D051901", "major_topic": false }, { "descriptor": "Wnt Proteins", "descriptor_ui": "D051153", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Aug 1", "date_precision": "day", "issue": "15", "normalized_date": "2023-08-01", "pages": "dev201734", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "150", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Wnt7b expressed by hypertrophic chondrocytes is a stimulatory factor for endochondral ossification that is regulated by Smad4 activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mika", "last_name": "Sawane", "name": null }, { "creator_type": "author", "first_name": "Enkhtuul", "last_name": "Gantumur", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kajiya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jdermsci.2023.07.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37580204" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Aug 1", "date_precision": "day", "issue": "", "normalized_date": "2023-08-01", "pages": "S0923-1811(23)00166-4", "proceedings_title": null, "publisher": "", "title": "Journal of dermatological science", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Apelin provides an alternative function to estrogen in regulating lymphatic vascular integrity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The unremitting emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants necessitates ongoing control measures. Given its rapid spread, the new Omicron subvariant BA.5 requires urgent characterization. Here, we comprehensively analyzed BA.5 with the other Omicron variants BA.1, BA.2, and ancestral B.1.1. Although in vitro growth kinetics of BA.5 was comparable among the Omicron subvariants, BA.5 was much more fusogenic than BA.1 and BA.2. Airway-on-a-chip analysis showed that, among Omicron subvariants, BA.5 had enhanced ability to disrupt the respiratory epithelial and endothelial barriers. Furthermore, in our hamster model, in vivo pathogenicity of BA.5 was slightly higher than that of the other Omicron variants and less than that of ancestral B.1.1. Notably, BA.5 gains efficient virus spread compared with BA.1 and BA.2, leading to prompt immune responses. Our findings suggest that BA.5 has low pathogenicity compared with the ancestral strain but enhanced virus spread /inflammation compared with earlier Omicron subvariants.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Yamasoba", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Kamasaki", "name": null }, { "creator_type": "author", "first_name": "Naganori", "last_name": "Nao", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Rigel", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yukie", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Yoshimatsu", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tetsuharu", "last_name": "Nagamoto", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Kanamune", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Matsuno", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takasuke", "last_name": "Fukuhara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-023-05081-w" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37488344" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Cricetinae", "descriptor_ui": "D006224", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false }, { "descriptor": "Virulence", "descriptor_ui": "D014774", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jul 24", "date_precision": "day", "issue": "1", "normalized_date": "2023-07-24", "pages": "772", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "6", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparative pathogenicity of SARS-CoV-2 Omicron subvariants including BA.1, BA.2, and BA.5.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Clustered protocadherin (Pcdh), a cell adhesion protein, is involved in the self-recognition and non-self-discrimination of neurons by conferring diversity on the cell surface. Although the roles of Pcdh in neurons have been elucidated, it has been challenging to visualize its adhesion activity in neurons, which is a molecular function of Pcdh. Here, we present fluorescent indicators, named IPADs, which visualize the interaction of protocadherin-alpha4 isoform (alpha4). IPADs successfully visualize not only homophilic alpha4 trans-interactions, but also combinatorial homophilic interactions between cells. The reversible nature of IPADs overcomes a drawback of the split-GFP technique and allows for monitoring the dissociation of alpha4 trans-interactions. Specially designed IPADs for self-recognition are able to monitor the formation and disruption of alpha4 trans-interactions between processes originating from the same neurons. We expect that IPADs will be useful tools for obtaining spatiotemporal information on Pcdh interactions in neuronal self-recognition and non-self-discrimination processes.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Kanadome", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Hoshino", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2023.107238" }, "pmcid": { "normalized": "PMC10392085" }, "pmid": { "normalized": "37534169" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Jul 21", "date_precision": "day", "issue": "7", "normalized_date": "2023-07-21", "pages": "107238", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "26", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualization of trans-interactions of a protocadherin-alpha between processes originating from single neurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Single-cell RNA sequencing is a valuable tool for dissecting cellular heterogeneity in complex systems. However, it is still challenging to estimate the proliferation and differentiation potentials of subpopulations within dormant tissue stem cells. Here, we established a new single-cell analysis method for profiling the organoid-forming capacity and differentiation potential of tissue stem cells to disclose stem cell subpopulations by integrating single-cell morphometrics, organoid-forming assay, and RNA sequencing, a method named scMORN. To explore lung epithelial stem cells, we initially developed feeder-free culture system, which could expand all major lung stem cells, including basal, club, and alveolar type 2 (AT2) cells, and found that club cells contained a subpopulation, which showed better survival rate and high proliferation capacity and could differentiate into alveolar cells. Using the scMORN method, we discovered a club cell subpopulation named Muc5b+ and large club (ML-club) cells that efficiently formed organoids than other club or AT2 cells in our feeder-free organoid culture and differentiated into alveolar cells in vitro. Single-cell transcriptome profiling and immunohistochemical analysis revealed that ML-club cells localized at the intrapulmonary proximal airway and distinct from known subpopulations of club cells such as BASCs. Furthermore, we identified CD14 as a cell surface antigen of ML-club cells and showed that purified CD14+ club cells engrafted into injured mouse lungs had better engraftment rate and expansion than other major lung stem cells, reflecting the observations in organoid culture systems. The scMORN method could be adapted to different stem cell tissues to discover useful stem-cell subpopulations.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Fujimura", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Katsura", "name": null }, { "creator_type": "author", "first_name": "Taisaku", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Yamaoka", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Morimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/stmcls/sxad044" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37468433" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jul 20", "date_precision": "day", "issue": "", "normalized_date": "2023-07-20", "pages": "sxad044", "proceedings_title": null, "publisher": "", "title": "Stem cells (Dayton, Ohio)", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000304" ] }, "title": "Identifying a Lung Stem Cell Subpopulation by Combining Single-Cell Morphometrics, Organoid Culture, and Transcriptomics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Plants adapt to periodic environmental changes, such as day and night, by using circadian clocks. Cell division and elongation are primary steps to adjust plant development according to their environments. In Arabidopsis, hypocotyl elongation has been studied as a representative model to understand how the circadian clock regulates cell elongation. However, it remains unknown whether similar phenomena exist in other organs, such as roots, where circadian clocks regulate physiological responses. Here, we show that root hair elongation is controlled by both light and the circadian clock. By developing machine-learning models to automatically analyze the images of root hairs, we found that genes encoding major components of the central oscillator, such as TIMING OF CAB EXPRESSION1 (TOC1) or CIRCADIAN CLOCK ASSOCIATED1 (CCA1), regulate the rhythmicity of root hair length. The partial illumination of light to either shoots or roots suggested that light received in shoots is mainly responsible for the generation of root hair rhythmicity. Furthermore, grafting experiments between wild-type (WT) and toc1 plants demonstrated that TOC1 in shoots is responsible for the generation of root hair rhythmicity. Our results illustrate the combinational effects of long-distance signaling and the circadian clock on the regulation of root hair length.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hikari", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Taiga", "last_name": "Uchikawa", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Shishikui", "name": null }, { "creator_type": "author", "first_name": "Masaaki K.", "last_name": "Watahiki", "name": null }, { "creator_type": "author", "first_name": "Akane", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Motomu", "last_name": "Endo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pcp/pcad076" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37552691" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Circadian Clocks", "descriptor_ui": "D057906", "major_topic": true }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jul 19", "date_precision": "day", "issue": "", "normalized_date": "2023-07-19", "pages": "pcad076", "proceedings_title": null, "publisher": "", "title": "Plant & cell physiology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Circadian Clock Controls Root Hair Elongation through Long-Distance Communication.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In eukaryotic motile cells, the active Ras (Ras-GTP)-enriched domain is generated in an asymmetric manner on the cell membrane through the excitable dynamics of an intracellular signaling network. This asymmetric Ras signaling regulates pseudopod formation for both spontaneous random migration and chemoattractant-induced directional migration. While membrane lipids, such as sphingomyelin and phosphatidylserine, contribute to Ras signaling in various cell types, whether they are involved in the Ras excitability for cell motility is unknown. Here we report that functional Ras excitability requires the normal metabolism of sphingomyelin for efficient cell motility and chemotaxis. The pharmacological blockade of sphingomyelin metabolism by an acid-sphingomyelinase inhibitor, fendiline, and other inhibitors suppressed the excitable generation of the stable Ras-GTP-enriched domain. The suppressed excitability failed to invoke enough basal motility to achieve directed migration under shallow chemoattractant gradients. The fendiline-induced defects in Ras excitability, motility and stimulation-elicited directionality were due to an accumulation of sphingomyelin on the membrane, which could be recovered by exogenous sphingomyelinase or phosphatidylserine without changing the expression of Ras. These results indicate a novel regulatory mechanism of the excitable system by membrane lipids, in which sphingomyelin metabolism provides a membrane environment to ensure Ras excitation for efficient cellular motility and chemotaxis. Key Words: Cell polarity, Cell migration, Ras, Excitability, Sphingomyelin.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Da Young", "last_name": "Shin", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1247/csf.23045" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37438131" } }, "mesh": [ { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Chemotactic Factors", "descriptor_ui": "D002630", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": true }, { "descriptor": "Fendiline", "descriptor_ui": "D005275", "major_topic": false }, { "descriptor": "Guanosine Triphosphate", "descriptor_ui": "D006160", "major_topic": false }, { "descriptor": "Phosphatidylserines", "descriptor_ui": "D010718", "major_topic": false }, { "descriptor": "Sphingomyelin Phosphodiesterase", "descriptor_ui": "D013108", "major_topic": false }, { "descriptor": "Sphingomyelins", "descriptor_ui": "D013109", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jul 12", "date_precision": "day", "issue": "", "normalized_date": "2023-07-12", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cell structure and function", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Sphingomyelin metabolism underlies Ras excitability for efficient cell migration and chemotaxis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A growing community is constructing a next-generation file format (NGFF) for bioimaging to overcome problems of scalability and heterogeneity. Organized by the Open Microscopy Environment (OME), individuals and institutes across diverse modalities facing these problems have designed a format specification process (OME-NGFF) to address these needs. This paper brings together a wide range of those community members to describe the cloud-optimized format itself-OME-Zarr-along with tools and data resources available today to increase FAIR access and remove barriers in the scientific process. The current momentum offers an opportunity to unify a key component of the bioimaging domain-the file format that underlies so many personal, institutional, and global data management and analysis tasks.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Josh", "last_name": "Moore", "name": null }, { "creator_type": "author", "first_name": "Daniela", "last_name": "Basurto-Lozada", "name": null }, { "creator_type": "author", "first_name": "Sebastien", "last_name": "Besson", "name": null }, { "creator_type": "author", "first_name": "John", "last_name": "Bogovic", "name": null }, { "creator_type": "author", "first_name": "Jordao", "last_name": "Bragantini", "name": null }, { "creator_type": "author", "first_name": "Eva M.", "last_name": "Brown", "name": null }, { "creator_type": "author", "first_name": "Jean-Marie", "last_name": "Burel", "name": null }, { "creator_type": "author", "first_name": "Xavier", "last_name": "Casas Moreno", "name": null }, { "creator_type": "author", "first_name": "Gustavo", "last_name": "de Medeiros", "name": null }, { "creator_type": "author", "first_name": "Erin E.", "last_name": "Diel", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Gault", "name": null }, { "creator_type": "author", "first_name": "Satrajit S.", "last_name": "Ghosh", "name": null }, { "creator_type": "author", "first_name": "Ilan", "last_name": "Gold", "name": null }, { "creator_type": "author", "first_name": "Yaroslav O.", "last_name": "Halchenko", "name": null }, { "creator_type": "author", "first_name": "Matthew", "last_name": "Hartley", "name": null }, { "creator_type": "author", "first_name": "Dave", "last_name": "Horsfall", "name": null }, { "creator_type": "author", "first_name": "Mark S.", "last_name": "Keller", "name": null }, { "creator_type": "author", "first_name": "Mark", "last_name": "Kittisopikul", "name": null }, { "creator_type": "author", "first_name": "Gabor", "last_name": "Kovacs", "name": null }, { "creator_type": "author", "first_name": "Aybuke", "last_name": "Kupcu Yoldas", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Albane", "last_name": "le Tournoulx de la Villegeorges", "name": null }, { "creator_type": "author", "first_name": "Tong", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Prisca", "last_name": "Liberali", "name": null }, { "creator_type": "author", "first_name": "Dominik", "last_name": "Lindner", "name": null }, { "creator_type": "author", "first_name": "Melissa", "last_name": "Linkert", "name": null }, { "creator_type": "author", "first_name": "Joel", "last_name": "Luthi", "name": null }, { "creator_type": "author", "first_name": "Jeremy", "last_name": "Maitin-Shepard", "name": null }, { "creator_type": "author", "first_name": "Trevor", "last_name": "Manz", "name": null }, { "creator_type": "author", "first_name": "Luca", "last_name": "Marconato", "name": null }, { "creator_type": "author", "first_name": "Matthew", "last_name": "McCormick", "name": null }, { "creator_type": "author", "first_name": "Merlin", "last_name": "Lange", "name": null }, { "creator_type": "author", "first_name": "Khaled", "last_name": "Mohamed", "name": null }, { "creator_type": "author", "first_name": "William", "last_name": "Moore", "name": null }, { "creator_type": "author", "first_name": "Nils", "last_name": "Norlin", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Ouyang", "name": null }, { "creator_type": "author", "first_name": "Bugra", "last_name": "Ozdemir", "name": null }, { "creator_type": "author", "first_name": "Giovanni", "last_name": "Palla", "name": null }, { "creator_type": "author", "first_name": "Constantin", "last_name": "Pape", "name": null }, { "creator_type": "author", "first_name": "Lucas", "last_name": "Pelkmans", "name": null }, { "creator_type": "author", "first_name": "Tobias", "last_name": "Pietzsch", "name": null }, { "creator_type": "author", "first_name": "Stephan", "last_name": "Preibisch", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Prete", "name": null }, { "creator_type": "author", "first_name": "Norman", "last_name": "Rzepka", "name": null }, { "creator_type": "author", "first_name": "Sameeul", "last_name": "Samee", "name": null }, { "creator_type": "author", "first_name": "Nicholas", "last_name": "Schaub", "name": null }, { "creator_type": "author", "first_name": "Hythem", "last_name": "Sidky", "name": null }, { "creator_type": "author", "first_name": "Ahmet Can", "last_name": "Solak", "name": null }, { "creator_type": "author", "first_name": "David R.", "last_name": "Stirling", "name": null }, { "creator_type": "author", "first_name": "Jonathan", "last_name": "Striebel", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Tischer", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Toloudis", "name": null }, { "creator_type": "author", "first_name": "Isaac", "last_name": "Virshup", "name": null }, { "creator_type": "author", "first_name": "Petr", "last_name": "Walczysko", "name": null }, { "creator_type": "author", "first_name": "Alan M.", "last_name": "Watson", "name": null }, { "creator_type": "author", "first_name": "Erin", "last_name": "Weisbart", "name": null }, { "creator_type": "author", "first_name": "Frances", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Kevin A.", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Omer", "last_name": "Bayraktar", "name": null }, { "creator_type": "author", "first_name": "Beth A.", "last_name": "Cimini", "name": null }, { "creator_type": "author", "first_name": "Nils", "last_name": "Gehlenborg", "name": null }, { "creator_type": "author", "first_name": "Muzlifah", "last_name": "Haniffa", "name": null }, { "creator_type": "author", "first_name": "Nathan", "last_name": "Hotaling", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Loic A.", "last_name": "Royer", "name": null }, { "creator_type": "author", "first_name": "Stephan", "last_name": "Saalfeld", "name": null }, { "creator_type": "author", "first_name": "Oliver", "last_name": "Stegle", "name": null }, { "creator_type": "author", "first_name": "Fabian J.", "last_name": "Theis", "name": null }, { "creator_type": "author", "first_name": "Jason R.", "last_name": "Swedlow", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00418-023-02209-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37428210" } }, "mesh": [ { "descriptor": "Community Support", "descriptor_ui": "D000091443", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": true }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jul 10", "date_precision": "day", "issue": "", "normalized_date": "2023-07-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "Histochemistry and cell biology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "OME-Zarr: a cloud-optimized bioimaging file format with international community support.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Non-negative tensor factorization (NTF) enables the extraction of a small number of latent components from high-dimensional biomedical data. However, NTF requires many steps, which is a hurdle to implementation. Here, we provide a protocol for TensorLyCV, an easy to run and reproducible NTF analysis pipeline using Snakemake workflow management system and Docker container. Using vaccine adverse reaction data as an example, we describe steps for data processing, tensor decomposition, optimal rank parameter estimation, and visualization of factor matrices. For complete details on the use and execution of this protocol, please refer to Kei Ikeda et al.(1).", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Koki", "last_name": "Tsuyuzaki", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Goshima", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xpro.2023.102318" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37421614" } }, "mesh": [ { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Workflow", "descriptor_ui": "D057188", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jul 7", "date_precision": "day", "issue": "3", "normalized_date": "2023-07-07", "pages": "102318", "proceedings_title": null, "publisher": "", "title": "STAR protocols", "volume": "4", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Non-negative tensor factorization workflow for time series biomedical data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A line illumination Raman microscope extracts the underlying spatial and spectral information of a sample, typically a few hundred times faster than raster scanning. This makes it possible to measure a wide range of biological samples such as cells and tissues - that only allow modest intensity illumination to prevent potential damage - within feasible time frame. However, a non-uniform intensity distribution of laser line illumination may induce some artifacts in the data and lower the accuracy of machine learning models trained to predict sample class membership. Here, using cancerous and normal human thyroid follicular epithelial cell lines, FTC-133 and Nthy-ori 3-1 lines, whose Raman spectral difference is not so large, we show that the standard pre-processing of spectral analyses widely used for raster scanning microscopes introduced some artifacts. To address this issue, we proposed a detrending scheme based on random forest regression, a nonparametric model-free machine learning algorithm, combined with a position-dependent wavenumber calibration scheme along the illumination line. It was shown that the detrending scheme minimizes the artifactual biases arising from non-uniform laser sources and significantly enhances the differentiability of the sample states, i.e., cancerous or normal epithelial cells, compared to the standard pre-processing scheme.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Abdul Halim", "last_name": "Bhuiyan", "name": null }, { "creator_type": "author", "first_name": "Jean-Emmanuel", "last_name": "Clement", "name": null }, { "creator_type": "author", "first_name": "Zannatul", "last_name": "Ferdous", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "James Nicholas", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Bocklitz", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d3an00516j" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37403759" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Calibration", "descriptor_ui": "D002138", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Lighting", "descriptor_ui": "D008029", "major_topic": true }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jul 5", "date_precision": "day", "issue": "", "normalized_date": "2023-07-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "The Analyst", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Differentiability of cell types enhanced by detrending a non-homogeneous pattern in a line-illumination Raman microscope.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Microdroplet co-culture system is useful for the parallel assessment of numerous possible cell-cell interactions by generating isolated subcommunities from a pool of heterogeneous cells. However, the integration of single-cell sequencing into such analysis has been limited due to the lack of effective molecular identifiers for each in-droplet subcommunity. Here, we present a strategy for generating in-droplet subcommunity identifiers using DNA-functionalized microparticles encapsulated within microdroplets. These microparticles serve as initial information carriers, where their combinations act as distinct identifiers for in-droplet subcommunity. Upon optical trigger, DNA barcoding molecules encoding the microparticle information are once released in the microdroplets and then tag cell membranes. The tagged DNA molecules then serves as a second information carrier readable by single-cell sequencing to reconstitute the community in silico in single-cell RNA sequencing data space.", "classifications": [ { "id": "21H00416", "label": "21H00416", "researcher": "Sadao Ota", "type": "grant" }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Fumiko", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Mimori", "name": null }, { "creator_type": "author", "first_name": "Issei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/chem.202301133" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37404204" } }, "mesh": [ { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": true }, { "descriptor": "DNA Barcoding, Taxonomic", "descriptor_ui": "D058893", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jul 5", "date_precision": "day", "issue": "", "normalized_date": "2023-07-05", "pages": "e202301133", "proceedings_title": null, "publisher": "", "title": "Chemistry (Weinheim an der Bergstrasse, Germany)", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of In-droplet Multicellular Communities by Light-induced Combinatorial DNA Barcoding.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mechanisms governing chemotaxis in Chlamydomonas reinhardtii are largely unknown compared to those regulating phototaxis despite equal importance on the migratory response in the ciliated microalga. To study chemotaxis, we made a simple modification to a conventional Petri dish assay. Using the assay, a novel mechanism governing Chlamydomonas ammonium chemotaxis was revealed. First, we found that light exposure enhances the chemotactic response of wild-type Chlamydomonas strains, yet phototaxis-incompetent mutant strains, eye3-2 and ptx1, exhibit normal chemotaxis. This suggests that Chlamydomonas transduces the light signal pathway in chemotaxis differently from that in phototaxis. Second, we found that Chlamydomonas collectively migrate during chemotaxis but not phototaxis. Collective migration during chemotaxis is not clearly observed when the assay is conducted in the dark. Third, the Chlamydomonas strain CC-124 carrying agg1−, the AGGREGATE1 gene (AGG1) null mutation, exhibited a more robust collective migratory response than strains carrying the wild-type AGG1 gene. The expression of a recombinant AGG1 protein in the CC-124 strain suppressed this collective migration during chemotaxis. Altogether, these findings suggest a unique mechanism; ammonium chemotaxis in Chlamydomonas is mainly driven by collective cell migration. Furthermore, it is proposed that collective migration is enhanced by light and suppressed by the AGG1 protein.", "classifications": [ { "id": "21H00420", "label": "21H00420", "researcher": "Ken-ichi Wakabayashi", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Gabela", "last_name": "Nelson", "name": null }, { "creator_type": "author", "first_name": "Alexis", "last_name": "Strain", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Isu", "name": null }, { "creator_type": "author", "first_name": "Alireza", "last_name": "Rahnama", "name": null }, { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Adam T.", "last_name": "Melvin", "name": null }, { "creator_type": "author", "first_name": "Naohiro", "last_name": "Kato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-36818-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-07-04", "date_precision": "day", "issue": "1", "normalized_date": "2023-07-04", "pages": "10781", "proceedings_title": null, "publisher": "Nature Publishing Group", "title": "Scientific Reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000329" ], "repository": [ "ssbd-repos-000329" ] }, "title": "Cells collectively migrate during ammonium chemotaxis in Chlamydomonas reinhardtii", "url": "https://www.nature.com/articles/s41598-023-36818-6", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Recent advances in single-cell RNA sequencing technology have improved our understanding of the immunological landscape of rheumatoid arthritis (RA). We aimed to stratify the synovium from Japanese patients with RA by immune cell compositions and gain insight into the inflammatory drivers of each synovial phenotype. METHODS: Synovial tissues were obtained from Japanese patients with RA (n = 41) undergoing articular surgery. The cellular composition was quantified by a deconvolution approach using a public single-cell-based reference. Inflammatory pathway activity was calculated by gene set variation analysis, and chromatin accessibility was evaluated using Assay of Transposase Accessible Chromatin (ATAC)-sequencing. RESULTS: We stratified RA synovium into three distinct subtypes based on the hierarchical clustering of cellular composition data. One subtype was characterized by abundant HLA-DRA(high) synovial fibroblasts, autoimmune-associated B cells (ABCs), GZMK(+) GZMB(+) CD8(+) T cells, IL1-beta(+) monocytes, and plasmablasts. In addition, TNF-alpha, interferons, and IL-6 signaling were highly activated in this subtype, and the expression of various chemokines was significantly enhanced. Moreover, we found an open chromatin region overlapping with RA risk locus rs9405192 near the IRF4 gene, suggesting the genetic background influences the development of this inflammatory synovial state. The other two subtypes were characterized by increased IFNs and IL-6 signaling, and expression of molecules associated with degeneration, respectively. CONCLUSION: This study adds insights into the synovial heterogeneity in Japanese patients, and shows a promising link with predominant inflammatory signals. Evaluating the site of inflammation has the potential to lead to appropriate drug selection that matches the individual pathology. This article is protected by copyright. All rights reserved.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Sotaro", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Mineto", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Saeko", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Ryochi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Harumi", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Ninagawa", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Fujieda", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Aizaki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kajiyama", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Mimura", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Ohmura", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Morinobu", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Atsumi", "name": null }, { "creator_type": "author", "first_name": "Yoshiya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Sakae", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tomohisa", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Keishi", "last_name": "Fujio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/art.42642" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37390361" } }, "mesh": [ { "descriptor": "Arthritis, Rheumatoid", "descriptor_ui": "D001172", "major_topic": true }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "East Asian People", "descriptor_ui": "D000095225", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interferons", "descriptor_ui": "D007372", "major_topic": false }, { "descriptor": "Interleukin-6", "descriptor_ui": "D015850", "major_topic": true }, { "descriptor": "Synovial Membrane", "descriptor_ui": "D013583", "major_topic": false }, { "descriptor": "Tumor Necrosis Factor-alpha", "descriptor_ui": "D014409", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jun 30", "date_precision": "day", "issue": "", "normalized_date": "2023-06-30", "pages": "", "proceedings_title": null, "publisher": "", "title": "Arthritis & rheumatology (Hoboken, N.J.)", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Synovial Tissue Heterogeneity in Japanese Patients with Rheumatoid Arthritis Elucidated Using a Cell-Type Deconvolution Approach.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Machine Learning has been increasingly used in the medical field, including managing patients undergoing hemodialysis. The random forest classifier is a Machine Learning method that can generate high accuracy and interpretability in the data analysis of various diseases. We attempted to apply Machine Learning to adjust dry weight, the appropriate volume status of patients undergoing hemodialysis, which requires a complex decision-making process considering multiple indicators and the patient's physical conditions. METHODS: All medical data and 69,375 dialysis records of 314 Asian patients undergoing hemodialysis at a single dialysis center in Japan between July 2018 and April 2020 were collected from the electronic medical record system. Using the random forest classifier, we developed models to predict the probabilities of adjusting the dry weight at each dialysis session. RESULTS: The areas under the receiver-operating-characteristic curves of the models for adjusting the dry weight upward and downward were 0.70 and 0.74, respectively. The average probability of upward adjustment of the dry weight had sharp a peak around the actual change over time, while the average probability of downward adjustment of the dry weight formed a gradual peak. Feature importance analysis revealed that median blood pressure decline was a strong predictor for adjusting the dry weight upward. In contrast, elevated serum levels of C-reactive protein and hypoalbuminemia were important indicators for adjusting the dry weight downward. CONCLUSIONS: The random forest classifier should provide a helpful guide to predict the optimal changes to the dry weight with relative accuracy and may be useful in clinical practice.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Oya", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Aizawa", "name": null }, { "creator_type": "author", "first_name": "Kyogo", "last_name": "Wagatsuma", "name": null }, { "creator_type": "author", "first_name": "Masatomo", "last_name": "Kamimae", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Hanae", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Narihito", "last_name": "Tatsumoto", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Asanuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12882-023-03248-5" }, "pmcid": { "normalized": "PMC10308746" }, "pmid": { "normalized": "37386392" } }, "mesh": [ { "descriptor": "Asian", "descriptor_ui": "D001213", "major_topic": true }, { "descriptor": "Blood Pressure", "descriptor_ui": "D001794", "major_topic": false }, { "descriptor": "Body Weight", "descriptor_ui": "D001835", "major_topic": false }, { "descriptor": "Body Weight Changes", "descriptor_ui": "D001836", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Random Forest", "descriptor_ui": "D000093743", "major_topic": false }, { "descriptor": "Renal Dialysis", "descriptor_ui": "D006435", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jun 29", "date_precision": "day", "issue": "1", "normalized_date": "2023-06-29", "pages": "196", "proceedings_title": null, "publisher": "", "title": "BMC nephrology", "volume": "24", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Predicting dry weight change in Hemodialysis patients using machine learning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Significant progress has been made in understanding the pathogenesis of pancreatic ductal adenocarcinoma (PDAC) by generating and using murine models. To accelerate drug discovery by identifying novel therapeutic targets on a systemic level, here we generated a Drosophila model mimicking the genetic signature in PDAC (KRAS, TP53, CDKN2A, and SMAD4 alterations), which is associated with the worst prognosis in patients. The '4-hit' flies displayed epithelial transformation and decreased survival. Comprehensive genetic screening of their entire kinome revealed kinases including MEK and AURKB as therapeutic targets. Consistently, a combination of the MEK inhibitor trametinib and the AURKB inhibitor BI-831266 suppressed the growth of human PDAC xenografts in mice. In patients with PDAC, the activity of AURKB was associated with poor prognosis. This fly-based platform provides an efficient whole-body approach that complements current methods for identifying therapeutic targets in PDAC. SIGNIFICANCE: Development of a Drosophila model mimicking genetic alterations in human pancreatic ductal adenocarcinoma provides a tool for genetic screening that identifies MEK and AURKB inhibition as a potential treatment strategy.", "classifications": [ { "id": "19H05412", "label": "19H05412", "researcher": "Masahiro Sonoshita", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Sho", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Junki", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Ryodai", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Ooshio", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kosuge", "name": null }, { "creator_type": "author", "first_name": "Reo", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kanako C.", "last_name": "Hatanaka", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Hatanaka", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Mitsuhashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Matsuno", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/0008-5472.can-22-3762" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37378549" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aurora Kinase B", "descriptor_ui": "D064107", "major_topic": false }, { "descriptor": "Carcinoma, Pancreatic Ductal", "descriptor_ui": "D021441", "major_topic": true }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase Kinases", "descriptor_ui": "D020929", "major_topic": false }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jun 28", "date_precision": "day", "issue": "", "normalized_date": "2023-06-28", "pages": "OF1-OF12", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Drosophila Screening Identifies Dual Inhibition of MEK and AURKB as an Effective Therapy for Pancreatic Ductal Adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Identification of the mechanisms of viral evasion from human antibodies is crucial both for understanding viral pathogenesis and for designing effective vaccines. Here we show in cell cultures that an N-glycan shield on the herpes simplex virus 1 (HSV-1) envelope glycoprotein B (gB) mediated evasion from neutralization and antibody-dependent cellular cytotoxicity due to pooled gamma-globulins derived from human blood. We also demonstrated that the presence of human gamma-globulins in mice and immunity to HSV-1 induced by viral infection in mice significantly reduced replication in their eyes of a mutant virus lacking the glycosylation site but had little effect on the replication of its repaired virus. These results suggest that an N-glycan shield on a specific site of HSV-1 envelope gB mediated evasion from human antibodies in vivo and from HSV-1 immunity induced by viral infection in vivo. Notably, we also found that an N-glycan shield on a specific site of HSV-1 gB was significant for HSV-1 neurovirulence and replication in the central nervous system of naive mice. Thus, we have identified a critical N-glycan shield on HSV-1 gB that has dual impacts, namely evasion from human antibodies in vivo and viral neurovirulence. IMPORTANCE Herpes simplex virus 1 (HSV-1) establishes lifelong latent and recurrent infections in humans. To produce recurrent infections that contribute to transmission of the virus to new human host(s), the virus must be able to evade the antibodies persisting in latently infected individuals. Here, we show that an N-glycan shield on the specific site of the envelope glycoprotein B (gB) of HSV-1 mediates evasion from pooled gamma-globulins derived from human blood both in cell cultures and mice. Notably, the N-glycan shield on the specific site of gB was also significant for HSV-1 neurovirulence in naive mice. Considering the clinical features of HSV-1 infection, these results suggest that the glycan shield not only facilitates recurrent HSV-1 infections in latently infected humans by evading antibodies but is also important for HSV-1 pathogenesis during the initial infection.", "classifications": [ { "id": "21H00417", "label": "21H00417", "researcher": "Yuhei Maruzuru", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ayano", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Shiho", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Moeka", "last_name": "Nobe", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Shinobu", "last_name": "Kitazume", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/mbio.00992-23" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37366623" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Neutralizing", "descriptor_ui": "D057134", "major_topic": false }, { "descriptor": "gamma-Globulins", "descriptor_ui": "D005719", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": true }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Reinfection", "descriptor_ui": "D000084063", "major_topic": false }, { "descriptor": "Viral Envelope Proteins", "descriptor_ui": "D014759", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jun 27", "date_precision": "day", "issue": "", "normalized_date": "2023-06-27", "pages": "e0099223", "proceedings_title": null, "publisher": "", "title": "mBio", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Dual impacts of a glycan shield on the envelope glycoprotein B of HSV-1: evasion from human antibodies in vivo and neurovirulence.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: The PACIFIC regimen of consolidation therapy with the programmed cell death-ligand 1 (PD-L1) inhibitor durvalumab after definitive concurrent chemoradiation therapy has become a standard of care for individuals with unresectable stage III non-small cell lung cancer (NSCLC). However, about half of treated patients experience disease progression within 1 year, with the mechanisms of treatment resistance being poorly understood. We here performed a nationwide prospective biomarker study to explore the resistance mechanisms (WJOG11518L/SUBMARINE). METHODS: A total of 135 patients with unresectable stage III NSCLC who received the PACIFIC regimen were included for comprehensive profiling of the tumor microenvironment by immunohistochemistry, transcriptome analysis, and genomic sequencing of pretreatment tumor tissue as well as flow cytometric analysis of circulating immune cells. Progression-free survival (PFS) was compared based on these biomarkers. RESULTS: The importance of preexisting effective adaptive immunity in tumors were revealed for treatment benefit regardless of genomic features. We also identified CD73-expression by cancer cells as a mechanism of resistance to the PACIFIC regimen. Multivariable analysis of immunohistochemistry data with key clinical factors as covariables indicated that low CD8(+) tumor-infiltrating lymphocytes (TILs) density and the high CD73(+) cancer cells were independently associated with poor durvalumab outcome (HRs, 4.05 [95% CI, 1.17-14.04] for CD8(+) TILs; 4.79 [95% CI, 1.12-20.58] for CD73). In addition, whole-exome sequencing of paired tumor samples suggested that cancer cells eventually escaped immune pressure as a result of neoantigen plasticity. CONCLUSIONS: Our study emphasizes the importance of functional adaptive immunity in stage III NSCLC, and implicates CD73 as a promising treatment target, thus providing insight forming a basis for development of a new treatment approach in NSCLC.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Haratani", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Nobuaki", "last_name": "Mamesaya", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Mitsuoka", "name": null }, { "creator_type": "author", "first_name": "Yasuto", "last_name": "Yoneshima", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Tanizaki", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Fujisaka", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Tsuruno", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Teraoka", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Otani", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Shuta", "last_name": "Tomida", "name": null }, { "creator_type": "author", "first_name": "Yasutaka", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2023.06.012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37364849" } }, "mesh": [ { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Chemoradiotherapy", "descriptor_ui": "D059248", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jun 24", "date_precision": "day", "issue": "", "normalized_date": "2023-06-24", "pages": "S1556-0864(23)00633-0", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Tumor microenvironment landscape of non-small cell lung cancer reveals resistance mechanisms for PD-L1 blockade following chemoradiotherapy: a multi-center prospective biomarker study (WJOG11518L/SUBMARINE).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Ascidians significantly change their body structure through metamorphosis, but the spatio-temporal cell dynamics in the early metamorphosis stage has not been clarified. A natural Ciona embryo is surrounded by maternally derived non-self-test cells before metamorphosis. However, after metamorphosis, the juvenile is surrounded by self-tunic cells derived from mesenchymal cell lineages. Both test cells and tunic cells are thought to be changed their distributions during metamorphosis, but the precise timing is unknown. RESULTS: Using a metamorphosis induction by mechanical stimulation, we investigated the dynamics of mesenchymal cells during metamorphosis in a precise time course. After the stimulation, two-round Ca(2+) transients were observed. Migrating mesenchymal cells came out through the epidermis within 10 min after the second phase. We named this event \"cell extravasation.\" The cell extravasation occurred at the same time as the backward movement of posterior trunk epidermal cells. Timelapse imaging of transgenic-line larva revealed that non-self-test cells and self-tunic cells temporarily coexist outside the body until the test cells are eliminated. At the juvenile stage, only extravasated self-tunic cells remained outside the body. CONCLUSIONS: We found that mesenchymal cells extravasated following two-round Ca(2+) transients, and distributions of test cells and tunic cells changed in the outer body after tail regression.", "classifications": [ { "id": "21H00440", "label": "21H00440", "researcher": "Kohji Hotta", "type": "grant" }, { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Nozomu M.", "last_name": "Totsuka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kuwana", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Sasakura", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/dvdy.636" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37341471" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ciona", "descriptor_ui": "D000077262", "major_topic": true }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": true }, { "descriptor": "Epidermal Cells", "descriptor_ui": "D000078404", "major_topic": false }, { "descriptor": "Epidermis", "descriptor_ui": "D004817", "major_topic": false }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": false }, { "descriptor": "Metamorphosis, Biological", "descriptor_ui": "D008675", "major_topic": false }, { "descriptor": "Urochordata", "descriptor_ui": "D014561", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jun 21", "date_precision": "day", "issue": "", "normalized_date": "2023-06-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "Developmental dynamics : an official publication of the American Association of Anatomists", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Distribution changes of non-self-test cells and self-tunic cells surrounding the outer body during Ciona metamorphosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Overlapping principles of embryonic and tumor biology have been described, with recent multi-omics campaigns uncovering shared molecular profiles between human pluripotent stem cells (hPSCs) and adult tumors. Here, using a chemical genomic approach, we provide biological evidence that early germ layer fate decisions of hPSCs reveal targets of human cancers. Single-cell deconstruction of hPSCs-defined subsets that share transcriptional patterns with transformed adult tissues. Chemical screening using a unique germ layer specification assay for hPSCs identified drugs that enriched for compounds that selectively suppressed the growth of patient-derived tumors corresponding exclusively to their germ layer origin. Transcriptional response of hPSCs to germ layer inducing drugs could be used to identify targets capable of regulating hPSC specification as well as inhibiting adult tumors. Our study demonstrates properties of adult tumors converge with hPSCs drug induced differentiation in a germ layer specific manner, thereby expanding our understanding of cancer stemness and pluripotency.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Luca", "last_name": "Orlando", "name": null }, { "creator_type": "author", "first_name": "Yannick D.", "last_name": "Benoit", "name": null }, { "creator_type": "author", "first_name": "Jennifer C.", "last_name": "Reid", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Allison L.", "last_name": "Boyd", "name": null }, { "creator_type": "author", "first_name": "Juan L.", "last_name": "Garcia-Rodriguez", "name": null }, { "creator_type": "author", "first_name": "Borko", "last_name": "Tanasijevic", "name": null }, { "creator_type": "author", "first_name": "Meaghan S.", "last_name": "Doyle", "name": null }, { "creator_type": "author", "first_name": "Artee", "last_name": "Luchman", "name": null }, { "creator_type": "author", "first_name": "Ian J.", "last_name": "Restall", "name": null }, { "creator_type": "author", "first_name": "Christopher J.", "last_name": "Bergin", "name": null }, { "creator_type": "author", "first_name": "Angelique N.", "last_name": "Masibag", "name": null }, { "creator_type": "author", "first_name": "Lili", "last_name": "Aslostovar", "name": null }, { "creator_type": "author", "first_name": "Justin", "last_name": "Di Lu", "name": null }, { "creator_type": "author", "first_name": "Sarah", "last_name": "Laronde", "name": null }, { "creator_type": "author", "first_name": "Tony J.", "last_name": "Collins", "name": null }, { "creator_type": "author", "first_name": "Samuel", "last_name": "Weiss", "name": null }, { "creator_type": "author", "first_name": "Mickie", "last_name": "Bhatia", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chembiol.2023.06.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37379846" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jun 16", "date_precision": "day", "issue": "", "normalized_date": "2023-06-16", "pages": "S2451-9456(23)00158-7", "proceedings_title": null, "publisher": "", "title": "Cell chemical biology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Chemical genomics reveals targetable programs of human cancers rooted in pluripotency.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The French and Japanese Developmental Biology Societies, teaming up with Human Frontier Science Program, were eager to meet back in person in November 2022 in the lovely city of Strasbourg. Top scientists in the developmental biology field from France and Japan, but also from United States, United Kingdom, Switzerland or Germany shared their exciting science during the 4 days of this meeting. Core fields of developmental biology such as morphogenesis, patterning, cell identity, and cell state transition, notably at the single cell level, were well represented, and a diversity of experimental models, including plants, animals, and other exotic organisms, as well as some in vitro cellular models, were covered. This event also extended the scope of classic scientific gatherings for two reasons. First the involvement of artists during the preparation of the event and on site. Second, part of the meeting was open for the general public through a series of outreach events, including a music and video presentation through projection mapping at Rohan palace, as well as public lectures.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Oginuma", "last_name": "Masayuki", "name": null }, { "creator_type": "author", "first_name": "Anne-Cecile", "last_name": "Reymann", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/dvg.23527" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37313745" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Developmental Biology", "descriptor_ui": "D015509", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jun 14", "date_precision": "day", "issue": "", "normalized_date": "2023-06-14", "pages": "e23527", "proceedings_title": null, "publisher": "", "title": "Genesis (New York, N.Y. : 2000)", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Meeting report: Third Franco-Japanese developmental biology meeting \"New Frontiers in developmental biology: Celebrating the diversity of life\".", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of motor neurons. Although repeat expansion in C9orf72 is its most common cause, the pathogenesis of ALS isn't fully clear. In this study, we show that repeat expansion in LRP12, a causative variant of oculopharyngodistal myopathy type 1 (OPDM1), is a cause of ALS. We identify CGG repeat expansion in LRP12 in five families and two simplex individuals. These ALS individuals (LRP12-ALS) have 61-100 repeats, which contrasts with most OPDM individuals with repeat expansion in LRP12 (LRP12-OPDM), who have 100-200 repeats. Phosphorylated TDP-43 is present in the cytoplasm of iPS cell-derived motor neurons (iPSMNs) in LRP12-ALS, a finding that reproduces the pathological hallmark of ALS. RNA foci are more prominent in muscle and iPSMNs in LRP12-ALS than in LRP12-OPDM. Muscleblind-like 1 aggregates are observed only in OPDM muscle. In conclusion, CGG repeat expansions in LRP12 cause ALS and OPDM, depending on the length of the repeat. Our findings provide insight into the repeat length-dependent switching of phenotypes.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kodai", "last_name": "Kume", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kurashige", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Morino", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Kikumoto", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Silvia Natsuko", "last_name": "Akutsu", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakamori", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Rumiko", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Niihori", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Ogasawara", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Eura", "name": null }, { "creator_type": "author", "first_name": "Tamaki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Yokomura", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Hidefumi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Riku", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Ichizo", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Yuishin", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ajhg.2023.05.014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37339631" } }, "mesh": [ { "descriptor": "Amyotrophic Lateral Sclerosis", "descriptor_ui": "D000690", "major_topic": true }, { "descriptor": "C9orf72 Protein", "descriptor_ui": "D000073885", "major_topic": false }, { "descriptor": "DNA Repeat Expansion", "descriptor_ui": "D042622", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Low Density Lipoprotein Receptor-Related Protein-1", "descriptor_ui": "D026503", "major_topic": false }, { "descriptor": "Motor Neurons", "descriptor_ui": "D009046", "major_topic": false }, { "descriptor": "Muscular Dystrophies", "descriptor_ui": "D009136", "major_topic": true }, { "descriptor": "Neurodegenerative Diseases", "descriptor_ui": "D019636", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jun 9", "date_precision": "day", "issue": "", "normalized_date": "2023-06-09", "pages": "S0002-9297(23)00198-2", "proceedings_title": null, "publisher": "", "title": "American journal of human genetics", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "CGG repeat expansion in LRP12 in amyotrophic lateral sclerosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human genetics strongly support the involvement of synaptopathy in psychiatric disorders. However, trans-scale causality linking synapse pathology to behavioral changes is lacking. To address this question, we examined the effects of synaptic inputs on dendrites, cells, and behaviors of mice with knockdown of SETD1A and DISC1, which are validated animal models of schizophrenia. Both models exhibited an overrepresentation of extra-large (XL) synapses, which evoked supralinear dendritic and somatic integration, resulting in increased neuronal firing. The probability of XL spines correlated negatively with working memory, and the optical prevention of XL spine generation restored working memory impairment. Furthermore, XL synapses were more abundant in the postmortem brains of patients with schizophrenia than in those of matched controls. Our findings suggest that working memory performance, a pivotal aspect of psychiatric symptoms, is shaped by distorted dendritic and somatic integration via XL spines.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kisho", "last_name": "Obi-Nagata", "name": null }, { "creator_type": "author", "first_name": "Norimitsu", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Ryuhei", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Matthew L.", "last_name": "MacDonald", "name": null }, { "creator_type": "author", "first_name": "Kenneth N.", "last_name": "Fish", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Nagahama", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Okimura", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Yugo", "last_name": "Fukazawa", "name": null }, { "creator_type": "author", "first_name": "Robert A.", "last_name": "Sweet", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Hayashi-Takagi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.ade5973" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-06-09", "date_precision": "day", "issue": "23", "normalized_date": "2023-06-09", "pages": "eade5973", "proceedings_title": null, "publisher": "American Association for the Advancement of Science", "title": "Science Advances", "volume": "9", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Distorted neurocomputation by a small number of extra-large spines in psychiatric disorders", "url": "https://www.science.org/doi/10.1126/sciadv.ade5973", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell extrusion is a universal mode of cell removal from tissues, and it plays an important role in regulating cell numbers and eliminating unwanted cells. However, the underlying mechanisms of cell delamination from the cell layer are unclear. Here, we report a conserved execution mechanism of apoptotic cell extrusion. We found extracellular vesicle (EV) formation in extruding mammalian and Drosophila cells at a site opposite to the extrusion direction. Lipid-scramblase-mediated local exposure of phosphatidylserine is responsible for EV formation and is crucial for executing cell extrusion. Inhibition of this process disrupts prompt cell delamination and tissue homeostasis. Although the EV has hallmarks of an apoptotic body, its formation is governed by the mechanism of microvesicle formation. Experimental and mathematical modeling analysis illustrated that EV formation promotes neighboring cells' invasion. This study showed that membrane dynamics play a crucial role in cell exit by connecting the actions of the extruding cell and neighboring cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihito", "last_name": "Kira", "name": null }, { "creator_type": "author", "first_name": "Ichiko", "last_name": "Tatsutomi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Machiko", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Haruna", "last_name": "Kajita", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Muraki", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Saya", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Seisuke", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Onoue", "name": null }, { "creator_type": "author", "first_name": "Shigenobu", "last_name": "Yonemura", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Arakawa", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null }, { "creator_type": "author", "first_name": "Kohki", "last_name": "Kawane", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2023.05.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37315563" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": false }, { "descriptor": "Extracellular Vesicles", "descriptor_ui": "D000067128", "major_topic": true }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Phosphatidylserines", "descriptor_ui": "D010718", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jun 7", "date_precision": "day", "issue": "", "normalized_date": "2023-06-07", "pages": "S1534-5807(23)00241-1", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Apoptotic extracellular vesicle formation via local phosphatidylserine exposure drives efficient cell extrusion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Kinetochore is an essential protein complex required for accurate chromosome segregation. The constitutive centromere-associated network (CCAN), a subcomplex of the kinetochore, associates with centromeric chromatin and provides a platform for the kinetochore assembly. The CCAN protein CENP-C is thought to be a central hub for the centromere/kinetochore organization. However, the role of CENP-C in CCAN assembly needs to be elucidated. Here, we demonstrate that both the CCAN-binding domain and the C-terminal region that includes the Cupin domain of CENP-C are necessary and sufficient for chicken CENP-C function. Structural and biochemical analyses reveal self-oligomerization of the Cupin domains of chicken and human CENP-C. We find that the CENP-C Cupin domain oligomerization is vital for CENP-C function, centromeric localization of CCAN, and centromeric chromatin organization. These results suggest that CENP-C facilitates the centromere/kinetochore assembly through its oligomerization.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Ariyoshi", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Ryu-Suke", "last_name": "Nozawa", "name": null }, { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Isabelle", "last_name": "Jansen", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Fukagawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.molcel.2023.05.023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37295434" } }, "mesh": [ { "descriptor": "Centromere", "descriptor_ui": "D002503", "major_topic": true }, { "descriptor": "Centromere Protein A", "descriptor_ui": "D000076247", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Chromosomal Proteins, Non-Histone", "descriptor_ui": "D002868", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kinetochores", "descriptor_ui": "D018386", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jun 6", "date_precision": "day", "issue": "", "normalized_date": "2023-06-06", "pages": "S1097-2765(23)00379-9", "proceedings_title": null, "publisher": "", "title": "Molecular cell", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Centromere/kinetochore is assembled through CENP-C oligomerization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Endothelial-to-hematopoietic transition (EHT) is crucial for hematopoietic stem cell (HSC) generation. During EHT, the morphology of hemogenic endothelial cells (HECs) changes from flat and adherent to spherical hematopoietic cells, which detach from the dorsal aorta. HECs attain a rounded shape in a mitosis-independent manner before cell adhesion termination, suggesting an atypical cell-rounding mechanism. However, the direct mechanisms underlying this change in cell morphology during EHT remain unclear. Here, we show that large vacuoles were transiently formed in avian HECs, and that aquaporin 1 (AQP1) was localized in the vacuole and plasma membranes. Overexpression of AQP1 in non-HECs induced ectopic vacuole expansion, cell rounding and subsequent cell detachment from the endothelium into the bloodstream, mimicking EHT. Loss of redundant AQP functions by CRISPR/Cas9 gene editing in HECs impeded the morphological EHT. Our findings provide the first evidence to indicate that morphological segregation of hematopoietic cells from endothelial cells is regulated by water influx into vacuoles. These findings provide important insights for further exploration of the mechanisms underlying cell/tissue morphogenesis through water-adoptive cellular responses.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Mugiho", "last_name": "Shigematsu", "name": null }, { "creator_type": "author", "first_name": "Maria", "last_name": "Shibata-Kanno", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Maejima", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.201275" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37272531" } }, "mesh": [ { "descriptor": "Aquaporins", "descriptor_ui": "D020346", "major_topic": true }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Hemangioblasts", "descriptor_ui": "D055018", "major_topic": true }, { "descriptor": "Hematopoiesis", "descriptor_ui": "D006410", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Vacuoles", "descriptor_ui": "D014617", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jun 1", "date_precision": "day", "issue": "11", "normalized_date": "2023-06-01", "pages": "dev201275", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "150", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000310" ], "repository": [ "ssbd-repos-000310" ] }, "title": "Aquaporin regulates cell rounding through vacuole formation during endothelial-to-hematopoietic transition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Abnormal alpha-synuclein aggregation is a key pathological feature of a group of neurodegenerative diseases known as synucleinopathies, which include Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy (MSA). The pathogenic beta-sheet seed conformation of alpha-synuclein is found in various tissues, suggesting potential as a biomarker, but few studies have been able to reliably detect these seeds in serum samples. In this study, we developed a modified assay system, called immunoprecipitation-based real-time quaking-induced conversion (IP/RT-QuIC), which enables the detection of pathogenic alpha-synuclein seeds in the serum of individuals with synucleinopathies. In our internal first and second cohorts, IP/RT-QuIC showed high diagnostic performance for differentiating PD versus controls (area under the curve (AUC): 0.96 (95% confidence interval (CI) 0.95-0.99)/AUC: 0.93 (95% CI 0.84-1.00)) and MSA versus controls (AUC: 0.64 (95% CI 0.49-0.79)/AUC: 0.73 (95% CI 0.49-0.98)). IP/RT-QuIC also showed high diagnostic performance in differentiating individuals with PD (AUC: 0.86 (95% CI 0.74-0.99)) and MSA (AUC: 0.80 (95% CI 0.65-0.97)) from controls in a blinded external cohort. Notably, amplified seeds maintained disease-specific properties, allowing the differentiation of samples from individuals with PD versus MSA. In summary, here we present a novel platform that may allow the detection of individuals with synucleinopathies using serum samples.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ayami", "last_name": "Okuzumi", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Shuko", "last_name": "Nojiri", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Imamichi-Tatano", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Kakuta", "name": null }, { "creator_type": "author", "first_name": "Akihide", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Yuanzhe", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Funayama", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Saiki", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Tsunemi", "name": null }, { "creator_type": "author", "first_name": "Deborah", "last_name": "McIntyre", "name": null }, { "creator_type": "author", "first_name": "Jean-Jacques", "last_name": "Gerardy", "name": null }, { "creator_type": "author", "first_name": "Michel", "last_name": "Mittelbronn", "name": null }, { "creator_type": "author", "first_name": "Rejko", "last_name": "Kruger", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Nukina", "name": null }, { "creator_type": "author", "first_name": "Nobutaka", "last_name": "Hattori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41591-023-02358-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37248302" } }, "mesh": [ { "descriptor": "alpha-Synuclein", "descriptor_ui": "D051844", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lewy Body Disease", "descriptor_ui": "D020961", "major_topic": true }, { "descriptor": "Multiple System Atrophy", "descriptor_ui": "D019578", "major_topic": true }, { "descriptor": "Parkinson Disease", "descriptor_ui": "D010300", "major_topic": true }, { "descriptor": "Synucleinopathies", "descriptor_ui": "D000080874", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 May 29", "date_precision": "day", "issue": "", "normalized_date": "2023-05-29", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature medicine", "volume": "", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000327" ], "repository": [ "ssbd-repos-000327" ] }, "title": "Propagative alpha-synuclein seeds as serum biomarkers for synucleinopathies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reproductive senescence is broadly observed across mammalian females, including humans, eventually leading to a loss of fertility. The pulsatile secretion of gonadotropin-releasing hormone (GnRH), which is essential for gonad function, is primarily controlled by kisspeptin neurons in the hypothalamic arcuate nucleus (ARC(kiss)), the pulse generator of GnRH. The pulsatility of GnRH release, as assessed by the amount of circulating gonadotropin, is markedly reduced in aged animals, suggesting that the malfunctions of ARC(kiss) may be responsible for reproductive aging and menopause-related disorders. However, the activity dynamics of ARC(kiss) during the natural transition to reproductive senescence remain unclear. Herein, we introduce chronic in vivo Ca(2+) imaging of ARC(kiss) in female mice by fiber photometry to monitor the synchronous episodes of ARC(kiss) (SEs(kiss)), a known hallmark of GnRH pulse generator activity, from the fully reproductive to acyclic phase over 1 year. During the reproductive phase, we find that not only the frequency, but also the intensities and waveforms of individual SEs(kiss), vary depending on the stage of the estrus cycle. During the transition to reproductive senescence, the integrity of SEs(kiss) patterns, including the frequency and waveforms, remains mostly unchanged, whereas the intensities tend to decline. These data illuminate the temporal dynamics of ARC(kiss) activities in aging female mice. More generally, our findings demonstrate the utility of fiber-photometry-based chronic imaging of neuroendocrine regulators in the brain to characterize aging-associated malfunction.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Teppei", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Mitsue", "last_name": "Hagihara", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.82533" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37223988" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gonadotropin-Releasing Hormone", "descriptor_ui": "D007987", "major_topic": false }, { "descriptor": "Kisspeptins", "descriptor_ui": "D059648", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Reproduction", "descriptor_ui": "D012098", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 May 24", "date_precision": "day", "issue": "", "normalized_date": "2023-05-24", "pages": "e82533", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "12", "year": 2023 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000297" ] }, "title": "Dynamics of pulsatile activities of arcuate kisspeptin neurons in aging female mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nuclear magnetic resonance (NMR) spectroscopy is one of the indispensable techniques in chemistry because it enables us to obtain accurate information on the chemical, electronic, and dynamic properties of molecules. Computational simulation of the NMR spectra requires time-consuming density functional theory (DFT) calculations for an ensemble of molecular conformations. For large flexible molecules, it is considered too high-cost since it requires time-averaging of the instantaneous chemical shifts of each nuclear spin across the conformational space of molecules for NMR timescales. Here, we present a Gaussian process/deep kernel learning-based machine learning (ML) method for enabling us to predict, average in time, and analyze the instantaneous chemical shifts of conformations in the molecular dynamics trajectory. We demonstrate the use of the method by computing the averaged 1H and 13C chemical shifts of each nuclear spin of a trefoil knot molecule consisting of 24 para-connected benzene rings (240 atoms). By training ML model with the chemical shift data obtained from DFT calculations, we predicted chemical shifts for each conformation during dynamics. We were able to observe the merging of the time-averaged chemical shifts of each nuclear spin in a singlet 1H NMR peak and two 13C NMR peaks for the knot molecule, in agreement with experimental measurements. The unique feature of the presented method is the use of the learned low-dimensional deep kernel representation of local spin environments for comparing and analyzing the local chemical environment histories of spins during dynamics. It allowed us to identify two groups of protons in the knot molecule, which implies that the observed singlet 1H NMR peak could be composed of the contributions from protons with two distinct local chemical environments.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mikhail", "last_name": "Tsitsvero", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/5.0147398" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37194718" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 May 21", "date_precision": "day", "issue": "19", "normalized_date": "2023-05-21", "pages": "194108", "proceedings_title": null, "publisher": "", "title": "The Journal of chemical physics", "volume": "158", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "NMR spectrum prediction for dynamic molecules by machine learning: A case study of trefoil knot molecule.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic disorder caused by overnutrition and can lead to nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). The transcription factor Forkhead box K1 (FOXK1) is implicated in regulation of lipid metabolism downstream of mechanistic target of rapamycin complex 1 (mTORC1), but its role in NAFLD-NASH pathogenesis is understudied. Here, we show that FOXK1 mediates nutrient-dependent suppression of lipid catabolism in the liver. Hepatocyte-specific deletion of Foxk1 in mice fed a NASH-inducing diet ameliorates not only hepatic steatosis but also associated inflammation, fibrosis, and tumorigenesis, resulting in improved survival. Genome-wide transcriptomic and chromatin immunoprecipitation analyses identify several lipid metabolism-related genes, including Ppara, as direct targets of FOXK1 in the liver. Our results suggest that FOXK1 plays a key role in the regulation of hepatic lipid metabolism and that its inhibition is a promising therapeutic strategy for NAFLD-NASH, as well as for HCC.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shun", "last_name": "Fujinuma", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Nakatsumi", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Shigeaki", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Goya", "name": null }, { "creator_type": "author", "first_name": "Masatake", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Motoyuki", "last_name": "Kohjima", "name": null }, { "creator_type": "author", "first_name": "Masatomo", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Mikako", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Dongchon", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Mayo", "last_name": "Shigeta", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Bamba", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Keiichi I.", "last_name": "Nakayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2023.112530" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37209098" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinoma, Hepatocellular", "descriptor_ui": "D006528", "major_topic": true }, { "descriptor": "Fatty Acids", "descriptor_ui": "D005227", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Lipid Metabolism", "descriptor_ui": "D050356", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": true }, { "descriptor": "Mechanistic Target of Rapamycin Complex 1", "descriptor_ui": "D000076222", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Non-alcoholic Fatty Liver Disease", "descriptor_ui": "D065626", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 May 18", "date_precision": "day", "issue": "5", "normalized_date": "2023-05-18", "pages": "112530", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "42", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "FOXK1 promotes nonalcoholic fatty liver disease by mediating mTORC1-dependent inhibition of hepatic fatty acid oxidation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We identified neutralizing monoclonal antibodies against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) variants (including Omicron variants BA.5 and BA.2.75) from individuals who received two doses of mRNA vaccination after they had been infected with the D614G virus. We named them MO1, MO2, and MO3. Among them, MO1 showed particularly high neutralizing activity against authentic variants: D614G, Delta, BA.1, BA.1.1, BA.2, BA.2.75, and BA.5. Furthermore, MO1 suppressed BA.5 infection in hamsters. A structural analysis revealed that MO1 binds to the conserved epitope of seven variants, including Omicron variants BA.5 and BA.2.75, in the receptor-binding domain of the spike protein. MO1 targets an epitope conserved among Omicron variants BA.1, BA.2, and BA.5 in a unique binding mode. Our findings confirm that D614G-derived vaccination can induce neutralizing antibodies that recognize the epitopes conserved among the SARS-CoV-2 variants.\nIMPORTANCE Omicron variants of SARS-CoV-2 acquired escape ability from host immunity and authorized antibody therapeutics and thereby have been spreading worldwide. We reported that patients infected with an early SARS-CoV-2 variant, D614G, and who received subsequent two-dose mRNA vaccination have high neutralizing antibody titer against Omicron lineages. It was speculated that the patients have neutralizing antibodies broadly effective against SARS-CoV-2 variants by targeting common epitopes. Here, we explored human monoclonal antibodies from B cells of the patients. One of the monoclonal antibodies, named MO1, showed high potency against broad SARS-CoV-2 variants including BA.2.75 and BA.5 variants. The results prove that monoclonal antibodies that have common neutralizing epitopes among several Omicrons were produced in patients infected with D614G and who received mRNA vaccination.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hanako", "last_name": "Ishimaru", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Lidya Handayani", "last_name": "Tjan", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Sutandhio", "name": null }, { "creator_type": "author", "first_name": "Maria Istiqomah", "last_name": "Marini", "name": null }, { "creator_type": "author", "first_name": "Gema Barlian", "last_name": "Effendi", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Shigematsu", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Kaito", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Yukiya", "last_name": "Kurahashi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Shinohara", "name": null }, { "creator_type": "author", "first_name": "Tomoka", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Sachiyo", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00286-23" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-05-16", "date_precision": "day", "issue": "0", "normalized_date": "2023-05-16", "pages": "e00286-23", "proceedings_title": null, "publisher": "American Society for Microbiology", "title": "Journal of Virology", "volume": "0", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification and Analysis of Monoclonal Antibodies with Neutralizing Activity against Diverse SARS-CoV-2 Variants", "url": "https://journals.asm.org/doi/10.1128/jvi.00286-23", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In late 2022, SARS-CoV-2 Omicron subvariants have become highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that XBB emerged through the recombination of two cocirculating BA.2 lineages, BJ.1 and BM.1.1.1 (a progeny of BA.2.75), during the summer of 2022. XBB.1 is the variant most profoundly resistant to BA.2/5 breakthrough infection sera to date and is more fusogenic than BA.2.75. The recombination breakpoint is located in the receptor-binding domain of spike, and each region of the recombinant spike confers immune evasion and increases fusogenicity. We further provide the structural basis for the interaction between XBB.1 spike and human ACE2. Finally, the intrinsic pathogenicity of XBB.1 in male hamsters is comparable to or even lower than that of BA.2.75. Our multiscale investigation provides evidence suggesting that XBB is the first observed SARS-CoV-2 variant to increase its fitness through recombination rather than substitutions.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Keiya", "last_name": "Uriu", "name": null }, { "creator_type": "author", "first_name": "Jiri", "last_name": "Zahradnik", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Kida", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Anraku", "name": null }, { "creator_type": "author", "first_name": "Hesham", "last_name": "Nasser", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Shofa", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Spyros", "last_name": "Lytras", "name": null }, { "creator_type": "author", "first_name": "Naganori", "last_name": "Nao", "name": null }, { "creator_type": "author", "first_name": "Yukari", "last_name": "Itakura", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Deguchi", "name": null }, { "creator_type": "author", "first_name": "Rigel", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Mst Monira", "last_name": "Begum", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Hisano", "last_name": "Yajima", "name": null }, { "creator_type": "author", "first_name": "Jiei", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Sasaki-Tabata", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kosugi", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Lin", "last_name": "Pan", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Sauter", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Yoshimatsu", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Asakura", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sadamasu", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tetsuharu", "last_name": "Nagamoto", "name": null }, { "creator_type": "author", "first_name": "Gideon", "last_name": "Schreiber", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Maenaka", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Hashiguchi", "name": null }, { "creator_type": "author", "first_name": "Terumasa", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Takasuke", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Akatsuki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Matsuno", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-38435-3" }, "pmcid": { "normalized": "PMC10187524" }, "pmid": { "normalized": "37193706" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Cricetinae", "descriptor_ui": "D006224", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Recombination, Genetic", "descriptor_ui": "D011995", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false }, { "descriptor": "Spike Glycoprotein, Coronavirus", "descriptor_ui": "D064370", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 May 16", "date_precision": "day", "issue": "1", "normalized_date": "2023-05-16", "pages": "2800", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including residues R346, K444, L452, N460, and F486. Here, we characterize the convergent evolution of Omicron subvariants and the properties of one recent lineage of concern, BQ.1.1. Our phylogenetic analysis suggests that these five substitutions are recurrently acquired, particularly in younger Omicron lineages. Epidemic dynamics modelling suggests that the five substitutions increase viral fitness, and a large proportion of the fitness variation within Omicron lineages can be explained by these substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 and BA.5 infection sera more efficiently, as demonstrated by neutralization assays. The pathogenicity of BQ.1.1 in hamsters is lower than that of BA.5. Our multiscale investigations illuminate the evolutionary rules governing the convergent evolution for known Omicron lineages as of 2022.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jumpei", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Rigel", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Keiya", "last_name": "Uriu", "name": null }, { "creator_type": "author", "first_name": "Yukari", "last_name": "Itakura", "name": null }, { "creator_type": "author", "first_name": "Jiri", "last_name": "Zahradnik", "name": null }, { "creator_type": "author", "first_name": "Kanako Terakado", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Deguchi", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Spyros", "last_name": "Lytras", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Kida", "name": null }, { "creator_type": "author", "first_name": "Hesham", "last_name": "Nasser", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Shofa", "name": null }, { "creator_type": "author", "first_name": "Mst Monira", "last_name": "Begum", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Tateki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Jiei", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Sasaki-Tabata", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Yoshimatsu", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Naganori", "last_name": "Nao", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Asakura", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sadamasu", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tetsuharu", "last_name": "Nagamoto", "name": null }, { "creator_type": "author", "first_name": "Jin", "last_name": "Kuramochi", "name": null }, { "creator_type": "author", "first_name": "Gideon", "last_name": "Schreiber", "name": null }, { "creator_type": "author", "first_name": "Akatsuki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Matsuno", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Hashiguchi", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takasuke", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Terumasa", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-38188-z" }, "pmcid": { "normalized": "PMC10175283" }, "pmid": { "normalized": "37169744" } }, "mesh": [ { "descriptor": "Amino Acid Substitution", "descriptor_ui": "D019943", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Neutralizing", "descriptor_ui": "D057134", "major_topic": false }, { "descriptor": "Antibodies, Viral", "descriptor_ui": "D000914", "major_topic": false }, { "descriptor": "Biological Assay", "descriptor_ui": "D001681", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Cricetinae", "descriptor_ui": "D006224", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 May 11", "date_precision": "day", "issue": "1", "normalized_date": "2023-05-11", "pages": "2671", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Convergent evolution of SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Omicron variants with immune evasion have emerged, and they continue to mutate rapidly, raising concerns about the weakening of vaccine efficacy, and the very elderly populations are vulnerable to Coronavirus Disease 2019 (COVID-19). Therefore, to investigate the effect of multiple doses of mRNA vaccine for the newly emerged variants on these populations, cross-neutralizing antibody titers were examined against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants, including BQ.1.1 and XBB. METHODS: Blood samples were taken from residents at four long-term care facilities in Hyogo prefecture, Japan (median age, 91 years), after 3rd (n = 67) and 4th (n = 48) mRNA vaccinations, from April to October 2022. A live virus microneutralization assay was performed to determine the neutralizing antibody titers in participants' sera. RESULTS: After 3rd vaccination, cross-neutralizing antibody prevalence against conventional (D614G) virus, Delta, Omicron BA.2, BA.5, BA.2.75, BQ.1.1, and XBB were 100%, 97%, 81%, 51%, 67%, 4%, and 21%, respectively. After 4th vaccination, the antibody positivity rates increased to 100%, 100%, 98%, 79%, 92%, 31%, and 52%, respectively. The 4th vaccination significantly increased cross-neutralizing antibody titers against all tested variants. CONCLUSION: The positivity rates for BQ.1.1 and XBB increased after 4th vaccination, although the titer value was lower than those of BA.5 and BA.2.75. Considering the rapid mutation of viruses and the efficacy of vaccines, it may be necessary to create a system that can develop vaccines suitable for each epidemic in consideration of the epidemic of the virus.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Silvia", "last_name": "Sutandhio", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Yukiya", "last_name": "Kurahashi", "name": null }, { "creator_type": "author", "first_name": "Maria Istiqomah", "last_name": "Marini", "name": null }, { "creator_type": "author", "first_name": "Gema Barlian", "last_name": "Effendi", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Hanako", "last_name": "Ishimaru", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jiph.2023.05.004" }, "pmcid": { "normalized": "PMC10163793" }, "pmid": { "normalized": "37196370" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Antibodies, Viral", "descriptor_ui": "D000914", "major_topic": false }, { "descriptor": "Broadly Neutralizing Antibodies", "descriptor_ui": "D000080908", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true }, { "descriptor": "Vaccination", "descriptor_ui": "D014611", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 May 6", "date_precision": "day", "issue": "7", "normalized_date": "2023-05-06", "pages": "1064-1072", "proceedings_title": null, "publisher": "", "title": "Journal of infection and public health", "volume": "16", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Fourth mRNA vaccination increases cross-neutralizing antibody titers against SARS-CoV-2 variants, including BQ.1.1 and XBB, in a very elderly population.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Data collection on adverse reactions in recipients after vaccination is vital to evaluate potential health issues, but health observation diaries are onerous for participants. Here, we present a protocol to collect time series information using a smartphone or web-based platform, thus eliminating the need for paperwork and data submission. We describe steps for setting up the platform using the Model-View-Controller web framework, uploading lists of recipients, sending notifications, and managing respondent data. For complete details on the use and execution of this protocol, please refer to Ikeda et al. (2022).(1).", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuo", "last_name": "Yamao", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Oami", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Taka-Aki", "last_name": "Nakada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xpro.2023.102284" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37148245" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 May 5", "date_precision": "day", "issue": "2", "normalized_date": "2023-05-05", "pages": "102284", "proceedings_title": null, "publisher": "", "title": "STAR protocols", "volume": "4", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Protocol to acquire time series data on adverse reactions following vaccination using a smartphone or web-based platform.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Of late, numerous microphysiological systems have been employed to model the renal proximal tubule. Yet there is lack of research on refining the functions of the proximal tubule epithelial layer-selective filtration and reabsorption. In this report, pseudo proximal tubule cells extracted from human-induced pluripotent stem cell-derived kidney organoids are combined and cultured with immortalized proximal tubule cells. It is shown that the cocultured tissue is an impervious epithelium that offers improved levels of certain transporters, extracellular matrix proteins collagen and laminin, and superior glucose transport and P-glycoprotein activity. mRNA expression levels higher than those obtained from each cell type were detected, suggesting an anomalous synergistic crosstalk between the two. Alongside, the improvements in morphological characteristics and performance of the immortalized proximal tubule tissue layer exposed, upon maturation, to human umbilical vein endothelial cells are thoroughly quantified and compared. Glucose and albumin reabsorption, as well as xenobiotic efflux rates through P-glycoprotein were all improved. The data presented abreast highlight the advantages of the cocultured epithelial layer and the non-iPSC-based bilayer. The in vitro models presented herein can be helpful in personalized nephrotoxicity studies.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ramin", "last_name": "Banan Sadeghian", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Cheng", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Toshikazu", "last_name": "Araoka", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Yokokawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-023-04862-7" }, "pmcid": { "normalized": "PMC10160057" }, "pmid": { "normalized": "37142732" } }, "mesh": [ { "descriptor": "ATP Binding Cassette Transporter, Subfamily B", "descriptor_ui": "D018435", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 May 4", "date_precision": "day", "issue": "1", "normalized_date": "2023-05-04", "pages": "483", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "6", "year": 2023 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000390" ] }, "title": "Cells sorted off hiPSC-derived kidney organoids coupled with immortalized cells reliably model the proximal tubule.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Abstract Adult autologous human epidermal stem cells can be extensively expanded ex vivo for cell and gene therapy. Identifying the mechanisms involved in stem cell maintenance and defining culture conditions to maintain stemness is critical, because an inadequate environment can result in the rapid conversion of stem cells into progenitors/transient amplifying cells (clonal conversion), with deleterious consequences on the quality of the transplants and their ability to engraft. Here, we demonstrate that cultured human epidermal stem cells respond to a small drop in temperature through thermoTRP channels via mTOR signaling. Exposure of cells to rapamycin or a small drop in temperature induces the nuclear translocation of mTOR with an impact on gene expression. We also demonstrate by single-cell analysis that long-term inhibition of mTORC1 reduces clonal conversion and favors the maintenance of stemness. Taken together, our results demonstrate that human keratinocyte stem cells can adapt to environmental changes (e.g., small variations in temperature) through mTOR signaling and constant inhibition of mTORC1 favors stem cell maintenance, a finding of high importance for regenerative medicine applications.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Nanba", "name": null }, { "creator_type": "author", "first_name": "Jun-Ichi", "last_name": "Sakabe", "name": null }, { "creator_type": "author", "first_name": "Johannes", "last_name": "Mosig", "name": null }, { "creator_type": "author", "first_name": "Michel", "last_name": "Brouard", "name": null }, { "creator_type": "author", "first_name": "Fujio", "last_name": "Toki", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Shimokawa", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Braschler", "name": null }, { "creator_type": "author", "first_name": "Fahd", "last_name": "Azzabi", "name": null }, { "creator_type": "author", "first_name": "Stéphanie", "last_name": "Droz-Georget Lathion", "name": null }, { "creator_type": "author", "first_name": "Kai", "last_name": "Johnsson", "name": null }, { "creator_type": "author", "first_name": "Keya", "last_name": "Roy", "name": null }, { "creator_type": "author", "first_name": "Christoph D", "last_name": "Schmid", "name": null }, { "creator_type": "author", "first_name": "Jean-Baptiste", "last_name": "Bureau", "name": null }, { "creator_type": "author", "first_name": "Ariane", "last_name": "Rochat", "name": null }, { "creator_type": "author", "first_name": "Yann", "last_name": "Barrandon", "name": null } ], "identifiers": { "doi": { "normalized": "10.15252/embr.202255439" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-05-04", "date_precision": "day", "issue": "n/a", "normalized_date": "2023-05-04", "pages": "e55439", "proceedings_title": null, "publisher": "John Wiley & Sons, Ltd", "title": "EMBO reports", "volume": "n/a", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Low temperature and mTOR inhibition favor stem cell maintenance in human keratinocyte cultures", "url": "https://www.embopress.org/doi/full/10.15252/embr.202255439", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Periprosthetic joint infection (PJI) is a serious complication after total joint arthroplasty. It is important to accurately identify PJI and monitor postoperative blood biochemical marker changes for the appropriate treatment strategy. In this study, we aimed to monitor the postoperative blood biochemical characteristics of PJI by contrasting with non-PJI joint replacement cases to understand how the characteristics change postoperatively. MATERIALS AND METHODS: A total of 144 cases (52 of PJI and 92 of non-PJI) were reviewed retrospectively and split into development and validation cohorts. After exclusion of 11 cases, a total of 133 (PJI: 50, non-PJI: 83) cases were enrolled finally. An RF classifier was developed to discriminate between PJI and non-PJI cases based on 18 preoperative blood biochemical tests. We evaluated the similarity/dissimilarity between cases based on the RF model and embedded the cases in a two-dimensional space by Uniform Manifold Approximation and Projection (UMAP). The RF model developed based on preoperative data was also applied to the same 18 blood biochemical tests at 3, 6, and 12 months after surgery to analyze postoperative pathological changes in PJI and non-PJI. A Markov chain model was applied to calculate the transition probabilities between the two clusters after surgery. RESULTS: PJI and non-PJI were discriminated with the RF classifier with the area under the receiver operating characteristic curve of 0.778. C-reactive protein, total protein, and blood urea nitrogen were identified as the important factors that discriminates between PJI and non-PJI patients. Two clusters corresponding to the high- and low-risk populations of PJI were identified in the UMAP embedding. The high-risk cluster, which included a high proportion of PJI patients, was characterized by higher CRP and lower hemoglobin. The frequency of postoperative recurrence to the high-risk cluster was higher in PJI than in non-PJI. CONCLUSIONS: Although there was overlap between PJI and non-PJI, we were able to identify subgroups of PJI in the UMAP embedding. The machine-learning-based analytical approach is promising in consecutive monitoring of diseases such as PJI with a low incidence and long-term course.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ichihara", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Hyonmin", "last_name": "Choe", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Tomoyama", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Inaba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00402-023-04898-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37115242" } }, "mesh": [ { "descriptor": "Arthritis, Infectious", "descriptor_ui": "D001170", "major_topic": true }, { "descriptor": "Arthroplasty, Replacement, Hip", "descriptor_ui": "D019644", "major_topic": true }, { "descriptor": "Arthroplasty, Replacement, Knee", "descriptor_ui": "D019645", "major_topic": true }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "C-Reactive Protein", "descriptor_ui": "D002097", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Prosthesis-Related Infections", "descriptor_ui": "D016459", "major_topic": true }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Apr 28", "date_precision": "day", "issue": "", "normalized_date": "2023-04-28", "pages": "", "proceedings_title": null, "publisher": "", "title": "Archives of orthopaedic and trauma surgery", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Monitoring of blood biochemical markers for periprosthetic joint infection using ensemble machine learning and UMAP embedding.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Accumulating evidence has implicated the role of neuroinflammation in the pathology of autism spectrum disorder (ASD), a neurodevelopmental disorder. OBJECTIVES: To investigate the expression of prostaglandin EP3 (EP3) receptor mRNA in the brain of ASD mice model. METHODS: Pregnant mice were injected with valproic acid (VPA) 500 mg/kg intraperitoneally at 12.5 d gestation. The offspring were tested at the age of 5-6 weeks old for their social interaction behavior. Each mouse was assessed for prostaglandin EP3 receptor expression in the prefrontal cortical, hippocampal and cerebellar areas one day after the behavioral test. RESULTS: Compared to the naive, mice born to dams treated with VPA demonstrated a significantly shorter duration of sniffing behavior, a model of social interaction. Results further showed that the expression of EP3 receptor mRNA was significantly lower in all three brain regions of the mice born to VPA-treated dams. CONCLUSION: The present study provides further evidence of the relevance of the arachidonic acid cascade as an essential part of neuroinflammation in the pathology of ASD.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kusnandar", "last_name": "Anggadiredja", "name": null }, { "creator_type": "author", "first_name": "Neng", "last_name": "Fisheri Kurniati", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.2174/2211536612666230427152647" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37106511" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autism Spectrum Disorder", "descriptor_ui": "D000067877", "major_topic": true }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": true }, { "descriptor": "Neuroinflammatory Diseases", "descriptor_ui": "D000090862", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Prostaglandins", "descriptor_ui": "D011453", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Valproic Acid", "descriptor_ui": "D014635", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Apr 27", "date_precision": "day", "issue": "", "normalized_date": "2023-04-27", "pages": "", "proceedings_title": null, "publisher": "", "title": "MicroRNA (Shariqah, United Arab Emirates)", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Decreased Expression of EP3 Receptor mRNA in the Brain of Mouse Model of Autism Spectrum Disorder.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Patients with depression almost inevitably exhibit abnormalities in sleep, such as shortened latency to enter rapid eye movement (REM) sleep and decrease in electroencephalogram delta power during non-REM sleep. Insufficient sleep can be stressful, and the accumulation of stress leads to the deterioration of mental health and contributes to the development of psychiatric disorders. Thus, it is likely that depression and sleep are bidirectionally related, i.e. development of depression contributes to sleep disturbances and vice versa. However, the relation between depression and sleep seems complicated. For example, acute sleep deprivation can paradoxically improve depressive symptoms. Thus, it is difficult to conclude whether sleep has beneficial or harmful effects in patients with depression. How antidepressants affect sleep in patients with depression might provide clues to understanding the effects of sleep, but caution is required considering that antidepressants have diverse effects other than sleep. Recent animal studies support the bidirectional relation between depression and sleep, and animal models of depression are expected to be beneficial for the identification of neuronal circuits that connect stress, sleep, and depression. This review provides a comprehensive overview regarding the current knowledge of the relationship between depression and sleep.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Yasugaki", "name": null }, { "creator_type": "author", "first_name": "Hibiki", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Ami", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2023.04.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-04-26", "date_precision": "day", "issue": "", "normalized_date": "2023-04-26", "pages": "", "proceedings_title": null, "publisher": "", "title": "Neuroscience Research", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Bidirectional relationship between sleep and depression", "url": "https://www.sciencedirect.com/science/article/pii/S0168010223000871", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Although cases of respiratory bacterial infections associated with coronavirus disease 2019 (COVID-19) have often been reported, their impact on the clinical course remains unclear. Herein, we evaluated and analyzed the complication rates of bacterial infections, causative organisms, patient backgrounds, and clinical outcome in Japanese patients with COVID-19. METHODS: We performed a retrospective cohort study that included inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021) and obtained demographic, epidemiological, and microbiological results and the clinical course and analyzed the cases of COVID-19 complicated by respiratory bacterial infections. RESULTS: Of the 1,863 patients with COVID-19 included in the analysis, 140 (7.5%) had respiratory bacterial infections. Community-acquired co-infection at COVID-19 diagnosis was uncommon (55/1,863, 3.0%) and was mainly caused by Staphylococcus aureus, Klebsiella pneumoniae and Streptococcus pneumoniae. Hospital-acquired bacterial secondary infections, mostly caused by Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia, were diagnosed in 86 patients (4.6%). Severity-associated comorbidities were frequently observed in hospital-acquired secondary infection cases, including hypertension, diabetes, and chronic kidney disease. The study results suggest that the neutrophil-lymphocyte ratio (> 5.28) may be useful in diagnosing complications of respiratory bacterial infections. COVID-19 patients with community-acquired or hospital-acquired secondary infections had significantly increased mortality. CONCLUSIONS: Respiratory bacterial co-infections and secondary infections are uncommon in patients with COVID-19 but may worsen outcomes. Assessment of bacterial complications is important in hospitalized patients with COVID-19, and the study findings are meaningful for the appropriate use of antimicrobial agents and management strategies.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kensuke", "last_name": "Nakagawara", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Kamata", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Chubachi", "name": null }, { "creator_type": "author", "first_name": "Ho", "last_name": "Namkoong", "name": null }, { "creator_type": "author", "first_name": "Hiromu", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ho", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Shiro", "last_name": "Otake", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Atsuho", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Azekawa", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Watase", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Asakura", "name": null }, { "creator_type": "author", "first_name": "Katsunori", "last_name": "Masaki", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Ishikura", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Norihiro", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kokutou", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yoshiyama", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Mutoh", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Tomohisa", "last_name": "Shoko", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Muranaka", "name": null }, { "creator_type": "author", "first_name": "Kodai", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Nobuaki", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Mochimaru", "name": null }, { "creator_type": "author", "first_name": "Mototaka", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Chihara", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Nagasaki", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Amishima", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Odani", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Tani", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Nishi", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Ryuya", "last_name": "Edahiro", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Naozumi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kagaya", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Miyazawa", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Fujitani", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Hirohito", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Tanino", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Otsuki", "name": null }, { "creator_type": "author", "first_name": "Shuko", "last_name": "Mashimo", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Kuramochi", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Hosoda", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Yotaro", "last_name": "Takaku", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Naota", "last_name": "Kuwahara", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Hagiwara", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Nakamori", "name": null }, { "creator_type": "author", "first_name": "Fukuki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Kono", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Tomoo", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Kusaka", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Kimizuka", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Kawana", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yukinori", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Ai", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kumanogoh", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Katsushi", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Miyano", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Seishi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fukunaga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12890-023-02418-3" }, "pmcid": { "normalized": "PMC10131342" }, "pmid": { "normalized": "37101265" } }, "mesh": [ { "descriptor": "Bacterial Infections", "descriptor_ui": "D001424", "major_topic": true }, { "descriptor": "Coinfection", "descriptor_ui": "D060085", "major_topic": true }, { "descriptor": "Community-Acquired Infections", "descriptor_ui": "D017714", "major_topic": true }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "COVID-19 Testing", "descriptor_ui": "D000086742", "major_topic": false }, { "descriptor": "Cross Infection", "descriptor_ui": "D003428", "major_topic": true }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "East Asian People", "descriptor_ui": "D000095225", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Respiratory Tract Infections", "descriptor_ui": "D012141", "major_topic": true }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false }, { "descriptor": "Staphylococcal Infections", "descriptor_ui": "D013203", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Apr 26", "date_precision": "day", "issue": "1", "normalized_date": "2023-04-26", "pages": "146", "proceedings_title": null, "publisher": "", "title": "BMC pulmonary medicine", "volume": "23", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Impact of respiratory bacterial infections on mortality in Japanese patients with COVID-19: a retrospective cohort study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Silicate ions (SiO(3)(2-)), or ionic silica, are known to cause silica scaling in industrial water applications when excess amounts are present; hence, concentrations must be monitored and kept at a constant low level. Ionic silica is conventionally measured by spectrophotometry in the form of its silicomolybdic complex based on the molybdenum blue reaction, but the operation process is complicated and not suitable for on-site detection. To solve these issues, microfluidic paper-based analytical devices (microPADs) have been gaining attention as portable, low-cost analytical devices suitable for on-site detection. The foldable origami type device described in this work enabled silica detection based on the molybdenum blue reaction, in the range of 50-1000 mg/L, with a practically detectable lowest concentration of 50 mg/L. The device showed selectivity for silicate ions and stability over 21 days when stored at 4 degrees C. The semi-quantitative analytical performance makes the proposed paper-based device attractive for on-site industrial monitoring.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mami", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Katoh", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Otsuka", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Sawatsubashi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s44211-023-00345-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37186078" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Apr 25", "date_precision": "day", "issue": "", "normalized_date": "2023-04-25", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical sciences : the international journal of the Japan Society for Analytical Chemistry", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Semi-quantitative microfluidic paper-based analytical device for ionic silica detection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In today's society, people are subjected to many social stressors, and excessive chronic stress causes functional disruption of the neuroendocrine system and many diseases. Although the exacerbation of atopic dermatitis with symptoms of itching and erectile dysfunction is induced by chronic stress, the details of the mechanisms are unknown. Here, we examined the effects of chronic stress on itch sensation and male sexual function at the behavioral and molecular levels, focusing on two distinct gastrin-releasing peptide (GRP) systems that independently regulate itch transmission, i.e., the somatosensory GRP system, and male sexual function, i.e., the lumbosacral autonomic GRP system, in the spinal cord. In a rat model of chronic stress induced by chronic corticosterone (CORT) administration, we observed increased plasma CORT concentrations, decreased body weight, and increased anxiety-like behavior, similar to that observed in humans. Chronic CORT exposure induced hypersensitivity to itch and increased the Grp mRNA level in the spinal somatosensory system, but there was no change in pain or tactile sensitivity. Antagonists of the somatosensory GRP receptor, an itch-specific mediator, suppressed itch hypersensitivity induced by chronic CORT exposure. In contrast, chronic CORT exposure decreased male sexual behavior, ejaculated semen volume, vesicular gland weight, and plasma testosterone levels. However, there were no effects on the expression of Grp mRNA or protein in the lumbosacral autonomic GRP system, which regulates male sexual function. In summary, chronic stress model rats showed itch hypersensitivity and impaired sexual function in males, and the involvement of the spinal GRP systems was apparent in itch hypersensitivity.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Takanami", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ygcen.2023.114289" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37094615" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Corticosterone", "descriptor_ui": "D003345", "major_topic": true }, { "descriptor": "Gastrin-Releasing Peptide", "descriptor_ui": "D019886", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Pruritus", "descriptor_ui": "D011537", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Apr 22", "date_precision": "day", "issue": "", "normalized_date": "2023-04-22", "pages": "114289", "proceedings_title": null, "publisher": "", "title": "General and comparative endocrinology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Chronic corticosterone exposure evokes itch hypersensitivity and sexual dysfunction in male rats: relationship between the two distinct gastrin-releasing peptide systems in the spinal cord.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Machine learning technology is expected to support diagnosis and prognosis prediction in medicine. We used machine learning to construct a new prognostic prediction model for prostate cancer patients based on longitudinal data obtained from age at diagnosis, peripheral blood and urine tests of 340 prostate cancer patients. Random survival forest (RSF) and survival tree were used for machine learning. In the time-series prognostic prediction model for metastatic prostate cancer patients, the RSF model showed better prediction accuracy than the conventional Cox proportional hazards model for almost all time periods of progression-free survival (PFS), overall survival (OS) and cancer-specific survival (CSS). Based on the RSF model, we created a clinically applicable prognostic prediction model using survival trees for OS and CSS by combining the values of lactate dehydrogenase (LDH) before starting treatment and alkaline phosphatase (ALP) at 120 days after treatment. Machine learning provides useful information for predicting the prognosis of metastatic prostate cancer prior to treatment intervention by considering the nonlinear and combined impacts of multiple features. The addition of data after the start of treatment would allow for more precise prognostic risk assessment of patients and would be beneficial for subsequent treatment selection.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shinpei", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Kodai", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Xue", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Wakai", "name": null }, { "creator_type": "author", "first_name": "Manato", "last_name": "Kanesaka", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Kamada", "name": null }, { "creator_type": "author", "first_name": "Nobuyoshi", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Sazuka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Naohiko", "last_name": "Anzai", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-32987-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37072487" } }, "mesh": [ { "descriptor": "Androgen Antagonists", "descriptor_ui": "D000726", "major_topic": false }, { "descriptor": "Androgens", "descriptor_ui": "D000728", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Prostatic Neoplasms", "descriptor_ui": "D011471", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Apr 18", "date_precision": "day", "issue": "1", "normalized_date": "2023-04-18", "pages": "6325", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Machine-learning predicts time-series prognosis factors in metastatic prostate cancer patients treated with androgen deprivation therapy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Controlling tumor-specific alterations in metabolic pathways is a useful strategy for treating tumors. The glyoxalase pathway, which metabolizes the toxic electrophile 2-methylglyoxal (MG), is thought to contribute to tumor pathology. We developed a live cell-based high-throughput screening system that monitors the metabolism of MG to generate D-lactate by glyoxalase I and II (GLO1 and GLO2). It utilizes an extracellular coupled assay that uses D-lactate to generate NAD(P)H, which is detected by a selective fluorogenic probe designed to respond exclusively to extracellular NAD(P)H. This metabolic pathway-oriented screening is able to identify compounds that control MG metabolism in live cells, and we have discovered compounds that can directly or indirectly inhibit glyoxalase activities in small cell lung carcinoma cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kouichi", "last_name": "Yanagi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Yuuta", "last_name": "Fujikawa", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42004-023-00864-y" }, "pmcid": { "normalized": "PMC10102174" }, "pmid": { "normalized": "37055561" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Apr 13", "date_precision": "day", "issue": "1", "normalized_date": "2023-04-13", "pages": "68", "proceedings_title": null, "publisher": "", "title": "Communications chemistry", "volume": "6", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of pathway-oriented screening to identify compounds to control 2-methylglyoxal metabolism in tumor cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Wnt signaling is required to maintain bipotent progenitors for neural and paraxial mesoderm cells, the neuromesodermal progenitor (NMP) cells that reside in the epiblast and tailbud. Since epiblast/tailbud cells receive Wnt ligands produced by one another, this exchange may average out the heterogeneity of Wnt signaling levels among these cells. Here, we examined this possibility by replacing endogenous Wnt3a with a receptor-fused form that activates signaling in producing cells, but not in neighboring cells. Mutant mouse embryos show a unique phenotype in which maintenance of many NMP cells is impaired, although some cells persist for long periods. The epiblast cell population of these embryos increases heterogeneity in Wnt signaling levels as embryogenesis progresses and are sensitive to retinoic acid, an endogenous antagonist of NMP maintenance. Thus, mutual intercellular exchange of Wnt ligands in the epiblast cell population reduces heterogeneity and achieves robustness to environmental stress.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yudai", "last_name": "Hatakeyama", "name": null }, { "creator_type": "author", "first_name": "Nen", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Mii", "name": null }, { "creator_type": "author", "first_name": "Ritsuko", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Shinozuka", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Honda", "last_name": "Naoki", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Takada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-37350-x" }, "pmcid": { "normalized": "PMC10079677" }, "pmid": { "normalized": "37024462" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Germ Layers", "descriptor_ui": "D005855", "major_topic": true }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Apr 6", "date_precision": "day", "issue": "1", "normalized_date": "2023-04-06", "pages": "1924", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Intercellular exchange of Wnt ligands reduces cell population heterogeneity during embryogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In eukaryotes, higher-order chromatin organization is spatiotemporally regulated as domains, for various cellular functions. However, their physical nature in living cells remains unclear (e.g., condensed domains or extended fiber loops; liquid-like or solid-like). Using novel approaches combining genomics, single-nucleosome imaging, and computational modeling, we investigated the physical organization and behavior of early DNA replicated regions in human cells, which correspond to Hi-C contact domains with active chromatin marks. Motion correlation analysis of two neighbor nucleosomes shows that nucleosomes form physically condensed domains with ~150-nm diameters, even in active chromatin regions. The mean-square displacement analysis between two neighbor nucleosomes demonstrates that nucleosomes behave like a liquid in the condensed domain on the ~150 nm/~0.5 s spatiotemporal scale, which facilitates chromatin accessibility. Beyond the micrometers/minutes scale, chromatin seems solid-like, which may contribute to maintaining genome integrity. Our study reveals the viscoelastic principle of the chromatin polymer; chromatin is locally dynamic and reactive but globally stable.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tadasu", "last_name": "Nozaki", "name": null }, { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Higashi", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Masa A.", "last_name": "Shimazoe", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Sasai", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Kurokawa", "name": null }, { "creator_type": "author", "first_name": "Shiori", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Maeshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adf1488" }, "pmcid": { "normalized": "PMC10075990" }, "pmid": { "normalized": "37018405" } }, "mesh": [ { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": true }, { "descriptor": "Chromatin Assembly and Disassembly", "descriptor_ui": "D042002", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Eukaryota", "descriptor_ui": "D056890", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nucleosomes", "descriptor_ui": "D009707", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Apr 5", "date_precision": "day", "issue": "14", "normalized_date": "2023-04-05", "pages": "eadf1488", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "9", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Condensed but liquid-like domain organization of active chromatin regions in living human cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: In recent years, efforts to apply artificial intelligence (AI) to the medical field have been growing. In general, a vast amount of high-quality training data is necessary to make great AI. For tumor detection AI, annotation quality is important. In diagnosis and detection of tumors using ultrasound images, humans use not only the tumor area but also the surrounding information, such as the back echo of the tumor. Therefore, we investigated changes in detection accuracy when changing the size of the region of interest (ROI, ground truth area) relative to liver tumors in the training data for the detection AI. METHODS: We defined D/L as the ratio of the maximum diameter (D) of the liver tumor to the ROI size (L). We created training data by changing the D/L value, and performed learning and testing with YOLOv3. RESULTS: Our results showed that the detection accuracy was highest when the training data were created with a D/L ratio between 0.8 and 1.0. In other words, it was found that the detection accuracy was improved by setting the ground true bounding box for detection AI training to be in contact with the tumor or slightly larger. We also found that when the D/L ratio was distributed in the training data, the wider the distribution, the lower the detection accuracy. CONCLUSIONS: Therefore, we recommend that the detector be trained with the D/L value close to a certain value between 0.8 and 1.0 for liver tumor detection from ultrasound images.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taisei", "last_name": "Tosaki", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10396-023-01301-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37014524" } }, "mesh": [ { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": false }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": true }, { "descriptor": "Ultrasonography", "descriptor_ui": "D014463", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Apr 4", "date_precision": "day", "issue": "", "normalized_date": "2023-04-04", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of medical ultrasonics (2001)", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "A study on the optimal condition of ground truth area for liver tumor detection in ultrasound images using deep learning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent epigenome-wide studies suggest an association between blood DNA methylation and kidney function. However, the pathological importance remains unclear. Here, we show that the homing endonuclease I-PpoI-induced DNA double-strand breaks in kidney glomerular podocytes cause proteinuria, glomerulosclerosis, and tubulointerstitial fibrosis with DNA methylation changes in blood cells as well as in podocytes. Single-cell RNA-sequencing analysis reveals an increase in cytotoxic CD8(+) T cells with the activating/costimulatory receptor NKG2D in the kidneys, which exhibit a memory precursor effector cell phenotype, and the CD44(high) memory CD8(+) T cells are also increased in the peripheral circulation. NKG2D blockade attenuates the renal phenotype caused by podocyte DNA damage. Blood methylome shows increased DNA methylation in binding sites for STAT1, a transcription factor contributing to CD8(+) T cell homeostasis. Collectively, podocyte DNA damage alters the blood methylome, leading to changes in CD8(+) T cells, which contribute to sustained renal injury in chronic kidney disease.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ran", "last_name": "Nakamichi", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Hishikawa", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Hashiguchi", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Tokuhara", "name": null }, { "creator_type": "author", "first_name": "Norifumi", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Erina Sugita", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Eriko Yoshida", "last_name": "Hama", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Azegami", "name": null }, { "creator_type": "author", "first_name": "Takashin", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Itoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2023.112302" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36989112" } }, "mesh": [ { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "NK Cell Lectin-Like Receptor Subfamily K", "descriptor_ui": "D055655", "major_topic": false }, { "descriptor": "Podocytes", "descriptor_ui": "D050199", "major_topic": true }, { "descriptor": "Proteinuria", "descriptor_ui": "D011507", "major_topic": false }, { "descriptor": "Renal Insufficiency, Chronic", "descriptor_ui": "D051436", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Mar 28", "date_precision": "day", "issue": "4", "normalized_date": "2023-03-28", "pages": "112302", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "42", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "DNA-damaged podocyte-CD8 T cell crosstalk exacerbates kidney injury by altering DNA methylation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Spectral tuning of visual pigments often facilitates adaptation to new environments, and it is intriguing to study the visual ecology of pelagic sharks with secondarily expanded habitats. The whale shark, which dives into the deep sea of nearly 2,000 meters besides near-surface filter feeding, was previously shown to possess the ‘blue-shifted’ rhodopsin (RHO), which is a signature of deep-sea adaptation. In this study, our spectroscopy of recombinant whale shark RHO mutants revealed that this blue shift is caused dominantly by an unprecedented spectral tuning site 94. In humans, the mutation at the site causes congenital stationary night blindness (CSNB) by reducing the thermal stability of RHO. Similarly, the RHO of deep-diving whale shark has reduced thermal stability, which was experimentally shown to be achieved by site 178 and 94. RHOs having the natural substitution at site 94 are also found in some Antarctic fishes, suggesting that the blue shift by the substitution at the CSNB site associated with the reduction in thermal stability might be allowed in cold-water deep-sea habitats.", "classifications": [ { "id": "21H00435", "label": "21H00435", "researcher": "Mitsumasa Koyanagi", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Kuraku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2220728120" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-03-28", "date_precision": "day", "issue": "13", "normalized_date": "2023-03-28", "pages": "e2220728120", "proceedings_title": null, "publisher": "Proceedings of the National Academy of Sciences", "title": "Proceedings of the National Academy of Sciences", "volume": "120", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Whale shark rhodopsin adapted to deep-sea lifestyle by a substitution associated with human disease", "url": "https://www.pnas.org/doi/10.1073/pnas.2220728120", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Axolotls have been considered to be able to regenerate their skin completely. Our recent study updated this theory with the finding that the lattice structure of dermal collagen fibers was not fully regenerated after skin injury. We also discovered that nerves induce the regeneration of collagen fibers. The mechanism of collagen fiber regeneration remains unknown, however. In this study, we focused on the structure of collagen fibers with collagen braiding cells, and cell origin in axolotl skin regeneration. In the wounded dermis, cells involved in skin repair/regeneration were derived from both the surrounding dermis and the subcutaneous tissue. Regardless of cell origin, cells acquired the proper cell morphology to braid collagen fiber with nerve presence. We also found that FGF signaling could substitute for the nerve roles in the conversion of subcutaneous fibroblasts to lattice-shaped dermal fibroblasts. Our findings contribute to the elucidation of the fundamental mechanisms of true skin regeneration and provide useful insights for pioneering new skin treatments.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Rena", "last_name": "Kashimoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kamei", "name": null }, { "creator_type": "author", "first_name": "Shigenori", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Sakiya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Saya", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Satoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2023.03.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36963624" } }, "mesh": [ { "descriptor": "Ambystoma mexicanum", "descriptor_ui": "D000558", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Collagen", "descriptor_ui": "D003094", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Wound Healing", "descriptor_ui": "D014945", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Mar 22", "date_precision": "day", "issue": "", "normalized_date": "2023-03-22", "pages": "14-25", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "498", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "FGF signaling induces the regeneration of collagen fiber structure during skin wound healing in axolotls.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The prostate is a male reproductive gland which secretes prostatic fluid that enhances male fertility. During development and instigated by fetal testosterone, prostate cells arise caudal to the bladder at the urogenital sinus (UGS), when the urogenital mesenchyme (UGM) secretes signals to the urogenital epithelium (UGE). These initial mesenchymal signals induce prostate-specific gene expression in the UGE, after which epithelial progenitor cells form prostatic buds. Although many important factors for prostate development have been described using UGS organ cultures, those necessary and sufficient for prostate budding have not been clearly identified. This has been in part due to the difficulty to dissect the intricate signaling and feedback between epithelial and mesenchymal UGS cells. In this study, we separated the UGM from the UGE and tested candidate growth factors to show that when FGF10 is present, testosterone is not required for initiating prostate budding from the UGE. Moreover, in the presence of low levels of FGF10, canonical WNT signaling enhances the expression of several prostate progenitor markers in the UGE before budding of the prostate occurs. At the later budding stage, higher levels of FGF10 are required to increase budding and retinoic acid is indispensable for the upregulation of prostate-specific genes. Lastly, we show that under optimized conditions, female UGE can be instructed towards a prostatic fate, and in vitro generated prostate buds from male UGE can differentiate into a mature prostate epithelium after in vivo transplantation. Taken together, our results clarify the signals that can induce fetal prostate buds in the urogenital epithelium in the absence of the surrounding, instructive mesenchyme.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Wataru", "last_name": "Uno", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Ofuji", "name": null }, { "creator_type": "author", "first_name": "Filip J.", "last_name": "Wymeersch", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2023.03.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36963625" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genitalia, Male", "descriptor_ui": "D005837", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Prostate", "descriptor_ui": "D011467", "major_topic": true }, { "descriptor": "Testosterone", "descriptor_ui": "D013739", "major_topic": false }, { "descriptor": "Urogenital System", "descriptor_ui": "D014566", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Mar 22", "date_precision": "day", "issue": "", "normalized_date": "2023-03-22", "pages": "S0012-1606(23)00049-0", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "In vitro induction of prostate buds from murine urogenital epithelium in the absence of mesenchymal cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Eggshell-based reversed-phase packing materials were applied to an analytical column for high-performance liquid chromatography. Commercially available eggshell powder was classified by a cyclone system to obtain three types of particles with different diameters (arithmetic mean +/- standard deviation: 4.3 +/- 3.8, 5.6 +/- 3.3, and 9.5 +/- 5.5 mum). Sedimentation separation removed tiny particles from each sample, resulting in particles with arithmetic means of 6.6 +/- 5.5, 7.3 +/- 4.5, and 10.2 +/- 5.0 mum, respectively. The unclassified particles and three particle types treated with sedimentation separation were subsequently packed into analytical columns (150 mm x 4.6 mm I.D.), and their separation efficiencies were evaluated by comparing their height equivalent to a theoretical plate (HETP). The column without sedimentation separation exhibited the highest HETP, whereas the columns with sedimentation separation showed better separation efficiency and lower back pressure. The column with the best separation efficiency was applied for the separation of 10 alkylbenzenes and 5 steroids, and all peaks were observed with complete separation (peak resolution: R(S) > 1.5). Finally, the column was used for quantitative analysis of voriconazole, an azole antifungal agent, and imatinib, a first-generation molecularly targeted drug for cancer treatment, in spiked whole blood. Excellent accuracy (99.1-102.8%) and precision (0.6-1.9%) were observed for the spiked drugs and long-term stability (>3000 column volumes of mobile phase flow) indicated good applicability of the developed eggshell-based column as an analytical column for routine analyses of therapeutic drugs in blood.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tomoka", "last_name": "Yoshii", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d3ay00219e" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36938787" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromatography, High Pressure Liquid", "descriptor_ui": "D002851", "major_topic": false }, { "descriptor": "Drug Monitoring", "descriptor_ui": "D016903", "major_topic": true }, { "descriptor": "Egg Shell", "descriptor_ui": "D004528", "major_topic": true }, { "descriptor": "Particle Size", "descriptor_ui": "D010316", "major_topic": false }, { "descriptor": "Porosity", "descriptor_ui": "D016062", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Mar 20", "date_precision": "day", "issue": "", "normalized_date": "2023-03-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical methods : advancing methods and applications", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Evaluation of separation performance for eggshell-based reversed-phase HPLC columns by controlling particle size and application in quantitative therapeutic drug monitoring.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Negative-pressure wound therapy (NPWT) promotes wound healing by applying negative pressure to the wound surface. A quarter of a century after its introduction, NPWT has been used in various clinical conditions, although molecular biological evidence is insufficient due to delay in basic research. Here, we have summarized the history of NPWT, its mechanism of action, what is currently known about it, and what is expected to be known in the future. Particularly, attention has shifted from the four main mechanisms of NPWT to the accompanying secondary effects, such as effects on various cells, bacteria, and surgical wounds. This chapter will help the reader to understand the current status and shortcomings of NPWT-related research, which could aid in the development of basic research and, eventually, clinical use with stronger scientific evidence.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Toshifumi", "last_name": "Yamashiro", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Yoshine", "last_name": "Mayumi", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Azuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/5584_2023_773" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36922487" } }, "mesh": [ { "descriptor": "Bandages", "descriptor_ui": "D001458", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Negative-Pressure Wound Therapy", "descriptor_ui": "D054843", "major_topic": true }, { "descriptor": "Surgical Wound Infection", "descriptor_ui": "D013530", "major_topic": false }, { "descriptor": "Wound Healing", "descriptor_ui": "D014945", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Mar 16", "date_precision": "day", "issue": "", "normalized_date": "2023-03-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "Advances in experimental medicine and biology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Negative-Pressure Wound Therapy: What We Know and What We Need to Know.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Alzheimer's disease (AD) is one of the neurodegenerative diseases and characterized by the appearance and accumulation of amyloid-beta (Abeta) aggregates and phosphorylated tau with aging. The aggregation of Abeta, which is the main component of senile plaques, is closely associated with disease progression. App(NL-G-F) mice, a mouse model of AD, have three familial AD mutations in the amyloid-beta precursor gene and exhibit age-dependent AD-like symptoms and pathology. Gut-brain interactions have attracted considerable attention and inflammatory bowel disease (IBD) has been associated with a higher risk of dementia, especially AD, in humans. However, the underlying mechanisms and the effects of intestinal inflammation on the brain in AD remain largely unknown. Therefore, we aimed to investigate the effects of intestinal inflammation on AD pathogenesis. METHODS: Wild-type and App(NL-G-F) mice at three months of age were fed with water containing 2% dextran sulfate sodium (DSS) to induce colitis. Immune cells in the brain were analyzed using single-cell RNA sequencing (scRNA-seq) analysis, and the aggregation of Abeta protein in the brain was analyzed via immunohistochemistry. RESULTS: An increase in aggregated Abeta was observed in the brains of App(NL-G-F) mice with acute intestinal inflammation. Detailed scRNA-seq analysis of immune cells in the brain showed that neutrophils in the brain increased after acute enteritis. Eliminating neutrophils by antibodies suppressed the accumulation of Abeta, which increased because of intestinal inflammation. CONCLUSION: These results suggest that neutrophils infiltrate the AD brain parenchyma when acute colitis occurs, and this infiltration is significantly related to disease progression. Therefore, we propose that neutrophil-targeted therapies could reduce Abeta accumulation observed in early AD and prevent the increased risk of AD due to colitis.", "classifications": [ { "id": "21H00432", "label": "21H00432", "researcher": "Minako Ito", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryusei", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Ako", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Mahiro", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Kanamori", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Awata", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kawazoe", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Takao", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Kikutake", "name": null }, { "creator_type": "author", "first_name": "Mikita", "last_name": "Suyama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takaomi C.", "last_name": "Saido", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s41232-023-00257-7" }, "pmcid": { "normalized": "PMC10015716" }, "pmid": { "normalized": "36922861" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Mar 15", "date_precision": "day", "issue": "1", "normalized_date": "2023-03-15", "pages": "20", "proceedings_title": null, "publisher": "", "title": "Inflammation and regeneration", "volume": "43", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Increased neutrophils in inflammatory bowel disease accelerate the accumulation of amyloid plaques in the mouse model of Alzheimer's disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sleep is regulated by peripheral tissues under fatigue. The molecular pathways in peripheral cells that trigger systemic sleep-related signals, however, are unclear. Here, a forward genetic screen in C. elegans identifies 3 genes that strongly affect sleep amount: sel-1, sel-11, and mars-1. sel-1 and sel-11 encode endoplasmic reticulum (ER)-associated degradation components, whereas mars-1 encodes methionyl-tRNA synthetase. We find that these machineries function in non-neuronal tissues and that the ER unfolded protein response components inositol-requiring enzyme 1 (IRE1)/XBP1 and protein kinase R-like ER kinase (PERK)/eukaryotic initiation factor-2alpha (eIF2alpha)/activating transcription factor-4 (ATF4) participate in non-neuronal sleep regulation, partly by reducing global translation. Neuronal epidermal growth factor receptor (EGFR) signaling is also required. Mouse studies suggest that this mechanism is conserved in mammals. Considering that prolonged wakefulness increases ER proteostasis stress in peripheral tissues, our results suggest that peripheral ER proteostasis factors control sleep homeostasis. Moreover, based on our results, peripheral tissues likely cope with ER stress not only by the well-established cell-autonomous mechanisms but also by promoting the individual's sleep.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Taizo", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Mitsuaki", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Kanuka", "name": null }, { "creator_type": "author", "first_name": "Chung-Kuan", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Yasugaki", "name": null }, { "creator_type": "author", "first_name": "Sena", "last_name": "Hatori", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Kaeko", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2023.112267" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36924492" } }, "mesh": [ { "descriptor": "Activating Transcription Factor 4", "descriptor_ui": "D051701", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": true }, { "descriptor": "eIF-2 Kinase", "descriptor_ui": "D019892", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum Stress", "descriptor_ui": "D059865", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Proteostasis", "descriptor_ui": "D000074702", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Unfolded Protein Response", "descriptor_ui": "D056811", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Mar 15", "date_precision": "day", "issue": "3", "normalized_date": "2023-03-15", "pages": "112267", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "42", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000313" ], "repository": [ "ssbd-repos-000313" ] }, "title": "ER proteostasis regulators cell-non-autonomously control sleep.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuto", "last_name": "Sunaga", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Katsumata", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Kono", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Hoshiai", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Inukai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10067-023-06555-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36918446" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Mar 15", "date_precision": "day", "issue": "", "normalized_date": "2023-03-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "Clinical rheumatology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Correction to: A simple scoring model based on machine learning predicts intravenous immunoglobulin resistance in Kawasaki disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Teleost fishes exhibit complex sexual characteristics in response to androgens, such as fin enlargement and courtship display. However, the molecular mechanisms underlying their evolutionary acquisition remain largely unknown. To address this question, we analyse medaka (Oryzias latipes) mutants deficient in teleost-specific androgen receptor ohnologs (ara and arb). We discovered that neither ar ohnolog was required for spermatogenesis, whilst they appear to be functionally redundant for the courtship display in males. However, both were required for reproductive success: ara for tooth enlargement and the reproductive behaviour eliciting female receptivity, arb for male-specific fin morphogenesis and sexual motivation. We further showed that differences between the two ar ohnologs in their transcription, cellular localisation of their encoded proteins, and their downstream genetic programmes could be responsible for the phenotypic diversity between the ara and arb mutants. These findings suggest that the ar ohnologs have diverged in two ways: first, through the loss of their roles in spermatogenesis and second, through gene duplication followed by functional differentiation that has likely resolved the pleiotropic roles derived from their ancestral gene. Thus, our results provide insights into how genome duplication impacts the massive diversification of sexual characteristics in the teleost lineage.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yukiko", "last_name": "Ogino", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ansai", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Yasugi", "name": null }, { "creator_type": "author", "first_name": "Yukitoshi", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Kataaki", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Ikuyo", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Touko", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kamei", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Naruse", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Ogino", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Miyagawa", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Michael E.", "last_name": "Baker", "name": null }, { "creator_type": "author", "first_name": "Taisen", "last_name": "Iguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-37026-6" }, "pmcid": { "normalized": "PMC10014959" }, "pmid": { "normalized": "36918573" } }, "mesh": [ { "descriptor": "Angiotensin Receptor Antagonists", "descriptor_ui": "D057911", "major_topic": false }, { "descriptor": "Angiotensin-Converting Enzyme Inhibitors", "descriptor_ui": "D000806", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fishes", "descriptor_ui": "D005399", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Oryzias", "descriptor_ui": "D009990", "major_topic": true }, { "descriptor": "Receptors, Androgen", "descriptor_ui": "D011944", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Mar 14", "date_precision": "day", "issue": "1", "normalized_date": "2023-03-14", "pages": "1428", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Evolutionary differentiation of androgen receptor is responsible for sexual characteristic development in a teleost fish.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular organelles of mammalian cells communicate with one another during various cellular processes. The functions and molecular mechanisms of such interorganelle association remain largely unclear, however. We here identify voltage-dependent anion channel 2 (VDAC2), a mitochondrial outer membrane protein, as a binding partner of phosphoinositide 3-kinase (PI3K), a regulator of clathrin-independent endocytosis downstream of the small GTPase Ras. VDAC2 tethers endosomes positive for the Ras-PI3K complex to mitochondria in response to cell stimulation with epidermal growth factor and promotes clathrin-independent endocytosis, as well as endosome maturation at membrane association sites. With an optogenetics system to induce mitochondrion-endosome association, we find that, in addition to its structural role in such association, VDAC2 is functionally implicated in the promotion of endosome maturation. The mitochondrion-endosome association thus plays a role in the regulation of clathrin-independent endocytosis and endosome maturation.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Aya O.", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Sasajima", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Nanbo", "name": null }, { "creator_type": "author", "first_name": "Maho", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2023.112229" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36906852" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Clathrin", "descriptor_ui": "D002966", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": false }, { "descriptor": "Endosomes", "descriptor_ui": "D011992", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Phosphatidylinositol 3-Kinase", "descriptor_ui": "D058539", "major_topic": true }, { "descriptor": "Phosphatidylinositol 3-Kinases", "descriptor_ui": "D019869", "major_topic": true }, { "descriptor": "Voltage-Dependent Anion Channel 2", "descriptor_ui": "D050996", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Mar 10", "date_precision": "day", "issue": "3", "normalized_date": "2023-03-10", "pages": "112229", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "42", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000299" ], "repository": [ "ssbd-repos-000299" ] }, "title": "Interaction between PI3K and the VDAC2 channel tethers Ras-PI3K-positive endosomes to mitochondria and promotes endosome maturation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Raman microscopy is an emerging tool for molecular imaging and analysis of living samples. Use of Raman microscopy in life sciences is, however, still limited because of its slow measurement speed for spectral imaging and analysis. We developed a multiline-illumination Raman microscope to achieve ultrafast Raman spectral imaging. A spectrophotometer equipped with a periodic array of confocal slits detects Raman spectra from a sample irradiated by multiple line illuminations. A comb-like Raman hyperspectral image is formed on a two-dimensional detector in the spectrophotometer, and a hyperspectral Raman image is acquired by scanning the sample with multiline illumination array. By irradiating a sample with 21 simultaneous illumination lines, we achieved high-throughput Raman hyperspectral imaging of mouse brain tissue, acquiring 1108800 spectra in 11.4 min. We also measured mouse kidney and liver tissue as well as conducted label-free live-cell molecular imaging. The ultrafast Raman hyperspectral imaging enabled by the presented technique will expand the possible applications of Raman microscopy in biological and medical fields.", "classifications": [ { "id": "18H05416", "label": "18H05416", "researcher": "Hitoshi Hashimoto", "type": "grant" }, { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Tanuma", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Takemura", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Nicholas Isaac", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/boe.480611" }, "pmcid": { "normalized": "PMC10026569" }, "pmid": { "normalized": "36950233" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Mar 1", "date_precision": "day", "issue": "3", "normalized_date": "2023-03-01", "pages": "1015-1026", "proceedings_title": null, "publisher": "", "title": "Biomedical optics express", "volume": "14", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000305" ], "repository": [ "ssbd-repos-000305" ] }, "title": "High-throughput line-illumination Raman microscopy with multislit detection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The flip-excision switch (FLEX) system with an adeno-associated viral (AAV) vector allows expression of transgenes in specific cell populations having Cre recombinase. A significant issue with this system is non-specific expression of transgenes in tissues after vector injection. We show here that Cre-independent recombination events in the AAV genome carrying the FLEX sequence occur mainly during the production of viral vectors in packaging cells, which results in transgene expression in off-target populations. Introduction of a relatively longer nucleotide sequence between two recognition sites at the unilateral side of the transgene cassette, termed a unilateral spacer sequence (USS), is useful to suppress the recombination in the viral genome, leading to the protection of non-specific transgene expression with enhanced gene expression selectivity. Our FLEX/USS system offers a powerful strategy for highly specific Cre-dependent transgene expression, aiming at various applications for structural and functional analyses of target cell populations.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Natsuki", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kayo", "last_name": "Nishizawa", "name": null }, { "creator_type": "author", "first_name": "Masateru", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Miyasaka", "name": null }, { "creator_type": "author", "first_name": "Tomoji", "last_name": "Mashimo", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.crmeth.2022.100393" }, "pmcid": { "normalized": "PMC10014282" }, "pmid": { "normalized": "36936079" } }, "mesh": [ { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": true }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "Recombination, Genetic", "descriptor_ui": "D011995", "major_topic": true }, { "descriptor": "Transgenes", "descriptor_ui": "D019076", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Feb 27", "date_precision": "day", "issue": "2", "normalized_date": "2023-02-27", "pages": "100393", "proceedings_title": null, "publisher": "", "title": "Cell reports methods", "volume": "3", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Highly selective transgene expression through the flip-excision switch system by using a unilateral spacer sequence.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Major depressive disorder (MDD) is among the most common mental illnesses. Serotonergic (5-HT) neurons are central to the pathophysiology and treatment of MDD. Repeatedly recalling positive episodes is effective for MDD. Stimulating 5-HT neurons of the dorsal raphe nucleus (DRN) or neuronal ensembles in the dorsal dentate gyrus (dDG) associated with positive memories reverses the stress-induced behavioral abnormalities. Despite this phenotypic similarity, their causal relationship is unclear. This study revealed that the DRN 5-HT neurons activate dDG neurons; surprisingly, this activation was specifically observed in positive memory ensembles rather than neutral or negative ensembles. Furthermore, we revealed that dopaminergic signaling induced by activation of DRN 5-HT neurons projecting to the ventral tegmental area mediates an increase in active coping behavior and positive dDG ensemble reactivation. Our study identifies a role of DRN 5-HT neurons as specific reactivators of positive memories and provides insights into how serotonin elicits antidepressive effects.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuma", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kisaka", "name": null }, { "creator_type": "author", "first_name": "Kento", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Nishitani", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Andoh", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Koda", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Shirakawa", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Kaneko", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2023.112149" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36821440" } }, "mesh": [ { "descriptor": "Dentate Gyrus", "descriptor_ui": "D018891", "major_topic": false }, { "descriptor": "Dorsal Raphe Nucleus", "descriptor_ui": "D065847", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Major Depressive Disorder", "descriptor_ui": "D003865", "major_topic": true }, { "descriptor": "Serotonergic Neurons", "descriptor_ui": "D059326", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Feb 22", "date_precision": "day", "issue": "3", "normalized_date": "2023-02-22", "pages": "112149", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "42", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Dorsal raphe serotonergic neurons preferentially reactivate dorsal dentate gyrus cell ensembles associated with positive experience.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: The pathogenesis of preeclampsia (PE) is known to be endothelial cell damage; however, the existence of dysfunction in glomerular endothelial glycocalyx, podocytes and tubules remains unclear. The glomerular endothelial glycocalyx, basement membrane, podocytes, and tubules are permeability barriers against albumin excretion. This study aimed to assess the relationship between urinary albumin leakage and injuries of the glomerular endothelial glycocalyx, podocytes, and tubules in patients with PE. METHODS: A total of 81 women with uncomplicated pregnancies (control, n = 22), PE (PE, n = 36), or gestational hypertension (GH) (GH, n = 23) were enrolled. We assessed urinary albumin and serum hyaluronan for glycocalyx injuries, podocalyxin for podocytes injuries, and urinary N-acetyl-beta-d-glucosaminidase (NAG) and liver-type fatty acid-binding protein (l-FABP) for renal tubular dysfunctions. RESULTS: The serum hyaluronan and the urinary podocalyxin levels were higher in the PE and GH groups. The urinary NAG and l-FABP levels were higher in the PE group. Urinary NAG and l-FABP levels positively correlated with urinary albumin excretion. CONCLUSIONS: Our findings suggest that increased urinary albumin leakage is related to injuries of the glycocalyx and podocytes, and associated with tubular dysfunction in pregnant women with PE. The clinical trial described in this paper was registered at the UMIN Clinical Trials Registry under registration number UMIN000047875. URL of registration: https://centre6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000054437.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazushi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tomohito", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Saitou", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Akimasa", "last_name": "Asai", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Wakatsuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.preghy.2023.02.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36801836" } }, "mesh": [ { "descriptor": "Albumins", "descriptor_ui": "D000418", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glycocalyx", "descriptor_ui": "D019276", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hyaluronic Acid", "descriptor_ui": "D006820", "major_topic": false }, { "descriptor": "Hypertension, Pregnancy-Induced", "descriptor_ui": "D046110", "major_topic": true }, { "descriptor": "Kidney Diseases", "descriptor_ui": "D007674", "major_topic": true }, { "descriptor": "Podocytes", "descriptor_ui": "D050199", "major_topic": true }, { "descriptor": "Pre-Eclampsia", "descriptor_ui": "D011225", "major_topic": true }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Feb 17", "date_precision": "day", "issue": "", "normalized_date": "2023-02-17", "pages": "1-6", "proceedings_title": null, "publisher": "", "title": "Pregnancy hypertension", "volume": "32", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Increased urinary albumin leakage is related to injuries of glomerular glycocalyx and podocytes, and associated with tubular dysfunction in preeclampsia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An essential challenge in diagnosing states of non-alcoholic fatty liver disease (NAFLD) is the early prediction of progression from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH) before the disease progresses. Histological diagnoses of NAFLD rely on the appearance of anomalous tissue morphologies, and it is difficult to segment the biomolecular environment of the tissue through a conventional histopathological approach. Here, we show that hyper-spectral Raman imaging provides diagnostic information on NAFLD in rats, as spectral changes among disease states can be detected before histological characteristics emerge. Our results demonstrate that Raman imaging of NAFLD can be a useful tool for histopathologists, offering biomolecular distinctions among tissue states that cannot be observed through standard histopathological means.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Khalifa Mohammad", "last_name": "Helal", "name": null }, { "creator_type": "author", "first_name": "Harsono", "last_name": "Cahyadi", "name": null }, { "creator_type": "author", "first_name": "J. Nicholas", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Okajima", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/1873-3468.14600" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36807196" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Non-alcoholic Fatty Liver Disease", "descriptor_ui": "D065626", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Feb 17", "date_precision": "day", "issue": "", "normalized_date": "2023-02-17", "pages": "", "proceedings_title": null, "publisher": "", "title": "FEBS letters", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000264" ] }, "title": "Raman imaging of rat non-alcoholic fatty liver tissues reveals distinct biomolecular states.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Heat stroke is a life-threatening illness caused by exposure to high ambient temperatures and relative humidity. The incidence of heat stroke is expected to increase due to climate change. Although pituitary adenylate cyclase-activating polypeptide (PACAP) has been implicated in thermoregulation, the role of PACAP on heat stress remains unclear. PACAP knockout (KO) and wild-type ICR mice were subjected to heat exposure at an ambient temperature of 36 degrees C and relative humidity of 99% for 30-150 min. After heat exposure, the PACAP KO mice had a greater survival rate and maintained a lower body temperature than the wild-type mice. Moreover, the gene expression and immunoreaction of c-Fos in the ventromedially preoptic area of the hypothalamus, which is known to harbor temperature-sensitive neurons, were significantly lower in PACAP KO mice than those in wild-type mice. In addition, differences were observed in the brown adipose tissue, the primary site of heat production, between PACAP KO and wild-type mice. These results suggest that PACAP KO mice are resistant to heat exposure. The heat production mechanism differs between PACAP KO and wild-type mice.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Yamaga", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Ohtaki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Hirako", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Motoyasu", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuho", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Dohi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms24043992" }, "pmcid": { "normalized": "PMC9963701" }, "pmid": { "normalized": "36835411" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Heat Stroke", "descriptor_ui": "D018883", "major_topic": true }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Feb 16", "date_precision": "day", "issue": "4", "normalized_date": "2023-02-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "24", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Effect of PACAP on Heat Exposure.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kumiko", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Yoshimi", "name": null }, { "creator_type": "author", "first_name": "Egi Tritya", "last_name": "Apdila", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Awai", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-29745-z" }, "pmcid": { "normalized": "PMC9932137" }, "pmid": { "normalized": "36792765" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Feb 15", "date_precision": "day", "issue": "1", "normalized_date": "2023-02-15", "pages": "2726", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Author Correction: Changes in intracellular energetic and metabolite states due to increased galactolipid levels in Synechococcus elongatus PCC 7942.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIMS: Current approaches to classify chronic heart failure (HF) subpopulations may be limited due to the diversity of pathophysiology and co-morbidities in chronic HF. We aimed to elucidate the clusters of chronic patients with HF by data-driven approaches with machine learning in a hospital-based registry. METHODS AND RESULTS: A total of 4649 patients with a broad spectrum of left ventricular ejection fraction (LVEF) in the CHART-2 (Chronic Heart Failure Analysis and Registry in the Tohoku District-2) study were enrolled to this study. Chronic HF patients were classified using random forest clustering with 56 multiscale clinical parameters. We assessed the influence of the clusters on cardiovascular death, non-cardiovascular death, all-cause death, and free from hospitalization by HF. Latent class analysis using random forest clustering identified 10 clusters with four primary components: cardiac function (LVEF, left atrial and ventricular diameters, diastolic blood pressure, and brain natriuretic peptide), renal function (glomerular filtration rate and blood urea nitrogen), anaemia (red blood cell, haematocrit, haemoglobin, and platelet count), and nutrition (albumin and body mass index). All 11 significant clinical parameters in the four primary components and two disease aetiologies (ischaemic heart disease and valvular heart disease) showed statistically significant differences among the 10 clusters (P < 0.01). Cluster 1 (26.7% of patients), which is characterized by preserved LVEF (<59%, 37% of the total) with lowest brain natriuretic peptide (>111.3 pg/mL, 0.9%) and lowest left atrial diameter (>42 mm, 37.4%), showed the best 5 year survival rate of 98.1% for cardiovascular death, 95.9% for non-cardiovascular death, 92.9% for all-cause death, and 91.7% for free from hospitalization by HF. Cluster 10 (6.0% of the total), which is co-morbid disorders of all four primary components, showed the worst survival rate of 39.1% for cardiovascular death, 68.9% for non-cardiovascular death, 23.9% for all-cause death, and 28.1% for free from hospitalization by HF. CONCLUSIONS: These results suggest the potential applicability of the machine leaning approach, providing useful clinical prognostic information to stratify complex heterogeneity in patients with HF.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Nochioka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Daito", "last_name": "Tamori", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shiroto", "name": null }, { "creator_type": "author", "first_name": "Yudai", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Eichi", "last_name": "Takaya", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Shimokawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/ehf2.14288" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36788745" } }, "mesh": [ { "descriptor": "Atrial Fibrillation", "descriptor_ui": "D001281", "major_topic": true }, { "descriptor": "Chronic Disease", "descriptor_ui": "D002908", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Natriuretic Peptide, Brain", "descriptor_ui": "D020097", "major_topic": false }, { "descriptor": "Stroke Volume", "descriptor_ui": "D013318", "major_topic": false }, { "descriptor": "Ventricular Function, Left", "descriptor_ui": "D016277", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Feb 14", "date_precision": "day", "issue": "", "normalized_date": "2023-02-14", "pages": "", "proceedings_title": null, "publisher": "", "title": "ESC heart failure", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Machine learning approach to stratify complex heterogeneity of chronic heart failure: A report from the CHART-2 study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Kuniya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Haruki", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpj.2022.11.2887" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36784823" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Feb 10", "date_precision": "day", "issue": "3S1", "normalized_date": "2023-02-10", "pages": "545a", "proceedings_title": null, "publisher": "", "title": "Biophysical journal", "volume": "122", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Fluctuation of Raman scattering can be an initial marker for iPSC differentiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chloroplast FoF1-ATP synthase (CFoCF1) converts proton motive force into chemical energy during photosynthesis. Although many studies have been done to elucidate the catalytic reaction and its regulatory mechanisms, biochemical analyses using the CFoCF1 complex have been limited because of various technical barriers, such as the difficulty in generating mutants and a low purification efficiency from spinach chloroplasts. By taking advantage of the powerful genetics available in the unicellular green alga Chlamydomonas reinhardtii, we analyzed the ATP synthesis reaction and its regulation in CFoCF1. The domains in the γ subunit involved in the redox regulation of CFoCF1 were mutated based on the reported structure. An in vivo analysis of strains harboring these mutations revealed the structural determinants of the redox response during the light/dark transitions. In addition, we established a half day purification method for the entire CFoCF1 complex from C. reinhardtii and subsequently examined ATP synthesis activity by the acid–base transition method. We found that truncation of the β-hairpin domain resulted in a loss of redox regulation of ATP synthesis (i.e., constitutively active state) despite retaining redox-sensitive Cys residues. In contrast, truncation of the redox loop domain containing the Cys residues resulted in a marked decrease in the activity. Based on this mutation analysis, we propose a model of redox regulation of the ATP synthesis reaction by the cooperative function of the β-hairpin and the redox loop domains specific to CFoCF1.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kentaro", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Toshiharu", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2218187120" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-02-07", "date_precision": "day", "issue": "6", "normalized_date": "2023-02-07", "pages": "e2218187120", "proceedings_title": null, "publisher": "Proceedings of the National Academy of Sciences", "title": "Proceedings of the National Academy of Sciences", "volume": "120", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Two specific domains of the γ subunit of chloroplast FoF1 provide redox regulation of the ATP synthesis through conformational changes", "url": "https://www.pnas.org/doi/10.1073/pnas.2218187120", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Immune reactions in the brain, the most complex organ that directly or indirectly regulates almost every part of the body and its actions, need to be tightly regulated. Recent findings in the field of neuroimmunology have enhanced our understanding of immune cells not just inside the brain but also in adjacent tissues. Multiple types of immune cells exist and are active in neighboring border tissues, even in the steady state. In addition, advances in technology have allowed researchers to characterize a broad range of cell types, including stromal cells that support immune reactions. This review presents a short overview of the roles of the immune system in the brain during health and disease, with focus on adaptive immunity and anatomical sites of action. We also discuss potential roles of stromal cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Kanamori", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jb/mvad010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36722182" } }, "mesh": [ { "descriptor": "Adaptive Immunity", "descriptor_ui": "D056704", "major_topic": true }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Feb 1", "date_precision": "day", "issue": "", "normalized_date": "2023-02-01", "pages": "mvad010", "proceedings_title": null, "publisher": "", "title": "Journal of biochemistry", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Immunity in the brain and surrounding tissues.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Opsins, light-sensitive G protein-coupled receptors, have been identified in corals but their properties are largely unknown. Here, we identified six opsin genes (acropsins 1-6) from a coral species Acropora millepora, including three novel opsins (acropsins 4-6), and successfully characterized the properties of four out of the six acropsins. Acropsins 1 and 6 exhibited light-dependent cAMP increases in cultured cells, suggesting that the acropsins could light-dependently activate Gs-type G protein like the box jellyfish opsin from the same opsin group. Spectral sensitivity curves having the maximum sensitivities at ~ 472 nm and ~ 476 nm were estimated for acropsins 1 and 6, respectively, based on the light wavelength-dependent cAMP increases in these opsins-expressing cells (heterologous action spectroscopy). Acropsin 2 belonging to the same group as acropsins 1 and 6 did not induce light-dependent cAMP or Ca(2+) changes. We then successfully estimated the acropsin 2 spectral sensitivity curve having its maximum value at ~ 471 nm with its chimera mutant which possessed the third cytoplasmic loop of the Gs-coupled jellyfish opsin. Acropsin 4 categorized as another group light-dependently induced intracellular Ca(2+) increases but not cAMP changes. Our results uncovered that the Acropora coral possesses multiple opsins coupling two distinct cascades, cyclic nucleotide and Ca(2+)signaling light-dependently.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Benjamin M.", "last_name": "Mason", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sugihara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Vladlen", "last_name": "Slepak", "name": null }, { "creator_type": "author", "first_name": "David J.", "last_name": "Miller", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-28476-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36710295" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anthozoa", "descriptor_ui": "D037421", "major_topic": true }, { "descriptor": "GTP-Binding Proteins", "descriptor_ui": "D019204", "major_topic": false }, { "descriptor": "Opsins", "descriptor_ui": "D055355", "major_topic": true }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Rod Opsins", "descriptor_ui": "D017299", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 29", "date_precision": "day", "issue": "1", "normalized_date": "2023-01-29", "pages": "1628", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Multiple opsins in a reef-building coral, Acropora millepora.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Large scale studies in individuals of European and Han Chinese ancestry populations found a series of rare gain-of-function microduplications in VIPR2, encoding VPAC2, a receptor that binds vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide with high affinity, that were associated with an up to 13-fold increased risk for schizophrenia. To address how VPAC2 receptor overactivity might affect brain development, we used a well-characterized Nestin-Cre mouse strain and a knock-in approach to overexpress human VPAC2 in the central nervous system. Mice that overexpressed VPAC2 were found to exhibit a significant reduction in brain weight. Magnetic resonance imaging analysis confirmed a decrease in brain size, a specific reduction in the hippocampus grey matter volume and a paradoxical increase in whole-brain white matter volume. Sex-specific changes in behavior such as impaired prepulse inhibition and contextual fear memory were observed in VPAC2 overexpressing mice. The data indicate the VPAC2 receptor may play a critical role in brain morphogenesis and suggest that overactive VPAC2 signaling during development plays a mechanistic role in some forms of schizophrenia.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Christina", "last_name": "Van", "name": null }, { "creator_type": "author", "first_name": "Michael C.", "last_name": "Condro", "name": null }, { "creator_type": "author", "first_name": "Haley", "last_name": "Hrncir", "name": null }, { "creator_type": "author", "first_name": "Anna L.", "last_name": "Diep", "name": null }, { "creator_type": "author", "first_name": "Abha K.", "last_name": "Rajbhandari", "name": null }, { "creator_type": "author", "first_name": "Michael S.", "last_name": "Fanselow", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Allan J.", "last_name": "MacKenzie-Graham", "name": null }, { "creator_type": "author", "first_name": "James A.", "last_name": "Waschek", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.expneurol.2023.114339" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36717013" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Prepulse Inhibition", "descriptor_ui": "D065808", "major_topic": false }, { "descriptor": "Receptors, Vasoactive Intestinal Peptide, Type II", "descriptor_ui": "D051239", "major_topic": true }, { "descriptor": "Vasoactive Intestinal Peptide", "descriptor_ui": "D014660", "major_topic": false }, { "descriptor": "White Matter", "descriptor_ui": "D066127", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jan 27", "date_precision": "day", "issue": "", "normalized_date": "2023-01-27", "pages": "114339", "proceedings_title": null, "publisher": "", "title": "Experimental neurology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Overexpression of VIPR2 in mice results in microencephaly with paradoxical increased white matter volume.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tetraploidy is a hallmark of cancer cells, and tetraploidy-selective cell growth suppression is a potential strategy for targeted cancer therapy. However, how tetraploid cells differ from normal diploids in their sensitivity to anti-proliferative treatments remains largely unknown. In this study, we found that tetraploid cells are significantly more susceptible to inhibitors of a mitotic kinesin (CENP-E) than diploids. Treatment with a CENP-E inhibitor preferentially diminished the tetraploid cell population in a diploid-tetraploid co-culture at optimum conditions. Live imaging revealed that a tetraploidy-linked increase in unsolvable chromosome misalignment caused substantially longer mitotic delay in tetraploids than in diploids upon moderate CENP-E inhibition. This time gap of mitotic arrest resulted in cohesion fatigue and subsequent cell death, specifically in tetraploids, leading to tetraploidy-selective cell growth suppression. In contrast, the microtubule-stabilizing compound paclitaxel caused tetraploidy-selective suppression through the aggravation of spindle multipolarization. We also found that treatment with a CENP-E inhibitor had superior generality to paclitaxel in its tetraploidy selectivity across a broader spectrum of cell lines. Our results highlight the unique properties of CENP-E inhibitors in tetraploidy-selective suppression and their potential use in the development of tetraploidy-targeting interventions in cancer.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Koya", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Matsura", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Sumire", "last_name": "Ishida-Ishihara", "name": null }, { "creator_type": "author", "first_name": "Fuyu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Yaguchi", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Kawamoto", "name": null }, { "creator_type": "author", "first_name": "Taruho", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Tamaoki", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Mithilesh", "last_name": "Mishra", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/1878-0261.13379" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36688680" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chromosomal Proteins, Non-Histone", "descriptor_ui": "D002868", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Paclitaxel", "descriptor_ui": "D017239", "major_topic": false }, { "descriptor": "Tetraploidy", "descriptor_ui": "D057891", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jan 23", "date_precision": "day", "issue": "", "normalized_date": "2023-01-23", "pages": "", "proceedings_title": null, "publisher": "", "title": "Molecular oncology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Tetraploidy-linked sensitization to CENP-E inhibition in human cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "N-methyl-D-aspartate receptor (NMDAR) hypofunction during brain development is likely to contribute to the manifestation of schizophrenia (SCZ) in young adulthood. The cellular targets of NMDAR hypofunction appear to be at least in part corticolimbic fast-spiking (FS) interneurons. However, functional alterations in parvalbumin (PV)-positive FS interneurons following NMDAR hypofunction are poorly understood. Paired patch-clamp recordings from murine cortical PV interneurons and pyramidal neurons revealed that genetic deletion of NMDAR subunit Grin1 in prospective PV interneurons before the second postnatal week impaired evoked- and synchronized-GABA release. Whereas intrinsic excitability and spiking characteristics were also disturbed by Grin1 deletion, neither restoring their excitability by K(+) channel blockade nor increasing extracellular Ca(2+) rescued the GABA release. GABA release was also insensitive to the Cav2.1 channel antagonist omega-agatoxin IVA. Heterozygous deletion of Cacna1a gene (encoding Cav2.1) in PV interneurons produced a similar GABA release phenotype as the Grin1 mutants. Treatment with the Cav2.1/2.2 channel agonist GV-58 augmented somatic Ca(2+) currents and GABA release in Cacna1a-haploinsufficient PV interneurons, but failed to enhance GABA release in the Grin1-deleted PV interneurons. Taken together, our results suggest that Grin1 deletion in prospective PV interneurons impairs proper maturation of membrane excitability and Cav2.1-recruited evoked GABA release. This may increase synaptic excitatory/inhibitory ratio in principal neurons, contributing to the emergence of SCZ-like phenotypes.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mahendra", "last_name": "Singh", "name": null }, { "creator_type": "author", "first_name": "Kiran", "last_name": "Sapkota", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Rita M.", "last_name": "Cowell", "name": null }, { "creator_type": "author", "first_name": "Linda", "last_name": "Overstreet-Wadiche", "name": null }, { "creator_type": "author", "first_name": "John J.", "last_name": "Hablitz", "name": null }, { "creator_type": "author", "first_name": "Kazu", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuroscience.2023.01.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36682446" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Channels, N-Type", "descriptor_ui": "D020864", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Interneurons", "descriptor_ui": "D007395", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neocortex", "descriptor_ui": "D019579", "major_topic": true }, { "descriptor": "Parvalbumins", "descriptor_ui": "D010320", "major_topic": false }, { "descriptor": "Prospective Studies", "descriptor_ui": "D011446", "major_topic": false }, { "descriptor": "Receptors, N-Methyl-D-Aspartate", "descriptor_ui": "D016194", "major_topic": true }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 20", "date_precision": "day", "issue": "", "normalized_date": "2023-01-20", "pages": "S0306-4522(23)00011-8", "proceedings_title": null, "publisher": "", "title": "Neuroscience", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Maturation of GABAergic Synaptic Transmission From Neocortical Parvalbumin Interneurons Involves N-methyl-D-aspartate Receptor Recruitment of Cav2.1 Channels.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The central serotonergic system has multiple roles in animal physiology and behavior, including sleep-wake control. However, its function in controlling brain energy metabolism according to the state of animals remains undetermined. Through in vivo monitoring of energy metabolites and signaling, we demonstrated that optogenetic activation of raphe serotonergic neurons increased cortical neuronal intracellular concentration of ATP, an indispensable cellular energy molecule, which was suppressed by inhibiting neuronal uptake of lactate derived from astrocytes. Raphe serotonergic neuronal activation induced cortical astrocytic Ca(2+) and cAMP surges and increased extracellular lactate concentrations, suggesting the facilitation of lactate release from astrocytes. Furthermore, chemogenetic inhibition of raphe serotonergic neurons partly attenuated the increase in cortical neuronal intracellular ATP levels as arousal increased in mice. Serotonergic neuronal activation promoted an increase in cortical neuronal intracellular ATP levels, partly mediated by the facilitation of the astrocyte-neuron lactate shuttle, contributing to state-dependent optimization of neuronal intracellular energy levels.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akiyo", "last_name": "Natsubori", "name": null }, { "creator_type": "author", "first_name": "Shinobu", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Soojin", "last_name": "Kwon", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Fei", "last_name": "Deng", "name": null }, { "creator_type": "author", "first_name": "Jinxia", "last_name": "Wan", "name": null }, { "creator_type": "author", "first_name": "Momoka", "last_name": "Miyazawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Okado", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Karashima", "name": null }, { "creator_type": "author", "first_name": "Yulong", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Kenji F.", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Honda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2022.105830" }, "pmcid": { "normalized": "PMC9881222" }, "pmid": { "normalized": "36713262" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Jan 20", "date_precision": "day", "issue": "1", "normalized_date": "2023-01-20", "pages": "105830", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "26", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Serotonergic neurons control cortical neuronal intracellular energy dynamics by modulating astrocyte-neuron lactate shuttle.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "There is an urgent need to develop novel drugs to reduce the mortality from severe infectious diseases with the emergence of new pathogens, including Coronavirus disease 2019 (COVID-19). Although current drugs effectively suppress the proliferation of pathogens, immune cell activation, and inflammatory cytokine functions, they cannot completely reduce mortality from severe infections and sepsis. In this study, we focused on the endothelial cell-specific protein, Roundabout 4 (Robo4), which suppresses vascular permeability by stabilizing endothelial cells, and investigated whether enhanced Robo4 expression could be a novel therapeutic strategy against severe infectious diseases. Endothelial-specific overexpression of Robo4 suppresses vascular permeability and reduces mortality in lipopolysaccharide (LPS)-treated mice. Screening of small molecules that regulate Robo4 expression and subsequent analysis revealed that two competitive small mothers against decapentaplegic (SMAD) signaling pathways, activin receptor-like kinase 5 (ALK5)-SMAD2/3 and ALK1-SMAD1/5, positively and negatively regulate Robo4 expression, respectively. An ALK1 inhibitor was found to increase Robo4 expression in mouse lungs, suppress vascular permeability, prevent extravasation of melanoma cells, and decrease mortality in LPS-treated mice. The inhibitor suppressed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced endothelial barrier disruption and decreased mortality in mice infected with SARS-CoV-2. These results indicate that enhancing Robo4 expression is an efficient strategy to suppress vascular permeability and mortality in severe infectious diseases, including COVID-19, and that small molecules that upregulate Robo4 can be potential therapeutic agents against these diseases.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Maaya", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Aki", "last_name": "Yoneda", "name": null }, { "creator_type": "author", "first_name": "Nagisa", "last_name": "Tokunoh", "name": null }, { "creator_type": "author", "first_name": "Tatsumi", "last_name": "Masaki", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Shirakura", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Shigesada", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Obana", "name": null }, { "creator_type": "author", "first_name": "Nobumasa", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Kazutake", "last_name": "Tsujikawa", "name": null }, { "creator_type": "author", "first_name": "Chikako", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yoshiharu", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Takefumi", "last_name": "Doi", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Fujio", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2213317120" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36634143" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Capillary Permeability", "descriptor_ui": "D002199", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Endotoxemia", "descriptor_ui": "D019446", "major_topic": true }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 17", "date_precision": "day", "issue": "3", "normalized_date": "2023-01-17", "pages": "e2213317120", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "120", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Upregulation of Robo4 expression by SMAD signaling suppresses vascular permeability and mortality in endotoxemia and COVID-19 models.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Circulating tumor cells (CTCs) are precursors to cancer metastasis. In blood circulation, they take various forms such as single CTCs, CTC clusters, and CTC-leukocyte clusters, all of which have unique characteristics in terms of physiological function and have been a subject of extensive research in the last several years. Unfortunately, conventional methods are limited in accurately analysing the highly heterogeneous nature of CTCs. Here we present an effective strategy for simultaneously analysing all forms of CTCs in blood by virtual-freezing fluorescence imaging (VIFFI) flow cytometry with 5-aminolevulinic acid (5-ALA) stimulation and antibody labeling. VIFFI is an optomechanical imaging method that virtually freezes the motion of fast-flowing cells on an image sensor to enable high-throughput yet sensitive imaging of every single event. 5-ALA stimulates cancer cells to induce the accumulation of protoporphyrin (PpIX), a red fluorescent substance, making it possible to detect all cancer cells even if they show no expression of the epithelial cell adhesion molecule, a typical CTC biomarker. Although PpIX signals are generally weak, VIFFI flow cytometry can detect them by virtue of its high sensitivity. As a proof-of-principle demonstration of the strategy, we applied cancer cells spiked in blood to the strategy to demonstrate image-based detection and accurate classification of single cancer cells, clusters of cancer cells, and clusters of a cancer cell(s) and a leukocyte(s). To show the clinical utility of our method, we used it to evaluate blood samples of four breast cancer patients and four healthy donors and identified EpCAM-positive PpIX-positive cells in one of the patient samples. Our work paves the way toward the determination of cancer prognosis, the guidance and monitoring of treatment, and the design of antitumor strategies for cancer patients.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Larina Tzu-Wei", "last_name": "Shen", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Isozaki", "name": null }, { "creator_type": "author", "first_name": "Hideharu", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Dan", "last_name": "Yuan", "name": null }, { "creator_type": "author", "first_name": "Taichi", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yoshika", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Yasumoto", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Yuhong", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Yunjie", "last_name": "Deng", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Yatomi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Goda", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Matsusaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d2lc00856d" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36648503" } }, "mesh": [ { "descriptor": "Aminolevulinic Acid", "descriptor_ui": "D000622", "major_topic": false }, { "descriptor": "Antibodies", "descriptor_ui": "D000906", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Epithelial Cell Adhesion Molecule", "descriptor_ui": "D000071858", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Freezing", "descriptor_ui": "D005615", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplastic Cells, Circulating", "descriptor_ui": "D009360", "major_topic": true }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 17", "date_precision": "day", "issue": "", "normalized_date": "2023-01-17", "pages": "", "proceedings_title": null, "publisher": "", "title": "Lab on a chip", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Virtual-freezing fluorescence imaging flow cytometry with 5-aminolevulinic acid stimulation and antibody labeling for detecting all forms of circulating tumor cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Controlling the physical stability of noncrystalline active pharmaceutical ingredients remains a major challenge in the development of amorphous formulations such as amorphous solid-dispersion (ASD) formulations. To establish new evaluation and formulation strategies, the spatial distribution of the crystal phase in bulk amorphous nifedipine (NFD) was investigated as a model. The crystallization of amorphous NFD and the effect of a deliberately added impurity were investigated using powder X-ray diffraction (PXRD), differential scanning calorimetry and real-time in situ X-ray micro-computed tomography (X-ray CT). The stability data of amorphous samples, i.e., NFD and a mixture of NFD with an oxidative degradation product of NFD, impurity A (Imp A), at a weight ratio of 90:10, presented as percent amorphous remaining, suggests that Imp A accelerates the bulk crystal growth of NFD. Real-time in situ X-ray CT results showed surface-enhanced crystal growth and cavity formation in solid NFD samples. Moreover, the crystals were heterogeneous in density. These results suggest that Imp A affects the physical stability of the amorphous NFD. X-ray CT equipped with a heating unit can aid in-situ evaluation and assessment of physicochemical properties and physical stability of amorphous samples and formulations.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Misawa", "name": null }, { "creator_type": "author", "first_name": "Tamaki", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Koide", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Izutsu", "name": null }, { "creator_type": "author", "first_name": "Hideko", "last_name": "Kanazawa", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jpba.2023.115248" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36645986" } }, "mesh": [ { "descriptor": "Calorimetry, Differential Scanning", "descriptor_ui": "D002152", "major_topic": false }, { "descriptor": "Carubicin", "descriptor_ui": "D002360", "major_topic": false }, { "descriptor": "Crystallization", "descriptor_ui": "D003460", "major_topic": false }, { "descriptor": "Drug Contamination", "descriptor_ui": "D004340", "major_topic": true }, { "descriptor": "Drug Stability", "descriptor_ui": "D004355", "major_topic": true }, { "descriptor": "Nifedipine", "descriptor_ui": "D009543", "major_topic": true }, { "descriptor": "Solubility", "descriptor_ui": "D012995", "major_topic": false }, { "descriptor": "X-Ray Diffraction", "descriptor_ui": "D014961", "major_topic": false }, { "descriptor": "X-Ray Microtomography", "descriptor_ui": "D055114", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 12", "date_precision": "day", "issue": "", "normalized_date": "2023-01-12", "pages": "115248", "proceedings_title": null, "publisher": "", "title": "Journal of pharmaceutical and biomedical analysis", "volume": "226", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Real-time in situ X-ray micro-computed tomography study of the effect of impurities on the crystallization of amorphous nifedipine.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Purification of basic drugs in reversed-phase mode is often difficult, mainly due to adsorption of positively charged compounds to the silica gel-based stationary phase. Since this adsorption can be suppressed under alkaline condition, columns with alkali-resistance are required. In addition, compounds with acid-sensitive structures are sometimes degraded during separation on silica gel-based columns which exhibit acidity due to their surface structure. We prepared an alkali-resistant reversed-phase packing material, Eggshell-PMAcO based on eggshells modified with an amphiphilic copolymer, poly(maleic acid-alt-1-octadecene) (PMAcO). The height equivalent to a theoretical plate (HETP) of the Eggshell-PMAcO column was improved by surface treatment with ammonium acetate buffer (900 mM, pH = 3.7), which is an inexpensive reagent, and the retention behavior for hydrophobic compounds was compared to a typical ODS column based on silica gel, resulting in sufficient selectivity of the eggshell-based column for hydrophobic compounds, as indicated by the ratio of retention factors of pentylbenzene and butylbenzene (Eggshell-PMAcO column: 1.55, ODS column: 1.65). Column temperature-dependent retention behavior of naphthalene was investigated in the temperature range from 25 degrees C to 45 degrees C, followed by the calculation of thermodynamic parameters. There was little difference in the standard molar enthalpy (Eggshell-PMAcO: -19.6 kJ/mol, ODS: -21.7 kJ/mol). The absolute value of the standard free Gibbs energy for the Eggshell-PMAcO column was much smaller than that of the ODS column (Eggshell-PMAcO: -0.284 kJ/mol, ODS: -13.0 kJ/mol), indicating that the Eggshell-PMAcO column had a weaker retention strength for naphthalene than the ODS column mainly due to the large difference in the standard molar entropy (Eggshell-PMAcO: -64.9 J/mol K, ODS column: -29.2 J/mol K). The retention capacities for imipramine under neutral (water/methanol) and alkaline (0.1% triethylamine water/methanol) conditions were 0.2 mg and 5 mg, respectively, based on injection mass-dependent HETP, retention factor and symmetry factor. Finally, the prepared column was applied to the purification of a building block for nucleic acid drugs. This study demonstrated that reversed-phase columns, which can be fabricated from eggshells and an amphiphilic copolymer in an inexpensive and eco-friendly way, have the ability to purify basic compounds and acid-sensitive compounds.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tomoka", "last_name": "Yoshii", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Sakama", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Kanamori", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chroma.2022.463722" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36571981" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromatography, High Pressure Liquid", "descriptor_ui": "D002851", "major_topic": false }, { "descriptor": "Egg Shell", "descriptor_ui": "D004528", "major_topic": true }, { "descriptor": "Methanol", "descriptor_ui": "D000432", "major_topic": true }, { "descriptor": "Naphthalenes", "descriptor_ui": "D009281", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Silica Gel", "descriptor_ui": "D058428", "major_topic": false }, { "descriptor": "Silicon Dioxide", "descriptor_ui": "D012822", "major_topic": false }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 11", "date_precision": "day", "issue": "", "normalized_date": "2023-01-11", "pages": "463722", "proceedings_title": null, "publisher": "", "title": "Journal of chromatography. A", "volume": "1688", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Fabrication process development and basic evaluation of eggshell-based column packing material for reversed-phase preparative separation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: In Kawasaki disease (KD), accurate prediction of intravenous immunoglobulin (IVIG) resistance is crucial to reduce a risk for developing coronary artery lesions. OBJECTIVE: To establish a simple scoring model predicting IVIG resistance in KD patients based on the machine learning model. METHODS: A retrospective cohort study of 1002 KD patients diagnosed at 12 facilities for 10 years, in which 22.7% were resistant to initial IVIG treatment. We performed machine learning with diverse models using 30 clinical variables at diagnosis in 801 and 201 cases for training and test datasets, respectively. SHAP was applied to identify the variables that influenced the prediction model. A scoring model was designed using the influential clinical variables based on the Shapley additive explanation results. RESULTS: Light gradient boosting machine model accurately predicted IVIG resistance (area under the receiver operating characteristic curve (AUC), 0.78; sensitivity, 0.50; specificity, 0.88). Next, using top three influential features (days of illness at initial therapy, serum levels of C-reactive protein, and total cholesterol), we designed a simple scoring system. In spite of its simplicity, it predicted IVIG resistance (AUC, 0.72; sensitivity, 0.49; specificity, 0.82) as accurately as machine learning models. Moreover, accuracy of our scoring system with three clinical features was almost identical to that of Gunma score with seven clinical features (AUC, 0.73; sensitivity, 0.53; specificity, 0.83), a well-known logistic regression scoring model. CONCLUSION: A simple scoring system based on the findings in machine learning seems to be a useful tool to accurately predict IVIG resistance in KD patients.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuto", "last_name": "Sunaga", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Katsumata", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Kono", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Hoshiai", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Inukai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10067-023-06502-1" }, "pmcid": { "normalized": "PMC9832252" }, "pmid": { "normalized": "36627530" } }, "mesh": [ { "descriptor": "Drug Resistance", "descriptor_ui": "D004351", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoglobulins, Intravenous", "descriptor_ui": "D016756", "major_topic": true }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Mucocutaneous Lymph Node Syndrome", "descriptor_ui": "D009080", "major_topic": true }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "ROC Curve", "descriptor_ui": "D012372", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 11", "date_precision": "day", "issue": "", "normalized_date": "2023-01-11", "pages": "1-11", "proceedings_title": null, "publisher": "", "title": "Clinical rheumatology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "A simple scoring model based on machine learning predicts intravenous immunoglobulin resistance in Kawasaki disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Long-term peritoneal dialysis (PD) is often associated with peritoneal dysfunction leading to withdrawal from PD. The characteristic pathologic features of peritoneal dysfunction are widely attributed to peritoneal fibrosis and angiogenesis. The detailed mechanisms remain unclear, and treatment targets in clinical settings have yet to be identified. We investigated transglutaminase 2 (TG2) as a possible novel therapeutic target for peritoneal injury. TG2 and fibrosis, inflammation, and angiogenesis were investigated in a chlorhexidine gluconate (CG)-induced model of peritoneal inflammation and fibrosis, representing a noninfectious model of PD-related peritonitis. Transforming growth factor (TGF)-beta type I receptor (TGFbetaR-I) inhibitor and TG2-knockout mice were used for TGF-beta and TG2 inhibition studies, respectively. Double immunostaining was performed to identify cells expressing TG2 and endothelial-mesenchymal transition (EndMT). In the rat CG model of peritoneal fibrosis, in situ TG2 activity and protein expression increased during the development of peritoneal fibrosis, as well as increases in peritoneal thickness and numbers of blood vessels and macrophages. TGFbetaR-I inhibitor suppressed TG2 activity and protein expression, as well as peritoneal fibrosis and angiogenesis. TGF-beta1 expression, peritoneal fibrosis, and angiogenesis were suppressed in TG2-knockout mice. TG2 activity was detected by alpha-smooth muscle actin-positive myofibroblasts, CD31-positive endothelial cells, and ED-1-positive macrophages. CD31-positive endothelial cells in the CG model were alpha-smooth muscle actin-positive, vimentin-positive, and vascular endothelial-cadherin-negative, suggesting EndMT. In the CG model, EndMT was suppressed in TG2-knockout mice. TG2 was involved in the interactive regulation of TGF-beta. As inhibition of TG2 reduced peritoneal fibrosis, angiogenesis, and inflammation associated with TGF-beta and vascular endothelial growth factor-A suppression, TG2 may provide a new therapeutic target for ameliorating peritoneal injuries in PD.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shunnosuke", "last_name": "Kunoki", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Tatsukawa", "name": null }, { "creator_type": "author", "first_name": "Yukinao", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kinashi", "name": null }, { "creator_type": "author", "first_name": "Tetsuyoshi", "last_name": "Kariya", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Sasakura", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Ikeno", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Ishimoto", "name": null }, { "creator_type": "author", "first_name": "Kiyotaka", "last_name": "Hitomi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.labinv.2022.100050" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36870292" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chlorhexidine", "descriptor_ui": "D002710", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Fibrosis", "descriptor_ui": "D005355", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Peritoneal Fibrosis", "descriptor_ui": "D056627", "major_topic": true }, { "descriptor": "Peritoneum", "descriptor_ui": "D010537", "major_topic": false }, { "descriptor": "Protein Glutamine gamma Glutamyltransferase 2", "descriptor_ui": "D000091345", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta1", "descriptor_ui": "D053773", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor A", "descriptor_ui": "D042461", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 10", "date_precision": "day", "issue": "4", "normalized_date": "2023-01-10", "pages": "100050", "proceedings_title": null, "publisher": "", "title": "Laboratory investigation; a journal of technical methods and pathology", "volume": "103", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Inhibition of Transglutaminase 2 Reduces Peritoneal Injury in a Chlorhexidine-Induced Peritoneal Fibrosis Model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Due to their low cost, simplicity, and pump-free liquid transport properties, colorimetric assays on paper spots and microfluidic paper-based analytical devices (microPADs) are regarded as useful tools for point-of-care testing (POCT). However, for certain types of colorimetric assays, the \"non-transparent\" and \"white\" characters of paper can be a disadvantage. In this work, the possibilities of using cellophane as an alternative platform for colorimetric assays have been investigated. Cellophane is a low cost and easy-to-handle transparent film made of regenerated cellulose. Owing to its hydrophilic character, cellophane-based microfluidic channels fabricated through a print-cut-laminate approach enabled pump-free liquid transport into multiple detection areas, similar to microPADs. In addition, the water absorption characteristics of cellophane allowed the stable immobilization of water-soluble colorimetric indicators without any surface modification or additional reagents. The transparency of cellophane provides possibilities for simple background coloring of the substrates, increasing the dynamic signal range for hue-based colorimetric assays, as demonstrated for two model assays targeting H(2)O(2) (46-fold increase) and creatinine (3.6-fold increase). Finally, a turbidity detection-based protein assay was realized on black background cellophane spots. The lowest limits of detection achieved with the cellophane-based devices were calculated as 7 microM for H(2)O(2), 2.7 mg dL(-1) for creatinine, and 3.5 mg dL(-1) for protein (human serum albumin).", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Shigemori", "name": null }, { "creator_type": "author", "first_name": "Kento", "last_name": "Maejima", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00604-022-05622-w" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36622479" } }, "mesh": [ { "descriptor": "Cellophane", "descriptor_ui": "D002476", "major_topic": false }, { "descriptor": "Colorimetry", "descriptor_ui": "D003124", "major_topic": false }, { "descriptor": "Creatinine", "descriptor_ui": "D003404", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": false }, { "descriptor": "Microfluidic Analytical Techniques", "descriptor_ui": "D046210", "major_topic": true }, { "descriptor": "Microfluidics", "descriptor_ui": "D044085", "major_topic": true }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 9", "date_precision": "day", "issue": "2", "normalized_date": "2023-01-09", "pages": "48", "proceedings_title": null, "publisher": "", "title": "Mikrochimica acta", "volume": "190", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Evaluation of cellophane as platform for colorimetric assays on microfluidic analytical devices.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Wild-type herpes simplex virus (HSV) strains infrequently mediate cell-cell fusion in cell cultures and barely induce large multinucleated cells. In this study, we established a system to quantify infrequent cell-cell fusion induced by wild-type HSV strains. The established system clarified that the HSV-1 envelope glycoprotein B and its N-glycosylation at asparagine at position 141 were required for efficient cell-cell fusion. This study provides a link between cell-cell fusion induced by wild-type HSV-1 and viral pathogenesis in vivo. This article is protected by copyright. All rights reserved.", "classifications": [ { "id": "21H00417", "label": "21H00417", "researcher": "Yuhei Maruzuru", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ayano", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/1348-0421.13050" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36606601" } }, "mesh": [ { "descriptor": "Cell Fusion", "descriptor_ui": "D002459", "major_topic": false }, { "descriptor": "Glycosylation", "descriptor_ui": "D006031", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": true }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Viral Envelope Proteins", "descriptor_ui": "D014759", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 6", "date_precision": "day", "issue": "", "normalized_date": "2023-01-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "Microbiology and immunology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Establishment of a System to Quantify Wild-type Herpes Simplex Virus (HSV)-induced Cell-cell Fusion Reveals a Role of N-glycosylation of HSV-1 Envelope Glycoprotein B in Cell-cell Fusion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The lipid composition of thylakoid membranes is conserved from cyanobacteria to green plants. However, the biosynthetic pathways of galactolipids, the major components of thylakoid membranes, are known to differ substantially between cyanobacteria and green plants. We previously reported on a transformant of the unicellular rod-shaped cyanobacterium Synechococcus elongatus PCC 7942, namely SeGPT, in which the synthesis pathways of the galactolipids monogalactosyldiacylglycerol and digalactosyldiacylglycerol are completely replaced by those of green plants. SeGPT exhibited increased galactolipid content and could grow photoautotrophically, but its growth rate was slower than that of wild-type S. elongatus PCC 7942. In the present study, we investigated pleiotropic effects that occur in SeGPT and determined how its increased lipid content affects cell proliferation. Microscopic observations revealed that cell division and thylakoid membrane development are impaired in SeGPT. Furthermore, physiological analyses indicated that the bioenergetic state of SeGPT is altered toward energy storage, as indicated by increased levels of intracellular ATP and glycogen. We hereby report that we have identified a new promising candidate as a platform for material production by modifying the lipid synthesis system in this way.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kumiko", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Yoshimi", "name": null }, { "creator_type": "author", "first_name": "Egi Tritya", "last_name": "Apdila", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Awai", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-26760-4" }, "pmcid": { "normalized": "PMC9816115" }, "pmid": { "normalized": "36604524" } }, "mesh": [ { "descriptor": "Galactolipids", "descriptor_ui": "D038983", "major_topic": true }, { "descriptor": "Glycogen", "descriptor_ui": "D006003", "major_topic": false }, { "descriptor": "Synechococcus", "descriptor_ui": "D046940", "major_topic": true }, { "descriptor": "Thylakoids", "descriptor_ui": "D020524", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 5", "date_precision": "day", "issue": "1", "normalized_date": "2023-01-05", "pages": "259", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Changes in intracellular energetic and metabolite states due to increased galactolipid levels in Synechococcus elongatus PCC 7942.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mammalian central circadian clock, located in the suprachiasmatic nucleus (SCN), coordinates the timing of physiology and behavior to local time cues. In the SCN, second messengers, such as cAMP and Ca2+, are suggested to be involved in the input and/or output of the molecular circadian clock. However, the functional roles of second messengers and their dynamics in the SCN remain largely unclear. In the present study, we visualized the spatiotemporal patterns of circadian rhythms of second messengers and neurotransmitter release in the SCN. Here, we show that neuronal activity regulates the rhythmic release of vasoactive intestinal peptides from the SCN, which drives the circadian rhythms of intracellular cAMP in the SCN. Furthermore, optical manipulation of intracellular cAMP levels in the SCN shifts molecular and behavioral circadian rhythms. Together, our study demonstrates that intracellular cAMP is a key molecule in the organization of the SCN circadian neuronal network.", "classifications": [ { "id": "21H00422", "label": "21H00422", "researcher": "Daisuke Ono", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Huan", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Chi Jung", "last_name": "Hung", "name": null }, { "creator_type": "author", "first_name": "Hsin-tzu", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Naohiro", "last_name": "Kon", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Yulong", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Sugiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abq7032" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-01-04", "date_precision": "day", "issue": "1", "normalized_date": "2023-01-04", "pages": "eabq7032", "proceedings_title": null, "publisher": "American Association for the Advancement of Science", "title": "Science Advances", "volume": "9", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Network-driven intracellular cAMP coordinates circadian rhythm in the suprachiasmatic nucleus", "url": "https://www.science.org/doi/10.1126/sciadv.abq7032", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Single-cell whole-transcriptome analysis is the gold standard approach to identifying molecularly defined cell phenotypes. However, this approach cannot be used for dynamics measurements such as live-cell imaging. Here, we developed a multifunctional robot, the automated live imaging and cell picking system (ALPS) and used it to perform single-cell RNA sequencing for microscopically observed cells with multiple imaging modes. Using robotically obtained data that linked cell images and the whole transcriptome, we successfully predicted transcriptome-defined cell phenotypes in a noninvasive manner using cell image-based deep learning. This noninvasive approach opens a window to determine the live-cell whole transcriptome in real time. Moreover, this work, which is based on a data-driven approach, is a proof of concept for determining the transcriptome-defined phenotypes (i.e., not relying on specific genes) of any cell from cell images using a model trained on linked datasets.", "classifications": [ { "id": "18H05411", "label": "18H05411", "researcher": "Katsuyuki Shiroguchi", "type": "grant" }, { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" }, { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Jianshi", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Taisaku", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Hojo", "name": null }, { "creator_type": "author", "first_name": "Kirill", "last_name": "Kryukov", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Tomokatsu", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Imanishi", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2210283120" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36577074" } }, "mesh": [ { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Robotic Surgical Procedures", "descriptor_ui": "D065287", "major_topic": true }, { "descriptor": "Robotics", "descriptor_ui": "D012371", "major_topic": true }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 3", "date_precision": "day", "issue": "1", "normalized_date": "2023-01-03", "pages": "e2210283120", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "120", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000237" ], "repository": [ "ssbd-repos-000237" ] }, "title": "Robotic data acquisition with deep learning enables cell image-based prediction of transcriptomic phenotypes.", "url": "https://www.pnas.org/doi/10.1073/pnas.2210283120", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PEGylated liposomes (PEG-liposomes) are a promising drug delivery vehicle for tumor targeting because of their efficient tumor disposition profiles via the enhanced permeability and retention (EPR) effect. However, tumor targeting of PEG-liposomes, particularly their delivery inside the tumors, is often disturbed by physical barriers in the tumor, including tumor cells themselves, extracellular matrices, and interstitial pressures. In this study, B16 melanoma tumor-bearing mice were injected intravenously with oncolytic reovirus before administration of PEG-liposomes to enhance PEG-liposomes' tumor disposition. Three days after reovirus administration, significant expression of reovirus sigma 3 protein, elevation of apoptosis-related gene expression, and activation of caspase 3 in the tumors were found. Apoptotic cells were found inside the tumors. These data indicated that reovirus efficiently replicated in the tumors and induced apoptosis of tumor cells. The tumor disposition levels of PEG-liposomes were approximately doubled by reovirus pre-administration, compared with a PBS-pretreated group. PEG-liposomes were widely distributed in the tumors of reovirus-pretreated mice, whereas in the PBS-pretreated group, PEG-liposomes were found mainly around or inside the blood vessels in the tumors. Pre-treatment with reovirus also improved the tumor accumulation of PEG-liposomes in human pancreatic BxPC-3 tumors. 3D imaging analysis of whole BxPC-3 tumors demonstrated that pretreatment with reovirus led to the enhancement of PEG-liposome accumulation inside the tumors. Combination treatment with reovirus and paclitaxel-loaded PEG-liposomes (PTX-PEG-liposomes) significantly suppressed B16 tumor growth. These results provide important information for clinical use of combination therapy of reovirus and nanoparticle-based drug delivery system (DDS).", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Maho", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Ikuho", "last_name": "Ishigami", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Shuwari", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Tanuma", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Ogawara", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mizuguchi", "name": null }, { "creator_type": "author", "first_name": "Fuminori", "last_name": "Sakurai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jconrel.2022.12.050" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36586673" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Combined Modality Therapy", "descriptor_ui": "D003131", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liposomes", "descriptor_ui": "D008081", "major_topic": true }, { "descriptor": "Melanoma, Experimental", "descriptor_ui": "D008546", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Paclitaxel", "descriptor_ui": "D017239", "major_topic": false }, { "descriptor": "Polyethylene Glycols", "descriptor_ui": "D011092", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 3", "date_precision": "day", "issue": "", "normalized_date": "2023-01-03", "pages": "35-44", "proceedings_title": null, "publisher": "", "title": "Journal of controlled release : official journal of the Controlled Release Society", "volume": "354", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Pre-treatment of oncolytic reovirus improves tumor accumulation and intratumoral distribution of PEG-liposomes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vasoactive intestinal peptide (VIP) receptor 2 (VIPR2) is a class B G protein-coupled receptor with the neuropeptide VIP as a ligand. Increased VIPR2 mRNA expression and/or VIPR2 gene copy number has been documented in several cancers including breast carcinoma. However, the pathophysiological role of increased VIPR2 in the proliferation of breast cancer cells remains largely unknown. In this study, we found that VIPR2 overexpression in MCF-7 and MDA-MB-231 cells, human breast cancer cell lines, promoted cell proliferation. Increased VIPR2 also exacerbated intraperitoneal proliferation of breast cancer MDA-MB-231 cells in a tumor nude mouse model in vivo. Treatment with KS-133, a VIPR2-selective antagonist peptide, significantly inhibited VIP-induced cell proliferation in VIPR2-overexpressing MCF-7 and MDA-MB-231 cells. Overexpressed VIPR2 caused increases in the levels of cAMP and phosphorylated extracellular signal-regulated kinase (ERK), which involves a VIPR2 signaling pathway through Gs protein. Additionally, phosphorylation of vasodilator-stimulated phosphoprotein (Ser157) and cAMP response element binding protein (Ser133) in VIPR2-overexpressing MCF-7 cells was greater than that in control cells, suggesting the increased PKA activity. Moreover, an inhibitor of mitogen-activated protein kinase kinase, U0126, attenuated tumor proliferation in exogenous VIPR2-expressing MCF-7 and MDA-MB-231 cells at the same level as observed in EGFP-expressing cells treated with U0126. Together, these findings suggest that VIPR2 controls breast tumor growth by regulating the cAMP/PKA/ERK signaling pathway, and the excessive expression of VIPR2 may lead to an exacerbation of breast carcinoma.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Ami", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Tanimoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.peptides.2023.170940" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36603770" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": true }, { "descriptor": "Butadienes", "descriptor_ui": "D002070", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nitriles", "descriptor_ui": "D009570", "major_topic": false }, { "descriptor": "Receptors, Vasoactive Intestinal Peptide, Type II", "descriptor_ui": "D051239", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Vasoactive Intestinal Peptide", "descriptor_ui": "D014660", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 2", "date_precision": "day", "issue": "", "normalized_date": "2023-01-02", "pages": "170940", "proceedings_title": null, "publisher": "", "title": "Peptides", "volume": "161", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Vasoactive intestinal peptide receptor 2 signaling promotes breast cancer cell proliferation by enhancing the ERK pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Multiphoton microscopy has enabled us to image cellular dynamics in vivo. However, the excitation wavelength for imaging with commercially available lasers is mostly limited between 0.65-1.04 microm. Here we develop a femtosecond fiber laser system that produces approximately 150 fs pulses at 1.8 microm. Our system starts from an erbium-doped silica fiber laser, and its wavelength is converted to 1.8 microm using a Raman shift fiber. The 1.8 microm pulses are amplified with a two-stage Tm:ZBLAN fiber amplifier. The final pulse energy is approximately 1 microJ, sufficient for in vivo imaging. We successfully observe TurboFP635-expressing cortical neurons at a depth of 0.7 mm from the brain surface by three-photon excitation and Clover-expressing astrocytes at a depth of 0.15 mm by four-photon excitation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Hiromi H.", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Ryuichiro", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Nagasawa", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Fuji", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/boe.477322" }, "pmcid": { "normalized": "PMC9841992" }, "pmid": { "normalized": "36698657" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Jan 1", "date_precision": "day", "issue": "1", "normalized_date": "2023-01-01", "pages": "326-334", "proceedings_title": null, "publisher": "", "title": "Biomedical optics express", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "In vivo three- and four-photon fluorescence microscopy using a 1.8 microm femtosecond fiber laser system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The invariant cell lineage of Caenorhabditis elegans allows unambiguous assignment of the identity for each cell, which offers a unique opportunity to study developmental dynamics such as the timing of cell division, dynamics of gene expression, and cell fate decisions at single-cell resolution. However, little is known about cell morphodynamics, including the extent to which they are variable between individuals, mainly due to the lack of sufficient amount and quality of quantified data. In this study, we systematically quantified the cell morphodynamics in 52 C. elegans embryos from the two-cell stage to mid-gastrulation at the high spatiotemporal resolution, 0.5 mum thickness of optical sections, and 30-second intervals of recordings. Our data allowed systematic analyses of the morphological features. We analyzed sphericity dynamics and found a significant increase at the end of metaphase in every cell, indicating the universality of the mitotic cell rounding. Concomitant with the rounding, the volume also increased in most but not all cells, suggesting less universality of the mitotic swelling. Combining all features showed that cell morphodynamics was unique for each cell type. The cells before the onset of gastrulation could be distinguished from all the other cell types. Quantification of reproducibility in cell-cell contact revealed that variability in division timings and cell arrangements produced variability in contacts between the embryos. However, the area of such contacts occupied less than 5% of the total area, suggesting the high reproducibility of spatial occupancies and adjacency relationships of the cells. By comparing the morphodynamics of identical cells between the embryos, we observed diversity in the variability between cells and found it was determined by multiple factors, including cell lineage, cell generation, and cell-cell contact. We compared the variabilities of cell morphodynamics and cell-cell contacts with those in ascidian Phallusia mammillata embryos. The variabilities were larger in C. elegans, despite smaller differences in embryo size and number of cells at each developmental stage.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Hatsumi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fbinf.2023.1082531" }, "pmcid": { "normalized": "PMC10070942" }, "pmid": { "normalized": "37026092" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "1082531", "proceedings_title": null, "publisher": "", "title": "Frontiers in bioinformatics", "volume": "3", "year": 2023 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000236" ] }, "title": "Systematic analysis of cell morphodynamics in C. elegans early embryogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A principal concept in developing antibacterial agents with selective toxicity is blocking metabolic pathways that are critical for bacterial growth but that mammalian cells lack. Serine O-acetyltransferase (CysE) is an enzyme in many bacteria that catalyzes the first step in l-cysteine biosynthesis by transferring an acetyl group from acetyl coenzyme A (acetyl-CoA) to l-serine to form O-acetylserine. Because mammalian cells lack this l-cysteine biosynthesis pathway, developing an inhibitor of CysE has been thought to be a way to establish a new class of antibacterial agents. Here, we demonstrated that alkyl gallates such as octyl gallate (OGA) could act as potent CysE inhibitors in vitro and in bacteria. Mass spectrometry analyses indicated that OGA treatment markedly reduced intrabacterial levels of l-cysteine and its metabolites including glutathione and glutathione persulfide in Escherichia coli to a level similar to that found in E. coli lacking the cysE gene. Consistent with the reduction of those antioxidant molecules in bacteria, E. coli became vulnerable to hydrogen peroxide-mediated bacterial killing in the presence of OGA. More important, OGA treatment intensified susceptibilities of metallo-β-lactamase-expressing Gram-negative bacteria (E. coli and Klebsiella pneumoniae) to carbapenem. Structural analyses showed that alkyl gallate bound to the binding site for acetyl-CoA that limits access of acetyl-CoA to the active site. Our data thus suggest that CysE inhibitors may be used to treat infectious diseases caused by drug-resistant Gram-negative bacteria not only via direct antibacterial activity but also by enhancing therapeutic potentials of existing antibiotics.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Touya", "last_name": "Toyomoto", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Tomoo", "last_name": "Shiba", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Momitani", "name": null }, { "creator_type": "author", "first_name": "Tianli", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Tsutsuki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Kanae", "last_name": "Hoso", "name": null }, { "creator_type": "author", "first_name": "Koma", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Azizur", "last_name": "Rahman", "name": null }, { "creator_type": "author", "first_name": "Liping", "last_name": "Wen", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Niidome", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fmicb.2023.1276447" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37965540" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Microbiology", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Alkyl gallates inhibit serine O-acetyltransferase in bacteria and enhance susceptibility of drug-resistant Gram-negative bacteria to antibiotics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A synthetic estrogen, diethylstilbestrol (DES), is known to cause adult vaginal carcinoma by neonatal administration of DES to mice. However, the carcinogenic process remains unclear. By Cap Analysis of Gene Expression method, we found that neonatal DES exposure up-regulated inflammatory Cxcl chemokines 2, 3, 5, and 7 located in the 5qE1 region in the vaginal epithelium of mice 70 days after birth. When we examined the gene expressions of these genes much earlier stages, we found that neonatal DES exposure increased these Cxcl chemokine genes expression even after 17 days after birth. It implies the DES-mediated persistent activation of inflammatory genes. Intriguingly, we also detected DES-induced non-coding RNAs from a region approximately 100 kb far from the Cxcl5 gene. The non-coding RNA up-regulation by DES exposure was confirmed on the 17-day vagina and continued throughout life, which may responsible for the activation of Cxcl chemokines located in the same region, 5qE1. This study shows that neonatal administration of DES to mice causes long-lasting up-regulation of inflammatory Cxcl chemokines in the vaginal epithelium. DES-mediated inflammation may be associated with the carcinogenic process.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ayaka", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Chen", "last_name": "Jiayue", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Suwa", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0280421" }, "pmcid": { "normalized": "PMC10019738" }, "pmid": { "normalized": "36928065" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Carcinogens", "descriptor_ui": "D002273", "major_topic": false }, { "descriptor": "Chemokines, CXC", "descriptor_ui": "D019743", "major_topic": true }, { "descriptor": "Diethylstilbestrol", "descriptor_ui": "D004054", "major_topic": true }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Estradiol Congeners", "descriptor_ui": "D045166", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Vagina", "descriptor_ui": "D014621", "major_topic": false }, { "descriptor": "Vaginal Neoplasms", "descriptor_ui": "D014625", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "3", "normalized_date": "2023", "pages": "e0280421", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "18", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Neonatal administration of synthetic estrogen, diethylstilbestrol to mice up-regulates inflammatory Cxclchemokines located in the 5qE1 region in the vaginal epithelium.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mutations in leucine rich-repeat kinase 2 (LRRK2) cause autosomal-dominant, late-onset Parkinson's disease (PD). Accumulating evidence indicates that PD-associated LRRK2 mutations induce neuronal cell death by increasing cellular reactive oxygen species levels. However, the mechanism of increased oxidative stress associated with LRRK2 kinase activity remains unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that protects cells from oxidative stress by inducing the expression of antioxidant genes. In the present, it was found that decreased expression of Nrf2 and mRNA expression of its target genes in Lrrk2-transgenic mouse brain and LRRK2 overexpressing SH-SY5Y cells. Furthermore, knockdown of glycogen synthase kinase-3beta (GSK-3beta) recovered Nrf2 expression and mRNA expression of its target genes in LRRK2 overexpressing SH-SY5Y cells. We concluded that since Nrf2 is transcriptional factor for antioxidative responses, therefore, reduction of Nrf2 expression by LRRK2 may be part of a mechanism that LRRK2-induces vulnerability to oxidative stress in neuronal cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Motoki", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Tamaki", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Kurosaki", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Ichikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1248/bpb.b22-00356" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36596520" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antioxidants", "descriptor_ui": "D000975", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Glycogen Synthase Kinase 3 beta", "descriptor_ui": "D000071679", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leucine-Rich Repeat Serine-Threonine Protein Kinase-2", "descriptor_ui": "D000071158", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neuroblastoma", "descriptor_ui": "D009447", "major_topic": true }, { "descriptor": "NF-E2-Related Factor 2", "descriptor_ui": "D051267", "major_topic": true }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "1", "normalized_date": "2023", "pages": "123-127", "proceedings_title": null, "publisher": "", "title": "Biological & pharmaceutical bulletin", "volume": "46", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Nrf2 Expression Is Decreased in LRRK2 Transgenic Mouse Brain and LRRK2 Overexpressing SH-SY5Y Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dendritic cell immunoreceptor (DCIR) is an inhibitory C-type lectin receptor that acts as a negative regulator in the immune system and bone metabolism. We previously revealed that DCIR deficiency enhanced osteoclastogenesis and antigen presentation of dendritic cells, and that asialo-biantennary N-glycan (NA2) functions as a ligand for DCIR. NA2 binding to DCIR suppressed murine and human osteoclastogenesis that occurs in the presence of M-CSF and RANKL. The DCIR-NA2 axis, therefore, plays an important role in regulating osteoclastogenesis in both mice and humans, although the underlying mechanisms remain unclear. Here we found that Dcir (-/-) bone marrow-derived macrophages (BMMs) exhibited greater proliferative and differentiation responses to M-CSF and RANKL, respectively, than wild-type (WT) BMMs. Moreover, Dcir (-/-) osteoclasts (OCs) increased resorptive activity and cell fusion more significantly than WT OCs. DCIR deficiency affects gene expression patterns in OCs, and we found that the expression of neuraminidase 4 was increased in Dcir (-/-) OCs. Furthermore, DCIR-NA2 interaction in WT BMMs, but not Dcir (-/-) BMMs, decreased Akt phosphorylation in response to M-CSF and RANKL. These data suggest that DCIR regulates osteoclastogenesis by downregulating M-CSF and RANKL signaling, and that DCIR-mediated signaling may contribute to the terminal modification of oligosaccharides by controlling the expression of glycosylation enzymes.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomonori", "last_name": "Kaifu", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Soo-Hyun", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Iwakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2023.1159058" }, "pmcid": { "normalized": "PMC10230091" }, "pmid": { "normalized": "37266426" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Resorption", "descriptor_ui": "D001862", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lectins, C-Type", "descriptor_ui": "D037181", "major_topic": false }, { "descriptor": "Macrophage Colony-Stimulating Factor", "descriptor_ui": "D016173", "major_topic": true }, { "descriptor": "Membrane Glycoproteins", "descriptor_ui": "D008562", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Osteoclasts", "descriptor_ui": "D010010", "major_topic": false }, { "descriptor": "Receptors, Immunologic", "descriptor_ui": "D011971", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "1159058", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "DCIR suppresses osteoclastic proliferation and resorption by downregulating M-CSF and RANKL signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Many patients with psychiatric conditions, such as bipolar disorder and major depressive disorder, frequently experience disruptions in their sleep-wake cycles. Several case studies and clinical trials have shown that the administration of aripiprazole, a commonly prescribed antipsychotic drug, alleviates the symptoms of circadian sleep disorders in these patients. This improvement may be attributed to the effects of aripiprazole on the circadian central clock, specifically the hypothalamic suprachiasmatic nucleus (SCN), which regulates various circadian physiological rhythms, including the sleep-wake cycle, in mammals. To examine whether aripiprazole facilitates adaptation to changes in the light-dark cycle, we orally administered aripiprazole to mice and subjected them to jet-lag experiments. Mice receiving aripiprazole were more rapidly entrained to 6 h advanced light-dark cycles. Moreover, we examined the effect of aripiprazole on the cellular rhythms of SCN slice cultures and found that aripiprazole disrupted cellular synchronization in the SCN, thereby accelerating the damping of the SCN rhythm at the population level. Adenosine 3'5' monophosphate (cAMP) assay using a bioluminescence indicator revealed that intracellular cAMP level in the SCN increased following aripiprazole treatment. However, this increase was blocked by pre-treatment with the serotonin 1A receptor (5-HT(1A)R) antagonist. Based on these findings, we propose that aripiprazole modulates intracellular signaling, including 5-HT(1A)R-mediated cAMP signaling, and desynchronizes SCN neurons, ultimately leading to enhanced entrainment to phase advanced light-dark cycles in mice. These findings indicate that the improvement in sleep symptoms reported in patients with psychiatric disorders receiving aripiprazole may be due to modulation of the circadian clock. Our study provides novel insights into the potential clinical applications of aripiprazole in patients with various circadian sleep disorders.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ruoshi", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Kosaku", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kanbayashi", "name": null }, { "creator_type": "author", "first_name": "Arisa", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Sakurai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2023.1201137" }, "pmcid": { "normalized": "PMC10445652" }, "pmid": { "normalized": "37621713" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "1201137", "proceedings_title": null, "publisher": "", "title": "Frontiers in neuroscience", "volume": "17", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Aripiprazole disrupts cellular synchrony in the suprachiasmatic nucleus and enhances entrainment to environmental light-dark cycles in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Regulatory T-cells (Treg) are considerably heterogeneous. Thymically derived Treg (tTreg) are those, which differentiate in the thymus, while peripherally derived Treg (pTreg) differentiate from peripheral mature CD4(+) T-cells. These two populations are often identified using markers such as neuropilin-1 and Helios (for tTreg) and ROR-gammat (for pTreg) in intestines (Tanoue et al., Nat Rev Immunol 16:295-309, 2016).", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Benjy Jek Yang", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yorifumi", "last_name": "Satou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-2647-4_17" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36180638" } }, "mesh": [ { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Neuropilin-1", "descriptor_ui": "D039942", "major_topic": false }, { "descriptor": "Nuclear Receptor Subfamily 1, Group F, Member 3", "descriptor_ui": "D057132", "major_topic": true }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "259-278", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2559", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-Cell Transcriptome Analysis of Treg.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein are primarily neuropathological features of a number of neurodegenerative diseases, collectively termed tauopathy. There is no disease-modifying drug available for tauopathy except anti-amyloid antibody therapies for Alzheimer’s disease. For tau-targeting therapy, experimental models recapitulating human tau pathologies are indispensable. However, there are limited numbers of animal models that display intracellular filamentous tau aggregations. At present, several lines of P301L/S mutant tau-expressing transgenic mice successfully developed neurofibrillary pathology in the central nervous system, while most non-mutant tau-expressing transgenic mice rarely developed tau pathology. Importantly, recent studies have revealed that transgenes disrupt the coding sequence of endogenous genes, resulting in deletions and/or structural variations at the insertion site. Although any impact on the pathogenesis of tauopathy is unknown, gene disruptions may affect age-related neurodegeneration including tangle formation and brain atrophy. Moreover, some mouse lines show strain-dependent pathological features. These limitations (FTDP-17 mutations, insertion/deletion mutations, and genetic background) are a major hindrance to the establishment of a precise disease model of tauopathy. In this review, we noticed both the utility and the pitfalls of current P301L/S mutant tau-expressing transgenic mice, and we propose future strategies of mouse modeling to replicate human tauopathies.", "classifications": [ { "id": "21H00446", "label": "21H00446", "researcher": "Naruhiko Sahara", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Rin", "last_name": "Yanai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2023.1149761" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37152607" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Neuroscience", "volume": "17", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Limitations of human tau-expressing mouse models and novel approaches of mouse modeling for tauopathy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Collective migration of cells is a fundamental behavior in biology. For the quantitative understanding of collective cell migration, live-cell imaging techniques have been used using e.g., phase contrast or fluorescence images. Particle tracking velocimetry (PTV) is a common recipe to quantify cell motility with those image data. However, the precise tracking of cells is not always feasible. Particle image velocimetry (PIV) is an alternative to PTV, corresponding to Eulerian picture of fluid dynamics, which derives the average velocity vector of an aggregate of cells. However, the accuracy of PIV in capturing the underlying cell motility and what values of the parameters should be chosen is not necessarily well characterized, especially for cells that do not adhere to a viscous flow. Here, we investigate the accuracy of PIV by generating images of simulated cells by the Vicsek model using trajectory data of agents at different noise levels. It was found, using an alignment score, that the direction of the PIV vectors coincides with the direction of nearby agents with appropriate choices of PIV parameters. PIV is found to accurately measure the underlying motion of individual agents for a wide range of noise level, and its condition is addressed.", "classifications": [ { "id": "18H05413", "label": "18H05413", "researcher": "Tamiki Komatsuzaki", "type": "grant" }, { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" }, { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Udoy S.", "last_name": "Basak", "name": null }, { "creator_type": "author", "first_name": "Sulimon", "last_name": "Sattari", "name": null }, { "creator_type": "author", "first_name": "Md Motaleb", "last_name": "Hossain", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Mikito", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-39635-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37532878" } }, "mesh": [ { "descriptor": "Blood Flow Velocity", "descriptor_ui": "D001783", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Hydrodynamics", "descriptor_ui": "D057446", "major_topic": true }, { "descriptor": "Rheology", "descriptor_ui": "D012212", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparison of particle image velocimetry and the underlying agents dynamics in collectively moving self propelled particles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background Although the clinical efficacy of negative-pressure wound therapy (NPWT) is well known, many of its molecular biological mechanisms remain unresolved, mainly due to the difficulty and paucity of relevant in vitro studies. We attempted to develop an in vitro cell culture system capable of real-time monitoring of cells during NPWT treatment. Materials and methods A novel negative-pressure cell culture system was developed by combining an inverted microscope, a stage-top incubator, a sealed metal chamber for cell culture, and an NPWT treatment device. Human keratinocytes, PSVK-1, were divided into ambient pressure (AP), continuous negative-pressure (NPc), and intermittent negative-pressure (NPi) groups and cultured for 24 h with scratch assay using our real-time monitoring system and device. Pressure inside the device, medium evaporation rate, and the residual wound area were compared across the groups. Results Pressure in the device was maintained at almost the same value as set in all groups. Medium evaporation rate was significantly higher in the NPi group than in the other two groups; however, it had negligible effect on cell culture. Residual wound area after 9 h evaluated by the scratch assay was significantly smaller in the NPc and NPi groups than in the AP group. Conclusion We developed a negative-pressure cell culture device that enables negative-pressure cell culture under conditions similar to those used in clinical practice and is able to monitor cells under NPWT. Further experiments using this device would provide high-quality molecular biological evidence for NPWT.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Toshifumi", "last_name": "Yamashiro", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Yoshine", "last_name": "Mayumi", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Azuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/srt.13262" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "1", "normalized_date": "2023", "pages": "e13262", "proceedings_title": null, "publisher": "", "title": "Skin Research and Technology", "volume": "29", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Novel cell culture system for monitoring cells during continuous and variable negative-pressure wound therapy", "url": "https://onlinelibrary.wiley.com/doi/abs/10.1111/srt.13262", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Several reports indicate that apelin is often over-expressed in tumors, and therefore it has been suggested that the apelin-apelin receptor (APJ) system may induce tumor progression. In contrast, our previous research revealed high expression of the apelin-APJ system in tumor blood vessels, suggesting its involvement in the regulation of tumor vessel formation and normalization, resulting in the suppression of tumor growth by promoting the infiltration of T cells. Thus, the effect of the apelin-APJ system on tumors remains controversial. In this report, to clarify the effect of apelin in tumor cells, we analyzed the function of APJ in tumor cells using APJ knock out (KO) mice. In APJ-KO mice, Apelin overexpression in B16/BL6 (B16) melanoma cells induced greater tumor growth than controls. In an APJ-KO melanoma inoculation model, although angiogenesis is suppressed compared to wild type, no difference is evident in tumor growth. We found that APJ deficiency promoted vascular mimicry in tumors. In vitro, cultured APJ-KO B16 cells demonstrated a spindle-like shape. This phenotypic change was thought to be induced by epithelial-mesenchymal transition (EMT) based on evidence that APJ-KO B16 cells show persistently high levels of the mesenchymal maker, Zeb1; however, we found that EMT did not correlate with the transforming growth factor-beta/smad signaling pathway in our model. We propose that apelin-APJ system in cancer cells induces tumor growth but negatively regulates EMT and tumor malignancy.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Koichi", "last_name": "Inukai", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Kise", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Weizhen", "last_name": "Jia", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Akuta", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/pore.2023.1610867" }, "pmcid": { "normalized": "PMC9912982" }, "pmid": { "normalized": "36776217" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apelin", "descriptor_ui": "D000073861", "major_topic": true }, { "descriptor": "Apelin Receptors", "descriptor_ui": "D000075244", "major_topic": true }, { "descriptor": "Cutaneous Malignant Melanoma", "descriptor_ui": "D000096142", "major_topic": false }, { "descriptor": "Melanoma", "descriptor_ui": "D008545", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "1610867", "proceedings_title": null, "publisher": "", "title": "Pathology oncology research : POR", "volume": "29", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Cancer apelin receptor suppresses vascular mimicry in malignant melanoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Amoeboid cell movement and migration are wide-spread across various cell types and species. Microscopy-based analysis of the model systems Dictyostelium and neutrophils over the years have uncovered generality in their overall cell movement pattern. Under no directional cues, the centroid movement can be quantitatively characterized by their persistence to move in a straight line and the frequency of re-orientation. Mathematically, the cells essentially behave as a persistent random walker with memory of two characteristic time-scale. Such quantitative characterization is important from a cellular-level ethology point of view as it has direct connotation to their exploratory and foraging strategies. Interestingly, outside the amoebozoa and metazoa, there are largely uncharacterized species in the excavate taxon Heterolobosea including amoeboflagellate Naegleria. While classical works have shown that these cells indeed show typical amoeboid locomotion on an attached surface, their quantitative features are so far unexplored. Here, we analyzed the cell movement of Naegleria gruberi by employing long-time phase contrast imaging that automatically tracks individual cells. We show that the cells move as a persistent random walker with two time-scales that are close to those known in Dictyostelium and neutrophils. Similarities were also found in the shape dynamics which are characterized by the appearance, splitting and annihilation of the curvature waves along the cell edge. Our analysis based on the Fourier descriptor and a neural network classifier point to importance of morphology features unique to Naegleria including complex protrusions and the transient bipolar dumbbell morphologies.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masahito", "last_name": "Uwamichi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2023.1274127" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38020930" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Cell and Developmental Biology", "volume": "11", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Random walk and cell morphology dynamics in Naegleria gruberi.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Motor neurons (MNs) are one of the most important components of Central Pattern Generators (CPG) in vertebrates (Brown, Proceedings of The Royal Society B: Biological Sciences (The Royal Society), 1911, 84(572), 308–319). However, it is unclear how the neural activities of these components develop during their embryogenesis. Our previous study revealed that in Ciona robusta (Ciona intestinalis type A), a model organism with a simple neural circuit, a single pair of MNs (MN2L/MN2R) was determining the rhythm of its spontaneous early motor behavior (developmental stage St.22-24). MN2s are known to be one of the main components of Ciona CPG, though the neural activities of MN2s in the later larval period (St.25-) were not yet investigated. In this study, we investigated the neural activities of MN2s during their later stages and how they are related to Ciona’s swimming CPG. Long-term simultaneous Ca2+ imaging of both MN2s with GCaMP6s/f (St.22-34) revealed that MN2s continued to determine the rhythm of motor behavior even in their later larval stages. Their activities were classified into seven phases (I-VII) depending on the interval and the synchronicity of MN2L and MN2R Ca2+ transients. Initially, each MN2 oscillates sporadically (I). As they develop into swimming larvae, they gradually oscillate at a constant interval (II-III), then start to synchronize (IV) and fully synchronize (V). Intervals become longer (VI) and sporadic again during the tail aggression period (VII). Interestingly, 76% of the embryos started to oscillate from MN2R. In addition, independent photostimulations on left and right MN2s were conducted. This is the first report of the live imaging of neural activities in Ciona’s developing swimming CPG. These findings will help to understand the development of motor neuron circuits in chordate animals.", "classifications": [ { "id": "21H00440", "label": "21H00440", "researcher": "Kohji Hotta", "type": "grant" }, { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Madoka K.", "last_name": "Utsumi", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2023.1100887" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36711039" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Cell and Developmental Biology", "volume": "11", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Transitions of motor neuron activities during Ciona development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The role of B cells in antitumor immunity has been reported to be either promotive or suppressive, but the specific mechanism remains to be comprehensively understood. However, this complicated situation likely depends on the temporal and spatial relationship between the developing tumor and B cells that recognize tumor antigens. Unlike responses against microbial or pathogenic infections, tumor cells are derived from autologous cells that have mutated and become aberrant; thus, elimination by the adaptive immune system is essentially inefficient. If tumor cells can evade immune attack at an early stage, non-destructive responses, such as tolerance and immunosuppression, are established over time. In tumor-draining lymph nodes (TDLNs), tumor antigen-reactive B cells potentially acquire immunoregulatory phenotypes and contribute to an immunosuppressive microenvironment. Therefore, triggering and enhancing antitumor responses by immunotherapies require selective control of these regulatory B cell subsets in TDLNs. In contrast, B cell infiltration and formation of tertiary lymphoid structures in tumors are positively correlated with therapeutic prognosis, suggesting that tumor antigen-specific activation of B cells and antibody production are advantageous for antitumor immunity in mid- to late-stage tumors. Given that the presence of B cells in tumor tissues may reflect the ongoing antitumor response in TDLNs, therapeutic induction and enhancement of these lymphocytes are expected to increase the overall effectiveness of immunotherapy. Therefore, B cells are promising targets, but the spatiotemporal balance of the subsets that exhibit opposite characteristics, that is, the protumor or antitumor state in TDLNs, should be understood, and strategies to separately control their functions should be developed to maximize the clinical outcome.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fonc.2023.1088129" }, "pmcid": { "normalized": "PMC9902938" }, "pmid": { "normalized": "36761946" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "1088129", "proceedings_title": null, "publisher": "", "title": "Frontiers in oncology", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Yin and yang roles of B lymphocytes in solid tumors: Balance between antitumor immunity and immune tolerance/immunosuppression in tumor-draining lymph nodes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurological diseases are often life threatening, with severely affecting an individual's quality of life. However, the disease mechanisms are still less understood, mainly because of lacking good disease models. Over the past decades, researchers developed many models using cell lines or animals, but most of them did not faithfully recapitulate the disease phenotypes. In particular, it is almost impossible to create animal models for multifactorial diseases or sporadic cases of unknown etiology. In these circumstances, it has come to be expected that induced pluripotent stem cells (iPSCs) can revolutionize neurological disease research as they retain patient's genetic information and provide an expandable source of disease-relevant neurons and glial cells. iPSC technologies are now widely used for disease modeling, and further for drug discovery and regenerative medicine. They are also enabling previously infeasible studies such as those uncovering how disease-associated single nucleotide polymorphism (SNP) and genetic variants increase the disease risk. This review describes a variety of iPSC technologies to produce various types of neurons and brain-like tissues (brain organoids) and summarize recent trends in iPSC technology-based neurological disease research. We also discuss the remaining challenges for understanding and overcoming brain disorders.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Toshiya", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/fpj.22084" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36596493" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Nervous System Diseases", "descriptor_ui": "D009422", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Quality of Life", "descriptor_ui": "D011788", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "1", "normalized_date": "2023", "pages": "57-63", "proceedings_title": null, "publisher": "", "title": "Nihon yakurigaku zasshi. Folia pharmacologica Japonica", "volume": "158", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "[iPS cell technologies toward overcoming neurological diseases].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "As the brain is a prime immune privileged organ, immune responses in it were not studied as intensively as other peripheral organs in the past. However, the brain is studded with immune cells called microglia, which play important roles particularly in diseased conditions. In addition, from recent descriptive works, we have learned a lot about immune cells in neighboring tissues. Recent progress has rather made it clearer that the immune responses in and around the brain are complicated reactions with both positive and negative effects. And we still have not identified the way(s) we should pursue for clinical applications. Here we introduce microglia and macrophages in the steady state. We also discuss their roles in stroke, a major cause of death and disability in Japan, and Alzheimer's disease, which account for 60 to 70% of dementia.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Kanamori", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/fpj.22155" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37394549" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": true }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Microglia", "descriptor_ui": "D017628", "major_topic": false }, { "descriptor": "Stroke", "descriptor_ui": "D020521", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "4", "normalized_date": "2023", "pages": "304-307", "proceedings_title": null, "publisher": "", "title": "Nihon yakurigaku zasshi. Folia pharmacologica Japonica", "volume": "158", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "[Microglia and macrophages in diseases].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The immune system is deeply involved in autoimmune diseases of the central nervous system (CNS), such as multiple sclerosis, N-methyl-d-aspartate (NMDA) receptor encephalitis, and narcolepsy. Additionally, the immune system is involved in various brain diseases including cerebral infarction and neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). In particular, reports related to T cells are increasing. T cells may also play important roles in brain deterioration and dementia that occur with aging. Our understanding of the role of immune cells in the context of the brain has been greatly improved by the use of acute ischemic brain injury models. Additionally, similar neural damage and repair events are shown to occur in more chronic brain neurodegenerative brain diseases. In this review, we focus on the role of T cells, including CD4(+) T cells, CD8(+) T cells and regulatory T cells (Tregs) in cerebral infarction and neurodegenerative diseases.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Ohyagi", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/bs.ai.2022.10.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37061287" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": true }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "Cerebral Infarction", "descriptor_ui": "D002544", "major_topic": false }, { "descriptor": "Encephalitis", "descriptor_ui": "D004660", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infectious Encephalitis", "descriptor_ui": "D000069544", "major_topic": true }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Neurodegenerative Diseases", "descriptor_ui": "D019636", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "29-58", "proceedings_title": null, "publisher": "", "title": "Advances in immunology", "volume": "157", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "T cells in the brain inflammation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Functionally mature neural circuits are shaped during postnatal development by eliminating redundant synapses formed during the perinatal period. In the cerebellum of neonatal rodents, each Purkinje cell (PC) receives synaptic inputs from multiple (more than 4) climbing fibers (CFs). During the first 3 postnatal weeks, synaptic inputs from a single CF become markedly larger and those from the other CFs are eliminated in each PC, leading to mono-innervation of each PC by a strong CF in adulthood. While molecules involved in the strengthening and elimination of CF synapses during postnatal development are being elucidated, much less is known about the molecular mechanisms underlying CF synapse formation during the early postnatal period. Here, we show experimental evidence that suggests that a synapse organizer, PTPdelta, is required for early postnatal CF synapse formation and the subsequent establishment of CF to PC synaptic wiring. We showed that PTPdelta was localized at CF-PC synapses from postnatal day 0 (P0) irrespective of the expression of Aldolase C (Aldoc), a major marker of PC that distinguishes the cerebellar compartments. We found that the extension of a single strong CF along PC dendrites (CF translocation) was impaired in global PTPdelta knockout (KO) mice from P12 to P29-31 predominantly in PCs that did not express Aldoc [Aldoc (-) PCs]. We also demonstrated via morphological and electrophysiological analyses that the number of CFs innervating individual PCs in PTPdelta KO mice were fewer than in wild-type (WT) mice from P3 to P13 with a significant decrease in the strength of CF synaptic inputs in cerebellar anterior lobules where most PCs are Aldoc (-). Furthermore, CF-specific PTPdelta-knockdown (KD) caused a reduction in the number of CFs innervating PCs with decreased CF synaptic inputs at P10-13 in anterior lobules. We found a mild impairment of motor performance in adult PTPdelta KO mice. These results indicate that PTPdelta acts as a presynaptic organizer for CF-PC formation and is required for normal CF-PC synaptic transmission, CF translocation, and presumably CF synapse maintenance predominantly in Aldoc (-) PCs. Furthermore, this study suggests that the impaired CF-PC synapse formation and development by the lack of PTPdelta causes mild impairment of motor performance.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuto", "last_name": "Okuno", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Sakoori", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Matsuyama", "name": null }, { "creator_type": "author", "first_name": "Miwako", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnmol.2023.1206245" }, "pmcid": { "normalized": "PMC10323364" }, "pmid": { "normalized": "37426069" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "1206245", "proceedings_title": null, "publisher": "", "title": "Frontiers in molecular neuroscience", "volume": "16", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000388" ], "repository": [ "ssbd-repos-000388" ] }, "title": "PTPdelta is a presynaptic organizer for the formation and maintenance of climbing fiber to Purkinje cell synapses in the developing cerebellum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ion currents associated with channel proteins in the presence of membrane potential are ubiquitous in cellular and organelle membranes. When an ion current occurs through a channel protein, Joule heating should occur. However, this Joule heating seems to have been largely overlooked in biology. Here we show theoretical investigation of Joule heating involving channel proteins in biological processes. We used electrochemical potential to derive the Joule’s law for an ion current through an ion transport protein in the presence of membrane potential, and we suggest that heat production and absorption can occur. Simulation of temperature distribution around a single channel protein with the Joule heating revealed that the temperature increase was as small as <10–3 K, although an ensemble of channel proteins was suggested to exhibit a noticeable temperature increase. Thereby, we theoretically investigated the Joule heating of systems containing ensembles of channel proteins. Nerve is known to undergo rapid heat production followed by heat absorption during the action potential, and our simulation of Joule heating for a squid giant axon combined with the Hodgkin-Huxley model successfully reproduced the feature of the heat. Furthermore, we extended the theory of Joule heating to uncoupling protein 1 (UCP1), a solute carrier family transporter, which is important to the non-shivering thermogenesis in brown adipose tissue mitochondria (BATM). Our calculations showed that the Joule heat involving UCP1 was comparable to the literature calorimetry data of BATM. Joule heating of ion transport proteins is likely to be one of important mechanisms of cellular thermogenesis.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuichi", "last_name": "Wazawa", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v20.0030" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38124793" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "3", "normalized_date": "2023", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biophysics and Physicobiology", "volume": "20", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Joule heating involving ion currents through channel proteins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Alexander", "last_name": "Walter", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Mitsuharu", "last_name": "Midorikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fncel.2023.1213640" }, "pmcid": { "normalized": "PMC10235784" }, "pmid": { "normalized": "37275775" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "1213640", "proceedings_title": null, "publisher": "", "title": "Frontiers in cellular neuroscience", "volume": "17", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Editorial: Functional and molecular insights of neural circuit adaptation, refinement, and remodeling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND AIMS: To examine the roles of microRNAs in the development of colitis, we conducted the RNA-sequencing studies using RNA derived from normal and colitogenic CD4+ T cells. Colitogenic CD4(+) T cells demonstrated the increased expression of miR-150. We focused on the involvement of miR-150 in the colitis. METHODS: We crossed miR-150 knockout mice and T-cell-specific Rap1KO mice, which is colitis model mice and spontaneously develop the colitis with tubular adenomas in microbiota-dependent manner. RESULTS: MiR-150 silencing completely inhibited the expansion of pathogenic Th17 cells and the development of colitis. CONCLUSION: MiR-150 is a potential therapeutic target of inflammatory bowel diseases.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Sayaka", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Fujikado", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Kotani", "name": null }, { "creator_type": "author", "first_name": "Koko", "last_name": "Katagiri", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.gastha.2023.01.021" }, "pmcid": { "normalized": "PMC11308117" }, "pmid": { "normalized": "39132043" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "4", "normalized_date": "2023", "pages": "487-496", "proceedings_title": null, "publisher": "", "title": "Gastro hep advances", "volume": "2", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Deletion of miR-150 Prevents Spontaneous T Cell Proliferation and the Development of Colitis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "B cell anergy plays a critical role in maintaining self-tolerance by inhibiting autoreactive B cell activation to prevent autoimmune diseases. Here, we demonstrated that Fc receptor-like 5 (Fcrl5) upregulation contributes to autoimmune disease pathogenesis by disrupting B cell anergy. Fcrl5-a gene whose homologs are associated with human autoimmune diseases-is highly expressed in age/autoimmunity-associated B cells (ABCs), an autoreactive B cell subset. By generating B cell-specific Fcrl5 transgenic mice, we demonstrated that Fcrl5 overexpression in B cells caused systemic autoimmunity with age. Additionally, Fcrl5 upregulation in B cells exacerbated the systemic lupus erythematosus-like disease model. Furthermore, an increase in Fcrl5 expression broke B cell anergy and facilitated toll-like receptor signaling. Thus, Fcrl5 is a potential regulator of B cell-mediated autoimmunity by regulating B cell anergy. This study provides important insights into the role of Fcrl5 in breaking B cell anergy and its effect on the pathogenesis of autoimmune diseases.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Chisato", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Myouzen", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Mahoko", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Yoshinao", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Kochi", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2023.1276014" }, "pmcid": { "normalized": "PMC10569490" }, "pmid": { "normalized": "37841260" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autoimmune Diseases", "descriptor_ui": "D001327", "major_topic": true }, { "descriptor": "Autoimmunity", "descriptor_ui": "D015551", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lupus Erythematosus, Systemic", "descriptor_ui": "D008180", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Receptors, Fc", "descriptor_ui": "D011961", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "1276014", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Upregulated Fcrl5 disrupts B cell anergy causes autoimmune disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Some evidence suggests that oxytocin, which is a neuropeptide conventionally thought to be synthesized in the hypothalamus and released by the posterior pituitary, is generated in peripheral keratinocytes, but the details are lacking and the mRNA analysis is further required. Oxytocin and neurophysin I are generated together as cleavage products after splitting the precursor molecule, preprooxyphysin. To confirm that oxytocin and neurophysin I are also generated in the peripheral keratinocytes, it must first be clarified that these molecules contained in peripheral keratinocytes did not originate in the posterior pituitary gland and then the expression of oxytocin and neurophysin I mRNAs must be established in keratinocytes. Therefore, we attempted to quantify preprooxyphysin mRNA in keratinocytes using various primers. Using real-time PCR, we observed that the mRNAs of both oxytocin and neurophysin I were located in keratinocytes. However, the mRNA amounts of oxytocin, neurophysin I, and preprooxyphysin were too small to confirm their co-existence in keratinocytes. Thus, we had to further determine whether the PCR-amplified sequence was identical to preprooxyphysin. The PCR products analyzed by DNA sequencing were identical to preprooxyphysin, finally determining the co-existence of both oxytocin and neurophysin I mRNAs in keratinocytes. In addition, the immunocytochemical experiments showed that oxytocin and neurophysin I proteins were located in keratinocytes. These results of the present study provided further support indicating that oxytocin and neurophysin I are generated in peripheral keratinocytes.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kanta", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Inada", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v20.0003" }, "pmcid": { "normalized": "PMC10205573" }, "pmid": { "normalized": "37234847" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "1", "normalized_date": "2023", "pages": "e200003", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "20", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Revisiting oxytocin generation in keratinocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Organismal transparency constitutes a significant concern in whole-body live imaging, yet its underlying structural, genetic, and physiological foundations remain inadequately comprehended. Diverse environmental and physiological factors (multimodal factors) are recognized for their influence on organismal transparency. However, a comprehensive and integrated quantitative evaluation system for biological transparency across a broad spectrum of wavelengths is presently lacking. In this study, we have devised an evaluation system to gauge alterations in organismal transparency induced by multimodal factors, encompassing a wide range of transmittance spanning from 380 to 1000 nm, utilizing hyperspectral microscopy. Through experimentation, we have scrutinized the impact of three environmental variables (temperature, salinity, and pH) and the effect of 11 drugs treatment containing inhibitors targeting physiological processes in the ascidian Ascidiella aspersa. This particular species, known for its exceptionally transparent eggs and embryos, serves as an ideal model. We calculated bio-transparency defined as the mean transmittance ratio of visible light within the range of 400-760 nm. Our findings reveal a positive correlation between bio-transparency and temperature, while an inverse relationship is observed with salinity levels. Notably, reduced pH levels and exposure to six drugs have led to significant decreasing in bio-transparency (ranging from 4.2% to 58.6%). Principal component analysis (PCA) on the measured transmittance data classified these factors into distinct groups. This suggest diverse pathways through which opacification occurs across different spectrum regions. The outcome of our quantitative analysis of bio-transparency holds potential applicability to diverse living organisms on multiple scales. This analytical framework also contributes to a holistic comprehension of the mechanisms underlying biological transparency, which is susceptible to many environmental and physiological modalities.", "classifications": [ { "id": "21H00440", "label": "21H00440", "researcher": "Kohji Hotta", "type": "grant" }, { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takumi T.", "last_name": "Shito", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0292524" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37819990" } }, "mesh": [ { "descriptor": "Hyperspectral Imaging", "descriptor_ui": "D000081862", "major_topic": true }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": true }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Principal Component Analysis", "descriptor_ui": "D025341", "major_topic": false }, { "descriptor": "Salinity", "descriptor_ui": "D054712", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "10", "normalized_date": "2023", "pages": "e0292524", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "18", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Multimodal factor evaluation system for organismal transparency by hyperspectral imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Optogenetic techniques offer a high spatiotemporal resolution to manipulate cellular activity. For instance, Channelrhodopsin-2 with global light illumination is the most widely used to control neuronal activity at the cellular level. However, the cellular scale is much larger than the diffraction limit of light (<1 mum) and does not fully exploit the features of the \"high spatial resolution\" of optogenetics. For instance, until recently, there were no optogenetic methods to induce synaptic plasticity at the level of single synapses. To address this, we developed an optogenetic tool named photoactivatable CaMKII (paCaMKII) by fusing a light-sensitive domain (LOV2) to CaMKIIalpha, which is a protein abundantly expressed in neurons of the cerebrum and hippocampus and essential for synaptic plasticity. Combining photoactivatable CaMKII with two-photon excitation, we successfully activated it in single spines, inducing synaptic plasticity (long-term potentiation) in hippocampal neurons. We refer to this method as \"Local Optogenetics\", which involves the local activation of molecules and measurement of cellular responses. In this review, we will discuss the characteristics of LOV2, the recent development of its derivatives, and the development and application of paCaMKII.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yutaro", "last_name": "Nagasawa", "name": null }, { "creator_type": "author", "first_name": "Hiromi H.", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Kawabata", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v20.0027" }, "pmcid": { "normalized": "PMC10941968" }, "pmid": { "normalized": "38496236" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "2", "normalized_date": "2023", "pages": "e200027", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "20", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "LOV2-based photoactivatable CaMKII and its application to single synapses: Local Optogenetics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We previously found that pituitary adenylate cyclase-activating polypeptide (PACAP)-deficient (PACAP(-/-)) mice exhibit dendritic spine morphology impairment and neurodevelopmental disorder (NDD)-like behaviors such as hyperactivity, increased novelty-seeking behavior, and deficient pre-pulse inhibition. Recent studies have indicated that rodent models of NDDs (e.g., attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder) show abnormalities in the axon initial segment (AIS). Here, we revealed that PACAP(-/-) mice exhibited a longer AIS length in layer 2/3 pyramidal neurons of the primary somatosensory barrel field compared with wild-type control mice. Further, we previously showed that a single injection of atomoxetine, an ADHD drug, improved hyperactivity in PACAP(-/-) mice. In this study, we found that repeated treatments of atomoxetine significantly improved AIS abnormality along with hyperactivity in PACAP(-/-) mice. These results suggest that AIS abnormalities are associated with NDDs-like behaviors in PACAP(-/-) mice. Thus, improvement in AIS abnormalities will be a novel drug therapy for NDDs.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Misaki", "last_name": "Iwahashi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Wakana", "last_name": "Harigai", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Taiichi", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphs.2023.08.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37770159" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Atomoxetine Hydrochloride", "descriptor_ui": "D000069445", "major_topic": false }, { "descriptor": "Attention Deficit Disorder with Hyperactivity", "descriptor_ui": "D001289", "major_topic": false }, { "descriptor": "Axon Initial Segment", "descriptor_ui": "D000071040", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neurodevelopmental Disorders", "descriptor_ui": "D065886", "major_topic": true }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": true }, { "descriptor": "Pyramidal Cells", "descriptor_ui": "D017966", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Nov", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "175-182", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "153", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Pituitary adenylate cyclase-activating polypeptide deficient mice show length abnormalities of the axon initial segment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Necitumumab plus gemcitabine and cisplatin (GCN) is a standard therapy for patients with advanced lung squamous cell carcinoma (LSqCC). However, the efficacy and tolerability of GCN in second-line or later treatment for patients previously treated with immune checkpoint inhibitors (ICIs) remain unknown. METHODS: This multicenter, retrospective, cohort study assessed the efficacy and tolerability of GCN initiated between November 1, 2019 and March 31, 2022 as second-line to fourth-line treatment in patients with advanced LSqCC who had been pretreated with ICIs. The primary end point was progression-free survival (PFS). RESULTS: A total of 93 patients from 35 institutions in Japan were enrolled. The median PFS, median overall survival (OS), and objective response rate were 4.4 months (95% confidence interval [CI]: 3.8-5.3), 13.3 months (95% CI: 9.6-16.5), and 27.3% (95% CI: 18.3-37.8), respectively. The median PFS, median OS, and objective response rate for second-line, third-line, and fourth-line treatment groups were 4.8 months, 3.8 months, and 4.3 months (p = 0.24); 15.7 months, 11.6 months, and 10.1 months (p = 0.06); and 31.0%, 13.6%, and 37.5% (p = 0.22), respectively. The severity of GCN-related skin disorders was associated with longer PFS (p < 0.05) and OS (p < 0.05). The frequencies of grade ≥3 skin disorders, hypomagnesemia, pneumonitis, and febrile neutropenia were 16.1%, 7.5%, 1.1%, and 4.3%, respectively. There were no treatment-related deaths. CONCLUSIONS: GCN for ICI-pretreated patients with LSqCC seems tolerable and offers promising efficacy regardless of treatment line, and ICI pretreatment might enhance GCN efficacy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yasunori", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Tanzawa", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Misumi", "name": null }, { "creator_type": "author", "first_name": "Hiroshige", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Eisaku", "last_name": "Miyauchi", "name": null }, { "creator_type": "author", "first_name": "Kiichiro", "last_name": "Ninomiya", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Takeshita", "name": null }, { "creator_type": "author", "first_name": "Kensaku", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Miyanaga", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Nojiri", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kozuki", "name": null }, { "creator_type": "author", "first_name": "Takahisa", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Teppei", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Tetsumoto", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Kakuhiro", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Shoichi", "last_name": "Kuyama", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Tsuruno", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Misumi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kuraishi", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Seki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtocrr.2023.100593" }, "pmcid": { "normalized": "PMC10689269" }, "pmid": { "normalized": "38046378" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "100593", "proceedings_title": null, "publisher": "", "title": "JTO clinical and research reports", "volume": "4", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Multicenter, Retrospective Study to Evaluate Necitumumab Plus Cisplatin and Gemcitabine After Immune Checkpoint Inhibitors in Advanced Squamous Cell Lung Cancer in Japan: The NINJA Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Although blue light is one of the therapeutic approaches used to treat acne vulgaris (AV), there is no consensus on its effectiveness. As a result, it is not recommended in the major acne vulgaris treatment guidelines. OBJECTIVE: The goal of this study was to look into the mechanism, safety, and efficacy of blue light therapy. We achieved this by examining the pathological response, inflammation, and depth of light penetration in a mouse model of cystic AV. METHODS: The aims of the study were addressed by exposing the mice to light with a wavelength of 415 nm under four different irradiation conditions. The exposure was done for five consecutive days followed by a no irradiation period of 72 h. RESULTS: Blue light treatment was most effective when irradiation was performed at 100 mW/cm(2) for 20 min for five consecutive days. Inflammatory responses emerged 72 h after the final irradiation dose was administered. These responses were not associated with apoptosis as cleaved caspase-3 staining revealed no significant increases in apoptosis in the skin under any of the tested conditions. Blue light reached the superficial layer of the acne cyst at 5% of the total irradiation power and was attenuated by half for every 50 mum of progress through the cyst. CONCLUSION: In conclusion, blue light could control severe dermatologic inflammatory responses; therefore, it can be used to irradiate AV with high inflammation levels on a daily basis until improvement is observed. In addition, porphyrin, a metabolite of Cutibacterium acnes, and reactive oxygen species generated by the surrounding skin tissue may have essential roles in AV treatment.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Eiko", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Yoshine", "last_name": "Mayumi", "name": null }, { "creator_type": "author", "first_name": "Seigo", "last_name": "Fushuku", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Tomoharu", "last_name": "Kiyosawa", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Azuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphotobiol.2023.112651" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36680809" } }, "mesh": [ { "descriptor": "Acne Vulgaris", "descriptor_ui": "D000152", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phototherapy", "descriptor_ui": "D010789", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Feb", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "112651", "proceedings_title": null, "publisher": "", "title": "Journal of photochemistry and photobiology. B, Biology", "volume": "239", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Optimal blue light irradiation conditions for the treatment of acne vulgaris in a mouse model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Estimation of dynamic change of crossbridge formation in living cardiomyocytes is expected to provide crucial information for elucidating cardiomyopathy mechanisms, efficacy of an intervention, and others. Here, we established an assay system to dynamically measure second harmonic generation (SHG) anisotropy derived from myosin filaments depended on their crossbridge status in pulsating cardiomyocytes. Experiments utilizing an inheritable mutation that induces excessive myosin–actin interactions revealed that the correlation between sarcomere length and SHG anisotropy represents crossbridge formation ratio during pulsation. Furthermore, the present method found that ultraviolet irradiation induced an increased population of attached crossbridges that lost the force-generating ability upon myocardial differentiation. Taking an advantage of infrared two-photon excitation in SHG microscopy, myocardial dysfunction could be intravitally evaluated in a Drosophila disease model. Thus, we successfully demonstrated the applicability and effectiveness of the present method to evaluate the actomyosin activity of a drug or genetic defect on cardiomyocytes. Because genomic inspection alone may not catch the risk of cardiomyopathy in some cases, our study demonstrated herein would be of help in the risk assessment of future heart failure.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Kaneshiro", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Rikako", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Umetsu", "name": null }, { "creator_type": "author", "first_name": "Erina", "last_name": "Kuranaga", "name": null }, { "creator_type": "author", "first_name": "Shuichiro", "last_name": "Higo", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sakata", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Miyagawa", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.26508/lsa.202302070" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37236659" } }, "mesh": [ { "descriptor": "Actomyosin", "descriptor_ui": "D000205", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": true }, { "descriptor": "Myosins", "descriptor_ui": "D009218", "major_topic": false }, { "descriptor": "Second Harmonic Generation Microscopy", "descriptor_ui": "D000073798", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023/07/01", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "Life Science Alliance", "title": "Life Science Alliance", "volume": "6", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Estimation of crossbridge-state during cardiomyocyte beating using second harmonic generation", "url": "https://www.life-science-alliance.org/content/6/7/e202302070", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Endometriosis is initiated by the movement of endometrial cells in the uterus to the fallopian tubes, the ovaries and the peritoneal cavity after the shedding of the uterus lining. To cause endometriosis, it is often necessary for these endometrial cells to migrate, invade and grow at the secondary site. In the present study, immortalized human endometriosis stromal cells (HESC) were employed to look for the inhibitors of migration and invasion. Using a chemical library of bioactive metabolites, it was found that an NF‑kappaB inhibitor, DHMEQ, inhibited the migration and invasion of HESC. Both whole‑genome array and metastasis PCR array analyses suggested the involvement of myosin light chain kinase (MLCK) in the mechanism of inhibition. DHMEQ was confirmed to inhibit the expression of MLCK and small inhibitory RNA knockdown of MLCK reduced cellular migration and invasion. The addition of DHMEQ to the knockdown cells did not further inhibit migration and invasion. DHMEQ is particularly effective in suppressing disease models by intraperitoneal (IP) administration and this therapy is being developed for the treatment of inflammation and cancer. DHMEQ IP therapy may also be useful for the treatment of endometriosis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yinzhi", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Shiori", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Umezawa", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Wakatsuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.3892/mmr.2023.13028" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37326118" } }, "mesh": [ { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Endometriosis", "descriptor_ui": "D004715", "major_topic": true }, { "descriptor": "Endometrium", "descriptor_ui": "D004717", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "I-kappa B Proteins", "descriptor_ui": "D020672", "major_topic": false }, { "descriptor": "Myosin-Light-Chain Kinase", "descriptor_ui": "D009219", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Stromal Cells", "descriptor_ui": "D017154", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Aug", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "141", "proceedings_title": null, "publisher": "", "title": "Molecular medicine reports", "volume": "28", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Inhibition of MLCK‑mediated migration and invasion in human endometriosis stromal cells by NF‑kappaB inhibitor DHMEQ.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Docetaxel plus ramucirumab could be a promising treatment for chemo-naive elderly patients with NSCLC, but high incidence of febrile neutropenia (FN) is a critical concern. We thus adopted a routine primary prophylactic pegylated-granulocyte-colony stimulating factor (PEG-G-CSF) to reduce FN and maximize the efficacy of docetaxel plus ramucirumab in elderly patients. METHODS: This is a single arm phase 2 trial for chemo-naive elderly patients (aged >/=75 y) with advanced NSCLC. Docetaxel (60 mg/m(2), d 1) plus ramucirumab (10 mg/kg, d 1) with PEG-G-CSF (3.6 mg, d 2) was administered every 3 weeks until progression. The primary end point was overall response rate (ORR) (expected ORR: 35%). RESULTS: Between February 2018 and January 2021, 54 patients were enrolled. Median age was 78 (range: 75-86). A total of 21 (38.9%) partial response, 22 (40.7%) stable disease, nine (16.7%) progressive disease, and two (3.7%) not assessable were confirmed, resulting in ORR of 38.9% (90% confidence interval [CI]: 27.7%-51.0%) and disease control rate of 79.6%. Median progression-free survival and overall survival were 5.2 (95% CI: 4.2-6.9) and 12.7 (95% CI: 10.2-18.9) months, respectively. There were one (1.9%) FN, two (3.7%) bleeding grade greater than or equal to 3, and one (1.9%) treatment-related death (pneumonitis). Pneumonitis occurred in five patients (9.3%). Main adverse events grade greater than or equal to 3 were observed: four (7%) thrombocytopenia; three (5.6%) neutropenia; six (11.1%) hyposodium; five (9.3%) infection; five (9.3%) hypertension; four (7.4%) anorexia; and three (5.6%) oral mucositis. CONCLUSIONS: Docetaxel plus ramucirumab with PEG-G-CSF revealed efficacy and safety for chemo-naive elderly patients with NSCLC. Primary prophylactic PEG-G-CSF highly prevented FN.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Motoko", "last_name": "Tachihara", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Tokito", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Toyozawa", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Kazushige", "last_name": "Wakuda", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Shimokawa", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Nakagawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtocrr.2023.100569" }, "pmcid": { "normalized": "PMC10563050" }, "pmid": { "normalized": "37822699" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "100569", "proceedings_title": null, "publisher": "", "title": "JTO clinical and research reports", "volume": "4", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Docetaxel Plus Ramucirumab With Primary Prophylactic Pegylated Granulocyte-Colony Stimulating Factor Support for Elderly Patients With Advanced NSCLC: A Multicenter Prospective Single Arm Phase 2 Trial: DRAGON Study (WJOG9416L).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vitamin D receptor (VDR) is essential for hair follicle homeostasis as its deficiency induces hair loss, although the mechanism involved remains unknown. Our research shows that, in Vdr-knockout mice, the hair cycle is halted during the catagen stage, preceding alopecia. In addition, in Vdr-knockout hair follicles, epithelial strands that normally regress during the catagen phase persist as \"surviving epithelial strands.\" Single-cell RNA sequencing analysis suggests that these surviving epithelial strands are formed by cells in the lower part of the hair follicle. These findings emphasize the importance of the regression phase in hair follicle regeneration and establish VDR as a regulator of the catagen stage.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yudai", "last_name": "Joko", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Shigeaki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Fukumoto", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Sawatsubashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.26508/lsa.202302014" }, "pmcid": { "normalized": "PMC10485823" }, "pmid": { "normalized": "37673445" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Hair Follicle", "descriptor_ui": "D018859", "major_topic": true }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Receptors, Calcitriol", "descriptor_ui": "D018167", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Life science alliance", "volume": "6", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "VDR is an essential regulator of hair follicle regression through the progression of cell death.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/pcn.13552" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37259974" } }, "mesh": [ { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mental Disorders", "descriptor_ui": "D001523", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "307", "proceedings_title": null, "publisher": "", "title": "Psychiatry and clinical neurosciences", "volume": "77", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Modeling mental disorders in a dish.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: We investigated the occurrence of non-respiratory bacterial and fungal secondary infections, causative organisms, impact on clinical outcomes, and association between the secondary pathogens and mortality in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: This was a retrospective cohort study that included data from inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021). We obtained demographic, epidemiological, and microbiological data throughout the course of hospitalization and analyzed the cases of COVID-19 complicated by non-respiratory bacterial infections. RESULTS: Of the 1914 patients included, non-respiratory bacterial infections with COVID-19 were diagnosed in 81 patients (4.2%). Of these, 59 (3.1%) were secondary infections. Bacteremia was the most frequent bacterial infection, occurring in 33 cases (55.9%), followed by urinary tract infections in 16 cases (27.1%). Staphylococcus epidermidis was the most common causative organism of bacteremia. Patients with COVID-19 with non-respiratory secondary bacterial infections had significantly higher mortality, and a multivariate logistic regression analysis demonstrated that those with bacteremia (aOdds Ratio = 15.3 [5.97-39.1]) were at higher risk of death. Multivariate logistic regression analysis showed that age, male sex, use of steroids to treat COVID-19, and intensive care unit admission increased the risk for nosocomial bacteremia. CONCLUSIONS: Secondary bacteremia is an important complication that may lead to poor prognosis in cases with COVID-19. An appropriate medical management strategy must be established, especially for patients with concomitant predisposing factors.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kensuke", "last_name": "Nakagawara", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Kamata", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Chubachi", "name": null }, { "creator_type": "author", "first_name": "Ho", "last_name": "Namkoong", "name": null }, { "creator_type": "author", "first_name": "Hiromu", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ho", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Shiro", "last_name": "Otake", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Atsuho", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Azekawa", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Watase", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Asakura", "name": null }, { "creator_type": "author", "first_name": "Katsunori", "last_name": "Masaki", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Ishikura", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Norihiro", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kokutou", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yoshiyama", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Mutoh", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Tomohisa", "last_name": "Shoko", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Muranaka", "name": null }, { "creator_type": "author", "first_name": "Kodai", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Nobuaki", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Mochimaru", "name": null }, { "creator_type": "author", "first_name": "Mototaka", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Chihara", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Nagasaki", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Amishima", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Odani", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Tani", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Nishi", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Ryuya", "last_name": "Edahiro", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Naozumi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kagaya", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Miyazawa", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Fujitani", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Hirohito", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Tanino", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Otsuki", "name": null }, { "creator_type": "author", "first_name": "Shuko", "last_name": "Mashimo", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Kuramochi", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Hosoda", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Yotaro", "last_name": "Takaku", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Naota", "last_name": "Kuwahara", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Hagiwara", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Nakamori", "name": null }, { "creator_type": "author", "first_name": "Fukuki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Kono", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Tomoo", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Kusaka", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Kimizuka", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Kawana", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yukinori", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Ai", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kumanogoh", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Katsushi", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Miyano", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Seishi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fukunaga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jiac.2023.01.006" }, "pmcid": { "normalized": "PMC9851919" }, "pmid": { "normalized": "36682606" } }, "mesh": [ { "descriptor": "Bacteremia", "descriptor_ui": "D016470", "major_topic": true }, { "descriptor": "Bacterial Infections", "descriptor_ui": "D001424", "major_topic": true }, { "descriptor": "Coinfection", "descriptor_ui": "D060085", "major_topic": true }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "COVID-19 Testing", "descriptor_ui": "D000086742", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mycoses", "descriptor_ui": "D009181", "major_topic": true }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "422-426", "proceedings_title": null, "publisher": "", "title": "Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy", "volume": "29", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Diagnostic significance of secondary bacteremia in patients with COVID-19.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The chemokine CCL21 regulates immune and cancer cell migration through its receptor CCR7. The Ccl21a gene encodes the isoform CCL21-Ser, predominantly expressed in the thymic medulla and the secondary lymphoid tissues. This study examined the roles of CCL21-Ser in the antitumor immune response in Ccl21a-knockout (KO) mice. The Ccl21a-KO mice showed significantly decreased growth of B16-F10 and YUMM1.7 melanomas and increased growth of MC38 colon cancer, despite no significant difference in LLC lung cancer and EO771 breast cancer. The B16-F10 tumor in Ccl21a-KO mice showed melanoma-specific activated CD8(+) T cell and NK cell infiltration and higher Treg counts than wild-type mice. B16-F10 tumors in Ccl21a-KO mice showed a reduction in the positive correlation between the ratio of regulatory T cells (Tregs) to activated CD8(+) T cells and tumor weight. In Ccl21a-KO tumor, the intratumoral Tregs showed lower co-inhibitory receptors TIM-3 and TIGIT. Taken together, these results suggest that endogenous CCL21-Ser supports melanoma growth in vivo by maintaining Treg function and suppressing antitumor immunity by CD8(+) T cells.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ryonosuke", "last_name": "Fujie", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Kurowarabe", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kakeru", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Nakatani", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Hinami", "last_name": "Kawahata", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Madoka", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null }, { "creator_type": "author", "first_name": "Yousuke", "last_name": "Takahama", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Ohigashi", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Hayasaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.heliyon.2023.e19215" }, "pmcid": { "normalized": "PMC10469598" }, "pmid": { "normalized": "37664721" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "e19215", "proceedings_title": null, "publisher": "", "title": "Heliyon", "volume": "9", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Endogenous CCL21-Ser deficiency reduces B16-F10 melanoma growth by enhanced antitumor immunity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a pivotal role in synaptic plasticity. It is a dodecameric serine/threonine kinase that has been highly conserved across metazoans for over a million years. Despite the extensive knowledge of the mechanisms underlying CaMKII activation, its behavior at the molecular level has remained unobserved. In this study, we used high-speed atomic force microscopy to visualize the activity-dependent structural dynamics of rat/hydra/C. elegans CaMKII with nanometer resolution. Our imaging results revealed that the dynamic behavior is dependent on CaM binding and subsequent pT286 phosphorylation. Among the species studies, only rat CaMKIIα with pT286/pT305/pT306 exhibited kinase domain oligomerization. Furthermore, we revealed that the sensitivity of CaMKII to PP2A in the three species differs, with rat, C. elegans, and hydra being less dephosphorylated in that order. The evolutionarily acquired features of mammalian CaMKIIα-specific structural arrangement and phosphatase tolerance may differentiate neuronal function between mammals and other species.", "classifications": [ { "id": "19H05434", "label": "19H05434", "researcher": "Hideji Murakoshi", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shotaro", "last_name": "Tsujioka", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Sumino", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Nagasawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Sumikama", "name": null }, { "creator_type": "author", "first_name": "Holger", "last_name": "Flechsig", "name": null }, { "creator_type": "author", "first_name": "Leonardo", "last_name": "Puppulin", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Yudai", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kakuta", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Ogoshi", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Kodera", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Mikihiro", "last_name": "Shibata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adh1069" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37390213" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinase Type 2", "descriptor_ui": "D054732", "major_topic": true }, { "descriptor": "Holoenzymes", "descriptor_ui": "D020035", "major_topic": false }, { "descriptor": "Hydra", "descriptor_ui": "D006829", "major_topic": true }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Microscopy, Atomic Force", "descriptor_ui": "D018625", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jun", "date_precision": "unknown", "issue": "26", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Science Advances", "volume": "9", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Imaging single CaMKII holoenzymes at work by high-speed atomic force microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Glioblastoma is characterized by diffuse infiltration into the normal brain. Invasive glioma stem cells (GSCs) are an underlying cause of treatment failure. Despite the use of multimodal therapies, the prognosis remains dismal. New therapeutic approach targeting invasive GSCs is required. Here, we show that neural stem cells (NSCs) derived from CRISRP/Cas9-edited human-induced pluripotent stem cell (hiPSC) expressing a suicide gene had higher tumor-trophic migratory capacity compared with mesenchymal stem cells (MSCs), leading to marked in vivo antitumor effects. High migratory capacity in iPSC-NSCs was related to self-repulsive action and pathotropism involved in EphB-ephrinB and CXCL12-CXCR4 signaling. The gene insertion to ACTB provided higher and stable transgene expression than other common insertion sites, such as GAPDH or AAVS1. Ferroptosis was associated with enhanced antitumor immune responses. The thymidylate synthase and dihydroprimidine dehydrogenase expressions predicted the treatment efficacy of therapeutic hiPSC-NSCs. Our results indicate the potential benefit of genome-edited iPS cells based gene therapy for invasive GSCs. Furthermore, the present research concept may become a platform to promote clinical studies using hiPSC.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryota", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Miyoshi", "name": null }, { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yo", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Kase", "name": null }, { "creator_type": "author", "first_name": "Tsukika", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Mizuto", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yukina", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Oltea", "last_name": "Sampetrean", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Kohyama", "name": null }, { "creator_type": "author", "first_name": "Munehisa", "last_name": "Shinozaki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Saya", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Toda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/btm2.10406" }, "pmcid": { "normalized": "PMC10487333" }, "pmid": { "normalized": "37693056" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Sep", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "e10406", "proceedings_title": null, "publisher": "", "title": "Bioengineering & translational medicine", "volume": "8", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Gene therapy using genome-edited iPS cells for targeting malignant glioma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The mortality rates of coronavirus disease 2019 (COVID-19) have been changed across the epidemiological waves. The aim was to investigate the differences in mortality rates of COVID-19 patients in Japan across the 6 epidemiological waves stratified by age group and Coronavirus Clinical Characterisation Consortium (4C) mortality score risk group. METHODS: A total of 56 986 COVID-19 patients in the COVID-19 Registry Japan from 2 March 2020 to 1 February 2022 were enrolled. These patients were categorized into 4 risk groups based on their 4C mortality score. Mortality rates of each risk group were calculated separately for different age groups: 18-64, 65-74, 75-89, and >/=90 years. In addition, mortality rates across the wave periods were calculated separately in 2 age groups: <75 and >/=75 years. All calculated mortality rates were compared with reported data from the United Kingdom (UK) during the early epidemic. RESULTS: The mortality rates of patients in Japan were significantly lower than in the UK across the board, with the exception of patients aged >/=90 years at very high risk. The mortality rates of patients aged >/=75 years at very high risk in the fourth and fifth wave periods showed no significant differences from those in the UK, whereas those in the sixth wave period were significantly lower in all age groups and in all risk groups. CONCLUSIONS: The present analysis showed that COVID-19 patients had a lower mortality rate in the most recent sixth wave period, even among patients >/=75 years old at very high risk.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Ikumi", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Asai", "name": null }, { "creator_type": "author", "first_name": "Nobuaki", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Ohmagari", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Kanamori", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Tokuda", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/ofid/ofac638" }, "pmcid": { "normalized": "PMC9846187" }, "pmid": { "normalized": "36686635" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "ofac638", "proceedings_title": null, "publisher": "", "title": "Open forum infectious diseases", "volume": "10", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Statistical Analysis of Mortality Rates of Coronavirus Disease 2019 (COVID-19) Patients in Japan Across the 4C Mortality Score Risk Groups, Age Groups, and Epidemiological Waves: A Report From the Nationwide COVID-19 Cohort.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Feeding behavior is adaptively regulated by external and internal environment, such that feeding is suppressed when animals experience pain, sickness, or fear. While the lateral parabrachial nucleus (lPB) plays key roles in nociception and stress, neuronal pathways involved in feeding suppression induced by fear are not fully explored. Here, we investigate the parasubthalamic nucleus (PSTN), located in the lateral hypothalamus and critically involved in feeding behaviors, as a target of lPB projection neurons. Optogenetic activation of lPB-PSTN terminals in male mice promote avoidance behaviors, aversive learning, and suppressed feeding. Inactivation of the PSTN and lPB-PSTN pathway reduces fear-induced feeding suppression. Activation of PSTN neurons expressing pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide enriched in the PSTN, is sufficient for inducing avoidance behaviors and feeding suppression. Blockade of PACAP receptors impaires aversive learning induced by lPB-PSTN photomanipulation. These findings indicate that lPB-PSTN pathway plays a pivotal role in fear-induced feeding suppression.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Tohyama", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Nagase", "name": null }, { "creator_type": "author", "first_name": "Mieko", "last_name": "Morishima", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Ayako M.", "last_name": "Watabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-022-35634-2" }, "pmcid": { "normalized": "PMC9803671" }, "pmid": { "normalized": "36585411" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fear", "descriptor_ui": "D005239", "major_topic": false }, { "descriptor": "Hypothalamic Area, Lateral", "descriptor_ui": "D007026", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pain", "descriptor_ui": "D010146", "major_topic": false }, { "descriptor": "Parabrachial Nucleus", "descriptor_ui": "D065823", "major_topic": true }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Dec 30", "date_precision": "day", "issue": "1", "normalized_date": "2022-12-30", "pages": "7913", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Parabrachial-to-parasubthalamic nucleus pathway mediates fear-induced suppression of feeding in male mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vertebrates have developed a network of blood vessels and nerves throughout the body that enables them to perform complex higher-order functions and maintain homeostasis. The 16th-century anatomical text 'De humani corporis fabrica' describes the networks of blood vessels and nerves as having a branching pattern in which they are closely aligned and run parallel one to another. This close interaction between adjacent blood vessels and nerves is essential not only for organogenesis during development and repair at the time of tissue damage but also for homeostasis and functional expression of blood vessels and nerves. Furthermore, it is now evident that disruptions in neurovascular interactions contribute to the progression of various diseases including cancer. Therefore, we highlight recent advances in vascular biology research, with a particular emphasis on neurovascular interactions.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takara", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Hayashi-Okada", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/life13010042" }, "pmcid": { "normalized": "PMC9862680" }, "pmid": { "normalized": "36675991" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Dec 23", "date_precision": "day", "issue": "1", "normalized_date": "2022-12-23", "pages": "", "proceedings_title": null, "publisher": "", "title": "Life (Basel, Switzerland)", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Neurovascular Interactions in the Development of the Vasculature.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In lymphocytes, Nr4a gene expression is specifically regulated by antigen receptor signalling, making them ideal targets for use as distal T cell receptor (TCR) reporters. Nr4a3-Timer of cell kinetics and activity (Tocky) mice are a ground-breaking tool to report TCR-driven Nr4a3 expression using Fluorescent Timer protein (FT). FT undergoes a time-dependent shift in its emission spectrum following translation, allowing for the temporal reporting of transcriptional events. Our recent work suggested that Nr4a1/Nur77 may be a more sensitive gene to distal TCR signals compared to Nr4a3, so we, therefore, generated Nur77-Timer-rapidly-expressed-in-lymphocytes (Tempo) mice that express FT under the regulation of Nur77. We validated the ability of Nur77-Tempo mice to report TCR and B cell receptor signals and investigated the signals regulating Nur77-FT expression. We found that Nur77-FT was sensitive to low-strength TCR signals, and its brightness was graded in response to TCR signal strength. Nur77-FT detected positive selection signals in the thymus, and analysis of FT expression revealed that positive selection signals are often persistent in nature, with most thymic Treg expressing FT Blue. We found that active TCR signals in the spleen are low frequency, but CD69(+) lymphoid T cells are enriched for FT Blue(+) Red(+) T cells, suggesting frequent TCR signalling. In non-lymphoid tissue, we saw a dissociation of FT protein from CD69 expression, indicating that tissue residency is not associated with tonic TCR signals. Nur77-Tempo mice, therefore, combine the temporal dynamics from the Tocky innovation with increased sensitivity of Nr4a1 to lower TCR signal strengths.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Thomas A. E.", "last_name": "Elliot", "name": null }, { "creator_type": "author", "first_name": "Emma K.", "last_name": "Jennings", "name": null }, { "creator_type": "author", "first_name": "David A. J.", "last_name": "Lecky", "name": null }, { "creator_type": "author", "first_name": "Sophie", "last_name": "Rouvray", "name": null }, { "creator_type": "author", "first_name": "Gillian M.", "last_name": "Mackie", "name": null }, { "creator_type": "author", "first_name": "Lisa", "last_name": "Scarfe", "name": null }, { "creator_type": "author", "first_name": "Lozan", "last_name": "Sheriff", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Kendle M.", "last_name": "Maslowski", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Bending", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/discim/kyac009" }, "pmcid": { "normalized": "PMC7614040" }, "pmid": { "normalized": "36704407" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Dec 22", "date_precision": "day", "issue": "1", "normalized_date": "2022-12-22", "pages": "kyac009", "proceedings_title": null, "publisher": "", "title": "Discovery immunology", "volume": "1", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Nur77-Tempo mice reveal T cell steady state antigen recognition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We recently reported that a neuronal population in the claustrum (CLA) identified under exposure to psychological stressors plays a key role in stress response processing. Upon stress exposure, the main inputs to the CLA come from the basolateral amygdala (BLA); however, the upstream brain regions that potentially regulate both the CLA and BLA during stressful experiences remain unclear. Here by combining activity-dependent viral retrograde labeling with whole brain imaging, we analyzed neurons projecting to the CLA and BLA activated by exposure to social defeat stress. The labeled CLA projecting neurons were mostly ipsilateral, excluding the prefrontal cortices, which had a distinctly labeled population in the contralateral hemisphere. Similarly, the labeled BLA projecting neurons were predominantly ipsilateral, aside from the BLA in the opposite hemisphere, which also had a notably labeled population. Moreover, we found co-labeled double-projecting single neurons in multiple brain regions such as the ipsilateral ectorhinal/perirhinal cortex, entorhinal cortex, and the contralateral BLA. These results suggest that CLA and BLA receive inputs from neuron collaterals in various brain regions during stress, which may regulate the CLA and BLA forming in a stress response circuitry.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masato", "last_name": "Tanuma", "name": null }, { "creator_type": "author", "first_name": "Misaki", "last_name": "Niu", "name": null }, { "creator_type": "author", "first_name": "Jin", "last_name": "Ohkubo", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13041-022-00987-8" }, "pmcid": { "normalized": "PMC9768926" }, "pmid": { "normalized": "36539776" } }, "mesh": [ { "descriptor": "Basolateral Nuclear Complex", "descriptor_ui": "D066272", "major_topic": true }, { "descriptor": "Claustrum", "descriptor_ui": "D000079482", "major_topic": true }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Social Defeat", "descriptor_ui": "D000083703", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Dec 20", "date_precision": "day", "issue": "1", "normalized_date": "2022-12-20", "pages": "100", "proceedings_title": null, "publisher": "", "title": "Molecular brain", "volume": "15", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Acute social defeat stress activated neurons project to the claustrum and basolateral amygdala.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Synovial inflammation plays a central role in joint destruction and pain in osteoarthritis (OA). The NF-kappaB pathway plays an important role in the inflammatory process and is activated in OA. A previous study reported that a jietacin derivative (JD), (Z)-2-(8-oxodec-9-yn-1-yl)-1-vinyldiazene 1-oxide, suppressed the nuclear translocation of NF-kappaB in a range of cancer cell lines. However, the effect of JD in synovial cells and the exact mechanism of JD as an NF-kappaB inhibitor remain to be determined. We investigated the effect of JD on TNF-alpha-induced inflammatory reaction in a synovial cell line, SW982 and human primary synovial fibroblasts (hPSFs). Additionally, we examined phosphorylated levels of p65 and p38 and expression of importin alpha3 and beta1 using Western blotting. RNA-Seq analysis revealed that JD suppressed TNF-alpha-induced differential expression: among 204 genes significantly differentially expressed between vehicle and TNF-alpha-stimulated SW982 (183 upregulated and 21 downregulated) (FC >/= 2, Q < 0.05), expression of 130 upregulated genes, including inflammatory cytokines (IL1A, IL1B, IL6, IL8) and chemokines (CCL2, CCL3, CCL5, CCL20, CXCL9, 10, 11), was decreased by JD treatment and that of 14 downregulated genes was increased. KEGG pathway analysis showed that DEGs were increased in the cytokine-cytokine receptor interaction, TNF signaling pathway, NF-kappaB signaling pathway, and rheumatoid arthritis. JD inhibited IL1B, IL6 and IL8 mRNA expression and IL-6 and IL-8 protein production in both SW982 and hPSFs. JD also suppressed p65 phosphorylation in both SW982 and hPSFs. In contrast, JD did not alter p38 phosphorylation. JD may inhibit TNF-alpha-mediated inflammatory cytokine production via suppression of p65 phosphorylation in both SW982 and hPSFs. Our results suggest that JD may have therapeutic potential for OA due to its anti-inflammatory action through selective suppression of the NF-kappaB pathway on synovial cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kyoko", "last_name": "Muneshige", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Inahashi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Itakura", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Iwatsuki", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Takaso", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Sunazuka", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Uchida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ph16010005" }, "pmcid": { "normalized": "PMC9862604" }, "pmid": { "normalized": "36678502" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Dec 20", "date_precision": "day", "issue": "1", "normalized_date": "2022-12-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "Pharmaceuticals (Basel, Switzerland)", "volume": "16", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Jietacin Derivative Inhibits TNF-alpha-Mediated Inflammatory Cytokines Production via Suppression of the NF-kappaB Pathway in Synovial Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Allogeneic cell therapies are not fully effective in treating osteoarthritis of the knee (OAK). We recently reported that transplantation of autologous chondrocyte cell-sheets along with open-wedge high tibial osteotomy promoted hyaline cartilage repair in humans. Here we describe our regenerative therapy for OAK using polydactyly-derived allogeneic chondrocyte cell-sheets (PD sheets) and temperature-responsive culture inserts. Ten patients with OAK and cartilage defects categorized arthroscopically as Outerbridge grade III or IV received the therapy. Cartilage viscoelasticity and thickness were assessed before and after transplantation. Arthroscopic biopsies obtained 12 months after transplantation were analyzed histologically. Gene expression was analyzed to evaluate the PD sheets. In this small initial longitudinal series, PD sheet transplantation was effective in treating OAK, as indicated by changes in cartilage properties. Gene marker sets in PD sheets may predict outcomes after therapy and provide markers for the selection of donor cells. This combined surgery may be an ideal regenerative therapy with disease-modifying effects in OAK patients.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Hamahashi", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Genya", "last_name": "Mitani", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Takagaki", "name": null }, { "creator_type": "author", "first_name": "Nagatoshi", "last_name": "Kaneshiro", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Matoba", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Akutsu", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Umezawa", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Akamatsu", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yamato", "name": null }, { "creator_type": "author", "first_name": "Teruo", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41536-022-00272-1" }, "pmcid": { "normalized": "PMC9755241" }, "pmid": { "normalized": "36522336" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Dec 16", "date_precision": "day", "issue": "1", "normalized_date": "2022-12-16", "pages": "71", "proceedings_title": null, "publisher": "", "title": "NPJ Regenerative medicine", "volume": "7", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Polydactyly-derived allogeneic chondrocyte cell-sheet transplantation with high tibial osteotomy as regenerative therapy for knee osteoarthritis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer stem cells (CSCs) has been a key target to cure cancer patients completely. Although many CSC markers have been identified, they are frequently cancer type-specific and those expressions are occasionally variable, which becomes an obstacle to elucidate the characteristics of the CSCs. Here we scrutinized the relationship between stemness elevation and geometrical features of single cells. The PAMPS hydrogel was utilized to create the CSCs from mouse myoblast C2C12 and its synovial sarcoma model cells. qRT-PCR analysis confirmed the significant increase in expression levels of Sox2, Nanog, and Oct3/4 on the PAMPS gel, which was higher in the synovial sarcoma model cells. Of note, the morphological heterogeneity was appeared on the PAMPS gel, mainly including flat spreading, elongated spindle, and small round cells, and the Sox2 expression was highest in the small round cells. To examine the role of morphological differences in the elevation of stemness, over 6,400 cells were segmented along with the Sox2 intensity, and 12 geometrical features were extracted at single cell level. A nonlinear mapping of the geometrical features by using uniform manifold approximation and projection (UMAP) clearly revealed the existence of relationship between morphological differences and the stemness elevation, especially for C2C12 and its synovial sarcoma model on the PAMPS gel in which the small round cells possess relatively high Sox2 expression on the PAMPS gel, which supports the strong relationship between morphological changes and the stemness elevation. Taken together, these geometrical features can be useful for morphological profiling of CSCs to classify and distinguish them for understanding of their role in disease progression and drug discovery.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Zannatul", "last_name": "Ferdous", "name": null }, { "creator_type": "author", "first_name": "Jean-Emmanuel", "last_name": "Clement", "name": null }, { "creator_type": "author", "first_name": "Jian Ping", "last_name": "Gong", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2022.12.040" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36549099" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Hydrogels", "descriptor_ui": "D020100", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Pathogen-Associated Molecular Pattern Molecules", "descriptor_ui": "D000069452", "major_topic": false }, { "descriptor": "Sarcoma", "descriptor_ui": "D012509", "major_topic": true }, { "descriptor": "Sarcoma, Synovial", "descriptor_ui": "D013584", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Dec 14", "date_precision": "day", "issue": "", "normalized_date": "2022-12-14", "pages": "41-49", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "642", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Geometrical analysis identified morphological features of hydrogel-induced cancer stem cells in synovial sarcoma model cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Progress has been made in the elucidation of sleep and wakefulness regulation at the neurocircuit level(1,2). However, the intracellular signalling pathways that regulate sleep and the neuron groups in which these intracellular mechanisms work remain largely unknown. Here, using a forward genetics approach in mice, we identify histone deacetylase 4 (HDAC4) as a sleep-regulating molecule. Haploinsufficiency of Hdac4, a substrate of salt-inducible kinase 3 (SIK3)(3), increased sleep. By contrast, mice that lacked SIK3 or its upstream kinase LKB1 in neurons or with a Hdac4(S245A) mutation that confers resistance to phosphorylation by SIK3 showed decreased sleep. These findings indicate that LKB1-SIK3-HDAC4 constitute a signalling cascade that regulates sleep and wakefulness. We also performed targeted manipulation of SIK3 and HDAC4 in specific neurons and brain regions. This showed that SIK3 signalling in excitatory neurons located in the cerebral cortex and the hypothalamus positively regulates EEG delta power during non-rapid eye movement sleep (NREMS) and NREMS amount, respectively. A subset of transcripts biased towards synaptic functions was commonly regulated in cortical glutamatergic neurons through the expression of a gain-of-function allele of Sik3 and through sleep deprivation. These findings suggest that NREMS quantity and depth are regulated by distinct groups of excitatory neurons through common intracellular signals. This study provides a basis for linking intracellular events and circuit-level mechanisms that control NREMS.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Staci J.", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Hotta-Hirashima", "name": null }, { "creator_type": "author", "first_name": "Fuyuki", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kitazono", "name": null }, { "creator_type": "author", "first_name": "Kanako", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Haruna", "last_name": "Komiya", "name": null }, { "creator_type": "author", "first_name": "Nodoka", "last_name": "Asama", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Fujiyama", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Ikkyu", "name": null }, { "creator_type": "author", "first_name": "Miyo", "last_name": "Kakizaki", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Kanno", "name": null }, { "creator_type": "author", "first_name": "Jinhwan", "last_name": "Choi", "name": null }, { "creator_type": "author", "first_name": "Deependra", "last_name": "Kumar", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Asmaa", "last_name": "Elhosainy", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Yousuke", "last_name": "Tsuneoka", "name": null }, { "creator_type": "author", "first_name": "Fumihiro", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Muratani", "name": null }, { "creator_type": "author", "first_name": "Qinghua", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Miyoshi", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Funato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41586-022-05450-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36477539" } }, "mesh": [ { "descriptor": "AMP-Activated Protein Kinases", "descriptor_ui": "D055372", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": false }, { "descriptor": "Delta Rhythm", "descriptor_ui": "D003700", "major_topic": false }, { "descriptor": "Electroencephalography", "descriptor_ui": "D004569", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Histone Deacetylases", "descriptor_ui": "D006655", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": true }, { "descriptor": "Sleep Deprivation", "descriptor_ui": "D012892", "major_topic": false }, { "descriptor": "Sleep Duration", "descriptor_ui": "D000094362", "major_topic": true }, { "descriptor": "Sleep, Slow-Wave", "descriptor_ui": "D000077310", "major_topic": false }, { "descriptor": "Wakefulness", "descriptor_ui": "D014851", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Dec 7", "date_precision": "day", "issue": "", "normalized_date": "2022-12-07", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Kinase signalling in excitatory neurons regulates sleep quantity and depth.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Understanding cellular signaling flow is required to comprehend living organisms. Various live cell imaging tools have been developed but challenges remain due to complex cross-talk between pathways and response heterogeneities among cells. We have focused on multiplex live cell imaging for statistical analysis to address the difficulties and developed simple multiple fluorescence imaging system to quantify cell signaling at single-cell resolution using Forster Resonance Energy Transfer (FRET)-based chimeric molecular sensors comprised of fluorescent proteins and dyes. The dye-fluorescent protein conjugate is robust for a wide selection of combinations, facilitating rearrangement for coordinating emission profile of molecular sensors to adjust for visualization conditions, target phenomena, and simultaneous use. As the molecular sensor could exhibit highly sensitive in detection for protease activity, we customized molecular sensor of caspase-9 and combine the established sensor for caspase-3 to validate the system by observation of caspase-9 and -3 dynamics simultaneously, key signaling flow of apoptosis. We found cumulative caspase-9 activity rather than reaction rate inversely regulated caspase-3 execution times for apoptotic cell death. Imaging-derived statistics were thus applied to discern the dominating aspects of apoptotic signaling unavailable by common live cell imaging and proteomics protein analysis. Adopted to various visualization targets, the technique can discriminate between rivalling explanations and should help unravel other protease involved signaling pathways.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Miho", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-25286-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36476686" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Caspase 3", "descriptor_ui": "D053148", "major_topic": false }, { "descriptor": "Caspase 9", "descriptor_ui": "D053453", "major_topic": false }, { "descriptor": "Caspases", "descriptor_ui": "D020169", "major_topic": true }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Dec 7", "date_precision": "day", "issue": "1", "normalized_date": "2022-12-07", "pages": "21160", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [ "ssbd-database-000279" ], "repository": [ "ssbd-repos-000279" ] }, "title": "Live imaging of apoptotic signaling flow using tunable combinatorial FRET-based bioprobes for cell population analysis of caspase cascades.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dysregulation of the tumor-intrinsic epigenetic circuit is a key driver event for the development of cancer. Accumulating evidence suggests that epigenetic and/or genetic drivers stimulate intrinsic oncogenic pathways as well as extrinsic factors that modulate the immune system. These modulations indeed shape the tumor microenvironment (TME), allowing pro-oncogenic factors to become oncogenic, thereby contributing to cancer development and progression. Here, we review the epigenetic dysregulation arising in cancer cells that disseminates throughout the TME and beyond. Recent CRISPR screening has elucidated key epigenetic drivers that play important roles in the proliferation of cancer cells (intrinsic) and inhibition of antitumor immunity (extrinsic), which lead to the development and progression of cancer. These epigenetic players can serve as promising targets for cancer therapy as a dual (two in one)-targeted approach. Considering the interplay between cancer and the immune system as a key determinant of immunotherapy, we discuss a novel lineage-tracing technology that enables longitudinal monitoring of cancer and immune phenotypic heterogeneity and fate paths during cancer development, progression, and therapeutic interventions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kato", "last_name": "Shinichiro", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hiroyoshi", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Kunihiko", "last_name": "Hinohara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.15681" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36468774" } }, "mesh": [ { "descriptor": "Epigenome", "descriptor_ui": "D000081122", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunotherapy", "descriptor_ui": "D007167", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Dec 5", "date_precision": "day", "issue": "", "normalized_date": "2022-12-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "The cancer epigenome: non-cell autonomous player in tumor immunity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Follicular neoplasms of the thyroid include follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA). However, the differences in cytological findings between FTC and FTA remain undetermined. Here, we aimed to evaluate the accumulation of lipid droplets (LDs) and the expression of adipophilin (perilipin 2/ADRP/ADFP), a known LD marker, in cultured FTC cells. We also immunohistochemically compared adipophilin expression in the FTC and FTA of resected human thyroid tissues. Cultured FTC (FTC-133 and RO82W-1) possessed increased populations of LDs compared to thyroid follicular epithelial (Nthy-ori 3-1) cells. In vitro treatment with phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling inhibitors (LY294002, MK2206, and rapamycin) in FTC-133 cells downregulated the PI3K/Akt/mTOR/sterol regulatory element-binding protein 1 (SREBP1) signaling pathway, resulting in a significant reduction in LD accumulation. SREBP1 is a master transcription factor that controls lipid metabolism. Fluorescence immunocytochemistry revealed adipophilin expression in the LDs of FTC-133 cells. Immunohistochemical analysis of surgically resected human thyroid tissues revealed significantly increased expression of adipophilin in FTC compared with FTA and adjacent non-tumorous thyroid epithelia. Taken together, LDs and adipophilin were abundant in cultured FTC; the evaluation of adipophilin expression can help distinguish FTC from FTA in surgical specimens.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Michiyo", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "J. Nicholas", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Ryuta", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2022.12.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36521425" } }, "mesh": [ { "descriptor": "Adenocarcinoma, Follicular", "descriptor_ui": "D018263", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lipid Droplets", "descriptor_ui": "D066292", "major_topic": false }, { "descriptor": "Perilipin-2", "descriptor_ui": "D000070780", "major_topic": false }, { "descriptor": "Phosphatidylinositol 3-Kinase", "descriptor_ui": "D058539", "major_topic": false }, { "descriptor": "Phosphatidylinositol 3-Kinases", "descriptor_ui": "D019869", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false }, { "descriptor": "Thyroid Neoplasms", "descriptor_ui": "D013964", "major_topic": true }, { "descriptor": "TOR Serine-Threonine Kinases", "descriptor_ui": "D058570", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Dec 5", "date_precision": "day", "issue": "", "normalized_date": "2022-12-05", "pages": "192-201", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "640", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Lipid droplet accumulation and adipophilin expression in follicular thyroid carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We investigated whether A-type lamins (lamin A/C) and lamin B receptor (LBR) are redundant during herpes simplex virus 1 (HSV-1) infection in HeLa cells expressing lamin A/C and LBR. Lamin A/C and LBR double knockout (KO) in HSV-1-infected HeLa cells significantly impaired expressions of HSV-1 early and late genes, maturation of replication compartments, marginalization of host chromatin to the nuclear periphery, enlargement of host cell nuclei, and viral DNA replication. Phenotypes of HSV-1-infected HeLa cells were restored by the ectopic expression of lamin A/C or LBR in lamin A/C and LBR double KO cells. Of note, lamin A/C single KO, but not LBR single KO, promoted the aberrant accumulation of virus particles outside the inner nuclear membrane (INM) and viral replication, as well as decreasing the frequency of virus particles inside the INM without affecting viral gene expression and DNA replication, time-spatial organization of replication compartments and host chromatin, and nuclear enlargement. These results indicated that lamin A/C and LBR had redundant and specific roles during HSV-1 infection. Thus, lamin A/C and LBR redundantly regulated the dynamics of the nuclear architecture, including the time-spatial organization of replication compartments and host chromatin, as well as promoting nuclear enlargement for efficient HSV-1 gene expression and DNA replication. In contrast, lamin A/C inhibited HSV-1 nuclear export through the INM during viral nuclear egress, which is a unique property of lamin A/C. IMPORTANCE This study demonstrated that lamin A/C and LBR had redundant functions associated with HSV-1 gene expression and DNA replication by regulating the dynamics of the nuclear architecture during HSV-1 infection. This is the first report to demonstrate the redundant roles of lamin A/C and LBR as well as the involvement of LBR in the regulation of these viral and cellular features in HSV-1-infected cells. These findings provide evidence for the specific property of lamin A/C to inhibit HSV-1 nuclear egress, which has long been considered but without direct proof.", "classifications": [ { "id": "21H00417", "label": "21H00417", "researcher": "Yuhei Maruzuru", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01429-22" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36448808" } }, "mesh": [ { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "DNA Replication", "descriptor_ui": "D004261", "major_topic": false }, { "descriptor": "DNA, Viral", "descriptor_ui": "D004279", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": true }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lamin B Receptor", "descriptor_ui": "D000097682", "major_topic": false }, { "descriptor": "Lamin Type A", "descriptor_ui": "D034904", "major_topic": false }, { "descriptor": "Lamins", "descriptor_ui": "D034882", "major_topic": true }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Nov 30", "date_precision": "day", "issue": "", "normalized_date": "2022-11-30", "pages": "e0142922", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Redundant and Specific Roles of A-Type Lamins and Lamin B Receptor in Herpes Simplex Virus 1 Infection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Optical control of G protein-coupled receptor (GPCR) signaling is a highly valuable approach for comprehensive understanding of GPCR-based physiologies and controlling them precisely. However, optogenetics for GPCR signaling is still developing and requires effective and versatile tools with performance evaluation from their molecular properties. Here, we systematically investigated performance of two bistable opsins that activate Gi/Go-type G protein (mosquito Opn3 (MosOpn3) and lamprey parapinopsin (LamPP)) in optical control in vivo using Caenorhabditis elegans. Transgenic worms expressing MosOpn3, which binds 13-cis retinal to form photopigments, in nociceptor neurons showed light-induced avoidance responses in the presence of all-trans retinal, a retinal isomer ubiquitously present in every tissue, like microbial rhodopsins and unlike canonical vertebrate opsins. Remarkably, transgenic worms expressing MosOpn3 were ~7,000 times more sensitive to light than transgenic worms expressing ChR2 in this light-induced behavior, demonstrating the advantage of MosOpn3 as a light switch. LamPP is a UV-sensitive bistable opsin having complete photoregenerative ability by green light. Accordingly, transgenic worms expressing LamPP in cholinergic motor neurons stopped moving upon violet light illumination and restored coordinate movement upon green light illumination, demonstrating color-dependent control of behavior using LamPP. Furthermore, we applied molecular engineering to produce MosOpn3-based tools enabling light-dependent upregulation of cAMP or Ca2+ levels and LamPP-based tool enabling clamping cAMP levels color dependently and context independently, extending their usability. These findings define the capacity of two bistable opsins with similar retinal requirement as ChR2, providing numerous strategies for optical control of various GPCR-based physiologies as well as GPCR signaling itself.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Baoguo", "last_name": "Shen", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Lanfang", "last_name": "Sun", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Kamimura", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Kage-Nakadai", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2204341119" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022-11-29", "date_precision": "day", "issue": "48", "normalized_date": "2022-11-29", "pages": "e2204341119", "proceedings_title": null, "publisher": "Proceedings of the National Academy of Sciences", "title": "Proceedings of the National Academy of Sciences", "volume": "119", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "High-performance optical control of GPCR signaling by bistable animal opsins MosOpn3 and LamPP in a molecular property–dependent manner", "url": "https://www.pnas.org/doi/10.1073/pnas.2204341119", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Retinoic acid (RA) and its synthetic derivatives, retinoids, have been established as promising anticancer agents based on their ability to regulate cell proliferation and survival. Clinical trials, however, have revealed that cancer cells often acquire resistance to retinoid therapy. Therefore, elucidation of underlying mechanisms of retinoid resistance has been considered key to developing more effective use of retinoids in cancer treatment. In this study, we show that constitutive activation of ERK MAP kinase signaling, which is often caused by oncogenic mutations in RAS or RAF genes, suppresses RA receptor (RAR) signaling in breast cancer cells. We show that activation of the ERK pathway suppresses, whereas its inhibition promotes, RA-induced transcriptional activation of RAR and the resultant upregulation of RAR-target genes in breast cancer cells. Importantly, ERK inhibition potentiates the tumor-suppressive activity of RA in breast cancer cells. Moreover, we also reveal that suppression of RAR signaling and activation of ERK signaling are associated with poor prognoses in breast cancer patients and represent hallmarks of specific subtypes of breast cancers, such as basal-like, HER2-enriched and luminal B. These results indicate that ERK-dependent suppression of RAR activity underlies retinoid resistance and is associated with cancer subtypes and patient prognosis in breast cancers.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Akira", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Jean-Emmanuel", "last_name": "Clement", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Tanikawa", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Nonoyama", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null }, { "creator_type": "author", "first_name": "Jian Ping", "last_name": "Gong", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Imajo", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers14235890" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36497371" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Nov 29", "date_precision": "day", "issue": "23", "normalized_date": "2022-11-29", "pages": "5890", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "14", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "ERK MAP Kinase Signaling Regulates RAR Signaling to Confer Retinoid Resistance on Breast Cancer Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Myokines, secreted factors from skeletal muscle, act locally on muscle cells or satellite cells, which is important in regulating muscle mass and function. Here, we found platelet-derived growth factor subunit B (PDGF-B) is constitutively secreted from muscle cells without muscle contraction. Furthermore, PDGF-B secretion increased with myoblast to myotube differentiation. To examine the role of PDGF-B as a paracrine or autocrine myokine, myoblasts or myotubes were treated with PDGF-B. As a result, myoblast proliferation was significantly enhanced via several signaling pathways. Intriguingly, myotubes treated with PDGF-B showed enhanced maturation as indicated by their increased myotube diameter, myosin heavy chain expression, and strengthened contractile force. These findings suggest that PDGF-B is constitutively secreted by myokines to enhance myoblast proliferation and myotube maturation, which may contribute to skeletal muscle regeneration.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Hamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kitora", "last_name": "Dohi", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Taoka", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Isobe", "name": null }, { "creator_type": "author", "first_name": "Tsubasa S.", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Deguchi", "name": null }, { "creator_type": "author", "first_name": "Yasuro", "last_name": "Furuichi", "name": null }, { "creator_type": "author", "first_name": "Nobuharu L.", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Manabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2022.11.085" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36521377" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle Fibers, Skeletal", "descriptor_ui": "D018485", "major_topic": true }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Satellite Cells, Skeletal Muscle", "descriptor_ui": "D032496", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Nov 28", "date_precision": "day", "issue": "", "normalized_date": "2022-11-28", "pages": "169-175", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "639", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "PDGF-B secreted from skeletal muscle enhances myoblast proliferation and myotube maturation via activation of the PDGFR signaling cascade.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The clinical characteristics of growth hormone (GH)-producing pituitary adenomas/somatotroph pituitary neuroendocrine tumors (GHomas/somatotroph PitNETs) vary across patients. In this study, we aimed to integrate the genetic alterations, protein expression profiles, transcriptomes, and clinical characteristics of GHomas/somatotroph PitNETs to identify molecules associated with acromegaly characteristics. Targeted capture sequencing and copy number analysis of 36 genes and nontargeted proteomics analysis were performed on fresh-frozen samples from 121 sporadic GHomas/somatotroph PitNETs. Targeted capture sequencing revealed GNAS as the only driver gene, as previously reported. Classification by consensus clustering using both RNA sequencing and proteomics revealed many similarities between the proteome and the transcriptome. Gene ontology analysis was performed for differentially expressed proteins between wild-type and mutant GNAS samples identified by nontargeted proteomics and involved in G protein-coupled receptor (GPCR) pathways. The results suggested that GNAS mutations impact endocrinological features in acromegaly through GPCR pathway induction. ATP2A2 and ARID5B correlated with the GH change rate in the octreotide loading test, and WWC3, SERINC1, and ZFAND3 correlated with the tumor volume change rate after somatostatin analog treatment. These results identified a biological connection between GNAS mutations and the clinical and biochemical characteristics of acromegaly, revealing molecules associated with acromegaly that may affect medical treatment efficacy.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Azusa", "last_name": "Yamato", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yue", "last_name": "Gao", "name": null }, { "creator_type": "author", "first_name": "Tatsuma", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akitoshi", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Yingbo", "last_name": "Gong", "name": null }, { "creator_type": "author", "first_name": "Xiaoyan", "last_name": "Shi", "name": null }, { "creator_type": "author", "first_name": "Siti Nurul", "last_name": "Zhahara", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kono", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Furuki", "name": null }, { "creator_type": "author", "first_name": "Motoi", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Horiguchi", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Iwadate", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Fukuyo", "name": null }, { "creator_type": "author", "first_name": "Bahityar", "last_name": "Rahmutulla", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kaneda", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Ohara", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Inoshita", "name": null }, { "creator_type": "author", "first_name": "Shozo", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nishioka", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-022-04272-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36435867" } }, "mesh": [ { "descriptor": "Acromegaly", "descriptor_ui": "D000172", "major_topic": true }, { "descriptor": "Adenoma", "descriptor_ui": "D000236", "major_topic": true }, { "descriptor": "Growth Hormone-Secreting Pituitary Adenoma", "descriptor_ui": "D049912", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neuroendocrine Tumors", "descriptor_ui": "D018358", "major_topic": true }, { "descriptor": "Pituitary Neoplasms", "descriptor_ui": "D010911", "major_topic": true }, { "descriptor": "Proteogenomics", "descriptor_ui": "D000071696", "major_topic": true }, { "descriptor": "Somatotrophs", "descriptor_ui": "D052683", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Nov 27", "date_precision": "day", "issue": "1", "normalized_date": "2022-11-27", "pages": "1304", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "5", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Proteogenomic landscape and clinical characterization of GH-producing pituitary adenomas/somatotroph pituitary neuroendocrine tumors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved pleiotropic neuropeptide, implicated in emotional stress responses and anxiety-related disorders. Here, we examined whether our recently developed small-molecule non-peptide PACAP receptor antagonists could ameliorate anxiety-like behaviors induced by acute restraint stress in mice. The antagonists PA-9 and its derivative PA-915 improved anxiety-like behaviors in mice subjected to restraint stress. An anxiolytic effect was observed with single acute dose, suggesting their fast-acting properties. PA-915 demonstrated a statistically significant anxiolytic effect whereas fluoxetine did not. These results indicate the potential of PAC1 antagonists as a novel treatment for anxiety.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Yamano", "name": null }, { "creator_type": "author", "first_name": "Manato", "last_name": "Kuta", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Takeshita", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Toyooka", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Takasaki", "name": null }, { "creator_type": "author", "first_name": "Atsuro", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2022.09.079" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36194909" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anti-Anxiety Agents", "descriptor_ui": "D014151", "major_topic": true }, { "descriptor": "Anxiety", "descriptor_ui": "D001007", "major_topic": false }, { "descriptor": "Fluoxetine", "descriptor_ui": "D005473", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": true }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I", "descriptor_ui": "D051237", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Nov 26", "date_precision": "day", "issue": "", "normalized_date": "2022-11-26", "pages": "146-151", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "631", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Small-molecule non-peptide antagonists of the PACAP receptor attenuate acute restraint stress-induced anxiety-like behaviors in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Photodynamic therapy (PDT) is a minimally invasive form of cancer therapy, and the development of a novel photosensitizer (PS) with optimal properties is important for enhancing PDT efficacy. Folate receptor (FR) membrane protein is frequently overexpressed in 40% of human cancer and a good candidate for tumor-specific targeting. Specific active targeting of PS to FR can be achieved by conjugation with the folate moiety. A folate-linked, near-infrared (NIR)-sensitive probe, folate-Si-rhodamine-1 (FolateSiR-1), was previously developed and is expected to be applicable to NIR-PDT. AIM: To investigate the therapeutic efficacy of NIR-PDT induced by FolateSiR-1, a FR-targeted PS, in preclinical cancer models. METHODS: FolateSiR-1 was developed by conjugating a folate moiety to the Si-rhodamine derivative through a negatively charged tripeptide linker. FR expression in the designated cell lines was examined by western blotting (WB). The selective binding of FolateSiR-1 to FR was confirmed in FR overexpressing KB cells (FR+) and tumors by fluorescence microscopy and in vivo fluorescence imaging. Low FR expressing OVCAR-3 and A4 cell lines were used as negative controls (FR-). The NIR light (635 +/- 3 nm)-induced phototoxic effect of FolateSiR-1 was evaluated by cell viability imaging assays. The time-dependent distribution of FolateSiR-1 and its specific accumulation in KB tumors was determined using in vivo longitudinal fluorescence imaging. The PDT effect of FolateSiR-1 was evaluated in KB tumor-bearing mice divided into four experimental groups: (1) FolateSiR-1 (100 mumol/L) alone; (2) FolateSiR-1 (100 mumol/L) followed by NIR irradiation (50 J/cm(2)); (3) NIR irradiation (50 J/cm(2)) alone; and (4) no treatment. Tumor volume measurement and immunohistochemical (IHC) and histological examinations of the tumors were performed to analyze the effect of PDT. RESULTS: High FR expression was observed in the KB cells by WB, but not in the OVCAR-3 and A4 cells. Substantial FR-specific binding of FolateSiR-1 was observed by in vitro and in vivo fluorescence imaging. Cell viability imaging assays showed that NIR-PDT induced cell death in KB cells. In vivo longitudinal fluorescence imaging showed rapid peak accumulation of FolateSiR-1 in the KB tumors 2 h after injection. In vivo PDT conducted at this time point caused tumor growth delay. The relative tumor volumes in the PDT group were significantly reduced compared to those in the other groups [5.81 +/- 1.74 (NIR-PDT) vs 12.24 +/- 2.48 (Folate-SiR-1), vs 11.84 +/- 3.67 (IR), vs 12.98 +/- 2.78 (Untreated), at Day 16, P < 0.05]. IHC analysis revealed reduced proliferation marker Ki-67-positive cells in the PDT treated tumors, and hematoxylin-eosin staining revealed features of necrotic- and apoptotic cell death. CONCLUSION: FolateSiR-1 has potential for use in PDT, and FR-targeted NIR-PDT may open a new effective strategy for the treatment of FR-overexpressing tumors.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Winn", "last_name": "Aung", "name": null }, { "creator_type": "author", "first_name": "Atsushi B.", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Higashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.5306/wjco.v13.i11.880" }, "pmcid": { "normalized": "PMC9724186" }, "pmid": { "normalized": "36483974" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Nov 24", "date_precision": "day", "issue": "11", "normalized_date": "2022-11-24", "pages": "880-895", "proceedings_title": null, "publisher": "", "title": "World journal of clinical oncology", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Folate receptor-targeted near-infrared photodynamic therapy for folate receptor-overexpressing tumors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell-cell interactions within tumour microenvironment play crucial roles in tumorigenesis. Genetic mosaic techniques available in Drosophila have provided a powerful platform to study the basic principles of tumour growth and progression via cell-cell communications. This led to the identification of oncogenic cell-cell interactions triggered by endocytic dysregulation, mitochondrial dysfunction, cell polarity defects, or Src activation in Drosophila imaginal epithelia. Such oncogenic cooperations can be caused by interactions among epithelial cells, mesenchymal cells, and immune cells. Moreover, microenvironmental factors such as nutrients, local tissue structures, and endogenous growth signalling activities critically affect tumorigenesis. Dissecting various types of oncogenic cell-cell interactions at the single-cell level in Drosophila will greatly increase our understanding of how tumours progress in living animals.", "classifications": [ { "id": "21H00425", "label": "21H00425", "researcher": "Masato Enomoto", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masato", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Tatsushi", "last_name": "Igaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/19336934.2022.2148828" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36413374" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": true }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022-11-22", "date_precision": "day", "issue": "1", "normalized_date": "2022-11-22", "pages": "367-381", "proceedings_title": null, "publisher": "", "title": "Fly", "volume": "16", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell-cell interactions that drive tumorigenesis in Drosophila.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The dynamical network biomarker (DNB) theory detects the early warning signals of state transitions utilizing fluctuations in and correlations between variables in complex systems. Although the DNB theory has been applied to gene expression in several diseases, destructive testing by microarrays is a critical issue. Therefore, other biological information obtained by non-destructive testing is desirable; one such piece of information is Raman spectra measured by Raman spectroscopy. Raman spectroscopy is a powerful tool in life sciences and many other fields that enable the label-free non-invasive imaging of live cells and tissues along with detailed molecular fingerprints. Naive and activated T cells have recently been successfully distinguished from each other using Raman spectroscopy without labeling. In the present study, we applied the DNB theory to Raman spectra of T cell activation as a model case. The dataset consisted of Raman spectra of the T cell activation process observed at 0 (naive T cells), 2, 6, 12, 24 and 48 h (fully activated T cells). In the DNB analysis, the F-test and hierarchical clustering were used to detect the transition state and identify DNB Raman shifts. We successfully detected the transition state at 6 h and related DNB Raman shifts during the T cell activation process. The present results suggest novel applications of the DNB theory to Raman spectra ranging from fundamental research on cellular mechanisms to clinical examinations.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takayuki", "last_name": "Haruki", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Yonezawa", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Makito", "last_name": "Oku", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Taketani", "name": null }, { "creator_type": "author", "first_name": "Moe", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kadowaki", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biom12121730" }, "pmcid": { "normalized": "PMC9776035" }, "pmid": { "normalized": "36551158" } }, "mesh": [ { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Nov 22", "date_precision": "day", "issue": "12", "normalized_date": "2022-11-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biomolecules", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Application of the Dynamical Network Biomarker Theory to Raman Spectra.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The centrohelid heliozoan Raphidocystis contractilis has many radiating axopodia, each containing axopodial microtubules. The axopodia show rapid contraction at nearly a video rate (30 frames per second) in response to mechanical stimuli. The axopodial contraction is accompanied by cytoskeletal microtubule depolymerization, but the molecular mechanism of this phenomenon has not been elucidated. In this study, we performed de novo transcriptome sequencing of R. contractilis to identify genes involved in microtubule dynamics such as the rapid axopodial contraction. The transcriptome sequencing generated 7.15-Gbp clean reads in total, which were assembled as 31,771 unigenes. Using the obtained gene sets, we identified several microtubule-severing proteins which might be involved in the rapid axopodial contraction, and kinesin-like genes that occur gene duplication. On the other hand, some genes for microtubule motor proteins involved in the formation and motility of flagella were not found in R. contractilis, suggesting that the gene repertoire of R. contractilis reflected the morphological features of non-flagellated protists. Our transcriptome analysis provides basic information for the analysis of the molecular mechanism underlying microtubule dynamics in R. contractilis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Risa", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Tosuke", "last_name": "Sakagami", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Toshimitsu", "last_name": "Hatabu", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Motonori", "last_name": "Ando", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/jeu.12955" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36409155" } }, "mesh": [ { "descriptor": "Eukaryota", "descriptor_ui": "D056890", "major_topic": true }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": true }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Nov 21", "date_precision": "day", "issue": "", "normalized_date": "2022-11-21", "pages": "e12955", "proceedings_title": null, "publisher": "", "title": "The Journal of eukaryotic microbiology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "De novo transcriptome analysis of the centrohelid Raphidocystis contractilis to identify genes involved in microtubule-based motility.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Normal and tumor regions within cancer tissue can be distinguished using various methods, such as histological analysis, tumor marker testing, X-ray imaging, or magnetic resonance imaging. Recently, new discrimination methods utilizing the Raman spectra of tissues have been developed and put into practical use. Because Raman spectral microscopy is a non-destructive and non-labeling method, it is potentially compatible for use in the operating room. In this review, we focus on the basics of Raman spectroscopy and Raman imaging in live cells and cell type discrimination, as these form the bases for current Raman scattering-based cancer diagnosis. We also review recent attempts to estimate the gene expression profile from the Raman spectrum of living cells using simple machine learning. Considering recent advances in machine learning techniques, we speculate that cancer type discrimination using Raman spectroscopy will be possible in the near future.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/genes13112127" }, "pmcid": { "normalized": "PMC9690875" }, "pmid": { "normalized": "36421802" } }, "mesh": [ { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Nov 16", "date_precision": "day", "issue": "11", "normalized_date": "2022-11-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "Genes", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Recent Advances in Raman Spectral Imaging in Cell Diagnosis and Gene Expression Prediction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The circadian rhythm is a biological oscillation of physiological activities with a period of approximately 24 h, that is driven by a cell-autonomous oscillator called the circadian clock. The current model of the mammalian circadian clock is based on a transcriptional-translational negative feedback loop in which the protein products of clock genes accumulate in a circadian manner and repress their own transcription. However, several studies have revealed that constitutively expressed clock genes can maintain circadian oscillations. To understand the underlying mechanism, we expressed Bmal1 in Bmal1-disrupted cells using a doxycycline-inducible promoter and monitored Bmal1 and Per2 promoter activity using luciferase reporters. Although the levels of BMAL1 and other clock proteins, REV-ERBalpha and CLOCK, showed no obvious rhythmicity, robust circadian oscillation in Bmal1 and Per2 promoter activities with the correct phase relationship was observed, which proceeded in a doxycycline-concentration-dependent manner. We applied transient response analysis to the Bmal1 promoter activity in the presence of various doxycycline concentrations. Based on the obtained transfer functions, we suggest that, at least in our experimental system, BMAL1 is not directly involved in the oscillatory process, but modulates the oscillation robustness by regulating basal clock gene promoter activity.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Apirada", "last_name": "Padlom", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Rio", "last_name": "Hamashima", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Nishiwaki-Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-24188-4" }, "pmcid": { "normalized": "PMC9663716" }, "pmid": { "normalized": "36376366" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "ARNTL Transcription Factors", "descriptor_ui": "D056930", "major_topic": true }, { "descriptor": "Circadian Clocks", "descriptor_ui": "D057906", "major_topic": true }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "CLOCK Proteins", "descriptor_ui": "D056926", "major_topic": false }, { "descriptor": "Doxycycline", "descriptor_ui": "D004318", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Nov 14", "date_precision": "day", "issue": "1", "normalized_date": "2022-11-14", "pages": "19519", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Level of constitutively expressed BMAL1 affects the robustness of circadian oscillations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Astrocytes, a type of glia, are abundant and morphologically complex cells. Here, we report astrocyte molecular profiles, diversity, and morphology across the mouse central nervous system (CNS). We identified shared and region-specific astrocytic genes and functions and explored the cellular origins of their regional diversity. We identified gene networks correlated with astrocyte morphology, several of which unexpectedly contained Alzheimer's disease (AD) risk genes. CRISPR/Cas9-mediated reduction of candidate genes reduced astrocyte morphological complexity and resulted in cognitive deficits. The same genes were down-regulated in human AD, in an AD mouse model that displayed reduced astrocyte morphology, and in other human brain disorders. We thus provide comprehensive molecular data on astrocyte diversity and mechanisms across the CNS and on the molecular basis of astrocyte morphology in health and disease.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Fumito", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Joselyn S.", "last_name": "Soto", "name": null }, { "creator_type": "author", "first_name": "Xinzhu", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Zhe", "last_name": "Qu", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Viviana", "last_name": "Gradinaru", "name": null }, { "creator_type": "author", "first_name": "Riki", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Baljit S.", "last_name": "Khakh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.adc9020" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36378959" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": true }, { "descriptor": "Central Nervous System", "descriptor_ui": "D002490", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Nov 4", "date_precision": "day", "issue": "6619", "normalized_date": "2022-11-04", "pages": "eadc9020", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "378", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular basis of astrocyte diversity and morphology across the CNS in health and disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorogenic probes for bioimaging have become essential tools for life science and medicine, and the key to their development is a precise understanding of the mechanisms available for fluorescence off/on control, such as photoinduced electron transfer (PeT) and Förster resonance energy transfer (FRET). Here we establish a new molecular design strategy to rationally develop activatable fluorescent probes, which exhibit a fluorescence off/on change in response to target biomolecules, by controlling the twisted intramolecular charge transfer (TICT) process. This approach was developed on the basis of a thorough investigation of the fluorescence quenching mechanism of N-phenyl rhodamine dyes (commercially available as the QSY series) by means of time-dependent density functional theory (TD-DFT) calculations and photophysical evaluation of their derivatives. To illustrate and validate this TICT-based design strategy, we employed it to develop practical fluorogenic probes for HaloTag and SNAP-tag. We further show that the TICT-controlled fluorescence off/on mechanism is generalizable by synthesizing a Si–rhodamine-based fluorogenic probe for HaloTag, thus providing a palette of chemical dyes that spans the visible and near-infrared range.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Shimpei", "last_name": "Iwaki", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Myochin", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ikeno", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Motokazu", "last_name": "Uchigashima", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Mikuni", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Tainaka", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tahara", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Tahei", "last_name": "Tahara", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.2c06397" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022-11-02", "date_precision": "day", "issue": "43", "normalized_date": "2022-11-02", "pages": "19778-19790", "proceedings_title": null, "publisher": "American Chemical Society", "title": "Journal of the American Chemical Society", "volume": "144", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "General Design Strategy to Precisely Control the Emission of Fluorophores via a Twisted Intramolecular Charge Transfer (TICT) Process", "url": "https://doi.org/10.1021/jacs.2c06397", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The microRNA (miR) miR-874, a potential tumour suppressor, causes cell death via target gene suppression in various cancer types. Mevalonate pathway inhibition also causes cell death in breast cancer. However, the relationship between the mevalonate pathway and miR-874-induced apoptosis or its association with the tumour suppressor p53 has not been elucidated. We identified phosphomevalonate kinase (PMVK), a key mevalonate pathway enzyme, and sterol regulatory element-binding factor 2 (SREBF2), the master cholesterol biosynthesis regulator, as direct miR874 targets. Next-generation sequencing analysis revealed a significant miR-874-mediated downregulation of PMVK and SREBF2 gene expression and p53 pathway enrichment. Luciferase reporter assays showed that miR-874 directly regulated PMVK and SREBF2. miR-874-induced apoptosis was p53 dependent, and single-cell RNA sequencing analysis demonstrated that miR-874 transfection resulted in apoptosis and p53 pathway activation. Downregulation of PMVK expression also caused cell cycle arrest and p53 pathway activation, which was rescued by geranylgeranyl pyrophosphate (GGPP) supplementation. Analysis of The Cancer Genome Atlas (TCGA) database indicated a negative correlation between miR-874 and PMVK expression and between miR-874 and SREBF2 expression. These findings suggest that miR-874 suppresses the mevalonate pathway by targeting SREBF2 and PMVK, resulting in GGPP depletion, which activates the p53 pathway and promotes cycle arrest or apoptosis.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Alimasi", "last_name": "Aersilan", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Akitoshi", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Xiaoyan", "last_name": "Shi", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Ikki", "last_name": "Sakuma", "name": null }, { "creator_type": "author", "first_name": "Nijiro", "last_name": "Nohata", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Naohiko", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Bahityar", "last_name": "Rahmutulla", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kaneda", "name": null }, { "creator_type": "author", "first_name": "Siti Nurul", "last_name": "Zhahara", "name": null }, { "creator_type": "author", "first_name": "Yingbo", "last_name": "Gong", "name": null }, { "creator_type": "author", "first_name": "Motoi", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Shoichiro", "last_name": "Kawauchi", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-23205-w" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36323841" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mevalonic Acid", "descriptor_ui": "D008798", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": true }, { "descriptor": "Phosphotransferases (Phosphate Group Acceptor)", "descriptor_ui": "D017856", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Nov 2", "date_precision": "day", "issue": "1", "normalized_date": "2022-11-02", "pages": "18443", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "MicroRNA-874 targets phosphomevalonate kinase and inhibits cancer cell growth via the mevalonate pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ventral tail bending, which is transient but pronounced, is found in many chordate embryos and constitutes an interesting model of how tissue interactions control embryo shape. Here, we identify one key upstream regulator of ventral tail bending in embryos of the ascidian Ciona. We show that during the early tailbud stages, ventral epidermal cells exhibit a boat-shaped morphology (boat cell) with a narrow apical surface where phosphorylated myosin light chain (pMLC) accumulates. We further show that interfering with the function of the BMP ligand Admp led to pMLC localizing to the basal instead of the apical side of ventral epidermal cells and a reduced number of boat cells. Finally, we show that cutting ventral epidermal midline cells at their apex using an ultraviolet laser relaxed ventral tail bending. Based on these results, we propose a previously unreported function for Admp in localizing pMLC to the apical side of ventral epidermal cells, which causes the tail to bend ventrally by resisting antero-posterior notochord extension at the ventral side of the tail.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki S.", "last_name": "Kogure", "name": null }, { "creator_type": "author", "first_name": "Hiromochi", "last_name": "Muraoka", "name": null }, { "creator_type": "author", "first_name": "Wataru C.", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Raphael", "last_name": "Gelin-Alessi", "name": null }, { "creator_type": "author", "first_name": "Benoit", "last_name": "Godard", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Carl-Philipp", "last_name": "Heisenberg", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.200215" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36227591" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ciona", "descriptor_ui": "D000077262", "major_topic": true }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": true }, { "descriptor": "Epidermal Cells", "descriptor_ui": "D000078404", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Myosin Light Chains", "descriptor_ui": "D018994", "major_topic": false }, { "descriptor": "Tail", "descriptor_ui": "D013623", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Nov 1", "date_precision": "day", "issue": "21", "normalized_date": "2022-11-01", "pages": "dev200215", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "149", "year": 2022 }, "ssbd": { "database": [ "ssbd-database-000281" ], "repository": [ "ssbd-repos-000281" ] }, "title": "Admp regulates tail bending by controlling ventral epidermal cell polarity via phosphorylated myosin localization in Ciona.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Cell groups containing catecholamines provide a useful model to study the molecular and cellular mechanisms underlying the morphogenesis, physiology, and pathology of the central nervous system. For this purpose, it is necessary to establish a system to induce catecholaminergic group-specific expression of Cre recombinase. Recently, we introduced a gene cassette encoding 2A peptide fused to Cre recombinase into the site between the C-terminus and translational termination codons of the rat tyrosine hydroxylase (TH) open reading frame by the Combi-CRISPR technology, which is a genomic editing method to enable an efficient knock-in (KI) of long DNA sequence into a target site. However, the expression patterns of the transgene and its function as well as the effect of the mutation on the biochemical and behavioral phenotypes in the KI strains have not been characterized yet. NEW METHOD: We aimed to evaluate the usefulness of TH-Cre KI rats as an experimental model for investigating the structure and function of catecholaminergic neurons in the brain. RESULTS: We detected cell type-specific expression of Cre recombinase and site-specific recombination activity in the representative catecholaminergic groups in the TH-Cre KI rat strains. In addition, we measured TH protein levels and catecholamine accumulation in the brain regions, as well as motor, reward-related, and anxiety-like behaviors, indicating that catecholamine metabolism and general behavior are apparently normal in these KI rats. CONCLUSIONS: TH-Cre KI rat strains produced by the Combi-CRISPR system offer a beneficial model to study the molecular and cellular mechanics for the morphogenesis, physiology, and pathology of catecholamine-containing neurons in the brain.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Natsuki", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Kayo", "last_name": "Nishizawa", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Iguchi", "name": null }, { "creator_type": "author", "first_name": "Ryoji", "last_name": "Fukabori", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Miyasaka", "name": null }, { "creator_type": "author", "first_name": "Tomoji", "last_name": "Mashimo", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jneumeth.2022.109707" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36089167" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Catecholamines", "descriptor_ui": "D002395", "major_topic": false }, { "descriptor": "Clustered Regularly Interspaced Short Palindromic Repeats", "descriptor_ui": "D064112", "major_topic": true }, { "descriptor": "Codon, Terminator", "descriptor_ui": "D018388", "major_topic": false }, { "descriptor": "Integrases", "descriptor_ui": "D019426", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Transgenic", "descriptor_ui": "D055647", "major_topic": false }, { "descriptor": "Technology", "descriptor_ui": "D013672", "major_topic": false }, { "descriptor": "Tyrosine 3-Monooxygenase", "descriptor_ui": "D014446", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Nov 1", "date_precision": "day", "issue": "", "normalized_date": "2022-11-01", "pages": "109707", "proceedings_title": null, "publisher": "", "title": "Journal of neuroscience methods", "volume": "381", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Catecholaminergic cell type-specific expression of Cre recombinase in knock-in transgenic rats generated by the Combi-CRISPR technology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Turn-on fluorescence probes can visualize the enzyme activity with high contrast. We have established a new turn-on mechanism, activator-induced nucleophilic quencher detachment (AiQd), and developed AiQd-based turn-on fluorescence probes for the detection of enzymes. Herein, we demonstrate that the precise steric control efficiently quenches the fluorescence of AiQd-based turn-on probes before the enzymatic transformation. Theoretical calculation appropriately predicted the ratio of the fluorescence-quenched closed-ring form of probes. βC5S-A, which has a sterically demanding methyl group at the β-position of a fluorescence-quenching nucleophilic mercapto group, showed a low background signal. βC5S-A responded to aldehyde dehydrogenase 1A1 (ALDH1A1) with high selectivity, thereby enabling high-contrast live imaging of cancer stem cells (signal-to-noise ratio >10). The ALDH1A1-responsiveness of βC5S-A was not significantly affected by amino acids and biological thiols, such as cysteine and glutathione.", "classifications": [ { "id": "21H00424", "label": "21H00424", "researcher": "Koji Miki", "type": "grant" }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Oe", "name": null }, { "creator_type": "author", "first_name": "Kanae", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Huiying", "last_name": "Mu", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cplu.202200319" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36416250" } }, "mesh": [ { "descriptor": "Aldehyde Dehydrogenase", "descriptor_ui": "D000444", "major_topic": true }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022-11", "date_precision": "month", "issue": "11", "normalized_date": "2022-11", "pages": "e202200319", "proceedings_title": null, "publisher": "", "title": "ChemPlusChem", "volume": "87", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Steric Control in Activator-Induced Nucleophilic Quencher Detachment-Based Probes: High-Contrast Imaging of Aldehyde Dehydrogenase 1A1 in Cancer Stem Cells", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The histone methyltransferase SET domain-containing protein 8 (SETD8), which methylates histone H4 lysine 20 (H4K20) and non-histone proteins such as p53, plays key roles in human carcinogenesis. Our aim was to determine the involvement of SETD8 in endometrial cancer and its therapeutic potential and identify the downstream genes regulated by SETD8 via H4K20 methylation and the p53 signaling pathway. We examined the expression profile of SETD8 and evaluated whether SETD8 plays a critical role in the proliferation of endometrial cancer cells using small interfering RNAs (siRNAs). We identified the prognostically important genes regulated by SETD8 via H4K20 methylation and p53 signaling using chromatin immunoprecipitation sequencing, RNA sequencing, and machine learning. We confirmed that SETD8 expression was elevated in endometrial cancer tissues. Our in vitro results suggest that the suppression of SETD8 using siRNA or a selective inhibitor attenuated cell proliferation and promoted the apoptosis of endometrial cancer cells. In these cells, SETD8 regulates genes via H4K20 methylation and the p53 signaling pathway. We also identified the prognostically important genes related to apoptosis, such as those encoding KIAA1324 and TP73, in endometrial cancer. SETD8 is an important gene for carcinogenesis and progression of endometrial cancer via H4K20 methylation.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Asako", "last_name": "Kukita", "name": null }, { "creator_type": "author", "first_name": "Kenbun", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Machiko", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Miku", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Toyohara", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Futaba", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Saki", "last_name": "Tanimoto", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Tanikawa", "name": null }, { "creator_type": "author", "first_name": "Mayuyo", "last_name": "Mori-Uchino", "name": null }, { "creator_type": "author", "first_name": "Tetsushi", "last_name": "Tsuruga", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Iriyama", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Nagasaka", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Wada-Hiraike", "name": null }, { "creator_type": "author", "first_name": "Katsutoshi", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Osuga", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers14215367" }, "pmcid": { "normalized": "PMC9655767" }, "pmid": { "normalized": "36358786" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Oct 31", "date_precision": "day", "issue": "21", "normalized_date": "2022-10-31", "pages": "5367", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "14", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "The Histone Methyltransferase SETD8 Regulates the Expression of Tumor Suppressor Genes via H4K20 Methylation and the p53 Signaling Pathway in Endometrial Cancer Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "While the molecular target of (R,S)-ketamine (ketamine) is thought to be the NMDA receptor, subanesthetic doses of ketamine have been known to modulate monoaminergic neurotransmission in the central nervous system. Although the involvement of the serotonergic system in the antidepressant effects of ketamine has been reported in most studies of this topic, some recent studies have reported that the dopaminergic system plays a key role in the effects of ketamine. Additionally, several lines of evidence suggest that the antidepressant-like effects of (R)-ketamine might be independent of the monoaminergic system. Ketamine metabolites also differ considerably in their ability to regulate monoamine neurotransmitters relative to (S)-ketamine and (R)-ketamine, while (2R,6R)-hydroxynorketamine might share common serotonergic signaling mechanisms with ketamine. In the current review, we summarize the effects of ketamine and its metabolites on monoamine neurotransmission in the brain and discuss the potential roles of the monoaminergic system in the mechanism of action of ketamine.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuropharm.2022.109313" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36328065" } }, "mesh": [ { "descriptor": "Antidepressive Agents", "descriptor_ui": "D000928", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Ketamine", "descriptor_ui": "D007649", "major_topic": true }, { "descriptor": "Receptors, N-Methyl-D-Aspartate", "descriptor_ui": "D016194", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 31", "date_precision": "day", "issue": "", "normalized_date": "2022-10-31", "pages": "109313", "proceedings_title": null, "publisher": "", "title": "Neuropharmacology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Roles of the monoaminergic system in the antidepressant effects of ketamine and its metabolites.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The neural bases of itchy eye transmission remain unclear compared with those involved in body itch. Here, we show in rodents that the gastrin-releasing peptide receptor (GRPR) of the trigeminal sensory system is involved in the transmission of itchy eyes. Interestingly, we further demonstrate a difference in scratching behaviour between the left and right hindfeet in rodents; histamine instillation into the conjunctival sac of both eyes revealed right-foot biased laterality in the scratching movements. Unilateral histamine instillation specifically induced neural activation in the ipsilateral sensory pathway, with no significant difference between the activations following left- and right-eye instillations. Thus, the behavioural laterality is presumably due to right-foot preference in rodents. Genetically modified rats with specific depletion of Grpr-expressing neurons in the trigeminal sensory nucleus caudalis of the medulla oblongata exhibited fewer and shorter histamine-induced scratching movements than controls and eliminated the footedness. These results taken together indicate that the Grpr-expressing neurons are required for the transmission of itch sensation from the eyes, but that foot preference is generated centrally. These findings could open up a new field of research on the mechanisms of the laterality in vertebrates and also offer new potential therapeutic approaches to refractory pruritic eye disorders.", "classifications": [ { "id": "21H00428", "label": "21H00428", "researcher": "Tatsuya Sakamoto", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yukitoshi", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Ayane", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Takanami", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1098/rspb.2022.1126" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36259204" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Eye", "descriptor_ui": "D005123", "major_topic": false }, { "descriptor": "Functional Laterality", "descriptor_ui": "D007839", "major_topic": true }, { "descriptor": "Histamine", "descriptor_ui": "D006632", "major_topic": true }, { "descriptor": "Pruritus", "descriptor_ui": "D011537", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Receptors, Bombesin", "descriptor_ui": "D018004", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Oct 26", "date_precision": "day", "issue": "1985", "normalized_date": "2022-10-26", "pages": "20221126", "proceedings_title": null, "publisher": "", "title": "Proceedings. Biological sciences", "volume": "289", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Footedness for scratching itchy eyes in rodents.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Binding of fluorescent ligand (FL) to the cyan fluorescent protein (CFP)-coupled ligand-binding domain of the inositol 1,4,5-trisphosphate (IP3) receptor (CFP-LBP) produces fluorescence (Forster) resonance energy transfer (FRET). A competitive fluorescent ligand assay (CFLA), using the FRET signal from competition between FLs and IP3, can measure IP3 concentration. The FRET signal should be enhanced by attaching a FRET donor to an appropriate position. Herein, we inserted five different circularly permuted CFPs in the loop between the second and third alpha-helices to generate membrane-targeted fluorescent ligand-binding proteins (LBPs). Two such proteins, LBP-cpC157 and LBP-cpC173, localized at the plasma membrane, displayed FRET upon binding the high-affinity ligand fluorescent adenophostin A (F-ADA), and exhibited a decreased fluorescence emission ratio (480 nm / 535 nm) by 1.6- to 1.8-fold that of CFP-LBP. In addition, binding of a fluorescent low-affinity ligand (F-LL) also reduced the fluorescence ratio in a concentration-dependent manner, with EC50 values for LBP-cpC157 and LBP-cpC173 of 34.7 nM and 27.6 nM, respectively. These values are comparable to that with CFP-LBP (29.2 nM), indicating that insertion of cpC157 and cpC173 did not disrupt LBP structure and function. The effect of 100 nM F-LL on the decrease in fluorescence ratio was reversed upon addition of IP3, indicating binding competition between F-LL and IP3. We also constructed cytoplasmic fluorescent proteins cyLBP-cpC157 and cyLBP-cpC173, and bound them to DYK beads for imaging analyses. Application of F-ADA decreased the fluorescence ratio of the beads from the periphery to the center over 3 - 5 min. Application of F-LL also decreased the fluorescence ratio of cyLBP-cpC157 and cyLBP-cpC173 by 20-25%, and subsequent addition of IP3 recovered the fluorescence ratio in a concentration-dependent manner. The EC50 value and Hill coefficient obtained by curve fitting against the IP3-dependent recovery of fluorescence ratio can be used to estimate the IP3 concentration.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Azmeree", "last_name": "Jahan", "name": null }, { "creator_type": "author", "first_name": "Mst Tahmina", "last_name": "Akter", "name": null }, { "creator_type": "author", "first_name": "Kiwamu", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Tai", "last_name": "Oura", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Shitara", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Semba", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Nezu", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Suto", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Tanimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ceca.2022.102668" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36335765" } }, "mesh": [ { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Inositol", "descriptor_ui": "D007294", "major_topic": true }, { "descriptor": "Inositol 1,4,5-Trisphosphate", "descriptor_ui": "D015544", "major_topic": false }, { "descriptor": "Inositol 1,4,5-Trisphosphate Receptors", "descriptor_ui": "D053496", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 26", "date_precision": "day", "issue": "", "normalized_date": "2022-10-26", "pages": "102668", "proceedings_title": null, "publisher": "", "title": "Cell calcium", "volume": "108", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Insertion of circularly permuted cyan fluorescent protein into the ligand-binding domain of inositol 1,4,5-trisphosphate receptor for enhanced FRET upon binding of fluorescent ligand.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Newly emerging transformed epithelial cells are recognized and apically removed by surrounding normal cells through a biological event termed \"cell competition\". However, little is known about the mechanisms underlying this process. In a recent study, we describe that RAS(G12V)/RasV12-transformed cells surrounded by normal cells exhibit decreased lysosomal activity accompanied with accumulation of autophagosomes. Restoration of low lysosomal activity or inhibition of autophagosome formation significantly antagonizes apical extrusion of RAS(G12V) cells, suggesting that non-degradable autophagosomes are required for cell competition. Notably, analysis of a cell competition mouse model demonstrates that macroautophagy/autophagy-ablated RAS(G12V) cells are less readily eliminated by cell competition, and remaining transformed cells destroy ductal integrity, leading to chronic pancreatitis. Thus, our findings illuminate a critical role for non-degradable autophagosomes in cell competition and reveal a homeostasis-preserving role of autophagy upon emergence of transformed cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Eilma", "last_name": "Akter", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kon", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/15548627.2022.2140559" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36286607" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autophagosomes", "descriptor_ui": "D000071182", "major_topic": false }, { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": true }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": true }, { "descriptor": "Lysosomes", "descriptor_ui": "D008247", "major_topic": false }, { "descriptor": "Macroautophagy", "descriptor_ui": "D000080550", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 26", "date_precision": "day", "issue": "", "normalized_date": "2022-10-26", "pages": "", "proceedings_title": null, "publisher": "", "title": "Autophagy", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Autophagic perturbation caused by reduced lysosomal activity positively regulates cell competition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Insect vision starts with light absorption by visual pigments based on opsins that drive Gq-type G protein-mediated phototransduction. Since Drosophila, the most studied insect in vision research, has only Gq-coupled opsins, the Gq-mediated phototransduction has been solely focused on insect vision for decades. However, genome projects on mosquitos uncovered non-canonical insect opsin genes, members of the Opn3 or c-opsin group composed of vertebrate and invertebrate non-visual opsins. Here, we report that a homologue of Opn3, MosOpn3 (Asop12) is expressed in eyes of a mosquito Anopheles stephensi. In situ hybridization analysis revealed that MosOpn3 is expressed in dorsal and ventral ommatidia, in which only R7 photoreceptor cells express MosOpn3. We also found that Asop9, a Gq-coupled visual opsin, exhibited co-localization with MosOpn3. Spectroscopic analysis revealed that Asop9 forms a blue-sensitive opsin-based pigment. Thus, the Gi/Go-coupled opsin MosOpn3, which forms a green-sensitive pigment, is co-localized with Asop9, a Gq-coupled opsin that forms a blue-sensitive visual pigment. Since these two opsin-based pigments trigger different phototransduction cascades, the R7 photoreceptors could generate complex photoresponses to blue to green light. This article is part of the theme issue 'Understanding colour vision: molecular, physiological, neuronal and behavioural studies in arthropods'.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Hirohisa", "last_name": "Yokono", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1098/rstb.2021.0274" }, "pmcid": { "normalized": "PMC9441228" }, "pmid": { "normalized": "36058246" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Insecta", "descriptor_ui": "D007313", "major_topic": false }, { "descriptor": "Opsins", "descriptor_ui": "D055355", "major_topic": true }, { "descriptor": "Photoreceptor Cells, Invertebrate", "descriptor_ui": "D017956", "major_topic": false }, { "descriptor": "Retinal Pigments", "descriptor_ui": "D012168", "major_topic": false }, { "descriptor": "Rod Opsins", "descriptor_ui": "D017299", "major_topic": true }, { "descriptor": "Vertebrates", "descriptor_ui": "D014714", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 24", "date_precision": "day", "issue": "1862", "normalized_date": "2022-10-24", "pages": "20210274", "proceedings_title": null, "publisher": "", "title": "Philosophical transactions of the Royal Society of London. Series B, Biological sciences", "volume": "377", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Expression of a homologue of a vertebrate non-visual opsin Opn3 in the insect photoreceptors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Various culture methods have been developed for maintaining human pluripotent stem cells (PSCs). These PSC maintenance methods exhibit biased differentiation; for example, feeder-dependent PSCs efficiently yield cerebral organoids, but it is difficult to generate organoids from feeder-free PSCs. It remains unknown how PSC maintenance conditions affect differentiation. In this study, we identified fibroblast growth factor (FGF) signaling in feeder-free PSC maintenance as a key factor that determines the differentiation toward cerebral organoids. The inhibition of FGF signaling in feeder-free PSCs rescued organoid generation to the same level in feeder-dependent cultures. FGF inhibition induced DNA methylation at the WNT5A locus, and this epigenetic change suppressed the future activation of non-canonical Wnt signaling after differentiation, leading to reliable cerebral organoid generation. This study underscores the importance of PSC culture conditions for directed differentiation into cerebral organoids, and the epigenetic status regulated by FGF signaling is involved in the underlying mechanisms.", "classifications": [ { "id": "21H00438", "label": "21H00438", "researcher": "Kent Imaizumi", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hirosato", "last_name": "Ideno", "name": null }, { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Sanosaka", "name": null }, { "creator_type": "author", "first_name": "Akisa", "last_name": "Nemoto", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Kohyama", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2022.105140" }, "pmcid": { "normalized": "PMC9523398" }, "pmid": { "normalized": "36185382" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Oct 21", "date_precision": "day", "issue": "10", "normalized_date": "2022-10-21", "pages": "105140", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "25", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Human PSCs determine the competency of cerebral organoid differentiation via FGF signaling and epigenetic mechanisms.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Symptoms of adverse reactions to vaccines evolve over time, but traditional studies have focused only on the frequency and intensity of symptoms. Here, we attempt to extract the dynamic changes in vaccine adverse reaction symptoms as a small number of interpretable components by using non-negative tensor factorization. We recruited healthcare workers who received two doses of the BNT162b2 mRNA COVID-19 vaccine at Chiba University Hospital and collected information on adverse reactions using a smartphone/web-based platform. We analyzed the adverse-reaction data after each dose obtained for 1,516 participants who received two doses of vaccine. The non-negative tensor factorization revealed four time-evolving components that represent typical temporal patterns of adverse reactions for both doses. These components were differently associated with background factors and post-vaccine antibody titers. These results demonstrate that complex adverse reactions against vaccines can be explained by a limited number of time-evolving components identified by tensor factorization.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kei", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Taka-Aki", "last_name": "Nakada", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Goshima", "name": null }, { "creator_type": "author", "first_name": "Natsuko", "last_name": "Otaki", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Iwami", "name": null }, { "creator_type": "author", "first_name": "Teppei", "last_name": "Shimamura", "name": null }, { "creator_type": "author", "first_name": "Toshibumi", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Igari", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Koutaro", "last_name": "Yokote", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Tsuyuzaki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2022.105237" }, "pmcid": { "normalized": "PMC9515008" }, "pmid": { "normalized": "36188188" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Oct 21", "date_precision": "day", "issue": "10", "normalized_date": "2022-10-21", "pages": "105237", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "25", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Detecting time-evolving phenotypic components of adverse reactions against BNT162b2 SARS-CoV-2 vaccine via non-negative tensor factorization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Invariant natural killer T (iNKT) cells are a group of innate-like T lymphocytes that recognize lipid antigens. They are supposed to be tissue resident and important for systemic and local immune regulation. To investigate the heterogeneity of iNKT cells, we recharacterized iNKT cells in the thymus and peripheral tissues. iNKT cells in the thymus were divided into three subpopulations by the expression of the natural killer cell receptor CD244 and the chemokine receptor CXCR6 and designated as C0 (CD244−CXCR6−), C1 (CD244−CXCR6+), or C2 (CD244+CXCR6+) iNKT cells. The development and maturation of C2 iNKT cells from C0 iNKT cells strictly depended on IL-15 produced by thymic epithelial cells. C2 iNKT cells expressed high levels of IFN-γ and granzymes and exhibited more NK cell–like features, whereas C1 iNKT cells showed more T cell–like characteristics. C2 iNKT cells were influenced by the microbiome and aging and suppressed the expression of the autoimmune regulator AIRE in the thymus. In peripheral tissues, C2 iNKT cells were circulating that were distinct from conventional tissue-resident C1 iNKT cells. Functionally, C2 iNKT cells protected mice from the tumor metastasis of melanoma cells by enhancing antitumor immunity and promoted antiviral immune responses against influenza virus infection. Furthermore, we identified human CD244+CXCR6+ iNKT cells with high cytotoxic properties as a counterpart of mouse C2 iNKT cells. Thus, this study reveals a circulating subset of iNKT cells with NK cell–like properties distinct from conventional tissue-resident iNKT cells.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Guangwei", "last_name": "Cui", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Shimba", "name": null }, { "creator_type": "author", "first_name": "Jianshi", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Taisaku", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Muramoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Asahi", "name": null }, { "creator_type": "author", "first_name": "Shizue", "last_name": "Tani-ichi", "name": null }, { "creator_type": "author", "first_name": "Johannes M.", "last_name": "Dijkstra", "name": null }, { "creator_type": "author", "first_name": "Yayoi", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Kirill", "last_name": "Kryukov", "name": null }, { "creator_type": "author", "first_name": "Yuanbo", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Takami", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Yan", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Moyu", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Lynn", "last_name": "Zreka", "name": null }, { "creator_type": "author", "first_name": "Keishi", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kanaya", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Yoshimasa", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Watarai", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Oike", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Imanishi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Ohteki", "name": null }, { "creator_type": "author", "first_name": "Nagahiro", "last_name": "Minato", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Georg A.", "last_name": "Holländer", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ikuta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciimmunol.abj8760" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022-10-21", "date_precision": "day", "issue": "76", "normalized_date": "2022-10-21", "pages": "eabj8760", "proceedings_title": null, "publisher": "American Association for the Advancement of Science", "title": "Science Immunology", "volume": "7", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "A circulating subset of iNKT cells mediates antitumor and antiviral immunity", "url": "https://www.science.org/doi/10.1126/sciimmunol.abj8760", "zotero": { "item_type": "journalArticle" } }, { "abstract": "When understanding the neuronal function of a specific neural circuit, single-cell level photoablation of a targeted cell is one of the useful experimental approaches. This protocol describes a method to photoablate specific motor neurons via the mini singlet oxygen generator (miniSOG2), a light-oxygen-voltage (LOV)-based optogenetic tool used for ablating targeted cells in arbitrary areas. MiniSOG2 could induce the cell death pathway by generating reactive oxygen species (ROS) upon blue light illumination. Photoablation of a specific cell using the miniSOG2 was performed to show that, in Ciona intestinalis type A ( Ciona robusta) , a single pair of motor neurons, MN2/A10.64, is necessary to drive their tail muscle contraction. The membrane targeted miniSOG2 combined with neuron-specific promoter (pSP-Neurog::miniSOG2-CAAX) was electroplated into the Ciona egg and transiently expressed at specific neurons of the embryo. MN2 labeled with pSP-Neurog:mCherry-CAAX was irradiated using a 440-nm laser from the lateral side for 10 min to ablate its neural function. The behavior of the embryo before and after the irradiation was recorded with a high-speed camera. Graphical abstract.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Madoka K.", "last_name": "Utsumi", "name": null }, { "creator_type": "author", "first_name": "Taichi", "last_name": "Akahoshi", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null } ], "identifiers": { "doi": { "normalized": "10.21769/bioprotoc.4537" }, "pmcid": { "normalized": "PMC9606450" }, "pmid": { "normalized": "36353720" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Oct 20", "date_precision": "day", "issue": "20", "normalized_date": "2022-10-20", "pages": "e4537", "proceedings_title": null, "publisher": "", "title": "Bio-protocol", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "MiniSOG2-mediated Specific Photoablation of Motor Neurons in Ascidian Embryos.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The SARS-CoV-2 Omicron BA.2.75 variant emerged in May 2022. BA.2.75 is a BA.2 descendant but is phylogenetically distinct from BA.5, the currently predominant BA.2 descendant. Here, we show that BA.2.75 has a greater effective reproduction number and different immunogenicity profile than BA.5. We determined the sensitivity of BA.2.75 to vaccinee and convalescent sera as well as a panel of clinically available antiviral drugs and antibodies. Antiviral drugs largely retained potency, but antibody sensitivity varied depending on several key BA.2.75-specific substitutions. The BA.2.75 spike exhibited a profoundly higher affinity for its human receptor, ACE2. Additionally, the fusogenicity, growth efficiency in human alveolar epithelial cells, and intrinsic pathogenicity in hamsters of BA.2.75 were greater than those of BA.2. Our multilevel investigations suggest that BA.2.75 acquired virological properties independent of BA.5, and the potential risk of BA.2.75 to global health is greater than that of BA.5.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akatsuki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Jiri", "last_name": "Zahradnik", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Deguchi", "name": null }, { "creator_type": "author", "first_name": "Koshiro", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Anraku", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Yamasoba", "name": null }, { "creator_type": "author", "first_name": "Hesham", "last_name": "Nasser", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Keiya", "last_name": "Uriu", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kosugi", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Shofa", "name": null }, { "creator_type": "author", "first_name": "Mst", "last_name": "Monira Begum", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Rigel", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Naganori", "last_name": "Nao", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Yoshimatsu", "name": null }, { "creator_type": "author", "first_name": "Jin", "last_name": "Kuramochi", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Sasaki-Tabata", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Maenaka", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tetsuharu", "last_name": "Nagamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Asakura", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sadamasu", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Gideon", "last_name": "Schreiber", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Takaori-Kondo", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Shirakawa", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Irie", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Hashiguchi", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Matsuno", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Terumasa", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Takasuke", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chom.2022.10.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36272413" } }, "mesh": [ { "descriptor": "Antibodies, Neutralizing", "descriptor_ui": "D057134", "major_topic": false }, { "descriptor": "Antibodies, Viral", "descriptor_ui": "D000914", "major_topic": false }, { "descriptor": "Antiviral Agents", "descriptor_ui": "D000998", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "COVID-19 Serotherapy", "descriptor_ui": "D000093522", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true }, { "descriptor": "Spike Glycoprotein, Coronavirus", "descriptor_ui": "D064370", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 18", "date_precision": "day", "issue": "", "normalized_date": "2022-10-18", "pages": "S1931-3128(22)00516-9", "proceedings_title": null, "publisher": "", "title": "Cell host & microbe", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Lidya Handayani", "last_name": "Tjan", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Yukiya", "last_name": "Kurahashi", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Sutandhio", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/infdis/jiac159" }, "pmcid": { "normalized": "PMC9383817" }, "pmid": { "normalized": "35481958" } }, "mesh": [ { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunization, Secondary", "descriptor_ui": "D007117", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Vaccination", "descriptor_ui": "D014611", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 17", "date_precision": "day", "issue": "8", "normalized_date": "2022-10-17", "pages": "1481-1483", "proceedings_title": null, "publisher": "", "title": "The Journal of infectious diseases", "volume": "226", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Induction of High Neutralizing Activity Against Both Omicron BA.2 and Omicron BA.1 by Coronavirus Disease 2019 Messenger RNA Booster Vaccination.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant omicron is now under investigation. We evaluated cross-neutralizing activity against omicron in coronavirus disease 2019 (COVID-19) convalescent patients (n = 23) who had received 2 doses of an mRNA vaccination (BNT162b2 or mRNA-1273). Intriguingly, after the second vaccination, the neutralizing antibody titers of subjects against SARS-CoV-2 variants, including omicron, all became seropositive, and significant fold-increases (21.1-52.0) were seen regardless of the disease severity. Our findings thus demonstrate that 2 doses of mRNA vaccination to SARS-CoV-2 convalescent patients can induce cross-neutralizing activity against omicron.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yukiya", "last_name": "Kurahashi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Sutandhio", "name": null }, { "creator_type": "author", "first_name": "Lidya Handayani", "last_name": "Tjan", "name": null }, { "creator_type": "author", "first_name": "Sachiyo", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Tohma", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Ohkita", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Kiriu", "name": null }, { "creator_type": "author", "first_name": "Masatsugu", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/infdis/jiac178" }, "pmcid": { "normalized": "PMC9129189" }, "pmid": { "normalized": "35512332" } }, "mesh": [ { "descriptor": "Antibodies, Neutralizing", "descriptor_ui": "D057134", "major_topic": false }, { "descriptor": "Antibodies, Viral", "descriptor_ui": "D000914", "major_topic": false }, { "descriptor": "BNT162 Vaccine", "descriptor_ui": "D000090982", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neutralization Tests", "descriptor_ui": "D009500", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true }, { "descriptor": "Vaccination", "descriptor_ui": "D014611", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 17", "date_precision": "day", "issue": "8", "normalized_date": "2022-10-17", "pages": "1391-1395", "proceedings_title": null, "publisher": "", "title": "The Journal of infectious diseases", "volume": "226", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Cross-Neutralizing Activity Against Omicron Could Be Obtained in SARS-CoV-2 Convalescent Patients Who Received Two Doses of mRNA Vaccination.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have previously shown that pituitary adenylate cyclase-activating polypeptide (PACAP) in the ventromedial hypothalamus (VMH) enhances feeding during the dark cycle and after fasting, and inhibits feeding during the light cycle. On the other hand, galanin is highly expressed in the hypothalamus and has been reported to be involved in feeding regulation. In this study, we investigated the involvement of the VMH-PACAP to the dorsomedial hypothalamus (DMH)-galanin signaling in the regulation of feeding. Galanin expression in the hypothalamus was significantly increased with fasting, but this increment was canceled in PACAP-knockout (KO) mice. Furthermore, overexpression of PACAP in the VMH increased the expression of galanin, while knockdown (KD) of PACAP in the VMH decreased the expression of galanin, indicating that the expression of galanin in the hypothalamus might be regulated by PACAP in the VMH. Therefore, we expressed the synaptophysin-EGFP fusion protein (SypEGFP) in PACAP neurons in the VMH and visualized the neural projection to the hypothalamic region where galanin was highly expressed. A strong synaptophysin-EGFP signal was observed in the DMH, indicating that PACAP-expressing cells of the VMH projected to the DMH. Furthermore, galanin immunostaining in the DMH showed that galanin expression was weak in PACAP-KO mice. When galanin in the DMH was knocked down, food intake during the dark cycle and after fasting was decreased, and food intake during the light cycle was increased, as in PACAP-KO mice. These results indicated that galanin in the DMH may regulate the feeding downstream of PACAP in the VMH.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Kambe", "name": null }, { "creator_type": "author", "first_name": "Thanh Trung", "last_name": "Nguyen", "name": null }, { "creator_type": "author", "first_name": "Toshiharu", "last_name": "Yasaka", "name": null }, { "creator_type": "author", "first_name": "Thu Thi", "last_name": "Nguyen", "name": null }, { "creator_type": "author", "first_name": "Yoshimune", "last_name": "Sameshima", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Hashiguchi", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Atsuro", "last_name": "Miyata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12035-022-03084-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36251233" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Appetite Regulation", "descriptor_ui": "D001069", "major_topic": false }, { "descriptor": "Galanin", "descriptor_ui": "D019004", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": true }, { "descriptor": "Synaptophysin", "descriptor_ui": "D016708", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 17", "date_precision": "day", "issue": "", "normalized_date": "2022-10-17", "pages": "", "proceedings_title": null, "publisher": "", "title": "Molecular neurobiology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "The Pivotal Role of Neuropeptide Crosstalk from Ventromedial-PACAP to Dorsomedial-Galanin in the Appetite Regulation in the Mouse Hypothalamus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Familial neurohypophyseal diabetes insipidus (FNDI) is a degenerative disease of vasopressin (AVP) neurons. Studies in mouse in vivo models indicate that accumulation of mutant AVP prehormone is associated with FNDI pathology. However, studying human FNDI pathology in vivo is technically challenging. Therefore, an in vitro human model needs to be developed. When exogenous signals are minimized in the early phase of differentiation in vitro, mouse embryonic stem cells (ESCs)/induced pluripotent stem cells (iPSCs) differentiate into AVP neurons, whereas human ESCs/iPSCs die. Human ESCs/iPSCs are generally more similar to mouse epiblast stem cells (mEpiSCs) compared to mouse ESCs. In this study, we converted human FNDI-specific iPSCs by the naive conversion kit. Although the conversion was partial, we found improved cell survival under minimal exogenous signals and differentiation into rostral hypothalamic organoids. Overall, this method provides a simple and straightforward differentiation direction, which may improve the efficiency of hypothalamic differentiation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hajime", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Hidetaka", "last_name": "Suga", "name": null }, { "creator_type": "author", "first_name": "Mayu", "last_name": "Sakakibara", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Soen", "name": null }, { "creator_type": "author", "first_name": "Natsuki", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Miwata", "name": null }, { "creator_type": "author", "first_name": "Shiori", "last_name": "Taga", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Mitsumoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Onoue", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hagiwara", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Iwama", "name": null }, { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Banno", "name": null }, { "creator_type": "author", "first_name": "Genzo", "last_name": "Iguchi", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Haruhisa", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Arima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-22405-8" }, "pmcid": { "normalized": "PMC9576732" }, "pmid": { "normalized": "36253431" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Diabetes Insipidus, Neurogenic", "descriptor_ui": "D020790", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Vasopressins", "descriptor_ui": "D014667", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 17", "date_precision": "day", "issue": "1", "normalized_date": "2022-10-17", "pages": "17381", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Differentiation of human induced pluripotent stem cells into hypothalamic vasopressin neurons with minimal exogenous signals and partial conversion to the naive state.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "After the global spread of the SARS-CoV-2 Omicron BA.2, some BA.2 subvariants, including BA.2.9.1, BA.2.11, BA.2.12.1, BA.4, and BA.5, emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these BA.2 subvariants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1/2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. We further provided the structure of the BA.4/5 spike receptor-binding domain that binds to human ACE2 and considered how the substitutions in the BA.4/5 spike play roles in ACE2 binding and immune evasion. Moreover, experiments using hamsters suggested that BA.4/5 is more pathogenic than BA.2. Our multiscale investigations suggest that the risk of BA.2 subvariants, particularly BA.4/5, to global health is greater than that of original BA.2.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Izumi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Yamasoba", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Naganori", "last_name": "Nao", "name": null }, { "creator_type": "author", "first_name": "Tateki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Shuya", "last_name": "Mitoma", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hesham", "last_name": "Nasser", "name": null }, { "creator_type": "author", "first_name": "Jiri", "last_name": "Zahradnik", "name": null }, { "creator_type": "author", "first_name": "Keiya", "last_name": "Uriu", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kosugi", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Rigel", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Mst Monira", "last_name": "Begum", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Yoshimatsu", "name": null }, { "creator_type": "author", "first_name": "Kanako Terakado", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Jiei", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Sasaki-Tabata", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tetsuharu", "last_name": "Nagamoto", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Kanamune", "name": null }, { "creator_type": "author", "first_name": "Kouji", "last_name": "Kobiyama", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Asakura", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sadamasu", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Shirakawa", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Takaori-Kondo", "name": null }, { "creator_type": "author", "first_name": "Jin", "last_name": "Kuramochi", "name": null }, { "creator_type": "author", "first_name": "Gideon", "last_name": "Schreiber", "name": null }, { "creator_type": "author", "first_name": "Ken J.", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Hashiguchi", "name": null }, { "creator_type": "author", "first_name": "Terumasa", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Akatsuki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takasuke", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Matsuno", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cell.2022.09.018" }, "pmcid": { "normalized": "PMC9472642" }, "pmid": { "normalized": "36198317" } }, "mesh": [ { "descriptor": "Angiotensin-Converting Enzyme 2", "descriptor_ui": "D000085962", "major_topic": true }, { "descriptor": "Antibodies, Viral", "descriptor_ui": "D000914", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Peptidyl-Dipeptidase A", "descriptor_ui": "D007703", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false }, { "descriptor": "Spike Glycoprotein, Coronavirus", "descriptor_ui": "D064370", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 13", "date_precision": "day", "issue": "21", "normalized_date": "2022-10-13", "pages": "3992-4007.e16", "proceedings_title": null, "publisher": "", "title": "Cell", "volume": "185", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Virological characteristics of the SARS-CoV-2 Omicron BA.2 subvariants, including BA.4 and BA.5.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Upon the initiation of collective cell migration, the cells at the free edge are specified as leader cells; however, the mechanism underlying the leader cell specification remains elusive. Here, we show that lamellipodial extension after the release from mechanical confinement causes sustained extracellular signal-regulated kinase (ERK) activation and underlies the leader cell specification. Live-imaging of Madin-Darby canine kidney (MDCK) cells and mouse epidermis through the use of Forster resonance energy transfer (FRET)-based biosensors showed that leader cells exhibit sustained ERK activation in a hepatocyte growth factor (HGF)-dependent manner. Meanwhile, follower cells exhibit oscillatory ERK activation waves in an epidermal growth factor (EGF) signaling-dependent manner. Lamellipodial extension at the free edge increases the cellular sensitivity to HGF. The HGF-dependent ERK activation, in turn, promotes lamellipodial extension, thereby forming a positive feedback loop between cell extension and ERK activation and specifying the cells at the free edge as the leader cells. Our findings show that the integration of physical and biochemical cues underlies the leader cell specification during collective cell migration.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naoya", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Kimiya", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Jikko", "name": null }, { "creator_type": "author", "first_name": "Gembu", "last_name": "Maryu", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tsukiji", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null }, { "creator_type": "author", "first_name": "Xavier", "last_name": "Trepat", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2022.09.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36174555" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Epidermal Growth Factor", "descriptor_ui": "D004815", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": true }, { "descriptor": "Feedback", "descriptor_ui": "D005246", "major_topic": false }, { "descriptor": "Hepatocyte Growth Factor", "descriptor_ui": "D017228", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 10", "date_precision": "day", "issue": "19", "normalized_date": "2022-10-10", "pages": "2290-2304.e7", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "57", "year": 2022 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000248" ] }, "title": "A feedback loop between lamellipodial extension and HGF-ERK signaling specifies leader cells during collective cell migration.", "url": "https://www.sciencedirect.com/science/article/pii/S1534580722006335?via%3Dihub", "zotero": { "item_type": "journalArticle" } }, { "abstract": "N-cadherin (NCad) is a classical cadherin that mediates cell-cell interactions in a Ca(2+)-dependent manner. NCad participates in various biological processes, from ontogenesis to higher brain functions, though the visualization of NCad interactions in living cells remains limited. Here, we present intensiometric NCad interaction indicators, named INCIDERs, that utilize dimerization-dependent fluorescent proteins. INCIDERs successfully visualize reversible NCad interactions across cells. Compared to FRET-based indicators, INCIDERs have a ~70-fold higher signal contrast, enabling clear identification of NCad interactions. In primary neuronal cells, NCad interactions are visualized between closely apposed processes. Furthermore, visualization of NCad interaction at cell adhesion sites in dense cell populations is achieved by two-photon microscopy. INCIDERs are useful tools in the spatiotemporal investigation of NCad interactions across cells; future research should evaluate the potential of INCIDERs in mapping complex three-dimensional architectures in multi-cellular systems.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Kanadome", "name": null }, { "creator_type": "author", "first_name": "Kanehiro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Seto", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-022-04023-2" }, "pmcid": { "normalized": "PMC9546846" }, "pmid": { "normalized": "36207396" } }, "mesh": [ { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": true }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Oct 7", "date_precision": "day", "issue": "1", "normalized_date": "2022-10-07", "pages": "1065", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "5", "year": 2022 }, "ssbd": { "database": [ "ssbd-database-000283" ], "repository": [ "ssbd-repos-000283" ] }, "title": "Development of intensiometric indicators for visualizing N-cadherin interaction across cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sleep stage-specific intervention is widely used to elucidate the functions of sleep and their underlying mechanisms. For this intervention, it is imperative to accurately classify rapid-eye-movement (REM) sleep. However, the proof of fully automatic real-time REM sleep classification in vivo has not been obtained in mice. Here, we report the in vivo implementation of a system that classifies sleep stages in real-time from a single-channel electroencephalogram (EEG). It enabled REM sleep-specific intervention with 90 % sensitivity and 86 % precision without prior configuration to each mouse. We further derived systems capable of classification with higher frequency sampling and time resolution. This attach-and-go sleep staging system provides a fully automatic accurate and scalable tool for investigating the functions of sleep.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Iyo", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tezuka", "name": null }, { "creator_type": "author", "first_name": "Jiahui", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Sakthivel", "last_name": "Srinivasan", "name": null }, { "creator_type": "author", "first_name": "Toshie", "last_name": "Naoi", "name": null }, { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Yasugaki", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Shimpei", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Sakaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2022.10.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36206953" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Electroencephalography", "descriptor_ui": "D004569", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": false }, { "descriptor": "Sleep Stages", "descriptor_ui": "D012894", "major_topic": true }, { "descriptor": "Sleep, REM", "descriptor_ui": "D012895", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Oct 4", "date_precision": "day", "issue": "", "normalized_date": "2022-10-04", "pages": "S0168-0102(22)00262-0", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Fully automatic REM sleep stage-specific intervention systems using single EEG in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shuhei", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Saki", "last_name": "Shigeyama", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Shiori", "last_name": "Akayama", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Alessandra", "last_name": "Esposito", "name": null }, { "creator_type": "author", "first_name": "Gennaro", "last_name": "Napolitano", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Kuma", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Namba-Hamano", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Miwa", "last_name": "Sasai", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Tokumura", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Oe", "name": null }, { "creator_type": "author", "first_name": "Toshiharu", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Seigo", "last_name": "Terawaki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Maho", "last_name": "Hamasaki", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yukinori", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Yoshitsugu", "last_name": "Takabatake", "name": null }, { "creator_type": "author", "first_name": "Haoxing", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Isaka", "name": null }, { "creator_type": "author", "first_name": "Andrea", "last_name": "Ballabio", "name": null }, { "creator_type": "author", "first_name": "Tamotsu", "last_name": "Yoshimori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41556-022-01017-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36195661" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Oct 4", "date_precision": "day", "issue": "", "normalized_date": "2022-10-04", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature cell biology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Author Correction: LC3 lipidation is essential for TFEB activation during the lysosomal damage response to kidney injury.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Depression and its increasing prevalence challenge patients, the healthcare system, and the economy. We recently created a mouse model based on the three-hit concept of depression. As genetic predisposition (first hit), we applied pituitary adenylate cyclase-activating polypeptide heterozygous mice on CD1 background. Maternal deprivation modeled the epigenetic factor (second hit), and the chronic variable mild stress was the environmental factor (third hit). Fluoxetine treatment was applied to test the predictive validity of our model. We aimed to examine the dynamics of the epigenetic marker acetyl-lysine 9 H3 histone (H3K9ac) and the neuronal activity marker FOSB in the prefrontal cortex (PFC) and hippocampus. Fluoxetine decreased H3K9ac in PFC in non-deprived animals, but a history of maternal deprivation abolished the effect of stress and SSRI treatment on H3K9ac immunoreactivity. In the hippocampus, stress decreased, while SSRI increased H3K9ac immunosignal, unlike in the deprived mice, where the opposite effect was detected. FOSB in stress was stimulated by fluoxetine in the PFC, while it was inhibited in the hippocampus. The FOSB immunoreactivity was almost completely abolished in the hippocampus of the deprived mice. This study showed that FOSB and H3K9ac were modulated in a territory-specific manner by early life adversities and later life stress interacting with the effect of fluoxetine therapy supporting the reliability of our model.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tamas", "last_name": "Gaszner", "name": null }, { "creator_type": "author", "first_name": "Jozsef", "last_name": "Farkas", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Kun", "name": null }, { "creator_type": "author", "first_name": "Balazs", "last_name": "Ujvari", "name": null }, { "creator_type": "author", "first_name": "Nora", "last_name": "Furedi", "name": null }, { "creator_type": "author", "first_name": "Laszlo Akos", "last_name": "Kovacs", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Dora", "last_name": "Reglodi", "name": null }, { "creator_type": "author", "first_name": "Viktoria", "last_name": "Kormos", "name": null }, { "creator_type": "author", "first_name": "Balazs", "last_name": "Gaszner", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms231911739" }, "pmcid": { "normalized": "PMC9570135" }, "pmid": { "normalized": "36233039" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Depression", "descriptor_ui": "D003863", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Fluoxetine", "descriptor_ui": "D005473", "major_topic": true }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Lysine", "descriptor_ui": "D008239", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": true }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 3", "date_precision": "day", "issue": "19", "normalized_date": "2022-10-03", "pages": "11739", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "23", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Epigenetic and Neuronal Activity Markers Suggest the Recruitment of the Prefrontal Cortex and Hippocampus in the Three-Hit Model of Depression in Male PACAP Heterozygous Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chloroplast FoF1-ATP synthase (CFoCF1) uses an electrochemical gradient of protons across the thylakoid membrane (DeltamuH(+)) as an energy source in the ATP synthesis reaction. CFoCF1 activity is regulated by the redox state of a Cys pair on its central axis, i.e., the gamma subunit (CF1-gamma). When the DeltamuH(+) is formed by the photosynthetic electron transfer chain under light conditions, CF1-gamma is reduced by thioredoxin (Trx), and the entire CFoCF1 enzyme is activated. The redox regulation of CFoCF1 is a key mechanism underlying the control of ATP synthesis under light conditions. In contrast, the oxidative deactivation process involving CFoCF1 has not been clarified. In the present study, we analyzed the oxidation of CF1-gamma by two physiological oxidants in the chloroplast, namely the proteins Trx-like 2 and atypical Cys-His-rich Trx. Using the thylakoid membrane containing the reduced form of CFoCF1, we were able to assess the CF1-gamma oxidation ability of these Trx-like proteins. Our kinetic analysis indicated that these proteins oxidized CF1-gamma with a higher efficiency than that achieved by a chemical oxidant and typical chloroplast Trxs. Additionally, the CF1-gamma oxidation rate due to Trx-like proteins and the affinity between them were changed markedly when DeltamuH(+) formation across the thylakoid membrane was manipulated artificially. Collectively, these results indicate that the formation status of the DeltamuH(+) controls the redox regulation of CFoCF1 to prevent energetic disadvantages in plants.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takatoshi", "last_name": "Sekiguchi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbc.2022.102541" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36174673" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Chloroplast Proton-Translocating ATPases", "descriptor_ui": "D025222", "major_topic": true }, { "descriptor": "Chloroplasts", "descriptor_ui": "D002736", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Plants", "descriptor_ui": "D010944", "major_topic": false }, { "descriptor": "Protons", "descriptor_ui": "D011522", "major_topic": true }, { "descriptor": "Thioredoxins", "descriptor_ui": "D013879", "major_topic": true }, { "descriptor": "Thylakoids", "descriptor_ui": "D020524", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Sep 26", "date_precision": "day", "issue": "", "normalized_date": "2022-09-26", "pages": "102541", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Dissipation of the proton electrochemical gradient in chloroplasts promotes the oxidation of ATP synthase by thioredoxin-like proteins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Koichi", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Yukiya", "last_name": "Kurahashi", "name": null }, { "creator_type": "author", "first_name": "Hanako", "last_name": "Ishimaru", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Tohma", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Ohkita", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Sachiyo", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/infdis/jiac395" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36161491" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "COVID-19 Vaccines", "descriptor_ui": "D000086663", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Sep 26", "date_precision": "day", "issue": "", "normalized_date": "2022-09-26", "pages": "jiac395", "proceedings_title": null, "publisher": "", "title": "The Journal of infectious diseases", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "The number of COVID-19 vaccine doses and severe clinical outcomes in older patients infected with a SARS-CoV-2 Omicron variant.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The neural crest (NC) is an important multipotent embryonic cell population and its impaired specification leads to various developmental defects, often in an anteroposterior (A-P) axial level-specific manner. The mechanisms underlying the correct A-P regionalisation of human NC cells remain elusive. Recent studies have indicated that trunk NC cells, the presumed precursors of childhood tumour neuroblastoma, are derived from neuromesodermal-potent progenitors of the postcranial body. Here we employ human embryonic stem cell differentiation to define how neuromesodermal progenitor (NMP)-derived NC cells acquire a posterior axial identity. We show that TBXT, a pro-mesodermal transcription factor, mediates early posterior NC/spinal cord regionalisation together with WNT signalling effectors. This occurs by TBXT-driven chromatin remodelling via its binding in key enhancers within HOX gene clusters and other posterior regulator-associated loci. This initial posteriorisation event is succeeded by a second phase of trunk HOX gene control that marks the differentiation of NMPs toward their TBXT-negative NC/spinal cord derivatives and relies predominantly on FGF signalling. Our work reveals a previously unknown role of TBXT in influencing posterior NC fate and points to the existence of temporally discrete, cell type-dependent modes of posterior axial identity control.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Antigoni", "last_name": "Gogolou", "name": null }, { "creator_type": "author", "first_name": "Celine", "last_name": "Souilhol", "name": null }, { "creator_type": "author", "first_name": "Ilaria", "last_name": "Granata", "name": null }, { "creator_type": "author", "first_name": "Filip J.", "last_name": "Wymeersch", "name": null }, { "creator_type": "author", "first_name": "Ichcha", "last_name": "Manipur", "name": null }, { "creator_type": "author", "first_name": "Matthew", "last_name": "Wind", "name": null }, { "creator_type": "author", "first_name": "Thomas J. R.", "last_name": "Frith", "name": null }, { "creator_type": "author", "first_name": "Maria", "last_name": "Guarini", "name": null }, { "creator_type": "author", "first_name": "Alessandro", "last_name": "Bertero", "name": null }, { "creator_type": "author", "first_name": "Christoph", "last_name": "Bock", "name": null }, { "creator_type": "author", "first_name": "Florian", "last_name": "Halbritter", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null }, { "creator_type": "author", "first_name": "Mario R.", "last_name": "Guarracino", "name": null }, { "creator_type": "author", "first_name": "Anestis", "last_name": "Tsakiridis", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.74263" }, "pmcid": { "normalized": "PMC9536837" }, "pmid": { "normalized": "36154671" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": true }, { "descriptor": "Neural Crest", "descriptor_ui": "D009432", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Sep 26", "date_precision": "day", "issue": "", "normalized_date": "2022-09-26", "pages": "e74263", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "11", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have succeeded in visualizing the spatial heterogeneity of the reaction ratio in epoxy resins by combining medium-angle X-ray scattering (MAXS) and computed tomography (CT). The reaction ratio is proportional to the degree of cross-linking between epoxy and amine in epoxy resins. The reaction ratio and its spatial inhomogeneity affect the toughness of epoxy resins. However, there has been no non-destructive method to measure the spatial inhomogeneity of the reaction ratio, although we can measure only the spatially averaged reaction ratio by Fourier-transform infrared spectroscopy (FT-IR). We found that the scattering peak reflected the cross-linking structures in the q region of MAXS and that the peak intensity is proportional to the reaction ratio. By reconstructing CT images from this peak intensity, we visualized the spatial heterogeneity of the reaction ratio. The application of this method may not be limited to epoxy resins but may extend to studying the heterogeneity of cross-linked structures in other materials.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Mikihito", "last_name": "Takenaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.langmuir.2c01741" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36082480" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Sep 20", "date_precision": "day", "issue": "37", "normalized_date": "2022-09-20", "pages": "11432-11439", "proceedings_title": null, "publisher": "", "title": "Langmuir : the ACS journal of surfaces and colloids", "volume": "38", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatial Distribution of the Network Structure in Epoxy Resin via the MAXS-CT Method.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "It is known that the human cellular models of Alzheimer's disease (AD) and tauopathy can only recapitulate the very early stage of the disease. To overcome these limitations, we developed a technology to make forebrain organoids (FBOs) from feeder-free induced pluripotent stem cells (iPSC)s by regulating a FGF2 concentration and applied this method to generate FBOs from patients with familial AD (fAD FBOs). The obtained fAD FBOs recapitulated the amyloid-beta pathology and increased tau phosphorylation but not tau aggregates. To fully induce the tau pathology, FBOs were injected with adeno-associated virus (AAV)-expressing P301L mutant tau. In these Tau-P301L FBOs, tau fibrils were observed in the neuronal cell body and neurites with immunoelectron microscopy, in addition to the sarkosyl-insoluble and thioflavin S-positive phospho-tau aggregates. Collectively, this model can be used as a platform for investigating pathogenetic mechanisms and evaluation of target molecules for drug discovery for tauopathy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Aki", "last_name": "Shimozawa", "name": null }, { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Sachiyo", "last_name": "Miyao", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Kiyama", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Junro", "last_name": "Kuromitsu", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Aoyagi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.crmeth.2022.100289" }, "pmcid": { "normalized": "PMC9499998" }, "pmid": { "normalized": "36160042" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": true }, { "descriptor": "Dependovirus", "descriptor_ui": "D000229", "major_topic": false }, { "descriptor": "Gene Transfer Techniques", "descriptor_ui": "D018014", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "Prosencephalon", "descriptor_ui": "D016548", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Sep 19", "date_precision": "day", "issue": "9", "normalized_date": "2022-09-19", "pages": "100289", "proceedings_title": null, "publisher": "", "title": "Cell reports methods", "volume": "2", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "A next-generation iPSC-derived forebrain organoid model of tauopathy with tau fibrils by AAV-mediated gene transfer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Columnar structure is one of the most fundamental morphological features of the cerebral cortex and is thought to be the basis of information processing in higher animals. Yet, how such a topographically precise structure is formed is largely unknown. Formation of columnar projection of layer 4 (L4) axons is preceded by thalamocortical formation, in which type 1 cannabinoid receptors (CB1R) play an important role in shaping barrel-specific targeted projection by operating spike timing-dependent plasticity during development (Itami et al., J. Neurosci. 36, 7039–7054 [2016]; Kimura & Itami, J. Neurosci. 39, 3784–3791 [2019]). Right after the formation of thalamocortical projections, CB1Rs start to function at L4 axon terminals (Itami & Kimura, J. Neurosci. 32, 15000–15011 [2012]), which coincides with the timing of columnar shaping of L4 axons. Here, we show that the endocannabinoid 2-arachidonoylglycerol (2-AG) plays a crucial role in columnar shaping. We found that L4 axon projections were less organized until P12 and then became columnar after CB1Rs became functional. By contrast, the columnar organization of L4 axons was collapsed in mice genetically lacking diacylglycerol lipase α, the major enzyme for 2-AG synthesis. Intraperitoneally administered CB1R agonists shortened axon length, whereas knockout of CB1R in L4 neurons impaired columnar projection of their axons. Our results suggest that endocannabinoid signaling is crucial for shaping columnar axonal projection in the cerebral cortex.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Chiaki", "last_name": "Itami", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Jui-Yen", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Hui-Chen", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Kimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2122700119" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022-09-13", "date_precision": "day", "issue": "37", "normalized_date": "2022-09-13", "pages": "e2122700119", "proceedings_title": null, "publisher": "Proceedings of the National Academy of Sciences", "title": "Proceedings of the National Academy of Sciences", "volume": "119", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Endocannabinoid-dependent formation of columnar axonal projection in the mouse cerebral cortex", "url": "https://www.pnas.org/doi/full/10.1073/pnas.2122700119", "zotero": { "item_type": "journalArticle" } }, { "abstract": "SUMMARY: High-throughput chromosome conformation capture (Hi-C) is a widely used assay for studying the three-dimensional (3D) genome organization across the whole genome. Here, we present PHi-C2, a Python package supported by mathematical and biophysical polymer modeling that converts input Hi-C matrix data into the polymer model's dynamics, structural conformations, and rheological features. The updated optimization algorithm for regenerating a highly similar Hi-C matrix provides a fast and accurate optimal solution compared to the previous version by eliminating the factors underlying the inefficiency of the optimization algorithm in the iterative optimization process. In addition, we have enabled a Google Colab workflow to run the algorithm, wherein users can easily change the parameters and check the results in the notebook. Overall, PHi-C2 represents a valuable tool for mining the dynamic 3D genome state embedded in Hi-C data. AVAILABILITY AND IMPLEMENTATION: PHi-C2 as the phic Python package is freely available under the GPL license and can be installed from the Python package index. The source code is available from GitHub at https://github.com/soyashinkai/PHi-C2. Moreover, users do not have to prepare a Python environment because PHi-C2 can run on Google Colab (https://bit.ly/3rlptGI). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.", "classifications": [ { "id": "18H05412", "label": "18H05412", "researcher": "Shuichi Onami", "type": "grant" }, { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Itoga", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/bioinformatics/btac613" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36087002" } }, "mesh": [ { "descriptor": "Chromosomes", "descriptor_ui": "D002875", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": true }, { "descriptor": "Molecular Conformation", "descriptor_ui": "D008968", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Sep 10", "date_precision": "day", "issue": "", "normalized_date": "2022-09-10", "pages": "btac613", "proceedings_title": null, "publisher": "", "title": "Bioinformatics (Oxford, England)", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "PHi-C2: interpreting Hi-C data as the dynamic 3D genome state.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the fruit fly Drosophila melanogaster, environmental light is required for maintaining long-term memory (LTM). Furthermore, the Pigment dispersing factor (Pdf), which is a circadian neuropeptide, and the neuronal activity of Pdf neurons are essential for light-dependent maintenance of courtship LTM. Since Pdf neurons can sense light directly via circadian photoreceptors [Rhodopsin 7 (Rh7) and Cryptochrome (Cry)], it is possible that Rh7 and Cry in Pdf neurons are involved in the maintenance of LTM. In this study, using a courtship conditioning assay, we demonstrated that circadian photoreceptors in Pdf neurons are required for maintaining courtship LTM.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Show", "last_name": "Inami", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2022.09.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36096270" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Cryptochromes", "descriptor_ui": "D056931", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": true }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": true }, { "descriptor": "Memory, Long-Term", "descriptor_ui": "D057567", "major_topic": false }, { "descriptor": "Rhodopsin", "descriptor_ui": "D012243", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Sep 9", "date_precision": "day", "issue": "", "normalized_date": "2022-09-09", "pages": "S0168-0102(22)00236-X", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Circadian photoreceptors are required for light-dependent maintenance of long-term memory in Drosophila.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alzheimer's disease (AD) is the leading cause of dementia which afflicts tens of millions of people worldwide. Despite many scientific progresses to dissect the AD's molecular basis from studies on various mouse models, it has been suffered from evolutionary species differences. Here, we report generation of a non-human primate (NHP), common marmoset model ubiquitously expressing Amyloid-beta precursor protein (APP) transgenes with the Swedish (KM670/671NL) and Indiana (V717F) mutations. The transgene integration of generated two transgenic marmosets (TG1&TG2) was thoroughly investigated by genomic PCR, whole-genome sequencing, and fluorescence in situ hybridization. By reprogramming, we confirmed the validity of transgene expression in induced neurons in vitro. Moreover, we discovered structural changes in specific brain regions of transgenic marmosets by magnetic resonance imaging analysis, including in the entorhinal cortex and hippocampus. In immunohistochemistry, we detected increased Abeta plaque-like structures in TG1 brain at 7 years old, although evident neuronal loss or glial inflammation was not observed. Thus, this study summarizes our attempt to establish an NHP AD model. Although the transgenesis approach alone seemed not sufficient to fully recapitulate AD in NHPs, it may be beneficial for drug development and further disease modeling by combination with other genetically engineered models and disease-inducing approaches.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sho", "last_name": "Yoshimatsu", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Okahara", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Sasaguri", "name": null }, { "creator_type": "author", "first_name": "Yawara", "last_name": "Haga", "name": null }, { "creator_type": "author", "first_name": "Jun-Ichi", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Sanosaka", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Mineshige", "name": null }, { "creator_type": "author", "first_name": "Chia-Ying", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Shinohara", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Kurotaki", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Komaki", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Kishi", "name": null }, { "creator_type": "author", "first_name": "Ayaka Y.", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Minamimoto", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Mayutaka", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Zhi", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Akisa", "last_name": "Nemoto", "name": null }, { "creator_type": "author", "first_name": "Tsukika", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ikeuchi", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Shiozawa", "name": null }, { "creator_type": "author", "first_name": "Takaomi C.", "last_name": "Saido", "name": null }, { "creator_type": "author", "first_name": "Erika", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2022.08.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36075457" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": true }, { "descriptor": "Amyloid beta-Peptides", "descriptor_ui": "D016229", "major_topic": false }, { "descriptor": "Amyloid beta-Protein Precursor", "descriptor_ui": "D016564", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Callithrix", "descriptor_ui": "D002144", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "In Situ Hybridization, Fluorescence", "descriptor_ui": "D017404", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Transgenes", "descriptor_ui": "D019076", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Sep 6", "date_precision": "day", "issue": "", "normalized_date": "2022-09-06", "pages": "S0168-0102(22)00232-2", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Multimodal analyses of a non-human primate model harboring mutant amyloid precursor protein transgenes driven by the human EF1alpha promoter.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Interstitial pneumonia (IP) is a poor prognostic comorbidity in patients with non-small cell lung cancer (NSCLC) and is also a risk factor for pneumonitis. The TORG1936/AMBITIOUS trial, the first known phase II study of atezolizumab in patients with NSCLC with comorbid IP, was terminated early because of the high incidence of severe pneumonitis. METHODS: This study included patients with idiopathic chronic fibrotic IP, with a predicted forced vital capacity (%FVC) of >70%, with or without honeycomb lung, who had previously been treated for NSCLC. The patients received atezolizumab every 3 weeks. The primary endpoint was the 1-year survival rate. RESULTS: A total of 17 patients were registered; the median %FVC was 85.4%, and 41.2% had honeycomb lungs. The 1-year survival rate was 53.3% (95% CI, 25.9-74.6). The median overall and progression-free survival times were 15.3 months (95% CI, 3.1-not reached) and 3.2 months (95% CI, 1.2-7.4), respectively. The incidence of pneumonitis was 29.4% for all grades, and 23.5% for grade >/=3. Tumor mutational burden and any of the detected somatic mutations were not associated with efficacy or risk of pneumonitis. CONCLUSION: Atezolizumab may be one of the treatment options for patients with NSCLC with comorbid IP, despite the high risk of developing pneumonitis. This clinical trial was retrospectively registered in the Japan Registry of Clinical Trials on August 26, 2019, (registry number: jRCTs031190084, https://jrct.niph.go.jp/en-latest-detail/jRCTs031190084).", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Terufumi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hirotsugu", "last_name": "Kenmotsu", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Aoi", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Tokito", "name": null }, { "creator_type": "author", "first_name": "Isamu", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Furuya", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Shinobu", "last_name": "Hosokawa", "name": null }, { "creator_type": "author", "first_name": "Tae", "last_name": "Iwasawa", "name": null }, { "creator_type": "author", "first_name": "Rika", "last_name": "Kasajima", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Misumi", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Okamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/oncolo/oyac118" }, "pmcid": { "normalized": "PMC9438913" }, "pmid": { "normalized": "35759340" } }, "mesh": [ { "descriptor": "Antibodies, Monoclonal, Humanized", "descriptor_ui": "D061067", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Idiopathic Interstitial Pneumonias", "descriptor_ui": "D054988", "major_topic": true }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Pneumonia", "descriptor_ui": "D011014", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Sep 2", "date_precision": "day", "issue": "9", "normalized_date": "2022-09-02", "pages": "720-e702", "proceedings_title": null, "publisher": "", "title": "The oncologist", "volume": "27", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Atezolizumab for Pretreated Non-Small Cell Lung Cancer with Idiopathic Interstitial Pneumonia: Final Analysis of Phase II AMBITIOUS Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Solitary fibrous tumors (SFTs) are rare mesenchymal tumors that can occur at any location. Since the identification of specific NAB2-STAT6 fusion in SFTs, the fusion gene variants, NAB2 exon 4-STAT6 exon 2/3 and NAB2 exon 5/6/7-STAT6 exon 16/17/18, have been reported to be associated with clinicopathological features, and the latter variant is predominant in meningeal SFTs. SFTs developing in the salivary glands are rare, and more rarely, those involving ectopic salivary glands (ESGs) have been reported in the cerebellopontine angle (CPA); however, their characteristics remain not well understood. In this study, we performed a clinicopathological and molecular analysis of 3 cases of meningeal SFT with ESGs. All cases presented with an extra-axial mass in the CPA, which is a rarer location for intracranial ESGs compared to the sellar region. Histologically, except for the presence of ESGs, there was no significant difference between current cases and ordinary SFTs. The ESGs demonstrated no cellular atypia, and although the spindle tumor cells were immunopositive for STAT6, the ESGs were negative in all cases, supporting that the ESGs are non-neoplastic components. In 1 case, ESGs were found only in the primary tumor and disappeared in recurrence/dissemination. Of note, molecular analysis identified NAB2 exon 4-STAT6 exon 2 in all cases. In conclusion, our results suggest that ESGs particularly in the CPA may be associated with SFTs and that meningeal SFTs with ESGs may be associated with the minor fusion variant of NAB2-STAT6 in the intracranial lesions.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takahiro", "last_name": "Shirakura", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Bunsho", "last_name": "Asayama", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Seo", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Tanikawa", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Nobukazu", "last_name": "Komoribayashi", "name": null }, { "creator_type": "author", "first_name": "Naohiko", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Monma", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Okura", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yoshinao", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Hirato", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yokoo", "name": null }, { "creator_type": "author", "first_name": "Sumihito", "last_name": "Nobusawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00428-022-03403-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36056239" } }, "mesh": [ { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Cerebellopontine Angle", "descriptor_ui": "D002530", "major_topic": false }, { "descriptor": "Gene Fusion", "descriptor_ui": "D050939", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Meningeal Neoplasms", "descriptor_ui": "D008577", "major_topic": true }, { "descriptor": "Oncogene Proteins, Fusion", "descriptor_ui": "D015514", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Salivary Glands", "descriptor_ui": "D012469", "major_topic": false }, { "descriptor": "Soft Tissue Neoplasms", "descriptor_ui": "D012983", "major_topic": true }, { "descriptor": "Solitary Fibrous Tumors", "descriptor_ui": "D054364", "major_topic": true }, { "descriptor": "STAT6 Transcription Factor", "descriptor_ui": "D050800", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Sep 2", "date_precision": "day", "issue": "", "normalized_date": "2022-09-02", "pages": "", "proceedings_title": null, "publisher": "", "title": "Virchows Archiv : an international journal of pathology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Analysis of clinicopathological features and NAB2-STAT6 fusion variants of meningeal solitary fibrous tumor with ectopic salivary gland components in the cerebellopontine angle.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell competition is a process by which unwanted cells are eliminated from tissues. Apical extrusion is one mode whereby normal epithelial cells remove transformed cells, but it remains unclear how this process is mechanically effected. In this study, we show that autophagic and endocytic fluxes are attenuated in RasV12-transformed cells surrounded by normal cells due to lysosomal dysfunction, and that chemical manipulation of lysosomal activity compromises apical extrusion. We further find that RasV12 cells deficient in autophagy initiation machinery are resistant to elimination pressure exerted by normal cells, suggesting that non-degradable autophagic vacuoles are required for cell competition. Moreover, in vivo analysis revealed that autophagy-ablated RasV12 cells are less readily eliminated by cell competition, and remaining transformed cells destroy ductal integrity, leading to chronic pancreatitis. Collectively, our findings illuminate a positive role for autophagy in cell competition and reveal a homeostasis-preserving function of autophagy upon emergence of transformed cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Eilma", "last_name": "Akter", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Tasaki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Hachiya", "name": null }, { "creator_type": "author", "first_name": "Hancheng", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Masamitsu", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Kamasaki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Yamano", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kon", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2022.111292" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36044857" } }, "mesh": [ { "descriptor": "Autophagosomes", "descriptor_ui": "D000071182", "major_topic": false }, { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": false }, { "descriptor": "Cell Competition", "descriptor_ui": "D000084502", "major_topic": true }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Lysosomes", "descriptor_ui": "D008247", "major_topic": false }, { "descriptor": "Vacuoles", "descriptor_ui": "D014617", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Aug 30", "date_precision": "day", "issue": "9", "normalized_date": "2022-08-30", "pages": "111292", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "40", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Non-degradable autophagic vacuoles are indispensable for cell competition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Several methods are used for hearing loss screening; however, their benefits are uncertain. In this study, we aimed to determine the predictive factors of acute sensorineural hearing loss for clinical application by primary care doctors. METHODS: This retrospective, cross-sectional study included 365 patients with acute sensorineural hearing loss without prior therapy. The patients' clinical data, demographic information, and medical histories were obtained, and they were asked about comorbidities. In addition, we assessed lifestyle factors such as stress level, alcohol consumption, marital status, and socioeconomic level. Logistic regression analysis was performed to investigate the diagnostic predictive ability of the selected factors associated with acute sensorineural hearing loss. The hearing levels of all patients were evaluated using pure tone audiometry. RESULTS: We identified significant predictive factors for acute sensorineural hearing loss. The absence of hyperacusis was a predictive factor for sudden sensorineural hearing loss. Younger age, female sex, and marital status were predictive factors for acute low-tone hearing loss. High body mass index, high socioeconomic level, low alcohol consumption, high stress level, hyperacusis, and vertigo/dizziness were predictive factors for Ménière's disease. High body mass index and ear fullness were predictive factors for perilymph fistula. Low stress level was a predictive factor for acoustic tumours. CONCLUSIONS: Our findings can be used to distinguish between the types of acute sensorineural hearing loss. Symptoms, physical status, and lifestyle factors identified during this study are useful markers for predicting acute sensorineural hearing loss occurrence.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Toru", "last_name": "Miwa", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Osaka", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Maetani", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Kanemaru", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12875-022-01830-8" }, "pmcid": { "normalized": "PMC9429655" }, "pmid": { "normalized": "36042422" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hearing Loss, Sensorineural", "descriptor_ui": "D006319", "major_topic": true }, { "descriptor": "Hearing Loss, Sudden", "descriptor_ui": "D003639", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hyperacusis", "descriptor_ui": "D012001", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Primary Health Care", "descriptor_ui": "D011320", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Aug 30", "date_precision": "day", "issue": "1", "normalized_date": "2022-08-30", "pages": "219", "proceedings_title": null, "publisher": "", "title": "BMC primary care", "volume": "23", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Predictive factors of acute sensorineural hearing loss in adult Japanese patients for clinical application by primary care doctors: a cross-sectional study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Abnormal/cancerous cells within healthy epithelial tissues undergo apical extrusion to protect against carcinogenesis, although they acquire invasive capacity once carcinogenesis progresses. However, the molecular mechanisms by which cancer cells escape from apical extrusion and invade surrounding tissues remain elusive. In this study, we demonstrate a molecular mechanism for cell fate switching during epithelial cell competition. We found that during competition within epithelial cell layers, Src transformation promotes maturation of focal adhesions and degradation of extracellular matrix. Src-transformed cells underwent basal delamination by Src activation within sphingolipid/cholesterol-enriched membrane microdomains/lipid rafts, whereas they were apically extruded when Src was outside of lipid rafts. A comparative analysis of contrasting phenotypes revealed that activation of the Src-STAT3-MMP axis through lipid rafts was required for basal delamination. CUB-domain-containing protein 1 (CDCP1) was identified as an Src-activating scaffold and as a Met regulator in lipid rafts, and its overexpression induced basal delamination. In renal cancer models, CDCP1 promoted epithelial-mesenchymal transition-mediated invasive behavior by activating the Src-STAT3-MMP axis through Met activation. Overall, these results suggest that spatial activation of Src signaling in lipid rafts confers resistance to apical extrusion and invasive potential on epithelial cells to promote carcinogenesis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kajiwara", "name": null }, { "creator_type": "author", "first_name": "Ping-Kuan", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kon", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Tomonaga", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2022.06.038" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35809567" } }, "mesh": [ { "descriptor": "Antigens, Neoplasm", "descriptor_ui": "D000951", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Cell Adhesion Molecules", "descriptor_ui": "D015815", "major_topic": false }, { "descriptor": "Cell Competition", "descriptor_ui": "D000084502", "major_topic": true }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Membrane Microdomains", "descriptor_ui": "D021962", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Aug 22", "date_precision": "day", "issue": "16", "normalized_date": "2022-08-22", "pages": "3460-3476.e6", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "32", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Src activation in lipid rafts confers epithelial cells with invasive potential to escape from apical extrusion during cell competition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Qingbo S.", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Ryuya", "last_name": "Edahiro", "name": null }, { "creator_type": "author", "first_name": "Ho", "last_name": "Namkoong", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Kyuto", "last_name": "Sonehara", "name": null }, { "creator_type": "author", "first_name": "Hiromu", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ho", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Ryunosuke", "last_name": "Saiki", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Hyugaji", "name": null }, { "creator_type": "author", "first_name": "Eigo", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Kotoe", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Noah", "last_name": "Sasa", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Norihiro", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Hiki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Haruhi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Sonoko", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yuuki", "last_name": "Sandhu", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kabata", "name": null }, { "creator_type": "author", "first_name": "Katsunori", "last_name": "Masaki", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Kamata", "name": null }, { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Ikemura", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Chubachi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Okamori", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Atsuho", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Asakura", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Morisaki", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Uwamino", "name": null }, { "creator_type": "author", "first_name": "Kosaku", "last_name": "Nanki", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Uno", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Takashri", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Isono", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yuma", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Hosoda", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yotaro", "last_name": "Takaku", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Takayanagi", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Masaomi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Reina", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Nagasaka", "name": null }, { "creator_type": "author", "first_name": "Sawako", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Tagaya", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Kawana", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Arimura", "name": null }, { "creator_type": "author", "first_name": "Kunihiko", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Anzai", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Uchimura", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Tateishi", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Tohda", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Sonobe", "name": null }, { "creator_type": "author", "first_name": "Chihiro Tani", "last_name": "Sassa", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Ryusuke", "last_name": "Anan", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Toshikatsu", "last_name": "Sado", "name": null }, { "creator_type": "author", "first_name": "Yoshimune", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Haruta", "name": null }, { "creator_type": "author", "first_name": "Tadao", "last_name": "Nagasaki", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Mutoh", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Reoto", "last_name": "Takei", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Hagimoto", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Yamano", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Sasano", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Nakamori", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Yoshiya", "name": null }, { "creator_type": "author", "first_name": "Fukuki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Hiromu", "last_name": "Iwamura", "name": null }, { "creator_type": "author", "first_name": "Syuji", "last_name": "Kanayama", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yoshiyama", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kokuto", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Arakawa", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Shimoda", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Osawa", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Tateno", "name": null }, { "creator_type": "author", "first_name": "Isano", "last_name": "Hase", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Hirohisa", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Fumitake", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Mitamura", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Hagihara", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Ochi", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Hagiwara", "name": null }, { "creator_type": "author", "first_name": "Genta", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Shunichiro", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Nakachi", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Hisatoshi", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Hirohito", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Shuichiro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yoshinao", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Sohei", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Masuzawa", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Namba", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Shiroyama", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Niitsu", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Takatoshi", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Amiya", "name": null }, { "creator_type": "author", "first_name": "Reina", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Teruaki", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Kuge", "name": null }, { "creator_type": "author", "first_name": "Kinnosuke", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Midori", "last_name": "Yoneda", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Tomono", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Hirata", "name": 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"first_name": "Masayuki", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Masakiyo", "last_name": "Yatomi", "name": null }, { "creator_type": "author", "first_name": "Toshitaka", "last_name": "Maeno", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Kuramochi", "name": null }, { "creator_type": "author", "first_name": "Isamu", "last_name": "Kamimaki", "name": null }, { "creator_type": "author", "first_name": "Yoshiteru", "last_name": "Tominaga", "name": null }, { "creator_type": "author", "first_name": "Tomoo", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Mitsuyoshi", "last_name": "Utsugi", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takeru", "last_name": "Kashiwada", "name": null }, { "creator_type": "author", "first_name": "Kazue", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Seike", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Matsuse", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Kodaka", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Oshio", "name": null }, { "creator_type": "author", "first_name": "Takatomo", "last_name": "Hirouchi", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Makino", "name": null }, { "creator_type": "author", "first_name": "Moritoki", "last_name": "Egi", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Omae", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Nannya", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Ai", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kumanogoh", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Katsushi", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Miyano", "name": null }, { "creator_type": "author", "first_name": "Seishi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fukunaga", "name": null }, { "creator_type": "author", "first_name": "Yukinori", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-022-32276-2" }, "pmcid": { "normalized": "PMC9395416" }, "pmid": { "normalized": "35995775" } }, "mesh": [ { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Lectins, C-Type", "descriptor_ui": "D037181", "major_topic": false }, { "descriptor": "Membrane Glycoproteins", "descriptor_ui": "D008562", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Quantitative Trait Loci", "descriptor_ui": "D040641", "major_topic": false }, { "descriptor": "Receptors, Immunologic", "descriptor_ui": "D011971", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Aug 22", "date_precision": "day", "issue": "1", "normalized_date": "2022-08-22", "pages": "4830", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Extracellular vesicles (EVs) are essential intercellular communication tools, but the regulatory mechanisms governing heterogeneous EV secretion are still unclear due to the lack of methods for precise analysis. Monitoring the dynamics of secretion from individually isolated cells is crucial because in bulk analysis, secretion activity can be perturbed by cell-cell interactions, and a cell population rarely performs secretion in a magnitude- or duration-synchronized manner. Although various microfluidic techniques have been adopted to evaluate the abundance of single-cell-derived EVs, none can track their secretion dynamics continually for extended periods. Here, we have developed a droplet array-based method that allowed us to optically quantify the EV secretion dynamics of >300 single cells every 2 h for 36 h, which covers the cell doubling time of many cell types. The experimental results clearly show the highly heterogeneous nature of single-cell EV secretion and suggest that cell division facilitates EV secretion, showing the usefulness of this platform for discovering EV regulation machinery.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuki", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Goda", "name": null }, { "creator_type": "author", "first_name": "Minato", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.2c01609" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35797226" } }, "mesh": [ { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Extracellular Vesicles", "descriptor_ui": "D000067128", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Aug 16", "date_precision": "day", "issue": "32", "normalized_date": "2022-08-16", "pages": "11209-11215", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "94", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Droplet Array-Based Platform for Parallel Optical Analysis of Dynamic Extracellular Vesicle Secretion from Single Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Considering the vulnerability of silica gel to alkaline mobile phases, a highly alkaline stable stationary phase for HPLC is required to separate basic compounds with high separation efficiency. To address this issue, we have developed a high alkaline stable packing material (CaCO3-PMAcO) based on mesoporous calcium carbonate microspheres modified with poly(maleic acid-alt-1-octadecene). In this study, we report further investigation of the separation performance of CaCO3-PMAcO column by systematically evaluating the effects of particle size and chromatographic conditions. Based on the theory of the van Deemter equation, the separation efficiency was related to the size of CaCO3-PMAcO particles (2.9 - 5.7 microm). The evaluation of thermodynamics of retention by changing the column temperature from 20 degrees C to 45 degrees C implied that the retention mode was dominated by hydrophobic interaction associated with the exothermic enthalpy changes (-11.1 to -12.5 kJ/mol). The results of column selectivity tests revealed that the CaCO3-PMAcO column had hydrophobic selectivity comparable to C18 silica gel columns (alphaP/B; CaCO3-PMAcO column: 1.53, C18 column: 1.69), and higher shape/steric selectivity (alphaTri/Ter; CaCO3-PMAcO column: 1.56, C18 column: 0.955). In practice, the CaCO3-PMAcO column could be applied to the separation of not only alkylbenzenes and polycyclic aromatic hydrocarbons, but also to basic tricyclic antidepressants by using an alkaline mobile phase (pH 12).", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kogi", "last_name": "Kaizu", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Mochida", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chroma.2022.463294" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35809518" } }, "mesh": [ { "descriptor": "Calcium Carbonate", "descriptor_ui": "D002119", "major_topic": true }, { "descriptor": "Chromatography, High Pressure Liquid", "descriptor_ui": "D002851", "major_topic": false }, { "descriptor": "Chromatography, Reverse-Phase", "descriptor_ui": "D056148", "major_topic": true }, { "descriptor": "Hydrophobic and Hydrophilic Interactions", "descriptor_ui": "D057927", "major_topic": false }, { "descriptor": "Microspheres", "descriptor_ui": "D008863", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Silica Gel", "descriptor_ui": "D058428", "major_topic": false }, { "descriptor": "Silicon Dioxide", "descriptor_ui": "D012822", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Aug 16", "date_precision": "day", "issue": "", "normalized_date": "2022-08-16", "pages": "463294", "proceedings_title": null, "publisher": "", "title": "Journal of chromatography. A", "volume": "1677", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative evaluation of reversed-phase packing material based on calcium carbonate microspheres modified with an alternating copolymer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Expectations for neural stem/progenitor cell (NS/PC) transplantation as a treatment for spinal cord injury (SCI) are increasing. However, whether and how grafted cells are incorporated into the host neural circuit and contribute to motor function recovery remain unknown. The aim of this project was to establish a novel non-invasive in vivo imaging system to visualize the activity of neural grafts by which we can simultaneously demonstrate the circuit-level integration between the graft and host and the contribution of graft neuronal activity to host behaviour. We introduced Akaluc, a newly engineered luciferase, under the control of enhanced synaptic activity-responsive element (E-SARE), a potent neuronal activity-dependent synthetic promoter, into NS/PCs and engrafted the cells into SCI model mice. Through the use of this system, we found that the activity of grafted cells was integrated with host behaviour and driven by host neural circuit inputs. This non-invasive system is expected to help elucidate the therapeutic mechanism of cell transplantation treatment for SCI.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kentaro", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Narihito", "last_name": "Nagoshi", "name": null }, { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Momotaro", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Kajikawa", "name": null }, { "creator_type": "author", "first_name": "Reo", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kamata", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Munehisa", "last_name": "Shinozaki", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Iwano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Masanari", "last_name": "Ohtsuka", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Bito", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Kohyama", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-022-03736-8" }, "pmcid": { "normalized": "PMC9365819" }, "pmid": { "normalized": "35948599" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": true }, { "descriptor": "Recovery of Function", "descriptor_ui": "D020127", "major_topic": false }, { "descriptor": "Spinal Cord Injuries", "descriptor_ui": "D013119", "major_topic": true }, { "descriptor": "Stem Cell Transplantation", "descriptor_ui": "D033581", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Aug 10", "date_precision": "day", "issue": "1", "normalized_date": "2022-08-10", "pages": "803", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "5", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "A non-invasive system to monitor in vivo neural graft activity after spinal cord injury.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Clec1A, a member of C-type lectin receptor family, has a carbohydrate recognition domain in its extracellular region, but no known signaling motif in the cytoplasmic domain. Clec1a is highly expressed in endothelial cells and weakly in dendritic cells. Although this molecule was reported to play an important role in the host defense against Aspergillus fumigatus by recognizing 1,8-dihydroxynaphthalene-melanin on the fungal surface, the roles of this molecule in un-infected animals remain to be elucidated. In this study, we found that Clec1a(-/-) mice develop milder symptoms upon induction of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. The maximum disease score was significantly lower, and demyelination and inflammation of the spinal cord were much milder in Clec1a(-/-) mice compared to wild-type mice. No abnormality was detected in the immune cell composition in the draining lymph nodes and spleen on day 10 and 16 after EAE induction. Recall memory T cell proliferation after restimulation with myelin oligodendrocyte glycoprotein peptide (MOG35-55) in vitro was decreased in Clec1a(-/-) mice, and antigen presenting ability of Clec1a(-/-) dendritic cells was impaired. Interestingly, RNA-Seq and RT-qPCR analyses clearly showed that the expression of inflammatory cytokines including Il17a, Il6 and Il1b was greatly decreased in Clec1a(-/-) mice after induction of EAE, suggesting that this reduced cytokine production is responsible for the amelioration of EAE in Clec1a(-/-) mice. These observations suggest a novel function of Clec1A in the immune system.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yulia", "last_name": "Makusheva", "name": null }, { "creator_type": "author", "first_name": "Soo-Hyun", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Aoi", "last_name": "Akitsu", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Xiao-Qi", "last_name": "Ye", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Kaifu", "name": null }, { "creator_type": "author", "first_name": "Shinobu", "last_name": "Saijo", "name": null }, { "creator_type": "author", "first_name": "Haiyang", "last_name": "Sun", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Ce", "last_name": "Tang", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Iwakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1538/expanim.21-0191" }, "pmcid": { "normalized": "PMC9388343" }, "pmid": { "normalized": "35135958" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigen Presentation", "descriptor_ui": "D017951", "major_topic": true }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": true }, { "descriptor": "Encephalomyelitis, Autoimmune, Experimental", "descriptor_ui": "D004681", "major_topic": true }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Interleukin-17", "descriptor_ui": "D020381", "major_topic": true }, { "descriptor": "Lectins, C-Type", "descriptor_ui": "D037181", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Aug 5", "date_precision": "day", "issue": "3", "normalized_date": "2022-08-05", "pages": "288-304", "proceedings_title": null, "publisher": "", "title": "Experimental animals", "volume": "71", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "The C-type lectin receptor Clec1A plays an important role in the development of experimental autoimmune encephalomyelitis by enhancing antigen presenting ability of dendritic cells and inducing inflammatory cytokine IL-17.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A small number of oncogenic mutated cells sporadically arise within the epithelial monolayer. Newly emerging Ras- or Src-transformed epithelial cells are often apically eliminated during competitive interactions between normal and transformed cells. Our recent electron microscopy (EM) analyses revealed that characteristic finger-like membrane protrusions are formed at the interface between normal and RasV12-transformed cells via the cdc42-formin-binding protein 17 (FBP17) pathway, potentially playing a positive role in intercellular recognition during apical extrusion. However, the spatial distribution and ultrastructural characteristics of finger-like protrusions remain unknown. In this study, we performed both X-Y and X-Z EM analyses of finger-like protrusions during the apical extrusion of RasV12-transformed cells. Quantification of the distribution and widths of the protrusions showed comparable results between the X-Y and X-Z sections. Finger-like protrusions were observed throughout the cell boundary between normal and RasV12 cells, except for apicalmost tight junctions. In addition, a non-cell-autonomous reduction in protrusion widths was observed between RasV12 cells and surrounding normal cells under the mix culture condition. In the finger-like protrusions, intercellular adhesions via thin electron-dense plaques were observed, implying that immature and transient forms of desmosomes, adherens junctions or unknown weak adhesions were distributed. Interestingly, unlike RasV12-transformed cells, Src-transformed cells form fewer evident protrusions, and FBP17 in Src cells is dispensable for apical extrusion. Collectively, these results suggest that the dynamic reorganization of intercellular adhesions via finger-like protrusions may positively control cell competition between normal and RasV12-transformed cells. Furthermore, our data indicate a cell context-dependent diversity in the modes of apical extrusion.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tomoko", "last_name": "Kamasaki", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jmicro/dfac017" }, "pmcid": { "normalized": "PMC9340795" }, "pmid": { "normalized": "35394538" } }, "mesh": [ { "descriptor": "Cell Competition", "descriptor_ui": "D000084502", "major_topic": true }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": true }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Aug 1", "date_precision": "day", "issue": "4", "normalized_date": "2022-08-01", "pages": "195-205", "proceedings_title": null, "publisher": "", "title": "Microscopy (Oxford, England)", "volume": "71", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Ultrastructural characteristics of finger-like membrane protrusions in cell competition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Some attempts have been made to detect atrial fibrillation (AF) with a wearable device equipped with photoelectric volumetric pulse wave technology, and it is expected to be applied under real clinical conditions. OBJECTIVE: This study is the second part of a 2-phase study aimed at developing a method for immediate detection of paroxysmal AF, using a wearable device with built-in photoplethysmography (PPG). The objective of this study is to develop an algorithm to immediately diagnose AF by an Apple Watch equipped with a PPG sensor that is worn by patients undergoing cardiac surgery and to use machine learning on the pulse data output from the device. METHODS: A total of 80 patients who underwent cardiac surgery at a single institution between June 2020 and March 2021 were monitored for postoperative AF, using a telemetry-monitored electrocardiogram (ECG) and an Apple Watch. AF was diagnosed by qualified physicians from telemetry-monitored ECGs and 12-lead ECGs; a diagnostic algorithm was developed using machine learning on the pulse rate data output from the Apple Watch. RESULTS: One of the 80 patients was excluded from the analysis due to redness caused by wearing the Apple Watch. Of 79 patients, 27 (34.2%) developed AF, and 199 events of AF including brief AF were observed. Of them, 18 events of AF lasting longer than 1 hour were observed, and cross-correlation analysis showed that pulse rate measured by Apple Watch was strongly correlated (cross-correlation functions [CCF]: 0.6-0.8) with 8 events and very strongly correlated (CCF>0.8) with 3 events. The diagnostic accuracy by machine learning was 0.9416 (sensitivity 0.909 and specificity 0.838 at the point closest to the top left) for the area under the receiver operating characteristic curve. CONCLUSIONS: We were able to safely monitor pulse rate in patients who wore an Apple Watch after cardiac surgery. Although the pulse rate measured by the PPG sensor does not follow the heart rate recorded by telemetry-monitored ECGs in some parts, which may reduce the accuracy of AF diagnosis by machine learning, we have shown the possibility of clinical application of using only the pulse rate collected by the PPG sensor for the early detection of AF.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Inui", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Oya", "name": null }, { "creator_type": "author", "first_name": "Ayumu", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Koya", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Yoshihito", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shiko", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Yakita", "name": null }, { "creator_type": "author", "first_name": "Goro", "last_name": "Matsumiya", "name": null } ], "identifiers": { "doi": { "normalized": "10.2196/35396" }, "pmcid": { "normalized": "PMC9379796" }, "pmid": { "normalized": "35916709" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Aug 1", "date_precision": "day", "issue": "8", "normalized_date": "2022-08-01", "pages": "e35396", "proceedings_title": null, "publisher": "", "title": "JMIR formative research", "volume": "6", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Diagnosis of Atrial Fibrillation Using Machine Learning With Wearable Devices After Cardiac Surgery: Algorithm Development Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Oral leukoplakia, which presents as white lesions in the oral cavity, including on the tongue, is precancerous in nature. Conservative treatment is preferable, since surgical removal can markedly reduce the patient's quality of life. In the present study, we focused on the flavonoid apigenin as a potential compound for preventing carcinogenesis, and an apigenin-loaded mucoadhesive oral film was prepared using a three-dimensional (3D) bioprinter (semi-solid extrusion-type 3D printer). Apigenin-loaded printer inks are composed of pharmaceutical excipients (HPMC, CARBOPOL, and Poloxamer), water, and ethanol to dissolve apigenin, and the appropriate viscosity of printer ink after adjusting the ratios allowed for the successful 3D printing of the film. After drying the 3D-printed object, the resulting film was characterized. The chemopreventive effect of the apigenin-loaded film was evaluated using an experimental rat model that had been exposed to 4-nitroquinoline 1-oxide (4NQO) to induce oral carcinogenesis. Treatment with the apigenin-loaded film showed a remarkable chemopreventive effect based on an analysis of the specimen by immunohistostaining. These results suggest that the apigenin-loaded mucoadhesive film may help prevent carcinogenesis. This successful preparation of apigenin-loaded films by a 3D printer provides useful information for automatically fabricating other tailored films (with individual doses and shapes) for patients with oral leukoplakia in a future clinical setting.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Tatsuaki", "last_name": "Tagami", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Heeju", "last_name": "Pae", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Ozeki", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Shibuya", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/pharmaceutics14081575" }, "pmcid": { "normalized": "PMC9415331" }, "pmid": { "normalized": "36015201" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Jul 28", "date_precision": "day", "issue": "8", "normalized_date": "2022-07-28", "pages": "", "proceedings_title": null, "publisher": "", "title": "Pharmaceutics", "volume": "14", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Three-Dimensional Printing of an Apigenin-Loaded Mucoadhesive Film for Tailored Therapy to Oral Leukoplakia and the Chemopreventive Effect on a Rat Model of Oral Carcinogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Machine learning can predict outcomes and determine variables contributing to precise prediction, and can thus classify patients with different risk factors of outcomes. This study aimed to investigate the predictive accuracy for mortality and length of stay in intensive care unit (ICU) patients using machine learning, and to identify the variables contributing to the precise prediction or classification of patients. Patients (n = 12,747) admitted to the ICU at Chiba University Hospital were randomly assigned to the training and test cohorts. After learning using the variables on admission in the training cohort, the area under the curve (AUC) was analyzed in the test cohort to evaluate the predictive accuracy of the supervised machine learning classifiers, including random forest (RF) for outcomes (primary outcome, mortality; secondary outcome, length of ICU stay). The rank of the variables that contributed to the machine learning prediction was confirmed, and cluster analysis of the patients with risk factors of mortality was performed to identify the important variables associated with patient outcomes. Machine learning using RF revealed a high predictive value for mortality, with an AUC of 0.945 (95% confidence interval [CI] 0.922-0.977). In addition, RF showed high predictive value for short and long ICU stays, with AUCs of 0.881 (95% CI 0.876-0.908) and 0.889 (95% CI 0.849-0.936), respectively. Lactate dehydrogenase (LDH) was identified as a variable contributing to the precise prediction in machine learning for both mortality and length of ICU stay. LDH was also identified as a contributing variable to classify patients into sub-populations based on different risk factors of mortality. The machine learning algorithm could predict mortality and length of stay in ICU patients with high accuracy. LDH was identified as a contributing variable in mortality and length of ICU stay prediction and could be used to classify patients based on mortality risk.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shinya", "last_name": "Iwase", "name": null }, { "creator_type": "author", "first_name": "Taka-Aki", "last_name": "Nakada", "name": null }, { "creator_type": "author", "first_name": "Tadanaga", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Oami", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shimazui", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Yamabe", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Yamao", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-17091-5" }, "pmcid": { "normalized": "PMC9334583" }, "pmid": { "normalized": "35902633" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": true }, { "descriptor": "Area Under Curve", "descriptor_ui": "D019540", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intensive Care Units", "descriptor_ui": "D007362", "major_topic": true }, { "descriptor": "Length of Stay", "descriptor_ui": "D007902", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Mortality", "descriptor_ui": "D009026", "major_topic": true }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jul 28", "date_precision": "day", "issue": "1", "normalized_date": "2022-07-28", "pages": "12912", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Prediction algorithm for ICU mortality and length of stay using machine learning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Despite improved sensitivity of nanothermometers, direct observation of heat transport inside single cells has remained challenging for the lack of high-speed temperature imaging techniques. Here, we identified insufficient temperature resolution under short signal integration time and slow sensor kinetics as two major bottlenecks. To overcome the limitations, we developed B-gTEMP, a nanothermometer based on the tandem fusion of mNeonGreen and tdTomato fluorescent proteins. We visualized the propagation of heat inside intracellular space by tracking the temporal variation of local temperature at a time resolution of 155 mus and a temperature resolution 0.042 degrees C. By comparing the fast in situ temperature dynamics with computer-simulated heat diffusion, we estimated the thermal diffusivity of live HeLa cells. The present thermal diffusivity in cells was about 1/5.3 of that of water and much smaller than the values reported for bulk tissues, which may account for observations of heterogeneous intracellular temperature distributions.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kai", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Tetsuichi", "last_name": "Wazawa", "name": null }, { "creator_type": "author", "first_name": "Joe", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Cong Quang", "last_name": "Vu", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kamei", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.nanolett.2c00608" }, "pmcid": { "normalized": "PMC9335883" }, "pmid": { "normalized": "35792763" } }, "mesh": [ { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Hot Temperature", "descriptor_ui": "D006358", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jul 27", "date_precision": "day", "issue": "14", "normalized_date": "2022-07-27", "pages": "5698-5707", "proceedings_title": null, "publisher": "", "title": "Nano letters", "volume": "22", "year": 2022 }, "ssbd": { "database": [ "ssbd-database-000259" ], "repository": [ "ssbd-repos-000259" ] }, "title": "Intracellular Heat Transfer and Thermal Property Revealed by Kilohertz Temperature Imaging with a Genetically Encoded Nanothermometer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cellular senescence and cell competition are important tumor suppression mechanisms that restrain cells with oncogenic mutations at the initial stage of cancer development. However, the link between cellular senescence and cell competition remains unclear. Senescent cells accumulated during the in vivo aging process contribute toward age-related cancers via the development of senescence-associated secretory phenotype (SASP). Here, we report that hepatocyte growth factor (HGF), a SASP factor, inhibits apical extrusion and promotes basal protrusion of Ras-mutated cells in the cell competition assay. Additionally, cellular senescence induced by a high-fat diet promotes the survival of cells with oncogenic mutations, whereas crizotinib, an inhibitor of HGF signaling, provokes the removal of mutated cells from mouse livers and intestines. Our study provides evidence that cellular senescence inhibits cell competition-mediated elimination of oncogenic cells through HGF signaling, suggesting that it may lead to cancer incidence during aging.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Nanase", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Tze Mun", "last_name": "Loo", "name": null }, { "creator_type": "author", "first_name": "Masatomo", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Aki", "last_name": "Hanyu", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Hao", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Toyokuni", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kon", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Moriyama", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-022-31642-4" }, "pmcid": { "normalized": "PMC9293948" }, "pmid": { "normalized": "35851277" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Cell Competition", "descriptor_ui": "D000084502", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": false }, { "descriptor": "Hepatocyte Growth Factor", "descriptor_ui": "D017228", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Oncogenes", "descriptor_ui": "D009857", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jul 18", "date_precision": "day", "issue": "1", "normalized_date": "2022-07-18", "pages": "4157", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Hepatocyte growth factor derived from senescent cells attenuates cell competition-induced apical elimination of oncogenic cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Antibodies that block interaction between PD-1 and PD-1 ligands (anti-PD-1) are in clinical use for treatment of cancer, yet the efficacy of which is limited. Pre-approved therapies that enhance the effect of anti-PD-1 in combination are beneficial. Small molecule inhibitors that attenuate T cell receptor signaling are reported to prevent T cell exhaustion, induce memory T cells with stem cell potential, resulting in durable effector T cell response in combination with anti-PD-1. In search of such targets, we focused on protein kinase D (PKD) which is suggested to be suppressive in both tumor growth and TCR signaling. We report that CRT0066101, a PKD inhibitor (PKDi) suppressed growth of mouse tumor at sub-micromolar concentration in vitro. Despite its inhibitory effects on tumors, a single treatment of tumor bearing mice with PKDi did not inhibit, but rather accelerated tumor growth, and reversed the therapeutic effect of anti-PD-1. Mice treated with PKDi showed reduced T cell infiltration and defects in generation of effector T cells, compared to that treated with anti-PD-1, suggesting that PKDi inhibited ongoing antitumor responses. Mechanistically, PKDi inhibited phosphorylation of AKT, a primary checkpoint that is reactivated by anti-PD-1. In conclusion, PKD is fundamentally required for T-cell reactivation by anti-PD-1, therefore inhibition of PKD is not appropriate for combination therapy with anti-PD-1. On the other hand, a single dose of PKDi was shown to strongly suppress experimental autoimmunity in mice, indicating that PKDi could be useful for treatment of immune related adverse events, that are frequently reported in anti-PD-1 therapy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhide", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Hodaka", "last_name": "Hayabuchi", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Tokifuji", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Onishi", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/intimm/dxac035" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35849090" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Immunotherapy", "descriptor_ui": "D007167", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Protein Kinase C", "descriptor_ui": "D011493", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": true }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jul 16", "date_precision": "day", "issue": "", "normalized_date": "2022-07-16", "pages": "dxac035", "proceedings_title": null, "publisher": "", "title": "International immunology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "A Protein Kinase D Inhibitor Suppresses AKT on T cells and Antagonizes Cancer Immunotherapy by Anti-PD-1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The morphology of collagen-producing cells and the structure of produced collagen in the dermis have not been well-described. This lack of insights has been a serious obstacle in the evaluation of skin regeneration. We succeeded in visualizing collagen-producing cells and produced collagen using the axolotl skin, which is highly transparent. The visualized dermal collagen had a lattice-like structure. The collagen-producing fibroblasts consistently possessed the lattice-patterned filopodia along with the lattice-patterned collagen network. The dynamics of this lattice-like structure were also verified in the skin regeneration process of axolotls, and it was found that the correct lattice-like structure was not reorganized after simple skin wounding but was reorganized in the presence of nerves. These findings are not only fundamental insights in dermatology but also valuable insights into the mechanism of skin regeneration.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Rena", "last_name": "Kashimoto", "name": null }, { "creator_type": "author", "first_name": "Saya", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Sakiya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kamei", "name": null }, { "creator_type": "author", "first_name": "Joe", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Shigenori", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Satoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2022.104524" }, "pmcid": { "normalized": "PMC9213773" }, "pmid": { "normalized": "35754731" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Jul 15", "date_precision": "day", "issue": "7", "normalized_date": "2022-07-15", "pages": "104524", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "25", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Lattice-patterned collagen fibers and their dynamics in axolotl skin regeneration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In vertebrates, newly emerging transformed cells are often apically extruded from epithelial layers through cell competition with surrounding normal epithelial cells. However, the underlying molecular mechanism remains elusive. Here, using phospho-SILAC screening, we show that phosphorylation of AHNAK2 is elevated in normal cells neighboring RasV12 cells soon after the induction of RasV12 expression, which is mediated by calcium-dependent protein kinase C. In addition, transient upsurges of intracellular calcium, which we call calcium sparks, frequently occur in normal cells neighboring RasV12 cells, which are mediated by mechanosensitive calcium channel TRPC1 upon membrane stretching. Calcium sparks then enhance cell movements of both normal and RasV12 cells through phosphorylation of AHNAK2 and promote apical extrusion. Moreover, comparable calcium sparks positively regulate apical extrusion of RasV12-transformed cells in zebrafish larvae as well. Hence, calcium sparks play a crucial role in the elimination of transformed cells at the early phase of cell competition.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Kuromiya", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Kojiro", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Moe", "last_name": "Yotabun", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Sekai", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Tanimura", "name": null }, { "creator_type": "author", "first_name": "Sayuri", "last_name": "Iijima", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Kamasaki", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Akieda", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Ishitani", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Chol Gyu", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Ippei", "last_name": "Usami", "name": null }, { "creator_type": "author", "first_name": "Haruki", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null }, { "creator_type": "author", "first_name": "Estelle", "last_name": "Gauquelin", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Sugimura", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2022.111078" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35830802" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jul 12", "date_precision": "day", "issue": "2", "normalized_date": "2022-07-12", "pages": "111078", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "40", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Calcium sparks enhance the tissue fluidity within epithelial layers and promote apical extrusion of transformed cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurodegenerative diseases involving pathological tau protein aggregation are collectively known as tauopathies and include Alzheimer's disease and Pick's disease. Recent studies show that the intake of tryptophan-tyrosine (Trp-Tyr)-related beta-lactopeptides, including beta-lactolin, attenuates cognitive decline in the elderly and prevents the amyloid pathology in mouse models of Alzheimer's disease. However, the effects of Trp-Tyr-related beta-lactopeptides on tau-related pathology have not been investigated. In the present study, we examined the effects of Trp-Tyr dipeptide intake on tauopathy in PS19 transgenic mice, a well-established tauopathy model. Intake of Trp-Tyr dipeptide improved the behavioral deficits observed in the open field test, prevented tau phosphorylation, and increased the dopamine turnover and synaptophysin expression in the frontal cortex. Levels of short-chain fatty acids in the cecum were lower in PS19 mice than those in wild-type mice and were increased by treatment with Trp-Tyr dipeptide. In addition, intake of Trp-Tyr dipeptide extended the lifespan of PS19 mice. These findings suggest that the intake of Trp-Tyr-related peptides improves tauopathy symptoms, resulting in improvements in behavioral deficits and longevity. Hence, the intake of Trp-Tyr-related peptides, including beta-lactolin, may be beneficial for preventing dementia.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Ano", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Takaichi", "name": null }, { "creator_type": "author", "first_name": "Rena", "last_name": "Ohya", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/1028415x.2022.2090075" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35816407" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dipeptides", "descriptor_ui": "D004151", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": true }, { "descriptor": "Tryptophan", "descriptor_ui": "D014364", "major_topic": false }, { "descriptor": "Tyrosine", "descriptor_ui": "D014443", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jul 11", "date_precision": "day", "issue": "", "normalized_date": "2022-07-11", "pages": "1-12", "proceedings_title": null, "publisher": "", "title": "Nutritional neuroscience", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Tryptophan-tyrosine dipeptide improves tau-related symptoms in tauopathy mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The African turquoise killifish Nothobranchius furzeri (N. furzeri) is a useful model organism for studying aging, age-related diseases, and embryonic diapause. CRISPR/Cas9-mediated gene knockout and Tol2 transposon-mediated transgenesis in N. furzeri have been reported previously. However, these methods take time to generate knockout and transgenic fish. In addition, knock-in technology that inserts large DNA fragments as fluorescent reporter constructs into the target gene in N. furzeri has not yet been established. Here, we show that triple-target CRISPR-mediated single gene disruption efficiently produces whole-body biallelic knockout and enables the examination of gene function in the F0 generation. In addition, we developed a method for creating the knock-in reporter N. furzeri without crossing by optimizing the CRISPR/Cas9 system. These methods drastically reduce the duration of experiments, and we think that these advances will accelerate aging and developmental studies using N. furzeri.", "classifications": [ { "id": "21H00427", "label": "21H00427", "researcher": "Masayuki Oginuma", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masayuki", "last_name": "Oginuma", "name": null }, { "creator_type": "author", "first_name": "Moana", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Ohmura-Adachi", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Ogamino", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Mogi", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Ishitani", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-15972-3" }, "pmcid": { "normalized": "PMC9270483" }, "pmid": { "normalized": "35804091" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Cyprinodontiformes", "descriptor_ui": "D003532", "major_topic": true }, { "descriptor": "Gene Transfer Techniques", "descriptor_ui": "D018014", "major_topic": false }, { "descriptor": "Reverse Genetics", "descriptor_ui": "D059386", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jul 8", "date_precision": "day", "issue": "1", "normalized_date": "2022-07-08", "pages": "11628", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [ "ssbd-database-000258" ], "repository": [ "ssbd-repos-000258" ] }, "title": "Rapid reverse genetics systems for Nothobranchius furzeri, a suitable model organism to study vertebrate aging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Monitoring the activities of proteases in vivo is an important requirement in biological and medical research. Near-infrared (NIR) fluorescent probes are particularly useful for in vivo fluorescence imaging, due to the high penetration of NIR and the low autofluorescence in tissue for this wavelength region, but most current NIR fluorescent probes for proteases are targeted to endopeptidase. Here, we describe a new molecular design for NIR fluorescent probes that target exopeptidase by utilizing the >110 nm blueshift of unsymmetrical Si-rhodamines upon amidation of the N atom of their xanthene moiety. Based on this molecular design, we developed Leu-SiR640 as a probe for leucine amino peptidase (LAP). Leu-SiR640 shows a one order of magnitude larger fluorescence increment (669-fold) upon reaction with LAP than existing NIR fluorescent probes. We similarly designed and synthesized EP-SiR640, a NIR fluorescent probe that targets dipeptidyl peptidase 4 (DPP-4). We show that this probe can monitor DPP-4 activity not only in living cells but also in mouse organs and tumors. This probe could also detect esophageal cancer in human clinical specimens, based on the overexpression of DPP-4 activity.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Hoshino", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yasunaga", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kotani", "name": null }, { "creator_type": "author", "first_name": "Ayumu", "last_name": "Nomoto", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takamaru", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Seto", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d1cb00253h" }, "pmcid": { "normalized": "PMC9257614" }, "pmid": { "normalized": "35866167" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Jul 6", "date_precision": "day", "issue": "7", "normalized_date": "2022-07-06", "pages": "859-867", "proceedings_title": null, "publisher": "", "title": "RSC chemical biology", "volume": "3", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular design of near-infrared (NIR) fluorescent probes targeting exopeptidase and application for detection of dipeptidyl peptidase 4 (DPP-4) activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Interleukin 2 (IL-2) is a key homeostatic cytokine, with therapeutic applications in both immunogenic and tolerogenic immune modulation. Clinical use has been hampered by pleiotropic functionality and widespread receptor expression, with unexpected adverse events. Here, we developed a novel mouse strain to divert IL-2 production, allowing identification of contextual outcomes. Network analysis identified priority access for Tregs and a competitive fitness cost of IL-2 production among both Tregs and conventional CD4 T cells. CD8 T and NK cells, by contrast, exhibited a preference for autocrine IL-2 production. IL-2 sourced from dendritic cells amplified Tregs, whereas IL-2 produced by B cells induced two context-dependent circuits: dramatic expansion of CD8+ Tregs and ILC2 cells, the latter driving a downstream, IL-5-mediated, eosinophilic circuit. The source-specific effects demonstrate the contextual influence of IL-2 function and potentially explain adverse effects observed during clinical trials. Targeted IL-2 production therefore has the potential to amplify or quench particular circuits in the IL-2 network, based on clinical desirability.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Carly E.", "last_name": "Whyte", "name": null }, { "creator_type": "author", "first_name": "Kailash", "last_name": "Singh", "name": null }, { "creator_type": "author", "first_name": "Oliver T.", "last_name": "Burton", "name": null }, { "creator_type": "author", "first_name": "Meryem", "last_name": "Aloulou", "name": null }, { "creator_type": "author", "first_name": "Lubna", "last_name": "Kouser", "name": null }, { "creator_type": "author", "first_name": "Rafael Valente", "last_name": "Veiga", "name": null }, { "creator_type": "author", "first_name": "Amy", "last_name": "Dashwood", "name": null }, { "creator_type": "author", "first_name": "Hanneke", "last_name": "Okkenhaug", "name": null }, { "creator_type": "author", "first_name": "Samira", "last_name": "Benadda", "name": null }, { "creator_type": "author", "first_name": "Alena", "last_name": "Moudra", "name": null }, { "creator_type": "author", "first_name": "Orian", "last_name": "Bricard", "name": null }, { "creator_type": "author", "first_name": "Stephanie", "last_name": "Lienart", "name": null }, { "creator_type": "author", "first_name": "Pascal", "last_name": "Bielefeld", "name": null }, { "creator_type": "author", "first_name": "Carlos P.", "last_name": "Roca", "name": null }, { "creator_type": "author", "first_name": "Francisco Jose", "last_name": "Naranjo-Galindo", "name": null }, { "creator_type": "author", "first_name": "Felix", "last_name": "Lombard-Vadnais", "name": null }, { "creator_type": "author", "first_name": "Steffie", "last_name": "Junius", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Bending", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Tino", "last_name": "Hochepied", "name": null }, { "creator_type": "author", "first_name": "Timotheus Y. F.", "last_name": "Halim", "name": null }, { "creator_type": "author", "first_name": "Susan", "last_name": "Schlenner", "name": null }, { "creator_type": "author", "first_name": "Sylvie", "last_name": "Lesage", "name": null }, { "creator_type": "author", "first_name": "James", "last_name": "Dooley", "name": null }, { "creator_type": "author", "first_name": "Adrian", "last_name": "Liston", "name": null } ], "identifiers": { "doi": { "normalized": "10.1084/jem.20212391" }, "pmcid": { "normalized": "PMC9202720" }, "pmid": { "normalized": "35699942" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": false }, { "descriptor": "Interleukin-2", "descriptor_ui": "D007376", "major_topic": true }, { "descriptor": "Killer Cells, Natural", "descriptor_ui": "D007694", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jul 4", "date_precision": "day", "issue": "7", "normalized_date": "2022-07-04", "pages": "e20212391", "proceedings_title": null, "publisher": "", "title": "The Journal of experimental medicine", "volume": "219", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Context-dependent effects of IL-2 rewire immunity into distinct cellular circuits.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: A postoperative change in pelvic flexion following total hip arthroplasty (THA) is considered to be one of the causes of dislocation. This study aimed to predict the change of pelvic flexion after THA integrating preoperative and postoperative information with artificial intelligence. METHODS: This study involved 415 hips which underwent primary THA. Pelvic flexion angle (PFA) is defined as the angle created by the anterior pelvic plane and the horizontal/vertical planes in the supine/standing positions, respectively. Changes in PFA from preoperative supine position to standing position at 5 years after THA were recorded and which were defined as a 5-year change in PFA. Machine learning analysis was performed to predict 5-year change in PFA less than -20 degrees using demographic, blood biochemical, and radiographic data as explanatory variables. Decision trees were constructed based on the important predictors for 5-year change in PFA that can be handled by humans in clinical practice. RESULTS: Among several machine learning models, random forest showed the highest accuracy (area under the curve = 0.852). Lumbo-lordotic angle, femoral anteversion angle, body mass index, pelvic tilt, and sacral slope were most important random forest predictors. By integrating these preoperative predictors with those obtained 1 year after the surgery, we developed a clinically applicable decision tree model that can predict 5-year change in PFA with area under the curve = 0.914. CONCLUSION: A machine learning model to predict 5-year change in PFA after THA has been developed by integrating preoperative and postoperative patient information, which may have capabilities for preoperative planning of THA.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Junpei", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tezuka", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Inaba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.arth.2022.06.020" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35788030" } }, "mesh": [ { "descriptor": "Arthroplasty, Replacement, Hip", "descriptor_ui": "D019644", "major_topic": true }, { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Pelvis", "descriptor_ui": "D010388", "major_topic": false }, { "descriptor": "Posture", "descriptor_ui": "D011187", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jul 2", "date_precision": "day", "issue": "", "normalized_date": "2022-07-02", "pages": "S0883-5403(22)00682-9", "proceedings_title": null, "publisher": "", "title": "The Journal of arthroplasty", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Prediction of Change in Pelvic Tilt After Total Hip Arthroplasty Using Machine Learning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: To explore the efficacy of retreatment with immune checkpoint inhibitors (ICI) in patients with advanced non-small cell lung cancer (NSCLC) who responded to prior ICI and had adequate ICI-free interval. PATIENTS AND METHODS: Patients with advanced NSCLC who had achieved complete response (CR), partial response (PR), or stable disease for >/=6 months with prior ICI therapy preceding progression were prospectively enrolled. All patients should have had ICI-free interval >/=60 days before registration. Patients were treated with nivolumab (240 mg) every 2 weeks until progression. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival, and safety (Trial Identifier, UMIN000028561). RESULTS: Sixty-one patients were enrolled during October 2017 to February 2020, with 59 analyzed for efficacy. Regarding prior ICI, 41 patients had CR or PR. Median treatment on ICI and median ICI-free intervals were 8.1 months and 9.2 months, respectively. Twenty patients experienced immune-related adverse events (irAE) that required discontinuation of prior ICI. Nivolumab retreatment demonstrated ORR of 8.5% [95% confidence interval (CI), 2.8-18.7%] and median PFS of 2.6 months (95% CI, 1.6-2.8 months) while 5 responders had 11.1 months of median PFS. In the multivariate analysis, ICI-free interval was the only predictive factor of PFS (HR, 2.02; P = 0.02), while prior efficacy or history of irAE was not. Common adverse events were skin disorders (23%), malaise (20%), and hypoalbuminemia (15%). CONCLUSIONS: Even in patients who initially responded to prior ICI and had ICI-free interval, once resistance occurred, retreatment with nivolumab had limited efficacy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Akamatsu", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Teraoka", "name": null }, { "creator_type": "author", "first_name": "Shinkichi", "last_name": "Takamori", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Toi", "name": null }, { "creator_type": "author", "first_name": "Yoshimasa", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Nobuaki", "last_name": "Mamesaya", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Furuya", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Oyanagi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Koh", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Misumi", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Nakagawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/1078-0432.ccr-22-0602" }, "pmcid": { "normalized": "PMC9662947" }, "pmid": { "normalized": "35762926" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Jun 28", "date_precision": "day", "issue": "", "normalized_date": "2022-06-28", "pages": "OF1-OF7", "proceedings_title": null, "publisher": "", "title": "Clinical cancer research : an official journal of the American Association for Cancer Research", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Nivolumab Retreatment in Non-Small Cell Lung Cancer Patients Who Responded to Prior Immune Checkpoint Inhibitors and Had ICI-Free Intervals (WJOG9616L).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has threatened human health and the global economy. Development of additional vaccines and therapeutics is urgently required, but such development with live virus must be conducted with biosafety level 3 confinement. Pseudotyped viruses have been widely adopted for studies of virus entry and pharmaceutical development to overcome this restriction. Here we describe a modified protocol to generate vesicular stomatitis virus (VSV) pseudotyped with SARS-CoV or SARS-CoV-2 spike protein in high yield. We found that a large proportion of pseudovirions produced with the conventional transient expression system lacked coronavirus spike protein at their surface as a result of inhibition of parental VSV infection by overexpression of this protein. Establishment of stable cell lines with an optimal expression level of coronavirus spike protein allowed the efficient production of progeny pseudoviruses decorated with spike protein. This improved VSV pseudovirus production method should facilitate studies of coronavirus entry and development of antiviral agents.Key words: severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, pseudovirus, vesicular stomatitis virus (VSV), spike protein.", "classifications": [ { "id": "19H05411", "label": "19H05411", "researcher": "Yusuke Ohba", "type": "grant" }, { "id": "21H00413", "label": "21H00413", "researcher": "Yoichiro Fujioka", "type": "grant" }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Aya O.", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Maho", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1247/csf.21047" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35491102" } }, "mesh": [ { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false }, { "descriptor": "Spike Glycoprotein, Coronavirus", "descriptor_ui": "D064370", "major_topic": true }, { "descriptor": "Vesicular stomatitis Indiana virus", "descriptor_ui": "D014721", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jun 25", "date_precision": "day", "issue": "1", "normalized_date": "2022-06-25", "pages": "43-53", "proceedings_title": null, "publisher": "", "title": "Cell structure and function", "volume": "47", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "A method for the generation of pseudovirus particles bearing SARS coronavirus spike protein in high yields.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Group I metabotropic glutamate receptors (mGluRs) include mGluR1 and mGluR5, which are coupled to the Gq family of heterotrimeric G-proteins and readily activated by their selective agonist 3,5-dihydroxyphenilglycine (DHPG). mGluR1 and mGluR5 exhibit nearly complementary distributions spatially or temporally in the central nervous system (CNS). In adult cerebellar Purkinje cells (PCs), mGluR1 is a dominant group I mGluR and mGluR5 is undetectable. mGluR1 expression increases substantially during the first three weeks of postnatal development and remains high throughout adulthood. On the other hand, mGluR5 expression is observed during the first two postnatal weeks and then decreases. However, functional differences between mGluR1 and mGluR5 in the CNS remains to be elucidated. To address this issue, we generated \"mGluR5-rescue\" mice in which mGluR5 is specifically expressed in PCs in global mGluR1-knockout (KO) mice. mGluR5-rescue mice exhibited apparently normal motor coordination, developmental elimination of redundant climbing fiber (CF)-PC synapses, and delay eyeblink conditioning, which were severely impaired in mGluR1-KO mice. We concluded that mGluR5 is functionally comparable with mGluR1 in cerebellar PCs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Maria", "last_name": "Harbers", "name": null }, { "creator_type": "author", "first_name": "Harumi", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Matsuyama", "name": null }, { "creator_type": "author", "first_name": "Shoichi", "last_name": "Tohyama", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Atsu", "last_name": "Aiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cells11132004" }, "pmcid": { "normalized": "PMC9265771" }, "pmid": { "normalized": "35805089" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": true }, { "descriptor": "Receptor, Metabotropic Glutamate 5", "descriptor_ui": "D064529", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jun 23", "date_precision": "day", "issue": "13", "normalized_date": "2022-06-23", "pages": "2004", "proceedings_title": null, "publisher": "", "title": "Cells", "volume": "11", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "mGluR5 Is Substitutable for mGluR1 in Cerebellar Purkinje Cells for Motor Coordination, Developmental Synapse Elimination, and Motor Learning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "TMEM79 is a predisposing gene for atopic dermatitis. Tmem79-deficient mice develop spontaneous dermatitis in a biphasic pattern. The first-phase dermatitis is unique because it occurs independent of microbiota status, whereas the second-phase dermatitis is microbiota dependent. In this study, we sought to identify the key factors mediating the development of first-phase dermatitis. Structural analysis showed that sebaceous gland hyperplasia started from first-phase dermatitis. Longitudinal RNA sequencing analysis revealed significant activation of fatty acid lipid metabolism pathways in first-phase dermatitis, whereas T helper 17based immune response genes were highly expressed in second-phase dermatitis. Quantitative RT-PCR analysis revealed that genes involved in fatty acid elongation and sebocyte differentiation were upregulated in first-phase dermatitis. The results of thin-layer chromatography supported these findings with an increased abundance of wax esters, cholesterol esters, and fatty alcohols in hair lipids. Further gas chromatography-tandem mass spectrometry analysis showed an increase in total fatty acid production, including that of elongated C20-24 saturated and C18-24 monounsaturated fatty acids. Collectively, these results suggest that aberrant production of sebaceous long-chain fatty acids is associated with microbiota-independent dermatitis. Further investigation of Tmem79-deficient mice may clarify the role of certain fatty acids in dermatitis.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ari", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Umi", "last_name": "Tahara", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Shiohama", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Naganuma", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Koseki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Amagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jid.2022.06.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35752300" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cholesterol Esters", "descriptor_ui": "D002788", "major_topic": false }, { "descriptor": "Dermatitis, Atopic", "descriptor_ui": "D003876", "major_topic": true }, { "descriptor": "Esters", "descriptor_ui": "D004952", "major_topic": false }, { "descriptor": "Fatty Acids", "descriptor_ui": "D005227", "major_topic": false }, { "descriptor": "Fatty Acids, Monounsaturated", "descriptor_ui": "D005229", "major_topic": false }, { "descriptor": "Fatty Alcohols", "descriptor_ui": "D005233", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microbiota", "descriptor_ui": "D064307", "major_topic": true }, { "descriptor": "Sebaceous Glands", "descriptor_ui": "D012627", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jun 23", "date_precision": "day", "issue": "", "normalized_date": "2022-06-23", "pages": "S0022-202X(22)01588-3", "proceedings_title": null, "publisher": "", "title": "The Journal of investigative dermatology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Microbiota-Independent Spontaneous Dermatitis Associated with Increased Sebaceous Lipid Production in Tmem79-Deficient Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Photo-isolation chemistry (PIC) enables isolation of transcriptome information from locally defined areas by photo-irradiation. Here, we present an optimized PIC protocol for formalin-fixed frozen and paraffin mouse sections and fresh-frozen mouse sections. We describe tissue section preparation and permeabilization, followed by in situ reverse transcription using photo-caged primers. We then detail immunostaining and UV-mediated uncaging to the target areas, followed by linear amplification of uncaged cDNAs, library preparation, and quantification. This protocol can be applied to various animal tissue types. For complete details on the use and execution of this protocol, please refer to Honda et al. (2021).", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mizuki", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Oki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xpro.2022.101346" }, "pmcid": { "normalized": "PMC9046621" }, "pmid": { "normalized": "35496796" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DNA, Complementary", "descriptor_ui": "D018076", "major_topic": false }, { "descriptor": "Formaldehyde", "descriptor_ui": "D005557", "major_topic": true }, { "descriptor": "Frozen Sections", "descriptor_ui": "D005629", "major_topic": false }, { "descriptor": "Gene Library", "descriptor_ui": "D015723", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jun 17", "date_precision": "day", "issue": "2", "normalized_date": "2022-06-17", "pages": "101346", "proceedings_title": null, "publisher": "", "title": "STAR protocols", "volume": "3", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Photo-isolation chemistry for high-resolution and deep spatial transcriptome with mouse tissue sections.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mechanisms underlying sleep homeostasis are poorly understood. The nematode Caenorhabditis elegans exhibits 2 types of sleep: lethargus, or developmentally timed, and stress-induced sleep. Lethargus is characterized by alternating cycles of sleep and motion bouts. Sleep bouts are homeostatically regulated, i.e., prolonged active bouts lead to prolonged sleep bouts. Here we reveal that the interneuron ALA is crucial for homeostatic regulation during lethargus. Intracellular Ca(2+) in ALA gradually increased during active bouts and rapidly decayed upon transitions to sleep bouts. Longer active bouts were accompanied by higher intracellular Ca(2+) peaks. Optogenetic activation of ALA during active bouts caused transitions to sleep bouts. Dysfunction of CEH-17, which is an LIM homeodomain transcription factor selectively expressed in ALA, impaired the characteristic patterns of ALA intracellular Ca(2+) and abolished the homeostatic regulation of sleep bouts. These findings indicate that ALA encodes sleep pressure and contributes to sleep homeostasis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinichi", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Taizo", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2022.104452" }, "pmcid": { "normalized": "PMC9189131" }, "pmid": { "normalized": "35707721" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Jun 17", "date_precision": "day", "issue": "6", "normalized_date": "2022-06-17", "pages": "104452", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "25", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Intracellular Ca(2+) dynamics in the ALA neuron reflect sleep pressure and regulate sleep in Caenorhabditis elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Phosphoribulokinase (PRK), one of the enzymes in the Calvin-Benson cycle, is a well-known target of thioredoxin (Trx), which regulates various enzyme activities by the reduction of disulfide bonds in a light-dependent manner. PRK has two Cys pairs conserved in the N-terminal and C-terminal regions, and the N-terminal one near the active site is thought to be responsible for the regulation. The flexible clamp loop located between the N-terminal two Cys residues has been deemed significant to Trx-mediated regulation. However, cyanobacterial PRK is also subject to Trx-dependent activation despite the lack of this clamp loop. We, therefore, compared Trx-mediated regulation of PRK from the cyanobacterium Anabaena sp. PCC 7120 (A.7120_PRK) and that from the land plant Arabidopsis thaliana (AtPRK). Interestingly, peptide mapping and site-directed mutagenesis analysis showed that Trx was more effective in changing the redox states of the C-terminal Cys pair in both A.7120_PRK and AtPRK. In addition, the effect of redox state change of the C-terminal Cys pair on PRK activity was different between A.7120_PRK and AtPRK. Trx-mediated redox regulation of the C-terminal Cys pair was also important for complex dissociation/formation with CP12 and glyceraldehyde 3-phosphate dehydrogenase. Furthermore, in vivo analysis of the redox states of PRK showed that only one disulfide bond is reduced in response to light. Based on the enzyme activity assay and the complex formation analysis, we concluded that Trx-mediated regulation of the C-terminal Cys pair of PRK is important for activity regulation in cyanobacteria and complex dissociation/formation in both organisms.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuha", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Yokochi", "name": null }, { "creator_type": "author", "first_name": "Takatoshi", "last_name": "Sekiguchi", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Mihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pcp/pcac050" }, "pmcid": { "normalized": "PMC9199185" }, "pmid": { "normalized": "35413120" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Cyanobacteria", "descriptor_ui": "D000458", "major_topic": true }, { "descriptor": "Disulfides", "descriptor_ui": "D004220", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Phosphotransferases (Alcohol Group Acceptor)", "descriptor_ui": "D017853", "major_topic": false }, { "descriptor": "Photosynthesis", "descriptor_ui": "D010788", "major_topic": false }, { "descriptor": "Thioredoxins", "descriptor_ui": "D013879", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jun 15", "date_precision": "day", "issue": "6", "normalized_date": "2022-06-15", "pages": "855-868", "proceedings_title": null, "publisher": "", "title": "Plant & cell physiology", "volume": "63", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "The Importance of the C-Terminal Cys Pair of Phosphoribulokinase in Phototrophs in Thioredoxin-Dependent Regulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takehiro", "last_name": "Nakagaki", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Kiyohito", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Kazunobu", "last_name": "Saiki", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Ogami-Takamura", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Ikematsu", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Akagi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Tsurumoto", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1056/nejmc2204116" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35675184" } }, "mesh": [ { "descriptor": "Anatomy", "descriptor_ui": "D000715", "major_topic": true }, { "descriptor": "Cadaver", "descriptor_ui": "D002102", "major_topic": true }, { "descriptor": "Dissection", "descriptor_ui": "D004210", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Prions", "descriptor_ui": "D011328", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jun 9", "date_precision": "day", "issue": "23", "normalized_date": "2022-06-09", "pages": "2245-2246", "proceedings_title": null, "publisher": "", "title": "The New England journal of medicine", "volume": "386", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Detection of Prions in a Cadaver for Anatomical Practice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dynamic chromatin behavior plays a critical role in various genome functions. However, it remains unclear how chromatin behavior changes during interphase, where the nucleus enlarges and genomic DNA doubles. While the previously reported chromatin movements varied during interphase when measured using a minute or longer time scale, we unveil that local chromatin motion captured by single-nucleosome imaging/tracking on a second time scale remained steady throughout G1, S, and G2 phases in live human cells. This motion mode appeared to change beyond this time scale. A defined genomic region also behaved similarly. Combined with Brownian dynamics modeling, our results suggest that this steady-state chromatin motion was mainly driven by thermal fluctuations. Steady-state motion temporarily increased following a DNA damage response. Our findings support the viscoelastic properties of chromatin. We propose that the observed steady-state chromatin motion allows cells to conduct housekeeping functions, such as transcription and DNA replication, under similar environments during interphase.", "classifications": [ { "id": "18H05412", "label": "18H05412", "researcher": "Shuichi Onami", "type": "grant" }, { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shiori", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Masato T.", "last_name": "Kanemaki", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Maeshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abn5626" }, "pmcid": { "normalized": "PMC9166292" }, "pmid": { "normalized": "35658044" } }, "mesh": [ { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": true }, { "descriptor": "DNA Replication", "descriptor_ui": "D004261", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interphase", "descriptor_ui": "D007399", "major_topic": false }, { "descriptor": "Nucleosomes", "descriptor_ui": "D009707", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jun 3", "date_precision": "day", "issue": "22", "normalized_date": "2022-06-03", "pages": "eabn5626", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "8", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-nucleosome imaging reveals steady-state motion of interphase chromatin in living human cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Three-dimensional (3D) fluorescence imaging is important to accurately capture and understand biological structures and phenomena. However, because of its slow acquisition speed, it was difficult to implement 3D fluorescence imaging for imaging flow cytometry. Especially, modern flow cytometers operate at a flow velocity of 1-10 m/s, and no 3D fluorescence imaging technique was able to capture cells at such high velocity. Here, we present a high-speed 3D fluorescence imaging technique in which a set of optical cross sections of a cell is captured within a single frame of a camera by combining strobe light-sheet excitation and optofluidic spatial transformation. Using this technique, we demonstrated 3D fluorescence imaging of cells flowing at a velocity of over 10 m/s, which is the fastest to our knowledge. Such technology can allow integration of 3D imaging with flow systems of common flow cytometers and cell sorters.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Ugawa", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/boe.455714" }, "pmcid": { "normalized": "PMC9208600" }, "pmid": { "normalized": "35781959" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Jun 1", "date_precision": "day", "issue": "6", "normalized_date": "2022-06-01", "pages": "3647-3656", "proceedings_title": null, "publisher": "", "title": "Biomedical optics express", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "High-speed 3D imaging flow cytometry with optofluidic spatial transformation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "While amyloid-beta lies upstream of tau pathology in Alzheimer's disease, key drivers for other tauopathies, including progressive supranuclear palsy (PSP), are largely unknown. Various tau mutations are known to facilitate tau aggregation, but how the nonmutated tau, which most cases with PSP share, increases its propensity to aggregate in neurons and glial cells has remained elusive. Here, we identified genetic variations and protein abundance of filamin-A in the PSP brains without tau mutations. We provided in vivo biochemical evidence that increased filamin-A levels enhance the phosphorylation and insolubility of tau through interacting actin filaments. In addition, reduction of filamin-A corrected aberrant tau levels in the culture cells from PSP cases. Moreover, transgenic mice carrying human filamin-A recapitulated tau pathology in the neurons. Our data highlight that filamin-A promotes tau aggregation, providing a potential mechanism by which filamin-A contributes to PSP pathology.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koyo", "last_name": "Tsujikawa", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Hamanaka", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Riku", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Norikazu", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Iguchi", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Ishigaki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Miyatake", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Mitsuhashi", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Li", "last_name": "Jiayi", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kuru", "name": null }, { "creator_type": "author", "first_name": "Haruki", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Kakita", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Miyashita", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Iwatsubo", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ikeuchi", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Sobue", "name": null }, { "creator_type": "author", "first_name": "Naomichi", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Sahashi", "name": null }, { "creator_type": "author", "first_name": "Masahisa", "last_name": "Katsuno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abm5029" }, "pmcid": { "normalized": "PMC9132466" }, "pmid": { "normalized": "35613261" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 May 27", "date_precision": "day", "issue": "21", "normalized_date": "2022-05-27", "pages": "eabm5029", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "8", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Actin-binding protein filamin-A drives tau aggregation and contributes to progressive supranuclear palsy pathology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Spermatozoa released from Sertoli cells must be transported to the epididymis. However, the mechanism of the luminal flow in seminiferous tubules has remained unclear to date. Therefore, in this study, we investigated luminal flow and movements in the seminiferous tubules by three-dimensional analysis and in vivo imaging. Serial 5-mum-thick mouse testicular sections at 50-microm-intervals were prepared and stained by Periodic Acid-Schiff-hematoxylin. After three-dimensional reconstruction of the seminiferous tubules, the localization of the released spermatozoa and the stages observed in the sections were recorded in each reconstructed tubule. Luminal movements in the seminiferous tubules were observed by in vivo imaging using a fluorescent-reporter mouse and two-photon excitation microscopy system. Spermatozoa without contact to the seminiferous epithelium were not accumulated toward the rete testis. Additionally, such spermatozoa were found on their way not only to the most proximal rete testis but also a more distant rete testis from any stage VIII seminiferous epithelia. In vivo imaging demonstrated that the direction of the flagella of spermatozoa attached to the seminiferous epithelium was repeatedly reversed. The epithelium at the inner curve of the seminiferous tubule was shaken more actively and had fewer spermatozoa attached compared with the epithelium at the outer curve. Our results hence suggest that the luminal flow in the seminiferous tubules is repeatedly reversed and that this physical force helps spermatozoa to be released from Sertoli cells. In brief: Spermatozoa are released from Sertoli cells and flow in the seminiferous tubule to the rete testis. Our results suggest that the luminal flow in the tubules is repeatedly reversed and that this physical force helps spermatozoa release from the Sertoli cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Kanazawa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Omotehara", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Itoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1530/rep-21-0400" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35521906" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microfluidics", "descriptor_ui": "D044085", "major_topic": true }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Rete Testis", "descriptor_ui": "D012152", "major_topic": false }, { "descriptor": "Rheology", "descriptor_ui": "D012212", "major_topic": false }, { "descriptor": "Seminiferous Epithelium", "descriptor_ui": "D012670", "major_topic": false }, { "descriptor": "Seminiferous Tubules", "descriptor_ui": "D012671", "major_topic": true }, { "descriptor": "Sertoli Cells", "descriptor_ui": "D012708", "major_topic": true }, { "descriptor": "Spermatozoa", "descriptor_ui": "D013094", "major_topic": true }, { "descriptor": "Testis", "descriptor_ui": "D013737", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 May 23", "date_precision": "day", "issue": "1", "normalized_date": "2022-05-23", "pages": "9-18", "proceedings_title": null, "publisher": "", "title": "Reproduction (Cambridge, England)", "volume": "164", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Three-dimensional analysis and in vivo imaging for sperm release and transport in the murine seminiferous tubule.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "For the maintenance of epithelial homeostasis, various aberrant or dysfunctional cells are actively eliminated from epithelial layers. This cell extrusion process mainly falls into two modes: cell-competition-mediated extrusion and apoptotic extrusion. However, it is not clearly understood whether and how these processes are governed by common molecular mechanisms. In this study, we demonstrate that the reactive oxygen species (ROS) levels are elevated within a wide range of epithelial layers around extruding transformed or apoptotic cells. The downregulation of ROS suppresses the extrusion process. Furthermore, ATP is extracellularly secreted from extruding cells, which promotes the ROS level and cell extrusion. Moreover, the extracellular ATP and ROS pathways positively regulate the polarized movements of surrounding cells toward extruding cells in both cell-competition-mediated and apoptotic extrusion. Hence, extracellular ATP acts as an \"extrude me\" signal and plays a prevalent role in cell extrusion, thereby sustaining epithelial homeostasis and preventing pathological conditions or disorders.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Naoka", "last_name": "Shiratsuchi", "name": null }, { "creator_type": "author", "first_name": "Nanami", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Azusa", "last_name": "Chaya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Tanimura", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Mugihiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Ikumi", "last_name": "Kameda", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kon", "name": null }, { "creator_type": "author", "first_name": "Yukinari", "last_name": "Haraoka", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Ishitani", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2022.03.057" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35417667" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": true }, { "descriptor": "Cell Competition", "descriptor_ui": "D000084502", "major_topic": true }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 May 23", "date_precision": "day", "issue": "10", "normalized_date": "2022-05-23", "pages": "2144-2159.e5", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "32", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Extracellular ATP facilitates cell extrusion from epithelial layers mediated by cell competition or apoptosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by altered social communication, restricted interests, and stereotypic behaviors. Although the molecular and cellular pathogeneses of ASD remain elusive, impaired neural stem cell differentiation and neuronal migration during cortical development are suggested to be critically involved in ASD. ANK2, which encodes for a cytoskeletal scaffolding protein involved in recruiting membrane proteins into specialized membrane domains, has been identified as a high-confidence ASD risk gene. However, the role of ANK2 in early neural development remains unclear. In this study, we analyzed the role of ANK2 in the cerebral cortex of developing mouse using in utero electroporation. We provide evidence suggesting that ANK2 regulates neural stem cell differentiation and neuronal migration in the embryonic cerebral cortex, where Ank2 is highly expressed. We also demonstrated that Ank2 knockdown alters the expression of genes involved in neural development. Taken together, these results support the view that ANK2 haploinsufficiency in patients may impair neural development, resulting in an increased risk of ASD. Our study findings provide new insights into the molecular and cellular pathogenesis of ASD, given that among high-confidence ASD genes, ANK2 is rare in that it encodes for a scaffolding protein for the membrane protein complex required for neuronal functions.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shotaro", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hotaka", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2022.03.058" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35313230" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ankyrins", "descriptor_ui": "D017487", "major_topic": false }, { "descriptor": "Autism Spectrum Disorder", "descriptor_ui": "D000067877", "major_topic": true }, { "descriptor": "Autistic Disorder", "descriptor_ui": "D001321", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": true }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 May 21", "date_precision": "day", "issue": "", "normalized_date": "2022-05-21", "pages": "45-50", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "605", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Autism-associated ANK2 regulates embryonic neurodevelopment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Phase-separated membraneless organelles or biomolecular condensates play diverse functions in cells, however recapturing their characteristics using small organic molecules has been a challenge. In the present study, cell-lysate-based screening of 843 self-assembling small molecules led to the discovery of a simple organic molecule, named huezole, that forms liquid droplets to selectively sequester tubulin. Remarkably, this small molecule enters cultured human cells and prevents cell mitosis by forming tubulin-concentrating condensates in cells. The present study demonstrates the feasibility of producing a synthetic condensate out of non-peptidic small molecules for exogenous control of cellular processes. The modular structure of huezole provides a framework for designing a class of organelle-emulating small molecules.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Genyir", "last_name": "Ado", "name": null }, { "creator_type": "author", "first_name": "Naotaka", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Hue T.", "last_name": "Vu", "name": null }, { "creator_type": "author", "first_name": "Amelie", "last_name": "Perron", "name": null }, { "creator_type": "author", "first_name": "Amarjyoti D.", "last_name": "Mahapatra", "name": null }, { "creator_type": "author", "first_name": "Karla Pineda", "last_name": "Arista", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Daniel M.", "last_name": "Packwood", "name": null }, { "creator_type": "author", "first_name": "Fumiyoshi", "last_name": "Ishidate", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Motonari", "last_name": "Uesugi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d1sc07151c" }, "pmcid": { "normalized": "PMC9116451" }, "pmid": { "normalized": "35694339" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 May 18", "date_precision": "day", "issue": "19", "normalized_date": "2022-05-18", "pages": "5760-5766", "proceedings_title": null, "publisher": "", "title": "Chemical science", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Discovery of a phase-separating small molecule that selectively sequesters tubulin in cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lymphocyte activation gene-3 (LAG-3) is a potent inhibitory co-receptor; yet, its functional ligand remains elusive, with distinct potential ligands identified. Here, we investigated the relative contribution of potential ligands, stable peptide-MHC class II complexes (pMHCII) and fibrinogen-like protein 1 (FGL1), to LAG-3 activity in vitro and in vivo. Binding of LAG-3 to stable pMHCII but not to FGL1 induced T cell suppression in vitro. Consistently, LAG-3 mutants lacking FGL1-binding capacity but not those lacking stable pMHCII-binding capacity retained suppressive activity in vitro. Accordingly, targeted disruption of stable pMHCII- but not FGL1-binding capacity of LAG-3 in NOD mice recapitulated diabetes exacerbation by LAG-3 deficiency. Additionally, the loss of stable pMHCII-binding capacity of LAG-3 augmented anti-cancer immunity comparably with LAG-3 deficiency in C57BL/6 mice. These results identify stable pMHCII as a functional ligand of LAG-3 both in autoimmunity and anti-cancer immunity. Thus, stable pMHCII-LAG-3 interaction is a potential therapeutic target in human diseases.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" }, { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Il-Mi", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Takeo K.", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Ikubo", "name": null }, { "creator_type": "author", "first_name": "Harunori", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Maenaka", "name": null }, { "creator_type": "author", "first_name": "Naozumi", "last_name": "Ishimaru", "name": null }, { "creator_type": "author", "first_name": "Hidetaka", "last_name": "Kosako", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Okazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.immuni.2022.03.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35413245" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, CD", "descriptor_ui": "D015703", "major_topic": true }, { "descriptor": "Autoimmunity", "descriptor_ui": "D015551", "major_topic": true }, { "descriptor": "Histocompatibility Antigens Class II", "descriptor_ui": "D000949", "major_topic": true }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Lymphocyte Activation Gene 3 Protein", "descriptor_ui": "D000093322", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 May 10", "date_precision": "day", "issue": "5", "normalized_date": "2022-05-10", "pages": "912-924.e8", "proceedings_title": null, "publisher": "", "title": "Immunity", "volume": "55", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Binding of LAG-3 to stable peptide-MHC class II limits T cell function and suppresses autoimmunity and anti-cancer immunity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although dorsal root ganglion (DRG) neurons have been so far classified according to the difference in their fibers (Abeta, Adelta, and C), this classification should be further subdivided according to gene expression patterns. We focused on oxytocin (OXT) and its related receptors, because OXT plays a local role in DRG neurons. We measured the mRNA levels of OXT, OXT receptor (OXTR), vasopressin V1a receptor (V1aR), transient receptor potential cation channel subfamily V member 1 (TRPV1), and piezo-type mechanosensitive ion channel component 2 (Piezo2) in single DRG neurons by using real-time PCR, and then performed a cluster analysis. According to the gene expression patterns, DRG neurons were classified into 4 clusters: Cluster 1 was characterized mainly by Piezo2, Cluster 2 by TRPV1, Cluster 4 by OXTR, and neurons in Cluster 3 did not express any of the target genes. The cell body diameter of OXT-expressing neurons was significantly larger in Cluster 1 than in Cluster 2. These results suggest that OXT-expressing DRG neurons with small cell bodies (Cluster 2) and large cell bodies (Cluster 1) probably correspond to C-fiber neurons and Abeta-fiber neurons, respectively. Furthermore, the OXT-expressing neurons contained not only TRPV1 but also Piezo2, suggesting that OXT may be released by mechanical stimulation regardless of nociception. Thus, mechanoreception and nociception themselves may induce the autocrine/paracrine function of OXT in the DRG, contributing to alleviation of pain.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Taisei", "last_name": "Noguri", "name": null }, { "creator_type": "author", "first_name": "Dai", "last_name": "Hatakeyama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kitahashi", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13041-022-00927-6" }, "pmcid": { "normalized": "PMC9082903" }, "pmid": { "normalized": "35534837" } }, "mesh": [ { "descriptor": "Ganglia, Spinal", "descriptor_ui": "D005727", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Oxytocin", "descriptor_ui": "D010121", "major_topic": true }, { "descriptor": "Pain", "descriptor_ui": "D010146", "major_topic": false }, { "descriptor": "Receptors, Oxytocin", "descriptor_ui": "D018045", "major_topic": false }, { "descriptor": "TRPV Cation Channels", "descriptor_ui": "D050916", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 May 9", "date_precision": "day", "issue": "1", "normalized_date": "2022-05-09", "pages": "44", "proceedings_title": null, "publisher": "", "title": "Molecular brain", "volume": "15", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Profile of dorsal root ganglion neurons: study of oxytocin expression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Since the historical experiment on the contraction of glycerinated muscle by adding ATP, which Szent-Gyorgyi demonstrated in the mid-20th century, in vitro reactivation of demembranated cells has been a traditional and potent way to examine cell motility. The fundamental advantage of this experimental method is that the composition of the reactivation solution may be easily changed. For example, a high-Ca(2+) concentration environment that occurs only temporarily due to membrane excitation in vivo can be replicated in the lab. Eukaryotic cilia (a.k.a. flagella) are elaborate motility machinery whose regulatory mechanisms are still to be clarified. The unicellular green alga Chlamydomonas reinhardtii is an excellent model organism in the research field of cilia. The reactivation experiments using demembranated cell models of C. reinhardtii and their derivatives, such as demembranated axonemes of isolated cilia, have significantly contributed to understanding the molecular mechanisms of ciliary motility. Those experiments clarified that ATP energizes ciliary motility and that various cellular signals, including Ca(2+), cAMP, and reactive oxygen species, modulate ciliary movements. The precise method for demembranation of C. reinhardtii cells and reactivation of the cell models is described here.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "contributor", "first_name": "Noriko", "last_name": "Ueki", "name": null }, { "creator_type": "contributor", "first_name": "Atsuko", "last_name": "Isu", "name": null }, { "creator_type": "contributor", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3791/63869" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 May 6", "date_precision": "day", "issue": "", "normalized_date": "2022-05-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Reactivation of Demembranated Cell Models in Chlamydomonas reinhardtii.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "For the survival of the motile phototrophic microorganisms, being under proper light conditions is crucial. Consequently, they show photo-induced behaviors (or photobehavior) and alter their direction of movement in response to light. Typical photobehaviors include photoshock (or photophobic) response and phototaxis. Photoshock is a response to a sudden change in light intensity (e.g., flash illumination), wherein organisms transiently stop moving or move backward. During phototaxis, organisms move toward the light source or in the opposite direction (called positive or negative phototaxis, respectively). The unicellular green alga Chlamydomonas reinhardtii is an excellent organism to study photobehavior because it rapidly changes its swimming pattern by modulating the beating of cilia (a.k.a., flagella) after photoreception. Here, various simple methods are shown to observe photobehaviors in C. reinhardtii. Research on C. reinhardtii's photobehaviors has led to the discovery of common regulatory mechanisms between eukaryotic cilia and channelrhodopsins, which may contribute to a better understanding of ciliopathies and the development of new optogenetics methods.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "contributor", "first_name": "Noriko", "last_name": "Ueki", "name": null }, { "creator_type": "contributor", "first_name": "Atsuko", "last_name": "Isu", "name": null }, { "creator_type": "contributor", "first_name": "Ayaka", "last_name": "Kyuji", "name": null }, { "creator_type": "contributor", "first_name": "Yuma", "last_name": "Asahina", "name": null }, { "creator_type": "contributor", "first_name": "Satoaki", "last_name": "So", "name": null }, { "creator_type": "contributor", "first_name": "Rina", "last_name": "Takahashi", "name": null }, { "creator_type": "contributor", "first_name": "Toru", "last_name": "Hisabori", "name": null }, { "creator_type": "contributor", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3791/63961" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 May 6", "date_precision": "day", "issue": "", "normalized_date": "2022-05-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Observation of Photobehavior in Chlamydomonas reinhardtii.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Importance: Although 2 and 3 doses of vaccine have been implemented against the SARS-CoV-2 pandemic, the level of immunity achieved by these additional vaccinations remains unclear. Objective: To investigate the induction of neutralizing antibodies against the SARS-CoV-2 Omicron variant after 2 and 3 doses of the BNT162b2 messenger RNA (mRNA) vaccine among recipients of different ages. Design, Setting, and Participants: A cohort study was conducted from June 1, 2021, to January 12, 2022, among 82 physicians at Kobe University Hospital who had received 2 doses of the BNT162b2 mRNA vaccine. Main Outcomes and Measures: The rates of positive test results and the titers of neutralizing antibodies against the Omicron variant after 2 and 3 doses of the vaccine were compared with those against other variants and compared among 3 age groups (/=59 years [older age group]). Results: A total of 82 physicians (71 men [87%]; median age, 44 years [IQR, 33-58 years]) participated; 31 (38%) were in the younger age group, 32 (39%) were in the intermediate age group, and 19 (23%) were in the older age group. At 2 months after 2 doses of the vaccine, 23 participants (28%) had neutralizing antibodies against the Omicron variant, with a titer of 1.3 (95% CI, 1.2-1.4), which was 11.8-fold (95% CI, 9.9-13.9) lower than the titer against the D614G variant and the lowest among the variants tested. Although the titer of the neutralizing antibody against the Delta variant tended to be low among the older age group (2.9 [95% CI, 2.0-4.1]), the titers of the neutralizing antibody against the Omicron variant were low among all age groups (younger age group, 1.3 [95% CI, 1.1-1.6]; intermediate age group, 1.3 (95% CI, [95% CI, 1.1-1.5]; and older age group, 1.2 [95% CI, 1.0-1.4]). At 7 months after 2 doses of the vaccine, 5 participants (6%) had the neutralizing antibody against the Omicron variant, but after the booster (third dose) vaccination, all 72 participants who received the booster had the neutralizing antibody, and the titer was 41 (95% CI, 34-49), much higher than that at 7 months after 2 doses of the vaccine (1.0 [95% CI, 1.0-1.1]). This increase in titers was observed regardless of age groups; the titers were 44 (95% CI, 32-59) among the younger age group, 44 (95% CI, 32-59) among the intermediate age group, and 30 (95% CI, 22-41) among the older age group. Conclusions and Relevance: In this cohort study of 82 Japanese participants, 2 doses of the BNT162b2 mRNA vaccine did not induce sufficient neutralizing antibody against the Omicron variant. However, booster vaccination was associated with induction of a high level of neutralizing antibodies against the Omicron variant, irrespective of the recipient's age.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Koichi", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Lidya Handayani", "last_name": "Tjan", "name": null }, { "creator_type": "author", "first_name": "Yukiya", "last_name": "Kurahashi", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Sutandhio", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1001/jamanetworkopen.2022.10780" }, "pmcid": { "normalized": "PMC9086840" }, "pmid": { "normalized": "35532938" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Antibodies, Neutralizing", "descriptor_ui": "D057134", "major_topic": false }, { "descriptor": "Antibodies, Viral", "descriptor_ui": "D000914", "major_topic": false }, { "descriptor": "BNT162 Vaccine", "descriptor_ui": "D000090982", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "COVID-19 Vaccines", "descriptor_ui": "D000086663", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "mRNA Vaccines", "descriptor_ui": "D000087503", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true }, { "descriptor": "Vaccines, Synthetic", "descriptor_ui": "D014614", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 May 2", "date_precision": "day", "issue": "5", "normalized_date": "2022-05-02", "pages": "e2210780", "proceedings_title": null, "publisher": "", "title": "JAMA network open", "volume": "5", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Assessment of Neutralizing Antibody Response Against SARS-CoV-2 Variants After 2 to 3 Doses of the BNT162b2 mRNA COVID-19 Vaccine.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "G-protein-coupled receptors (GPCRs) play an important role in sensing various extracellular stimuli, such as neurotransmitters, hormones, and tastants, and transducing the input information into the cell. While the human genome encodes more than 800 GPCR genes, only four Galpha-proteins (Galphas, Galphai/o, Galphaq/11, and Galpha12/13) are known to couple with GPCRs. It remains unclear how such divergent GPCR information is translated into the downstream G-protein signaling dynamics. To answer this question, we report a live-cell fluorescence imaging system for monitoring GPCR downstream signaling dynamics. Genetically encoded biosensors for cAMP, Ca2+, RhoA, and ERK were selected as markers for GPCR downstream signaling, and were stably expressed in HeLa cells. GPCR was further transiently overexpressed in the cells. As a proof-of-concept, we visualized GPCR signaling dynamics of five dopamine receptors and 12 serotonin receptors, and found heterogeneity between GPCRs and between cells. Even when the same Galpha proteins were known to be coupled, the patterns of dynamics in GPCR downstream signaling, including the signal strength and duration, were substantially distinct among GPCRs. These results suggest the importance of dynamical encoding in GPCR signaling.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Tany", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1042/bcj20220021" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35383830" } }, "mesh": [ { "descriptor": "GTP-Binding Proteins", "descriptor_ui": "D019204", "major_topic": true }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Apr 29", "date_precision": "day", "issue": "8", "normalized_date": "2022-04-29", "pages": "883-900", "proceedings_title": null, "publisher": "", "title": "The Biochemical journal", "volume": "479", "year": 2022 }, "ssbd": { "database": [ "ssbd-database-000232" ], "repository": [ "ssbd-repos-000232" ] }, "title": "Quantitative live-cell imaging of GPCR downstream signaling dynamics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This study developed a system consisting of two rounds of screening cellular proteins involved in the nuclear egress of herpes simplex virus 1 (HSV-1). Using this system, we first screened cellular proteins that interacted with the HSV-1 nuclear egress complex (NEC) consisting of UL34 and UL31 in HSV-1-infected cells, which are critical for the nuclear egress of HSV-1, by tandem affinity purification coupled with mass spectrometry-based proteomics technology. Next, we performed CRISPR/Cas9-based screening of live HSV-1-infected reporter cells under fluorescence microscopy using single guide RNAs targeting the cellular proteins identified in the first proteomic screening to detect the mislocalization of the lamin-associated protein emerin, which is a phenotype for defects in HSV-1 nuclear egress. This study focused on a cellular orphan transporter SLC35E1, one of the cellular proteins identified by the screening system. Knockout of SLC35E1 reduced HSV-1 replication and induced membranous invaginations containing perinuclear enveloped virions (PEVs) adjacent to the nuclear membrane (NM), aberrant accumulation of PEVs in the perinuclear space between the inner and outer NMs and the invagination structures, and mislocalization of the NEC. These effects were similar to those of previously reported mutation(s) in HSV-1 proteins and depletion of cellular proteins that are important for HSV-1 de-envelopment, one of the steps required for HSV-1 nuclear egress. Our newly established screening system enabled us to identify a novel cellular protein required for efficient HSV-1 de-envelopment.IMPORTANCE The identification of cellular protein(s) that interact with viral effector proteins and function in important viral procedures is necessary for enhancing our understanding of the mechanics of various viral processes. In this study, we established a new system consisting of interactome screening for the herpes simplex virus 1 (HSV-1) nuclear egress complex (NEC), followed by loss-of-function screening to target the identified putative NEC-interacting cellular proteins to detect a defect in HSV-1 nuclear egress. This newly established system identified SLC35E1, an orphan transporter, as a novel cellular protein required for efficient HSV-1 de-envelopment, providing an insight into the mechanisms involved in this viral procedure.", "classifications": [ { "id": "21H00417", "label": "21H00417", "researcher": "Yuhei Maruzuru", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Fumio", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Misato", "last_name": "Shibazaki", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kozuka-Hata", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Eigo", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Miyano", "name": null }, { "creator_type": "author", "first_name": "Shungo", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Natsume", "name": null }, { "creator_type": "author", "first_name": "Koh", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Arii", "last_name": "Jun", "name": null }, { "creator_type": "author", "first_name": "Kawaguchi", "last_name": "Yasushi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00306-22" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35475666" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Membrane Transport Proteins", "descriptor_ui": "D026901", "major_topic": true }, { "descriptor": "Nuclear Envelope", "descriptor_ui": "D009685", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virus Release", "descriptor_ui": "D057074", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022-04-27", "date_precision": "day", "issue": "10", "normalized_date": "2022-04-27", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of Virology", "volume": "96", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of the Orphan Transporter SLC35E1 in the Nuclear Egress of Herpes Simplex Virus 1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Taste recognition mediated by taste receptors is critical for the survival of animals in nature and is an important determinant of nutritional status and quality of life in humans. However, many factors including aging, diabetes, zinc deficiency, infection with influenza or cold viruses, and chemotherapy can trigger dysgeusia, for which a standard treatment has not been established. We here established an engineered strain of medaka (Oryzias latipes) that expresses green fluorescent protein (GFP) from the endogenous taste 1 receptor 3 (T1R3) gene locus with the use of the CRISPR-Cas9 system. This T1R3-GFP knock-in (KI) strain allows direct visualization of expression from this locus by monitoring of GFP fluorescence. The pattern of GFP expression in the T1R3-GFP KI fish thus mimicked that of endogenous T1R3 gene expression. Furthermore, exposure of T1R3-GFP KI medaka to water containing monosodium glutamate or the anticancer agent 5-fluorouracil resulted in an increase or decrease, respectively, in GFP fluorescence intensity, effects that also recapitulated those on T1R3 mRNA abundance. Finally, screening for agents that affect GFP fluorescence intensity in T1R3-GFP KI medaka identified tryptophan as an amino acid that increases T1R3 gene expression. The establishment of this screening system for taste receptor expression in medaka provides a new tool for the development of potential therapeutic agents for dysgeusia.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kana", "last_name": "Beppu", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ansai", "name": null }, { "creator_type": "author", "first_name": "Nana", "last_name": "Ochiai", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Terakawa", "name": null }, { "creator_type": "author", "first_name": "Marie", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Tomoi", "name": null }, { "creator_type": "author", "first_name": "Joe", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kamei", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Naruse", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sakaue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2022.02.082" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35228123" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Dysgeusia", "descriptor_ui": "D004408", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Oryzias", "descriptor_ui": "D009990", "major_topic": true }, { "descriptor": "Quality of Life", "descriptor_ui": "D011788", "major_topic": false }, { "descriptor": "Taste", "descriptor_ui": "D013649", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Apr 23", "date_precision": "day", "issue": "", "normalized_date": "2022-04-23", "pages": "65-72", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "601", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a screening system for agents that modulate taste receptor expression with the CRISPR-Cas9 system in medaka.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescent probes that can selectively detect tumour lesions have great potential for fluorescence imaging-guided surgery. Here, we established a library-based approach for efficient screening of probes for tumour-selective imaging based on discovery of biomarker enzymes. We constructed a combinatorial fluorescent probe library for aminopeptidases and proteases, which is composed of 380 probes with various substrate moieties. Using this probe library, we performed lysate-based in vitro screening and/or direct imaging-based ex vivo screening of freshly resected clinical specimens from lung or gastric cancer patients, and found promising probes for tumour-selective visualization. Further, we identified two target enzymes as novel biomarker enzymes for discriminating between tumour and non-tumour tissues. This library-based approach is expected to be an efficient tool to develop tumour-imaging probes and to discover new biomarker enzyme activities for various tumours and other diseases.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yugo", "last_name": "Kuriki", "name": null }, { "creator_type": "author", "first_name": "Takafusa", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takamaru", "name": null }, { "creator_type": "author", "first_name": "Kyohhei", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Hirohisa", "last_name": "Iwaki", "name": null }, { "creator_type": "author", "first_name": "Aika", "last_name": "Nanjo", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Akagi", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Takeshita", "name": null }, { "creator_type": "author", "first_name": "Haruaki", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Rumi", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Seiichiro", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d1sc06889j" }, "pmcid": { "normalized": "PMC9019911" }, "pmid": { "normalized": "35656140" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Apr 20", "date_precision": "day", "issue": "16", "normalized_date": "2022-04-20", "pages": "4474-4481", "proceedings_title": null, "publisher": "", "title": "Chemical science", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a fluorescent probe library enabling efficient screening of tumour-imaging probes based on discovery of biomarker enzymatic activities.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Thioredoxin (Trx) is a key protein of the redox regulation system in chloroplasts, where it modulates various enzyme activities. Upon light irradiation, Trx reduces the disulfide bonds of Trx target proteins (thereby turning on their activities) using reducing equivalents obtained from the photosynthetic electron transport chain. This reduction process involves a differential response, i.e., some Trx target proteins in the stroma respond slowly to the change in redox condition caused by light/dark changes, while the ATP synthase gamma subunit (CF1-gamma) located on the surface of thylakoid membrane responds with high sensitivity. The factors that determine this difference in redox kinetics are not yet known, although here, we hypothesize that it is due to each protein's localization in the chloroplast, i.e., the reducing equivalents generated under light conditions can be transferred more efficiently to the proteins on thylakoid membrane than to stromal proteins. To explore this possibility, we anchored SBPase, one of the stromal Trx target proteins, to the thylakoid membrane in Arabidopsis thaliana. Analyses of the redox behaviors of the anchored and unanchored proteins showed no significant difference in their reduction kinetics, implying that protein sensitivity to redox regulation is determined by other factors.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuka", "last_name": "Fukushi", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Yokochi", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/antiox11040773" }, "pmcid": { "normalized": "PMC9032623" }, "pmid": { "normalized": "35453458" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Apr 13", "date_precision": "day", "issue": "4", "normalized_date": "2022-04-13", "pages": "773", "proceedings_title": null, "publisher": "", "title": "Antioxidants (Basel, Switzerland)", "volume": "11", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Verification of the Relationship between Redox Regulation of Thioredoxin Target Proteins and Their Proximity to Thylakoid Membranes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Estrogen receptor alpha (ERalpha) is a transcription factor that induces cell proliferation and exhibits increased expression in a large subset of breast cancers. The molecular mechanisms underlying the up-regulation of ERalpha activity, however, remain poorly understood. We identified FK506-binding protein 52 (FKBP52) as a factor associated with poor prognosis of individuals with ERalpha-positive breast cancer. We found that FKBP52 interacts with breast cancer susceptibility gene 1 and stabilizes ERalpha, and is essential for breast cancer cell proliferation. FKBP52 depletion resulted in decreased ERalpha expression and proliferation in breast cancer cell lines, including MCF7-derived fulvestrant resistance (MFR) cells, suggesting that inhibiting FKBP52 may provide a therapeutic effect for endocrine therapy-resistant breast cancer. In contrast, FKBP51, a closely related molecule to FKBP52, reduced the stability of ERalpha. Consistent with these findings, FKBP51 was more abundantly expressed in normal tissues than in cancer cells, suggesting that these FKBPs may function in the opposite direction. Collectively, our study shows that FKBP52 and FKBP51 regulate ERalpha stability in a reciprocal manner and reveals a regulatory mechanism by which the expression of ERalpha is controlled.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Habara", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Goshima", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Hanaki", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Masaki", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Midori", "last_name": "Shimada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2110256119" }, "pmcid": { "normalized": "PMC9169630" }, "pmid": { "normalized": "35394865" } }, "mesh": [ { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Estrogen Receptor alpha", "descriptor_ui": "D047628", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MCF-7 Cells", "descriptor_ui": "D061986", "major_topic": false }, { "descriptor": "Protein Stability", "descriptor_ui": "D055550", "major_topic": false }, { "descriptor": "Tacrolimus Binding Protein 5", "descriptor_ui": "D000099159", "major_topic": false }, { "descriptor": "Tacrolimus Binding Proteins", "descriptor_ui": "D022021", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Apr 12", "date_precision": "day", "issue": "15", "normalized_date": "2022-04-12", "pages": "e2110256119", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "119", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "FKBP52 and FKBP51 differentially regulate the stability of estrogen receptor in breast cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Various things propagate through the medium of individuals. Some individuals follow the others and take the states similar to their states a small number of time steps later. In this paper, we study the problem of estimating the state propagation order of individuals from the real-valued state sequences of all the individuals.We propose a method of constructing a state propagation graph from individuals' time series of observed states. The propagation order estimated by our proposed method is demonstrated to be significantly more accurate than that by a baseline method (optimal constant delay model) for our synthetic datasets, and also to be consistent with visually recognizable propagation orders for the dataset of Japanese stock price time series and biological cell firing state sequences.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Atsuyoshi", "last_name": "Nakamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-10031-3" }, "pmcid": { "normalized": "PMC9005560" }, "pmid": { "normalized": "35414707" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Apr 12", "date_precision": "day", "issue": "1", "normalized_date": "2022-04-12", "pages": "6078", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Propagation graph estimation from individuals' time series of observed states.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Kazumasa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13041-022-00920-z" }, "pmcid": { "normalized": "PMC9004141" }, "pmid": { "normalized": "35410247" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Apr 11", "date_precision": "day", "issue": "1", "normalized_date": "2022-04-11", "pages": "34", "proceedings_title": null, "publisher": "", "title": "Molecular brain", "volume": "15", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Correction to: Oxytocin ameliorates impaired social behavior in a mouse model of 3q29 deletion syndrome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Application of the CRISPR/Cas9 system to knock in fluorescent proteins to endogenous genes of interest in human pluripotent stem cells (hPSCs) has the potential to facilitate hPSC-based disease modeling, drug screening, and optimization of transplantation therapy. To evaluate the capability of fluorescent reporter hPSC lines for high-content screening approaches, we targeted EGFP to the endogenous OCT4 locus. Resulting hPSC-OCT4-EGFP lines generated expressed EGFP coincident with pluripotency markers and could be adapted to multi-well formats for high-content screening (HCS) campaigns. However, after long-term culture, hPSCs transiently lost their EGFP expression. Alternatively, through EGFP knock-in to the AAVS1 locus, we established a stable and consistent EGFP-expressing hPSC-AAVS1-EGFP line that maintained EGFP expression during in vitro hematopoietic and neural differentiation. Thus, hPSC-AAVS1-EGFP-derived sensory neurons could be adapted to a high-content screening platform that can be applied to high-throughput small-molecule screening and drug discovery campaigns. Our observations are consistent with recent findings indicating that high-frequency on-target complexities appear following CRISPR/Cas9 genome editing at the OCT4 locus. In contrast, we demonstrate that the AAVS1 locus is a safe genomic location in hPSCs with high gene expression that does not impact hPSC quality and differentiation. Our findings suggest that the CRISPR/Cas9-integrated AAVS1 system should be applied for generating stable reporter hPSC lines for long-term HCS approaches, and they underscore the importance of careful evaluation and selection of the applied reporter cell lines for HCS purposes.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kinga", "last_name": "Vojnits", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Deanna", "last_name": "Porras", "name": null }, { "creator_type": "author", "first_name": "Yeonjoon", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Zhuohang", "last_name": "Feng", "name": null }, { "creator_type": "author", "first_name": "Diana", "last_name": "Golubeva", "name": null }, { "creator_type": "author", "first_name": "Mick", "last_name": "Bhatia", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/molecules27082434" }, "pmcid": { "normalized": "PMC9025795" }, "pmid": { "normalized": "35458632" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": true }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Apr 9", "date_precision": "day", "issue": "8", "normalized_date": "2022-04-09", "pages": "", "proceedings_title": null, "publisher": "", "title": "Molecules (Basel, Switzerland)", "volume": "27", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Developing CRISPR/Cas9-Mediated Fluorescent Reporter Human Pluripotent Stem-Cell Lines for High-Content Screening.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In contrast to prokaryotes wherein GUG and UUG are permissive start codons, initiation frequencies from non-AUG codons are generally low in eukaryotes, with CUG being considered as strongest. Here, we report that combined 5-cytosine methylation (5mC) and pseudouridylation (Psi) of near-cognate non-AUG start codons convert GUG and UUG initiation strongly favored over CUG initiation in eukaryotic translation under a certain context. This prokaryotic-like preference is attributed to enhanced NUG initiation by Psi in the second base and reduced CUG initiation by 5mC in the first base. Molecular dynamics simulation analysis of tRNAi(Met) anticodon base pairing to the modified codons demonstrates that Psi universally raises the affinity of codon:anticodon pairing within the ribosomal preinitiation complex through partially mitigating discrimination against non-AUG codons imposed by eukaryotic initiation factor 1. We propose that translational control by chemical modifications of start codon bases can offer a new layer of proteome diversity regulation and therapeutic mRNA technology.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Takeru", "last_name": "Kameda", "name": null }, { "creator_type": "author", "first_name": "Chingakham Ranjit", "last_name": "Singh", "name": null }, { "creator_type": "author", "first_name": "Whitney", "last_name": "Pepper", "name": null }, { "creator_type": "author", "first_name": "Ariana", "last_name": "Cecil", "name": null }, { "creator_type": "author", "first_name": "Madelyn", "last_name": "Hilgers", "name": null }, { "creator_type": "author", "first_name": "Mackenzie", "last_name": "Thornton", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Carter", "last_name": "Moravek", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Togashi", "name": null }, { "creator_type": "author", "first_name": "Hirohide", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Katsura", "last_name": "Asano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abm8501" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35394828" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Apr 8", "date_precision": "day", "issue": "14", "normalized_date": "2022-04-08", "pages": "eabm8501", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "8", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Translational recoding by chemical modification of non-AUG start codon ribonucleotide bases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are standard of care for patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) with common mutations (Del19 or L858R); however, 7%-23% of NSCLC tumors harbor uncommon EGFR mutations. These mutations are highly heterogeneous, and developments in detection techniques are helping to identify mutations with little or no clinical data. PATIENTS AND METHODS: In this retrospective, global, multi-center study (NCT04179890), existing health records were identified for consecutive EGFR TKI-naïve patients with uncommon EGFR mutations (T790M, ex20ins, major uncommon [G719X, L861Q, or S768I], or \"other\" mutations; compound mutations) treated with erlotinib, gefitinib, afatinib, or osimertinib in first or second line. Endpoints included time-to-treatment failure (TTF), objective response rate (ORR), and overall survival (OS). RESULTS: Overall, 246 patients (median age: 69.5 years; Asian: 84%) were included from 9 countries. Most patients (92%) received an EGFR TKI as first-line therapy; 54%, 43% and 3% received afatinib, first-generation TKIs, and osimertinib, respectively. Median TTF and OS with EGFR TKIs were 9.9 and 24.4 months; ORR was 43%. In patients treated with first-line chemotherapy (n = 20), median TTF and ORR were 6.6 months and 41%. Outcomes were most favorable in patients with major uncommon or compound mutations. Overall, TTF was 11.3 months with afatinib and 8.8 months with first-generation EGFR TKIs across mutation categories. In most mutation categories, median OS was >2 years. CONCLUSION: In a real-world setting, EGFR TKIs were the preferred treatment option in patients with uncommon EGFR mutations; strongest outcomes were seen in patients with major uncommon and compound mutations.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sanjay", "last_name": "Popat", "name": null }, { "creator_type": "author", "first_name": "Te-Chun", "last_name": "Hsia", "name": null }, { "creator_type": "author", "first_name": "Jen-Yu", "last_name": "Hung", "name": null }, { "creator_type": "author", "first_name": "Hyun Ae", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Jin-Yuan", "last_name": "Shih", "name": null }, { "creator_type": "author", "first_name": "Cheol Kyu", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Seung Hyeun", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Hee Kyung", "last_name": "Ahn", "name": null }, { "creator_type": "author", "first_name": "Yong Chul", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Sung Sook", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Celine", "last_name": "Mascaux", "name": null }, { "creator_type": "author", "first_name": "Hasan", "last_name": "Daoud", "name": null }, { "creator_type": "author", "first_name": "Angela", "last_name": "Märten", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Miura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/oncolo/oyac022" }, "pmcid": { "normalized": "PMC8982383" }, "pmid": { "normalized": "35274704" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Apr 5", "date_precision": "day", "issue": "4", "normalized_date": "2022-04-05", "pages": "255-265", "proceedings_title": null, "publisher": "", "title": "The oncologist", "volume": "27", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Tyrosine Kinase Inhibitor Activity in Patients with NSCLC Harboring Uncommon EGFR Mutations: A Retrospective International Cohort Study (UpSwinG).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer cachexia consists of dramatic body weight loss with rapid muscle depletion due to imbalanced protein homeostasis. We found that the mRNA levels of apelin decrease in muscles from cachectic hepatoma-bearing rats and three mouse models of cachexia. Furthermore, apelin expression inversely correlates with MuRF1 in muscle biopsies from cancer patients. To shed light on the possible role of apelin in cachexia in vivo, we generated apelin 13 carrying all the last 13 amino acids of apelin in D isomers, ultimately extending plasma stability. Notably, apelin D-peptides alter cAMP-based signaling in vitro as the L-peptides, supporting receptor binding. In vitro apelin 13 protects myotube diameter from dexamethasone-induced atrophy, restrains rates of degradation of long-lived proteins and MuRF1 expression, but fails to protect mice from atrophy. D-apelin 13 given intraperitoneally for 13 days in colon adenocarcinoma C26-bearing mice does not reduce catabolic pathways in muscles, as it does in vitro. Puzzlingly, the levels of circulating apelin seemingly deriving from cachexia-inducing tumors, increase in murine plasma during cachexia. Muscle electroporation of a plasmid expressing its receptor APJ, unlike apelin, preserves myofiber area from C26-induced atrophy, supporting apelin resistance in vivo. Altogether, we believe that during cachexia apelin resistance occurs, contributing to muscle wasting and nullifying any possible peptide-based treatment.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Andrea David", "last_name": "Re Cecconi", "name": null }, { "creator_type": "author", "first_name": "Mara", "last_name": "Barone", "name": null }, { "creator_type": "author", "first_name": "Mara", "last_name": "Forti", "name": null }, { "creator_type": "author", "first_name": "Martina", "last_name": "Lunardi", "name": null }, { "creator_type": "author", "first_name": "Alfredo", "last_name": "Cagnotto", "name": null }, { "creator_type": "author", "first_name": "Mario", "last_name": "Salmona", "name": null }, { "creator_type": "author", "first_name": "Davide", "last_name": "Olivari", "name": null }, { "creator_type": "author", "first_name": "Lorena", "last_name": "Zentilin", "name": null }, { "creator_type": "author", "first_name": "Andrea", "last_name": "Resovi", "name": null }, { "creator_type": "author", "first_name": "Perla", "last_name": "Persichitti", "name": null }, { "creator_type": "author", "first_name": "Dorina", "last_name": "Belotti", "name": null }, { "creator_type": "author", "first_name": "Federica", "last_name": "Palo", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Rosanna", "last_name": "Piccirillo", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers14071814" }, "pmcid": { "normalized": "PMC8997437" }, "pmid": { "normalized": "35406586" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Apr 2", "date_precision": "day", "issue": "7", "normalized_date": "2022-04-02", "pages": "1814", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "14", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Apelin Resistance Contributes to Muscle Loss during Cancer Cachexia in Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by specific social symptoms, restricted interests, stereotyped repetitive behaviors, and delayed language development. The 3q29 microdeletion (3q29del), a recurrent copy number variant, confers a high risk for ASD and schizophrenia, and serves as an important pathological model for investigating the molecular pathogenesis of a large number of neurodevelopmental and psychiatric conditions. Recently, mouse models carrying a deletion of the chromosomal region corresponding to the human 3q29 region (Df/+ mice) were generated and demonstrated neurodevelopmental and psychiatric conditions associated behavioral abnormalities, pointing to the relevance of Df/+ mice as a model for these conditions with high construct and face validity. Currently, the molecular pathogenesis of these behavioral phenotypes in Df/+ mice remains unclear. The oxytocin (OXT) system plays a central role in social behavior across species and has a potential role in ASD. In this study, to elucidate the molecular mechanisms behind impaired social behavior in Df/+ mice, we investigated the possible involvement of OXT signaling in impaired social behavior in Df/+ mice. We demonstrated that OXT administration restored the impaired social behavior in Df/+ mice. We also demonstrated that the number of OXT-positive cells in the paraventricular nucleus (PVN) was significantly lower in Df/+ mice than in wild-type (WT) littermates. Consistent with this, the level of OXT peptide in the cerebral cortex of Df/+ mice was lower than in WT littermates. Our study may provide important insights into the molecular pathophysiological basis of neurodevelopmental and psychiatric conditions, including ASD.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Kazumasa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13041-022-00915-w" }, "pmcid": { "normalized": "PMC8962454" }, "pmid": { "normalized": "35346312" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autism Spectrum Disorder", "descriptor_ui": "D000067877", "major_topic": true }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Chromosome Deletion", "descriptor_ui": "D002872", "major_topic": true }, { "descriptor": "Chromosomes, Human, Pair 3", "descriptor_ui": "D002893", "major_topic": false }, { "descriptor": "Developmental Disabilities", "descriptor_ui": "D002658", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Intellectual Disability", "descriptor_ui": "D008607", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Oxytocin", "descriptor_ui": "D010121", "major_topic": true }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Mar 28", "date_precision": "day", "issue": "1", "normalized_date": "2022-03-28", "pages": "26", "proceedings_title": null, "publisher": "", "title": "Molecular brain", "volume": "15", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular brain (micro report) oxytocin ameliorates impaired social behavior in a mouse model of 3q29 deletion syndrome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Atopic dermatitis (AD) is an eczematous skin disorder characterized by type 2 inflammation, barrier disruption, and intense itch. In addition to type 2 cytokines, many other cytokines, such as interferon gamma (IFN-gamma), interleukin 17 (IL-17), and interleukin 22 (IL-22), play roles in the pathogenesis of AD. It has been reported that the extracellular signal-regulated kinase (ERK) is downstream of such cytokines. However, the involvement of the ERK pathway in the pathogenesis of AD has not yet been investigated. We examined the expression of p-ERK in mouse and human AD skin. We also investigated the effects of the topical application of an ERK inhibitor on the dermatitis score, transepidermal water loss (TEWL), histological change, and expression of filaggrin, using an AD-like NC/Nga murine model. The effects of an ERK inhibitor on filaggrin expression in normal human epidermal keratinocytes (NHEKs) and on chemokine production from bone marrow-derived dendritic cells (BMDCs) were also evaluated. p-ERK was highly expressed in mouse and human AD skin. Topical application of an ERK inhibitor alleviated the clinical symptoms, histological changes, TEWL, and decrease in expression of filaggrin in the AD-like NC/Nga murine model. The ERK inhibitor also restored the IL-4 induced reduction in the expression of filaggrin in NHEK, and inhibited chemokine production from BMDC induced by IL-4. These results indicate that the ERK pathway is involved in the pathogenesis of AD, and suggest that the ERK pathway has potential as a therapeutic target for AD in the future.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Nahoko", "last_name": "Zeze", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Kido-Nakahara", "name": null }, { "creator_type": "author", "first_name": "Gaku", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Sawako", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Fujishima", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Hashimoto-Hachiya", "name": null }, { "creator_type": "author", "first_name": "Masutaka", "last_name": "Furue", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nakahara", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms23073467" }, "pmcid": { "normalized": "PMC8999015" }, "pmid": { "normalized": "35408826" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chemokines", "descriptor_ui": "D018925", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Dermatitis, Atopic", "descriptor_ui": "D003876", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Interleukin-4", "descriptor_ui": "D015847", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Mar 23", "date_precision": "day", "issue": "7", "normalized_date": "2022-03-23", "pages": "3467", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "23", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of ERK Pathway in the Pathogenesis of Atopic Dermatitis and Its Potential as a Therapeutic Target.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The processing of stress responses involves brain-wide communication among cortical and subcortical regions; however, the underlying mechanisms remain elusive. Here, we show that the claustrum (CLA) is crucial for the control of stress-induced anxiety-related behaviors. A combined approach using brain activation mapping and machine learning showed that the CLA activation serves as a reliable marker of exposure to acute stressors. In TRAP2 mice, which allow activity-dependent genetic labeling, chemogenetic activation of the CLA neuronal ensemble tagged by acute social defeat stress (DS) elicited anxiety-related behaviors, whereas silencing of the CLA ensemble attenuated DS-induced anxiety-related behaviors. Moreover, the CLA received strong input from DS-activated basolateral amygdala neurons, and its circuit-selective optogenetic photostimulation temporarily elicited anxiety-related behaviors. Last, silencing of the CLA ensemble during stress exposure increased resistance to chronic DS. The CLA thus bidirectionally controls stress-induced emotional responses, and its inactivation can serve as a preventative strategy to increase stress resilience.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Misaki", "last_name": "Niu", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Tanuma", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuwaki", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Miyaji", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Seo", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Jin", "last_name": "Ohkubo", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Misuzu", "last_name": "Hayashida", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Okuno", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abi6375" }, "pmcid": { "normalized": "PMC8932664" }, "pmid": { "normalized": "35302853" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Mar 18", "date_precision": "day", "issue": "11", "normalized_date": "2022-03-18", "pages": "eabi6375", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "8", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Claustrum mediates bidirectional and reversible control of stress-induced anxiety responses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bioluminescence (BL) imaging, which utilizes light emitted through the enzymatic reaction of luciferase oxidizing its substrate luciferin, enables sensitive and noninvasive monitoring of life phenomena. Herein, we developed a series of caged furimazine (FMZ) derivatives by introducing a protective group at the C-3 position and a hydroxy group at the C-6 phenyl ring to realize long-term live-cell BL imaging based on the NanoLuc (NLuc)/NanoKAZ (NKAZ)–FMZ system. The membrane permeability and cytotoxicity of the substrates were evaluated and related to their hydrophobicity. Among the series, the derivative with the bulkiest protective group (adamantanecarbonyl group) and a hydroxy substituent (named Ad-FMZ-OH) showed significantly prolonged and constant BL signal in cells expressing NLuc compared to the native FMZ substrate. This derivative enabled continuous BL imaging at the single-cell level for 24 h. Furthermore, we applied Ad-FMZ-OH to BL imaging of myocyte fusion and succeeded in the consecutive and sensitive monitoring at a single-cell level over a day. In summary, NLuc/NKAZ-caged FMZ derivatives have the potential to be applied to live-cell BL imaging of various life phenomena that require long-term observation.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mariko", "last_name": "Orioka", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Mizui", "name": null }, { "creator_type": "author", "first_name": "Yuma", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Sakama", "name": null }, { "creator_type": "author", "first_name": "Qiaojing", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.bioconjchem.2c00035" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022-03-16", "date_precision": "day", "issue": "3", "normalized_date": "2022-03-16", "pages": "496-504", "proceedings_title": null, "publisher": "American Chemical Society", "title": "Bioconjugate Chemistry", "volume": "33", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "A Series of Furimazine Derivatives for Sustained Live-Cell Bioluminescence Imaging and Application to the Monitoring of Myogenesis at the Single-Cell Level", "url": "https://doi.org/10.1021/acs.bioconjchem.2c00035", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We previously showed that spraying the fluorescent probe gGlu-HMRG (γ-glutamyl hydroxymethyl rhodamine green) can visualize even tiny tumors on the mesentery and peritoneal wall of tumor-bearing mice. However, during surgery, repeated spraying is necessary to detect tumors located deep within organs. Here, we examine whether deeply located tumors can be stained by intravenous administration of this probe. In mice bearing subcutaneous tumors, intravenous administration of gGlu-HMRG resulted in a rapid and specific increase of fluorescence in the tumor, which was visible to the naked eye within 5 min, and the maximum fluorescence intensity ratio of tumor to normal tissue (T/N = 4.3) was reached at 30 min. In mice bearing lung tumors, the T/N ratio reached approximately 20 at 30 min after administration, and deeply located tumors were clearly visualized. These results suggest that intravenous administration of gGlu-HMRG may be a useful technique in fluorescence-guided surgery of tumors.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akihiro", "last_name": "Nakada", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.bioconjchem.2c00039" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022-03-16", "date_precision": "day", "issue": "3", "normalized_date": "2022-03-16", "pages": "523-529", "proceedings_title": null, "publisher": "American Chemical Society", "title": "Bioconjugate Chemistry", "volume": "33", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Rapid Visualization of Deeply Located Tumors In Vivo by Intravenous Administration of a γ-Glutamyltranspeptidase-Activated Fluorescent Probe", "url": "https://doi.org/10.1021/acs.bioconjchem.2c00039", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Despite previous intensive investigations on epiblast cell migration in avian embryos during primitive streak development before stage (st.) 4, this migration at later stages of brain development has remained uninvestigated. By live imaging of epiblast cells sparsely labeled with green fluorescence protein, we investigated anterior epiblast cell migration to form individual brain portions. Anterior epiblast cells from a broad area migrated collectively towards the head axis during st. 5-7 at a rate of 70-110 microm/h, changing directions from diagonal to parallel and forming the brain portions and abutting head ectoderm. This analysis revised the previously published head portion precursor map in anterior epiblasts at st. 4/5. Grafting outside the brain precursor region of mCherry-expressing nodes producing anterior mesendoderm (AME) or isolated AME tissues elicited new cell migration towards ectopic AME tissues. These locally convergent cells developed into secondary brains with portions that depended on the ectopic AME position in the anterior epiblast. Thus, anterior epiblast cells are bipotent for brain/head ectoderm development with given brain portion specificities. A brain portion potential map is proposed, also accounting for previous observations.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koya", "last_name": "Yoshihi", "name": null }, { "creator_type": "author", "first_name": "Kagayaki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Machiko", "last_name": "Teramoto", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Yusaku", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Mitsuo", "last_name": "Nunome", "name": null }, { "creator_type": "author", "first_name": "Mikiharu", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hidenobu", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Iwasato", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Kondoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.199999" }, "pmcid": { "normalized": "PMC9017232" }, "pmid": { "normalized": "35132990" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Birds", "descriptor_ui": "D001717", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Ectoderm", "descriptor_ui": "D004475", "major_topic": false }, { "descriptor": "Gastrula", "descriptor_ui": "D005775", "major_topic": true }, { "descriptor": "Germ Layers", "descriptor_ui": "D005855", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Mar 15", "date_precision": "day", "issue": "6", "normalized_date": "2022-03-15", "pages": "dev199999", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "149", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Live imaging of avian epiblast and anterior mesendoderm grafting reveals the complexity of cell dynamics during early brain development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reactive oxygen species (ROS) can both act as a poison causing cell death and important signaling molecules among various organisms. Photosynthetic organisms inevitably produce ROS, making the appropriate elimination of ROS an essential strategy for survival. Interestingly, the unicellular green alga Chlamydomonas reinhardtii expresses a mammalian form of thioredoxin reductase, TR1, which functions as a ROS scavenger in animal cells. To investigate the properties of TR1 in C. reinhardtii, we generated TR1 knockout strains using CRISPR/Cas9-based genome editing. We found a reduced tolerance to high-light and ROS stresses in the TR1 knockout strains compared to the parental strain. In addition, the regulation of phototactic orientation, known to be regulated by ROS, was affected in the knockout strains. These results suggest that TR1 contributes to a ROS-scavenging pathway in C. reinhardtii.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuma", "last_name": "Asahina", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2022.01.088" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35121375" } }, "mesh": [ { "descriptor": "Algal Proteins", "descriptor_ui": "D020418", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chlamydomonas reinhardtii", "descriptor_ui": "D016825", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": false }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": true }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Oxidants", "descriptor_ui": "D016877", "major_topic": false }, { "descriptor": "Photosynthesis", "descriptor_ui": "D010788", "major_topic": false }, { "descriptor": "Phototaxis", "descriptor_ui": "D000071444", "major_topic": false }, { "descriptor": "Radiation Tolerance", "descriptor_ui": "D011836", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "RNA-Seq", "descriptor_ui": "D000081246", "major_topic": false }, { "descriptor": "Thioredoxin Reductase 1", "descriptor_ui": "D054481", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Mar 12", "date_precision": "day", "issue": "", "normalized_date": "2022-03-12", "pages": "97-103", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "596", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "The mammalian-type thioredoxin reductase 1 confers a high-light tolerance to the green alga Chlamydomonas reinhardtii.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Engineering G-protein-coupled receptors (GPCRs) for improved stability or altered function is of great interest, as GPCRs consist of the largest protein family, are involved in many important signaling pathways, and thus, are one of the major drug targets. Here, we report the development of a high-throughput screening method for GPCRs using a reconstituted in vitro transcription–translation (IVTT) system. Human endothelin receptor type-B (ETBR), a class A GPCR that binds endothelin-1 (ET-1), a 21-residue peptide hormone, was synthesized in the presence of nanodisc (ND) composed of a phospholipid, 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (POPG). The ET-1 binding of ETBR was significantly reduced or was undetectable when other phospholipids were used for ND preparation. However, when functional ETBR purified from Sf9 cells was reconstituted into NDs, ET-1 binding was observed with two different phospholipids tested, including POPG. These results suggest that POPG likely supports the folding of ETBR into its functional form in the IVTT system. Using the same conditions as ETBR, whose three-dimensional structure has been solved, human endothelin receptor type-A (ETAR), whose three-dimensional structure remains unsolved, was also synthesized in its functional form. By adding POPG-ND to the IVTT system, both ETAR and ETBR were successfully subjected to ribosome display, a method of in vitro directed evolution that facilitates the screening of up to 1012 mutants. Finally, using a mock library, we showed that ribosome display can be applied for gene screening of ETBR, suggesting that high-throughput screening and directed evolution of GPCRs is possible in vitro.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Kinuka", "last_name": "Isshiki", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Maehira", "name": null }, { "creator_type": "author", "first_name": "Tatsumi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Hohsaka", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Shihoya", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Nureki", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.1c04714" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022-03-08", "date_precision": "day", "issue": "9", "normalized_date": "2022-03-08", "pages": "3831-3839", "proceedings_title": null, "publisher": "American Chemical Society", "title": "Analytical Chemistry", "volume": "94", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell-Free Synthesis of Human Endothelin Receptors and Its Application to Ribosome Display", "url": "https://doi.org/10.1021/acs.analchem.1c04714", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vasopressin/oxytocin (VP/OT)-related peptides are essential for mammalian antidiuresis, sociosexual behavior, and reproduction. However, the evolutionary origin of this peptide system is still uncertain. Here, we identify orthologous genes to those for VP/OT in Platyhelminthes, intertidal planarians that have a simple bilaterian body structure but lack a coelom and body-fluid circulatory system. We report a comprehensive characterization of the neuropeptide derived from this VP/OT-type gene, identifying its functional receptor, and name it the \"platytocin\" system. Our experiments with these euryhaline planarians, living where environmental salinities fluctuate due to evaporation and rainfall, suggest that platytocin functions as an \"antidiuretic hormone\" and also organizes diverse actions including reproduction and chemosensory-associated behavior. We propose that bilaterians acquired physiological adaptations to amphibious lives by such regulation of the body fluids. This neuropeptide-secreting system clearly became indispensable for life even without the development of a vascular circulatory system or relevant synapses.", "classifications": [ { "id": "21H00428", "label": "21H00428", "researcher": "Tatsuya Sakamoto", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Aoshi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Masa-Aki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Naoaki", "last_name": "Tsutsui", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Sekiguchi", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Matsukawa", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Maejima", "name": null }, { "creator_type": "author", "first_name": "Joseph J.", "last_name": "Gingell", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Sekiguchi", "name": null }, { "creator_type": "author", "first_name": "Ayumu", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Debbie L.", "last_name": "Hay", "name": null }, { "creator_type": "author", "first_name": "John F.", "last_name": "Morris", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abk0331" }, "pmcid": { "normalized": "PMC8896804" }, "pmid": { "normalized": "35245108" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Mar 4", "date_precision": "day", "issue": "9", "normalized_date": "2022-03-04", "pages": "eabk0331", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "8", "year": 2022 }, "ssbd": { "database": [ "ssbd-database-000234" ], "repository": [ "ssbd-repos-000234" ] }, "title": "Vasopressin-oxytocin-type signaling is ancient and has a conserved water homeostasis role in euryhaline marine planarians.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The spatiotemporal regulation of gene expression is essential to ensure robust phenotypic outcomes. Pigmentation patterns in Drosophila are determined by pigments biosynthesized in the developing epidermis and the cis-regulatory elements of the genes involved in this process are well-characterized. Here, we report that the known primary epidermal enhancer is dispensable for the transcriptional activation of ebony (involved in light-colored pigment synthesis) in the developing epidermis of Drosophila melanogaster. The evidence was obtained by introducing an approximately 1 kbp deletion at the primary epidermal enhancer by genome editing. The effect of the primary epidermal enhancer deletion on pigmentation and on the endogenous expression pattern of a mCherry-fused ebony allele was examined in the abdomen. The expression levels of the mCherry-fused ebony in the primary epidermal enhancer-deleted strains were slightly higher than that of the control strain, indicating that the sequences outside the primary epidermal enhancer have an ability to drive an expression of this gene in the epidermis. Interestingly, the primary epidermal enhancer deletion resulted in a derepression of this gene in the dorsal midline of the abdominal tergites, where dark pigmentation is present in the wild-type individuals. This indicated that the primary epidermal enhancer fragment contains a silencer. Furthermore, the endogenous expression pattern of ebony in the 2 additional strains with partially deleted primary epidermal enhancer revealed that the silencer resides within a 351-bp fragment in the 5' portion of the primary epidermal enhancer. These results demonstrated that deletion assays combined with reporter assays are highly effective in detecting the presence of positively and negatively regulating sequences within and outside the focal cis-regulatory elements.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Noriyoshi", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Shoma", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kentaro M.", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/g3journal/jkac010" }, "pmcid": { "normalized": "PMC8895987" }, "pmid": { "normalized": "35100378" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": true }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": true }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": true }, { "descriptor": "Enhancer Elements, Genetic", "descriptor_ui": "D004742", "major_topic": true }, { "descriptor": "Epidermis", "descriptor_ui": "D004817", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Pigmentation", "descriptor_ui": "D010858", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Mar 4", "date_precision": "day", "issue": "3", "normalized_date": "2022-03-04", "pages": "jkac010", "proceedings_title": null, "publisher": "", "title": "G3 (Bethesda, Md.)", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "The role of the epidermis enhancer element in positive and negative transcriptional regulation of ebony in Drosophila melanogaster.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Longitudinal bone growth is achieved by a tightly controlled process termed endochondral bone formation. C-type natriuretic peptide (CNP) stimulates endochondral bone formation through binding to its specific receptor, guanylyl cyclase (GC)-B. However, CNP/GC-B signaling dynamics in different stages of endochondral bone formation have not been fully clarified, especially in terms of the interaction between the cyclic guanine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) pathways. Here, we demonstrated that CNP activates the cAMP/protein kinase A (PKA) pathway and that this activation contributed to the elongation of the hypertrophic zone in the growth plate. Cells of the chondrogenic line ATDC5 were transfected with Forster resonance energy transfer (FRET)-based cGMP and PKA biosensors. Dual-FRET imaging revealed that CNP increased intracellular cGMP levels and PKA activities in chondrocytes. Further, CNP-induced PKA activation was enhanced following differentiation of ATDC5 cells. Live imaging of the fetal growth plate of transgenic mice, expressing a FRET biosensor for PKA, PKAchu mice, showed that CNP predominantly activates the PKA in the hypertrophic chondrocytes. Additionally, histological analysis of the growth plate of PKAchu mice demonstrated that CNP increased the length of the growth plate, but coadministration of a PKA inhibitor, H89, inhibited the growth-promoting effect of CNP only in the hypertrophic zone. In summary, we revealed that CNP-induced cGMP elevation activated the cAMP/PKA pathway, and clarified that this PKA activation contributed to the bone growth-promoting effect of CNP in hypertrophic chondrocytes. These results provide insights regarding the cross-talk between cGMP and cAMP signaling in endochondral bone formation and in the physiological role of the CNP/GC-B system.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Keisho", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yasoda", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1210/endocr/bqac005" }, "pmcid": { "normalized": "PMC8826897" }, "pmid": { "normalized": "35041746" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chondrocytes", "descriptor_ui": "D019902", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Cyclic AMP-Dependent Protein Kinases", "descriptor_ui": "D017868", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Growth Plate", "descriptor_ui": "D006132", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Natriuretic Peptide, C-Type", "descriptor_ui": "D020098", "major_topic": false }, { "descriptor": "Osteogenesis", "descriptor_ui": "D010012", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Mar 1", "date_precision": "day", "issue": "3", "normalized_date": "2022-03-01", "pages": "bqac005", "proceedings_title": null, "publisher": "", "title": "Endocrinology", "volume": "163", "year": 2022 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000221" ] }, "title": "C-type Natriuretic Peptide-induced PKA Activation Promotes Endochondral Bone Formation in Hypertrophic Chondrocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Several studies suggest the involvement of dietary habits and gut microbiome in allergic diseases. However, little is known about the nutritional and gut microbial factors associated with the risk of allergic rhinitis (AR). We recruited 186 participants with symptoms of AR and 106 control subjects without symptoms of AR at the Hitachi Health Care Center, Japan. The habitual consumption of 42 selected nutrients were examined using the brief-type self-administered diet history questionnaire. Faecal samples were collected and subjected to amplicon sequencing of the 16S ribosomal RNA gene hypervariable regions. Association analysis revealed that four nutrients (retinol, vitamin A, cryptoxanthin, and copper) were negatively associated with AR. Among 40 genera examined, relative abundance of Prevotella and Escherichia were associated with AR. Furthermore, significant statistical interactions were observed between retinol and Prevotella. The age- and sex-adjusted odds of AR were 25-fold lower in subjects with high retinol intake and high Prevotella abundance compared to subjects with low retinol intake and low Prevotella abundance. Our data provide insights into complex interplay between dietary nutrients, gut microbiome, and the development of AR.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukari", "last_name": "Sahoyama", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Hamazato", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Shiozawa", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hachiya", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Masahira", "last_name": "Hattori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-07398-8" }, "pmcid": { "normalized": "PMC8888718" }, "pmid": { "normalized": "35233003" } }, "mesh": [ { "descriptor": "Feces", "descriptor_ui": "D005243", "major_topic": false }, { "descriptor": "Gastrointestinal Microbiome", "descriptor_ui": "D000069196", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Prevotella", "descriptor_ui": "D018720", "major_topic": false }, { "descriptor": "Rhinitis, Allergic", "descriptor_ui": "D065631", "major_topic": true }, { "descriptor": "RNA, Ribosomal, 16S", "descriptor_ui": "D012336", "major_topic": false }, { "descriptor": "Vitamin A", "descriptor_ui": "D014801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Mar 1", "date_precision": "day", "issue": "1", "normalized_date": "2022-03-01", "pages": "3359", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Multiple nutritional and gut microbial factors associated with allergic rhinitis: the Hitachi Health Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genetically encoded calcium indicators (GECIs) are widely used to measure calcium transients in neuronal somata and processes, and their use enables the determination of action potential temporal series in a large population of neurons. Here, we generate a transgenic mouse line expressing a highly sensitive green GECI, G-CaMP9a, in a Flp-dependent manner in excitatory and inhibitory neuronal subpopulations downstream of a strong CAG promoter. Combining this reporter mouse with viral or mouse genetic Flp delivery methods produces a robust and stable G-CaMP9a expression in defined neuronal populations without detectable detrimental effects. In vivo two-photon imaging reveals spontaneous and sensory-evoked calcium transients in excitatory and inhibitory ensembles with cellular resolution. Our results show that this reporter line allows long-term, cell-type-specific investigation of neuronal activity with enhanced resolution in defined populations and facilitates dissecting complex dynamics of neural networks in vivo.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masayuki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Atsuya", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Shigetaka", "last_name": "Kobari", "name": null }, { "creator_type": "author", "first_name": "Tatsushi", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Horigane", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Takemoto-Kimura", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Bito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.crmeth.2022.100168" }, "pmcid": { "normalized": "PMC9017135" }, "pmid": { "normalized": "35474964" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neuroimaging", "descriptor_ui": "D059906", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Feb 28", "date_precision": "day", "issue": "2", "normalized_date": "2022-02-28", "pages": "100168", "proceedings_title": null, "publisher": "", "title": "Cell reports methods", "volume": "2", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "A Flp-dependent G-CaMP9a transgenic mouse for neuronal imaging in vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The bacterial microbiota works as a community that consists of many individual organisms, i.e., cells. To fully understand the function of bacterial microbiota, individual cells must be identified; however, it is difficult with current techniques. Here, we develop a method, Barcoding Bacteria for Identification and Quantification (BarBIQ), which classifies single bacterial cells into taxa-named herein cell-based operational taxonomy units (cOTUs)-based on cellularly barcoded 16S rRNA sequences with single-base accuracy, and quantifies the cell number for each cOTU in the microbiota in a high-throughput manner. We apply BarBIQ to murine cecal microbiotas and quantify in total 3.4 x 10(5) bacterial cells containing 810 cOTUs. Interestingly, we find location-dependent global differences in the cecal microbiota depending on the dietary vitamin A deficiency, and more differentially abundant cOTUs at the proximal location than the distal location. Importantly, these location differences are not clearly shown by conventional 16S rRNA gene-amplicon sequencing methods, which quantify the 16S rRNA genes, not the cells. Thus, BarBIQ enables microbiota characterization with the identification and quantification of individual constituent bacteria, which is a cornerstone for microbiota studies.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Jianshi", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Guangwei", "last_name": "Cui", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Miyauchi", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Hojo", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ikuta", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-022-28426-1" }, "pmcid": { "normalized": "PMC8863893" }, "pmid": { "normalized": "35194029" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": false }, { "descriptor": "DNA, Bacterial", "descriptor_ui": "D004269", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microbiota", "descriptor_ui": "D064307", "major_topic": true }, { "descriptor": "RNA, Ribosomal, 16S", "descriptor_ui": "D012336", "major_topic": false }, { "descriptor": "Sequence Analysis, DNA", "descriptor_ui": "D017422", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Feb 22", "date_precision": "day", "issue": "1", "normalized_date": "2022-02-22", "pages": "863", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "High-throughput identification and quantification of single bacterial cells in the microbiota.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell tracking is one of the most critical tools for time-lapse image analysis to observe cell behavior and cell lineages over a long period of time. However, the accompanying graphical user interfaces are often difficult to use and do not incorporate seamless manual correction, data analysis tools, or simple training set design tools if it is machine learning based. In this paper, we introduce our cell tracking software \"LIM Tracker\". This software has a conventional tracking function consisting of recognition processing and link processing, a sequential search-type tracking function based on pattern matching, and a manual tracking function. LIM Tracker enables the seamless use of these functions. In addition, the system incorporates a highly interactive and interlocking data visualization method, which displays analysis result in real time, making it possible to flexibly correct the data and reduce the burden of tracking work. Moreover, recognition functions with deep learning (DL) are also available, which can be used for a wide range of targets including stain-free images. LIM Tracker allows researchers to track living objects with good usability and high versatility for various targets. We present a tracking case study based on fluorescence microscopy images (NRK-52E/EKAREV-NLS cells or MCF-10A/H2B-iRFP-P2A-mScarlet-I-hGem-P2A-PIP-NLS-mNeonGreen cells) and phase contrast microscopy images (Glioblastoma-astrocytoma U373 cells). LIM Tracker is implemented as a plugin for ImageJ/Fiji. The software can be downloaded from https://github.com/LIMT34/LIM-Tracker .", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hideya", "last_name": "Aragaki", "name": null }, { "creator_type": "author", "first_name": "Katsunori", "last_name": "Ogoh", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-06269-6" }, "pmcid": { "normalized": "PMC8854686" }, "pmid": { "normalized": "35177675" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Tracking", "descriptor_ui": "D058948", "major_topic": false }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Feb 17", "date_precision": "day", "issue": "1", "normalized_date": "2022-02-17", "pages": "2702", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "LIM Tracker: a software package for cell tracking and analysis with advanced interactivity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the crustacean Daphnia magna, studying homology-directed repair (HDR) is important to understand genome maintenance during parthenogenesis, effects of environmental toxicants on the genome, and improvement of HDR-mediated genome editing. Here we developed a transgenic D. magna that expresses green fluorescence protein (GFP) upon HDR occurrence. We utilized the previously established reporter plasmid named DR-GFP that has a mutated eGFP gene (SceGFP) and the tandemly located donor GFP gene fragment (iGFP). Upon double-strand break (DSB) introduction on SceGFP, the iGFP gene fragment acts as the HDR template and restores functional eGFP expression. We customized this reporter plasmid to allow bicistronic expression of the mCherry gene under the control of the D. magna EF1alpha-1 promoter/enhancer. By CRISPR/Cas-mediated knock-in of this plasmid via non-homologous joining, we generated the transgenic D. magna that expresses mCherry ubiquitously, suggesting that the DR-GFP reporter gene is expressed in most cells. Introducing DSB on the SceGFP resulted in eGFP expression and this HDR event could be detected by fluorescence, genomic PCR, and quantitative reverse-transcription PCR, suggesting this line could be used for evaluating HDR. The established reporter line might expand our understanding of the HDR mechanism and also improve the HDR-based gene-editing system in this species.", "classifications": [ { "id": "19H05423", "label": "19H05423", "researcher": "Yasuhiko Kato", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Rizky Mutiara", "last_name": "Fatimah", "name": null }, { "creator_type": "author", "first_name": "Nikko", "last_name": "Adhitama", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-06526-8" }, "pmcid": { "normalized": "PMC8847417" }, "pmid": { "normalized": "35169221" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "DNA End-Joining Repair", "descriptor_ui": "D059766", "major_topic": false }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Recombinational DNA Repair", "descriptor_ui": "D059767", "major_topic": false }, { "descriptor": "Red Fluorescent Protein", "descriptor_ui": "D000097573", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Feb 15", "date_precision": "day", "issue": "1", "normalized_date": "2022-02-15", "pages": "2497", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of transgenic Daphnia magna for visualizing homology-directed repair of DNA.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Microfluidic paper-based analytical devices (muPADs) have attracted great attention as potential candidates for point-of-care testing (POCT). Nevertheless, only a limited number of muPADs expected to satisfy the standard of Clinical Laboratory Improvement Amendments (CLIA) waived tests as issued by the US Food and Drug Administration (FDA) have been reported. This work introduces a \"traffic light type muPAD\", enabling highly intuitive semi-quantitative equipment-free naked-eye readout with no need for calibration, subjective interpretation or calculation. Assay results are displayed as traffic light colours reporting 5 analyte concentration levels (green/green & yellow/yellow/yellow & red/red). The device has been designed to never display all three colours simultaneously, eliminating any risk for misinterpretation. The mechanism relies on the modulation of sample flow through a network of paperfluidic channels modified with a hydrophobic to hydrophilic phase-switching substance responsive to H2O2. User operation is limited to sample application, followed by observing a clear and time-independent traffic light signal after approximately 10-30 min. Multiple factors influencing the H2O2 concentration-dependent appearance of a specific traffic light signal were studied. Making use of the possibilities for customising the concentration threshold levels for traffic light colour appearance, quantification of glucose at 5 levels in a clinically relevant concentration range was demonstrated in artificial urine as a model proof-of-concept. This platform is expected to offer the possibility for the future detection of other important metabolites.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sera", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Ryuya", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d1lc01060c" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35059696" } }, "mesh": [ { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": false }, { "descriptor": "Lab-On-A-Chip Devices", "descriptor_ui": "D056656", "major_topic": false }, { "descriptor": "Microfluidic Analytical Techniques", "descriptor_ui": "D046210", "major_topic": true }, { "descriptor": "Paper", "descriptor_ui": "D010209", "major_topic": true }, { "descriptor": "Point-of-Care Testing", "descriptor_ui": "D000067716", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Feb 15", "date_precision": "day", "issue": "4", "normalized_date": "2022-02-15", "pages": "717-726", "proceedings_title": null, "publisher": "", "title": "Lab on a chip", "volume": "22", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Traffic light type paper-based analytical device for intuitive and semi-quantitative naked-eye signal readout.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Photobiomodulation studies have reported that blue light irradiation induces the production of reactive oxygen species. We investigated the effect of blue laser (405 nm) irradiation on the ATP levels in mouse skin and determined the types of reactive oxygen species and reactive nitrogen species using cultured mouse fibroblasts. Blue laser irradiation caused a decrease in the ATP level in the mouse skin and triggered the generation of superoxide anion and hypochlorous acid, whereas nitric oxide and peroxynitrite were not detected. Moreover, blue laser irradiation resulted in reduced cell viability. It is believed that the decrease in the skin ATP level due to blue light irradiation results from the increased levels of oxidative stress due to the generation of reactive oxygen species. This method of systematically measuring the levels of reactive oxygen species and reactive nitrogen species may be useful for understanding the effects of irradiation conditions.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Eiko", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Yoshine", "last_name": "Mayumi", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Tomoharu", "last_name": "Kiyosawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biology11020301" }, "pmcid": { "normalized": "PMC8869339" }, "pmid": { "normalized": "35205166" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Feb 12", "date_precision": "day", "issue": "2", "normalized_date": "2022-02-12", "pages": "301", "proceedings_title": null, "publisher": "", "title": "Biology", "volume": "11", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Blue Laser Irradiation Decreases the ATP Level in Mouse Skin and Increases the Production of Superoxide Anion and Hypochlorous Acid in Mouse Fibroblasts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pairwise interactions are fundamental drivers of collective behavior-responsible for group cohesion. The abiding question is how each individual influences the collective. However, time-delayed mutual information and transfer entropy, commonly used to quantify mutual influence in aggregated individuals, can result in misleading interpretations. Here, we show that these information measures have substantial pitfalls in measuring information flow between agents from their trajectories. We decompose the information measures into three distinct modes of information flow to expose the role of individual and group memory in collective behavior. It is found that decomposed information modes between a single pair of agents reveal the nature of mutual influence involving many-body nonadditive interactions without conditioning on additional agents. The pairwise decomposed modes of information flow facilitate an improved diagnosis of mutual influence in collectives.", "classifications": [ { "id": "18H05413", "label": "18H05413", "researcher": "Tamiki Komatsuzaki", "type": "grant" }, { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Sulimon", "last_name": "Sattari", "name": null }, { "creator_type": "author", "first_name": "Udoy S.", "last_name": "Basak", "name": null }, { "creator_type": "author", "first_name": "Ryan G.", "last_name": "James", "name": null }, { "creator_type": "author", "first_name": "Louis W.", "last_name": "Perrin", "name": null }, { "creator_type": "author", "first_name": "James P.", "last_name": "Crutchfield", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abj1720" }, "pmcid": { "normalized": "PMC8827646" }, "pmid": { "normalized": "35138896" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Feb 11", "date_precision": "day", "issue": "6", "normalized_date": "2022-02-11", "pages": "eabj1720", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "8", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Modes of information flow in collective cohesion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Regenerative medicine relies on basic research outcomes that are only practical when cost effective. The human eyeball requires the retinal pigment epithelium (RPE) to interface the neural retina and the choroid at large. Millions of people suffer from age-related macular degeneration (AMD), a blinding multifactor genetic disease among RPE degradation pathologies. Recently, autologous pluripotent stem-cell-derived RPE cells were prohibitively expensive due to time; therefore, we developed a faster reprogramming system. We stably induced RPE-like cells (iRPE) from human fibroblasts (Fibs) by conditional overexpression of both broad plasticity and lineage-specific transcription factors (TFs). iRPE cells displayed critical RPE benchmarks and significant in vivo integration in transplanted retinas. Herein, we detail the iRPE system with comprehensive single-cell RNA sequencing (scRNA-seq) profiling to interpret and characterize its best cells. We anticipate that our system may enable robust retinal cell induction for basic research and affordable autologous human RPE tissue for regenerative cell therapy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ivo Ngundu", "last_name": "Woogeng", "name": null }, { "creator_type": "author", "first_name": "Bogumil", "last_name": "Kaczkowski", "name": null }, { "creator_type": "author", "first_name": "Imad", "last_name": "Abugessaisa", "name": null }, { "creator_type": "author", "first_name": "Haiming", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Chung-Chau", "last_name": "Hon", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Hashimita", "last_name": "Sanyal", "name": null }, { "creator_type": "author", "first_name": "Junki", "last_name": "Sho", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Kajita", "name": null }, { "creator_type": "author", "first_name": "Takeya", "last_name": "Kasukawa", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null }, { "creator_type": "author", "first_name": "Piero", "last_name": "Carninci", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Mandai", "name": null }, { "creator_type": "author", "first_name": "Erik", "last_name": "Arner", "name": null }, { "creator_type": "author", "first_name": "Masayo", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Cody", "last_name": "Kime", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2021.12.008" }, "pmcid": { "normalized": "PMC8828536" }, "pmid": { "normalized": "35030321" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": true }, { "descriptor": "Disulfides", "descriptor_ui": "D004220", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Indole Alkaloids", "descriptor_ui": "D026121", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Niacinamide", "descriptor_ui": "D009536", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Retinal Pigment Epithelium", "descriptor_ui": "D055213", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Feb 8", "date_precision": "day", "issue": "2", "normalized_date": "2022-02-08", "pages": "289-306", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "17", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Inducing human retinal pigment epithelium-like cells from somatic tissue.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Natural killer (NK) cells lyse invading tumor cells to limit metastatic growth in the lung, but how some cancers evade this host protective mechanism to establish a growing lesion is unknown. Here, we have combined ultra-sensitive bioluminescence imaging with intravital two-photon microscopy involving genetically encoded biosensors to examine this question. NK cells eliminated disseminated tumor cells from the lung within 24 hr of arrival, but not thereafter. Intravital dynamic imaging revealed that 50% of NK-tumor cell encounters lead to tumor cell death in the first 4 hr after tumor cell arrival, but after 24 hr of arrival, nearly 100% of the interactions result in the survival of the tumor cell. During this 24-hr period, the probability of ERK activation in NK cells upon encountering the tumor cells was decreased from 68% to 8%, which correlated with the loss of the activating ligand CD155/PVR/Necl5 from the tumor cell surface. Thus, by quantitatively visualizing, the NK-tumor cell interaction at the early stage of metastasis, we have revealed the crucial parameters of NK cell immune surveillance in the lung.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ichise", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Choji", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tsukiji", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Iwano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Sumiyama", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.76269" }, "pmcid": { "normalized": "PMC8849286" }, "pmid": { "normalized": "35113018" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Immunologic Surveillance", "descriptor_ui": "D007157", "major_topic": true }, { "descriptor": "Intravital Microscopy", "descriptor_ui": "D000069416", "major_topic": false }, { "descriptor": "Killer Cells, Natural", "descriptor_ui": "D007694", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false }, { "descriptor": "Neoplastic Cells, Circulating", "descriptor_ui": "D009360", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Feb 3", "date_precision": "day", "issue": "", "normalized_date": "2022-02-03", "pages": "e76269", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "11", "year": 2022 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000162" ] }, "title": "Functional visualization of NK cell-mediated killing of metastatic single tumor cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report a choline ester-grafted turn-on fluorescence probe to detect acetylcholinesterase (AChE) in living cells. The AChE-mediated hydrolysis of the choline ester moiety producing carboxylate initiates the activation of the Cy5 fluorophore quenched by an intramolecular nucleophilic mercapto group. The probe has the advantages of high AChE affinity and low cytotoxicity.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Oe", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Nogita", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d1cc05132f" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34874369" } }, "mesh": [ { "descriptor": "Acetylcholinesterase", "descriptor_ui": "D000110", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carbocyanines", "descriptor_ui": "D002232", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Cholinesterase Inhibitors", "descriptor_ui": "D002800", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Hydrolysis", "descriptor_ui": "D006868", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Feb 1", "date_precision": "day", "issue": "10", "normalized_date": "2022-02-01", "pages": "1510-1513", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "58", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "An activator-induced quencher-detachment-based turn-on probe with a cationic substrate moiety for acetylcholinesterase.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intercellular signals induce various cellular responses, including growth, proliferation, and differentiation, via the dynamic processes of signal transduction pathways. For cell fate decisions, ligand-binding induces the phosphorylation of ERBB receptors, which in turn activate downstream molecules. The ERBB family includes four subtypes, which diverged through two gene duplications from a common ancestor. Differences in the expression patterns of the subtypes have been reported between different organs in the human body. However, how these different expression properties influence the diverse phosphorylation levels of ERBB proteins is not well understood. Here we study the origin of the phosphorylation responses by experimental and mathematical analyses. The experimental measurements clarified that the phosphorylation levels heavily depend on the ERBB expression profiles. We developed a mathematical model consisting of the four subtypes as monomers, homodimers, and heterodimers and estimated the rate constants governing the phosphorylation responses from the experimental data. To understand the origin of the diversity, we analyzed the effects of the expression levels and reaction rates of the ERBB subtypes on the diversity. The difference in phosphorylation rates between ERBB subtypes showed a much greater contribution to the diversity than did the dimerization rates. This result implies that divergent evolution in phosphorylation reactions rather than in dimerization reactions after whole genome duplications was essential for increasing the diversity of the phosphorylation responses.", "classifications": [ { "id": "18H05414", "label": "18H05414", "researcher": "Hiroko Bannai", "type": "grant" }, { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Hiraku", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpj.2021.12.031" }, "pmcid": { "normalized": "PMC8822607" }, "pmid": { "normalized": "34958777" } }, "mesh": [ { "descriptor": "Erb-b2 Receptor Tyrosine Kinases", "descriptor_ui": "D018719", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Feb 1", "date_precision": "day", "issue": "3", "normalized_date": "2022-02-01", "pages": "470-480", "proceedings_title": null, "publisher": "", "title": "Biophysical journal", "volume": "121", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Origin of diverse phosphorylation patterns in the ERBB system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In this study, second harmonic generation (SHG) and third harmonic generation (THG) spectroscopic imaging were performed on biological samples using a femtosecond laser source in the third near-infrared (NIR) optical window (NIR-III). Using a visible-NIR spectrometer, the SHG and THG signals were simultaneously detected and were extracted using spectral analysis. Visualization of biological samples such as cultured cells (HEK293 T), mouse brain slices, and the nematode Caenorhabditis elegans was performed in a label-free manner. In particular, in an SHG image of an entire coronal brain section (8 x 6 mm(2)), we observed mesh-like and filamentous structures in the arachnoid mater and wall of the cerebral ventricle, probably corresponding to the collagen fibers, cilia, and rootlet. Moreover, the THG images clearly depicted the densely packed axons in the white matter and cell nuclei at the cortex of the mouse brain slice sample and lipid-rich granules such as lipid droplets inside the nematode. The observations and conclusions drawn from this technique confirm that it can be utilized for various biological applications, including in vivo label-free imaging of living animals.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Minori", "last_name": "Masaki", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Oketani", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Sakiko", "last_name": "Honjoh", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/boe.446273" }, "pmcid": { "normalized": "PMC8884214" }, "pmid": { "normalized": "35284173" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Feb 1", "date_precision": "day", "issue": "2", "normalized_date": "2022-02-01", "pages": "694-708", "proceedings_title": null, "publisher": "", "title": "Biomedical optics express", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Spectroscopic second and third harmonic generation microscopy using a femtosecond laser source in the third near-infrared (NIR-III) optical window.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The chemical and mechanical responses of cells via the exchange of information during growth and development result in the formation of biological tissues. Information processing within the cells through the signaling pathways and networks inherent to the constituent cells has been well-studied. However, the cell signaling mechanisms responsible for generating dynamic multicellular responses in developing tissues remain unclear. Here, I review the dynamic multicellular response systems during the development and growth of vertebrate tissues based on the extracellular signal-regulated kinase (ERK) pathway. First, an overview of the function of the ERK signaling network in cells is provided, followed by descriptions of biosensors essential for live imaging of the quantification of ERK activity in tissues. Then adducing four examples, I highlight the contribution of live imaging techniques for studying the involvement of spatio-temporal patterns of ERK activity change in tissue development and growth. In addition, theoretical implications of ERK signaling are also discussed from the viewpoint of dynamic systems. This review might help in understanding ERK-mediated dynamic multicellular responses and tissue morphogenesis.", "classifications": [ { "id": "21H00426", "label": "21H00426", "researcher": "Tsuyoshi Hirashima", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1042/bcj20210557" }, "pmcid": { "normalized": "PMC8883488" }, "pmid": { "normalized": "35050327" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Receptor Protein-Tyrosine Kinases", "descriptor_ui": "D020794", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jan 28", "date_precision": "day", "issue": "2", "normalized_date": "2022-01-28", "pages": "129-143", "proceedings_title": null, "publisher": "", "title": "The Biochemical journal", "volume": "479", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Live imaging approach of dynamic multicellular responses in ERK signaling during vertebrate tissue development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During the nuclear export of nascent nucleocapsids of herpesviruses, the nucleocapsids bud through the inner nuclear membrane (INM) by acquiring the INM as a primary envelope (primary envelopment). We recently reported that herpes simplex virus 1 (HSV-1) nuclear egress complex (NEC), which consists of UL34 and UL31, interacts with an endosomal sorting complex required for transport III (ESCRT-III) adaptor ALIX and recruits ESCRT-III machinery to the INM for efficient primary envelopment. In this study, we identified a cluster of six arginine residues in the disordered domain of UL34 as a minimal region required for the interaction with ALIX, as well as the recruitment of ALIX and an ESCRT-III protein CHMP4B to the INM in HSV-1-infected cells. Mutations in the arginine cluster exhibited phenotypes similar to those with ESCRT-III inhibition reported previously, including the mislocalization of NEC, induction of membranous invagination structures containing enveloped virions, aberrant accumulation of enveloped virions in the invaginations and perinuclear space, and reduction of viral replication. We also showed that the effect of the arginine cluster in UL34 on HSV-1 replication was dependent primarily on ALIX. These results indicated that the arginine cluster in the disordered domain of UL34 was required for the interaction with ALIX and the recruitment of ESCRT-III machinery to the INM to promote primary envelopment. IMPORTANCE Herpesvirus UL34 homologs contain conserved amino-terminal domains that mediate vesicle formation through interactions with UL31 homologs during primary envelopment. UL34 homologs also comprise other domains adjacent to their membrane-anchoring regions, which differ in length, are variable in herpesviruses, and do not form distinguished secondary structures. However, the role of these disordered domains in infected cells remains to be elucidated. In this study, we present data suggesting that the arginine cluster in the disordered domain of HSV-1 UL34 mediates the interaction with ALIX, thereby leading to the recruitment of ESCRT-III machinery to the INM for efficient primary envelopment. This is the first study to report the role of the disordered domain of a UL34 homolog in herpesvirus infections.", "classifications": [ { "id": "19H05417", "label": "19H05417", "researcher": "Jun Arii", "type": "grant" }, { "id": "21H00417", "label": "21H00417", "researcher": "Yuhei Maruzuru", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01704-21" }, "pmcid": { "normalized": "PMC8791252" }, "pmid": { "normalized": "34730397" } }, "mesh": [ { "descriptor": "Arginine", "descriptor_ui": "D001120", "major_topic": true }, { "descriptor": "Calcium-Binding Proteins", "descriptor_ui": "D002135", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Endosomal Sorting Complexes Required for Transport", "descriptor_ui": "D056827", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Nuclear Envelope", "descriptor_ui": "D009685", "major_topic": false }, { "descriptor": "Nucleocapsid", "descriptor_ui": "D019251", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virion", "descriptor_ui": "D014771", "major_topic": false }, { "descriptor": "Virus Release", "descriptor_ui": "D057074", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jan 26", "date_precision": "day", "issue": "2", "normalized_date": "2022-01-26", "pages": "e0170421", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "96", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of the Arginine Cluster in the Disordered Domain of Herpes Simplex Virus 1 UL34 for the Recruitment of ESCRT-III for Viral Primary Envelopment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: There is a gradual progression from paroxysmal to persistent atrial fibrillation (AF) in humans. To elucidate the mechanism involved, the creation of an artificial atrial substrate to persist AF in mice was attempted.Methods and Results:This study used wild type (WT) mice, but it is difficult to induce AF in them. A novel antegrade perfusion method from the left ventricle (LV) to enlarge both atria for artificial atrial modification was proposed in this study. Short duration AF was induced by burst pacing under this method. Optical mapping analysis revealed non-sustained focal type and meandering spiral reentrants after short duration AF. A tiny artificial substrate (~1.2 mm in diameter) was added in by laser irradiation to create a critical atrial arrhythmogenic substrate. Burst pacing was performed in a non-laser group (n=8), a circular-shape laser group (n=8), and a wedge-shaped dent laser group (n=8). We defined AF and atrial tachycardia (AT) as atrial arrhythmia (AA). Long-lasting AA was defined as lasting for >/=30 min. Long-lasting AA was observed in 0/8, 0/8, and 6/8 (75%) mice in each group. Optical mapping analysis revealed that the mechanism was AT with a stationary rotor around the irradiated margin. CONCLUSIONS: Regrettably, this study failed to reproduce persistent AF, but succeeded in creating an arrhythmic substrate that causes sustained AT in WT mice.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shunpei", "last_name": "Horii", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Yada", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Tsujita", "name": null }, { "creator_type": "author", "first_name": "Ayumu", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Kagami", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Toyokazu", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Risako", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Toya", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Namba", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Nagatomo", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Ido", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Masaki", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Bonpei", "last_name": "Takase", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Adachi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1253/circj.cj-20-1286" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34544960" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Atrial Fibrillation", "descriptor_ui": "D001281", "major_topic": true }, { "descriptor": "Cardiac Pacing, Artificial", "descriptor_ui": "D002304", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Heart Atria", "descriptor_ui": "D006325", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Tachycardia, Supraventricular", "descriptor_ui": "D013617", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jan 25", "date_precision": "day", "issue": "2", "normalized_date": "2022-01-25", "pages": "319-329", "proceedings_title": null, "publisher": "", "title": "Circulation journal : official journal of the Japanese Circulation Society", "volume": "86", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Artificially Created Reentry Circuit by Laser Irradiation Causes Atrial Tachycardia to Persist in Murine Atria.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Signaling-biased ligands acting on G-protein-coupled receptors (GPCRs) differentially activate heterotrimeric G proteins and beta-arrestins. Although a wealth of structural knowledge about signaling bias at the GPCR level exists (preferential engagement of a specific transducer), little is known about the bias at the transducer level (different functions mediated by a single transducer), partly due to a poor understanding of GPCR kinase (GRK)-mediated GPCR phosphorylation. Here, we reveal a unique role of the Gq heterotrimer as a determinant for GRK-subtype selectivity that regulates subsequent beta-arrestin conformation and function. Using the angiotensin II (Ang II) type-1 receptor (AT1R), we show that beta-arrestin recruitment depends on both GRK2/3 and GRK5/6 upon binding of Ang II, but solely on GRK5/6 upon binding of the beta-arrestin-biased ligand TRV027. With pharmacological inhibition or genetic loss of Gq, GRK-subtype selectivity and beta-arrestin functionality by Ang II is shifted to those of TRV027. Single-molecule imaging identifies relocation of AT1R and GRK5, but not GRK2, to an immobile phase under the Gq-inactive, AT1R-stimulated conditions. These findings uncover a previously unappreciated Gq-regulated mechanism that encodes GRK-subtype selectivity and imparts distinct phosphorylation-barcodes directing downstream beta-arrestin functions.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kouki", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Yanagawa", "name": null }, { "creator_type": "author", "first_name": "Suzune", "last_name": "Hiratsuka", "name": null }, { "creator_type": "author", "first_name": "Misaki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Junken", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-022-28056-7" }, "pmcid": { "normalized": "PMC8789823" }, "pmid": { "normalized": "35078997" } }, "mesh": [ { "descriptor": "Angiotensin II", "descriptor_ui": "D000804", "major_topic": false }, { "descriptor": "beta-Arrestins", "descriptor_ui": "D000071557", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "G-Protein-Coupled Receptor Kinase 2", "descriptor_ui": "D054769", "major_topic": false }, { "descriptor": "G-Protein-Coupled Receptor Kinase 5", "descriptor_ui": "D054774", "major_topic": false }, { "descriptor": "GTP-Binding Protein alpha Subunits, Gq-G11", "descriptor_ui": "D043802", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Oligopeptides", "descriptor_ui": "D009842", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Receptor, Angiotensin, Type 1", "descriptor_ui": "D044140", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Vasoconstrictor Agents", "descriptor_ui": "D014662", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jan 25", "date_precision": "day", "issue": "1", "normalized_date": "2022-01-25", "pages": "487", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Heterotrimeric Gq proteins act as a switch for GRK5/6 selectivity underlying beta-arrestin transducer bias.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of extracellular amyloid-beta peptides (Abeta) resulting in senile plaques and intracellular hyperphosphorylated tau protein resulting in neurofibrillary tangles (NFTs). Mucuna beans (Mucuna pruriences (L.) DC. var. utilis) are unique plants containing 3-9% L-3,4-dihydroxyphenylalanine (L-DOPA). Here we investigated the effect of the administration of Mucuna beans on AD prevention by feeding triple-transgenic mice (3 x Tg-AD mice) with a diet containing Mucuna beans for 13 months. The levels of Abeta oligomers and detergent-insoluble phosphorylated tau decreased in the brain of mice fed with Mucuna beans (Mucuna group) compared to those of the Control group. Abeta accumulation and phosphorylated tau accumulation in the brain in the Mucuna group were also reduced. In addition, administration of Mucuna beans improved cognitive function. These results suggest that administration of Mucuna beans may have a preventive effect on AD development in 3 x Tg-AD mice.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Fumiko", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Tadasu", "last_name": "Furusho", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Soeda", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Sarasa", "last_name": "Kogure", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Takekoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-04777-z" }, "pmcid": { "normalized": "PMC8770455" }, "pmid": { "normalized": "35046433" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Amyloid beta-Peptides", "descriptor_ui": "D016229", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain Chemistry", "descriptor_ui": "D001923", "major_topic": false }, { "descriptor": "Cognition", "descriptor_ui": "D003071", "major_topic": false }, { "descriptor": "Diet", "descriptor_ui": "D004032", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Levodopa", "descriptor_ui": "D007980", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Mucuna", "descriptor_ui": "D031299", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jan 19", "date_precision": "day", "issue": "1", "normalized_date": "2022-01-19", "pages": "996", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Administration of mucuna beans (Mucuna pruriences (L.) DC. var. utilis) improves cognition and neuropathology of 3 x Tg-AD mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tertiary lymphoid tissues (TLTs) facilitate local T and B cell interactions in chronically inflamed organs. However, the cells and molecular pathways that govern TLT formation are poorly defined. Here, we identified TNF superfamily CD153/CD30 signaling between 2 unique age-dependent lymphocyte subpopulations, CD153+PD-1+CD4+ senescence-associated T (SAT) cells and CD30+T-bet+ age-associated B cells (ABCs), as a driver for TLT expansion. SAT cells, which produced ABC-inducing factors IL-21 and IFN-gamma, and ABCs progressively accumulated within TLTs in aged kidneys after injury. Notably, in kidney injury models, CD153 or CD30 deficiency impaired functional SAT cell induction, which resulted in reduced ABC numbers and attenuated TLT formation with improved inflammation, fibrosis, and renal function. Attenuated TLT formation after transplantation of CD153-deficient bone marrow further supported the importance of CD153 in immune cells. Clonal analysis revealed that SAT cells and ABCs in the kidneys arose from both local differentiation and recruitment from the spleen. In the synovium of aged rheumatoid arthritis patients, T peripheral helper/T follicular helper cells and ABCs also expressed CD153 and CD30, respectively. Together, our data reveal a previously unappreciated function of CD153/CD30 signaling in TLT formation and propose targeting the CD153/CD30 signaling pathway as a therapeutic target for slowing kidney disease progression.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "contributor", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "contributor", "first_name": "Akiko", "last_name": "Oguchi", "name": null }, { "creator_type": "contributor", "first_name": "Yuji", "last_name": "Fukushima", "name": null }, { "creator_type": "contributor", "first_name": "Kyoko", "last_name": "Masuda", "name": null }, { "creator_type": "contributor", "first_name": "Naoya", "last_name": "Toriu", "name": null }, { "creator_type": "contributor", "first_name": "Keisuke", "last_name": "Taniguchi", "name": null }, { "creator_type": "contributor", "first_name": "Takahisa", "last_name": "Yoshikawa", "name": null }, { "creator_type": "contributor", "first_name": "Xiaotong", "last_name": "Cui", "name": null }, { "creator_type": "contributor", "first_name": "Makiko", "last_name": "Kondo", "name": null }, { "creator_type": "contributor", "first_name": "Takeshi", "last_name": "Hosoi", "name": null }, { "creator_type": "contributor", "first_name": "Shota", "last_name": "Komidori", "name": null }, { "creator_type": "contributor", "first_name": "Yoko", "last_name": "Shimizu", "name": null }, { "creator_type": "contributor", "first_name": "Harumi", "last_name": "Fujita", "name": null }, { "creator_type": "contributor", "first_name": "Li", "last_name": "Jiang", "name": null }, { "creator_type": "contributor", "first_name": "Yingyi", "last_name": "Kong", "name": null }, { "creator_type": "contributor", "first_name": "Takashi", "last_name": "Yamanashi", "name": null }, { "creator_type": "contributor", "first_name": "Jun", "last_name": "Seita", "name": null }, { "creator_type": "contributor", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "contributor", "first_name": "Shinya", "last_name": "Toyokuni", "name": null }, { "creator_type": "contributor", "first_name": "Yoko", "last_name": "Hamazaki", "name": null }, { "creator_type": "contributor", "first_name": "Masakazu", "last_name": "Hattori", "name": null }, { "creator_type": "contributor", "first_name": "Yasunobu", "last_name": "Yoshikai", "name": null }, { "creator_type": "contributor", "first_name": "Peter", "last_name": "Boor", "name": null }, { "creator_type": "contributor", "first_name": "Jurgen", "last_name": "Floege", "name": null }, { "creator_type": "contributor", "first_name": "Hiroshi", "last_name": "Kawamoto", "name": null }, { "creator_type": "contributor", "first_name": "Yasuhiro", "last_name": "Murakawa", "name": null }, { "creator_type": "contributor", "first_name": "Nagahiro", "last_name": "Minato", "name": null }, { "creator_type": "contributor", "first_name": "Motoko", "last_name": "Yanagita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci146071" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Jan 18", "date_precision": "day", "issue": "", "normalized_date": "2022-01-18", "pages": "", "proceedings_title": null, "publisher": "", "title": "", "volume": "132", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "CD153/CD30 signaling promotes age-dependent tertiary lymphoid tissue expansion and kidney injury.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In this study, we demonstrate an acoustofluidic device that enables single-file focusing of submicron particles and bacteria using a two-dimensional (2D) acoustic standing wave. The device consists of a 100 mum x 100 mum square channel that supports 2D particle focusing in the channel center at an actuation frequency of 7.39 MHz. This higher actuation frequency compared with conventional bulk acoustic systems enables radiation-force-dominant motion of submicron particles and overcomes the classical size limitation ( approximately 2 mum) of acoustic focusing. We present acoustic radiation force-based focusing of particles with diameters less than 0.5 mum at a flow rate of 12 muL min(-1), and 1.33 mum particles at flow rates up to 80 muL min(-1). The device focused 0.25 mum particles by the 2D acoustic radiation force while undergoing a channel cross-section centered, single-vortex acoustic streaming. A suspension of bacteria was also investigated to evaluate the biological relevance of the device, which demonstrated the alignment of bacteria in the channel at a flow rate of up to 20 muL min(-1). The developed acoustofluidic device can align submicron particles within a narrow flow stream in a highly robust manner, validating its use as a flow-through focusing chamber to perform high-throughput and accurate flow cytometry of submicron objects.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Ugawa", "name": null }, { "creator_type": "author", "first_name": "Hoyeon", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Thierry", "last_name": "Baasch", "name": null }, { "creator_type": "author", "first_name": "Minho", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Soyun", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "OkChan", "last_name": "Jeong", "name": null }, { "creator_type": "author", "first_name": "Yong-Hoon", "last_name": "Choi", "name": null }, { "creator_type": "author", "first_name": "Daewon", "last_name": "Sohn", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Laurell", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "SangWook", "last_name": "Lee", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d1an01891d" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34889326" } }, "mesh": [ { "descriptor": "Acoustics", "descriptor_ui": "D000162", "major_topic": true }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Particle Size", "descriptor_ui": "D010316", "major_topic": false }, { "descriptor": "Sound", "descriptor_ui": "D013016", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jan 17", "date_precision": "day", "issue": "2", "normalized_date": "2022-01-17", "pages": "274-281", "proceedings_title": null, "publisher": "", "title": "The Analyst", "volume": "147", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Reduced acoustic resonator dimensions improve focusing efficiency of bacteria and submicron particles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Non-linear microscopy, such as multi-photon excitation microscopy, offers spatial localities of excitations, thereby achieving 3D cross-sectional imaging with low phototoxicity even in thick biological specimens. We had developed a multi-point scanning two-photon excitation microscopy system using a spinning-disk confocal scanning unit. However, its severe color cross-talk has precluded multi-color simultaneous imaging. Therefore, in this study, we introduced a mechanical switching system to select either of two NIR laser light pulses and an image-splitting detection system for 3- or 4-color imaging. As a proof of concept, we performed multi-color fluorescent imaging of actively dividing human HeLa cells and tobacco BY-2 cells. We found that the proposed microscopy system enabled time-lapse multi-color 3D imaging of cell divisions while avoiding photodamage. Moreover, the application of a linear unmixing method to the 5D dataset enabled the precise separation of individual intracellular components in multi-color images. We thus demonstrated the versatility of our new microscopy system in capturing the dynamic processes of cellular components that could have multitudes of application.", "classifications": [ { "id": "19H05413", "label": "19H05413", "researcher": "Ryota Uehara", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takafumi", "last_name": "Kamada", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Otomo", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Kaito", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Hiruma", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Mitsuyasu", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Nemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-04543-7" }, "pmcid": { "normalized": "PMC8764092" }, "pmid": { "normalized": "35039530" } }, "mesh": [ { "descriptor": "Color", "descriptor_ui": "D003116", "major_topic": false }, { "descriptor": "Datasets as Topic", "descriptor_ui": "D066264", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false }, { "descriptor": "Organelles", "descriptor_ui": "D015388", "major_topic": false }, { "descriptor": "Photons", "descriptor_ui": "D017785", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jan 17", "date_precision": "day", "issue": "1", "normalized_date": "2022-01-17", "pages": "809", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [ "ssbd-database-000224" ], "repository": [ "ssbd-repos-000224" ] }, "title": "Low-invasive 5D visualization of mitotic progression by two-photon excitation spinning-disk confocal microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transplantation of neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) is considered to be a promising therapy for spinal cord injury (SCI) and will soon be translated to the clinical phase. However, how grafted neuronal activity influences functional recovery has not been fully elucidated. Here, we show the locomotor functional changes caused by inhibiting the neuronal activity of grafted cells using a designer receptor exclusively activated by designer drugs (DREADD). In vitro analyses of inhibitory DREADD (hM4Di)-expressing cells demonstrated the precise inhibition of neuronal activity via administration of clozapine N-oxide. This inhibition led to a significant decrease in locomotor function in SCI mice with cell transplantation, which was exclusively observed following the maturation of grafted neurons. Furthermore, trans-synaptic tracing revealed the integration of graft neurons into the host motor circuitry. These results highlight the significance of engrafting functionally competent neurons by hiPSC-NS/PC transplantation for sufficient recovery from SCI.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Narihito", "last_name": "Nagoshi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kamata", "name": null }, { "creator_type": "author", "first_name": "Momotaro", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Kajikawa", "name": null }, { "creator_type": "author", "first_name": "Reo", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Munehisa", "last_name": "Shinozaki", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Kohyama", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2021.12.005" }, "pmcid": { "normalized": "PMC8758967" }, "pmid": { "normalized": "35021049" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Disease Management", "descriptor_ui": "D019468", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Piperazines", "descriptor_ui": "D010879", "major_topic": false }, { "descriptor": "Recovery of Function", "descriptor_ui": "D020127", "major_topic": false }, { "descriptor": "Spinal Cord Injuries", "descriptor_ui": "D013119", "major_topic": false }, { "descriptor": "Stem Cell Transplantation", "descriptor_ui": "D033581", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jan 11", "date_precision": "day", "issue": "1", "normalized_date": "2022-01-11", "pages": "127-142", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "17", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Modulation by DREADD reveals the therapeutic effect of human iPSC-derived neuronal activity on functional recovery after spinal cord injury.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Synaptic plasticity is long-lasting changes in synaptic currents and structure. When neurons are exposed to signals that induce aberrant neuronal excitation, they increase the threshold for the induction of long-term potentiation (LTP), known as metaplasticity. However, the metaplastic regulation of structural LTP (sLTP) remains unclear. We investigate glutamate uncaging/photoactivatable (pa)CaMKII-dependent sLTP induction in hippocampal CA1 neurons after chronic neuronal excitation by GABA(A) receptor antagonists. We find that the neuronal excitation decreases the glutamate uncaging-evoked Ca(2+) influx mediated by GluN2B-containing NMDA receptors and suppresses sLTP induction. In addition, single-spine optogenetic stimulation using paCaMKII indicates the suppression of CaMKII signaling. While the inhibition of Ca(2+) influx is protein synthesis independent, the paCaMKII-induced sLTP suppression depends on it. Our findings demonstrate that chronic neuronal excitation suppresses sLTP in two independent ways (i.e., dual inhibition of Ca(2+) influx and CaMKII signaling). This dual inhibition mechanism may contribute to robust neuronal protection in excitable environments.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hiromi H.", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Nagasawa", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Onda", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2021.110153" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34986356" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CA1 Region, Hippocampal", "descriptor_ui": "D056547", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinase Type 2", "descriptor_ui": "D054732", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "GABA-A Receptor Antagonists", "descriptor_ui": "D058787", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Long-Term Potentiation", "descriptor_ui": "D017774", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Receptors, GABA-A", "descriptor_ui": "D011963", "major_topic": false }, { "descriptor": "Receptors, N-Methyl-D-Aspartate", "descriptor_ui": "D016194", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jan 4", "date_precision": "day", "issue": "1", "normalized_date": "2022-01-04", "pages": "110153", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "38", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Chronic neuronal excitation leads to dual metaplasticity in the signaling for structural long-term potentiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Most cartilaginous fishes live in seawater (SW), but a few exceptional elasmobranchs (sharks and rays) are euryhaline and can acclimate to freshwater (FW) environments. The plasma of elasmobranchs is high in NaCl and urea concentrations, which constrains osmotic water loss. However, these euryhaline elasmobranchs maintain high levels of plasma NaCl and urea even when acclimating to low salinity, resulting in a strong osmotic gradient from external environment to body fluid. The kidney consequently produces a large volume of dilute urine to cope with the water influx. In the present study, we investigated the molecular mechanisms of dilute urine production in the kidney of Japanese red stingray, Hemitrygon akajei, transferred from SW to low-salinity environments. We showed that red stingray maintained high plasma NaCl and urea levels by reabsorbing more osmolytes in the kidney when transferred to low salinity. RNA-seq and qPCR analyses were conducted to identify genes involved in NaCl and urea reabsorption under the low-salinity conditions, and the upregulated gene expressions of Na(+)-K(+)-Cl(-) cotransporter 2 (nkcc2) and Na(+)/K(+)-ATPase (nka) were found in the FW-acclimated individuals. These upregulations occurred in the early distal tubule (EDT) in the bundle zone of the kidney, which coils around the proximal and collecting tubules to form the highly convoluted structure of batoid nephron. Considering the previously proposed model for urea reabsorption, the upregulation of nkcc2 and nka not only causes the reabsorption of NaCl in the EDT, but potentially also supports enhanced urea reabsorption and eventually the production of dilute urine in FW-acclimated individuals. We propose advantageous characteristics of the batoid-type nephron that facilitate acclimation to a wide range of salinities, which might have allowed the batoids to expand their habitats.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naotaka", "last_name": "Aburatani", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Marty Kwok-Shing", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Kuraku", "name": null }, { "creator_type": "author", "first_name": "Chiharu", "last_name": "Tanegashima", "name": null }, { "creator_type": "author", "first_name": "Mitsutaka", "last_name": "Kadota", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Waichiro", "last_name": "Godo", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Hyodo", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fphys.2022.953665" }, "pmcid": { "normalized": "PMC9396271" }, "pmid": { "normalized": "36017340" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "953665", "proceedings_title": null, "publisher": "", "title": "Frontiers in physiology", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular and morphological investigations on the renal mechanisms enabling euryhalinity of red stingray Hemitrygon akajei.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for the Coronavirus Disease 2019 (COVID-19) pandemic. The emergence of variants of concern (VOCs) has become one of the most pressing issues in public health. To control VOCs, it is important to know which COVID-19 convalescent sera have cross-neutralizing activity against VOCs and how long the sera maintain this protective activity. Methods: Sera of patients infected with SARS-CoV-2 from March 2020 to January 2021 and admitted to Hyogo Prefectural Kakogawa Medical Center were selected. Blood was drawn from patients at 1-3, 3-6, and 6-8 months post onset. Then, a virus neutralization assay against SARS-CoV-2 variants (D614G mutation as conventional strain; B.1.1.7, P.1, and B.1.351 as VOCs) was performed using authentic viruses. Results: We assessed 97 sera from 42 patients. Sera from 28 patients showed neutralizing activity that was sustained for 3-8 months post onset. The neutralizing antibody titer against D614G significantly decreased in sera of 6-8 months post onset compared to those of 1-3 months post onset. However, the neutralizing antibody titers against the three VOCs were not significantly different among 1-3, 3-6, and 6-8 months post onset. Discussion: Our results indicate that neutralizing antibodies that recognize the common epitope for several variants may be maintained for a long time, while neutralizing antibodies having specific epitopes for a variant, produced in large quantities immediately after infection, may decrease quite rapidly.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yukiya", "last_name": "Kurahashi", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Sutandhio", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Lidya Handayani", "last_name": "Tjan", "name": null }, { "creator_type": "author", "first_name": "Sachiyo", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Tohma", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Ohkita", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Kiriu", "name": null }, { "creator_type": "author", "first_name": "Masatsugu", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2022.773652" }, "pmcid": { "normalized": "PMC8907139" }, "pmid": { "normalized": "35281007" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Antibodies, Viral", "descriptor_ui": "D000914", "major_topic": false }, { "descriptor": "Broadly Neutralizing Antibodies", "descriptor_ui": "D000080908", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": false }, { "descriptor": "Cross Reactions", "descriptor_ui": "D003429", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunity, Humoral", "descriptor_ui": "D056724", "major_topic": false }, { "descriptor": "Immunodominant Epitopes", "descriptor_ui": "D016056", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "773652", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Cross-Neutralizing Breadth and Longevity Against SARS-CoV-2 Variants After Infections.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The precursor of heme, protoporphyrin IX (PPIX), accumulates abundantly in the uteri of birds, such as Japanese quail, Coturnix japonica, which has brown-speckled eggshells; however, the molecular basis of PPIX production in the uterus remains largely unknown. Here, we investigated the cause of low PPIX production in a classical Japanese quail mutant exhibiting white eggshells by comparing its gene expression in the uterus with that of the wild type using transcriptome analysis. We also performed genetic linkage analysis to identify the causative genomic region of the white eggshell phenotype. We found that 11 genes, including 5'-aminolevulinate synthase 1 (ALAS1) and hephaestin-like 1 (HEPHL1), were specifically upregulated in the wild-type uterus and downregulated in the mutant. We mapped the 172 kb candidate genomic region on chromosome 6, which contains several genes, including a part of the paired-like homeodomain 3 (PITX3), which encodes a transcription factor. ALAS1, HEPHL1, and PITX3 were expressed in the apical cells of the luminal epithelium and lamina propria cells of the uterine mucosa of the wild-type quail, while their expression levels were downregulated in the cells of the mutant quail. Biochemical analysis using uterine homogenates indicated that the restricted availability of 5'-aminolevulinic acid is the main cause of low PPIX production. These results suggest that uterus-specific transcriptional regulation of heme-biosynthesis-related genes is an evolutionarily acquired mechanism of eggshell pigment production in Japanese quail. Based on these findings, we discussed the molecular basis of PPIX production in the uteri of Japanese quails.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ishishita", "name": null }, { "creator_type": "author", "first_name": "Shumpei", "last_name": "Kitahara", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Sakura", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Tatsumoto", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Katsushi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yasushige", "last_name": "Ohmori", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Go", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Shigenobu", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0265008" }, "pmcid": { "normalized": "PMC8912178" }, "pmid": { "normalized": "35271636" } }, "mesh": [ { "descriptor": "Aminolevulinic Acid", "descriptor_ui": "D000622", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Coturnix", "descriptor_ui": "D003370", "major_topic": true }, { "descriptor": "Egg Shell", "descriptor_ui": "D004528", "major_topic": true }, { "descriptor": "Eggs", "descriptor_ui": "D004531", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Heme", "descriptor_ui": "D006418", "major_topic": false }, { "descriptor": "Quail", "descriptor_ui": "D011784", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Uterus", "descriptor_ui": "D014599", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "3", "normalized_date": "2022", "pages": "e0265008", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "17", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Uterus-specific transcriptional regulation underlies eggshell pigment production in Japanese quail.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A newly formed memory is initially unstable. However, if it is consolidated into the brain, the consolidated memory is stored as stable long-term memory (LTM). Despite the recent progress, the molecular and cellular mechanisms of LTM have not yet been fully elucidated. The fruitfly Drosophila melanogaster, for which various genetic tools are available, has been used to clarify the molecular mechanisms of LTM. Using the Drosophila courtship-conditioning assay as a memory paradigm, we previously identified that the circadian clock gene period (per) plays a vital role in consolidating LTM, suggesting that per-expressing clock neurons are critically involved in LTM. However, it is still incompletely understood which clock neurons are essential for LTM. Here, we show that dorsal–lateral clock neurons (LNds) play a crucial role in LTM. Using an LNd-specific split-GAL4 line, we confirmed that disruption of synaptic transmission in LNds impaired LTM maintenance. On the other hand, induction of per RNAi or the dominant-negative transgene of Per in LNds impaired LTM consolidation. Our results reveal that transmitter release and Per function in LNds are involved in courtship memory processing.", "classifications": [ { "id": "21H00434", "label": "21H00434", "researcher": "Takaomi Sakai", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Kurata", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.12923" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "4", "normalized_date": "2022", "pages": "266-279", "proceedings_title": null, "publisher": "", "title": "Genes to Cells", "volume": "27", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Dorsal–lateral clock neurons modulate consolidation and maintenance of long-term memory in Drosophila", "url": "https://onlinelibrary.wiley.com/doi/abs/10.1111/gtc.12923", "zotero": { "item_type": "journalArticle" } }, { "abstract": "With the development of laser technology in the 1960s, a technique was developed to inject intradermal vaccines immediately after irradiating the skin with laser light to elicit an adjuvant effect, referred to as \"laser adjuvant.\" We have been investigating the mechanism of laser adjuvant in influenza mouse models using noninvasive continuous-wave (CW) near-infrared (NIR) light mainly at a wavelength of 1064 nm, and have shown that the production of reactive-oxygen-species (ROS) in the skin and mast cells in the skin tissue plays an important role in the laser adjuvant effect. The new wavelength of 1270 nm NIR light is characterized by its ability to elicit the same vaccine adjuvant effect as other wavelengths at a lower energy, and may be suitable for clinical applications. In this study, we investigated the physiological activity of CW1270 nm NIR light in mast cells, its biological activity on mouse skin, and the durability of the vaccine adjuvant effect in influenza vaccine mouse models. We show that irradiation of mast cells with 1270 nm NIR light produced ROS and ATP, and irradiation of isolated mitochondria also produced ATP. In mouse skin, the relative expression levels of chemokine mRNAs, such as Ccl2 and Ccl20, were increased by irradiation with 1270 and 1064 nm NIR light at minimum safe irradiance. However, the relative expression of Nfkb1 was increased at 1064 nm, but not at 1270 nm. Serum anti-influenza IgG antibody titers increased early after immunization with 1064 nm, whereas with 1270 nm, there was not only an early response of antibody production but also persistence of antibody titers over the medium- to long-term. Thus, to our knowledge, we show for the first time that 1270 nm NIR light induces ROS and ATP production in mitochondria as photoreceptors, initiating a cascade of laser adjuvant effects for intradermal vaccines. Additionally, we demonstrate that there are wavelength-specific variations in the mechanisms and effects of laser adjuvants. In conclusion, CW1270 nm NIR light is expected to be clinically applicable as a novel laser adjuvant that is equivalent or superior to 1064 nm NIR light, because it can be operated at low energy and has a wavelength-specific adjuvant effect with medium- to long-lasting antibody titer.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Takunori", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Komai", "name": null }, { "creator_type": "author", "first_name": "Shusaku", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Kitagami", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Serizawa", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Nagaoka", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Yokomizo", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Miyahira", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Kawana", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Kimizuka", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2022.1028733" }, "pmcid": { "normalized": "PMC9684730" }, "pmid": { "normalized": "36439134" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Adjuvants, Immunologic", "descriptor_ui": "D000276", "major_topic": false }, { "descriptor": "Adjuvants, Pharmaceutic", "descriptor_ui": "D000277", "major_topic": false }, { "descriptor": "Adjuvants, Vaccine", "descriptor_ui": "D000089582", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Influenza Vaccines", "descriptor_ui": "D007252", "major_topic": true }, { "descriptor": "Infrared Rays", "descriptor_ui": "D007259", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "1028733", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "1270 nm near-infrared light as a novel vaccine adjuvant acts on mitochondrial photoreception in intradermal vaccines.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer is one of the most severe health problems worldwide accounting for the second leading cause of death. Studies have indicated that cancers utilize different metabolic systems as compared with normal cells to produce extra energy and substances required for their survival, which contributes to tumor formation and progression. Recently, the fruit fly Drosophila has been attracting significant attention as a whole-body model for elucidating the cancer mechanisms including metabolism. This tiny organism offers a valuable toolkit with various advantages such as high genetic conservation and similar drug response to mammals. In this review, we introduce flies modeling for cancer patient genotypes which have pinpointed novel therapeutic targets and drug candidates in the salivary gland, thyroid, colon, lung, and brain. Furthermore, we introduce fly models for metabolic diseases such as diabetes mellitus, obesity, and cachexia. Diabetes mellitus and obesity are widely acknowledged risk factors for cancer, while cachexia is a cancer-related metabolic condition. In addition, we specifically focus on two cancer metabolic alterations: the Warburg effect and redox metabolism. Indeed, flies proved useful to reveal the relationship between these metabolic changes and cancer. Such accumulating achievements indicate that Drosophila offers an efficient platform to clarify the mechanisms of cancer as a systemic disease.", "classifications": [ { "id": "19H05412", "label": "19H05412", "researcher": "Masahiro Sonoshita", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hui", "last_name": "Jiang", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Han", "last_name": "Hai", "name": null }, { "creator_type": "author", "first_name": "Ryodai", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fonc.2022.982751" }, "pmcid": { "normalized": "PMC9458318" }, "pmid": { "normalized": "36091180" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "982751", "proceedings_title": null, "publisher": "", "title": "Frontiers in oncology", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Drosophila as a toolkit to tackle cancer and its metabolism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cladoceran crustacean Daphnia produces only females by parthenogenesis in a healthy population. However, in response to environmental declines such as crowding and lack of foods, it produces eggs destined to become males that are genetically identical to females. During the development of the sexually committed eggs, DM domain-containing transcription factor Doublesex1 (Dsx1) orchestrates male trait formation globally both in somatic and gonadal tissues. Recent studies have revealed that Dsx1 expression is tightly controlled at transcriptional, post-transcriptional, and epigenetic levels to avoid sexual ambiguity. In this review, together with basic information on Dsx1 structure and expression, we introduce the multi-layered Dsx1 regulation and discuss how each regulation is interconnected for controlling male development in environmental sex-determining Daphnia.", "classifications": [ { "id": "19H05423", "label": "19H05423", "researcher": "Yasuhiko Kato", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2022.881255" }, "pmcid": { "normalized": "PMC9043111" }, "pmid": { "normalized": "35493103" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "881255", "proceedings_title": null, "publisher": "", "title": "Frontiers in cell and developmental biology", "volume": "10", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Regulation of Doublesex1 Expression for Environmental Sex Determination in the Cladoceran Crustacean Daphnia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: There is currently no subjective, definitive evaluation method for therapeutic indication other than symptoms in aortic regurgitation. Energy loss, a novel parameter of cardiac workload, can be visualized and quantified using echocardiography vector flow mapping. The purpose of the present study was to evaluate whether energy loss in patients with chronic aortic regurgitation can quantify their subjective symptoms more clearly than other conventional metrics. METHODS: We studied 15 patients undergoing elective aortic valve surgery for aortic regurgitation. We divided the patients into symptomatic and asymptomatic groups using their admission records. We analyzed the mean energy loss in one cardiac cycle using transesophageal echocardiography during the preoperative period. The relationships between symptoms, energy loss, and other conventional metrics were statistically analyzed. RESULTS: There were seven and eight patients in the symptomatic and asymptomatic groups, respectively. The mean energy loss of one cardiac cycle was higher in the symptomatic group (121 mW/m [96-184]) than in the asymptomatic group (87 mW/m [80-103]) (p = 0.040), whereas the diastolic diameter was higher in the asymptomatic group (65 mm [59-78]) than in the symptomatic group (57 mm [51-57]) (p = 0.040). There was no significant difference between the symptomatic and asymptomatic groups in terms of other conventional metrics. CONCLUSIONS: An energy loss can quantify patients' subjective symptoms more clearly than other conventional metrics. The small sample size is the primary limitation of our study, further studies assessing larger cohort of patients are warranted to validate our findings.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kainuma", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Itatani", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Ohara", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Numata", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Yaku", "name": null }, { "creator_type": "author", "first_name": "Teiji", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fsurg.2022.739743" }, "pmcid": { "normalized": "PMC8889468" }, "pmid": { "normalized": "35252323" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "739743", "proceedings_title": null, "publisher": "", "title": "Frontiers in surgery", "volume": "9", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Preoperative Left Ventricular Energy Loss in the Operating Theater Reflects Subjective Symptoms in Chronic Aortic Regurgitation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fused in sarcoma (FUS), a DNA/RNA-binding protein, undergoes liquid-liquid phase separation to form granules in cells. Aberrant FUS granulation is associated with neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal lobar degeneration. We found that FUS granules contain a multifunctional AAA ATPase, valosin-containing protein (VCP), which is known as a key regulator of protein degradation. FUS granule stability depends on ATP concentrations in cells. VCP ATPase changes the FUS granule stability time-dependently by consuming ATP to reduce its concentrations in the granules: VCPs in de novo FUS granules stabilize the granules, while long-lasting VCP colocalization destabilizes the granules. The proteolysis-promoting function of VCP may subsequently dissolve the unstabilized granules. We propose that VCP colocalized to the FUS granules acts as a timer to limit the residence time of the granules in cells.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kyota", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Myeong-Gyun", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Jeong Kon", "last_name": "Seo", "name": null }, { "creator_type": "author", "first_name": "Hyun-Woo", "last_name": "Rhee", "name": null }, { "creator_type": "author", "first_name": "Shin-ichi", "last_name": "Tate", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/1873-3468.14353" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "11", "normalized_date": "2022", "pages": "1412-1423", "proceedings_title": null, "publisher": "", "title": "FEBS Letters", "volume": "596", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Valosin-containing protein regulates the stability of fused in sarcoma granules in cells by changing ATP concentrations", "url": "https://onlinelibrary.wiley.com/doi/abs/10.1002/1873-3468.14353", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To support the detection, recording, and analysis of nucleation events during in situ observations, we developed an early detection system for nucleation events observed using a liquid-cell transmission electron microscope. Detectability was achieved using the machine learning equivalent of detection by humans watching a video numerous times. The detection system was applied to the nucleation of sodium chloride crystals from a saturated acetone solution of sodium chlorate. Nanoparticles with a radius of more greater than 150 nm were detected in a viewing area of 12 mum x 12 mum by the detection system. The analysis of the change in the size of the growing particles as a function of time suggested that the crystal phase of the particles with a radius smaller than 400 nm differed from that of the crystals larger than 400 nm. Moreover, the use of machine learning enabled the detection of numerous nanometer sized nuclei. The nucleation rate estimated from the machine-learning-based detection was of the same order as that estimated from the detection using manual procedures.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Katsuno", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fchem.2022.818230" }, "pmcid": { "normalized": "PMC8819544" }, "pmid": { "normalized": "35141199" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "818230", "proceedings_title": null, "publisher": "", "title": "Frontiers in chemistry", "volume": "10", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Early Detection of Nucleation Events From Solution in LC-TEM by Machine Learning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The taxon Elasmobranchii (sharks and rays) contains one of the long-established evolutionary lineages of vertebrates with a tantalizing collection of species occupying critical aquatic habitats. To overcome the current limitation in molecular resources, we launched the Squalomix Consortium in 2020 to promote a genome-wide array of molecular approaches, specifically targeting shark and ray species. Among the various bottlenecks in working with elasmobranchs are their elusiveness and low fecundity as well as the large and highly repetitive genomes. Their peculiar body fluid composition has also hindered the establishment of methods to perform routine cell culturing required for their karyotyping. In the Squalomix consortium, these obstacles are expected to be solved through a combination of in-house cytological techniques including karyotyping of cultured cells, chromatin preparation for Hi-C data acquisition, and high fidelity long-read sequencing. The resources and products obtained in this consortium, including genome and transcriptome sequences, a genome browser powered by JBrowse2 to visualize sequence alignments, and comprehensive matrices of gene expression profiles for selected species are accessible through https://github.com/Squalomix/info.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Osamu", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "John", "last_name": "Rozewicki", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tatsumi", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Ohishi", "name": null }, { "creator_type": "author", "first_name": "Tazro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Yagura", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Chiharu", "last_name": "Tanegashima", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Teramura", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Hirase", "name": null }, { "creator_type": "author", "first_name": "Akane", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Milton", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Salvatore", "last_name": "D'Aniello", "name": null }, { "creator_type": "author", "first_name": "Filipe", "last_name": "Castro", "name": null }, { "creator_type": "author", "first_name": "Andre", "last_name": "Machado", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Misawa", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Junna", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Asahida", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kiyomi", "last_name": "Murakumo", "name": null }, { "creator_type": "author", "first_name": "Rui", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Iker", "last_name": "Irisarri", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Semba", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kiyonori", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Itsuki", "last_name": "Kiyatake", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Hyodo", "name": null }, { "creator_type": "author", "first_name": "Mitsutaka", "last_name": "Kadota", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Uno", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Kuraku", "name": null } ], "identifiers": { "doi": { "normalized": "10.12688/f1000research.123591.1" }, "pmcid": { "normalized": "PMC9561540" }, "pmid": { "normalized": "36262334" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "Information Dissemination", "descriptor_ui": "D033181", "major_topic": false }, { "descriptor": "Sharks", "descriptor_ui": "D012754", "major_topic": true }, { "descriptor": "Vertebrates", "descriptor_ui": "D014714", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "1077", "proceedings_title": null, "publisher": "", "title": "F1000Research", "volume": "11", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Squalomix: shark and ray genome analysis consortium and its data sharing platform.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "According to the three hit concept of depression, interaction of genetic predisposition altered epigenetic programming and environmental stress factors contribute to the disease. Earlier we demonstrated the construct and face validity of our three hit concept-based mouse model. In the present work, we aimed to examine the predictive validity of our model, the third willnerian criterion. Fluoxetine treatment was applied in chronic variable mild stress (CVMS)-exposed (environmental hit) CD1 mice carrying one mutated allele of pituitary adenylate cyclase-activating polypeptide gene (genetic hit) that were previously exposed to maternal deprivation (epigenetic hit) vs. controls. Fluoxetine reduced the anxiety level in CVMS-exposed mice in marble burying test, and decreased the depression level in tail suspension test if mice were not deprived maternally. History of maternal deprivation caused fundamental functional-morphological changes in response to CVMS and fluoxetine treatment in the corticotropin-releasing hormone-producing cells of the bed nucleus of the stria terminalis and central amygdala, in tyrosine-hydroxylase content of ventral tegmental area, in urocortin 1-expressing cells of the centrally projecting Edinger-Westphal nucleus, and serotonergic cells of the dorsal raphe nucleus. The epigenetic background of alterations was approved by altered acetylation of histone H3. Our findings further support the validity of both the three hit concept and that of our animal model. Reversal of behavioral and functional-morphological anomalies by fluoxetine treatment supports the predictive validity of the model. This study highlights that early life stress does not only interact with the genetic and environmental factors, but has strong influence also on therapeutic efficacy.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tamas", "last_name": "Gaszner", "name": null }, { "creator_type": "author", "first_name": "Jozsef", "last_name": "Farkas", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Kun", "name": null }, { "creator_type": "author", "first_name": "Balazs", "last_name": "Ujvari", "name": null }, { "creator_type": "author", "first_name": "Gergely", "last_name": "Berta", "name": null }, { "creator_type": "author", "first_name": "Valer", "last_name": "Csernus", "name": null }, { "creator_type": "author", "first_name": "Nora", "last_name": "Furedi", "name": null }, { "creator_type": "author", "first_name": "Laszlo Akos", "last_name": "Kovacs", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Dora", "last_name": "Reglodi", "name": null }, { "creator_type": "author", "first_name": "Viktoria", "last_name": "Kormos", "name": null }, { "creator_type": "author", "first_name": "Balazs", "last_name": "Gaszner", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fendo.2022.995900" }, "pmcid": { "normalized": "PMC9537566" }, "pmid": { "normalized": "36213293" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Carbonate", "descriptor_ui": "D002119", "major_topic": false }, { "descriptor": "Corticotropin-Releasing Hormone", "descriptor_ui": "D003346", "major_topic": false }, { "descriptor": "Depression", "descriptor_ui": "D003863", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Fluoxetine", "descriptor_ui": "D005473", "major_topic": true }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mixed Function Oxygenases", "descriptor_ui": "D006899", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": true }, { "descriptor": "Stress, Psychological", "descriptor_ui": "D013315", "major_topic": false }, { "descriptor": "Tyrosine", "descriptor_ui": "D014443", "major_topic": false }, { "descriptor": "Urocortins", "descriptor_ui": "D054832", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "995900", "proceedings_title": null, "publisher": "", "title": "Frontiers in endocrinology", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Fluoxetine treatment supports predictive validity of the three hit model of depression in male PACAP heterozygous mice and underpins the impact of early life adversity on therapeutic efficacy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Type-2 bitter taste receptors (Tas2Rs) are a large family of G protein-coupled receptors that are expressed in the oral cavity and serve to detect substances with bitter tastes in foods and medicines. Recent evidence suggests that Tas2Rs are also expressed extraorally, including in immune cells. However, the role of Tas2Rs in immune cells remains controversial. Here, we demonstrate that Tas2R126, Tas2R135, and Tas2R143 are expressed in mouse neutrophils, but not in other immune cells such as macrophages or T and B lymphocytes. Treatment of bone marrow-derived neutrophils from wild-type mice with the Tas2R126/143 agonists arbutin and d-salicin led to enhanced C-X-C motif chemokine ligand 2 (CXCL2)-stimulated migration in vitro, but this response was not observed in neutrophils from Tas2r126/135/143-deficient mice. Enhancement of CXCL2-stimulated migration by Tas2R agonists was accompanied by increased phosphorylation of myosin light chain 2 (MLC2) and was blocked by pretreatment of neutrophils with inhibitors of Rho-associated coiled-coil-containing protein kinase (ROCK), but not by inhibitors of the small GTPase RhoA. Taken together, these results demonstrate that mouse neutrophils express functional Tas2R126/143 and suggest a role for Tas2R126/143-ROCK-MLC2-dependent signaling in the regulation of neutrophil migration.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Daichi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Watarai", "name": null }, { "creator_type": "author", "first_name": "Madoka", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Fumihiro", "last_name": "Saika", "name": null }, { "creator_type": "author", "first_name": "Norikazu", "last_name": "Kiguchi", "name": null }, { "creator_type": "author", "first_name": "Arata", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Matsuzaki", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2022.973880" }, "pmcid": { "normalized": "PMC9436316" }, "pmid": { "normalized": "36059440" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neutrophils", "descriptor_ui": "D009504", "major_topic": true }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Taste", "descriptor_ui": "D013649", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "973880", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Tas2R signaling enhances mouse neutrophil migration via a ROCK-dependent pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The RNA polymerase II-associated factor 1 complex (PAF1C) is a protein complex that consists of LEO1, RTF1, PAF1, CDC73, and CTR9, and has been shown to be involved in RNA polymerase II-mediated transcriptional and chromatin regulation. Although it has been shown to regulate a variety of biological processes, the precise role of the PAF1C during germ line development has not been clarified. In this study, we found that reduction in the function of the PAF1C components, LEO-1, RTFO-1, PAFO-1, CDC-73, and CTR-9, in Caenorhabditis elegans affects oogenesis. Defects in oogenesis were also confirmed using an oocyte maturation marker, OMA-1::GFP. While four to five OMA-1::GFP-positive oocytes were observed in wild-type animals, their numbers were significantly decreased in pafo-1 mutant and leo-1(RNAi), pafo-1(RNAi), and cdc-73(RNAi) animals. Expression of a functional PAFO-1::mCherry transgene in the germline significantly rescued the oogenesis-defective phenotype of the pafo-1 mutants, suggesting that expression of the PAF1C in germ cells is required for oogenesis. Notably, overexpression of OMA-1::GFP partially rescued the oogenesis defect in the pafo-1 mutants. Based on our findings, we propose that the PAF1C promotes oogenesis in a cell-autonomous manner by positively regulating the expression of genes involved in oocyte maturation.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Takatsuka", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Unno", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.12938" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "6", "normalized_date": "2022", "pages": "409-420", "proceedings_title": null, "publisher": "", "title": "Genes to Cells", "volume": "27", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "The PAF1 complex cell autonomously promotes oogenesis in Caenorhabditis elegans", "url": "https://onlinelibrary.wiley.com/doi/abs/10.1111/gtc.12938", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background and Aims The coronavirus disease 2019 (COVID-19) pandemic precipitated lifestyle changes. We aimed to clarify whether COVID-19–induced lifestyle changes affected the development of metabolic dysfunction–associated fatty liver disease (MAFLD). Methods This retrospective longitudinal study included 973 participants who underwent health check-ups between 2018 and 2020. We used data from the MedCity21 health examination registry. Participants' clinical characteristics and lifestyle habits were investigated. Independent lifestyle predictors of MAFLD development before the pandemic (2018-2019) and during the pandemic (2019-2020) were identified using logistic regression analysis. Results In 2018, 261 (27%) patients were diagnosed with MAFLD. Before the pandemic, 22 patients developed new MAFLD. During this time, routine late-night meals were identified as an independent lifestyle predictor of MAFLD development (hazard ratio [HR] 2.54, 95% confidence interval [CI] 1.02-6.36, P = .046). In contrast, 44 patients developed new MAFLD during the pandemic. During this time, higher daily alcohol intake was identified as an independent lifestyle predictor of MAFLD development (HR 1.03, 95% CI 1.01-1.05, P = .008). In participants aged <60 years, daily alcohol intake and the proportion of participants who ate 2 times/day were significantly higher in patients who developed MAFLD during the pandemic than in those who did not. In participants aged ≥60 years, no lifestyle habits were associated with MAFLD development before or during the pandemic. Conclusions New MAFLD diagnoses increased during the COVID-19 pandemic. Changes in lifestyle factors, particularly in those aged <60 years, must be monitored and addressed as the pandemic continues.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hideki", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Fukumoto", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Akemi", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Nadatani", "name": null }, { "creator_type": "author", "first_name": "Yukie", "last_name": "Tauchi", "name": null }, { "creator_type": "author", "first_name": "Yuuko", "last_name": "Nishii", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kamada", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Norifumi", "last_name": "Kawada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/liv.15158" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "5", "normalized_date": "2022", "pages": "995-1004", "proceedings_title": null, "publisher": "", "title": "Liver International", "volume": "42", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Lifestyle changes during the coronavirus disease 2019 pandemic impact metabolic dysfunction–associated fatty liver disease", "url": "https://onlinelibrary.wiley.com/doi/abs/10.1111/liv.15158", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Membrane receptors provide interfaces of various extracellular stimuli to transduce the signal into the cell. Receptors are required to possess such conflicting properties as high sensitivity and noise reduction for the cell to keep its homeostasis and appropriate responses. To understand the mechanisms by which these functions are achieved, single-molecule monitoring of the motilities of receptors and signaling molecules on the plasma membrane is one of the most direct approaches. This review article introduces several recent single-molecule imaging studies of receptors, including the author's recent work on triple-color single-molecule imaging of G protein-coupled receptors. Based on these researches, advantages and perspectives of the single-molecule imaging approach to solving the mechanisms of receptor functions are illustrated.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v19.0007" }, "pmcid": { "normalized": "PMC8968032" }, "pmid": { "normalized": "35435651" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "1-9", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "19", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Triple-color single-molecule imaging for analysis of the role of receptor oligomers in signal transduction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Phosphoinositide metabolism is critically involved in human cancer cell migration and metastatic growth. The formation of lamellipodia at the leading edge of migrating cells is regulated by metabolism of the inositol phospholipid PI(4,5)P2 into PI(3,4,5)P3. The synthesized PI(3,4,5)P3 promotes the translocation of WASP family verprolin homologous protein 2 (WAVE2) to the plasma membrane and regulates guanine nucleotide exchange factor Rac-mediated actin filament remodeling. Here, we investigated if VIPR2, a receptor for vasoactive intestinal peptide (VIP), has a potential role in regulating cell migration via this pathway. We found that silencing of VIPR2 in MDA-MB-231 and MCF-7 human breast cancer cells inhibited VIP-induced cell migration. In contrast, stable expression of exogenous VIPR2 promoted VIP-induced tumor cell migration, an effect that was inhibited by the addition of a PI3-kinase (PI3K)gamma inhibitor or a VIPR2-selective antagonist. VIPR2 stably-expressing cells exhibited increased PI3K activity. Membrane localization of PI(3,4,5)P3 was significantly attenuated by VIPR2-silencing. VIPR2-silencing in MDA-MB-231 cells suppressed lamellipodium extension; in VIPR2-overexpressing cells, VIPR2 accumulated in the cell membrane on lamellipodia and co-localized with WAVE2. Conversely, VIPR2-silencing reduced WAVE2 level on the cell membrane and inhibited the interaction between WAVE2, actin-related protein 3, and actin. These findings suggest that VIP-VIPR2 signaling controls cancer migration by regulating WAVE2-mediated actin nucleation and elongation for lamellipodium formation through the synthesis of PI(3,4,5)P3.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Misa", "last_name": "Yamasaka", "name": null }, { "creator_type": "author", "first_name": "Kairi", "last_name": "Ozasa", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "James A.", "last_name": "Waschek", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fonc.2022.852358" }, "pmcid": { "normalized": "PMC9550923" }, "pmid": { "normalized": "36237322" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "852358", "proceedings_title": null, "publisher": "", "title": "Frontiers in oncology", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Vasoactive intestinal peptide-VIPR2 signaling regulates tumor cell migration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "GABAergic neurons in the ventral tegmental area (VTA) have brain-wide projections and are involved in multiple behavioral and physiological functions. Here, we revealed the responsiveness of Gad67+ neurons in VTA (VTAGad67+) to various neurotransmitters involved in the regulation of sleep/wakefulness by slice patch clamp recording. Among the substances tested, a cholinergic agonist activated, but serotonin, dopamine and histamine inhibited these neurons. Dense VTAGad67+ neuronal projections were observed in brain areas regulating sleep/wakefulness, including the central amygdala (CeA), dorsal raphe nucleus (DRN), and locus coeruleus (LC). Using a combination of electrophysiology and optogenetic studies, we showed that VTAGad67+ neurons inhibited all neurons recorded in the DRN, but did not inhibit randomly recorded neurons in the CeA and LC. Further examination revealed that the serotonergic neurons in the DRN (DRN5-HT) were monosynaptically innervated and inhibited by VTAGad67+ neurons. All recorded DRN5-HT neurons received inhibitory input from VTAGad67+ neurons, while only one quarter of them received inhibitory input from local GABAergic neurons. Gad67+ neurons in the DRN (DRNGad67+) also received monosynaptic inhibitory input from VTAGad67+ neurons. Taken together, we found that VTAGad67+ neurons were integrated in many inputs, and their output inhibits DRN5-HT neurons, which may regulate physiological functions including sleep/wakefulness.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sheikh Mizanur", "last_name": "Rahaman", "name": null }, { "creator_type": "author", "first_name": "Srikanta", "last_name": "Chowdhury", "name": null }, { "creator_type": "author", "first_name": "Yasutaka", "last_name": "Mukai", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2022.877054" }, "pmcid": { "normalized": "PMC9160575" }, "pmid": { "normalized": "35663550" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "877054", "proceedings_title": null, "publisher": "", "title": "Frontiers in neuroscience", "volume": "16", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Functional Interaction Between GABAergic Neurons in the Ventral Tegmental Area and Serotonergic Neurons in the Dorsal Raphe Nucleus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chronic pain often has an unknown cause, and many patients with chronic pain learn to accept that their pain is incurable and pharmacologic treatments are only temporarily effective. Complementary and integrative health approaches for pain are thus in high demand. One such approach is soft touch, e.g., adhesion of pyramidal thorn patches in a pain region. The effects of patch adhesion on pain relief have been confirmed in patients with various types of pain. A recent study using near-infrared spectroscopy revealed that the dorsolateral prefrontal cortex (DLPFC), especially the left side, is likely to be inactivated in patients experiencing pain relief during patch treatment. Mindfulness meditation is another well-known complementary and integrative approach for achieving pain relief. The relation between pain relief due to mindfulness meditation and changes in brain regions, including the DLPFC, has long been examined. In the present review article, we survey the literature describing the effects of the above-mentioned complementary and integrative treatments on pain relief, and outline the important brain regions, including the DLPFC, that are involved in analgesia. We hope that the present article will provide clues to researchers who hope to advance neurosensory treatments for pain relief without medication.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Fusako", "last_name": "Koshikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v19.0014" }, "pmcid": { "normalized": "PMC9173858" }, "pmid": { "normalized": "35797407" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "1-10", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "19", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Dorsolateral prefrontal cortex sensing analgesia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sponges (Porifera) are a large phylum that includes an enormous number of species. They are classified into four classes. Among these four classes, class Demospongiae is the largest and contains more than 90% of sponge species. In the last decade, methodologies for molecular studies and sequencing resources in sponge biology have dramatically advanced and made it possible to clearly define particular types of cells based on the genes they are expressing. Here we describe in detail the method of high-resolution WISH (whole mount in situ hybridization) and dual color fluorescent detection of in situ hybridization (dual color FISH) that we have established to detect particular types of cells, especially their stem cells known as archeocytes, in juveniles of freshwater demosponge, E. fluviatilis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Chiaki", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Funayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-2172-1_17" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35359316" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fresh Water", "descriptor_ui": "D005618", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Porifera", "descriptor_ui": "D011161", "major_topic": true }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "335-346", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2450", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "In Situ Hybridization to Identify Stem Cells in the Freshwater Sponge Ephydatia fluviatilis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Joan", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null }, { "creator_type": "author", "first_name": "Qihe", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Roel", "last_name": "Bijkerk", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2022.1105402" }, "pmcid": { "normalized": "PMC9877212" }, "pmid": { "normalized": "36712966" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "1105402", "proceedings_title": null, "publisher": "", "title": "Frontiers in cell and developmental biology", "volume": "10", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Editorial: Epithelial plasticity and complexity in development, disease and regeneration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The epidermis, outermost layer of the skin, forms a barrier and is involved in innate and adaptive immunity in an organism. Keratinocytes participate in all these three protective processes. However, a regulator of keratinocyte protective responses against external dangers and stresses remains elusive. We found that upregulation of the orphan gene 2610528A11Rik was a common factor in the skin of mice with several types of inflammation. In the human epidermis, peptide expression of G protein-coupled receptor 15 ligand (GPR15L), encoded by the human ortholog C10orf99, was highly induced in the lesional skin of patients with atopic dermatitis or psoriasis. C10orf99 gene transfection into normal human epidermal keratinocytes (NHEKs) induced the expression of inflammatory mediators and reduced the expression of barrier-related genes. Gene ontology analyses showed its association with translation, mitogen-activated protein kinase (MAPK), mitochondria, and lipid metabolism. Treatment with GPR15L reduced the expression levels of filaggrin and loricrin in human keratinocyte 3D cultures. Instead, their expression levels in mouse primary cultured keratinocytes did not show significant differences between the wild-type and 2610528A11Rik deficient keratinocytes. Lipopolysaccharide-induced expression of Il1b and Il6 was less in 2610528A11Rik deficient mouse keratinocytes than in wild-type, and imiquimod-induced psoriatic dermatitis was blunted in 2610528A11Rik deficient mice. Furthermore, repetitive subcutaneous injection of GPR15L in mouse ears induced skin inflammation in a dose-dependent manner. These results suggest that C10orf99/GPR15L is a primary inducible regulator that reduces the barrier formation and induces the inflammatory response of keratinocytes.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Teruki", "last_name": "Dainichi", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Doi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Nakamizo", "name": null }, { "creator_type": "author", "first_name": "Saeko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Farkas", "name": null }, { "creator_type": "author", "first_name": "Pui Mun", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Vipin", "last_name": "Narang", "name": null }, { "creator_type": "author", "first_name": "Ricardo", "last_name": "Moreno Traspas", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Emma", "last_name": "Guttman-Yassky", "name": null }, { "creator_type": "author", "first_name": "Oliver", "last_name": "Dreesen", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Litman", "name": null }, { "creator_type": "author", "first_name": "Bruno", "last_name": "Reversade", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kabashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2022.825032" }, "pmcid": { "normalized": "PMC8902463" }, "pmid": { "normalized": "35273606" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antimicrobial Cationic Peptides", "descriptor_ui": "D023181", "major_topic": false }, { "descriptor": "Dermatitis, Atopic", "descriptor_ui": "D003876", "major_topic": true }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": true }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "825032", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "C10orf99/GPR15L Regulates Proinflammatory Response of Keratinocytes and Barrier Formation of the Skin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Regulatory T cells (Tregs) are normally born in the thymus and activated in secondary lymphoid tissues to suppress immune responses in the lymph node and at sites of inflammation. Tregs are also resident in various tissues or accumulate in damaged tissues, which are now called tissue Tregs, and contribute to homeostasis and tissue repair by interacting with non-immune cells. We have shown that Tregs accumulate in the brain during the chronic phase in a mouse cerebral infarction model, and these Tregs acquire the characteristic properties of brain Tregs and contribute to the recovery of neurological damage by interacting with astrocytes. However, the mechanism of tissue Treg development is not fully understood. We developed a culture method that confers brain Treg characteristics in vitro. Naive Tregs from the spleen were activated and efficiently amplified by T-cell receptor (TCR) stimulation in the presence of primary astrocytes. Furthermore, adding IL-33 and serotonin could confer part of the properties of brain Tregs, such as ST2, peroxisome proliferator-activated receptor gamma (PPARgamma), and serotonin receptor 7 (Htr7) expression. Transcriptome analysis revealed that in vitro generated brain Treg-like Tregs (induced brain Tregs; iB-Tregs) showed similar gene expression patterns as those in in vivo brain Tregs, although they were not identical. Furthermore, in Parkinson's disease models, in which T cells have been shown to be involved in disease progression, iB-Tregs infiltrated into the brain more readily and ameliorated pathological symptoms more effectively than splenic Tregs. These data indicate that iB-Tregs contribute to our understanding of brain Treg development and could also be therapeutic for inflammatory brain diseases.", "classifications": [ { "id": "21H00432", "label": "21H00432", "researcher": "Minako Ito", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinichi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Ako", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Ohyagi", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Kikutake", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Iizuka-Koga", "name": null }, { "creator_type": "author", "first_name": "Mikita", "last_name": "Suyama", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2022.960036" }, "pmcid": { "normalized": "PMC9335882" }, "pmid": { "normalized": "35911740" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": true }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false }, { "descriptor": "Receptors, Serotonin", "descriptor_ui": "D011985", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "960036", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "In Vitro Generation of Brain Regulatory T Cells by Co-culturing With Astrocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Osmoregulatory behaviours should have evolutionarily modified for terrestrialisation of vertebrates. In mammals, sensations of buccal food and drying have immediate effects on postprandial thirst to prevent future systemic dehydration, and is thereby considered to be 'anticipatory thirst'. However, it remains unclear whether such an anticipatory response has been acquired in the non-tetrapod lineage. Using the mudskipper goby (Periophthalmus modestus) as a semi-terrestrial ray-finned fish, we herein investigated postprandial drinking and other unique features like full-body 'rolling' over on the back although these behaviours had not been considered to have osmoregulatory functions. In our observations on tidal flats, mudskippers migrated into water areas within a minute after terrestrial eating, and exhibited rolling behaviour with accompanying pectoral-fin movements. In aquarium experiments, frequency of migration into a water area for drinking increased within a few minutes after eating onset, without systemic dehydration. During their low humidity exposure, frequency of the rolling behaviour and pectoral-fin movements increased by more than five times to moisten the skin before systemic dehydration. These findings suggest anticipatory responses which arise from oral/gastrointestinal and cutaneous sensation in the goby. These sensation and motivation seem to have evolved in distantly related species in order to solve osmoregulatory challenges during terrestrialisation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yukitoshi", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Hyodo", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0277968" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36477197" } }, "mesh": [ { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "12", "normalized_date": "2022", "pages": "e0277968", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "17", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Behavioural osmoregulation during land invasion in fish: Prandial drinking and wetting of the dry skin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Potassium-sensing oligonucleotide, PSO, a conjugate of a quadruplex structure-forming oligonucleotide with a peptide incorporating a Forster Resonance Energy Transfer (FRET) chromophore pair, has been developed for fluorescent detection of potassium ion (K(+)) in aqueous medium. PSO 1 could be introduced into cells for real-time imaging of cytoplasmic K(+) concentrations. To perform fluorescent imaging of K(+) on the cell surface, we synthesized twelve PSO derivatives with different types of peptide types and lengths, and oligonucleotide sequences including thrombin-binding aptamer (TBA) sequences with FAM and TAMRA as a FRET chromophore pair, and evaluated their performance. 1 was shown to respond selectively to K(+), not to most ions present in vivo, and to show reciprocal fluorescence changes in response to K(+) concentration. For the peptide chains and oligonucleotide sequences examined in this study, the PSO derivatives had K d values for K(+) in the range of 5-30 mM. All PSO derivatives showed high K(+) selectivity even in the presence of excess Na(+). The PSO derivatives were successfully localized to the cell surface by biotinylated concanavalin A (ConA) or sulfo-NHS-biotin via streptavidin (StAv). Fluorescence imaging of extracellular K(+) upon addition of apoptosis inducers was successfully achieved by 1 localized to the cell surface.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shinobu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Ohzawa", "name": null }, { "creator_type": "author", "first_name": "Kojiro", "last_name": "Sota", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Udo", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Sueda", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Shigeori", "last_name": "Takenaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fchem.2022.922094" }, "pmcid": { "normalized": "PMC9306769" }, "pmid": { "normalized": "35873036" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "922094", "proceedings_title": null, "publisher": "", "title": "Frontiers in chemistry", "volume": "10", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Fluorescence Imaging of Extracellular Potassium Ion Using Potassium Sensing Oligonucleotide.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human T-cell leukemia virus type 1 (HTLV-1), a retrovirus which mainly infects CD4(+) T cells and causes adult T-cell leukemia/lymphoma (ATL), is primarily transmitted via direct cell-to-cell transmission. This feature generates a wide variety of infected clones in hosts, which are maintained via clonal proliferation, resulting in the persistence and survival of the virus. The maintenance of the pool of infected cells is achieved by sculpting the immunophenotype of infected cells and modulating host immune responses to avoid immune surveillance. Here, we review the processes undertaken by HTLV-1 to modulate and subvert host immune responses which contributes to viral persistence and development of ATL.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Benjy J. Y.", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sugata", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yorifumi", "last_name": "Satou", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2022.991928" }, "pmcid": { "normalized": "PMC9591123" }, "pmid": { "normalized": "36300109" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Human T-lymphotropic virus 1", "descriptor_ui": "D015368", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunophenotyping", "descriptor_ui": "D016130", "major_topic": false }, { "descriptor": "Leukemia-Lymphoma, Adult T-Cell", "descriptor_ui": "D015459", "major_topic": true }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "991928", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "HTLV-1 persistence and leukemogenesis: A game of hide-and-seek with the host immune system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ruiqing", "last_name": "Ni", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Bin", "last_name": "Ji", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2022.952449" }, "pmcid": { "normalized": "PMC9310556" }, "pmid": { "normalized": "35898408" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "952449", "proceedings_title": null, "publisher": "", "title": "Frontiers in neuroscience", "volume": "16", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Editorial: Translational imaging in neurodegenerative proteinopathies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The avian egg is a closed system that protects the growing embryo from external factors but prevents direct observation of embryo development. Various culture systems exist in the literature to study the development of the embryo for short periods of incubation (from 12 h up to a maximum of 60 h of egg incubation). A common flaw to these culture techniques is the inability to culture the unincubated avian blastoderm with intact tissue tensions on its native yolk. The goal of this work is to create a unique novel egg-in-cube system that can be used for long-term quail embryo culture initiated from its unincubated blastoderm stage. The egg-in-cube acts as an artificial transparent eggshell system that holds the growing embryo, making it amenable to microscopy. With the egg-in-cube system, quail embryos can be grown up to 9 days from the unincubated blastoderm (incubated in air, 20.9% O2), which improves to 15 days on switching to a hyperoxic environment of 60% O2. Using transgenic fluorescent quail embryos in the egg-in-cube system, cell movements in the unincubated blastoderm are imaged dynamically using inverted confocal microscopy, which has been challenging to achieve with other culture systems. Apart from these observations, several other imaging applications of the system are described in this work using transgenic fluorescent quail embryos with upright confocal or epifluorescence microscopy. To demonstrate the usefulness of the egg-in-cube system in perturbation experiments, the quail neural tube is electroporated with fluorescent mRNA \"in cubo\", followed by the incubation of the electroporated embryo and microscopy of the electroporated region with the embryo in the cube. The egg-in-cube culture system in combination with the \"in cubo\" electroporation and dynamic imaging capabilities described here will enable researchers to investigate several fundamental questions in early embryogenesis with the avian (quail) embryo on its native yolk.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mohit", "last_name": "Dave", "name": null }, { "creator_type": "author", "first_name": "Joshua", "last_name": "Levin", "name": null }, { "creator_type": "author", "first_name": "Seth Walter", "last_name": "Ruffins", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Scott", "last_name": "Fraser", "name": null }, { "creator_type": "author", "first_name": "Rusty", "last_name": "Lansford", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kawahara", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fphys.2022.893736" }, "pmcid": { "normalized": "PMC9133561" }, "pmid": { "normalized": "35634159" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "893736", "proceedings_title": null, "publisher": "", "title": "Frontiers in physiology", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "A Novel Egg-In-Cube System Enables Long-Term Culture and Dynamic Imaging of Early Embryonic Development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epidermal cells, such as keratinocytes, are regarded as the first sensory cells to transmit nociception and mechanoreception to free nerve endings extended from the dorsal root ganglion (DRG). Previous studies suggested that this transmission occurs as Ca(2+) propagation via ATP receptors. Conversely, the influence of gap junctions on this Ca(2+) propagation is largely unknown. Thus, we examined the localization and the role of connexin 43 among keratinocytes and DRG neurons. We co-cultured keratinocytes and DRG neurons and investigated the effect of pharmacological blockade of gap junctions on Ca(2+) propagation upon stimulation of a single keratinocyte. Immunocytochemical experiments showed that connexin 43 is localized between keratinocytes and between keratinocytes and DRG neurons. Octanol, a gap junction inhibitor, significantly suppressed the concentrical Ca(2+) propagation. Therefore, we conclude that the Ca(2+) propagation mechanism via gap junctions from stimulated keratinocytes to free nerve endings should be taken into account.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Chiaki", "last_name": "Seto", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Kousuke", "last_name": "Inada", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v19.0041" }, "pmcid": { "normalized": "PMC9592570" }, "pmid": { "normalized": "36349331" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "e190041", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "19", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Influence of gap junctions upon Ca(2+) propagation from stimulated keratinocytes to DRG neurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bioluminescence imaging of cellular function is a promising strategy. It has advantages over fluorescence imaging such as high sensitivity, no phototoxicity or no autofluorescence, and compatibility to deep-tissue imaging or optogenetics. However, functional imaging of cellular signaling by bioluminescence is not so easy due to the limited availability of bright bioluminescent indicators.Here we describe a detailed strategy to detect cellular cAMP dynamics by using Nano-lantern (cAMP1.6), one of the brightest bioluminescent indicator for cAMP . Both induced and spontaneous cAMP signaling in social amoeba, with a large and small signal change, respectively, were imaged by this method.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-2245-2_14" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35286679" } }, "mesh": [ { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": true }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "231-240", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2483", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Live Imaging of cAMP Signaling in D. discoideum Based on a Bioluminescent Indicator, Nano-lantern (cAMP).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In sex determination of the crustacean Daphnia magna, male-specific expression of DM-domain transcription factor Doublesex1 (Dsx1) orchestrates the male developmental program triggered by environmental stimuli. We previously identified the CELF1 ortholog as a candidate of proteins associated with the 5' UTR of the Dsx1alpha isoform. Here we report the CELF1-dependent suppression of Dsx1 expression in D. magna. During embryogenesis, CELF1 expression was not sexually dimorphic. Silencing of CELF1 led to the activation of Dsx1 expression both in female and male embryos. Overexpression of CELF1 in male embryos resulted in a reduction of Dsx1 expression. By these manipulations of CELF1 expression, the Dsx1 transcript level was not significantly changed. To investigate whether the CELF1 controls Dsx1 expression via its 5' UTR, we injected the GFP reporter mRNA having intact Dsx1alpha 5' UTR or mutated one lacking the GU-rich element (GRE) that is known as a binding site of the CELF1 ortholog. We found that deletion of the GRE significantly increased the reporter gene expression. These results indicate that CELF1 suppresses Dsx1 expression both in females and males, possibly at the post-transcriptional level. We speculate that CELF1 may avoid unintended Dsx1 expression and generation of sexual ambiguity by setting a threshold of Dsx1 expression.", "classifications": [ { "id": "19H05423", "label": "19H05423", "researcher": "Yasuhiko Kato", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yusrifar Kharisma", "last_name": "Tirta", "name": null }, { "creator_type": "author", "first_name": "Shungo", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Christelle Alexa Garcia", "last_name": "Perez", "name": null }, { "creator_type": "author", "first_name": "Nikko", "last_name": "Adhitama", "name": null }, { "creator_type": "author", "first_name": "Quang Dang", "last_name": "Nong", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Natsume", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0275526" }, "pmcid": { "normalized": "PMC9565731" }, "pmid": { "normalized": "36240182" } }, "mesh": [ { "descriptor": "5' Untranslated Regions", "descriptor_ui": "D020121", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CELF1 Protein", "descriptor_ui": "D000067879", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "10", "normalized_date": "2022", "pages": "e0275526", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "17", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "CELF1 represses Doublesex1 expression via its 5' UTR in the crustacean Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "For the treatment of autoimmune diseases, depletion of B cells specific for auto-antigens is important because they will be a source of plasmablasts/plasma cells to produce autoantibodies. However, because some types of B cells like naive B cells and memory B cells are at quiescent phase, they are insensitive to anticancer drugs which exert cytotoxicity by arresting the cell cycle. Here we show that B cell receptor (BCR) stimulation increases the sensitivity of anticancer drugs by promoting the proliferation of quiescent B cells. The BCR stimulation to primary naive B cells enhanced sensitivity to several anticancer drugs which arrest the cell cycle through different mechanisms. The present results indicated that combination of the BCR stimulation and anticancer drugs is a promising strategy for the antigen-specific depletion of pathogenic quiescent B cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takanatsu", "last_name": "Hosokawa", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Katayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1248/bpb.b22-00176" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35786592" } }, "mesh": [ { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": true }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Cycle Checkpoints", "descriptor_ui": "D059447", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Receptors, Antigen, B-Cell", "descriptor_ui": "D011947", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "7", "normalized_date": "2022", "pages": "847-850", "proceedings_title": null, "publisher": "", "title": "Biological & pharmaceutical bulletin", "volume": "45", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Quiescent B Cells Acquire Sensitivity to Cell Cycle Arresting Agents by B Cell Receptor Stimulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The neuropeptide pigment-dispersing factor (Pdf) is critically involved in the regulation of circadian rhythms in various insects. The function of Pdf in circadian rhythms has been best studied in the fruitfly, i.e., Drosophila melanogaster. Drosophila Pdf is produced in a small subset of circadian clock neurons in the adult brain and functions as a circadian output signal. Recently, however, Pdf has been shown to play important roles not only in regulating circadian rhythms but also in innate and learned behaviors in Drosophila. In this mini-review, we will focus on the current findings that Pdf signaling and Pdf-producing neurons are essential for consolidating and maintaining long-term memory induced by the courtship conditioning in Drosophila and discuss the mechanisms of courtship memory processing through Pdf-producing neurons.", "classifications": [ { "id": "21H00434", "label": "21H00434", "researcher": "Takaomi Sakai", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Show", "last_name": "Inami", "name": null }, { "creator_type": "author", "first_name": "Tomohito", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnmol.2022.934222" }, "pmcid": { "normalized": "PMC9326319" }, "pmid": { "normalized": "35909447" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "934222", "proceedings_title": null, "publisher": "", "title": "Frontiers in molecular neuroscience", "volume": "15", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Circadian Neuropeptide-Expressing Clock Neurons as Regulators of Long-Term Memory: Molecular and Cellular Perspectives.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Continuous appearance of SARS-CoV-2 variants and mass vaccination have been intricately influencing on the COVID-19 situation. To elucidate the current status in Japan, we analyzed totally 2,000 sera in August (n = 1,000) and December (n = 1,000) 2021 collected from individuals who underwent a health check-up. The anti-N seropositive rate were 2.1% and 3.9% in August and December 2021, respectively, demonstrating a Delta variant endemic during that time; it was approximately twofold higher than the rate based on the PCR-based diagnosis. The anti-S seropositive rate was 38.7% in August and it reached 90.8% in December, in concordance with the vaccination rate in Japan. In the December cohort, 78.7% of the sera showed neutralizing activity against the Delta variant, whereas that against the Omicron was much lower at 36.6%. These analyses revealed that effective immunity against the Delta variant was established in December 2021, however, prompt three-dose vaccination is needed to overcome Omicron's outbreak.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Zhenxiao", "last_name": "Ren", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Lidya Handayani", "last_name": "Tjan", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Yukiya", "last_name": "Kurahashi", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Sutandhio", "name": null }, { "creator_type": "author", "first_name": "Kaito", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Uto", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Itsuko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Saegusa", "name": null }, { "creator_type": "author", "first_name": "Nonoka", "last_name": "Godai", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Takeshita", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0266270" }, "pmcid": { "normalized": "PMC8982849" }, "pmid": { "normalized": "35381036" } }, "mesh": [ { "descriptor": "Antibodies, Neutralizing", "descriptor_ui": "D057134", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true }, { "descriptor": "Vaccination", "descriptor_ui": "D014611", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "4", "normalized_date": "2022", "pages": "e0266270", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "17", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Large-scale serosurveillance of COVID-19 in Japan: Acquisition of neutralizing antibodies for Delta but not for Omicron and requirement of booster vaccination to overcome the Omicron's outbreak.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Developments in high-throughput microscopy have made it possible to collect huge amounts of cell image data that are difficult to analyse manually. Machine learning (e.g., deep learning) is often employed to automate the extraction of information from these data, such as cell counting, cell type classification and image segmentation. However, the effects of different imaging methods on the accuracy of image processing have not been examined systematically. We studied the effects of different imaging methods on the performance of machine learning-based cell type classifiers. We observed lymphoid-primed multipotential progenitor (LMPP) and pro-B cells using three imaging methods: differential interference contrast (DIC), phase contrast (Ph) and bright-field (BF). We examined the classification performance of convolutional neural networks (CNNs) with each of them and their combinations. CNNs achieved an area under the receiver operating characteristic (ROC) curve (AUC) of ~0.9, which was significantly better than when the classifier used only cell size or cell contour shape as input. However, no significant differences were found between imaging methods and focal positions.", "classifications": [ { "id": "18H05411", "label": "18H05411", "researcher": "Katsuyuki Shiroguchi", "type": "grant" }, { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taisaku", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Ochiai", "name": null }, { "creator_type": "author", "first_name": "Tomoharu", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Tomokatsu", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Tsuzuki", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0262397" }, "pmcid": { "normalized": "PMC8794178" }, "pmid": { "normalized": "35085287" } }, "mesh": [ { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Lymphocytes", "descriptor_ui": "D008214", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "ROC Curve", "descriptor_ui": "D012372", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "1", "normalized_date": "2022", "pages": "e0262397", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "17", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Different cell imaging methods did not significantly improve immune cell image classification performance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recently, Schlafen family member 11 (SLFN11) has been reported to increase the sensitivity of cancer cells to DNA-damaging agents, including platinum derivatives; thus, SLFN11 may be a predictive biomarker for platinum-based chemoradiotherapy (CRT). In this study, we examined whether SLFN11 expression was associated with the therapeutic outcome of platinum-based CRT in head and neck squamous cell carcinoma (HNSCC). We performed immunohistochemical analyses for SLFN11 expression in 161 HNSCC tissues from patients who had been administered cisplatin-based CRT and examined the correlation between SLFN11 expression and progression-free survival (PFS). Additionally, SLFN11 expression was examined in 10 paired samples obtained before and after CRT in patients with local failure. Furthermore, in vitro experiments were performed using several HNSCC cell lines and isogenic SLFN11-knockout cells to assess the association between SLFN11 expression and drug sensitivity. PFS was found to be significantly better in the SLFN11-positive group than in the SLFN11-negative group among the 161 patients (5-year PFS: 78.8% vs. 52.8%, respectively, p < 0.001). Similar results were observed for the PFS at each primary site. The percentage of SLFN11 positivity was lower in tumor samples from patients with local failure after CRT than that in the corresponding primary tumors before CRT in 8 of 10 cases. Results of the in vitro assay demonstrated that SLFN11-knockout cells exhibited reduced sensitivity to DNA-damaging agents but not to the non-DNA-damaging agent docetaxel. Our findings suggest that SLFN11 may serve as a potential biomarker for predicting the response of HNSCC patients to platinum-based CRT.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Seijiro", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Nayuta", "last_name": "Tsushima", "name": null }, { "creator_type": "author", "first_name": "Takatsugu", "last_name": "Mizumachi", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Taniyama", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Homma", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fonc.2022.978875" }, "pmcid": { "normalized": "PMC9892834" }, "pmid": { "normalized": "36741698" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "978875", "proceedings_title": null, "publisher": "", "title": "Frontiers in oncology", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Schlafen family member 11 indicates favorable prognosis of patients with head and neck cancer following platinum-based chemoradiotherapy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "With the recent progress in structural biology and genome biology, structural dynamics of molecular systems that include nucleic acids has attracted attention in the context of gene regulation. The structure-function relationship is an important topic that highlights the importance of the physicochemical properties of nucleotides, as well as that of amino acids in proteins. Simulations are a useful tool for the detailed analysis of molecular dynamics that complement experiments in molecular biology; however, molecular simulation of nucleic acids is less well developed than that of proteins partly due to the physical nature of nucleic acids. In this review, we briefly describe the current status and future directions of the field as a guide to promote collaboration between experimentalists and computational biologists.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takeru", "last_name": "Kameda", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Awazu", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Togashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v19.0027" }, "pmcid": { "normalized": "PMC9592887" }, "pmid": { "normalized": "36349319" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "e190027", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "19", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular dynamics analysis of biomolecular systems including nucleic acids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bioluminescent indicators facilitate determination of bioactive molecules in blood samples with high sensitivity. Using a bright luciferase, its bioluminescence (BL) can be easily detected by conventional light sensing devices. In this chapter, we describe a protocol to measure bioactive molecules in blood by taking the BL images with a smartphone camera. We exemplify the measurement of unconjugated bilirubin (UCBR) concentration in the blood of mice using a ratiometric bioluminescent UCBR indicator, BABI (bilirubin assessment with a bioluminescent indicator), and a smartphone camera. We show the UCBR concentration is easily determined through measuring the variance in the BL color with a smartphone camera. This method provides a practical method to lead to future point-of-care diagnosis with quick and simple procedures.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Yukino", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-2473-9_16" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35836071" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bilirubin", "descriptor_ui": "D001663", "major_topic": true }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Smartphone", "descriptor_ui": "D000068997", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "219-226", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2525", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Method for Measuring Bioactive Molecules in Blood by a Smartphone Using Bioluminescent Ratiometric Indicators.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Riki", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Soeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.nbas.2021.100026" }, "pmcid": { "normalized": "PMC9999443" }, "pmid": { "normalized": "36908878" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "100026", "proceedings_title": null, "publisher": "", "title": "Aging brain", "volume": "2", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Can the entorhinal cortex help distinguish healthy aging brains from pathological aging brains?", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Many biological phenomena have spatio-temporal characteristics, such as the expression of molecular activity locally or at a limited time. Such phenomena have been observed in various organisms from slime mold to mammals, and are considered to be one of the basic patterns in biological reactions. Live imaging studies using the fluorescent protein GFP and fluorescence microscopy have become a standard technique in the life sciences to reveal the dynamics of these characteristic biological phenomena. On the other hand, the characteristic behaviors of molecules and cells captured by microscopy only correlate with life phenomena, and the causal relationship of whether they really matter is unknown. It is unclear whether they are really important or not. Therefore, to elucidate their physiological significance, it is important to introduce spatiotemporal manipulation techniques to manipulate molecules and cells locally and at arbitrary timing, and to perform causal analysis in vivo. The chromophore-assisted light inactivation (CALI) method, which uses light to inactivate molecular functions, is an optical technology that enables such spatiotemporal manipulation, and has recently been used in vivo in various model organisms, attracting widespread attention. In this section, we will review the principle of the CALI method, actual research examples, in particular, its in vivo application, and future prospects.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kiwamu", "last_name": "Takemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/fpj.22009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35781452" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromophore-Assisted Light Inactivation", "descriptor_ui": "D061885", "major_topic": true }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "4", "normalized_date": "2022", "pages": "238-243", "proceedings_title": null, "publisher": "", "title": "Nihon yakurigaku zasshi. Folia pharmacologica Japonica", "volume": "157", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "[Optical inactivation of molecular functions in vivo by chromophore-assisted light inactivation].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the lymphatic vascular system, lymph nodes (LNs) play a pivotal role in filtering and removing lymph-borne substances. The filtering function of LNs involves resident macrophages tightly associated with unique lymphatic sinus structures. Moreover, an intermittently arranged LN in the lymphatic pathway is considered to cooperatively prevent lymph-borne substances from entering blood circulation. However, the functional significance of tissue microarchitecture, cellular composition, and individual LNs in the \"LN chain\" system is not fully understood. To explore the mechanistic and histo-anatomical significance of LNs as lymph fluid filters, we subcutaneously injected fluorescent tracers into mice and examined the details of lymphatic transport to the LNs qualitatively and quantitatively. Lymph-borne tracers were selectively accumulated in the MARCO(+) subcapsular-medullary sinus border (SMB) region of the LN, in which reticular lymphatic endothelial cells and CD169(+)F4/80(+) medullary sinus macrophages construct a dense meshwork of the physical barrier, forming the main body to capture the tracers. We also demonstrated stepwise filtration via the LN chain in the lymphatic basin, which prevented tracer leakage into the blood. Furthermore, inflammatory responses that induce the remodeling of LN tissue as well as the lymphatic pathway reinforce the overall filtering capacity of the lymphatic basin. Taken together, specialized tissue infrastructure in the LNs and their systematic orchestration constitute an integrated filtering system for lymphatic recirculation.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Madoka", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Shihori", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Tomii", "name": null }, { "creator_type": "author", "first_name": "Nan-Jun", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Watarai", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Arata", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2022.902601" }, "pmcid": { "normalized": "PMC9251010" }, "pmid": { "normalized": "35794860" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "902601", "proceedings_title": null, "publisher": "", "title": "Frontiers in cell and developmental biology", "volume": "10", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Micro- and Macro-Anatomical Frameworks of Lymph Nodes Indispensable for the Lymphatic System Filtering Function.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To perform correlation analysis between different physiological parameters using fluorescent protein-based functional probes, diversification of wavelength properties of fluorescent proteins is underway. However, the shortest emission wavelength of fluorescent proteins has not been updated for more than 10 years. Here, we report the development of Sumire, a fluorescent protein emitting 414 nm violet fluorescence from a hydrated chromophore. The Sumire’s fluorescence property allows for the creation of FRET probes that can be used simultaneously with CFP-YFP based FRET probes for multi-parameter analysis.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-022-04153-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36329112" } }, "mesh": [ { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022", "date_precision": "year", "issue": "", "normalized_date": "2022", "pages": "", "proceedings_title": null, "publisher": "", "title": "Communications Biology", "volume": "5", "year": 2022 }, "ssbd": { "database": [ "ssbd-database-000267" ], "repository": [ "ssbd-repos-000267" ] }, "title": "Extension of the short wavelength side of fluorescent proteins using hydrated chromophores, and its application.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND & AIMS: Colorectal cancer (CRC) is one of the most common cancers in the world. A small proportion of CRCs can be attributed to recognizable hereditary germline variants of known CRC susceptibility genes. To better understand cancer risk, it is necessary to explore the prevalence of hereditary CRC and pathogenic variants of multiple cancer-predisposing genes in non-European populations. METHODS: We analyzed the coding regions of 27 cancer-predisposing genes in 12,503 unselected Japanese CRC patients and 23,705 controls by target sequencing and genome-wide SNP chip. Their clinical significance was assessed using ClinVar and the guidelines by ACMG/AMP. RESULTS: We identified 4,804 variants in the 27 genes and annotated them as pathogenic in 397 and benign variants in 941, of which 43.6% were novel. In total, 3.3% of the unselected CRC patients and 1.5% of the controls had a pathogenic variant. The pathogenic variants of MSH2 (odds ratio (OR) = 18.1), MLH1 (OR = 8.6), MSH6 (OR = 4.9), APC (OR = 49.4), BRIP1 (OR=3.6), BRCA1 (OR = 2.6), BRCA2 (OR = 1.9), and TP53 (OR = 1.7) were significantly associated with CRC development in the Japanese population (P-values<0.01, FDR<0.05). These pathogenic variants were significantly associated with diagnosis age and personal/family history of cancer. In total, at least 3.5% of the Japanese CRC population had a pathogenic variant or CNV of the 27 cancer-predisposing genes, indicating hereditary cancers. CONCLUSIONS: This largest study of CRC heredity in Asia can contribute to the development of guidelines for genetic testing and variant interpretation for heritable CRCs.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Xiaoxi", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Chikashi", "last_name": "Terao", "name": null }, { "creator_type": "author", "first_name": "Keijiro", "last_name": "Mizukami", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Sadaaki", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Inai", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Aoi", "name": null }, { "creator_type": "author", "first_name": "Misaki", "last_name": "Mizukoshi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Maejima", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Kamatani", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Kiwamu", "last_name": "Akagi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Hidewaki", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Momozawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cgh.2020.12.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33309985" } }, "mesh": [ { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": true }, { "descriptor": "Early Detection of Cancer", "descriptor_ui": "D055088", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Genetic Testing", "descriptor_ui": "D005820", "major_topic": false }, { "descriptor": "Germ-Line Mutation", "descriptor_ui": "D018095", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "2132-2141.e9", "proceedings_title": null, "publisher": "", "title": "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "volume": "20", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Population-based Screening for Hereditary Colorectal Cancer Variants in Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Low electron dose observation is indispensable for observing various samples using a transmission electron microscope; consequently, image processing has been used to improve transmission electron microscopy (TEM) images. To apply such image processing to in situ observations, we here apply a convolutional neural network to TEM imaging. Using a dataset that includes short-exposure images and long-exposure images, we develop a pipeline for processed short-exposure images, based on end-to-end training. The quality of images acquired with a total dose of approximately $5$$e^{-}$ per pixel becomes comparable to that of images acquired with a total dose of approximately $1{,}000$$e^{-}$ per pixel. Because the conversion time is approximately 8 ms, in situ observation at 125 fps is possible. This imaging technique enables in situ observation of electron-beam-sensitive specimens.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Katsuno", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1017/s1431927621013799" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35177140" } }, "mesh": [ { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Electrons", "descriptor_ui": "D004583", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Microscopy, Electron, Transmission", "descriptor_ui": "D046529", "major_topic": false }, { "descriptor": "Neural Networks, Computer", "descriptor_ui": "D016571", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Feb", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "138-144", "proceedings_title": null, "publisher": "", "title": "Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada", "volume": "28", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Fast Improvement of TEM Images with Low-Dose Electrons by Deep Learning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To assess if magnetic resonance spectroscopy (MRS)-measured Glutamate (Glu) and GABA reflect excitatory and inhibitory neural activities, respectively, we conducted MRS measurements along with two-photon mesoscopic imaging of calcium signals in excitatory and inhibitory neurons of living, unanesthetized mice. For monitoring stimulus-driven activations of a brain region, MRS signals and mesoscopic neural activities were measured during two consecutive sessions of 15-min prolonged sensory stimulations. In the first session, putative excitatory neuronal activities were increased, while inhibitory neuronal activities remained at the baseline level. In the second half, while excitatory neuronal activities remained elevated, inhibitory neuronal activities were significantly enhanced. We assessed regional neurochemical statuses by measuring MRS signals, which were overall in accordance with the neural activities, and neuronal activities and neurochemical statuses in a mouse model of Dravet syndrome under resting condition. Mesoscopic assessments showed that activities of inhibitory neurons in the cortex were diminished relative to wild-type mice in contrast to spared activities of excitatory neurons. Consistent with these observations, the Dravet model exhibited lower concentrations of GABA than wild-type controls. Collectively, the current investigations demonstrate that MRS-measured Glu and GABA can reflect spontaneous and stimulated activities of neurons producing and releasing these neurotransmitters in an awake condition.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuhei", "last_name": "Takado", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takuwa", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Sampei", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Urushihata", "name": null }, { "creator_type": "author", "first_name": "Manami", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Shimojo", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Nitta", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Ochi", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Jamie", "last_name": "Near", "name": null }, { "creator_type": "author", "first_name": "Ichio", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1177/0271678x211045449" }, "pmcid": { "normalized": "PMC8721779" }, "pmid": { "normalized": "34515548" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Epilepsies, Myoclonic", "descriptor_ui": "D004831", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "GABAergic Neurons", "descriptor_ui": "D059330", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Magnetic Resonance Spectroscopy", "descriptor_ui": "D009682", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Wakefulness", "descriptor_ui": "D014851", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "197-212", "proceedings_title": null, "publisher": "", "title": "Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism", "volume": "42", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "MRS-measured glutamate versus GABA reflects excitatory versus inhibitory neural activities in awake mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Flaviviruses, which are globally distributed and cause a spectrum of potentially severe illnesses, pose a major threat to public health. Although Flaviviridae viruses, including flaviviruses, possess similar genome structures, only the flaviviruses encode the non-structural protein NS1, which resides in the endoplasmic reticulum (ER) and is secreted from cells after oligomerization. The ER-resident NS1 is known to be involved in viral genome replication, but the essential roles of secretory NS1 in the virus life cycle are not fully understood. Here we characterized the roles of secretory NS1 in the particle formation of flaviviruses. We first identified an amino acid residue essential for the NS1 secretion but not for viral genome replication by using protein-protein interaction network analyses and mutagenesis scanning. By using the recombinant flaviviruses carrying the identified NS1 mutation, we clarified that the mutant flaviviruses employed viral genome replication. We then constructed a recombinant NS1 with the identified mutation and demonstrated by physicochemical assays that the mutant NS1 was unable to form a proper oligomer or associate with liposomes. Finally, we showed that the functions of NS1 that were lost by the identified mutation could be compensated for by the in trans-expression of Erns of pestiviruses and host exchangeable apolipoproteins, which participate in the infectious particle formation of pestiviruses and hepaciviruses in the family Flaviviridae, respectively. Collectively, our study suggests that secretory NS1 plays a role in the particle formation of flaviviruses through its interaction with the lipid membrane.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Shiho", "last_name": "Torii", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kajiwara", "name": null }, { "creator_type": "author", "first_name": "Itsuki", "last_name": "Anzai", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Kisho", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Taguwa", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Morioka", "name": null }, { "creator_type": "author", "first_name": "Rigel", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yuzy", "last_name": "Fauzyah", "name": null }, { "creator_type": "author", "first_name": "Chikako", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Takasuke", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Yoshiharu", "last_name": "Matsuura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.ppat.1010593" }, "pmcid": { "normalized": "PMC9200304" }, "pmid": { "normalized": "35658055" } }, "mesh": [ { "descriptor": "Flaviviridae", "descriptor_ui": "D018067", "major_topic": true }, { "descriptor": "Flavivirus", "descriptor_ui": "D005416", "major_topic": true }, { "descriptor": "Glycoproteins", "descriptor_ui": "D006023", "major_topic": false }, { "descriptor": "Viral Nonstructural Proteins", "descriptor_ui": "D017361", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "e1010593", "proceedings_title": null, "publisher": "", "title": "PLoS pathogens", "volume": "18", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Secretory glycoprotein NS1 plays a crucial role in the particle formation of flaviviruses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "GFP-like chromoproteins (CPs) with non-fluorescence ability have been used as bioimaging probes. Existing CPs have voids in the optical absorption window which limits their extensibility. The development of new CP color is therefore ongoing. Here, we cloned CPs from the jellyfish, Olindias formosa, and developed a completely non-fluorescent monomeric red CP, R-Velour, with an absorption peak at 528 nm. To analyze the photophysical properties from a structural aspect, we determined the crystal structure of R-Velour at a 2.1 A resolution. R-Velour has a trans-chromophore similar to the green fluorescence protein, Gamillus, derived from the same jellyfish. However, in contrast to the two coplanar chromophoric rings in Gamillus, R-Velour has a large torsion inducing non-fluorescence property. Through site-directed mutagenesis, we surveyed residues surrounding the chromophore and found a key residue, Ser155, which contributes to the generation of four-color variants with the bathochromic and hypsochromic shift of the absorption peak, ranging from 506 to 554 nm. The recently proposed spectrum shift theory, based on the Marcus-Hush model, supports the spectrum shift of these mutants. These findings may support further development of R-Velour variants with useful absorption characteristics for bioimaging, including fluorescence lifetime imaging and photoacoustic imaging.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Le", "last_name": "Zhai", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Shinoda", "name": null }, { "creator_type": "author", "first_name": "Yoshimasa", "last_name": "Ike", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/pro.4285" }, "pmcid": { "normalized": "PMC8994484" }, "pmid": { "normalized": "35481635" } }, "mesh": [ { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": true }, { "descriptor": "Mutagenesis, Site-Directed", "descriptor_ui": "D016297", "major_topic": false }, { "descriptor": "Taiwan", "descriptor_ui": "D013624", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "e4285", "proceedings_title": null, "publisher": "", "title": "Protein science : a publication of the Protein Society", "volume": "31", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Structure-based analysis and evolution of a monomerized red-colored chromoprotein from the Olindias formosa jellyfish.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In June 2019, the Japanese National Health Insurance (NHI) system introduced coverage for two types of tumor genomic profiling (TGP): FoundationOne() CDx (F1) and OncoGuide NCC OncoPanel System (NCCOP). TGP sometimes reveals germline variants that are potentially pathogenic as secondary findings (SFs). We conducted a questionnaire-based survey to find out the operational statuses of F1 and NCCOP at institutions where TGP was performed to elucidate issues related to SFs. Responses were received from 97 of 112 institutions (86.6%). As of May 31, 2020, 88 (90.7%) and 78 (80.4%) institutions started performing F1 and NCCOP, respectively. Since F1 only examines tumor samples, germline confirmatory testing is necessary to determine whether they are actually germline pathogenic variants (GPVs). When physicians are obtaining informed consent all but 2.3% of the patients requested SF disclosure. Conversely, when presumed germline pathogenic variants (PGPVs) were detected, 46.2% were not willing to receive confirmatory tests as they wanted to prioritize cancer treatment over SFs investigation, while only 23.3% underwent confirmatory tests. Problems in cancer genomic medicine reported by clinical genetics departments included short-staffing (n = 10), insufficient interdepartmental cooperation (n = 9), inconsistent understanding of genetics among healthcare professionals (n = 8), and low utilization rate of SFs due to lack of insurance coverage for confirmatory tests and post-test health checkups (n = 8). Solutions include; determining the appropriate timing to confirm patient intent on SF disclosure, covering confirmatory tests for PGPVs by the NHI, and establishing cooperation between the oncology and clinical genetics departments.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akari", "last_name": "Minamoto", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Saki", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Katsutoshi", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Arisa", "last_name": "Ueki", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Higashigawa", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Morikawa", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Muto", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kosugi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s10038-022-01028-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35322199" } }, "mesh": [ { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insurance", "descriptor_ui": "D007341", "major_topic": true }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "557-563", "proceedings_title": null, "publisher": "", "title": "Journal of human genetics", "volume": "67", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Current status and issues related to secondary findings in the first public insurance covered tumor genomic profiling in Japan: multi-site questionnaire survey.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Understanding the long-term effects of stress on brain function is crucial for understanding the mechanisms of depression. The BALB/c mouse strain has high susceptibility to stress and is thus an effective model for depression. The long-term effects of repeated social defeat stress (SDS) on BALB/c mice, however, are not clear. Here, we investigated the effects of repeated SDS in male BALB/c mice over the subsequent two weeks. Some defeated mice immediately exhibited social avoidance, whereas anxiety-like behavior was only evident at later periods. Furthermore, defeated mice segregated into two groups based on the level of social avoidance, namely, avoidant and nonavoidant mice. The characteristic of avoidance or nonavoidance in each individual was not fixed over the two weeks. In addition, we developed a semi-automated method for analyzing c-Fos expression in the mouse brain to investigate the effect of repeated SDS on brain activity more than two weeks after the end of the stress exposure. Following social interaction, c-Fos expression was reduced in several brain regions in the defeated mice compared with control mice. The correlation of c-Fos expression among these brain areas, with exception of the medial prefrontal cortex (mPFC) and central amygdala (CeA), was increased in defeated mice, suggesting increased synchrony. Notably, c-Fos expression in the lateral habenula (LHb) was different between mice that exhibited social avoidance from immediately after the repeated SDS and those that exhibited social avoidance only at later periods. These observations provide insight into the long-term effects of social stress on behavior and brain activity.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hibiki", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Yasugaki", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Suzuki-Abe", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Katsuyasu", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Hotaka", "last_name": "Takizawa", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/eneuro.0068-22.2022" }, "pmcid": { "normalized": "PMC9070729" }, "pmid": { "normalized": "35437264" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-fos", "descriptor_ui": "D016760", "major_topic": false }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": false }, { "descriptor": "Social Defeat", "descriptor_ui": "D000083703", "major_topic": true }, { "descriptor": "Social Interaction", "descriptor_ui": "D000083505", "major_topic": true }, { "descriptor": "Stress, Psychological", "descriptor_ui": "D013315", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 May-Jun", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "ENEURO.0068-22.2022", "proceedings_title": null, "publisher": "", "title": "eNeuro", "volume": "9", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Long-Term Effects of Repeated Social Defeat Stress on Brain Activity during Social Interaction in BALB/c Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Schizophrenia was initially defined as \"dementia praecox\" by E. Kraepelin, which implies progressive deterioration. However, recent studies have revealed that early effective intervention may lead to social and functional recovery in schizophrenia. In this review, we provide an overview of current concepts in schizophrenia and pathophysiological hypotheses. In addition, we present recent findings from clinical and basic research on schizophrenia. Recent neuroimaging and neurophysiological studies have consistently revealed specific biological differences in the structure and function of the brain in those with schizophrenia. From a basic research perspective, to determine the essential pathophysiology underlying schizophrenia, it is crucial that findings from all lines of inquiry-induced pluripotent stem cell (iPSC)-derived neural cells from patients, murine models expressing genetic mutations identified in patients, and patient clinical data-be integrated to contextualize the analysis results. However, the findings remain insufficient to serve as a diagnostic tool or a biomarker for predicting schizophrenia-related outcomes. Collaborations to conduct clinical research based on the patients' and their families' values are just beginning, and further development is expected.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Onitsuka", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Kayo", "last_name": "Ichihashi", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Inada", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Mitoma", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Yasui-Furukori", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/pcn.13342" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35235256" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Schizophrenia", "descriptor_ui": "D012559", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "282-291", "proceedings_title": null, "publisher": "", "title": "Psychiatry and clinical neurosciences", "volume": "76", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Toward recovery in schizophrenia: Current concepts, findings, and future research directions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chondroitin sulfate proteoglycan (CSPG), one of the major extracellular matrices, plays an important part in organogenesis. Its core protein and chondroitin sulfate (CS) chain have a specific biological function. To elucidate the role of CS in the developmental and healing process of the dental pulp, we performed an experimental tooth replantation in CS N-acethylgalactosaminyltransferase-1 (T1) gene knockout (KO) mice. We also performed cell proliferation assay and qRT-PCR analysis for the WT and T1KO primary dental pulp cells using T1-siRNA technique and external CS. During tooth development, CS was diffusely expressed in the dental papilla, and with dental pulp maturation, CS disappeared from the differentiated areas, including the odontoblasts. In fully developed molars, CS was restricted to the root apex region colocalizing with Gli1-positive cells. In the healing process after tooth replantation, CD31-positive cells accumulated in the CS-positive stroma in WT molars. In T1KO molars, the appearance of Ki67- and Gli1-positive cells in the dental pulp was significantly fewer than in WT molars in the early healing stage, and collagen I-positive reparative dentin formation was not obvious in T1KO mice. In primary culture experiments, siRNA knockdown of T1 gene significantly suppressed cell proliferation in WT dental pulp cells, and the mRNA expression of cyclin D1 and CD31 was significantly upregulated by external CS in T1KO dental pulp cells. These results suggest that CS is involved in the cell proliferation and functional differentiation of dental pulp constituent cells, including vascular cells, in the healing process of dental pulp tissue after tooth injury.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Ida-Yonemochi", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Ohshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00441-022-03575-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35067724" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chondroitin Sulfates", "descriptor_ui": "D002809", "major_topic": true }, { "descriptor": "Dental Pulp", "descriptor_ui": "D003782", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molar", "descriptor_ui": "D008963", "major_topic": false }, { "descriptor": "Odontoblasts", "descriptor_ui": "D009804", "major_topic": false }, { "descriptor": "Tooth Replantation", "descriptor_ui": "D014090", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Apr", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "133-148", "proceedings_title": null, "publisher": "", "title": "Cell and tissue research", "volume": "388", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of chondroitin sulfate in the developmental and healing process of the dental pulp in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer invasion and metastasis are the major causes of cancer patient mortality. Various growth factors, including hepatocyte growth factor (HGF), are known to promote cancer invasion and metastasis, but the regulatory mechanisms involved are not fully understood. Here, we show that HGF-promoted migration and invasion of breast cancer cells are regulated by CUB domain-containing protein 1 (CDCP1), a transmembrane activator of SRC kinase. In metastatic human breast cancer cell line MDA-MB-231, which highly expresses the HGF receptor MET and CDCP1, we show that CDCP1 knockdown attenuated HGF-induced MET activation, followed by suppression of lamellipodia formation and cell migration/invasion. In contrast, in the low invasive/nonmetastatic breast cancer cell line T47D, which had no detectable MET and CDCP1 expression, ectopic MET expression stimulated the HGF-dependent activation of invasive activity, and concomitant CDCP1 expression activated SRC and further promoted invasive activity. In these cells, CDCP1 expression dramatically activated HGF-induced membrane remodeling, which was accompanied by activation of the small GTPase Rac1. Analysis of guanine nucleotide exchange factors revealed that ARHGEF7 was specifically required for CDCP1-dependent induction of HGF-induced invasive ability. Furthermore, immunofluorescence staining demonstrated that CDCP1 coaccumulated with ARHGEF7. Finally, we confirmed that the CDCP1-SRC axis was also crucial for HGF and ARHGEF7-RAC1 signaling in MDA-MB-231 cells. Altogether, these results demonstrate that the CDCP1-SRC-ARHGEF7-RAC1 pathway plays an important role in the HGF-induced invasion of a subset of breast cancer cells.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Kawase", "name": null }, { "creator_type": "author", "first_name": "Atsuya", "last_name": "Sugihara", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kajiwara", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Kanako", "last_name": "Akamatsu", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Nada", "name": null }, { "creator_type": "author", "first_name": "Kunio", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbc.2022.101630" }, "pmcid": { "normalized": "PMC8867115" }, "pmid": { "normalized": "35085554" } }, "mesh": [ { "descriptor": "Antigens, Neoplasm", "descriptor_ui": "D000951", "major_topic": true }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": true }, { "descriptor": "Cell Adhesion Molecules", "descriptor_ui": "D015815", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hepatocyte Growth Factor", "descriptor_ui": "D017228", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-met", "descriptor_ui": "D019859", "major_topic": false }, { "descriptor": "Rho Guanine Nucleotide Exchange Factors", "descriptor_ui": "D064067", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "src-Family Kinases", "descriptor_ui": "D019061", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "101630", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "298", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "SRC kinase activator CDCP1 promotes hepatocyte growth factor-induced cell migration/invasion of a subset of breast cancer cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Targeted blockade of the checkpoint molecule programmed cell death 1 (PD-1) can activate tumor-specific T cells to destroy tumors, whereas targeted potentiation of PD-1 is expected to suppress autoreactive T cells and alleviate autoimmune diseases. However, the development of methods to potentiate PD-1 remains challenging. Here we succeeded in eliciting PD-1 function by targeting the cis-PD-L1-CD80 duplex, formed by binding of CD80 to the PD-1 ligand PD-L1, that attenuates PD-L1-PD-1 binding and abrogates PD-1 function. By generating anti-CD80 antibodies that detach CD80 from the cis-PD-L1-CD80 duplex and enable PD-L1 to engage PD-1 in the presence of CD80, we demonstrate that the targeted dissociation of cis-PD-L1-CD80 duplex elicits PD-1 function in the condition where PD-1 function is otherwise restricted. We demonstrate using murine models that the removal of PD-1 restriction is effective in alleviating autoimmune disease symptoms. Our findings establish a method to potentiate PD-1 function and propose the removal of restraining mechanisms as an efficient strategy to potentiate the function of inhibitory molecules.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" }, { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Il-Mi", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Takeo K.", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Rieko", "last_name": "Arakaki", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Naozumi", "last_name": "Ishimaru", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Okazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41590-021-01125-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35145298" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autoimmune Diseases", "descriptor_ui": "D001327", "major_topic": true }, { "descriptor": "Autoimmunity", "descriptor_ui": "D015551", "major_topic": false }, { "descriptor": "B7-1 Antigen", "descriptor_ui": "D018122", "major_topic": false }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "399-410", "proceedings_title": null, "publisher": "", "title": "Nature immunology", "volume": "23", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "PD-1 agonism by anti-CD80 inhibits T cell activation and alleviates autoimmunity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The dynamics of microscopic marine plankton in coastal areas is a fundamental theme in marine biodiversity research, but studies have been limited because the only available methodology was collection of plankton using plankton-nets and microscopic observation. In recent years, environmental DNA (eDNA) analysis has exhibited potential for conducting comprehensive surveys of marine plankton diversity in water at fixed points and depths in the ocean. However, few studies have examined how eDNA analysis reflects the actual distribution and dynamics of organisms in the field, and further investigation is needed to determine whether it can detect distinct differences in plankton density in the field. To address this, we analyzed eDNA in seawater samples collected at 1 km intervals at three depths over a linear distance of approximately 3.0 km in the Seto Inland Sea. The survey area included a location with a high density of Acoela (Praesagittifera naikaiensis). However, the eDNA signal for this was little to none, and its presence would not have been noticed if we did not have this information beforehand. Meanwhile, eDNA analysis enabled us to confirm the presence of a species of Placozoa that was previously undiscovered in the area. In summary, our results suggest that the number of sequence reads generated from eDNA samples in our project was not sufficient to predict the density of a particular species. However, eDNA can be useful for detecting organisms that have been overlooked using other methods.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Masa-Aki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Miyazawa", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Natumi", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Hamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.2108/zs210073" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35107003" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biodiversity", "descriptor_ui": "D044822", "major_topic": false }, { "descriptor": "DNA, Environmental", "descriptor_ui": "D000080309", "major_topic": true }, { "descriptor": "Environmental Monitoring", "descriptor_ui": "D004784", "major_topic": false }, { "descriptor": "Seawater", "descriptor_ui": "D012623", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Feb", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "157-165", "proceedings_title": null, "publisher": "", "title": "Zoological science", "volume": "39", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Observing Phylum-Level Metazoan Diversity by Environmental DNA Analysis at the Ushimado Area in the Seto Inland Sea.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mutation status of tumor tissue DNA (n = 389) of resected stage II-III non-squamous non-small-cell lung cancer (Ns-NSCLC) was analyzed using targeted deep sequencing as an exploratory biomarker study (JIPANG-TR) for the JIPANG study, a randomized phase III study of pemetrexed/cisplatin (Pem/Cis) vs vinorelbine/cisplatin (Vnr/Cis). The TP53 mutation, common EGFR mutations (exon 19 deletion and L858R), and KRAS mutations were frequently detected. The frequency of the EGFR mutation was significant among female patients. Patients with an EGFR mutation-positive status had a significantly shorter recurrence-free survival (RFS) time (24 mo vs not reached) (HR, 1.64; 95% CI, 1.22-2.21; P = .0011 for EGFR mutation status). Multivariable analysis identified both the pathological stage and EGFR mutation status as independent prognostic factors for RFS (HR, 1.78; 95% CI, 1.30-2.44; P = .0003 for disease stage; and HR, 1.57; 95% CI, 1.15-2.16; P = .0050 for EGFR mutation status). This study demonstrated that the EGFR mutation has either a poor prognostic or predictive impact on a poor response to postoperative chemotherapy with platinum doublet chemotherapy for stage II-III Ns-NSCLC patients. This result supports a role for mandatory molecular diagnosis of early-stage Ns-NSCLC for precision oncology and signifies the importance of adjuvant for the 3rd generation tyrosine kinase inhibitor rather than platinum-based chemotherapy. This study is registered with the UMIN Clinical Trial Registry (UMIN 000012237).", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Hirotsugu", "last_name": "Kenmotsu", "name": null }, { "creator_type": "author", "first_name": "Kiyotaka", "last_name": "Yoh", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Daga", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Ohira", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Hosomi", "name": null }, { "creator_type": "author", "first_name": "Toyofumi F.", "last_name": "Chen-Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Takiguchi", "name": null }, { "creator_type": "author", "first_name": "Akimasa", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Haruki", "name": null }, { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Akamatsu", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Seto", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Saeki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sugio", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Inokawa", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tsuboi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.15171" }, "pmcid": { "normalized": "PMC8748214" }, "pmid": { "normalized": "34689382" } }, "mesh": [ { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Chemotherapy, Adjuvant", "descriptor_ui": "D017024", "major_topic": false }, { "descriptor": "Cisplatin", "descriptor_ui": "D002945", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Pemetrexed", "descriptor_ui": "D000068437", "major_topic": false }, { "descriptor": "Precision Medicine", "descriptor_ui": "D057285", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Sequence Analysis, DNA", "descriptor_ui": "D017422", "major_topic": false }, { "descriptor": "Survival Analysis", "descriptor_ui": "D016019", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false }, { "descriptor": "Vinorelbine", "descriptor_ui": "D000077235", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "287-296", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "113", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Predictive value of EGFR mutation in non-small-cell lung cancer patients treated with platinum doublet postoperative chemotherapy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Programmed death (PD)-1/PD-ligand 1 (PD-L1) antibodies have shown an intense clinical effect in some patients with PD-L1(+) tumors, and their applications have rapidly expanded to various cancer types with or without the application of new companion diagnostics (CDx) with a lower cutoff value and inclusion of macrophage evaluation. However, the pathological background explaining the difference in the cutoff value remains unknown. To address this, we evaluated tissue array samples from 231 patients with lung adenocarcinoma, 186 with lung squamous cell carcinoma, and 38 with renal cell carcinoma (RCC) who were not receiving PD-1/PD-L1 antibodies to investigate the relationship between PD-L1 expression on tumor cells and CD8(+) T-cell infiltration in tumor tissues. PD-L1 expression in RCC was clearly lower than that in non-small-cell lung cancer (NSCLC) tissue, whereas CD8(+) T-cell infiltration was low in all cancers. We next analyzed PD-L1 expression by interferon (alpha, beta, and gamma) and LPS stimulation in both macrophages and 41 cancer cell lines derived from various organs and histological types. The PD-L1 expression patterns were classified into three types, which differed depending on each organ or tissue type. Interestingly, NSCLC cell lines showed highly diverse PD-L1 expression patterns compared with RCC cell lines. Conversely, PD-L1 expression was stronger and more prolonged in macrophages than in typical cell lines. Here, we revealed the diversity of the PD-L1 expression patterns in tumor cells and macrophages, demonstrating the pathological and cytological significance of the transition of cutoff values in PD-L1 CDx for PD-1/PD-L1 antibody administration.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoichi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Shinchi", "name": null }, { "creator_type": "author", "first_name": "Remi", "last_name": "Mito", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Koei", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Urakami", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Sakagami", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Komohara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.15442" }, "pmcid": { "normalized": "PMC9459416" }, "pmid": { "normalized": "35633190" } }, "mesh": [ { "descriptor": "Antibodies", "descriptor_ui": "D000906", "major_topic": false }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Carcinoma, Renal Cell", "descriptor_ui": "D002292", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kidney Neoplasms", "descriptor_ui": "D007680", "major_topic": true }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "3255-3266", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "113", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Classification of PD-L1 expression in various cancers and macrophages based on immunohistocytological analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Through the decades, 2-photon fluorescence microscopy has allowed visualization of microstructures, such as synapses, with high spatial resolution in deep brain tissue. However, signal transduction, such as protein activity and protein-protein interaction in neurons in tissues and in vivo, has remained elusive because of the technical difficulty of observing biochemical reactions at the level of subcellular resolution in light-scattering tissues. Recently, 2-photon fluorescence microscopy combined with fluorescence lifetime imaging microscopy (2pFLIM) has enabled visualization of various protein activities and protein-protein interactions at submicrometer resolution in tissue with a reasonable temporal resolution. Thus far, 2pFLIM has been extensively applied for imaging kinase and small GTPase activation in dendritic spines of hippocampal neurons in slice cultures. However, it has been recently applied to various subcellular structures, such as axon terminals and nuclei, and has increased our understanding of spatially organized molecular dynamics. One of the future directions of 2pFLIM utilization is to combine various optogenetic tools for manipulating protein activity. This combination allows the activation of specific proteins with light and visualization of its readout as the activation of downstream molecules. Here, we have introduced the recent application of 2pFLIM for neurons and present the utilization of a new optogenetic tool in combination with 2pFLIM.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hiromi H.", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Nagasawa", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2021.10.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34666101" } }, "mesh": [ { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence, Multiphoton", "descriptor_ui": "D036641", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jun", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "31-38", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "179", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Imaging intracellular protein interactions/activity in neurons using 2-photon fluorescence lifetime imaging microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Induced pluripotent stem cell (iPSC) technology, which enables the direct analysis of neuronal cells with the same genetic background as patients, has recently garnered significant attention in schizophrenia research. This technology is important because it enables a comprehensive interpretation using mice and human clinical research and cross-species verification. Here I review recent advances in modeling schizophrenia using iPSC technology, alongside the utility of disease mouse models.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2021.08.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34411680" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Schizophrenia", "descriptor_ui": "D012559", "major_topic": true }, { "descriptor": "Technology", "descriptor_ui": "D013672", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Feb", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "46-52", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "175", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Modeling schizophrenia with iPS cell technology and disease mouse models.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular accumulation of filamentous tau aggregates with progressive neuronal loss is a common characteristic of tauopathies. Although the neurodegenerative mechanism of tau-associated pathology remains unclear, molecular elements capable of degrading and/or sequestering neurotoxic tau species may suppress neurodegenerative progression. Here, we provide evidence that p62/SQSTM1, a ubiquitinated cargo receptor for selective autophagy, acts protectively against neuronal death and neuroinflammation provoked by abnormal tau accumulation. P301S mutant tau transgenic mice (line PS19) exhibited accumulation of neurofibrillary tangles with localization of p62 mostly in the brainstem, but neuronal loss with few neurofibrillary tangles in the hippocampus. In the hippocampus of PS19 mice, the p62 level was lower compared to the brainstem, and punctate accumulation of phosphorylated tau unaccompanied by co-localization of p62 was observed. In PS19 mice deficient in p62 (PS19/p62-KO), increased accumulation of phosphorylated tau, acceleration of neuronal loss, and exacerbation of neuroinflammation were observed in the hippocampus as compared with PS19 mice. In addition, increase of abnormal tau and neuroinflammation were observed in the brainstem of PS19/p62-KO. Immunostaining and dot-blot analysis with an antibody selectively recognizing tau dimers and higher-order oligomers revealed that oligomeric tau species in PS19/p62-KO mice were significantly accumulated as compared to PS19 mice, suggesting the requirement of p62 to eliminate disease-related oligomeric tau species. Our findings indicated that p62 exerts neuroprotection against tau pathologies by eliminating neurotoxic tau species, suggesting that the manipulative p62 and selective autophagy may provide an intrinsic therapy for the treatment of tauopathy.", "classifications": [ { "id": "21H00446", "label": "21H00446", "researcher": "Naruhiko Sahara", "type": "grant" }, { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Maiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Bin", "last_name": "Ji", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Takado", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Shimojo", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Minamihisamatsu", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Warabi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Yanagawa", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Ichio", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Nicholas M.", "last_name": "Kanaan", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/acel.13615" }, "pmcid": { "normalized": "PMC9282839" }, "pmid": { "normalized": "35662390" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neurofibrillary Tangles", "descriptor_ui": "D016874", "major_topic": false }, { "descriptor": "Sequestosome-1 Protein", "descriptor_ui": "D000071456", "major_topic": true }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": true }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "e13615", "proceedings_title": null, "publisher": "", "title": "Aging cell", "volume": "21", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Central role for p62/SQSTM1 in the elimination of toxic tau species in a mouse model of tauopathy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Despite the existence of central tolerance mechanisms, including clonal deletion and receptor editing to eliminate self-reactive B cells, moderately self-reactive cells still survive in the periphery (about 20% of peripheral B cells). These cells normally exist in a functionally silenced state called anergy; thus, anergy has been thought to contribute to tolerance by active-silencing of potentially dangerous B cells. However, a positive rationale for the existence of these anergic B cells has recently been suggested by discoveries that broadly neutralizing antibodies for HIV and influenza virus possess poly- and/or auto-reactivity. Given the conundrum of generating inherent holes in the immune repertoire, retaining weakly self-reactive BCRs on anergic B cells could allow these antibodies to serve as an effective defense against pathogens, particularly in the case of pathogens that mimic forbidden self-epitopes to evade the host immune system. Thus, anergic B cells should be brought into a silenced or activated state, depending on their contexts. Here, we review recent progress in our understanding of how the anergic B cell state is controlled in B cell-intrinsic and B cell-extrinsic ways.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Ise", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kurosaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/imr.13053" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34908172" } }, "mesh": [ { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": true }, { "descriptor": "Clonal Anergy", "descriptor_ui": "D017635", "major_topic": true }, { "descriptor": "Epitopes", "descriptor_ui": "D000939", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Tolerance", "descriptor_ui": "D007108", "major_topic": false }, { "descriptor": "Lymphocyte Count", "descriptor_ui": "D018655", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 May", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "43-52", "proceedings_title": null, "publisher": "", "title": "Immunological reviews", "volume": "307", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Silencing and activating anergic B cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The development of functional eggs and sperm are critical processes in mammalian development as they ensure successful reproduction and species propagation. While past studies have identified important genes that regulate these processes, the roles of luminal flow and fluid stress in reproductive biology remain less well understood. Here, we discuss recent evidence that support the diverse functions of luminal fluid in oogenesis, spermatogenesis and embryogenesis. We also review emerging techniques that allow for precise quantification and perturbation of tissue hydraulics in female and male reproductive systems, and propose new questions and approaches in this field. We hope this review will provide a useful resource to inspire future research in tissue hydraulics in reproductive biology and diseases.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Chii Jou", "last_name": "Chan", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.semcdb.2022.05.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35606275" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Oogenesis", "descriptor_ui": "D009866", "major_topic": false }, { "descriptor": "Reproduction", "descriptor_ui": "D012098", "major_topic": true }, { "descriptor": "Semen", "descriptor_ui": "D012661", "major_topic": true }, { "descriptor": "Spermatogenesis", "descriptor_ui": "D013091", "major_topic": false }, { "descriptor": "Spermatozoa", "descriptor_ui": "D013094", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Nov", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "124-133", "proceedings_title": null, "publisher": "", "title": "Seminars in cell & developmental biology", "volume": "131", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Tissue hydraulics in reproduction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "3D light-sheet microscopy is a powerful tool to obtain content-rich information of cell populations. However, the limited frame rate of high-quantum-efficiency cameras hinders its application in high-throughput flow cytometry. Herein, a high-throughput 3D-imaging flow cytometry technique based on light-sheet microscopy that can screen thousands of cells per second is introduced. This method enables fast, parallel optofluidic scanning of cells by performing 1D acoustofluidic focusing on multiple cells under wide-field light-sheet microscopy with a single objective lens. Multicolor 3D-imaging flow cytometry with cell-line samples at a record detection throughput of over 2000 cells s(-1) is demonstrated. Furthermore, an unprecedentedly large-scale 3D-morphology-based flow cytometric analysis at an order of 10(5) cells is demonstrated. Results show that the system is able to capture subcellular structures even at high throughputs and obtain cellular information that is overlooked under 2D-imaging cytometry.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Ugawa", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/smsc.202100126" }, "pmcid": { "normalized": "PMC11935936" }, "pmid": { "normalized": "40213114" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "2100126", "proceedings_title": null, "publisher": "", "title": "Small science", "volume": "2", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "High-Throughput Parallel Optofluidic 3D-Imaging Flow Cytometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Microvascular dysfunction accompanied by a dramatic alteration of stable capillary structure is a major hallmark of numerous age-related diseases. In skin, although the role of angiogenesis during dermal reconstitution is well documented, the functional relevance of the extracellular matrix (ECM) stiffness to vascular remodeling and its molecular mechanisms was poorly understood. Here, we developed an ex vivo 3-dimensional angiogenic model using human fat, revealing that \"appropriate\" stiffness induces vascular maturation associated with upregulated APJ expression, whereas the overexpression of APJ promotes the formation of large vessels even in the absence of the \"appropriate\" stiffness. Taken together, APJ could be a novel mechanotransducer that accelerates the maturation of cutaneous blood vessels, leading to the prevention of human skin aging.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mika", "last_name": "Sawane", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Otaka", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Katsujiro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kajiya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10456-021-09821-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34617195" } }, "mesh": [ { "descriptor": "Blood Vessels", "descriptor_ui": "D001808", "major_topic": false }, { "descriptor": "Capillaries", "descriptor_ui": "D002196", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 May", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "151-154", "proceedings_title": null, "publisher": "", "title": "Angiogenesis", "volume": "25", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Blood vessels sense dermal stiffness via a novel mechanotransducer, APJ.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Live-cell imaging with fluorescent proteins (FPs) is a powerful tool for investigating the exocytosis processes of hormones. However, the secretion process of glucagon-like peptide-1 (GLP-1) has not been visualized by FPs, which might be because tagging FPs inhibits GLP-1 synthesis through the post-translational processing from proglucagon. Here, we have developed FP-tagged GLP-1 by inserting FPs into the middle of GLP-1 and adding the proglucagon signal peptide. Confocal imaging confirmed that GLP-1 fused to FPs with high folding efficiency showed granular structure, in which secretory vesicle markers colocalized. The fluorescence intensity of FP in the culture supernatant from cells treated with KCl or forskolin was significantly increased compared with those from untreated cells. Furthermore, FP-tagged GLP-1 enables direct visualization of stimulation-dependent exocytosis of GLP-1 at a single granule resolution with total internal reflection fluorescence microscopy. FP-tagged GLP-1 might facilitate the screening of GLP-1 secretagogues and the discovery of new antidiabetic drugs.", "classifications": [ { "id": "21H00413", "label": "21H00413", "researcher": "Yoichiro Fujioka", "type": "grant" }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tsuzuki", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Maho", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Hira", "name": null }, { "creator_type": "author", "first_name": "Akinobu", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Miyoshi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Atsumi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/jdi.13800" }, "pmcid": { "normalized": "PMC9248420" }, "pmid": { "normalized": "35377537" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Exocytosis", "descriptor_ui": "D005089", "major_topic": false }, { "descriptor": "Glucagon-Like Peptide 1", "descriptor_ui": "D052216", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Peptide Fragments", "descriptor_ui": "D010446", "major_topic": false }, { "descriptor": "Proglucagon", "descriptor_ui": "D052336", "major_topic": false }, { "descriptor": "Secretory Vesicles", "descriptor_ui": "D022142", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "1134-1139", "proceedings_title": null, "publisher": "", "title": "Journal of diabetes investigation", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Direct visualization of glucagon-like peptide-1 secretion by fluorescent fusion proteins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Plant root absorbs water and nutrients from the soil, and the root apoplastic fluid (AF) is an important intermediate between cells and the surrounding environment. The acid growth theory suggests that an acidic AF is needed for cell wall expansion during root growth. However, technical limitations have precluded the quantification of root apoplastic fluid pH (AF-pH). Here, we used Green-enhanced Nano-lantern (GeNL), a chimeric protein of the luciferase NanoLuc (Nluc) and the green fluorescent protein mNeonGreen (mNG), as a ratiometric pH indicator based on the pH dependency of bioluminescence resonance energy transfer efficiency from Nluc to mNG. Luminescence spectrum of GeNL changed reciprocally from pH 4.5 to 7.5, with a pKa of 5.5. By fusing GeNL to a novel signal peptide from Arabidopsis thaliana Cellulase 1, we localised GeNL in A. thaliana AF. We visualised AF dynamics at subcellular resolution over 30 min and determined flow velocity in the maturation zone to be 0.97+/- 0.06 mum/s. We confirmed that the developing root AF is acidic in the pH range of 5.1-5.7, suggesting that the AF-pH is tightly regulated during root elongation. These results support the acid growth theory and provide evidence for AF-pH maintenance despite changes in ambient pH.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Quang", "last_name": "Tran", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Osabe", "name": null }, { "creator_type": "author", "first_name": "Tetsuyuki", "last_name": "Entani", "name": null }, { "creator_type": "author", "first_name": "Tetsuichi", "last_name": "Wazawa", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/pce.14404" }, "pmcid": { "normalized": "PMC9542637" }, "pmid": { "normalized": "35864560" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Plant Roots", "descriptor_ui": "D018517", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "3157-3170", "proceedings_title": null, "publisher": "", "title": "Plant, cell & environment", "volume": "45", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Application of Green-enhanced Nano-lantern as a bioluminescent ratiometric indicator for measurement of Arabidopsis thaliana root apoplastic fluid pH.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This manuscript reports on a simple paper-based bienzymatic colorimetric assay for sarcosine as an important urinary biomarker of prostate cancer. All required assay reagents are pre-deposited on hydrophilic filter paper spots surrounded by a hydrophobic barrier. Sarcosine in the sample solution is selectively oxidized in the presence of sarcosine oxidase (SOx), resulting in the formation of hydrogen peroxide, which is subsequently detected through the horseradish peroxidase (HRP)-catalyzed conversion of the colorless indicator 3,3',5,5'-tetramethylbenzidine (TMB) into its blue-colored oxidation product. By the modification of the paper with positively charged poly(allylamine hydrochloride) (PAH), a linear response to sarcosine between 0 and 10 muM and a significant lowering of the limit of detection (LOD) (0.6 muM) compared to the unmodified paper substrate (12.6 muM) has been achieved. The improvement of the LOD was attributed to the fact that the presence of the polymer limits the enzyme-driven colorimetric reaction to the surface of the paper substrate, resulting in stronger color development. In experiments in artificial urine matrix, the bicarbonate anion was identified as an inhibitor of the colorimetric reaction. This inhibition was successfully eliminated through on-device sample pH adjustments with pH-buffer components pre-deposited onto assay devices. The LOD for sarcosine achieved in artificial urine matrix (2.5 muM) is below the 5 muM threshold value for this urinary biomarker required for diagnostic purposes. Finally, good selectivity over all 20 natural amino acids and satisfactory long-term storage stability of reagent-modified paper substrates at - 20 degrees C for a period of 50 days were confirmed.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mayu", "last_name": "Masumoto", "name": null }, { "creator_type": "author", "first_name": "Sera", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Misaki", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00216-021-03682-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34657964" } }, "mesh": [ { "descriptor": "Colorimetry", "descriptor_ui": "D003124", "major_topic": true }, { "descriptor": "Horseradish Peroxidase", "descriptor_ui": "D006735", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": false }, { "descriptor": "Limit of Detection", "descriptor_ui": "D057230", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Sarcosine", "descriptor_ui": "D012521", "major_topic": true }, { "descriptor": "Sarcosine Oxidase", "descriptor_ui": "D050879", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "691-701", "proceedings_title": null, "publisher": "", "title": "Analytical and bioanalytical chemistry", "volume": "414", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Colorimetric paper-based sarcosine assay with improved sensitivity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mitochondria are fundamentally important in cell function, and their malfunction can cause the development of cancer, cardiovascular disease, and neuronal disorders. Myosin 19 (Myo19) shows discrete localization with mitochondria and is thought to play an important role in mitochondrial dynamics and function; however, the function of Myo19 in mitochondrial dynamics at the cellular and molecular levels is poorly understood. Critical missing information is whether Myo19 is a processive motor that is suitable for transportation of mitochondria. Here, we show for the first time that single Myo19 molecules processively move on actin filaments and can transport mitochondria in cells. We demonstrate that Myo19 dimers having a leucine zipper processively moved on cellular actin tracks in demembraned cells with a velocity of 50 to 60 nm/s and a run length of approximately 0.4 mum, similar to the movement of isolated mitochondria from Myo19 dimer-transfected cells on actin tracks, suggesting that the Myo19 dimer can transport mitochondria. Furthermore, we show single molecules of Myo19 dimers processively moved on single actin filaments with a large step size of approximately 34 nm. Importantly, WT Myo19 single molecules without the leucine zipper processively move in filopodia in living cells similar to Myo19 dimers, whereas deletion of the tail domain abolished such active movement. These results suggest that Myo19 can processively move on actin filaments when two Myo19 monomers form a dimer, presumably as a result of tail-tail association. In conclusion, Myo19 molecules can directly transport mitochondria on actin tracks within living cells.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Osamu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Young-Yeon", "last_name": "Choo", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Ikebe", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Mitsuo", "last_name": "Ikebe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbc.2022.101883" }, "pmcid": { "normalized": "PMC9065997" }, "pmid": { "normalized": "35367209" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": true }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Mitochondrial Dynamics", "descriptor_ui": "D063154", "major_topic": false }, { "descriptor": "Myosins", "descriptor_ui": "D009218", "major_topic": true }, { "descriptor": "Pseudopodia", "descriptor_ui": "D011554", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "101883", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "298", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Mitochondria-associated myosin 19 processively transports mitochondria on actin tracks in living cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Circadian rhythms are defined as approximately 24-hour oscillations in physiology and behavior. In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus is known as the central circadian clock. Based on current understanding, circadian rhythms are believed to be generated by transcription-translation feedback loops (TTFL) involving several clock genes and their protein products. However, several studies have shown that circadian oscillation in single SCN cells is still detectable in several clock gene deficient mice. These results suggest that there might be some oscillatory mechanisms without TTFL in mammalian cells. Other important aspects of circadian rhythms include neuronal circuits in the brain that regulate timing of physiological functions. Especially, functional output pathways from the SCN that regulate sleep and wakefulness have not been identified. In this review, I describe recent findings on circadian rhythm in the SCN, and of neuronal mechanisms that control circadian clock regulated sleep and wakefulness in mice.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2022.05.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35597406" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Circadian Clocks", "descriptor_ui": "D057906", "major_topic": true }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": false }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": false }, { "descriptor": "Wakefulness", "descriptor_ui": "D014851", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Sep", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "1-6", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "182", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Neural circuits in the central circadian clock and their regulation of sleep and wakefulness in mammals.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transactivating response element DNA-binding protein of 43 kDa (TDP-43), which is encoded by the TARDBP gene, is an RNA-binding protein with fundamental RNA processing activities, and its loss-of-function (LOF) has a central role in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). TARDBP mutations are postulated to inactivate TDP-43 functions, leading to impaired RNA processing. However, it has not been fully examined how mutant TDP-43 affects global RNA regulation, especially in human cell models. Here, we examined global RNA processing in forebrain cortical neurons derived from human induced pluripotent stem cells (iPSCs) with a pathogenic TARDBP mutation encoding the TDP-43(K263E) protein. In neurons expressing mutant TDP-43, we detected disrupted RNA regulation, including global changes in gene expression, missplicing, and aberrant polyadenylation, all of which were highly similar to those induced by TDP-43 knock-down. This mutation-induced TDP-43 LOF was not because of the cytoplasmic mislocalization of TDP-43. Intriguingly, in nonneuronal cells, including iPSCs and neural progenitor cells (NPCs), we did not observe impairments in RNA processing, thus indicating that the K263E mutation results in neuron-specific LOF of TDP-43. This study characterizes global RNA processing impairments induced by mutant TDP-43 and reveals the unprecedented cell type specificity of TDP-43 LOF in ALS/FTLD pathogenesis.", "classifications": [ { "id": "21H00438", "label": "21H00438", "researcher": "Kent Imaizumi", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Hirosato", "last_name": "Ideno", "name": null }, { "creator_type": "author", "first_name": "Tsukika", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/eneuro.0061-22.2022" }, "pmcid": { "normalized": "PMC9186108" }, "pmid": { "normalized": "35641224" } }, "mesh": [ { "descriptor": "Amyotrophic Lateral Sclerosis", "descriptor_ui": "D000690", "major_topic": true }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Frontotemporal Dementia", "descriptor_ui": "D057180", "major_topic": true }, { "descriptor": "Frontotemporal Lobar Degeneration", "descriptor_ui": "D057174", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "RNA Processing, Post-Transcriptional", "descriptor_ui": "D012323", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 May-Jun", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "ENEURO.0061-22.2022", "proceedings_title": null, "publisher": "", "title": "eNeuro", "volume": "9", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Pathogenic Mutation of TDP-43 Impairs RNA Processing in a Cell Type-Specific Manner: Implications for the Pathogenesis of ALS/FTLD.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge(1-5). Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ho", "last_name": "Namkoong", "name": null }, { "creator_type": "author", "first_name": "Ryuya", "last_name": "Edahiro", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nishihara", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Kyuto", "last_name": "Sonehara", "name": null }, { "creator_type": "author", "first_name": "Hiromu", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Azekawa", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Ho", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okudela", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Okuzaki", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Motooka", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Qingbo S.", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Ryunosuke", "last_name": "Saiki", "name": null }, { "creator_type": "author", "first_name": "Rino", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Natsuo", "last_name": "Tachikawa", "name": null }, { "creator_type": "author", "first_name": "Emmy", "last_name": "Yanagita", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Hyugaji", "name": null }, { "creator_type": "author", "first_name": "Eigo", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Kotoe", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Norihiro", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Hiki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Haruhi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Ryousuke", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Sonoko", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Sasano", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kabata", "name": null }, { "creator_type": "author", "first_name": "Katsunori", "last_name": "Masaki", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Kamata", "name": null }, { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Ikemura", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Chubachi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Okamori", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Atsuho", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Asakura", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Morisaki", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Uwamino", "name": null }, { "creator_type": "author", "first_name": "Kosaku", "last_name": "Nanki", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Uno", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Isono", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yuma", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Hosoda", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yotaro", "last_name": "Takaku", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Takayanagi", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Masaomi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Reina", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Nagasaka", "name": null }, { "creator_type": "author", "first_name": "Sawako", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Tagaya", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Kawana", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Arimura", "name": null }, { "creator_type": "author", "first_name": "Kunihiko", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Anzai", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Uchimura", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Tateishi", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Tohda", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Sonobe", "name": null }, { "creator_type": "author", "first_name": "Chihiro Tani", "last_name": "Sassa", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Ryusuke", "last_name": "Anan", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Toshikatsu", "last_name": "Sado", "name": null }, { "creator_type": "author", "first_name": "Yoshimune", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Haruta", "name": null }, { "creator_type": "author", "first_name": "Tadao", "last_name": "Nagasaki", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Mutoh", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Reoto", "last_name": "Takei", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Hagimoto", "name": null }, { 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"first_name": "Norio", "last_name": "Kodaka", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Oshio", "name": null }, { "creator_type": "author", "first_name": "Takatomo", "last_name": "Hirouchi", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Makino", "name": null }, { "creator_type": "author", "first_name": "Moritoki", "last_name": "Egi", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Omae", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Nannya", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Ai", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kumanogoh", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Katsushi", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Miyano", "name": null }, { "creator_type": "author", "first_name": "Seishi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fukunaga", "name": null }, { "creator_type": "author", "first_name": "Yukinori", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41586-022-05163-5" }, "pmcid": { "normalized": "PMC9492544" }, "pmid": { "normalized": "35940203" } }, "mesh": [ { "descriptor": "Alleles", "descriptor_ui": "D000483", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": true }, { "descriptor": "GTPase-Activating Proteins", "descriptor_ui": "D020690", "major_topic": true }, { "descriptor": "Guanine Nucleotide Exchange Factors", "descriptor_ui": "D020662", "major_topic": true }, { "descriptor": "Host Microbial Interactions", "descriptor_ui": "D000076662", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interferon Type I", "descriptor_ui": "D007370", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mesocricetus", "descriptor_ui": "D008647", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Pneumonia", "descriptor_ui": "D011014", "major_topic": false }, { "descriptor": "Pyrazoles", "descriptor_ui": "D011720", "major_topic": false }, { "descriptor": "RNA-Seq", "descriptor_ui": "D000081246", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true }, { "descriptor": "Viral Load", "descriptor_ui": "D019562", "major_topic": false }, { "descriptor": "Weight Loss", "descriptor_ui": "D015431", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Sep", "date_precision": "unknown", "issue": "7928", "normalized_date": null, "pages": "754-760", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "609", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "DOCK2 is involved in the host genetics and biology of severe COVID-19.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dynamic nuclear polarization (DNP) is a cutting-edge technique that markedly enhances the detection sensitivity of molecules using nuclear magnetic resonance (NMR)/magnetic resonance imaging (MRI). This methodology enables real-time imaging of dynamic metabolic status in vivo using MRI. To expand the targetable metabolic reactions, there is a demand for developing exogenous, i.e., artificially designed, DNP-NMR molecular probes; however, complying with the requirements of practical DNP-NMR molecular probes is challenging because of the lack of established design guidelines. Here, we report Ala-[1-(13)C]Gly-d(2)-NMe(2) as a DNP-NMR molecular probe for in vivo detection of aminopeptidase N activity. We developed this probe rationally through precise structural investigation, calculation, biochemical assessment, and advanced molecular design to achieve rapid and detectable responses to enzyme activity in vivo. With the fabricated probe, we successfully detected enzymatic activity in vivo. This report presents a comprehensive approach for the development of artificially derived, practical DNP-NMR molecular probes through structure-guided molecular design.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yutaro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Iori", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Hiraga", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Takakusagi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Nobu", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ishikita", "name": null }, { "creator_type": "author", "first_name": "Kazutoshi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Murali C.", "last_name": "Krishna", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Sando", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abj2667" }, "pmcid": { "normalized": "PMC8967239" }, "pmid": { "normalized": "35353577" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Apr", "date_precision": "unknown", "issue": "13", "normalized_date": null, "pages": "eabj2667", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "8", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Structure-guided design enables development of a hyperpolarized molecular probe for the detection of aminopeptidase N activity in vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Ultrasonography (US) is widely used for the diagnosis of liver tumors. However, the accuracy of the diagnosis largely depends on the visual perception of humans. Hence, we aimed to construct artificial intelligence (AI) models for the diagnosis of liver tumors in US. METHODS: We constructed three AI models based on still B-mode images: model-1 using 24,675 images, model-2 using 57,145 images, and model-3 using 70,950 images. A convolutional neural network was used to train the US images. The four-class liver tumor discrimination by AI, namely, cysts, hemangiomas, hepatocellular carcinoma, and metastatic tumors, was examined. The accuracy of the AI diagnosis was evaluated using tenfold cross-validation. The diagnostic performances of the AI models and human experts were also compared using an independent test cohort of video images. RESULTS: The diagnostic accuracies of model-1, model-2, and model-3 in the four tumor types are 86.8%, 91.0%, and 91.1%, whereas those for malignant tumor are 91.3%, 94.3%, and 94.3%, respectively. In the independent comparison of the AIs and physicians, the percentages of correct diagnoses (accuracies) by the AIs are 80.0%, 81.8%, and 89.1% in model-1, model-2, and model-3, respectively. Meanwhile, the median percentages of correct diagnoses are 67.3% (range 63.6%-69.1%) and 47.3% (45.5%-47.3%) by human experts and non-experts, respectively. CONCLUSION: The performance of the AI models surpassed that of human experts in the four-class discrimination and benign and malignant discrimination of liver tumors. Thus, the AI models can help prevent human errors in US diagnosis.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Naoshi", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Mekada", "name": null }, { "creator_type": "author", "first_name": "Mutsumi", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Iijima", "name": null }, { "creator_type": "author", "first_name": "Toshiko", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Tateishi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Chikara", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Kudo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00535-022-01849-9" }, "pmcid": { "normalized": "PMC8938378" }, "pmid": { "normalized": "35220490" } }, "mesh": [ { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": true }, { "descriptor": "Neural Networks, Computer", "descriptor_ui": "D016571", "major_topic": false }, { "descriptor": "Ultrasonography", "descriptor_ui": "D014463", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "309-321", "proceedings_title": null, "publisher": "", "title": "Journal of gastroenterology", "volume": "57", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Artificial intelligence (AI) models for the ultrasonographic diagnosis of liver tumors and comparison of diagnostic accuracies between AI and human experts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Hattori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41570-022-00413-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37118010" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "522-523", "proceedings_title": null, "publisher": "", "title": "Nature reviews. Chemistry", "volume": "6", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Tiny but bright.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: To evaluate the ability of photocurable gelatin to prevent stricture recurrence after urethral dilation in a rabbit urethral stricture model. METHODS: We created urethral strictures in the bulbar urethras of 10 male Japanese white rabbits using electrocoagulation. After 1 month, the rabbits were randomly divided into Group A (n = 5; urethral stricture dilation and the local application of photocurable gelatin using a ruthenium photoinitiator and irradiation with a light-emitting diode light [lambda = 455 nm, 50 mW/cm(2) ] for 1 min) and Group B (n = 5; dilation only). Urethral stricture status was evaluated 1-2 months later by retrograde urethrography and urethroscopy. The lumen ratio (urethral width at the stricture site to the normal urethral width on retrograde urethrography) was calculated. Urethral patency was considered to be improved when the urethral lumen could accommodate a 10-Fr urethroscope without resistance. Urethral specimens were harvested for histopathological examination. RESULTS: The mean lumen ratio did not differ significantly between Groups A and B before dilation (25.8% vs 23.4%; P = 0.40), but differed significantly after dilation (65.5% vs 27.3%, respectively; P = 0.03). Urethral patency improved in all rabbits in Group A (100%) versus one rabbit in Group B (20%; P = 0.02). The mean circumference of the regenerated urethral epithelium at the stricture site was larger in Group A than in Group B (14 mm vs 6.6 mm; P = 0.06). CONCLUSIONS: Photocurable gelatin can reduce urethral stricture recurrence after dilation in a rabbit model.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Ojima", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Yoshine", "last_name": "Mayumi", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Miyai", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shinchi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Horiguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/iju.14730" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34664326" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Constriction, Pathologic", "descriptor_ui": "D003251", "major_topic": false }, { "descriptor": "Dilatation", "descriptor_ui": "D004106", "major_topic": false }, { "descriptor": "Gelatin", "descriptor_ui": "D005780", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Recurrence", "descriptor_ui": "D012008", "major_topic": false }, { "descriptor": "Urethra", "descriptor_ui": "D014521", "major_topic": true }, { "descriptor": "Urethral Stricture", "descriptor_ui": "D014525", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "170-175", "proceedings_title": null, "publisher": "", "title": "International journal of urology : official journal of the Japanese Urological Association", "volume": "29", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Ability of photocurable gelatin to prevent stricture recurrence after urethral dilation in rabbits.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Measuring mechanical parameters in tissues, such as the elastic modulus of cell-cell junctions, is essential to decipher the mechanical control of morphogenesis. However, their in vivo measurement is technically challenging. Here, we formulated an image-based statistical approach to estimate the mechanical parameters of epithelial cells. Candidate mechanical models are constructed based on force-cell shape correlations obtained from image data. Substitution of the model functions into force-balance equations at the cell vertex leads to an equation with respect to the parameters of the model, by which one can estimate the parameter values using a least-squares method. A test using synthetic data confirmed the accuracy of parameter estimation and model selection. By applying this method to Drosophila epithelial tissues, we found that the magnitude and orientation of feedback between the junction tension and shrinkage, which are determined by the spring constant of the junction, were correlated with the elevation of tension and myosin-II on shrinking junctions during cell rearrangement. Further, this method clarified how alterations in tissue polarity and stretching affect the anisotropy in tension parameters. Thus, our method provides a novel approach to uncovering the mechanisms governing epithelial morphogenesis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Goshi", "last_name": "Ogita", "name": null }, { "creator_type": "author", "first_name": "Takefumi", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Sugimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1010209" }, "pmcid": { "normalized": "PMC9223404" }, "pmid": { "normalized": "35737656" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": true }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Intercellular Junctions", "descriptor_ui": "D007365", "major_topic": true }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "e1010209", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "18", "year": 2022 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000270" ] }, "title": "Image-based parameter inference for epithelial mechanics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Combination herpes simplex virus (HSV) oncolytic virotherapy and BRAF inhibitors (BRAFi) represent promising immunogenic treatments for BRAF mutant melanoma, but an improved understanding of the immunobiology of combinations is needed to improve on the benefit of immune checkpoint inhibitors (ICI). METHODS: Using a BRAF(V600E)-driven murine melanoma model, we tested the immunogenicity of HSV/BRAFi in immunocompetent C57BL mice. In addition to standard FACS analysis, we used the 'Timer of Cell Kinetics and Activity' system, which can analyze the temporal dynamics of different T cell subsets. This immune data was used to inform the selection of ICI for triple combination therapy, the effects of which were then further characterized using transcriptomics. RESULTS: Adding BRAFi treatment to HSV improved anti-tumor effects in vivo but not in vitro. Immune characterization showed HSV or dual therapy led to fewer intratumoral Treg, although with a more activated phenotype, together with more effector CD8 +T cells. Tocky analysis further showed that HSV/BRAFi dual treatment reduced the Tocky signal (reflecting engagement with cognate antigen), in both Treg and conventional subsets of CD4+, but not in CD8 +cells. However, a higher percentage of Treg than of conventional CD4 +maintained frequent engagement with antigens on treatment, reflecting a predominance of suppressive over effector function within the CD4 +compartment. The only T cell subset which correlated with a reduction in tumor growth was within Tocky signal positive conventional CD4+, supporting their therapeutic role. Targeting CD25 high, antigen-engaged Treg with a depleting anti-CD25 ICI, achieved complete cures in 100% of mice with triple therapy. Transcriptomic analysis confirmed reduction in Foxp3 on addition of anti-CD25 to HSV/BRAFi, as well as increases in expression of genes reflecting interferon signaling and cytotoxic activity. CONCLUSIONS: Combination HSV/BRAFi is an immunogenic therapy for BRAF mutant melanoma, but cannot fully control tumors. Dual therapy results in changes in T cell dynamics within tumors, with relatively maintained antigen signaling in Treg compared with conv CD4+. Antigen-engaged CD4 +effectors correlate with tumor growth control, and depletion of Treg by addition of an anti-CD25 ICI, releasing suppression of conventional CD4 +effectors by Treg, enhances survival and activates immune signaling within tumors.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Galabina", "last_name": "Bozhanova", "name": null }, { "creator_type": "author", "first_name": "Jehanne", "last_name": "Hassan", "name": null }, { "creator_type": "author", "first_name": "Lizzie", "last_name": "Appleton", "name": null }, { "creator_type": "author", "first_name": "Victoria", "last_name": "Jennings", "name": null }, { "creator_type": "author", "first_name": "Shane", "last_name": "Foo", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "McLaughlin", "name": null }, { "creator_type": "author", "first_name": "Charleen Ml", "last_name": "Chan Wah Hak", "name": null }, { "creator_type": "author", "first_name": "Emmanuel C.", "last_name": "Patin", "name": null }, { "creator_type": "author", "first_name": "Eva", "last_name": "Crespo-Rodriguez", "name": null }, { "creator_type": "author", "first_name": "Gabby", "last_name": "Baker", "name": null }, { "creator_type": "author", "first_name": "Edward", "last_name": "Armstrong", "name": null }, { "creator_type": "author", "first_name": "Matthew", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Hardev", "last_name": "Pandha", "name": null }, { "creator_type": "author", "first_name": "Adel", "last_name": "Samson", "name": null }, { "creator_type": "author", "first_name": "Victoria", "last_name": "Roulstone", "name": null }, { "creator_type": "author", "first_name": "Joan", "last_name": "Kyula", "name": null }, { "creator_type": "author", "first_name": "Richard", "last_name": "Vile", "name": null }, { "creator_type": "author", "first_name": "Fiona", "last_name": "Errington-Mais", "name": null }, { "creator_type": "author", "first_name": "Malin", "last_name": "Pedersen", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Harrington", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Alan", "last_name": "Melcher", "name": null } ], "identifiers": { "doi": { "normalized": "10.1136/jitc-2021-004410" }, "pmcid": { "normalized": "PMC8961178" }, "pmid": { "normalized": "35338089" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CD4-Positive T-Lymphocytes", "descriptor_ui": "D015496", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunity", "descriptor_ui": "D007109", "major_topic": false }, { "descriptor": "Melanoma", "descriptor_ui": "D008545", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Oncolytic Viruses", "descriptor_ui": "D050504", "major_topic": true }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins B-raf", "descriptor_ui": "D048493", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "e004410", "proceedings_title": null, "publisher": "", "title": "Journal for immunotherapy of cancer", "volume": "10", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "CD4 T cell dynamics shape the immune response to combination oncolytic herpes virus and BRAF inhibitor therapy for melanoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "At the initial stage of carcinogenesis, oncogenic transformation occurs in single cells within epithelial layers. However, the behavior and fate of the newly emerging transformed cells remain enigmatic. Here, using originally established mouse models, we investigate the fate of RasV12-transformed cells that appear in a mosaic manner within epithelial tissues. In the lung bronchial epithelium, most majority of RasV12-transformed cells are apically extruded, whereas noneliminated RasV12 cells are often basally delaminated leading to various noncell-autonomous changes in surrounding environments; macrophages and activated fibroblasts are accumulated, and normal epithelial cells overlying RasV12 cells overproliferate and form a convex multilayer, which is termed a 'dome-like structure'. In addition, basally extruded RasV12 cells acquire certain features of epithelial-mesenchymal transition (EMT). Furthermore, the expression of COX-2 is profoundly elevated in RasV12 cells in dome-like structures, and treatment with the COX inhibitor ibuprofen suppresses the recruitment of activated fibroblasts and moderately diminishes the formation of dome-like structures. Therefore, basal extrusion of single-oncogenic mutant cells can induce a tumor microenvironment and EMT and generate characteristic precancerous lesions, providing molecular insights into the earlier steps of cancer development.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takanobu", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Sekai", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Kozawa", "name": null }, { "creator_type": "author", "first_name": "Nanami", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Tanimura", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kon", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Takeru", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Andrew", "last_name": "Tilston-Lunel", "name": null }, { "creator_type": "author", "first_name": "Xaralabos", "last_name": "Varelas", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.15483" }, "pmcid": { "normalized": "PMC9633292" }, "pmid": { "normalized": "35816400" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": true }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": true }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Oncogenes", "descriptor_ui": "D009857", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "3710-3721", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "113", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Basal extrusion of single-oncogenic mutant cells induces dome-like structures with altered microenvironments.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The underlying pathologies of psychiatric disorders, which cause substantial personal and social losses, remain unknown, and their elucidation is an urgent issue. To clarify the core pathological mechanisms underlying psychiatric disorders, in addition to laboratory-based research that incorporates the latest findings, it is necessary to conduct large-sample-size research and verify reproducibility. For this purpose, it is critical to conduct multicenter collaborative research across various fields, such as psychiatry, neuroscience, molecular biology, genomics, neuroimaging, cognitive science, neurophysiology, psychology, and pharmacology. Moreover, collaborative research plays an important role in the development of young researchers. In this respect, the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium and Cognitive Genetics Collaborative Research Organization (COCORO) have played important roles. In this review, we first overview the importance of multicenter collaborative research and our target psychiatric disorders. Then, we introduce research findings on the pathophysiology of psychiatric disorders from neurocognitive, neurophysiological, neuroimaging, genetic, and basic neuroscience perspectives, focusing mainly on the findings obtained by COCORO. It is our hope that multicenter collaborative research will contribute to the elucidation of the pathological basis of psychiatric disorders.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Onitsuka", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Kiyotaka", "last_name": "Nemoto", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Kushima", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Koshiyama", "name": null }, { "creator_type": "author", "first_name": "Michihiko", "last_name": "Koeda", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Takatoshi", "last_name": "Hikida", "name": null }, { "creator_type": "author", "first_name": "Kiyoto", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/pcn.13311" }, "pmcid": { "normalized": "PMC9306748" }, "pmid": { "normalized": "34716732" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Big Data", "descriptor_ui": "D000077558", "major_topic": true }, { "descriptor": "Data Analysis", "descriptor_ui": "D000078332", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mental Disorders", "descriptor_ui": "D001523", "major_topic": true }, { "descriptor": "Meta-Analysis as Topic", "descriptor_ui": "D015201", "major_topic": false }, { "descriptor": "Multicenter Studies as Topic", "descriptor_ui": "D015337", "major_topic": true }, { "descriptor": "Neuroimaging", "descriptor_ui": "D059906", "major_topic": false }, { "descriptor": "Psychiatry", "descriptor_ui": "D011570", "major_topic": true }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Translational Research, Biomedical", "descriptor_ui": "D057170", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "1-14", "proceedings_title": null, "publisher": "", "title": "Psychiatry and clinical neurosciences", "volume": "76", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Trends in big data analyses by multicenter collaborative translational research in psychiatry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In most multispectral optical-resolution photoacoustic microscopy (OR-PAM), spatial scanning is repeated for each excitation wavelength, which decreases throughput and causes motion artifacts during spectral processing. This study proposes a new spectroscopic OR-PAM technique to acquire information on the photoacoustic signal intensity and excitation wavelength from single spatial scans. The technique involves irradiating an imaging target with two broadband optical pulses with and without wavelength-dependent time delays. The excitation wavelength of the sample is then calculated by measuring the time delay between the photoacoustic signals generated by the two optical pulses. This technique is validated by measuring the excitation wavelengths of dyes in tubes. Furthermore, we demonstrate the three-dimensional spectroscopic OR-PAM of cells stained with suitable dyes. Although the tradeoff between excitation efficiency and excitation bandwidth must be adjusted based on the application, combining the proposed technique with fast spatial scanning methods can significantly contribute to recent OR-PAM applications, such as monitoring quick biological events and microscale tracking of moving materials.", "classifications": [ { "id": "19H05436", "label": "19H05436", "researcher": "Miya Ishihara", "type": "grant" }, { "id": "21H00445", "label": "21H00445", "researcher": "Miya Ishihara", "type": "grant" }, { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Tachi", "name": null }, { "creator_type": "author", "first_name": "Manami", "last_name": "Miyashita", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Okawa", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.pacs.2022.100364" }, "pmcid": { "normalized": "PMC9096666" }, "pmid": { "normalized": "35574189" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Jun", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "100364", "proceedings_title": null, "publisher": "", "title": "Photoacoustics", "volume": "26", "year": 2022 }, "ssbd": { "database": [ "ssbd-database-000245" ], "repository": [ "ssbd-repos-000245" ] }, "title": "Spectroscopic photoacoustic microscopic imaging during single spatial scan using broadband excitation light pulses with wavelength-dependent time delay.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: An aberrant increase in the diastolic calcium concentration ([Ca(2+)]i) level is a hallmark of heart failure (HF) and the cause of delayed afterdepolarization and ventricular arrhythmia (VA). Although mitochondria play a role in regulating [Ca(2+)]i, whether they can compensate for the [Ca(2+)]i abnormality in ventricular myocytes is unknown. OBJECTIVE: The purpose of this study was to investigate whether enhanced Ca(2+) uptake of mitochondria may compensate for an abnormal increase in the [Ca(2+)]i of ventricular myocytes in HF to effectively mitigate VA. METHODS: We used a HF mouse model in which myocardial infarction was induced by permanent left anterior descending coronary artery ligation. The mitochondrial Ca(2+) uniporter was stimulated by kaempferol. Ca(2+) dynamics and membrane potential were measured using an epifluorescence microscope, a confocal microscope, and the perforated patch-clamp technique. VA was induced in Langendorff-perfused hearts, and hemodynamic parameters were measured using a microtip transducer catheter. RESULTS: Protein expression of the mitochondrial Ca(2+) uniporter, as assessed by its subunit expression, did not change between HF and sham mice. Treatment of cardiomyocytes with kaempferol, isolated from HF mice 28 days after coronary ligation, reduced the appearance of aberrant diastolic [Ca(2+)]i waves and sparks and spontaneous action potentials. Kaempferol effectively reduced VA occurring in Langendorff-perfused hearts. Intravenous administration of kaempferol did not markedly affect left ventricular hemodynamic parameters. CONCLUSION: The effects of kaempferol in HF of mice implied that mitochondria may have the potential to compensate for abnormal [Ca(2+)]i. Mechanisms involved in mitochondrial Ca(2+) uptake may provide novel targets for treatment of HF-associated VA.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hikaru", "last_name": "Hagiwara", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Takahide", "last_name": "Kadosaka", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Koya", "name": null }, { "creator_type": "author", "first_name": "Motoki", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Rui", "last_name": "Kamada", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Temma", "name": null }, { "creator_type": "author", "first_name": "Kazufumi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Jose Antonio", "last_name": "Moreno", "name": null }, { "creator_type": "author", "first_name": "Ohyun", "last_name": "Kwon", "name": null }, { "creator_type": "author", "first_name": "Hisakata", "last_name": "Sabe", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Toshihisa", "last_name": "Anzai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.hrthm.2022.05.034" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35660475" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arrhythmias, Cardiac", "descriptor_ui": "D001145", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": true }, { "descriptor": "Calcium Channels", "descriptor_ui": "D015220", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": true }, { "descriptor": "Kaempferols", "descriptor_ui": "D044949", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "1725-1735", "proceedings_title": null, "publisher": "", "title": "Heart rhythm", "volume": "19", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Stimulation of the mitochondrial calcium uniporter mitigates chronic heart failure-associated ventricular arrhythmia in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: We examined whether artificial intelligence (AI) used with the novel digital image enhancement system modalities (CLARA+CHROMA, SPECTRA A, and SPECTRA B) could distinguish the cholesteatoma matrix, cholesteatoma debris, and normal middle ear mucosa, and observe the middle ear cavity during middle ear cholesteatoma surgery. METHODS: A convolutional neural network (CNN) was trained with a set of images chosen by an otologist. To evaluate the diagnostic accuracy of the constructed CNN, an independent test data set of middle ear images was collected from 14 consecutive patients with 26 cholesteatoma matrix lesions, who underwent transcanal endoscopic ear surgery at a single hospital from August 2018 to September 2019. The final test data set included 58 total images, with 15 images from each modality for each case. RESULTS: The CNN required only 10 s to analyze more than 58 test images. Using SPECTRA A and SPECTRA B, the CNN correctly diagnosed 15 and 15 of 26 cholesteatoma matrix lesions, with a sensitivity of 34.6% and 42.3%, and with a specificity of 81.3% and 87.5%, respectively. CONCLUSION: Our preliminary study revealed that AI and novel imaging modalities are potentially useful tools for identifying and visualizing the cholesteatoma matrix during endoscopic ear surgery. The diagnostic ability of the CNN is not yet appropriate for implementation in daily clinical practice, based on our study findings. However, in the future, these techniques and AI tools could help to reduce the burden on surgeons and will facilitate telemedicine in remote and rural areas, as well as in developing countries where the number of surgeons is limited.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Toru", "last_name": "Miwa", "name": null }, { "creator_type": "author", "first_name": "Ryosei", "last_name": "Minoda", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Osaka", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Kanemaru", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Omori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.anl.2021.03.018" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33824034" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Cholesteatoma, Middle Ear", "descriptor_ui": "D018424", "major_topic": false }, { "descriptor": "Diagnosis, Differential", "descriptor_ui": "D003937", "major_topic": false }, { "descriptor": "Ear, Middle", "descriptor_ui": "D004432", "major_topic": false }, { "descriptor": "Endoscopy", "descriptor_ui": "D004724", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Enhancement", "descriptor_ui": "D007089", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neural Networks, Computer", "descriptor_ui": "D016571", "major_topic": true }, { "descriptor": "Surgery, Computer-Assisted", "descriptor_ui": "D025321", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Feb", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "11-17", "proceedings_title": null, "publisher": "", "title": "Auris, nasus, larynx", "volume": "49", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Application of artificial intelligence using a convolutional neural network for detecting cholesteatoma in endoscopic enhanced images.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: To quantify the bias of shear wave speed (SWS) measurements in a viscoelastic phantom across six different ultrasound (US) systems and to compare the SWS with those from transient elastography (TE) and magnetic resonance elastography (MRE). METHODS: A viscoelastic phantom of stiffness representing fibrotic liver or healthy thyroid was measured with nine (linear probe) and 10 (convex probe) modes of six different US-based shear wave elastography (SWE) systems using linear and convex probes. SWS measurements of three regions of interest were repeated thrice at two focal depths, coupling the probe to the phantom using a jig. An MRE system using three motion-encoding gradient frequencies of 60, 90, and 120 Hz and TE were also used to measure the stiffness of the phantom. RESULTS: The SWS from different SWE systems had mean coefficients of variation of 9.0-9.2% and 5.4-5.6% with linear and convex probes, respectively, in viscoelastic phantom measurement. The focal depth was a less significant source of SWS variability than the system. The total average SWS obtained with US-SWE systems was 19.9% higher than that obtained with MRE at 60 Hz, which is commonly used in clinical practice, and 31.5% higher than that obtained with TE using the M probe. CONCLUSIONS: Despite the measurement biases associated with the SWE systems, biases were not necessarily consistent, and they changed with the probes used and depth measured. The SWS of the viscoelastic phantom obtained using different modalities increased according to the shear wave frequency used.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Riwa", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Mikio", "last_name": "Suga", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Usumura", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Iijima", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Hachiya", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Obata", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Yamaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10396-022-01190-x" }, "pmcid": { "normalized": "PMC9038798" }, "pmid": { "normalized": "35061118" } }, "mesh": [ { "descriptor": "Bias", "descriptor_ui": "D015982", "major_topic": false }, { "descriptor": "Elasticity Imaging Techniques", "descriptor_ui": "D054459", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Liver Cirrhosis", "descriptor_ui": "D008103", "major_topic": false }, { "descriptor": "Phantoms, Imaging", "descriptor_ui": "D019047", "major_topic": false }, { "descriptor": "Ultrasonography", "descriptor_ui": "D014463", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "143-152", "proceedings_title": null, "publisher": "", "title": "Journal of medical ultrasonics (2001)", "volume": "49", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Shear wave speed measurement bias in a viscoelastic phantom across six ultrasound elastography systems: a comparative study with transient elastography and magnetic resonance elastography.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: In Alzheimer's disease (AD), abnormally phosphorylated tau in the somatodendrite compartment of brain neurons causes synaptic loss, resulting in neuron death. Although the mechanism by which hyperphosphorylated tau appears in dendrites remains unclear, we have previously reported that local translation of tau mRNA and GSK3beta mRNA in response to glutamatergic stimulation triggers an increase of tau protein and initiation of a cycle for amplification of reactivated preexisting GSK3beta, respectively. In this study, we investigated the mechanism responsible for neural excitation-dependent activation of another major tau kinase, CDK5, within dendrites. METHODS: Primary hippocampal neurons were treated with glutamate and examined by in situ hybridization, immunocytochemistry and Western blotting. RESULTS: The mRNAs for both CDK5 and its neural-specific activator, p35, were found to be constitutively distributed in dendrites. Glutamate treatment induced immediate local dendritic translation of these proteins as well as conversion of p35 to p25, which forms the hyper-activated CDK5/p25 complex. This neural excitation-dependent tau phosphorylation by CDK5 was suppressed in the presence of a calpain inhibitor or a NMDA receptor antagonist. CONCLUSION: Our results indicate that in addition to an increase of dendritic tau and reactivation of preexisting GSK3beta, increase and hyper-activation of CDK5 are evoked by translation of dendrite-distributed mRNAs upon NMDA receptor-mediated neural excitation. GENERAL SIGNIFICANCE: Hyperphosphorylated tau with AD epitopes is locally produced in dendrites via translational activation of dendrite-distributed mRNAs in response to glutamatergic stimulation. Therefore, tau hyperphosphorylation may play a crucial role in synaptic transduction.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Toru", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Sachiyo", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbagen.2022.130135" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35358667" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase 5", "descriptor_ui": "D051360", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Glycogen Synthase Kinase 3 beta", "descriptor_ui": "D000071679", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Phosphotransferases", "descriptor_ui": "D010770", "major_topic": false }, { "descriptor": "Receptors, N-Methyl-D-Aspartate", "descriptor_ui": "D016194", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "130135", "proceedings_title": null, "publisher": "", "title": "Biochimica et biophysica acta. General subjects", "volume": "1866", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Dendritic distribution of CDK5 mRNA and p35 mRNA, and a glutamate-responsive increase of CDK5/p25 complex contribute to tau hyperphosphorylation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Gastrin-releasing peptide (GRP) and its receptor (GRPR) have been identified as itch mediators in the spinal and trigeminal somatosensory systems in rodents. In primates, there are few reports of GRP/GRPR expression or function in the spinal sensory system and virtually nothing is known in the trigeminal system. The aim of the present study was to characterize GRP and GRPR in the trigeminal and spinal somatosensory system of Japanese macaque monkeys (Macaca fuscata). cDNA encoding GRP was isolated from the macaque dorsal root ganglion (DRG) and exhibited an amino acid sequence that was highly conserved among mammals and especially in primates. Immunohistochemical analysis demonstrated that GRP was expressed mainly in the small-sized trigeminal ganglion and DRG in adult macaque monkeys. Densely stained GRP-immunoreactive (ir) fibers were observed in superficial layers of the spinal trigeminal nucleus caudalis (Sp5C) and the spinal cord. In contrast, GRP-ir fibers were rarely observed in the principal sensory trigeminal nucleus and oral and interpolar divisions of the spinal trigeminal nucleus. cDNA cloning, in situ hybridization, and Western blot revealed substantial expression of GRPR mRNA and GRPR protein in the macaque spinal dorsal horn and Sp5C. Our Western ligand blot and ligand derivative stain for GRPR revealed that GRP directly bound in the macaque Sp5C and spinal dorsal horn as reported in rodents. Finally, GRP-ir fibers were also detected in the human spinal dorsal horn. The spinal and trigeminal itch neural circuits labeled with GRP and GRPR appear to function also in primates.", "classifications": [ { "id": "21H00428", "label": "21H00428", "researcher": "Tatsuya Sakamoto", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Takanami", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Oti", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Naoaki", "last_name": "Tsutsui", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Earl", "last_name": "Carstens", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cne.25376" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35686563" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DNA, Complementary", "descriptor_ui": "D018076", "major_topic": false }, { "descriptor": "Gastrin-Releasing Peptide", "descriptor_ui": "D019886", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Macaca fuscata", "descriptor_ui": "D000080527", "major_topic": true }, { "descriptor": "Pruritus", "descriptor_ui": "D011537", "major_topic": false }, { "descriptor": "Receptors, Bombesin", "descriptor_ui": "D018004", "major_topic": false }, { "descriptor": "Sense Organs", "descriptor_ui": "D012679", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Nov", "date_precision": "unknown", "issue": "16", "normalized_date": null, "pages": "2804-2819", "proceedings_title": null, "publisher": "", "title": "The Journal of comparative neurology", "volume": "530", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Characterization of the expression of gastrin-releasing peptide and its receptor in the trigeminal and spinal somatosensory systems of Japanese macaque monkeys: Insight into humans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Organoids are being widely introduced as novel research models in multiple research fields. Human-induced pluripotent stem cells-derived kidney organoids became an indispensable tool to study human kidney development, model various diseases and infections leading to kidney damage, and offer a new route towards better drug development and validation, personalized drug screening, and regenerative medicine. In this review, we provide an update of the most recent developments in kidney organoid induction: their main goals, advantages, and shortcomings. We further discuss their current applications in providing modeling and treatment avenues to various kidney injuries, their use in genome-wide screening of kidney diseases, and the cell interactions occurring in these kidney structures.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Olena", "last_name": "Trush", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.gde.2022.101944" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35785592" } }, "mesh": [ { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": true }, { "descriptor": "Regenerative Medicine", "descriptor_ui": "D044968", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Aug", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "101944", "proceedings_title": null, "publisher": "", "title": "Current opinion in genetics & development", "volume": "75", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Kidney organoid research: current status and applications.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The water flea Daphnia magna is a small freshwater planktonic animal in the Cladocera. In this study, we assembled the genome of the D. magna NIES strain, which is widely used for gene targeting but has no reported genome. We used the long-read sequenced data of the Oxford nanopore sequencing tool for assembly. Using 3,231 genetic markers, the draft genome of the D. magna NIES strain was built into ten linkage groups (LGs) with 483 unanchored contigs, comprising a genome size of 173.47 Mb. The N50 value of the genome was 12.54 Mb and the benchmarking universal single-copy ortholog value was 98.8%. Repeat elements in the D. magna NIES genome were 40.8%, which was larger than other Daphnia spp. In the D. magna NIES genome, 15,684 genes were functionally annotated. To assess the genome of the D. magna NIES strain for CRISPR/Cas9 gene targeting, we selected glutathione S-transferase omega 2 (GST-O2), which is an important gene for the biotransformation of arsenic in aquatic organisms, and targeted it with an efficient make-up (25.0%) of mutant lines. In addition, we measured reactive oxygen species and antioxidant enzymatic activity between wild type and a mutant of the GST-O2 targeted D. magna NIES strain in response to arsenic. In this study, we present the genome of the D. magna NIES strain using GST-O2 as an example of gene targeting, which will contribute to the construction of deletion mutants by CRISPR/Cas9 technology.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Eunjin", "last_name": "Byeon", "name": null }, { "creator_type": "author", "first_name": "Min-Sub", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Duck-Hyun", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Yoseop", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Haksoo", "last_name": "Jeong", "name": null }, { "creator_type": "author", "first_name": "Jin-Sol", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Sung-Ah", "last_name": "Hong", "name": null }, { "creator_type": "author", "first_name": "Jun Chul", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Hye-Min", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Alaa El-Din H.", "last_name": "Sayed", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Sangsu", "last_name": "Bae", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Young Hwan", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Jae-Seong", "last_name": "Lee", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.aquatox.2021.106021" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34856461" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": true }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": true }, { "descriptor": "Gene Targeting", "descriptor_ui": "D018390", "major_topic": true }, { "descriptor": "Glutathione Transferase", "descriptor_ui": "D005982", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jan", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "106021", "proceedings_title": null, "publisher": "", "title": "Aquatic toxicology (Amsterdam, Netherlands)", "volume": "242", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "The freshwater water flea Daphnia magna NIES strain genome as a resource for CRISPR/Cas9 gene targeting: The glutathione S-transferase omega 2 gene.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Analytical pipeline, which is used for various analysis application, of CellProfiler, an open-source software for cell imaging analysis, is very important. In the present study, to examine whether intracellular proteins can be discriminated using a combination of CellProfiler and ImageJ, we analyzed neuroblastoma and monocytic cell lines, and disease-specific induced pluripotent stem cell (iPSC)-derived neurons. This revealed that scattered puncta of Rab7 and transferrin in neuroblastoma lines were clearly detectable by created analytical pipelines in CellProfiler. We then constructed pipelines for measuring the distance from the center of the nucleus to allow investigation of the intracellular localization of Rab7 or transferrin. Using CellProfiler and ImageJ in combination, we confirmed that our pipelines were applicable both quantitatively and objectively to analysis of membrane trafficking of proteins such as Rab proteins and transferrin. In addition, when applied to quantitative measurement of phagocytosis, our pipelines clearly detected monocytic cell lines that had engulfed bioparticles. Finally, we developed new pipelines for analysis of disease phenotype using iPSCs from a patient with familial Parkinson's disease (PD), harboring the I2020T LRRK2 mutation (PARK8). These were able to successfully detect Rab5 puncta and Rab7 puncta in PARK8 patient iPSC-derived neurons. Interestingly, in long-term culture, we found that the numbers of Rab7 puncta in a single PARK8 patient iPSC-derived neurons were lower than that of control iPSC-derived neurons. On the other hands, at 14 days in vitro, the numbers of Rab5 puncta in PARK8 patient iPSC-derived neurons were lower than those of isogenic iPSC-derived neurons, but not Rab7 puncta. Furthermore, Rab5 puncta of PARK8 patient iPSC-derived neurons exhibited distinct localization pattern relative to isogenic iPSC-derived neurons. These present results suggest that this new analytical tool can be used as a supporting method for quantification of intracellular protein.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akito", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Iwabuchi", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ymeth.2021.04.019" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33915291" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Neuroblastoma", "descriptor_ui": "D009447", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Transferrins", "descriptor_ui": "D061250", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jul", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "233-241", "proceedings_title": null, "publisher": "", "title": "Methods (San Diego, Calif.)", "volume": "203", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "A new approach to analysis of intracellular proteins and subcellular localization using cellprofiler and imageJ in combination.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Objective: Photoacoustic (PA) imaging is a novel noninvasive technique that offers high-contrast tomographic imaging with ultrasound-like resolution at depths of centimeters, enabling visualization of deep small vessels. The aim of this pilot study was to survey the characteristics of deep vessel networks in the mucosa of neoplastic gastrointestinal (GI) lesions using PA imaging. Methods: Specimens of patients who had undergone surgical and endoscopic resection for GI lesions were included in this study. The PA/ultrasound imaging system for clinical research is characterized by a technology that can superimpose a PA image over an ultrasound image. Three-dimensional PA images were acquired for the resected specimen before fixation. The stomach and colon of live pigs were incised, and the walls were scanned from the mucosa. Results: A total of 32 specimens (nine esophageal, 12 gastric, 11 colorectal) were scanned. The pathological diagnoses were adenomas (n = 2), intramucosal cancers (n = 14), and invasive cancers (n = 16). The deep vessel networks of all lesions could be visualized. In the intramucosal lesions, the deep vessel network was similar to that of a normal tissue. In invasive cancers, the thick and prominent vessel network was visible in the surface layer of esophageal cancers, infiltrated area of gastric cancers, and surface layer and infiltrated area of colorectal cancers. In the images of living pigs, visualizing the vascular network deeper than the submucosa in both the stomach and large intestine was possible. Conclusion: Our study confirmed that the deep vessel networks of neoplastic GI lesions were visible by PA imaging.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Ikematsu", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Okawa", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Minamide", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Mitsui", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kuwata", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Omori", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Dai", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Kaku", "last_name": "Irisawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Ochiai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/deo2.28" }, "pmcid": { "normalized": "PMC8828192" }, "pmid": { "normalized": "35310764" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Apr", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "e28", "proceedings_title": null, "publisher": "", "title": "DEN open", "volume": "2", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Photoacoustic imaging of fresh human surgically and endoscopically resected gastrointestinal specimens.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tardigrades are able to tolerate almost complete dehydration by entering a reversible ametabolic state called anhydrobiosis and resume their animation upon rehydration. Dehydrated tardigrades are exceptionally stable and withstand various physical extremes. Although trehalose and late embryogenesis abundant (LEA) proteins have been extensively studied as potent protectants against dehydration in other anhydrobiotic organisms, tardigrades produce high amounts of tardigrade-unique protective proteins. Cytoplasmic-abundant heat-soluble (CAHS) proteins are uniquely invented in the lineage of eutardigrades, a major class of the phylum Tardigrada and are essential for their anhydrobiotic survival. However, the precise mechanisms of their action in this protective role are not fully understood. In the present study, we first postulated the presence of tolerance proteins that form protective condensates via phase separation in a stress-dependent manner and searched for tardigrade proteins that reversibly form condensates upon dehydration-like stress. Through a comprehensive search using a desolvating agent, trifluoroethanol (TFE), we identified 336 proteins, collectively dubbed \"TFE-Dependent ReversiblY condensing Proteins (T-DRYPs).\" Unexpectedly, we rediscovered CAHS proteins as highly enriched in T-DRYPs, 3 of which were major components of T-DRYPs. We revealed that these CAHS proteins reversibly polymerize into many cytoskeleton-like filaments depending on hyperosmotic stress in cultured cells and undergo reversible gel-transition in vitro. Furthermore, CAHS proteins increased cell stiffness in a hyperosmotic stress-dependent manner and counteract the cell shrinkage caused by osmotic pressure, and even improved the survival against hyperosmotic stress. The conserved putative helical C-terminal region is necessary and sufficient for filament formation by CAHS proteins, and mutations disrupting the secondary structure of this region impaired both the filament formation and the gel transition. On the basis of these results, we propose that CAHS proteins are novel cytoskeleton-like proteins that form filamentous networks and undergo gel-transition in a stress-dependent manner to provide on-demand physical stabilization of cell integrity against deformative forces during dehydration and could contribute to the exceptional physical stability in a dehydrated state.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akihiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Kento", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kazutoshi", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Kamata", "name": null }, { "creator_type": "author", "first_name": "Reitaro", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kozuka-Hata", "name": null }, { "creator_type": "author", "first_name": "Chiho", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Chinen", "name": null }, { "creator_type": "author", "first_name": "Daiju", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Takekazu", "last_name": "Kunieda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pbio.3001780" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36067153" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dehydration", "descriptor_ui": "D003681", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Protein Structure, Secondary", "descriptor_ui": "D017433", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Tardigrada", "descriptor_ui": "D058467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "e3001780", "proceedings_title": null, "publisher": "", "title": "PLoS biology", "volume": "20", "year": 2022 }, "ssbd": { "database": [ "ssbd-database-000271" ], "repository": [ "ssbd-repos-000271" ] }, "title": "Stress-dependent cell stiffening by tardigrade tolerance proteins that reversibly form a filamentous network and gel.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND/AIM: Aldehyde dehydrogenase (ALDH) 1A1 is a well-known marker for cancer stem cells (CSCs), characterized by self-renewal capacity and multidrug resistance in breast cancer. We developed a near-infrared turn-on fluorescence probe for ALDH1A1, C5S-A, which is suitable for observing and analyzing viable cells. Here, we demonstrated the utility of C5S-A in CSC research using breast cancer cell lines. MATERIALS AND METHODS: To evaluate concordance between C5S-A and conventional stem cell markers, breast cancer cells sorted for ALDEFLUOR-positive cells and for CD44(+)/CD24(-) cell populations were stained with C5S-A. Tumorigenicity of C5S-A-positive cells was examined by mammosphere formation assay and subcutaneous transplantation to immunodeficient mice. Additionally, to determine how long fluorescence from a single staining remained observable, we cultured breast cancer cells for 5 days after C5S-A staining. We then evaluated whether C5S-A-positive cells possessed resistance to cytotoxic drugs by chronological imaging. RESULTS: C5S-A staining showed good concordance with conventional breast CSC markers, and good utility for research into CSC characteristics in breast cancer cell lines, including tumorigenesis. Additionally, C5S-A was observable for more than 3 days with a single staining. Using this property, we then confirmed that C5S-A-positive cells possessed resistance to cytotoxic drugs, which is one of the characteristics of CSCs. CONCLUSION: We showed that C5S-A is suitable for CSC research using breast cancer cell lines, and confirmed its utility in observing cells over time.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Aoi", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Funakoshi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Oe", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Takai", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Suto", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Nagatani", "name": null }, { "creator_type": "author", "first_name": "Meiko", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Tomonari", "last_name": "Kunihisa", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Kiyota", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Tanino", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Minami", "name": null } ], "identifiers": { "doi": { "normalized": "10.21873/anticanres.15586" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35220209" } }, "mesh": [ { "descriptor": "Aldehyde Dehydrogenase 1 Family", "descriptor_ui": "D000080924", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Separation", "descriptor_ui": "D002469", "major_topic": false }, { "descriptor": "Doxorubicin", "descriptor_ui": "D004317", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Mice, SCID", "descriptor_ui": "D016513", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Paclitaxel", "descriptor_ui": "D017239", "major_topic": false }, { "descriptor": "Retinal Dehydrogenase", "descriptor_ui": "D050697", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "1199-1205", "proceedings_title": null, "publisher": "", "title": "Anticancer research", "volume": "42", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of Breast Cancer Stem Cells Using a Newly Developed Long-acting Fluorescence Probe, C5S-A, Targeting ALDH1A1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Parapharyngeal space tumors have poor subjective symptoms and often grow until diagnosed; therefore, mandibular transection may be needed to obtain a wider field of view during surgery. However, if a median lower lip incision is performed for the mandibular transection, esthetic problems occur after surgery. Here, we report two cases of parapharyngeal space tumors that were removed with a mandibular lateral segment-osteotomy technique without median lower lip incision to avoid esthetic problems. Case 1 was a 49-year-old woman. She was aware of a right tonsillar swelling, and an imaging test revealed a tumor lesion 60 mm in size in the right parapharyngeal space. Case 2 was a 40-year-old woman with an abnormal position of the uvula, and an imaging test showed the left parapharyngeal space tumor lesion 45 mm in size. Both cases were diagnosed as a pleomorphic adenoma, and surgery under general anesthesia was performed jointly with otolaryngology and oral surgery. The incision was performed from the lower part of the right auricle to the anterior part of the submandibular area. After the tumor resection, the mandible was repositioned, fixed by plates, and the intermaxillary fixation was performed with a surgical stent. In both cases, slight paralysis of the mandibular branch of the facial nerve and the mental nerve was observed after the operation, but they were improved immediately. One year after the operation, the plates were removed. There have been no recurrences until now.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Ijichi", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Tomohisa", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Nabeta", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Sumiyo", "last_name": "Hishida", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Shibuya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/ccr3.6786" }, "pmcid": { "normalized": "PMC9792645" }, "pmid": { "normalized": "36583200" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "e6786", "proceedings_title": null, "publisher": "", "title": "Clinical case reports", "volume": "10", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Two cases of parapharyngeal space tumor resected by a double split mandibular osteotomy technique.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The deposition of amyloid beta (Abeta) in blood vessels of the brain, known as cerebral amyloid angiopathy (CAA), is observed in most patients with Alzheimer's disease (AD). Compared with the pathology of CAA in humans, the pathology in most mouse models of AD is not as evident, making it difficult to examine the contribution of CAA to the pathogenesis of AD. On the basis of biochemical analyses that showed blood levels of soluble amyloid precursor protein (APP) in rats and mice were markedly lower than those measured in human samples, we hypothesized that endothelial APP expression would be markedly lower in rodents and subsequently generated mice that specifically express human WT APP (APP770) in endothelial cells (ECs). The resulting EC-APP770(+) mice exhibited increased levels of serum Abeta and soluble APP, indicating that endothelial APP makes a critical contribution to blood Abeta levels. Even though aged EC-APP770(+) mice did not exhibit Abeta deposition in the cortical blood vessels, crossing these animals with APP knock-in mice (App(NL-F/NL-F)) led to an expanded CAA pathology, as evidenced by increased amounts of amyloid accumulated in the cortical blood vessels. These results highlight an overlooked interplay between neuronal and endothelial APP in brain vascular Abeta deposition. We propose that these EC-APP770(+):App(NL-F/NL-F) mice may be useful to study the basic molecular mechanisms behind the possible breakdown of the blood-brain barrier upon administration of anti-Abeta antibodies.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuriko", "last_name": "Tachida", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Muto", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takuwa", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Matsuba", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Tomimoto", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Saido", "name": null }, { "creator_type": "author", "first_name": "Shinobu", "last_name": "Kitazume", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbc.2022.101880" }, "pmcid": { "normalized": "PMC9144051" }, "pmid": { "normalized": "35367207" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": true }, { "descriptor": "Amyloid beta-Peptides", "descriptor_ui": "D016229", "major_topic": true }, { "descriptor": "Amyloid beta-Protein Precursor", "descriptor_ui": "D016564", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "Cerebral Amyloid Angiopathy", "descriptor_ui": "D016657", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": true }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "101880", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "298", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Endothelial expression of human amyloid precursor protein leads to amyloid beta in the blood and induces cerebral amyloid angiopathy in knock-in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Thioredoxin (Trx) is a protein that mediates the reducing power transfer from the photosynthetic electron transport system to target enzymes in chloroplasts and regulates their activities. Redox regulation governed by Trx is a system that is central to the adaptation of various chloroplast functions to the ever-changing light environment. However, the factors involved in the opposite reaction (i.e., the oxidation of various enzymes) have yet to be revealed. Recently, it has been suggested that Trx and Trx-like proteins could oxidize Trx-targeted proteins in vitro. To elucidate the in vivo function of these proteins as oxidation factors, we generated mutant plant lines deficient in Trx or Trx-like proteins and studied how the proteins are involved in oxidative regulation in chloroplasts. We found that f-type Trx and two types of Trx-like proteins, Trx-like 2 and atypical Cys His-rich Trx (ACHT), seemed to serve as oxidation factors for Trx-targeted proteins, such as fructose-1,6-bisphosphatase, Rubisco activase, and the gamma-subunit of ATP synthase. In addition, ACHT was found to be involved in regulating nonphotochemical quenching, which is the mechanism underlying the thermal dissipation of excess light energy. Overall, these results indicate that Trx and Trx-like proteins regulate chloroplast functions in concert by controlling the redox state of various photosynthesis-related proteins in vivo.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuichi", "last_name": "Yokochi", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Fukushi", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2114952118" }, "pmcid": { "normalized": "PMC8713810" }, "pmid": { "normalized": "34907017" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Chloroplasts", "descriptor_ui": "D002736", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Enzymologic", "descriptor_ui": "D015971", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": false }, { "descriptor": "Thioredoxins", "descriptor_ui": "D013879", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec 21", "date_precision": "day", "issue": "51", "normalized_date": "2021-12-21", "pages": "e2114952118", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "118", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Oxidative regulation of chloroplast enzymes by thioredoxin and thioredoxin-like proteins in Arabidopsis thaliana.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Characterization and isolation of a large population of cells are indispensable procedures in biological sciences. Flow cytometry is one of the standards that offers a method to characterize and isolate cells at high throughput. When performing flow cytometry, cells are molecularly stained with fluorescent labels to adopt biomolecular specificity which is essential for characterizing cells. However, molecular staining is costly and its chemical toxicity can cause side effects to the cells which becomes a critical issue when the cells are used downstream as medical products or for further analysis. Here, we introduce a high-throughput stain-free flow cytometry called in silico-labeled ghost cytometry which characterizes and sorts cells using machine-predicted labels. Instead of detecting molecular stains, we use machine learning to derive the molecular labels from compressive data obtained with diffractive and scattering imaging methods. By directly using the compressive 'imaging' data, our system can accurately assign the designated label to each cell in real time and perform sorting based on this judgment. With this method, we were able to distinguish different cell states, cell types derived from human induced pluripotent stem (iPS) cells, and subtypes of peripheral white blood cells using only stain-free modalities. Our method will find applications in cell manufacturing for regenerative medicine as well as in cell-based medical diagnostic assays in which fluorescence labeling of the cells is undesirable.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Ugawa", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Teranishi", "name": null }, { "creator_type": "author", "first_name": "Hikari", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Tamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Nomaru", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Keiki", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Evgeniia", "last_name": "Borisova", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "An", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Seiichiro", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Soji", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Misa", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Tomoiku", "last_name": "Takaku", "name": null }, { "creator_type": "author", "first_name": "Marito", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Issei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Horisaki", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Noji", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.67660" }, "pmcid": { "normalized": "PMC8691837" }, "pmid": { "normalized": "34930522" } }, "mesh": [ { "descriptor": "Coloring Agents", "descriptor_ui": "D004396", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Leukocytes", "descriptor_ui": "D007962", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Staining and Labeling", "descriptor_ui": "D013194", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec 21", "date_precision": "day", "issue": "", "normalized_date": "2021-12-21", "pages": "e67660", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "10", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "In silico-labeled ghost cytometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human T cell leukemia virus type 1 (HTLV-1) mainly infects CD4+ T cells and induces chronic, persistent infection in infected individuals, with some developing adult T cell leukemia/lymphoma (ATL). HTLV-1 alters cellular differentiation, activation, and survival; however, it is unknown whether and how these changes contribute to the malignant transformation of infected cells. In this study, we used single-cell RNA-sequencing and T cell receptor-sequencing to investigate the differentiation and HTLV-1-mediated transformation of T cells. We analyzed 87,742 PBMCs from 12 infected and 3 uninfected individuals. Using multiple independent bioinformatics methods, we demonstrated the seamless transition of naive T cells into activated T cells, whereby HTLV-1-infected cells in an activated state further transformed into ATL cells, which are characterized as clonally expanded, highly activated T cells. Notably, the greater the activation state of ATL cells, the more they acquire Treg signatures. Intriguingly, the expression of HLA class II genes in HTLV-1-infected cells was uniquely induced by the viral protein Tax and further upregulated in ATL cells. Functional assays revealed that HTLV-1-infected cells upregulated HLA class II molecules and acted as tolerogenic antigen-presenting cells to induce anergy of antigen-specific T cells. In conclusion, our study revealed the in vivo mechanisms of HTLV-1-mediated transformation and immune escape at the single-cell level.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Benjy Jy", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sugata", "name": null }, { "creator_type": "author", "first_name": "Omnia", "last_name": "Reda", "name": null }, { "creator_type": "author", "first_name": "Misaki", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Kyosuke", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Paola", "last_name": "Miyazato", "name": null }, { "creator_type": "author", "first_name": "Vincent", "last_name": "Hahaut", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamagishi", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Uchimaru", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Suzushima", "name": null }, { "creator_type": "author", "first_name": "Hiroo", "last_name": "Katsuya", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Eisaburo", "last_name": "Sueoka", "name": null }, { "creator_type": "author", "first_name": "Atae", "last_name": "Utsunomiya", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yorifumi", "last_name": "Satou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci150472" }, "pmcid": { "normalized": "PMC8670839" }, "pmid": { "normalized": "34907908" } }, "mesh": [ { "descriptor": "Cell Transformation, Viral", "descriptor_ui": "D002472", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Products, tax", "descriptor_ui": "D016356", "major_topic": false }, { "descriptor": "HLA Antigens", "descriptor_ui": "D006680", "major_topic": false }, { "descriptor": "Human T-lymphotropic virus 1", "descriptor_ui": "D015368", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia-Lymphoma, Adult T-Cell", "descriptor_ui": "D015459", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec 15", "date_precision": "day", "issue": "24", "normalized_date": "2021-12-15", "pages": "e150472", "proceedings_title": null, "publisher": "", "title": "The Journal of clinical investigation", "volume": "131", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "HTLV-1 infection promotes excessive T cell activation and transformation into adult T cell leukemia/lymphoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Loss-of-function mutations of JAK1/2 impair cancer cell responsiveness to IFNgamma and immunogenicity. Therefore, an understanding of compensatory pathways to activate IFNgamma signaling in cancer cells is clinically important for the success of immunotherapy. Here we demonstrate that the transcription factor SOX10 hinders immunogenicity of melanoma cells through the IRF4-IRF1 axis. Genetic and pharmacologic approaches revealed that SOX10 repressed IRF1 transcription via direct induction of a negative regulator, IRF4. The SOX10-IRF4-IRF1 axis regulated PD-L1 expression independently of JAK-STAT pathway activity, and suppression of SOX10 increased the efficacy of combination therapy with an anti-PD-1 antibody and histone deacetylase inhibitor against a clinically relevant melanoma model. Thus, the SOX10-IRF4-IRF1 axis serves as a potential target that can bypass JAK-STAT signaling to immunologically warm up melanoma with a \"cold\" tumor immune microenvironment. SIGNIFICANCE: This study identifies a novel SOX10/IRF4 pathway that regulates noncanonical induction of IRF1 independent of the JAK-STAT pathway and can be targeted to improve the efficacy of anti-PD-1 therapy in melanoma.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Soshi", "last_name": "Nishibu", "name": null }, { "creator_type": "author", "first_name": "Jennifer A.", "last_name": "Lo", "name": null }, { "creator_type": "author", "first_name": "Miroslav", "last_name": "Hejna", "name": null }, { "creator_type": "author", "first_name": "Wooyoung M.", "last_name": "Moon", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yue", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "F. Stephen", "last_name": "Hodi", "name": null }, { "creator_type": "author", "first_name": "Jun S.", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "David E.", "last_name": "Fisher", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Hayakawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/0008-5472.can-21-2078" }, "pmcid": { "normalized": "PMC8678351" }, "pmid": { "normalized": "34728538" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Drug Therapy, Combination", "descriptor_ui": "D004359", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Histone Deacetylase Inhibitors", "descriptor_ui": "D056572", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Checkpoint Inhibitors", "descriptor_ui": "D000082082", "major_topic": false }, { "descriptor": "Immunotherapy", "descriptor_ui": "D007167", "major_topic": false }, { "descriptor": "Interferon Regulatory Factor-1", "descriptor_ui": "D050856", "major_topic": false }, { "descriptor": "Interferon Regulatory Factor-4", "descriptor_ui": "D000099218", "major_topic": false }, { "descriptor": "Interferon Regulatory Factors", "descriptor_ui": "D050835", "major_topic": false }, { "descriptor": "Melanoma", "descriptor_ui": "D008545", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "SOXE Transcription Factors", "descriptor_ui": "D055757", "major_topic": false }, { "descriptor": "Survival Rate", "descriptor_ui": "D015996", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec 15", "date_precision": "day", "issue": "24", "normalized_date": "2021-12-15", "pages": "6131-6141", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "81", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "SOX10 Regulates Melanoma Immunogenicity through an IRF4-IRF1 Axis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Near-infrared fluorescent protein (iRFP) is a bright and stable fluorescent protein with near-infrared excitation and emission maxima. Unlike the other conventional fluorescent proteins, iRFP requires biliverdin (BV) as a chromophore. Here, we report that phycocyanobilin (PCB) functions as a brighter chromophore for iRFP than BV, and that biosynthesis of PCB allows live-cell imaging with iRFP in the fission yeast Schizosaccharomyces pombe. We initially found that fission yeast cells did not produce BV and therefore did not show any iRFP fluorescence. The brightness of iRFP-PCB was higher than that of iRFP-BV both in vitro and in fission yeast. We introduced SynPCB2.1, a PCB biosynthesis system, into fission yeast, resulting in the brightest iRFP fluorescence. To make iRFP readily available in fission yeast, we developed an endogenous gene tagging system with iRFP and all-in-one integration plasmids carrying the iRFP-fused marker proteins together with SynPCB2.1. These tools not only enable the easy use of multiplexed live-cell imaging in fission yeast with a broader color palette, but also open the door to new opportunities for near-infrared fluorescence imaging in a wider range of living organisms. This article has an associated First Person interview with the first author of the paper.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Hiroyoshi", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Goto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/jcs.259315" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34806750" } }, "mesh": [ { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Phycobilins", "descriptor_ui": "D052980", "major_topic": false }, { "descriptor": "Phycocyanin", "descriptor_ui": "D010798", "major_topic": false }, { "descriptor": "Schizosaccharomyces", "descriptor_ui": "D012568", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Dec 15", "date_precision": "day", "issue": "24", "normalized_date": "2021-12-15", "pages": "jcs259315", "proceedings_title": null, "publisher": "", "title": "Journal of cell science", "volume": "134", "year": 2021 }, "ssbd": { "database": [ "ssbd-database-000217" ], "repository": [ "ssbd-repos-000217" ] }, "title": "Near-infrared imaging in fission yeast using a genetically encoded phycocyanobilin biosynthesis system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In fast-moving cells such as amoeba and immune cells, dendritic actin filaments are spatiotemporally regulated to shape large-scale plasma membrane protrusions. Despite their importance in migration, as well as in particle and liquid ingestion, how their dynamics are affected by micrometer-scale features of the contact surface is still poorly understood. Here, through quantitative image analysis of Dictyostelium on microfabricated surfaces, we show that there is a distinct mode of topographical guidance directed by the macropinocytic membrane cup. Unlike other topographical guidance known to date that depends on nanometer-scale curvature sensing protein or stress fibers, the macropinocytic membrane cup is driven by the Ras/PI3K/F-actin signaling patch and its dependency on the micrometer-scale topographical features, namely PI3K/F-actin-independent accumulation of Ras-GTP at the convex curved surface, PI3K-dependent patch propagation along the convex edge, and its actomyosin-dependent constriction at the concave edge. Mathematical model simulations demonstrate that the topographically dependent initiation, in combination with the mutually defining patch patterning and the membrane deformation, gives rise to the topographical guidance. Our results suggest that the macropinocytic cup is a self-enclosing structure that can support liquid ingestion by default; however, in the presence of structured surfaces, it is directed to faithfully trace bent and bifurcating ridges for particle ingestion and cell guidance.", "classifications": [ { "id": "19H05416", "label": "19H05416", "researcher": "Satoshi Sawai", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Gen", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Nen", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Taihei", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Hashimura", "name": null }, { "creator_type": "author", "first_name": "Mitsuru J.", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2110281118" }, "pmcid": { "normalized": "PMC8685668" }, "pmid": { "normalized": "34876521" } }, "mesh": [ { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": true }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Movement", "descriptor_ui": "D009068", "major_topic": false }, { "descriptor": "Phosphatidylinositol 3-Kinases", "descriptor_ui": "D019869", "major_topic": false }, { "descriptor": "Pinocytosis", "descriptor_ui": "D010873", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec 14", "date_precision": "day", "issue": "50", "normalized_date": "2021-12-14", "pages": "e2110281118", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "118", "year": 2021 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000182" ] }, "title": "Microtopographical guidance of macropinocytic signaling patches.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent work in tunicate supports the similarity between the motor circuits of vertebrates and basal deuterostome lineages. To understand how the rhythmic activity in motor circuits is acquired during development of protochordate Ciona, we investigated the coordination of the motor response by identifying a single pair of oscillatory motor neurons (MN2/A10.64). The MN2 neurons had Ca(2+) oscillation with an ~80-s interval that was cell autonomous even in a dissociated single cell. The Ca(2+) oscillation of MN2 coincided with the early tail flick (ETF). The spikes of the membrane potential in MN2 gradually correlated with the rhythm of ipsilateral muscle contractions in ETFs. The optogenetic experiments indicated that MN2 is a necessary and sufficient component of ETFs. These results indicate that MN2 is indispensable for the early spontaneous rhythmic motor behavior of Ciona. Our findings shed light on the understanding of development and evolution of chordate rhythmical locomotion.", "classifications": [ { "id": "21H00440", "label": "21H00440", "researcher": "Kohji Hotta", "type": "grant" }, { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Taichi", "last_name": "Akahoshi", "name": null }, { "creator_type": "author", "first_name": "Madoka K.", "last_name": "Utsumi", "name": null }, { "creator_type": "author", "first_name": "Kouhei", "last_name": "Oonuma", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Takehiro G.", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abl6053" }, "pmcid": { "normalized": "PMC8664258" }, "pmid": { "normalized": "34890229" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Dec 10", "date_precision": "day", "issue": "50", "normalized_date": "2021-12-10", "pages": "eabl6053", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "7", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "A single motor neuron determines the rhythm of early motor behavior in Ciona.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The skin is exposed to various external stimuli. Keratinocytes, which are the main cell type in the epidermis, interact with peripheral sensory neurons and modulate neuronal activity. Recent studies have revealed that keratinocytes play crucial roles in nociception, and that ATP is one of the main mediators of signal transduction from keratinocytes to sensory neurons. However, no quantitative cellular level analyses of ATP-mediated information flow from keratinocytes to sensory dorsal root ganglion (DRG) neurons have been conducted. In this study, we performed simultaneous imaging of cell surface ATP and intracellular Ca(2+) signals using both iATPSnFR, a genetically encoded ATP probe localized to the outside of the cell membrane, and the Ca(2+) probe, Fura-red. Upon mechanical stimulation of the keratinocyte with a glass needle, an increase in Ca(2+) and ATP release were observed around the stimulated area, and these phenomena were positively correlated. In cultured DRG neurons and keratinocytes neighboring the stimulated keratinocyte, increased intracellular Ca(2+) concentration and levels of cell surface ATP on the side closer to the stimulated cell were detected. The ratio of Ca(2+) response to input ATP signal was significantly larger in DRG neurons than in keratinocytes. We found that DRG neurons were more sensitive to ATP than keratinocytes, and therefore, only DRG neurons responded to ATP at 1 muM or lower concentrations when in co-culture with keratinocytes. Moreover, signals caused by moderate mechanical stimulation of keratinocytes were transmitted predominantly to DRG neurons. These findings would be important in the further determination of the detailed mechanism of nociception in the epidermis.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Fujio", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2021.10.046" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34710828" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzofurans", "descriptor_ui": "D001572", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cations, Divalent", "descriptor_ui": "D002413", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Epidermis", "descriptor_ui": "D004817", "major_topic": false }, { "descriptor": "Ganglia, Spinal", "descriptor_ui": "D005727", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Imidazoles", "descriptor_ui": "D007093", "major_topic": false }, { "descriptor": "Infant, Newborn", "descriptor_ui": "D007231", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": false }, { "descriptor": "Mechanotransduction, Cellular", "descriptor_ui": "D040542", "major_topic": true }, { "descriptor": "Molecular Probes", "descriptor_ui": "D015335", "major_topic": false }, { "descriptor": "Nociception", "descriptor_ui": "D059225", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Sensory Receptor Cells", "descriptor_ui": "D011984", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec 10", "date_precision": "day", "issue": "", "normalized_date": "2021-12-10", "pages": "131-136", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "582", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Mechanical stimulus-evoked signal transduction between keratinocytes and sensory neurons via extracellular ATP.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Actomyosin contractility generated cooperatively by nonmuscle myosin II and actin filaments plays essential roles in a wide range of biological processes, such as cell motility, cytokinesis, and tissue morphogenesis. However, subcellular dynamics of actomyosin contractility underlying such processes remains elusive. Here, we demonstrate an optogenetic method to induce relaxation of actomyosin contractility at the subcellular level. The system, named OptoMYPT, combines a protein phosphatase 1c (PP1c)-binding domain of MYPT1 with an optogenetic dimerizer, so that it allows light-dependent recruitment of endogenous PP1c to the plasma membrane. Blue-light illumination is sufficient to induce dephosphorylation of myosin regulatory light chains and a decrease in actomyosin contractile force in mammalian cells and Xenopus embryos. The OptoMYPT system is further employed to understand the mechanics of actomyosin-based cortical tension and contractile ring tension during cytokinesis. We find that the relaxation of cortical tension at both poles by OptoMYPT accelerated the furrow ingression rate, revealing that the cortical tension substantially antagonizes constriction of the cleavage furrow. Based on these results, the OptoMYPT system provides opportunities to understand cellular and tissue mechanics.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kei", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Motohiko", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Mii", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-021-27458-3" }, "pmcid": { "normalized": "PMC8654997" }, "pmid": { "normalized": "34880255" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Actomyosin", "descriptor_ui": "D000205", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cytokinesis", "descriptor_ui": "D048749", "major_topic": false }, { "descriptor": "Cytoskeletal Proteins", "descriptor_ui": "D003598", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Intercellular Junctions", "descriptor_ui": "D007365", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mechanical Phenomena", "descriptor_ui": "D055595", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Muscle Contraction", "descriptor_ui": "D009119", "major_topic": false }, { "descriptor": "Myosin Type II", "descriptor_ui": "D024462", "major_topic": false }, { "descriptor": "Myosin-Light-Chain Phosphatase", "descriptor_ui": "D043263", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": true }, { "descriptor": "Synthetic Biology", "descriptor_ui": "D058615", "major_topic": false }, { "descriptor": "Xenopus", "descriptor_ui": "D014981", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec 8", "date_precision": "day", "issue": "1", "normalized_date": "2021-12-08", "pages": "7145", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000215" ] }, "title": "Optogenetic relaxation of actomyosin contractility uncovers mechanistic roles of cortical tension during cytokinesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The complexity of gas and condensed phase chemical reactions has generally been uncovered either approximately through transition state theories or exactly through (analytic or computational) integration of trajectories. These approaches can be improved by recognizing that the dynamics and associated geometric structures exist in phase space, ensuring that the propagator is symplectic as in velocity-Verlet integrators and by extending the space of dividing surfaces to optimize the rate variationally, respectively. The dividing surface can be analytically or variationally optimized in phase space, not just over configuration space, to obtain more accurate rates. Thus, a phase space perspective is of primary importance in creating a deeper understanding of the geometric structure of chemical reactions. A key contribution from dynamical systems theory is the generalization of the transition state (TS) in terms of the normally hyperbolic invariant manifold (NHIM) whose geometric phase-space structure persists under perturbation. The NHIM can be regarded as an anchor of a dividing surface in phase space and it gives rise to an exact non-recrossing TS theory rate in reactions that are dominated by a single bottleneck. Here, we review recent advances of phase space geometrical structures of particular relevance to chemical reactions in the condensed phase. We also provide conjectures on the promise of these techniques toward the design and control of chemical reactions.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yutaka", "last_name": "Nagahata", "name": null }, { "creator_type": "author", "first_name": "Rigoberto", "last_name": "Hernandez", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/5.0059618" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34879678" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Dec 7", "date_precision": "day", "issue": "21", "normalized_date": "2021-12-07", "pages": "210901", "proceedings_title": null, "publisher": "", "title": "The Journal of chemical physics", "volume": "155", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Phase space geometry of isolated to condensed chemical reactions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dendritic cell immunoreceptor (DCIR) is a C-type lectin receptor with a carbohydrate recognition domain and an immunoreceptor tyrosine-based inhibitory motif. Previously, we showed that Dcir-/- mice spontaneously develop autoimmune enthesitis and sialadenitis, and also develop metabolic bone abnormalities. However, the ligands for DCIR functionality remain to be elucidated. Here we showed that DCIR is expressed on osteoclasts and DCs and binds to an asialo-biantennary N-glycan(s) (NA2) on bone cells and myeloid cells. Osteoclastogenesis was enhanced in Dcir-/- cells, and NA2 inhibited osteoclastogenesis. Neuraminidase treatment, which exposes excess NA2 by removing the terminal sialic acid of N-glycans, suppressed osteoclastogenesis and DC function. Neuraminidase treatment of mice ameliorated collagen-induced arthritis and experimental autoimmune encephalomyelitis in a DCIR-dependent manner, due to suppression of antigen presentation by DCs. These results suggest that DCIR activity is regulated by the modification of the terminal sialylation of biantennary N-glycans, and this interaction is important for the control of both autoimmune and bone metabolic diseases.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomonori", "last_name": "Kaifu", "name": null }, { "creator_type": "author", "first_name": "Rikio", "last_name": "Yabe", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Soo-Hyun", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Tateno", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Fujikado", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Hirabayashi", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Iwakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1084/jem.20210435" }, "pmcid": { "normalized": "PMC8624811" }, "pmid": { "normalized": "34817551" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arthritis, Experimental", "descriptor_ui": "D001169", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": false }, { "descriptor": "Encephalomyelitis, Autoimmune, Experimental", "descriptor_ui": "D004681", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lectins, C-Type", "descriptor_ui": "D037181", "major_topic": false }, { "descriptor": "Membrane Glycoproteins", "descriptor_ui": "D008562", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Mutant Strains", "descriptor_ui": "D008817", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "N-Acetylglucosaminyltransferases", "descriptor_ui": "D017351", "major_topic": false }, { "descriptor": "Neuraminidase", "descriptor_ui": "D009439", "major_topic": false }, { "descriptor": "Osteoclasts", "descriptor_ui": "D010010", "major_topic": false }, { "descriptor": "Osteogenesis", "descriptor_ui": "D010012", "major_topic": false }, { "descriptor": "Polysaccharides", "descriptor_ui": "D011134", "major_topic": false }, { "descriptor": "Receptors, Immunologic", "descriptor_ui": "D011971", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec 6", "date_precision": "day", "issue": "12", "normalized_date": "2021-12-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "The Journal of experimental medicine", "volume": "218", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "DCIR and its ligand asialo-biantennary N-glycan regulate DC function and osteoclastogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Naomi", "last_name": "Nihonmatsu-Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Xiu-Jun", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Kazuhito", "last_name": "Satou", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Kaname", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Akagi", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Shuta", "last_name": "Toru", "name": null }, { "creator_type": "author", "first_name": "Katsuiku", "last_name": "Hirokawa", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Uchihara", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Tatebayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-021-02905-5" }, "pmcid": { "normalized": "PMC8639774" }, "pmid": { "normalized": "34857866" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Dec 2", "date_precision": "day", "issue": "1", "normalized_date": "2021-12-02", "pages": "1372", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "4", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Publisher Correction: Essential roles of plexin-B3(+) oligodendrocyte precursor cells in the pathogenesis of Alzheimer's disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Small-angle X-ray scattering (SAXS) coupled with computed tomography (CT), denoted SAXS-CT, has enabled the spatial distribution of the characteristic parameters (e.g. size, shape, surface, length) of nanoscale structures inside samples to be visualized. In this work, a new scheme with Tikhonov regularization was developed to remove the effects of artifacts caused by streak scattering originating from the reflection of the incident beam in the contour regions of the sample. The noise due to streak scattering was successfully removed from the sinogram image and hence the CT image could be reconstructed free from artifacts in the contour regions.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Nishitsuji", "name": null }, { "creator_type": "author", "first_name": "Taizo", "last_name": "Kabe", "name": null }, { "creator_type": "author", "first_name": "Mikihito", "last_name": "Takenaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1107/s1600576721011523" }, "pmcid": { "normalized": "PMC8662970" }, "pmid": { "normalized": "34963766" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Dec 1", "date_precision": "day", "issue": "Pt 6", "normalized_date": "2021-12-01", "pages": "1784-1792", "proceedings_title": null, "publisher": "", "title": "Journal of applied crystallography", "volume": "54", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Artifact removal in the contour areas of SAXS-CT images by Tikhonov-L1 minimization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We describe a case of massive epistaxis that occurred after removal of a nasal endotracheal tube, prompting emergent reintubation. Mask ventilation could not be performed because the nasal cavity was packed with gauze and the airway was being evacuated with a suction catheter. Therefore, instead of inhalational anesthetics and muscle relaxants, boluses of midazolam and remifentanil were administered, and reintubation was promptly performed. Sedation was maintained with dexmedetomidine infusion and midazolam. Nasal cautery was performed near the left sphenopalatine foramen. The patient was extubated without agitation or additional hemorrhage. Immediate recognition of the potential for airway loss, sufficient control of active bleeding, and drug selection in accordance with the emergent circumstances enabled prompt resecuring of the airway without pulmonary aspiration of blood.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yukiko", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Akari", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Aki", "last_name": "Kameda", "name": null }, { "creator_type": "author", "first_name": "Saki", "last_name": "Mitani", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yozo", "last_name": "Manabe", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Momota", "name": null } ], "identifiers": { "doi": { "normalized": "10.2344/anpr-68-03-04" }, "pmcid": { "normalized": "PMC8674848" }, "pmid": { "normalized": "34911063" } }, "mesh": [ { "descriptor": "Airway Extubation", "descriptor_ui": "D060666", "major_topic": true }, { "descriptor": "Cautery", "descriptor_ui": "D002425", "major_topic": false }, { "descriptor": "Epistaxis", "descriptor_ui": "D004844", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intubation, Intratracheal", "descriptor_ui": "D007442", "major_topic": false }, { "descriptor": "Nasal Mucosa", "descriptor_ui": "D009297", "major_topic": false }, { "descriptor": "Suction", "descriptor_ui": "D013396", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec 1", "date_precision": "day", "issue": "4", "normalized_date": "2021-12-01", "pages": "235-237", "proceedings_title": null, "publisher": "", "title": "Anesthesia progress", "volume": "68", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "A Case of Nasal Mucosa Cautery With Reintubation Under Pharyngeal Suction for Massive Epistaxis After Extubation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Biomaterials traditionally used for wound healing can act as a temporary barrier to halt bleeding, prevent infection, and enhance regeneration. Hydrogels are among the best candidates for wound healing owing to their moisture retention and drug-releasing properties. Photo-polymerization using visible light irradiation is a promising method for hydrogel preparation since it can easily control spatiotemporal reaction kinetics and rapidly induce a single-step reaction under mild conditions. In this study, photocrosslinked gelatin hydrogels were imparted with properties namely fast wound adherence, strong wet tissue surface adhesion, greater biocompatibility, long-term bFGF release, and importantly, ease of use through the modification and combination of natural bio-macromolecules. The production of a gelatin hydrogel made of natural gelatin (which is superior to chemically modified gelatin), crosslinked by visible light, which is more desirable than UV light irradiation, will enable its prolonged application to uneven wound surfaces. This is due to its flexible shape, along with the administration of cell growth factors, such as bFGF, for tissue regeneration. Further, the sustained release of bFGF enhances wound healing and skin flap survival. The photocrosslinking gelatin hydrogel designed in this study is a potential candidate to enhance wound healing and better skin flap survival.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Yoshine", "last_name": "Mayumi", "name": null }, { "creator_type": "author", "first_name": "Eiko", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Ojima", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Horiguchi", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-02589-1" }, "pmcid": { "normalized": "PMC8630120" }, "pmid": { "normalized": "34845307" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bandages", "descriptor_ui": "D001458", "major_topic": false }, { "descriptor": "Biocompatible Materials", "descriptor_ui": "D001672", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cross-Linking Reagents", "descriptor_ui": "D003432", "major_topic": false }, { "descriptor": "Delayed-Action Preparations", "descriptor_ui": "D003692", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fibroblast Growth Factor 2", "descriptor_ui": "D016222", "major_topic": false }, { "descriptor": "Gelatin", "descriptor_ui": "D005780", "major_topic": false }, { "descriptor": "Hydrogels", "descriptor_ui": "D020100", "major_topic": false }, { "descriptor": "Materials Testing", "descriptor_ui": "D008422", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Neovascularization, Physiologic", "descriptor_ui": "D018919", "major_topic": false }, { "descriptor": "Pressure", "descriptor_ui": "D011312", "major_topic": false }, { "descriptor": "Rheology", "descriptor_ui": "D012212", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Surface Properties", "descriptor_ui": "D013499", "major_topic": false }, { "descriptor": "Surgical Flaps", "descriptor_ui": "D013524", "major_topic": true }, { "descriptor": "Tissue Engineering", "descriptor_ui": "D023822", "major_topic": false }, { "descriptor": "Wound Healing", "descriptor_ui": "D014945", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Nov 29", "date_precision": "day", "issue": "1", "normalized_date": "2021-11-29", "pages": "23094", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Photocrosslinked gelatin hydrogel improves wound healing and skin flap survival by the sustained release of basic fibroblast growth factor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer immunotherapies that target PD-1 (programmed cell death 1) aim to destroy tumors by activating tumor-specific T cells that are otherwise inactivated by PD-1. Although these therapies have significantly improved the outcomes of patients with diverse cancer types and have revolutionized cancer treatment, only a limited proportion of patients benefits from the therapies currently. Therefore, there is a continued need to decipher the complex biology of PD-1 to improve therapeutic efficacies as well as to prevent immune-related adverse events. Especially, the spaciotemporal context in which PD-1 functions and the properties of T cells that are restrained by PD-1 are only vaguely understood. We have recently revealed that PD-1 function is strictly restricted at the activation phase of T-cell responses by the cis-interactions of PD-L1 and CD80 on antigen-presenting cells, which is critical for the induction of optimal T-cell responses. We also found that the sensitivity to the effects of PD-1 in T cells is essentially determined by T-cell-intrinsic factors. In T cells bearing T-cell antigen-receptors (TCRs) with lower affinity to antigenic peptides, PD-1 inhibits the expression of TCR-inducible genes more efficiently; thereby PD-1 preferentially suppresses low-affinity T cells. Thus, PD-1 function is coordinately regulated by various T-cell-intrinsic and -extrinsic factors that alter the responsiveness of T cells and the availability of PD-1 ligands. Precise and deeper understanding of the regulatory mechanisms of PD-1 is expected to facilitate the rational development of effective and safe immunotherapies.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Il-Mi", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Okazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/intimm/dxab077" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34596210" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Nov 25", "date_precision": "day", "issue": "12", "normalized_date": "2021-11-25", "pages": "693-698", "proceedings_title": null, "publisher": "", "title": "International immunology", "volume": "33", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "T-cell-intrinsic and -extrinsic regulation of PD-1 function.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cytokines are important intercellular communication tools for immunity. Many cytokines promote gene transcription and proliferation through the JAK/STAT (Janus kinase/signal transducers and activators of transcription) and the Ras/ERK (GDP/GTP-binding rat sarcoma protein/extracellular signal-regulated kinase) pathways, and these signaling pathways are tightly regulated. The SOCS (suppressor of cytokine signaling) family members are representative negative regulators of JAK/STAT-mediated cytokine signaling and regulate the differentiation and function of T cells, thus being involved in immune tolerance. Human genetic analysis has shown that SOCS family members are strongly associated with autoimmune diseases, allergy and tumorigenesis. SOCS family proteins also function as immune-checkpoint molecules that contribute to the unresponsiveness of T cells to cytokines.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Setsuko", "last_name": "Mise-Omata", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ando", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/intimm/dxab055" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34415326" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Tolerance", "descriptor_ui": "D007108", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Suppressor of Cytokine Signaling Proteins", "descriptor_ui": "D050826", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Nov 25", "date_precision": "day", "issue": "12", "normalized_date": "2021-11-25", "pages": "711-716", "proceedings_title": null, "publisher": "", "title": "International immunology", "volume": "33", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "SOCS: negative regulators of cytokine signaling for immune tolerance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In cell transplantation therapy for spinal cord injury (SCI), grafted human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs) mainly differentiate into neurons, forming synapses in a process similar to neurodevelopment. In the developing nervous system, the activity of immature neurons has an important role in constructing and maintaining new synapses. Thus, we investigate how enhancing the activity of transplanted hiPSC-NS/PCs affects both the transplanted cells themselves and the host tissue. We find that chemogenetic stimulation of hiPSC-derived neural cells enhances cell activity and neuron-to-neuron interactions in vitro. In a rodent model of SCI, consecutive and selective chemogenetic stimulation of transplanted hiPSC-NS/PCs also enhances the expression of synapse-related genes and proteins in surrounding host tissues and prevents atrophy of the injured spinal cord, thereby improving locomotor function. These findings provide a strategy for enhancing activity within the graft to improve the efficacy of cell transplantation therapy for SCI.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Momotaro", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Munehisa", "last_name": "Shinozaki", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Kajikawa", "name": null }, { "creator_type": "author", "first_name": "Reo", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kamata", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Ushiba", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Hidemasa", "last_name": "Furue", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Narihito", "last_name": "Nagoshi", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2021.110019" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34818559" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, SCID", "descriptor_ui": "D016513", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Recovery of Function", "descriptor_ui": "D020127", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false }, { "descriptor": "Spinal Cord Injuries", "descriptor_ui": "D013119", "major_topic": false }, { "descriptor": "Stem Cell Transplantation", "descriptor_ui": "D033581", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Nov 23", "date_precision": "day", "issue": "8", "normalized_date": "2021-11-23", "pages": "110019", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "37", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Long-term selective stimulation of transplanted neural stem/progenitor cells for spinal cord injury improves locomotor function.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Among the inheritance of cellular components during cell division, deoxyribonucleic acid (DNA) and its condensate (chromosome) are conventionally visualized using chemical tag-labeled nucleotide analogs. However, associated mutagenesis with nucleotide analogs in the visualization of chromosomes is cause for concern. This study investigated the efficiency of using stable isotope labels in visualizing the replicating cultured human cell-chromosomes, in the absence of analog labels, at a high spatial resolution of 100 nm. The distinct carbon isotope ratio between sister chromatids reflected the semi-conservative replication of individual DNA strands through cell cycles and suggested the renewal of histone molecules in daughter chromosomes. Thus, this study provides a new, powerful approach to trace and visualize cellular components with stable isotope labeling.Key words: stable isotope, chromosome replication, semi-conservative replication, imaging, mass spectrometry.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Bajo", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Mitomo", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Kuniharu", "last_name": "Ijiro", "name": null }, { "creator_type": "author", "first_name": "Hisayoshi", "last_name": "Yurimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1247/csf.21011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34565768" } }, "mesh": [ { "descriptor": "Carbon Isotopes", "descriptor_ui": "D002247", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Chromatids", "descriptor_ui": "D002842", "major_topic": true }, { "descriptor": "DNA Replication", "descriptor_ui": "D004261", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Isotope Labeling", "descriptor_ui": "D007553", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Nov 20", "date_precision": "day", "issue": "2", "normalized_date": "2021-11-20", "pages": "95-101", "proceedings_title": null, "publisher": "", "title": "Cell structure and function", "volume": "46", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualization of DNA Replication in Single Chromosome by Stable Isotope Labeling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Actin is a ubiquitous cytoskeletal protein, forming a dynamic network that generates mechanical forces in the cell. There is a growing demand for practical and accessible tools for dissecting the role of the actin cytoskeleton in cellular function, and the discovery of a new actin-binding small molecule is an important advance in the field, offering the opportunity to design and synthesize of new class of functional molecules. Here, we found an F-actin-binding small molecule and introduced two powerful tools based on a new class of actin-binding small molecule: One enables visualization of the actin cytoskeleton, including super-resolution imaging, and the other enables highly specific green light-controlled fragmentation of actin filaments, affording unprecedented control of the actin cytoskeleton and its force network in living cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takeru", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Asanuma", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Shin-Nosuke", "last_name": "Uno", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Okimura", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Iwadate", "name": null }, { "creator_type": "author", "first_name": "Kenzo", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Sugimura", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abg8585" }, "pmcid": { "normalized": "PMC8604405" }, "pmid": { "normalized": "34797716" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Nov 19", "date_precision": "day", "issue": "47", "normalized_date": "2021-11-19", "pages": "eabg8585", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "7", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Discovery of an F-actin-binding small molecule serving as a fluorescent probe and a scaffold for functional probes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Despite the established roles of the dopaminergic system in promoting arousal, the effects of loss of dopamine on the patterns of sleep and wakefulness remain elusive. Here, we examined the sleep architecture of dopamine-deficient (DD) mice, which were previously developed by global knockout of tyrosine hydroxylase and its specific rescue in noradrenergic and adrenergic neurons. We found that DD mice have reduced time spent in wakefulness. Unexpectedly, DD mice also exhibited a marked reduction in the time spent in rapid eye movement (REM) sleep. The electroencephalogram power spectrum of all vigilance states in DD mice were also affected. These results support the current understanding of the critical roles of the dopaminergic system in maintaining wakefulness and also implicate its previously unknown effects on REM sleep.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuaki", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Kanuka", "name": null }, { "creator_type": "author", "first_name": "Kaeko", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Masayo", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Tatsuzawa", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13041-021-00879-3" }, "pmcid": { "normalized": "PMC8600805" }, "pmid": { "normalized": "34794460" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Electroencephalography", "descriptor_ui": "D004569", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": false }, { "descriptor": "Sleep, REM", "descriptor_ui": "D012895", "major_topic": true }, { "descriptor": "Wakefulness", "descriptor_ui": "D014851", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Nov 18", "date_precision": "day", "issue": "1", "normalized_date": "2021-11-18", "pages": "170", "proceedings_title": null, "publisher": "", "title": "Molecular brain", "volume": "14", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Impaired wakefulness and rapid eye movement sleep in dopamine-deficient mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dynamic nuclear polarization (DNP) is an emerging cutting-edge method of acquiring metabolic and physiological information in vivo. We recently developed γ-glutamyl-[1-(13)C]glycine (γ-Glu-[1-(13)C]Gly) as a DNP nuclear magnetic resonance (NMR) molecular probe to detect γ-glutamyl transpeptidase (GGT) activity in vivo. However, the detailed enzymatic and magnetic properties of this probe remain unknown. Here, we evaluate a γ-Glu-Gly scaffold and develop a deuterated probe, γ-Glu-[1-(13)C]Gly-d (2), that can realize a longer lifetime of the hyperpolarized signal. We initially evaluated the GGT-mediated enzymatic conversion of γ-Glu-Gly and the magnetic properties of (13)C-enriched γ-Glu-Gly (γ-Glu-[1-(13)C]Gly and γ-[5-(13)C]Glu-Gly) to support the validity of γ-Glu-[1-(13)C]Gly as a DNP NMR molecular probe for GGT. We then examined the spin-lattice relaxation time (T (1)) of γ-Glu-[1-(13)C]Gly and γ-Glu-[1-(13)C]Gly-d (2) under various conditions (D(2)O, PBS, and serum) and confirmed that the T (1) of γ-Glu-[1-(13)C]Gly and γ-Glu-[1-(13)C]Gly-d (2) was maintained for 30 s (9.4 T) and 41 s (9.4 T), respectively, even in serum. Relaxation analysis of γ-Glu-[1-(13)C]Gly revealed a significant contribution of the dipole-dipole interaction and the chemical shift anisotropy relaxation pathway (71% of the total relaxation rate at 9.4 T), indicating the potential of deuteration and the use of a lower magnetic field for realizing a longer T (1). In fact, by using γ-Glu-[1-(13)C]Gly-d (2) as a DNP probe, we achieved longer retention of the hyperpolarized signal at 1.4 T.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Abdelazim Elsayed", "last_name": "Elhelaly", "name": null }, { "creator_type": "author", "first_name": "Fuminori", "last_name": "Hyodo", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Nishihara", "name": null }, { "creator_type": "author", "first_name": "Marino", "last_name": "Itoda", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Sando", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d1ra07343e" }, "pmcid": { "normalized": "PMC9043577" }, "pmid": { "normalized": "35496407" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Nov 17", "date_precision": "day", "issue": "59", "normalized_date": "2021-11-17", "pages": "37011-37018", "proceedings_title": null, "publisher": "", "title": "RSC advances", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Evaluation of enzymatic and magnetic properties of γ-glutamyl-[1-(13)C]glycine and its deuteration toward longer retention of the hyperpolarized state.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Clustered protocadherins (Pcdhs), which are cell adhesion molecules, play a fundamental role in self-recognition and non-self-discrimination by conferring diversity on the cell surface. Although systematic cell-based aggregation assays provide information regarding the binding properties of Pcdhs, direct visualization of Pcdh trans interactions across cells remains challenging. Here, we present Forster resonance energy transfer (FRET)-based indicators for directly visualizing Pcdh trans interactions. We developed the indicators by individually inserting FRET donor and acceptor fluorescent proteins (FPs) into the ectodomain of Pcdh molecules. They enabled successful visualization of specific trans interactions of Pcdh and revealed that the Pcdh trans interaction is highly sensitive to changes in extracellular Ca(2+) levels. We expect that FRET-based indicators for visualizing Pcdh trans interactions will provide a new approach for investigating the roles of Pcdh in self-recognition and non-self-discrimination processes.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Kanadome", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Hoshino", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Yagi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-01481-2" }, "pmcid": { "normalized": "PMC8593154" }, "pmid": { "normalized": "34782670" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Interaction Domains and Motifs", "descriptor_ui": "D054730", "major_topic": false }, { "descriptor": "Protein Multimerization", "descriptor_ui": "D055503", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Protocadherins", "descriptor_ui": "D000091363", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Nov 15", "date_precision": "day", "issue": "1", "normalized_date": "2021-11-15", "pages": "22237", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [ "ssbd-database-000228" ], "repository": [ "ssbd-repos-000228" ] }, "title": "Development of FRET-based indicators for visualizing homophilic trans interaction of a clustered protocadherin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Positron emission tomography (PET) allows biomolecular tracking but PET monitoring of brain networks has been hampered by a lack of suitable reporters. Here, we take advantage of bacterial dihydrofolate reductase, ecDHFR, and its unique antagonist, TMP, to facilitate in vivo imaging in the brain. Peripheral administration of radiofluorinated and fluorescent TMP analogs enabled PET and intravital microscopy, respectively, of neuronal ecDHFR expression in mice. This technique can be used to the visualize neuronal circuit activity elicited by chemogenetic manipulation in the mouse hippocampus. Notably, ecDHFR-PET allows mapping of neuronal projections in non-human primate brains, demonstrating the applicability of ecDHFR-based tracking technologies for network monitoring. Finally, we demonstrate the utility of TMP analogs for PET studies of turnover and self-assembly of proteins tagged with ecDHFR mutants. These results establish opportunities for a broad spectrum of previously unattainable PET analyses of mammalian brain circuits at the molecular level.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masafumi", "last_name": "Shimojo", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takuwa", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Mimura", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Fujinaga", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Takado", "name": null }, { "creator_type": "author", "first_name": "Manami", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Minamihisamatsu", "name": null }, { "creator_type": "author", "first_name": "Ming-Rong", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Norihiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Anton", "last_name": "Maximov", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Minamimoto", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.15252/embj.2021107757" }, "pmcid": { "normalized": "PMC8591537" }, "pmid": { "normalized": "34636430" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Callithrix", "descriptor_ui": "D002144", "major_topic": false }, { "descriptor": "Carbon Radioisotopes", "descriptor_ui": "D002250", "major_topic": false }, { "descriptor": "Fluorine Radioisotopes", "descriptor_ui": "D005462", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Positron-Emission Tomography", "descriptor_ui": "D049268", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Radiopharmaceuticals", "descriptor_ui": "D019275", "major_topic": false }, { "descriptor": "Tetrahydrofolate Dehydrogenase", "descriptor_ui": "D013762", "major_topic": false }, { "descriptor": "Trimethoprim", "descriptor_ui": "D014295", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Nov 15", "date_precision": "day", "issue": "22", "normalized_date": "2021-11-15", "pages": "e107757", "proceedings_title": null, "publisher": "", "title": "The EMBO journal", "volume": "40", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "A genetically targeted reporter for PET imaging of deep neuronal circuits in mammalian brains.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Memories are initially encoded in the hippocampus but subsequently consolidated to the cortex. Although synaptic plasticity is key to these processes, its precise spatiotemporal profile remains poorly understood. Using optogenetics to selectively erase long-term potentiation (LTP) within a defined temporal window, we found that distinct phases of synaptic plasticity play differential roles. The first wave acts locally in the hippocampus to confer context specificity. The second wave, during sleep on the same day, organizes these neurons into synchronously firing assemblies. Finally, LTP in the anterior cingulate cortex during sleep on the second day is required for further stabilization of the memory. This demonstrates the precise localization, timing, and characteristic contributions of the plasticity events that underlie the early phase of memory consolidation.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Akihiro", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Bota", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Miya", "name": null }, { "creator_type": "author", "first_name": "Jingbo", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Suzune", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Xinzhi", "last_name": "Jiang", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Thomas J.", "last_name": "McHugh", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.abj9195" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34762472" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CA1 Region, Hippocampal", "descriptor_ui": "D056547", "major_topic": false }, { "descriptor": "Chromophore-Assisted Light Inactivation", "descriptor_ui": "D061885", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Long-Term Potentiation", "descriptor_ui": "D017774", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory Consolidation", "descriptor_ui": "D000069077", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": true }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Pyramidal Cells", "descriptor_ui": "D017966", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Nov 12", "date_precision": "day", "issue": "6569", "normalized_date": "2021-11-12", "pages": "857-863", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "374", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Stepwise synaptic plasticity events drive the early phase of memory consolidation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Because of the high frequency of chronic edema formation in the current \"aged\" society, analyses and detailed observation of post-surgical edema are getting more required. Post-surgical examination of the dynamic vasculature including L.V. (Lymphatic Vasculature) to monitor edema formation has not been efficiently performed. Hence, procedures for investigating such vasculature are essential. By inserting transparent sheet into the cutaneous layer of mouse tails as a novel surgery model (the Tail Edema by Silicone sheet mediated Transparency protocol; TEST), the novel procedures are introduced and analyzed by series of histological analyses including video-based L.V. observation and 3D histological reconstruction of vasculatures in mouse tails. RESULTS: The dynamic generation of post-surgical main and fine (neo) L.V. connective structure during the edematous recovery process was visualized by series of studies with a novel surgery model. Snapshot images taken from live binocular image recording for TEST samples suggested the presence of main and elongating fine (neo) L.V. structure. After the ligation of L.V., the enlargement of main L.V. was confirmed. In the case of light sheet fluorescence microscopy (LSFM) observation, such L.V. connections were also suggested by using transparent 3D samples. Finally, the generation of neo blood vessels particularly in the region adjacent to the silicone sheet and the operated boundary region was suggested in 3D reconstruction images. However, direct detection of elongating fine (neo) L.V. was not suitable for analysis by such LSFM and 3D reconstruction procedures. Thus, such methods utilizing fixed tissues are appropriate for general observation for the operated region including of L.V. CONCLUSIONS: The current surgical procedures and analysis on the post-surgical status are the first case to observe vasculatures in vivo with a transparent sheet. Systematic analyses including the FITC-dextran mediated snap shot images observation suggest the elongation of fine (neo) lymphatic vasculature. Post-surgical analyses including LSFM and 3D histological structural reconstruction, are suitable to reveal the fixed structures of blood and lymphatic vessels formation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinji", "last_name": "Kumegawa", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Kyoichi", "last_name": "Isono", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Masatsugu", "last_name": "Ema", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Asamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12575-021-00159-3" }, "pmcid": { "normalized": "PMC8582144" }, "pmid": { "normalized": "34758723" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Nov 11", "date_precision": "day", "issue": "1", "normalized_date": "2021-11-11", "pages": "21", "proceedings_title": null, "publisher": "", "title": "Biological procedures online", "volume": "23", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of Surgical and Visualization Procedures to Analyze Vasculatures by Mouse Tail Edema Model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Innate-like T cell populations expressing conserved TCRs play critical roles in immunity through diverse developmentally acquired effector functions. Focusing on the prototypical lineage of invariant natural killer T (iNKT) cells, we sought to dissect the mechanisms and timing of fate decisions and functional effector differentiation. Utilizing induced expression of the semi-invariant NKT cell TCR on double positive thymocytes, an initially highly synchronous wave of iNKT cell development was triggered by brief homogeneous TCR signaling. After reaching a uniform progenitor state characterized by IL-4 production potential and proliferation, effector subsets emerged simultaneously, but then diverged toward different fates. While NKT17 specification was quickly completed, NKT1 cells slowly differentiated and expanded. NKT2 cells resembled maturing progenitors, which gradually diminished in numbers. Thus, iNKT subset diversification occurs in dividing progenitor cells without acute TCR input but utilizes multiple active cytokine signaling pathways. These data imply a two-step model of iNKT effector differentiation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sabrina", "last_name": "Bortoluzzi", "name": null }, { "creator_type": "author", "first_name": "Nyambayar", "last_name": "Dashtsoodol", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Engleitner", "name": null }, { "creator_type": "author", "first_name": "Christoph", "last_name": "Drees", "name": null }, { "creator_type": "author", "first_name": "Sabine", "last_name": "Helmrath", "name": null }, { "creator_type": "author", "first_name": "Jonas", "last_name": "Mir", "name": null }, { "creator_type": "author", "first_name": "Albulena", "last_name": "Toska", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Flossdorf", "name": null }, { "creator_type": "author", "first_name": "Rupert", "last_name": "Ollinger", "name": null }, { "creator_type": "author", "first_name": "Maria", "last_name": "Solovey", "name": null }, { "creator_type": "author", "first_name": "Maria", "last_name": "Colome-Tatche", "name": null }, { "creator_type": "author", "first_name": "Bahire", "last_name": "Kalfaoglu", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Thorsten", "last_name": "Buch", "name": null }, { "creator_type": "author", "first_name": "Tim", "last_name": "Ammon", "name": null }, { "creator_type": "author", "first_name": "Roland", "last_name": "Rad", "name": null }, { "creator_type": "author", "first_name": "Marc", "last_name": "Schmidt-Supprian", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.immuni.2021.09.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34562377" } }, "mesh": [ { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Natural Killer T-Cells", "descriptor_ui": "D055611", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Nov 9", "date_precision": "day", "issue": "11", "normalized_date": "2021-11-09", "pages": "2497-2513.e9", "proceedings_title": null, "publisher": "", "title": "Immunity", "volume": "54", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Brief homogeneous TCR signals instruct common iNKT progenitors whose effector diversification is characterized by subsequent cytokine signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Viral infection induces host cells to mount a variety of immune responses, which may either limit viral propagation or create conditions conducive to virus replication in some instances. In this regard, activation of the NF-kappaB transcription factor is known to modulate virus replication. Human herpesvirus 6A (HHV-6A), which belongs to the Betaherpesvirinae subfamily, is frequently found in patients with neuroinflammatory diseases, although its role in disease pathogenesis has not been elucidated. In this study, we found that the HHV-6A-encoded U14 protein activates NF-kappaB signaling following interaction with the NF-kappaB complex protein, p65. Through induction of nuclear translocation of p65, U14 increases the expression of interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein 1 transcripts. We also demonstrated that activation of NF-kappaB signaling is important for HHV-6A replication, since inhibition of this pathway reduced virus protein accumulation and viral genome copy number. Taken together, our results suggest that HHV-6A infection activates the NF-kappaB pathway and promotes viral gene expression via late gene products, including U14. IMPORTANCE Human herpesvirus 6A (HHV-6A) is frequently found in patients with neuro-inflammation, although its role in the pathogenesis of this disease has not been elucidated. Most viral infections activate the NF-kappaB pathway, which causes the transactivation of various genes, including those encoding proinflammatory cytokines. Our results indicate that HHV-6A U14 activates the NF-kappaB pathway, leading to upregulation of proinflammatory cytokines. We also found that activation of the NF-kappaB transcription factor is important for efficient viral replication. This study provides new insight into HHV-6A U14 function in host cell signaling and identifies potential cellular targets involved in HHV-6A pathogenesis and replication.", "classifications": [ { "id": "19H05417", "label": "19H05417", "researcher": "Jun Arii", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Salma", "last_name": "Aktar", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Lidya Handayani", "last_name": "Tjan", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01269-21" }, "pmcid": { "normalized": "PMC8577390" }, "pmid": { "normalized": "34549982" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Genes, Viral", "descriptor_ui": "D005814", "major_topic": false }, { "descriptor": "Genome, Viral", "descriptor_ui": "D016679", "major_topic": false }, { "descriptor": "Herpesvirus 6, Human", "descriptor_ui": "D015654", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neuroinflammatory Diseases", "descriptor_ui": "D000090862", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Receptor, EphB2", "descriptor_ui": "D036183", "major_topic": false }, { "descriptor": "Roseolovirus Infections", "descriptor_ui": "D019349", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Nov 9", "date_precision": "day", "issue": "23", "normalized_date": "2021-11-09", "pages": "e0126921", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "95", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Human Herpesvirus 6A Tegument Protein U14 Induces NF-kappaB Signaling by Interacting with p65.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Domesticated plants display diverse phenotypic traits. However, the influence of breeding effort on this phenotypic diversity remains unknown. Here, we demonstrate that a single nucleotide deletion in the homeobox motif of BIPINNATA, a BEL-LIKE HOMEODOMAIN gene, led to a highly complex leaf phenotype in an heirloom tomato (Solanum lycopersicum), Silvery Fir Tree (SiFT), which is used as a landscaping and ornamental plant. A comparative gene network analysis revealed that repression of SOLANIFOLIA, the ortholog of WUSCHEL RELATED HOMEOBOX 1, caused the narrow leaflet phenotype seen in SiFT. Comparative genomics indicated that the bip mutation in SiFT likely arose de novo and is unique to SiFT and not introgressed from other tomato genomes. These results provide new insights into the natural variation in phenotypic traits introduced into crops during improvement processes after domestication and establish homeobox genes as evolutionary hotspots.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hokuto", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Steven D.", "last_name": "Rowland", "name": null }, { "creator_type": "author", "first_name": "Zizhang", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Kristina", "last_name": "Zumstein", "name": null }, { "creator_type": "author", "first_name": "Julie", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Neelima R.", "last_name": "Sinha", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2021.08.023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34473947" } }, "mesh": [ { "descriptor": "Genes, Homeobox", "descriptor_ui": "D005801", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Plant Breeding", "descriptor_ui": "D000069600", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": false }, { "descriptor": "Solanum lycopersicum", "descriptor_ui": "D018551", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Nov 8", "date_precision": "day", "issue": "21", "normalized_date": "2021-11-08", "pages": "4788-4799.e5", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "31", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Leaf form diversification in an ornamental heirloom tomato results from alterations in two different HOMEOBOX genes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Replacing an N,N-dimethylamino group in a classical fluorophore with a four membered azetidine ring provides an improved luminescence quantum yield. Herein, we extended this strategy to bioluminescent firefly luciferin analogues and evaluated its general validity. For this purpose, four types of luciferin cores were employed, and a total of eight analogues were evaluated. Among these analogues, unexpectedly, only the benzothiazole core analogue benefited from an azetidine substitution and showed enhanced bioluminescence. In addition, fluorescence measurements revealed that an azetidine substitution improved the fluorescence quantum yield by 2.3-times compared to a N,N-dimethylamino group. These findings clarify the differential effects of azetidine substituents in luciferins and present one possible strategy for enhancing photon output in benzothiazole type luciferins through a synthetic approach.", "classifications": [ { "id": "19H05429", "label": "19H05429", "researcher": "Yuki Hiruta", "type": "grant" }, { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuma", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Orioka", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Nomoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cbic.202100310" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34402160" } }, "mesh": [ { "descriptor": "Azetidines", "descriptor_ui": "D001384", "major_topic": false }, { "descriptor": "Firefly Luciferin", "descriptor_ui": "D049454", "major_topic": false }, { "descriptor": "Luminescent Agents", "descriptor_ui": "D049408", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Nov 3", "date_precision": "day", "issue": "21", "normalized_date": "2021-11-03", "pages": "3067-3074", "proceedings_title": null, "publisher": "", "title": "Chembiochem : a European journal of chemical biology", "volume": "22", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Differential Effect of Azetidine Substitution in Firefly Luciferin Analogues.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Skin regenerative capacity declines with age, but the underlying mechanisms are largely unknown. Here we demonstrate a functional link between epidermal growth factor receptor (EGFR) signaling and type XVII collagen (COL17A1) proteolysis on age-associated alteration of keratinocyte stem cell dynamics in skin regeneration. Live-imaging and computer simulation experiments predicted that human keratinocyte stem cell motility is coupled with self-renewal and epidermal regeneration. Receptor tyrosine kinase array identified the age-associated decline of EGFR signaling in mouse skin wound healing. Culture experiments proved that EGFR activation drives human keratinocyte stem cell motility with increase of COL17A1 by inhibiting its proteolysis through the secretion of tissue inhibitor of metalloproteinases 1 (TIMP1). Intriguingly, COL17A1 directly regulated keratinocyte stem cell motility and collective cell migration by coordinating actin and keratin filament networks. We conclude that EGFR-COL17A1 axis-mediated keratinocyte stem cell motility drives epidermal regeneration, which provides a novel therapeutic approach for age-associated impaired skin regeneration.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Nanba", "name": null }, { "creator_type": "author", "first_name": "Fujio", "last_name": "Toki", "name": null }, { "creator_type": "author", "first_name": "Kyosuke", "last_name": "Asakawa", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Sayama", "name": null }, { "creator_type": "author", "first_name": "Kyoichi", "last_name": "Matsuzaki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Toki", "name": null }, { "creator_type": "author", "first_name": "Emi K.", "last_name": "Nishimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1083/jcb.202012073" }, "pmcid": { "normalized": "PMC8563287" }, "pmid": { "normalized": "34550317" } }, "mesh": [ { "descriptor": "3T3 Cells", "descriptor_ui": "D016475", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autoantigens", "descriptor_ui": "D001324", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Collagen Type XVII", "descriptor_ui": "D000097805", "major_topic": false }, { "descriptor": "Epidermal Cells", "descriptor_ui": "D000078404", "major_topic": false }, { "descriptor": "Epidermal Growth Factor", "descriptor_ui": "D004815", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Hair Follicle", "descriptor_ui": "D018859", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Non-Fibrillar Collagens", "descriptor_ui": "D024041", "major_topic": false }, { "descriptor": "Proteolysis", "descriptor_ui": "D059748", "major_topic": false }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Wound Healing", "descriptor_ui": "D014945", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Nov 1", "date_precision": "day", "issue": "11", "normalized_date": "2021-11-01", "pages": "e202012073", "proceedings_title": null, "publisher": "", "title": "The Journal of cell biology", "volume": "220", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "EGFR-mediated epidermal stem cell motility drives skin regeneration through COL17A1 proteolysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An increasing body of evidence suggests that impaired synapse development and function are associated with schizophrenia; however, the underlying molecular pathophysiological mechanism of the disease remains largely unclear. We conducted a family-based study combined with molecular and cellular analysis using induced pluripotent stem cell (iPSC) technology. We generated iPSCs from patients with familial schizophrenia, differentiated these cells into neurons, and investigated the molecular and cellular phenotypes of the patient's neurons. We identified multiple altered synaptic functions, including increased glutamatergic synaptic transmission, higher synaptic density, and altered splicing of dopamine D2 receptor mRNA in iPSC-derived neurons from patients. We also identified patients' specific genetic mutations using whole-exome sequencing. Our findings support the notion that altered synaptic function may underlie the molecular and cellular pathophysiology of schizophrenia, and that multiple genetic factors cooperatively contribute to the development of schizophrenia.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kana", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Kuriu", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Tsurusaki", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Hidenaga", "last_name": "Yamamori", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Mikiya", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Nanaka", "last_name": "Gotoda-Nishimura", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kida", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Fumihito", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Naomichi", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41398-021-01676-1" }, "pmcid": { "normalized": "PMC8547217" }, "pmid": { "normalized": "34697299" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Receptors, Dopamine D2", "descriptor_ui": "D017448", "major_topic": false }, { "descriptor": "Schizophrenia", "descriptor_ui": "D012559", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Oct 25", "date_precision": "day", "issue": "1", "normalized_date": "2021-10-25", "pages": "548", "proceedings_title": null, "publisher": "", "title": "Translational psychiatry", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Multiple alterations in glutamatergic transmission and dopamine D2 receptor splicing in induced pluripotent stem cell-derived neurons from patients with familial schizophrenia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Macropinocytosis refers to the non-specific uptake of extracellular fluid, which plays ubiquitous roles in cell growth, immune surveillance, and virus entry. Despite its widespread occurrence, it remains unclear how its initial cup-shaped plasma membrane extensions form without any external solid support, as opposed to the process of particle uptake during phagocytosis. Here, by developing a computational framework that describes the coupling between the bistable reaction-diffusion processes of active signaling patches and membrane deformation, we demonstrated that the protrusive force localized to the edge of the patches can give rise to a self-enclosing cup structure, without further assumptions of local bending or contraction. Efficient uptake requires a balance among the patch size, magnitude of protrusive force, and cortical tension. Furthermore, our model exhibits cyclic cup formation, coexistence of multiple cups, and cup-splitting, indicating that these complex morphologies self-organize via a common mutually-dependent process of reaction-diffusion and membrane deformation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Nen", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2021.103087" }, "pmcid": { "normalized": "PMC8560551" }, "pmid": { "normalized": "34755081" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Oct 22", "date_precision": "day", "issue": "10", "normalized_date": "2021-10-22", "pages": "103087", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "24", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Three-dimensional morphodynamic simulations of macropinocytic cups.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fukuyama congenital muscular dystrophy (FCMD) is a severe, intractable genetic disease that affects the skeletal muscle, eyes, and brain and is attributed to a defect in alpha dystroglycan (alphaDG) O-mannosyl glycosylation. We previously established disease models of FCMD; however, they did not fully recapitulate the phenotypes observed in human patients. In this study, we generated induced pluripotent stem cells (iPSCs) from a human FCMD patient and differentiated these cells into three-dimensional brain organoids and skeletal muscle. The brain organoids successfully mimicked patient phenotypes not reliably reproduced by existing models, including decreased alphaDG glycosylation and abnormal radial glial (RG) fiber migration. The basic polycyclic compound Mannan-007 (Mn007) restored alphaDG glycosylation in the brain and muscle models tested and partially rescued the abnormal RG fiber migration observed in cortical organoids. Therefore, our study underscores the importance of alphaDG O-mannosyl glycans for normal RG fiber architecture and proper neuronal migration in corticogenesis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mariko", "last_name": "Taniguchi-Ikeda", "name": null }, { "creator_type": "author", "first_name": "Michiyo", "last_name": "Koyanagi-Aoi", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takaori", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Hosoya", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Tezuka", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Nagase", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kadoshima", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Ishigaki", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Mizoguchi", "name": null }, { "creator_type": "author", "first_name": "Bennett G.", "last_name": "Novitch", "name": null }, { "creator_type": "author", "first_name": "Tatsushi", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Momoko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Aoi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2021.103140" }, "pmcid": { "normalized": "PMC8487058" }, "pmid": { "normalized": "34632335" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Oct 22", "date_precision": "day", "issue": "10", "normalized_date": "2021-10-22", "pages": "103140", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "24", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Restoration of the defect in radial glial fiber migration and cortical plate organization in a brain organoid model of Fukuyama muscular dystrophy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Protein malnutrition is epidemiologically suggested as a potential risk factor for senile dementia, although molecular mechanisms linking dietary proteins and amino acids to neurodegeneration remain unknown. Here, we show that a low-protein diet resulted in down-regulated expression of synaptic components and a modest acceleration of brain atrophy in mice modeling neurodegenerative tauopathies. Notably, these abnormal phenotypes were robustly rescued by the administration of seven selected essential amino acids. The up-regulation of inflammation-associated gene expression and progressive brain atrophy in the tauopathy model were profoundly suppressed by treatment with these essential amino acids without modifications of tau depositions. Moreover, the levels of kynurenine, an initiator of a pathway inducing neuroinflammatory gliosis and neurotoxicity in the brain, were lowered by treatment through inhibition of kynurenine uptake in the brain. Our findings highlight the importance of specific amino acids as systemic mediators of brain homeostasis against neurodegenerative processes.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hideaki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Takado", "name": null }, { "creator_type": "author", "first_name": "Sakiko", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Tsukamoto-Yasui", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Minatohara", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takuwa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Urushihata", "name": null }, { "creator_type": "author", "first_name": "Manami", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Shimojo", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Asumi", "last_name": "Orihara", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Ichio", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Sachise", "last_name": "Karakawa", "name": null }, { "creator_type": "author", "first_name": "Muneki", "last_name": "Isokawa", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Mayuka", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Mitsui", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abd5046" }, "pmcid": { "normalized": "PMC8535828" }, "pmid": { "normalized": "34678069" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Oct 22", "date_precision": "day", "issue": "43", "normalized_date": "2021-10-22", "pages": "eabd5046", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "7", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Neurodegenerative processes accelerated by protein malnutrition and decelerated by essential amino acids in a tauopathy mouse model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydrogen sulfide and its oxidation products are involved in many biological processes, and sulfane sulfur compounds, which contain sulfur atoms bonded to other sulfur atom(s), as found in hydropersulfides (R-S-SH), polysulfides (R-S-Sn-S-R), hydrogen polysulfides (H2Sn), etc., have attracted increasing interest. To characterize their physiological and pathophysiological roles, selective detection techniques are required. Classically, sulfane sulfur compounds can be detected by cyanolysis, involving nucleophilic attack by cyanide ion to cleave the sulfur-sulfur bonds. The generated thiocyanate reacts with ferric ion, and the resulting ferric thiocyanate complex can be easily detected by absorption spectroscopy. Recent exploration of the properties of sulfane sulfur compounds as both nucleophiles and electrophiles has led to the development of various chemical techniques for detection, isolation, and bioimaging of sulfane sulfur compounds in biological samples. These include tag-switch techniques, LC-MS/MS, Raman spectroscopy, and fluorescent probes. Herein, we present an overview of the techniques available for specific detection of sulfane sulfur species in biological contexts.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Honami", "last_name": "Echizen", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biom11111553" }, "pmcid": { "normalized": "PMC8616024" }, "pmid": { "normalized": "34827552" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false }, { "descriptor": "Sulfur Compounds", "descriptor_ui": "D013457", "major_topic": false }, { "descriptor": "Tandem Mass Spectrometry", "descriptor_ui": "D053719", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Oct 20", "date_precision": "day", "issue": "11", "normalized_date": "2021-10-20", "pages": "1553", "proceedings_title": null, "publisher": "", "title": "Biomolecules", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Recent Advances in Detection, Isolation, and Imaging Techniques for Sulfane Sulfur-Containing Biomolecules.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Accumulation of microtubule-associated tau protein is thought to cause neuron loss in a group of neurodegenerative diseases called tauopathies. In diseased brains, tau molecules adopt pathological structures that propagate into insoluble forms with disease-specific patterns. Several types of posttranslational modifications in tau are known to modulate its aggregation propensity in vitro, but their influence on tau accumulation and toxicity at the whole-organism level has not been fully elucidated. Herein, we utilized a series of transgenic Drosophila models to compare systematically the toxicity induced by five tau constructs with mutations or deletions associated with aggregation, including substitutions at seven disease-associated phosphorylation sites (S7A and S7E), deletions of PHF6 and PHF6* sequences (DeltaPHF6 and DeltaPHF6*), and substitutions of cysteine residues in the microtubule binding repeats (C291/322A). We found that substitutions and deletions resulted in different patterns of neurodegeneration and accumulation, with C291/322A having a dramatic effect on both tau accumulation and neurodegeneration. These cysteines formed disulfide bonds in mouse primary cultured neurons and in the fly retina, and stabilized tau proteins. Additionally, they contributed to tau accumulation under oxidative stress. We also found that each of these cysteine residues contributes to the microtubule polymerization rate and microtubule levels at equilibrium, but none of them affected tau binding to polymerized microtubules. Since tau proteins expressed in the Drosophila retina are mostly present in the early stages of tau filaments self-assembly, our results suggest that disulfide bond formation by these cysteine residues could be attractive therapeutic targets.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Chiku", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Wada-Kakuda", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Nobuhara", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Oba", "name": null }, { "creator_type": "author", "first_name": "Kanako", "last_name": "Shinno", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Sumioka", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Miyasaka", "name": null }, { "creator_type": "author", "first_name": "Kanae", "last_name": "Ando", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/hmg/ddab162" }, "pmcid": { "normalized": "PMC8522637" }, "pmid": { "normalized": "34137825" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Disease Susceptibility", "descriptor_ui": "D004198", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Protein Aggregation, Pathological", "descriptor_ui": "D066263", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Multimerization", "descriptor_ui": "D055503", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Oct 13", "date_precision": "day", "issue": "21", "normalized_date": "2021-10-13", "pages": "1955-1967", "proceedings_title": null, "publisher": "", "title": "Human molecular genetics", "volume": "30", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Disulfide bond formation in microtubule-associated tau protein promotes tau accumulation and toxicity in vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Single-molecule live-cell imaging is the most direct approach for monitoring the motility of molecules in living cells. Considering the relationship between the motility of molecules and their function, information obtained from single-molecule imaging involves essential clues for understanding the regulatory mechanisms of the processes of target molecules, and translation to applied sciences such as drug discovery. In this Concept, examples of single-molecule imaging studies on G protein-coupled receptors (GPCRs) are mainly introduced, and recent techniques of single-molecule imaging for overcoming the limitation of single-molecule live-cell imaging are discussed. Based on these studies, the prospects of single-molecule imaging will be outlined.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cbic.202100258" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34254418" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Single Molecule Imaging", "descriptor_ui": "D000072760", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Oct 13", "date_precision": "day", "issue": "20", "normalized_date": "2021-10-13", "pages": "2941-2945", "proceedings_title": null, "publisher": "", "title": "Chembiochem : a European journal of chemical biology", "volume": "22", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Potential of Single-Molecule Live-Cell Imaging for Chemical Translational Biology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hemostasis is an essential function that repairs tissues and maintains the survival of living organisms. To prevent diseases caused by the abnormality of the blood coagulation mechanism, it is important to carry out a blood test periodically by a method that is convenient and less burdensome for examiners. Thrombin is a protease that catalyzes the conversion of fibrinogen, and its cleavage activity can be an index of coagulation activity. Here, we developed a ratiometric bioluminescent indicator, Thrombastor (thrombin activity sensing indicator), which reflects the thrombin cleavage activity in blood by changing the emission color from green to blue. Compared to the current thrombin activity indicator, the rapid color change of the emission indicated a 2.5-fold decrease in the Km for thrombin, and the cleavage rate was more than two times faster. By improving the absolute bioluminescence intensity, detection from a small amount of plasma could be achieved with a smartphone camera. Using Thrombastor and a versatile device, an effective diagnosis for preventing coagulation disorders can be provided.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Nae", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Tetsuichi", "last_name": "Wazawa", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.1c02396" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34570461" } }, "mesh": [ { "descriptor": "Blood Coagulation", "descriptor_ui": "D001777", "major_topic": false }, { "descriptor": "Fibrinogen", "descriptor_ui": "D005340", "major_topic": false }, { "descriptor": "Plasma", "descriptor_ui": "D010949", "major_topic": false }, { "descriptor": "Smartphone", "descriptor_ui": "D000068997", "major_topic": true }, { "descriptor": "Thrombin", "descriptor_ui": "D013917", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Oct 12", "date_precision": "day", "issue": "40", "normalized_date": "2021-10-12", "pages": "13520-13526", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "93", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Ratiometric Bioluminescent Indicator for a Simple and Rapid Measurement of Thrombin Activity Using a Smartphone.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Heart failure is a major public health problem, and inflammation is involved in its pathogenesis. Inflammatory Ly6C(hi) monocytes accumulate in mouse hearts after pressure overload and are detrimental to the heart; however, the types of cells that drive inflammatory cell recruitment remain uncertain. Here, we showed that a distinct subset of mouse cardiac fibroblasts became activated by pressure overload and recruited Ly6C(hi) monocytes to the heart. Single-cell sequencing analysis revealed that a subset of cardiac fibroblasts highly expressed genes transcriptionally activated by the transcription factor NF-kappaB, as well as C-C motif chemokine ligand 2 (Ccl2) mRNA, which encodes a major factor in Ly6C(hi) monocyte recruitment. The deletion of the NF-kappaB activator IKKbeta in activated cardiac fibroblasts attenuated Ly6C(hi) monocyte recruitment and preserved cardiac function in mice subjected to pressure overload. Pseudotime analysis indicated two single-branch trajectories from quiescent fibroblasts into inflammatory fibroblasts and myofibroblasts. Our results provide insight into the mechanisms underlying cardiac inflammation and fibroblast-mediated inflammatory responses that could be therapeutically targeted to treat heart failure.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hajime", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Tanada", "name": null }, { "creator_type": "author", "first_name": "Shigemiki", "last_name": "Omiya", "name": null }, { "creator_type": "author", "first_name": "Mihai-Nicolae", "last_name": "Podaru", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Murakawa", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Ajay M.", "last_name": "Shah", "name": null }, { "creator_type": "author", "first_name": "Simon J.", "last_name": "Conway", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Kinya", "last_name": "Otsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/scisignal.abe4932" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34637330" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Monocytes", "descriptor_ui": "D009000", "major_topic": true }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Oct 12", "date_precision": "day", "issue": "704", "normalized_date": "2021-10-12", "pages": "eabe4932", "proceedings_title": null, "publisher": "", "title": "Science signaling", "volume": "14", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "NF-kappaB activation in cardiac fibroblasts results in the recruitment of inflammatory Ly6C(hi) monocytes in pressure-overloaded hearts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The generation of mature synaptic structures using neurons differentiated from human-induced pluripotent stem cells (hiPSC-neurons) is expected to be applied to physiological studies of synapses in human cells and to pathological studies of diseases that cause abnormal synaptic function. Although it has been reported that synapses themselves change from an immature to a mature state as neurons mature, there are few reports that clearly show when and how human stem cell-derived neurons change to mature synaptic structures. This study was designed to elucidate the synapse formation process of hiPSC-neurons. We propagated hiPSC-derived neural progenitor cells (hiPSC-NPCs) that expressed localized markers of the ventral hindbrain as neurospheres by dual SMAD inhibition and then differentiated them into hiPSC-neurons in vitro. After 49 days of in vitro differentiation, hiPSC-neurons significantly expressed pre- and postsynaptic markers at both the transcript and protein levels. However, the expression of postsynaptic markers was lower than in normal human or normal rat brain tissues, and immunostaining analysis showed that it was relatively modest and was lower than that of presynaptic markers and that its localization in synaptic structures was insufficient. Neurophysiological analysis using a microelectrode array also revealed that no synaptic activity was generated on hiPSC-neurons at 49 days of differentiation. Analysis of subtype markers by immunostaining revealed that most hiPSC-neurons expressed vesicular glutamate transporter 2 (VGLUT2). The presence or absence of NGF, which is required for the survival of cholinergic neurons, had no effect on their cell fractionation. These results suggest that during the synaptogenesis of hiPSC-neurons, the formation of presynaptic structures is not the only requirement for the formation of postsynaptic structures and that the mRNA expression of postsynaptic markers does not correlate with the formation of their mature structures. Technically, we also confirmed a certain level of robustness and reproducibility of our neuronal differentiation method in a multicenter setting, which will be helpful for future research. Synapse formation with mature postsynaptic structures will remain an interesting issue for stem cell-derived neurons, and the present method can be used to obtain early and stable quality neuronal cultures from hiPSC-NPCs.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Togo", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Fukusumi", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Shofuda", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohnishi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Mariko Kato", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Nana", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takei", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Kousuke", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Sekino", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Shirao", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Yonehiro", "last_name": "Kanemura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13041-021-00851-1" }, "pmcid": { "normalized": "PMC8504131" }, "pmid": { "normalized": "34629097" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Nerve Growth Factor", "descriptor_ui": "D020932", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Presynaptic Terminals", "descriptor_ui": "D017729", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Vesicular Glutamate Transport Protein 1", "descriptor_ui": "D050598", "major_topic": false }, { "descriptor": "Vesicular Glutamate Transport Protein 2", "descriptor_ui": "D050599", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Oct 11", "date_precision": "day", "issue": "1", "normalized_date": "2021-10-11", "pages": "149", "proceedings_title": null, "publisher": "", "title": "Molecular brain", "volume": "14", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Postsynaptic structure formation of human iPS cell-derived neurons takes longer than presynaptic formation during neural differentiation in vitro.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Designing synthetic surrogates of functional proteins is an important, albeit challenging, task in the field of chemistry. A strategy toward the design of synthetic agonists for growth factor or cytokine receptors that elicit a desired signal activity has been in high demand, as such ligands hold great promise as safer and more effective therapeutics. In the present study, we used a DNA aptamer as a building block and described the strategy-guided design of a synthetic receptor agonist with fine-tuned agonism. The developed synthetic partial agonist can regulate therapeutically relevant cellular activities by eliciting fine-tuned receptor signaling.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Momoko", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Ueki", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Yanagawa", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Sando", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.202105314" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34142433" } }, "mesh": [ { "descriptor": "A549 Cells", "descriptor_ui": "D000072283", "major_topic": false }, { "descriptor": "Aptamers, Nucleotide", "descriptor_ui": "D052157", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Dimerization", "descriptor_ui": "D019281", "major_topic": false }, { "descriptor": "Hepatocyte Growth Factor", "descriptor_ui": "D017228", "major_topic": false }, { "descriptor": "Human Umbilical Vein Endothelial Cells", "descriptor_ui": "D061307", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-met", "descriptor_ui": "D019859", "major_topic": false }, { "descriptor": "Receptors, Cytokine", "descriptor_ui": "D018121", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Oct 11", "date_precision": "day", "issue": "42", "normalized_date": "2021-10-11", "pages": "22745-22752", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "60", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "DNA-Based Synthetic Growth Factor Surrogates with Fine-Tuned Agonism*.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The characterization of aortic valve interstitial cells (VICs) cultured under optimal conditions is essential for understanding the molecular mechanisms underlying aortic valve stenosis. Here, we propose 2% hypoxia as an optimum VIC culture condition. Leaflets harvested from patients with aortic valve regurgitation were digested using collagenase and VICs were cultured under the 2% hypoxic condition. A significant increase in VIC growth was observed in 2% hypoxia (hypo-VICs), compared to normoxia (normo-VICs). RNA-sequencing revealed that downregulation of oxidative stress-marker genes (such as superoxide dismutase) and upregulation of cell cycle accelerators (such as cyclins) occurred in hypo-VICs. Accumulation of reactive oxygen species was observed in normo-VICs, indicating that low oxygen tension can avoid oxidative stress with cell-cycle arrest. Further mRNA quantifications revealed significant upregulation of several mesenchymal and hematopoietic progenitor markers, including CD34, in hypo-VICs. The stemness of hypo-VICs was confirmed using osteoblast differentiation assays, indicating that hypoxic culture is beneficial for maintaining growth and stemness, as well as for avoiding senescence via oxidative stress. The availability of hypoxic culture was also demonstrated in the molecular screening using proteomics. Therefore, hypoxic culture can be helpful for the identification of therapeutic targets and the evaluation of VIC molecular functions in vitro.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kaho", "last_name": "Kanno", "name": null }, { "creator_type": "author", "first_name": "Tomohisa", "last_name": "Sakaue", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Hamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Namiguchi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Nanba", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Aono", "name": null }, { "creator_type": "author", "first_name": "Mie", "last_name": "Kurata", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Masumoto", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Izutani", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms221910534" }, "pmcid": { "normalized": "PMC8508607" }, "pmid": { "normalized": "34638873" } }, "mesh": [ { "descriptor": "Antigens, CD34", "descriptor_ui": "D018952", "major_topic": false }, { "descriptor": "Aortic Valve", "descriptor_ui": "D001021", "major_topic": false }, { "descriptor": "Aortic Valve Insufficiency", "descriptor_ui": "D001022", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": true }, { "descriptor": "Cell Hypoxia", "descriptor_ui": "D015687", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 29", "date_precision": "day", "issue": "19", "normalized_date": "2021-09-29", "pages": "10534", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "22", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Hypoxic Culture Maintains Cell Growth of the Primary Human Valve Interstitial Cells with Stemness.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Clock genes Cry1 and Cry2, inhibitory components of core molecular feedback loop, are regarded as critical molecules for the circadian rhythm generation in mammals. A double knockout of Cry1 and Cry2 abolishes the circadian behavioral rhythm in adult mice under constant darkness. However, robust circadian rhythms in PER2::LUC expression are detected in the cultured suprachiasmatic nucleus (SCN) of Cry1/Cry2 deficient neonatal mice and restored in adult SCN by co-culture with wild-type neonatal SCN. These findings led us to postulate the compensatory molecule(s) for Cry1/Cry2 deficiency in circadian rhythm generation. We examined the roles of Chrono and Dec1/Dec2 proteins, the suppressors of Per(s) transcription similar to CRY(s). Unexpectedly, knockout of Chrono or Dec1/Dec2 in the Cry1/Cry2 deficient mice did not abolish but decoupled the coherent circadian rhythm into three different periodicities or significantly shortened the circadian period in neonatal SCN. DNA microarray analysis for the SCN of Cry1/Cry2 deficient mice revealed substantial increases in Per(s), Chrono and Dec(s) expression, indicating disinhibition of the transactivation by BMAL1/CLOCK. Here, we conclude that Chrono and Dec1/Dec2 do not compensate for absence of CRY1/CRY2 in the circadian rhythm generation but contribute to the coherent circadian rhythm expression in the neonatal mouse SCN most likely through integration of cellular circadian rhythms.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Christoph", "last_name": "Schmal", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takumi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kawamoto", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Sato", "last_name": "Honma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-98532-5" }, "pmcid": { "normalized": "PMC8479135" }, "pmid": { "normalized": "34584158" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Cryptochromes", "descriptor_ui": "D056931", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 28", "date_precision": "day", "issue": "1", "normalized_date": "2021-09-28", "pages": "19240", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "CHRONO and DEC1/DEC2 compensate for lack of CRY1/CRY2 in expression of coherent circadian rhythm but not in generation of circadian oscillation in the neonatal mouse SCN.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Exposure to hydrogen sulfide (H2S) can cause neurotoxicity and cardiopulmonary arrest. Resuscitating victims of sulfide intoxication is extremely difficult, and survivors often exhibit persistent neurological deficits. However, no specific antidote is available for sulfide intoxication. The objective of this study was to examine whether administration of a sulfonyl azide-based sulfide-specific scavenger, SS20, would rescue mice in models of H2S intoxication: ongoing exposure and post-cardiopulmonary arrest. In the ongoing exposure model, SS20 (1250 micromol/kg) or vehicle was administered to awake CD-1 mice intraperitoneally at 10 min after breathing 790 ppm of H2S followed by another 30 min of H2S inhalation. Effects of SS20 on survival were assessed. In the post-cardiopulmonary arrest model, cardiopulmonary arrest was induced by an intraperitoneal administration of sodium sulfide nonahydrate (125 mg/kg) in anesthetized mice. After 1 min of cardiopulmonary arrest, mice were resuscitated with intravenous administration of SS20 (250 micromol/kg) or vehicle. Effects of SS20 on survival, neurological outcomes, and plasma H2S levels were evaluated. Administration of SS20 during ongoing H2S inhalation improved 24-h survival (6/6 [100%] in SS20 vs 1/6 [17%] in vehicle; p = .0043). Post-arrest administration of SS20 improved 7-day survival (4/10 [40%] in SS20 vs 0/10 [0%] in vehicle; p = .0038) and neurological outcomes after resuscitation. SS20 decreased plasma H2S levels to pre-arrest baseline immediately after reperfusion and shortened the time to return of spontaneous circulation and respiration. These results suggest that SS20 is an effective antidote against lethal H2S intoxication, even when administered after cardiopulmonary arrest.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Eizo", "last_name": "Marutani", "name": null }, { "creator_type": "author", "first_name": "Takamitsu", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Xiang", "last_name": "Ni", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Xian", "name": null }, { "creator_type": "author", "first_name": "Fumito", "last_name": "Ichinose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/toxsci/kfab088" }, "pmcid": { "normalized": "PMC8478331" }, "pmid": { "normalized": "34270781" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antidotes", "descriptor_ui": "D000931", "major_topic": false }, { "descriptor": "Azides", "descriptor_ui": "D001386", "major_topic": false }, { "descriptor": "Heart Arrest", "descriptor_ui": "D006323", "major_topic": true }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 28", "date_precision": "day", "issue": "2", "normalized_date": "2021-09-28", "pages": "393-403", "proceedings_title": null, "publisher": "", "title": "Toxicological sciences : an official journal of the Society of Toxicology", "volume": "183", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "A Sulfonyl Azide-Based Sulfide Scavenger Rescues Mice from Lethal Hydrogen Sulfide Intoxication.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Male sexual function in mammals is controlled by the brain neural circuits and the spinal cord centers located in the lamina X of the lumbar spinal cord (L3-L4). Recently, we reported that hypothalamic oxytocin neurons project to the lumbar spinal cord to activate the neurons located in the dorsal lamina X of the lumbar spinal cord (dXL) via oxytocin receptors, thereby facilitating male sexual activity. Sexual experiences can influence male sexual activity in rats. However, how this experience affects the brain-spinal cord neural circuits underlying male sexual activity remains unknown. Focusing on dXL neurons that are innervated by hypothalamic oxytocinergic neurons controlling male sexual function, we examined whether sexual experience affects such neural circuits. We found that >50% of dXL neurons were activated in the first ejaculation group and ~30% in the control and intromission groups in sexually naive males. In contrast, in sexually experienced males, ~50% of dXL neurons were activated in both the intromission and ejaculation groups, compared to ~30% in the control group. Furthermore, sexual experience induced expressions of gastrin-releasing peptide and oxytocin receptors in the lumbar spinal cord. This is the first demonstration of the effects of sexual experience on molecular expressions in the neural circuits controlling male sexual activity in the spinal cord.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Oti", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Ryoko", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Junta", "last_name": "Nagafuchi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms221910362" }, "pmcid": { "normalized": "PMC8508609" }, "pmid": { "normalized": "34638701" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ejaculation", "descriptor_ui": "D004542", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gastrin-Releasing Peptide", "descriptor_ui": "D019886", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Penile Erection", "descriptor_ui": "D010410", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Long-Evans", "descriptor_ui": "D020318", "major_topic": false }, { "descriptor": "Receptors, Oxytocin", "descriptor_ui": "D018045", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 26", "date_precision": "day", "issue": "19", "normalized_date": "2021-09-26", "pages": "10362", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "22", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Sexual Experience Induces the Expression of Gastrin-Releasing Peptide and Oxytocin Receptors in the Spinal Ejaculation Generator in Rats.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "At the initial stage of carcinogenesis, cell competition often occurs between newly emerging transformed cells and the neighboring normal cells, leading to the elimination of transformed cells from the epithelial layer. For instance, when RasV12-transformed cells are surrounded by normal cells, RasV12 cells are apically extruded from the epithelium. However, the underlying mechanisms of this tumor-suppressive process still remain enigmatic. We first show by electron microscopic analysis that characteristic finger-like membrane protrusions are projected from both normal and RasV12 cells at their interface. In addition, FBP17, a member of the F-BAR proteins, accumulates in RasV12 cells, as well as surrounding normal cells, which plays a positive role in the formation of finger-like protrusions and apical elimination of RasV12 cells. Furthermore, cdc42 acts upstream of these processes. These results suggest that the cdc42/FBP17 pathway is a crucial trigger of cell competition, inducing \"protrusion to protrusion response\" between normal and RasV12-transformed cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tomoko", "last_name": "Kamasaki", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Hoshiba", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Kuromiya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Tanimura", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Motosuke", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Nemoto", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Shiro", "last_name": "Suetsugu", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2021.102994" }, "pmcid": { "normalized": "PMC8405961" }, "pmid": { "normalized": "34485872" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Sep 24", "date_precision": "day", "issue": "9", "normalized_date": "2021-09-24", "pages": "102994", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "24", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "FBP17-mediated finger-like membrane protrusions in cell competition between normal and RasV12-transformed cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Accumulating evidence supports that cancer stem cells (CSCs) are responsible for cancer proliferation, metastasis, and therapy resistance; therefore, an effective strategy to identify and isolate CSCs is required urgently. Because of their low invasiveness and high signal/noise ratio, \"turn-on\" fluorescence probes working in the deep-red/near-infrared (DR/NIR) region are one of the most attractive yet undeveloped tools for CSC detection. Herein, we report DR/NIR turn-on fluorescence probes, CS5-A and CS7-A, targeted to aldehyde dehydrogenase 1A1 as an intracellular CSC marker. In contrast to the conventional \"always-on\" green-fluorescent ALDEFLUOR, we succeeded in generating high-contrast (signal/noise ratio > 8.3) and wash-free in vitro CSC imaging with the DR probe C5S-A. This probe can facilitate CSC isolation with minimal contamination by autofluorescence from other tissues through fluorescence-activated cell sorting. Furthermore, the NIR absorbance/emission and turn-on properties of C7S-A allow simple and rapid CSC detection in vivo within 15 min.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Oe", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Aoi", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Funakoshi", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acssensors.1c01136" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34445866" } }, "mesh": [ { "descriptor": "Aldehyde Dehydrogenase", "descriptor_ui": "D000444", "major_topic": true }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 24", "date_precision": "day", "issue": "9", "normalized_date": "2021-09-24", "pages": "3320-3329", "proceedings_title": null, "publisher": "", "title": "ACS sensors", "volume": "6", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Deep-Red/Near-Infrared Turn-On Fluorescence Probes for Aldehyde Dehydrogenase 1A1 in Cancer Stem Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Pineal-related organs in cyclostomes, teleosts, amphibians, and reptiles exhibit color opponency, generating antagonistic neural responses to different wavelengths of light and thereby sensory information about its \"color\". Our previous studies suggested that in zebrafish and iguana pineal-related organs, a single photoreceptor cell expressing both UV-sensitive parapinopsin and green-sensitive parietopsin generates color opponency in a \"one-cell system.\" However, it remains unknown to what degree these opsins and the single cell-based mechanism in the pineal color opponency are conserved throughout non-mammalian vertebrates. RESULTS: We found that in the lamprey pineal organ, the two opsins are conserved but that, in contrast to the situation in other vertebrate pineal-related organs, they are expressed in separate photoreceptor cells. Intracellular electrophysiological recordings demonstrated that the parietopsin-expressing photoreceptor cells with Go-type G protein evoke a depolarizing response to visible light. Additionally, spectroscopic analyses revealed that parietopsin with 11-cis 3-dehydroretinal has an absorption maximum at ~570 nm, which is in approximate agreement with the wavelength (~560 nm) that produces the maximum rate of neural firing in pineal ganglion cells exposed to visible light. The vesicular glutamate transporter is localized at both the parietopsin- and parapinopsin-expressing photoreceptor terminals, suggesting that both types of photoreceptor cells use glutamate as a transmitter. Retrograde tracing of the pineal ganglion cells revealed that the terminal of the parietopsin-expressing cells is located close enough to form a neural connection with the ganglion cells, which is similar to our previous observation for the parapinopsin-expressing photoreceptor cells and the ganglion cells. In sum, our observations point to a \"two-cell system\" in which parietopsin and parapinopsin, expressed separately in two different types of photoreceptor cells, contribute to the generation of color opponency in the pineal ganglion cells. CONCLUSION: Our results indicate that the jawless vertebrate, lamprey, employs a system for color opponency that differes from that described previously in jawed vertebrates. From a physiological viewpoint, we propose an evolutionary insight, the emergence of pineal \"one-cell system\" from the ancestral \"multiple (two)-cell system,\" showing the opposite evolutionary direction to that of the ocular color opponency.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Seiji", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Kawano-Yamashita", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sugihara", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Tamotsu", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12915-021-01121-1" }, "pmcid": { "normalized": "PMC8444496" }, "pmid": { "normalized": "34526036" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Lampreys", "descriptor_ui": "D007798", "major_topic": false }, { "descriptor": "Opsins", "descriptor_ui": "D055355", "major_topic": false }, { "descriptor": "Pineal Gland", "descriptor_ui": "D010870", "major_topic": true }, { "descriptor": "Rivers", "descriptor_ui": "D045483", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 16", "date_precision": "day", "issue": "1", "normalized_date": "2021-09-16", "pages": "188", "proceedings_title": null, "publisher": "", "title": "BMC biology", "volume": "19", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Insights into the evolutionary origin of the pineal color discrimination mechanism from the river lamprey.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Carbon fiber and carbon fiber disc microelectrodes are widely used for electrochemical detection of biochemicals released from cells. However, fabricating these types of microelectrodes is difficult and time-consuming. Here, we report an easy-to-fabricate, carbon powder-filled microelectrode consisting of a pulled glass capillary backfilled with carbon powder. Carbon tip size and responsiveness can be controlled by adjusting the settings of the puller. Carbon powder-filled microelectrodes with tip opening diameters of 7-24 mum detected sub-micromolar to sub-millimolar levels of dopamine and catecholamines released from PC-12 cells. This simple microelectrode should promote further work on cellular and tissue electrochemistry.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Asuka", "last_name": "Tsujimura", "name": null }, { "creator_type": "author", "first_name": "Yuhi", "last_name": "Kamae", "name": null }, { "creator_type": "author", "first_name": "Hikaru", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Haruki", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Tabata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ab.2021.114316" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34314725" } }, "mesh": [ { "descriptor": "Carbon", "descriptor_ui": "D002244", "major_topic": false }, { "descriptor": "Catecholamines", "descriptor_ui": "D002395", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Electrochemical Techniques", "descriptor_ui": "D055664", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microelectrodes", "descriptor_ui": "D008839", "major_topic": false }, { "descriptor": "Neurotransmitter Agents", "descriptor_ui": "D018377", "major_topic": false }, { "descriptor": "Powders", "descriptor_ui": "D011208", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 15", "date_precision": "day", "issue": "", "normalized_date": "2021-09-15", "pages": "114316", "proceedings_title": null, "publisher": "", "title": "Analytical biochemistry", "volume": "629", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Carbon powder-filled microelectrode: An easy-to-fabricate probe for cellular electrochemistry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The extracellular signal-regulated kinase (ERK) pathway governs cell proliferation, differentiation and migration, and therefore plays key roles in various developmental and regenerative processes. Recent advances in genetically encoded fluorescent biosensors have unveiled hitherto unrecognized ERK activation dynamics in space and time and their functional importance mainly in cultured cells. However, ERK dynamics during embryonic development have still only been visualized in limited numbers of model organisms, and we are far from a sufficient understanding of the roles played by developmental ERK dynamics. In this Review, we first provide an overview of the biosensors used for visualization of ERK activity in live cells. Second, we highlight the applications of the biosensors to developmental studies of model organisms and discuss the current understanding of how ERK dynamics are encoded and decoded for cell fate decision-making.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akinobu", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.199767" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34338283" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 15", "date_precision": "day", "issue": "18", "normalized_date": "2021-09-15", "pages": "dev199767", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "148", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Shedding light on developmental ERK signaling with genetically encoded biosensors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The migration status of T cells within the densely packed tissue environment of lymph nodes reflects the ongoing activation state of adaptive immune responses. Upon encountering antigen-presenting dendritic cells, actively migrating T cells that are specific to cognate antigens slow down and are eventually arrested on dendritic cells to form immunological synapses. This dynamic transition of T cell motility is a fundamental strategy for the efficient scanning of antigens, followed by obtaining the adequate activation signals. After receiving antigenic stimuli, T cells begin to proliferate, and the expression of immunoregulatory receptors (such as CTLA-4 and PD-1) is induced on their surface. Recent findings have revealed that these 'immune checkpoint' molecules control the activation as well as motility of T cells in various situations. Therefore, the outcome of tumor immunotherapy using checkpoint inhibitors is assumed to be closely related to the alteration of T cell motility, particularly in tumor-draining lymph nodes (TDLNs). In this review, we discuss the migration dynamics of T cells during their activation in TDLNs, and the roles of checkpoint molecules in T cell motility, to provide some insight into the effect of tumor immunotherapy via checkpoint blockade, in terms of T cell dynamics and the importance of TDLNs.", "classifications": [ { "id": "18H05417", "label": "18H05417", "researcher": "Taku Okazaki", "type": "grant" }, { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers13184616" }, "pmcid": { "normalized": "PMC8465463" }, "pmid": { "normalized": "34572844" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Sep 15", "date_precision": "day", "issue": "18", "normalized_date": "2021-09-15", "pages": "4616", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "13", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Motility Dynamics of T Cells in Tumor-Draining Lymph Nodes: A Rational Indicator of Antitumor Response and Immune Checkpoint Blockade.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The simultaneous accumulation of multiple pathological proteins, such as hyperphosphorylated tau (hp-tau) and phosphorylated alpha-synuclein (p-alphaSyn), has been reported in the brains of patients with various neurodegenerative diseases. We previously demonstrated that hp-tau-dependent p-alphaSyn accumulation was associated with the activation of GSK-3beta in the brains of P301L tau transgenic mice. To confirm the effects of another mutant tau on p-alphaSyn accumulation in vivo, we herein examined the brains of PS19 mice that overexpress human P301S mutant tau. Immunohistochemically, hp-tau and p-alphaSyn aggregates were detected in the same neuronal cells in the cerebrum and brain stem of aged PS19 mice. A semiquantitative analysis showed a positive correlation between hp-tau and p-alphaSyn accumulation. Furthermore, an activated form of GSK-3beta was detected within cells containing both hp-tau and p-alphaSyn aggregates in PS19 mice. Western blotting showed a decrease in inactivated PP2A levels in PS19 mice. The present results suggest that the overexpression of human P301S mutant tau induces p-alphaSyn accumulation that is accompanied by not only GSK-3beta, but also PP2A activation in PS19 mice, and highlight the synergic effects between tau and alphaSyn in the pathophysiology of neurodegenerative diseases that show the codeposition of tau and alphaSyn.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Takaichi", "name": null }, { "creator_type": "author", "first_name": "James K.", "last_name": "Chambers", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Ano", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Uchida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jnen/nlab054" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34151989" } }, "mesh": [ { "descriptor": "alpha-Synuclein", "descriptor_ui": "D051844", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Glycogen Synthase Kinase 3 beta", "descriptor_ui": "D000071679", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Presenilins", "descriptor_ui": "D053763", "major_topic": false }, { "descriptor": "Protein Phosphatase 2", "descriptor_ui": "D054648", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 10", "date_precision": "day", "issue": "8", "normalized_date": "2021-09-10", "pages": "731-740", "proceedings_title": null, "publisher": "", "title": "Journal of neuropathology and experimental neurology", "volume": "80", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Deposition of Phosphorylated alpha-Synuclein and Activation of GSK-3beta and PP2A in the PS19 Mouse Model of Tauopathy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Polycomb repressive complexes-1 and -2 (PRC1 and 2) silence developmental genes in a spatiotemporal manner during embryogenesis. How Polycomb group (PcG) proteins orchestrate down-regulation of target genes upon differentiation, however, remains elusive. Here, by differentiating embryonic stem cells into embryoid bodies, we reveal a crucial role for the PCGF1-containing variant PRC1 complex (PCGF1-PRC1) to mediate differentiation-associated down-regulation of a group of genes. Upon differentiation cues, transcription is down-regulated at these genes, in association with PCGF1-PRC1-mediated deposition of histone H2AK119 mono-ubiquitination (H2AK119ub1) and PRC2 recruitment. In the absence of PCGF1-PRC1, both H2AK119ub1 deposition and PRC2 recruitment are disrupted, leading to aberrant expression of target genes. PCGF1-PRC1 is, therefore, required for initiation and consolidation of PcG-mediated gene repression during differentiation.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Sugishita", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Nayuta", "last_name": "Yakushiji-Kaminatsui", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Koseki", "name": null }, { "creator_type": "author", "first_name": "Yasuhide", "last_name": "Ohinata", "name": null }, { "creator_type": "author", "first_name": "Jafar", "last_name": "Sharif", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Harachi", "name": null }, { "creator_type": "author", "first_name": "Neil P.", "last_name": "Blackledge", "name": null }, { "creator_type": "author", "first_name": "Robert J.", "last_name": "Klose", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Koseki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-021-24894-z" }, "pmcid": { "normalized": "PMC8429492" }, "pmid": { "normalized": "34504070" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Embryoid Bodies", "descriptor_ui": "D058732", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Kruppel-Like Factor 4", "descriptor_ui": "D000090062", "major_topic": false }, { "descriptor": "Kruppel-Like Transcription Factors", "descriptor_ui": "D051741", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Mouse Embryonic Stem Cells", "descriptor_ui": "D000066450", "major_topic": false }, { "descriptor": "Platelet-Derived Growth Factor", "descriptor_ui": "D010982", "major_topic": false }, { "descriptor": "Polycomb Repressive Complex 1", "descriptor_ui": "D063150", "major_topic": false }, { "descriptor": "Polycomb Repressive Complex 2", "descriptor_ui": "D063151", "major_topic": false }, { "descriptor": "Primary Cell Culture", "descriptor_ui": "D061251", "major_topic": false }, { "descriptor": "SOXC Transcription Factors", "descriptor_ui": "D055751", "major_topic": false }, { "descriptor": "T-Box Domain Proteins", "descriptor_ui": "D020825", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false }, { "descriptor": "Ubiquitination", "descriptor_ui": "D054875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 9", "date_precision": "day", "issue": "1", "normalized_date": "2021-09-09", "pages": "5341", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Variant PCGF1-PRC1 links PRC2 recruitment with differentiation-associated transcriptional inactivation at target genes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We previously reported that intramuscular injections of ubiquitin ligase CBLB inhibitory pentapeptide (Cblin; Asp-Gly-pTyr-Met-Pro) restored lost muscle mass caused by sciatic denervation. Here, we detected Cblin on the basolateral side of Caco-2 cells after being placed on the apical side, and found that cytochalasin D, a tight junction opener, enhanced Cblin transport. Orally administered Cblin was found in rat plasma, indicating that intact Cblin was absorbed in vitro and in vivo. Furthermore, transgenic Cblin peptide-enriched rice (CbR) prevented the denervation-induced loss of muscle mass and the upregulation of muscle atrophy-related ubiquitin ligases in mice. These findings indicated that CbR could serve as an alternative treatment for muscle atrophy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Reiko", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Weilin", "last_name": "Shen", "name": null }, { "creator_type": "author", "first_name": "Yasuka", "last_name": "Shimajiri", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Kainou", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Anayt", "last_name": "Ulla", "name": null }, { "creator_type": "author", "first_name": "Kohta", "last_name": "Ohnishi", "name": null }, { "creator_type": "author", "first_name": "Miyuki", "last_name": "Ninomiya", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kazuhito", "last_name": "Akama", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41538-021-00108-0" }, "pmcid": { "normalized": "PMC8429733" }, "pmid": { "normalized": "34504092" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Sep 9", "date_precision": "day", "issue": "1", "normalized_date": "2021-09-09", "pages": "25", "proceedings_title": null, "publisher": "", "title": "NPJ science of food", "volume": "5", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Oral intake of rice overexpressing ubiquitin ligase inhibitory pentapeptide prevents atrophy in denervated skeletal muscle.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "MyoD, a myogenic differentiation protein, has been studied for its critical role in skeletal muscle differentiation. MyoD-expressing myoblasts have a potency to be differentiated with proliferation of ectopic cells. However, little is known about the effect on chromatin structure of MyoD binding in proliferative myoblasts. In this study, we evaluated the chromatin structure around MyoD-bound genome regions during the cell cycle by chromatin immunoprecipitation sequencing. Genome-wide analysis of histone modifications was performed in proliferative mouse C2C12 myoblasts during three phases (G1, S, G2/M) of the cell cycle. We found that MyoD-bound genome regions had elevated levels of active histone modifications, such as H3K4me1/2/3 and H3K27ac, compared with MyoD-unbound genome regions during the cell cycle. We also demonstrated that the elevated H3K4me2/3 modification level was maintained during the cell cycle, whereas the H3K27ac and H3K4me1 modification levels decreased to the same level as MyoD-unbound genome regions during the later phases. Immunoblot analysis revealed that MyoD abundance was high in the G1 phase then decreased in the S and G2/M phases. Our results suggest that MyoD binding formed selective epigenetic memories with H3K4me2/3 during the cell cycle in addition to myogenic gene induction via active chromatin formation coupled with transcription.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Qianmei", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Takeru", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Tomimatsu", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Miyawaki-Kuwakado", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jb/mvab001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33479729" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": true }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle Development", "descriptor_ui": "D024510", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Myoblasts", "descriptor_ui": "D032446", "major_topic": false }, { "descriptor": "MyoD Protein", "descriptor_ui": "D017570", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 7", "date_precision": "day", "issue": "6", "normalized_date": "2021-09-07", "pages": "653-661", "proceedings_title": null, "publisher": "", "title": "Journal of biochemistry", "volume": "169", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Genome-wide analysis of chromatin structure changes upon MyoD binding in proliferative myoblasts during the cell cycle.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To understand the physiological role of NADPH-thioredoxin reductase C (NTRC) in cyanobacteria, we investigated an NTRC-deficient mutant strain of Anabaena sp., PCC 7120, cultivated under different regimes of nitrogen supplementation and light exposure. The deletion of ntrC did not induce a change in the cell structure and metabolic pathways. However, time-dependent changes in the abundance of specific proteins and metabolites were observed. A decrease in chlorophyll a was correlated with a decrease in chlorophyll a biosynthesis enzymes and photosystem I subunits. The deletion of ntrC led to a deregulation of nitrogen metabolism, including the NtcA accumulation and heterocyst-specific proteins while nitrate ions were available in the culture medium. Interestingly, this deletion resulted in a redox imbalance, indicated by higher peroxide levels, higher catalase activity and the induction of chaperones such as MsrA. Surprisingly, the antioxidant protein 2-CysPrx was downregulated. The deficiency in ntrC also resulted in the accumulation of metabolites such as 6-phosphogluconate, ADP and ATP. Higher levels of NADP+ and NADPH partly correlated with higher G6PDH activity. Rather than impacting protein expression levels, NTRC appears to be involved in the direct regulation of enzymes, especially during the dark-to-light transition period.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Frederic", "last_name": "Deschoenmaeker", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Mihara", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Toyoshima", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jb/mvab014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33537746" } }, "mesh": [ { "descriptor": "Anabaena", "descriptor_ui": "D017033", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Chlorophyll A", "descriptor_ui": "D000077194", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "NADP", "descriptor_ui": "D009249", "major_topic": false }, { "descriptor": "Nitrogen", "descriptor_ui": "D009584", "major_topic": false }, { "descriptor": "Photosystem I Protein Complex", "descriptor_ui": "D045331", "major_topic": false }, { "descriptor": "Thioredoxin-Disulfide Reductase", "descriptor_ui": "D013880", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 7", "date_precision": "day", "issue": "6", "normalized_date": "2021-09-07", "pages": "709-719", "proceedings_title": null, "publisher": "", "title": "Journal of biochemistry", "volume": "169", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Thioredoxin pathway in Anabaena sp. PCC 7120: activity of NADPH-thioredoxin reductase C.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Anti-PD-1 therapies can activate tumor-specific T cells to destroy tumors. However, whether and how T cells with different antigen specificity and affinity are differentially regulated by PD-1 remain vaguely understood. Upon antigen stimulation, a variety of genes is induced in T cells. Recently, we found that T cell receptor (TCR) signal strength required for the induction of genes varies across different genes and PD-1 preferentially inhibits the induction of genes that require stronger TCR signal. As each T cell has its own response characteristics, inducibility of genes likely differs across different T cells. Accordingly, the inhibitory effects of PD-1 are also expected to differ across different T cells. In the current study, we investigated whether and how factors that modulate T cell responsiveness to antigenic stimuli influence PD-1 function. By analyzing TCRs with different affinities to peptide-MHC complexes (pMHC) and pMHCs with different affinities to TCR, we demonstrated that PD-1 inhibits the expression of TCR-inducible genes efficiently when TCR:pMHC affinity is low. In contrast, affinities of peptides to MHC and MHC expression levels did not affect PD-1 sensitivity of TCR-inducible genes although they markedly altered the dose responsiveness of T cells by changing the efficiency of pMHC formation, suggesting that the strength of individual TCR signal is the key determinant of PD-1 sensitivity. Accordingly, we observed a preferential expansion of T cells with low-affinity to tumor-antigen in PD-1-deficient mice upon inoculation of tumor cells. These results demonstrate that PD-1 imposes qualitative control of T cell responses by preferentially suppressing low-affinity T cells.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" }, { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Il-Mi", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Okazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2107141118" }, "pmcid": { "normalized": "PMC8536324" }, "pmid": { "normalized": "34433672" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, Neoplasm", "descriptor_ui": "D000951", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false }, { "descriptor": "Thymoma", "descriptor_ui": "D013945", "major_topic": false }, { "descriptor": "Thymus Neoplasms", "descriptor_ui": "D013953", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 31", "date_precision": "day", "issue": "35", "normalized_date": "2021-08-31", "pages": "e2107141118", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "118", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "PD-1 preferentially inhibits the activation of low-affinity T cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Translational research often requires the testing of experimental therapies in primates, but research in non-human primates is now stringently controlled by law around the world. Tissues fixed in formaldehyde without glutaraldehyde have been thought to be inappropriate for use in electron microscopic analysis, particularly those of the brain. Here we report the immunoelectron microscopic characterization of arginine vasopressin (AVP)-producing neurons in macaque hypothalamo-pituitary axis tissues fixed by perfusion with 4% formaldehyde and stored at -25 degrees C for several years (4-6 years). The size difference of dense-cored vesicles between magnocellular and parvocellular AVP neurons was detectable in their cell bodies and perivascular nerve endings located, respectively, in the posterior pituitary and median eminence. Furthermore, glutamate and the vesicular glutamate transporter 2 could be colocalized with AVP in perivascular nerve endings of both the posterior pituitary and the external layer of the median eminence, suggesting that both magnocellular and parvocellular AVP neurons are glutamatergic in primates. Both ultrastructure and immunoreactivity can therefore be sufficiently preserved in macaque brain tissues stored long-term, initially for light microscopy. Taken together, these results suggest that this methodology could be applied to the human post-mortem brain and be very useful in translational research.", "classifications": [ { "id": "21H00428", "label": "21H00428", "researcher": "Tatsuya Sakamoto", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akito", "last_name": "Otubo", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Maejima", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Oti", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "John F.", "last_name": "Morris", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms22179180" }, "pmcid": { "normalized": "PMC8430530" }, "pmid": { "normalized": "34502087" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cryopreservation", "descriptor_ui": "D015925", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fixatives", "descriptor_ui": "D005404", "major_topic": false }, { "descriptor": "Formaldehyde", "descriptor_ui": "D005557", "major_topic": false }, { "descriptor": "Hypothalamo-Hypophyseal System", "descriptor_ui": "D007030", "major_topic": false }, { "descriptor": "Macaca fuscata", "descriptor_ui": "D000080527", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microscopy, Immunoelectron", "descriptor_ui": "D016253", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Tissue Fixation", "descriptor_ui": "D016707", "major_topic": false }, { "descriptor": "Vasopressins", "descriptor_ui": "D014667", "major_topic": false }, { "descriptor": "Vesicular Glutamate Transport Proteins", "descriptor_ui": "D050496", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 25", "date_precision": "day", "issue": "17", "normalized_date": "2021-08-25", "pages": "9180", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "22", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Immunoelectron Microscopic Characterization of Vasopressin-Producing Neurons in the Hypothalamo-Pituitary Axis of Non-Human Primates by Use of Formaldehyde-Fixed Tissues Stored at -25 degrees C for Several Years.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Enzyme-activatable photoacoustic probes are powerful contrast agents to visualize diseases in which a specific enzyme is overexpressed. In this study, aluminum and silicon naphthalocyanines (AlNc and SiNc, respectively) conjugated with matrix metalloprotease-2 (MMP-2)-responsive PLGLAG peptide sequence and poly(ethylene glycol) (PEG) as an axial ligand were designed and synthesized. AlNc-peptide-PEG conjugates AlNc-pep-PEG formed dimeric species interacting with each other through face-to-face H-aggregation in water, while SiNc-based conjugates SiNc-pep-PEG hardly interacted with each other because of the two bulky hydrophilic axial ligands. Both conjugates formed spherical nanometer-sized self-assemblies in water, generating photoacoustic waves under near-infrared photoirradiation. The treatment of MNc-peptide-PEG conjugates (M = Al, Si) with MMP-2 smoothly induced the cleavage of the PLGLAG sequence to release the hydrophilic PEG moiety, resulting in the aggregation of MNcs. By comparing the PA signal intensity changes at 680 and 760 nm, the photoacoustic signal intensity ratios were shown to be enhanced by 3-5 times after incubation with MMP-2. We demonstrated that MNc-peptide-PEG conjugates (M = Al, Si) could work as activatable photoacoustic probes in the in vitro experiment of MMP-2-overexpressed cell line HT-1080 as well as the in vivo photoacoustic imaging of HT-1080-bearing mice.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Nogita", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Oe", "name": null }, { "creator_type": "author", "first_name": "Huiying", "last_name": "Mu", "name": null }, { "creator_type": "author", "first_name": "Wenting", "last_name": "Huo", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.bioconjchem.1c00266" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34167292" } }, "mesh": [ { "descriptor": "Aluminum Compounds", "descriptor_ui": "D017607", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carbocyanines", "descriptor_ui": "D002232", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Drug Design", "descriptor_ui": "D015195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Matrix Metalloproteinase 2", "descriptor_ui": "D020778", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Molecular Probes", "descriptor_ui": "D015335", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Neoplasms, Experimental", "descriptor_ui": "D009374", "major_topic": false }, { "descriptor": "Photoacoustic Techniques", "descriptor_ui": "D061088", "major_topic": false }, { "descriptor": "Silicon Compounds", "descriptor_ui": "D017655", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 18", "date_precision": "day", "issue": "8", "normalized_date": "2021-08-18", "pages": "1773-1781", "proceedings_title": null, "publisher": "", "title": "Bioconjugate chemistry", "volume": "32", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "MMP-2-Activatable Photoacoustic Tumor Imaging Probes Based on Al- and Si-Naphthalocyanines.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sleep is generally viewed as a period of recovery, but how the supply of cerebral blood flow (CBF) changes across sleep/wake states has remained unclear. Here, we directly observe red blood cells (RBCs) within capillaries, where the actual substance exchange between the blood and neurons/glia occurs, by two-photon microscopy. Across multiple cortical areas, average capillary CBF is largely increased during rapid eye movement (REM) sleep, whereas it does not differ between periods of active wakefulness and non-REM sleep. Capillary RBC flow during REM sleep is further elevated following REM sleep deprivation, suggesting that capillary CBF reflects REM sleep pressure. At the molecular level, signaling via adenosine A2a receptors is crucial; in A2a-KO mice, capillary CBF upsurge during REM sleep is dampened, and effects of REM sleep pressure are abolished. These results provide evidence regarding the dynamics of capillary CBF across sleep/wake states and insights to the underlying mechanisms.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Chia-Jung", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Chih-Yao", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Suganuma", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Kai", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Saitoh", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nagase", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Lazarus", "name": null }, { "creator_type": "author", "first_name": "Kaspar E.", "last_name": "Vogt", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2021.109558" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34407410" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Capillaries", "descriptor_ui": "D002196", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": false }, { "descriptor": "Cerebrovascular Circulation", "descriptor_ui": "D002560", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Receptor, Adenosine A2A", "descriptor_ui": "D043705", "major_topic": false }, { "descriptor": "Sleep, REM", "descriptor_ui": "D012895", "major_topic": false }, { "descriptor": "Wakefulness", "descriptor_ui": "D014851", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 17", "date_precision": "day", "issue": "7", "normalized_date": "2021-08-17", "pages": "109558", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "36", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Cerebral capillary blood flow upsurge during REM sleep is mediated by A2a receptors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In many phenomena of biological systems, not a majority, but a minority of cells act on the entire multicellular system causing drastic changes in the system properties. To understand the mechanisms underlying such phenomena, it is essential to observe the spatiotemporal dynamics of a huge population of cells at sub-cellular resolution, which is difficult with conventional tools such as microscopy and flow cytometry. Here, we describe an imaging system named AMATERAS that enables optical imaging with an over-one-centimeter field-of-view and a-few-micrometer spatial resolution. This trans-scale-scope has a simple configuration, composed of a low-power lens for machine vision and a hundred-megapixel image sensor. We demonstrated its high cell-throughput, capable of simultaneously observing more than one million cells. We applied it to dynamic imaging of calcium ions in HeLa cells and cyclic-adenosine-monophosphate in Dictyostelium discoideum, and successfully detected less than 0.01% of rare cells and observed multicellular events induced by these cells.", "classifications": [ { "id": "18H05415", "label": "18H05415", "researcher": "Kazuki Horikawa", "type": "grant" }, { "id": "18H05416", "label": "18H05416", "researcher": "Hitoshi Hashimoto", "type": "grant" }, { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" }, { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "T.", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "T.", "last_name": "Kakizuka", "name": null }, { "creator_type": "author", "first_name": "K.", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "K.", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "A.", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "H.", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "K.", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "T. M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "T.", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-95930-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Aug 16", "date_precision": "day", "issue": "", "normalized_date": "2021-08-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "", "volume": "11", "year": 2021 }, "ssbd": { "database": [ "ssbd-database-000199" ], "repository": [ "ssbd-repos-000199" ] }, "title": "Exploring rare cellular activity in more than one million cells by a transscale scope.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cerebellum is essential for the control, coordination, and learning of movements, and for certain aspects of cognitive function. Purkinje cells are the sole output neurons in the cerebellar cortex and therefore play crucial roles in the diverse functions of the cerebellum. The type 1 metabotropic glutamate receptor (mGluR1) is prominently enriched in Purkinje cells and triggers downstream signaling pathways that are required for functional and structural plasticity, and for synaptic responses. To understand how mGluR1 contributes to cerebellar functions, it is important to consider not only the operational properties of this receptor, but also its spatial organization and the molecular interactions that enable its proper functioning. In this review, we highlight how mGluR1 and its related signaling molecules are organized into tightly coupled microdomains to fulfill physiological functions. We also describe emerging evidence that altered mGluR1 signaling in Purkinje cells underlies cerebellar dysfunction in ataxias of human patients and mouse models.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Miwako", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Atsu", "last_name": "Aiba", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuropharm.2021.108629" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34089728" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 15", "date_precision": "day", "issue": "", "normalized_date": "2021-08-15", "pages": "108629", "proceedings_title": null, "publisher": "", "title": "Neuropharmacology", "volume": "194", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "mGluR1 signaling in cerebellar Purkinje cells: Subcellular organization and involvement in cerebellar function and disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genetically encoded temperature indicators (GETIs) allow for real-time measurement of subcellular temperature dynamics in live cells. However, GETIs have suffered from poor temperature sensitivity, which may not be sufficient to resolve small heat production from a biological process. Here, we develop a highly-sensitive GETI, denoted as ELP-TEMP, comprised of a temperature-responsive elastin-like polypeptide (ELP) fused with a cyan fluorescent protein (FP), mTurquoise2 (mT), and a yellow FP, mVenus (mV), as the donor and acceptor, respectively, of Forster resonance energy transfer (FRET). At elevated temperatures, the ELP moiety in ELP-TEMP undergoes a phase transition leading to an increase in the FRET efficiency. In HeLa cells, ELP-TEMP responded to the temperature from 33 to 40 degrees C with a maximum temperature sensitivity of 45.1 +/- 8.1%/ degrees C, which was the highest ever temperature sensitivity among hitherto-developed fluorescent nanothermometers. Although ELP-TEMP showed sensitivity not only to temperature but also to macromolecular crowding and self-concentration, we were able to correct the output of ELP-TEMP to achieve accurate temperature measurements at a subcellular resolution. We successfully applied ELP-TEMP to accurately measure temperature changes in cells induced by a local heat spot, even if the temperature difference was as small as < 1 degrees C, and to visualize heat production from stimulated Ca(2+) influx in live HeLa cells induced by a chemical stimulation. Furthermore, we investigated temperatures in the nucleus and cytoplasm of live HeLa cells and found that their temperatures were almost the same within the temperature resolution of our measurement. Our study would contribute to better understanding of cellular temperature dynamics, and ELP-TEMP would be a useful GETI for the investigation of cell thermobiology.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Cong Quang", "last_name": "Vu", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Tetsuichi", "last_name": "Wazawa", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-96049-5" }, "pmcid": { "normalized": "PMC8363741" }, "pmid": { "normalized": "34389773" } }, "mesh": [ { "descriptor": "Elastin", "descriptor_ui": "D004549", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": true }, { "descriptor": "Thermometry", "descriptor_ui": "D062125", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 13", "date_precision": "day", "issue": "1", "normalized_date": "2021-08-13", "pages": "16519", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [ "ssbd-database-000241" ], "repository": [ "ssbd-repos-000241" ] }, "title": "A highly-sensitive genetically encoded temperature indicator exploiting a temperature-responsive elastin-like polypeptide.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Additionally, the efficacy of targeted molecular therapies with multiple tyrosine kinase inhibitors is limited. In this study, we focused on the cellular signaling pathways common to diverse HCC cells and used quantitative reverse phase protein array (RPPA) and statistical analyses to elucidate the molecular mechanisms determining its malignancy. We examined the heterogeneity of 17 liver cancer cell lines by performing cluster analysis of their expression of CD90 and EpCAM cancer stem cell markers. Gaussian mixture model clustering identified three dominant clusters: CD90-positive and EpCAM-negative (CD90+), EpCAM-positive and CD90-negative (EpCAM+) and EpCAM-negative and CD90-negative (Neutral). A multivariate analysis by partial least squares revealed that the former two cell populations showed distinct patterns of protein expression and phosphorylation in the EGFR and EphA2 signaling pathways. The CD90+ cells exhibited higher abundance of AKT, EphA2 and its phosphorylated form at Ser(897), whereas the EpCAM+ cells exhibited higher abundance of ERK, RSK and its phosphorylated form. This demonstrates that pro-oncogenic, ligand-independent EphA2 signaling plays a dominant role in CD90+ cells with higher motility and metastatic activity than EpCAM+ cells. We also showed that an AKT inhibitor reduced the proliferation and survival of CD90+ cells but did not affect those of EpCAM+ cells. Taken together, our results suggest that AKT activation may be a key pro-oncogenic regulator in HCC.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Asakura", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Muroi", "name": null }, { "creator_type": "author", "first_name": "Yosui", "last_name": "Nojima", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Naohiko", "last_name": "Koshikawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms22168652" }, "pmcid": { "normalized": "PMC8395527" }, "pmid": { "normalized": "34445353" } }, "mesh": [ { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Carcinoma, Hepatocellular", "descriptor_ui": "D006528", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Epithelial Cell Adhesion Molecule", "descriptor_ui": "D000071858", "major_topic": false }, { "descriptor": "Hep G2 Cells", "descriptor_ui": "D056945", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Receptor, EphA2", "descriptor_ui": "D036104", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Thy-1 Antigens", "descriptor_ui": "D018800", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 11", "date_precision": "day", "issue": "16", "normalized_date": "2021-08-11", "pages": "8652", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "22", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Expression of Cancer Stem Cell Markers EpCAM and CD90 Is Correlated with Anti- and Pro-Oncogenic EphA2 Signaling in Hepatocellular Carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer tissue often comprises multiple tumor clones with distinct oncogenic alterations such as Ras or Src activation, yet the mechanism by which tumor heterogeneity drives cancer progression remains elusive. Here, we show in Drosophila imaginal epithelium that clones of Ras- or Src-activated benign tumors interact with each other to mutually promote tumor malignancy. Mechanistically, Ras-activated cells upregulate the cell-surface ligand Delta while Src-activated cells upregulate its receptor Notch, leading to Notch activation in Src cells. Elevated Notch signaling induces the transcriptional repressor Zfh1/ZEB1, which downregulates E-cadherin and cell death gene hid, leading to Src-activated invasive tumors. Simultaneously, Notch activation in Src cells upregulates the cytokine Unpaired/IL-6, which activates JAK-STAT signaling in neighboring Ras cells. Elevated JAK-STAT signaling upregulates the BTB-zinc-finger protein Chinmo, which downregulates E-cadherin and thus generates Ras-activated invasive tumors. Our findings provide a mechanistic explanation for how tumor heterogeneity triggers tumor progression via cell-cell interactions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masato", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Daisaku", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Tatsushi", "last_name": "Igaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2021.07.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34324859" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Genes, ras", "descriptor_ui": "D011905", "major_topic": false }, { "descriptor": "Imaginal Discs", "descriptor_ui": "D060227", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Oncogene Protein pp60(v-src)", "descriptor_ui": "D015688", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Zinc Fingers", "descriptor_ui": "D016335", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 9", "date_precision": "day", "issue": "15", "normalized_date": "2021-08-09", "pages": "2223-2236.e5", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "56", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Interaction between Ras and Src clones causes interdependent tumor malignancy via Notch signaling in Drosophila.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reversibly photoswitchable fluorescent proteins (RSFPs) are a class of fluorescent proteins whose fluorescence can be turned on and off by light irradiation. RSFPs have become essential tools for super-resolution (SR) imaging. Because most SR imaging techniques require high-power-density illumination, mitigating phototoxicity in cells due to intense light irradiation has been a challenge. Although we previously developed an RSFP named Kohinoor to achieve SR imaging with low phototoxicity, the photoproperties were insufficient to move a step further to explore the cellular dynamics by SR imaging. Here, we show an improved version of RSFP, Kohinoor2.0, which is suitable for SR imaging of cellular processes. Kohinoor2.0 shows a 2.6-fold higher fluorescence intensity, 2.5-fold faster chromophore maturation and 1.5-fold faster off-switching than Kohinoor. The analysis of the pH dependence of the visible absorption band revealed that Kohinoor2.0 and Kohinoor were in equilibria among multiple fluorescently bright and dark states, with the mutations introduced into Kohinoor2.0 bringing about a higher stabilization of the fluorescently bright states compared to Kohinoor. Using Kohinoor2.0 with our SR imaging technique, super-resolution polarization demodulation/on-state polarization angle narrowing, we conducted 4-h time-lapse SR imaging of an actin filament network in mammalian cells with a total acquisition time of 480 s without a noticeable indication of phototoxicity. Furthermore, we demonstrated the SR imaging of mitochondria dynamics at a time resolution of 0.5 s, in which the fusion and fission processes were clearly visualized. Thus, Kohinoor2.0 is shown to be an invaluable RSFP for the SR imaging of cellular dynamics.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuichi", "last_name": "Wazawa", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Noma", "name": null }, { "creator_type": "author", "first_name": "Shusaku", "last_name": "Uto", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Washio", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jmicro/dfab001" }, "pmcid": { "normalized": "PMC8350982" }, "pmid": { "normalized": "33481018" } }, "mesh": [ { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 9", "date_precision": "day", "issue": "4", "normalized_date": "2021-08-09", "pages": "340-352", "proceedings_title": null, "publisher": "", "title": "Microscopy (Oxford, England)", "volume": "70", "year": 2021 }, "ssbd": { "database": [ "ssbd-database-000242" ], "repository": [ "ssbd-repos-000242" ] }, "title": "A photoswitchable fluorescent protein for hours-time-lapse and sub-second-resolved super-resolution imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "TRPV1 and TRPV4, members of the transient receptor potential vanilloid family, are multimodal ion channels activated by various stimuli, including temperature and chemicals. It has been demonstrated that TRPV channels function as tetramers; however, the dynamics of the diffusion, oligomerization, and endocytosis of these channels in living cells are unclear. Here we undertook single-molecule time-lapse imaging of TRPV1 and TRPV4 in HEK 293 cells. Differences were observed between TRPV1 and TRPV4 before and after agonist stimulation. In the resting state, TRPV4 was more likely to form higher-order oligomers within immobile membrane domains than TRPV1. TRPV1 became immobile after capsaicin stimulation, followed by its gradual endocytosis. In contrast, TRPV4 was rapidly internalized upon stimulation with GSK1016790A. The selective loss of immobile higher-order oligomers from the cell surface through endocytosis increased the proportion of the fast-diffusing state for both subtypes. With the increase in the fast state, the association rate constants of TRPV1 and TRPV4 increased, regenerating the higher-order oligomers. Our results provide a possible mechanism for the different rates of endocytosis of TRPV1 and TRPV4 based on the spatial organization of the higher-order structures of the two TRPV channels.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yutaro", "last_name": "Kuwashima", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Yanagawa", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms22168473" }, "pmcid": { "normalized": "PMC8395219" }, "pmid": { "normalized": "34445178" } }, "mesh": [ { "descriptor": "Diffusion", "descriptor_ui": "D004058", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": false }, { "descriptor": "Single Molecule Imaging", "descriptor_ui": "D000072760", "major_topic": false }, { "descriptor": "TRPV Cation Channels", "descriptor_ui": "D050916", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 6", "date_precision": "day", "issue": "16", "normalized_date": "2021-08-06", "pages": "8473", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "22", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparative Analysis of Single-Molecule Dynamics of TRPV1 and TRPV4 Channels in Living Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ultraviolet (UV) light and incompletely understood genetic and epigenetic variations determine skin color. Here we describe an UV- and microphthalmia-associated transcription factor (MITF)-independent mechanism of skin pigmentation. Targeting the mitochondrial redox-regulating enzyme nicotinamide nucleotide transhydrogenase (NNT) resulted in cellular redox changes that affect tyrosinase degradation. These changes regulate melanosome maturation and, consequently, eumelanin levels and pigmentation. Topical application of small-molecule inhibitors yielded skin darkening in human skin, and mice with decreased NNT function displayed increased pigmentation. Additionally, genetic modification of NNT in zebrafish alters melanocytic pigmentation. Analysis of four diverse human cohorts revealed significant associations of skin color, tanning, and sun protection use with various single-nucleotide polymorphisms within NNT. NNT levels were independent of UVB irradiation and redox modulation. Individuals with postinflammatory hyperpigmentation or lentigines displayed decreased skin NNT levels, suggesting an NNT-driven, redox-dependent pigmentation mechanism that can be targeted with NNT-modifying topical drugs for medical and cosmetic purposes.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jennifer", "last_name": "Allouche", "name": null }, { "creator_type": "author", "first_name": "Inbal", "last_name": "Rachmin", "name": null }, { "creator_type": "author", "first_name": "Kaustubh", "last_name": "Adhikari", "name": null }, { "creator_type": "author", "first_name": "Luba M.", "last_name": "Pardo", "name": null }, { "creator_type": "author", "first_name": "Ju Hee", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Alicia M.", "last_name": "McConnell", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Shaohua", "last_name": "Fan", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Suita", "name": null }, { "creator_type": "author", "first_name": "Kazumasa", "last_name": "Wakamatsu", "name": null }, { "creator_type": "author", "first_name": "Vivien", "last_name": "Igras", "name": null }, { "creator_type": "author", "first_name": "Jianming", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Paula P.", "last_name": "Navarro", "name": null }, { "creator_type": "author", "first_name": "Camila Makhlouta", "last_name": "Lugo", "name": null }, { "creator_type": "author", "first_name": "Haley R.", "last_name": "Noonan", "name": null }, { "creator_type": "author", "first_name": "Kathleen A.", "last_name": "Christie", "name": null }, { "creator_type": "author", "first_name": "Kaspar", "last_name": "Itin", "name": null }, { "creator_type": "author", "first_name": "Nisma", "last_name": "Mujahid", "name": null }, { "creator_type": "author", "first_name": "Jennifer A.", "last_name": "Lo", "name": null }, { "creator_type": "author", "first_name": "Chong Hyun", "last_name": "Won", "name": null }, { "creator_type": "author", "first_name": "Conor L.", "last_name": "Evans", "name": null }, { "creator_type": "author", "first_name": "Qing Yu", "last_name": "Weng", "name": null }, { "creator_type": "author", "first_name": "Hequn", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Sam", "last_name": "Osseiran", "name": null }, { "creator_type": "author", "first_name": "Alyssa", "last_name": "Lovas", "name": null }, { "creator_type": "author", "first_name": "Istvan", "last_name": "Nemeth", "name": null }, { "creator_type": "author", "first_name": "Antonio", "last_name": "Cozzio", "name": null }, { "creator_type": "author", "first_name": "Alexander A.", "last_name": "Navarini", "name": null }, { "creator_type": "author", "first_name": "Jennifer J.", "last_name": "Hsiao", "name": null }, { "creator_type": "author", "first_name": "Nhu", "last_name": "Nguyen", "name": null }, { "creator_type": "author", "first_name": "Lajos V.", "last_name": "Kemeny", "name": null }, { "creator_type": "author", "first_name": "Othon", "last_name": "Iliopoulos", "name": null }, { "creator_type": "author", "first_name": "Carola", "last_name": "Berking", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Ruzicka", "name": null }, { "creator_type": "author", "first_name": "Rolando", "last_name": "Gonzalez-Jose", "name": null }, { "creator_type": "author", "first_name": "Maria-Catira", "last_name": "Bortolini", "name": null }, { "creator_type": "author", "first_name": "Samuel", "last_name": "Canizales-Quinteros", "name": null }, { "creator_type": "author", "first_name": "Victor", "last_name": "Acuna-Alonso", "name": null }, { "creator_type": "author", "first_name": "Carla", "last_name": "Gallo", "name": null }, { "creator_type": "author", "first_name": "Giovanni", "last_name": "Poletti", "name": null }, { "creator_type": "author", "first_name": "Gabriel", "last_name": "Bedoya", "name": null }, { "creator_type": "author", "first_name": "Francisco", "last_name": "Rothhammer", "name": null }, { "creator_type": "author", "first_name": "Shosuke", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Maria Vittoria", "last_name": "Schiaffino", "name": null }, { "creator_type": "author", "first_name": "Luke H.", "last_name": "Chao", "name": null }, { "creator_type": "author", "first_name": "Benjamin P.", "last_name": "Kleinstiver", "name": null }, { "creator_type": "author", "first_name": "Sarah", "last_name": "Tishkoff", "name": null }, { "creator_type": "author", "first_name": "Leonard I.", "last_name": "Zon", "name": null }, { "creator_type": "author", "first_name": "Tamar", "last_name": "Nijsten", "name": null }, { "creator_type": "author", "first_name": "Andres", "last_name": "Ruiz-Linares", "name": null }, { "creator_type": "author", "first_name": "David E.", "last_name": "Fisher", "name": null }, { "creator_type": "author", "first_name": "Elisabeth", "last_name": "Roider", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cell.2021.06.022" }, "pmcid": { "normalized": "PMC8349839" }, "pmid": { "normalized": "34233163" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Melanocytes", "descriptor_ui": "D008544", "major_topic": false }, { "descriptor": "Melanosomes", "descriptor_ui": "D020460", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Microphthalmia-Associated Transcription Factor", "descriptor_ui": "D051739", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Monophenol Monooxygenase", "descriptor_ui": "D014442", "major_topic": false }, { "descriptor": "NADP Transhydrogenases", "descriptor_ui": "D009250", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Proteasome Endopeptidase Complex", "descriptor_ui": "D046988", "major_topic": false }, { "descriptor": "Proteolysis", "descriptor_ui": "D059748", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Skin Pigmentation", "descriptor_ui": "D012880", "major_topic": false }, { "descriptor": "Ubiquitin", "descriptor_ui": "D025801", "major_topic": false }, { "descriptor": "Ultraviolet Rays", "descriptor_ui": "D014466", "major_topic": true }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 5", "date_precision": "day", "issue": "16", "normalized_date": "2021-08-05", "pages": "4268-4283.e20", "proceedings_title": null, "publisher": "", "title": "Cell", "volume": "184", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "NNT mediates redox-dependent pigmentation via a UVB- and MITF-independent mechanism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Early differential diagnosis between malignant and benign tumors and their underlying intrinsic differences are the most critical issues for life-threatening cancers. To study whether human acral melanomas, deadly cancers that occur on non-hair-bearing skin, have distinct origins that underlie their invasive capability, we develop fate-tracing technologies of melanocyte stem cells in sweat glands (glandular McSCs) and in melanoma models in mice and compare the cellular dynamics with human melanoma. Herein, we report that glandular McSCs self-renew to expand their migratory progeny in response to genotoxic stress and trauma to generate invasive melanomas in mice that mimic human acral melanomas. The analysis of melanocytic lesions in human volar skin reveals that genetically unstable McSCs expand in sweat glands and in the surrounding epidermis in melanomas but not in nevi. The detection of such cell spreading dynamics provides an innovative method for an early differential diagnosis of acral melanomas from nevi.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sally", "last_name": "Eshiba", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Namiki", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Mohri", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Aida", "name": null }, { "creator_type": "author", "first_name": "Naotaka", "last_name": "Serizawa", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Morinaga", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Nanba", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Kohichi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Uhara", "name": null }, { "creator_type": "author", "first_name": "Hiroo", "last_name": "Yokozeki", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Saida", "name": null }, { "creator_type": "author", "first_name": "Emi K.", "last_name": "Nishimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2021.109492" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34348144" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cyclin D1", "descriptor_ui": "D019938", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Epidermis", "descriptor_ui": "D004817", "major_topic": false }, { "descriptor": "Gene Amplification", "descriptor_ui": "D005784", "major_topic": false }, { "descriptor": "Genomic Instability", "descriptor_ui": "D042822", "major_topic": false }, { "descriptor": "Melanocytes", "descriptor_ui": "D008544", "major_topic": false }, { "descriptor": "Melanoma", "descriptor_ui": "D008545", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Nevus", "descriptor_ui": "D009506", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Skin Pigmentation", "descriptor_ui": "D012880", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Sweat Glands", "descriptor_ui": "D013545", "major_topic": false }, { "descriptor": "Ultraviolet Rays", "descriptor_ui": "D014466", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 3", "date_precision": "day", "issue": "5", "normalized_date": "2021-08-03", "pages": "109492", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "36", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Stem cell spreading dynamics intrinsically differentiate acral melanomas from nevi.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "There are sex differences in somatosensory sensitivity. Circulating estrogens appear to have a pronociceptive effect that explains why females are reported to be more sensitive to pain than males. Although itch symptoms develop during pregnancy in many women, the underlying mechanism of female-specific pruritus is unknown. Here, we demonstrate that estradiol, but not progesterone, enhances histamine-evoked scratching behavior indicative of itch in female rats. Estradiol increased the expression of the spinal itch mediator, gastrin-releasing peptide (GRP), and increased the histamine-evoked activity of itch-processing neurons that express the GRP receptor (GRPR) in the spinal dorsal horn. The enhancement of itch behavior by estradiol was suppressed by intrathecal administration of a GRPR blocker. In vivo electrophysiological analysis showed that estradiol increased the histamine-evoked firing frequency and prolonged the response of spinal GRP-sensitive neurons in female rats. On the other hand, estradiol did not affect the threshold of noxious thermal pain and decreased touch sensitivity, indicating that estradiol separately affects itch, pain, and touch modalities. Thus, estrogens selectively enhance histamine-evoked itch in females via the spinal GRP/GRPR system. This may explain why itch sensation varies with estrogen levels and provides a basis for treating itch in females by targeting GRPR.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Takanami", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Uta", "name": null }, { "creator_type": "author", "first_name": "Ken Ichi", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Earl", "last_name": "Carstens", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2103536118" }, "pmcid": { "normalized": "PMC8346901" }, "pmid": { "normalized": "34312228" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Estradiol", "descriptor_ui": "D004958", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Histamine", "descriptor_ui": "D006632", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Progesterone", "descriptor_ui": "D011374", "major_topic": false }, { "descriptor": "Pruritus", "descriptor_ui": "D011537", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Sex Factors", "descriptor_ui": "D012737", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 3", "date_precision": "day", "issue": "31", "normalized_date": "2021-08-03", "pages": "e2103536118", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "118", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Estrogens influence female itch sensitivity via the spinal gastrin-releasing peptide receptor neurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During positive selection at the transition from CD4+CD8+ double-positive (DP) to single-positive (SP) thymocyte, TCR signalling results in appropriate MHC restriction and signals for survival and progression. We show that the pioneer transcription factors Foxa1 and Foxa2 are required to regulate RNA splicing during positive selection of mouse T cells and that Foxa1 and Foxa2 have overlapping/compensatory roles. Conditional deletion of both Foxa1 and Foxa2 from DP thymocytes reduced positive selection and development of CD4SP, CD8SP and peripheral naive CD4+ T cells. Foxa1 and Foxa2 regulated the expression of many genes encoding splicing factors and regulators, including Mbnl1, H1f0, Sf3b1, Hnrnpa1, Rnpc3, Prpf4b, Prpf40b and Snrpd3. Within the positively selecting CD69+DP cells, alternative RNA splicing was dysregulated in the double Foxa1/Foxa2 conditional knockout, leading to >850 differentially used exons. Many genes important for this stage of T-cell development (Ikzf1-3, Ptprc, Stat5a, Stat5b, Cd28, Tcf7) and splicing factors (Hnrnpab, Hnrnpa2b1, Hnrnpu, Hnrnpul1, Prpf8) showed multiple differentially used exons. Thus, Foxa1 and Foxa2 are required during positive selection to regulate alternative splicing of genes essential for T-cell development, and, by also regulating splicing of splicing factors, they exert widespread control of alternative splicing.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ching-In", "last_name": "Lau", "name": null }, { "creator_type": "author", "first_name": "Jasmine", "last_name": "Rowell", "name": null }, { "creator_type": "author", "first_name": "Diana C.", "last_name": "Yanez", "name": null }, { "creator_type": "author", "first_name": "Anisha", "last_name": "Solanki", "name": null }, { "creator_type": "author", "first_name": "Susan", "last_name": "Ross", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Tessa", "last_name": "Crompton", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.199754" }, "pmcid": { "normalized": "PMC8353164" }, "pmid": { "normalized": "34323272" } }, "mesh": [ { "descriptor": "Alternative Splicing", "descriptor_ui": "D017398", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Exons", "descriptor_ui": "D005091", "major_topic": false }, { "descriptor": "Hepatocyte Nuclear Factor 3-alpha", "descriptor_ui": "D051541", "major_topic": false }, { "descriptor": "Hepatocyte Nuclear Factor 3-beta", "descriptor_ui": "D051542", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "RNA Splicing", "descriptor_ui": "D012326", "major_topic": false }, { "descriptor": "RNA Splicing Factors", "descriptor_ui": "D000072260", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false }, { "descriptor": "Thymocytes", "descriptor_ui": "D060168", "major_topic": false }, { "descriptor": "Thymus Gland", "descriptor_ui": "D013950", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 1", "date_precision": "day", "issue": "15", "normalized_date": "2021-08-01", "pages": "dev199754", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "148", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "The pioneer transcription factors Foxa1 and Foxa2 regulate alternative RNA splicing during thymocyte positive selection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neuronal birthdate is one of the major determinants of neuronal phenotypes. However, most birthdating methods are retrospective in nature, allowing very little experimental access to the classified neuronal subsets. Here, we introduce four neurogenic tagging mouse lines, which can assign CreER-loxP recombination to neuron subsets that share the same differentiation timing in living animals and enable various experimental manipulations of the classified subsets. We constructed a brain atlas of the neurogenic tagging mouse lines (NeuroGT), which includes holistic image data of the loxP-recombined neurons and their processes across the entire brain that were tagged on each single day during the neurodevelopmental period. This image database, which is open to the public, offers investigators the opportunity to find specific neurogenic tagging driver lines and the stages of tagging appropriate for their own research purposes.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsumi", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Tohsato", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Itoga", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Shioi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyonari", "name": null }, { "creator_type": "author", "first_name": "Sanae", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.crmeth.2021.100012" }, "pmcid": { "normalized": "PMC9017123" }, "pmid": { "normalized": "35474959" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jul 26", "date_precision": "day", "issue": "3", "normalized_date": "2021-07-26", "pages": "100012", "proceedings_title": null, "publisher": "", "title": "Cell reports methods", "volume": "1", "year": 2021 }, "ssbd": { "database": [ "ssbd-database-000140" ], "repository": [ "ssbd-repos-000140" ] }, "title": "NeuroGT: A brain atlas of neurogenic tagging CreER drivers for birthdate-based classification and manipulation of mouse neurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Using the lux operon (luxCDABE) of bacterial bioluminescence system as an autonomous luminous reporter has been demonstrated in bacteria, plant and mammalian cells. However, applications of bacterial bioluminescence-based imaging have been limited because of its low brightness. Here, we engineered the bacterial luciferase (heterodimer of luxA and luxB) by fusion with Venus, a bright variant of yellow fluorescent protein, to induce bioluminescence resonance energy transfer (BRET). By using decanal as an externally added substrate, color change and ten-times enhancement of brightness was achieved in Escherichia coli when circularly permuted Venus was fused to the C-terminus of luxB. Expression of the Venus-fused luciferase in human embryonic kidney cell lines (HEK293T) or in Nicotiana benthamiana leaves together with the substrate biosynthesis-related genes (luxC, luxD and luxE) enhanced the autonomous bioluminescence. We believe the improved luciferase will forge the way towards the potential development of autobioluminescent reporter system allowing spatiotemporal imaging in live cells.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomomi", "last_name": "Kaku", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Tetsuyuki", "last_name": "Entani", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Osabe", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-94551-4" }, "pmcid": { "normalized": "PMC8298465" }, "pmid": { "normalized": "34294849" } }, "mesh": [ { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Bioluminescence Resonance Energy Transfer Techniques", "descriptor_ui": "D060807", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luciferases, Bacterial", "descriptor_ui": "D049453", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Nicotiana", "descriptor_ui": "D014026", "major_topic": false }, { "descriptor": "Plants, Genetically Modified", "descriptor_ui": "D030821", "major_topic": false }, { "descriptor": "Protein Engineering", "descriptor_ui": "D015202", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jul 22", "date_precision": "day", "issue": "1", "normalized_date": "2021-07-22", "pages": "14994", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Enhanced brightness of bacterial luciferase by bioluminescence resonance energy transfer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In multicellular organisms, expression profiling in spatially defined regions is crucial to elucidate cell interactions and functions. Here, we establish a transcriptome profiling method coupled with photo-isolation chemistry (PIC) that allows the determination of expression profiles specifically from photo-irradiated regions of interest. PIC uses photo-caged oligodeoxynucleotides for in situ reverse transcription. PIC transcriptome analysis detects genes specifically expressed in small distinct areas of the mouse embryo. Photo-irradiation of single cells demonstrated that approximately 8,000 genes were detected with 7 x 10(4) unique read counts. Furthermore, PIC transcriptome analysis is applicable to the subcellular and subnuclear microstructures (stress granules and nuclear speckles, respectively), where hundreds of genes can be detected as being specifically localised. The spatial density of the read counts is higher than 100 per square micrometre. Thus, PIC enables high-depth transcriptome profiles to be determined from limited regions up to subcellular and subnuclear resolutions.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mizuki", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Chikara", "last_name": "Meno", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-021-24691-8" }, "pmcid": { "normalized": "PMC8292322" }, "pmid": { "normalized": "34285220" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Feasibility Studies", "descriptor_ui": "D005240", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Genetic Techniques", "descriptor_ui": "D005821", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "Oligodeoxyribonucleotides", "descriptor_ui": "D009838", "major_topic": false }, { "descriptor": "Reverse Transcription", "descriptor_ui": "D048348", "major_topic": false }, { "descriptor": "Spatial Analysis", "descriptor_ui": "D062206", "major_topic": true }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false }, { "descriptor": "Ultraviolet Rays", "descriptor_ui": "D014466", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jul 20", "date_precision": "day", "issue": "1", "normalized_date": "2021-07-20", "pages": "4416", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "High-depth spatial transcriptome analysis by photo-isolation chemistry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The most motile phototrophic organisms exhibit photo-induced behavioral responses (photobehavior) to inhabit better light conditions for photosynthesis. The unicellular green alga Chlamydomonas reinhardtii is an excellent model organism to study photobehavior. Several years ago, we found that C. reinhardtii cells reverse their phototactic signs (i.e., positive and negative phototaxis) depending on the amount of reactive oxygen species (ROS) accumulated in the cell. However, its molecular mechanism is unclear. In this study, we isolated seven mutants showing positive phototaxis, even after the induction of negative phototaxis (ap1~7: always positive) to understand the ROS-dependent regulatory mechanism for the phototactic sign. We found no common feature in the mutants regarding their growth, high-light tolerance, and photosynthetic phenotypes. Interestingly, five of them grew faster than the wild type. These data suggest that the ROS-dependent regulation of the phototactic sign is not a single pathway and is affected by various cellular factors. Additionally, the isolation and analyses of mutants with defects in phototactic-sign regulation may provide clues for their application to the efficient cultivation of algae.", "classifications": [ { "id": "21H00420", "label": "21H00420", "researcher": "Ken-ichi Wakabayashi", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Ryutaro", "last_name": "Tokutsu", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Minagawa", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/plants10071483" }, "pmcid": { "normalized": "PMC8309459" }, "pmid": { "normalized": "34371686" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jul 20", "date_precision": "day", "issue": "7", "normalized_date": "2021-07-20", "pages": "1483", "proceedings_title": null, "publisher": "", "title": "Plants (Basel, Switzerland)", "volume": "10", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Characterization of Chlamydomonas reinhardtii Mutants That Exhibit Strong Positive Phototaxis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The role of oligodendrocyte lineage cells, the largest glial population in the adult central nervous system (CNS), in the pathogenesis of Alzheimer's disease (AD) remains elusive. Here, we developed a culture method for adult oligodendrocyte progenitor cells (aOPCs). Fibroblast growth factor 2 (FGF2) promotes survival and proliferation of NG2(+) aOPCs in a serum-free defined medium; a subpopulation (~5%) of plexin-B3(+) aOPCs was also found. FGF2 withdrawal decreased NG2(+), but increased plexin-B3(+) aOPCs and Abeta1-42 secretion. Plexin-B3(+) aOPCs were distributed throughout the adult rat brain, although less densely than NG2(+) aOPCs. Spreading depolarization induced delayed cortical plexin-B3(+) aOPC gliosis in the ipsilateral remote cortex. Furthermore, extracellular Abeta1-42 accumulation was occasionally found around plexin-B3(+) aOPCs near the lesions. In AD brains, virtually all cortical SPs were immunostained for plexin-B3, and plexin-B3 levels increased significantly in the Sarkosyl-soluble fractions. These findings suggest that plexin-B3(+) aOPCs may play essential roles in AD pathogenesis, as natural Abeta-secreting cells.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Naomi", "last_name": "Nihonmatsu-Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Xiu-Jun", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Kazuhito", "last_name": "Satou", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Kaname", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Akagi", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Shuta", "last_name": "Toru", "name": null }, { "creator_type": "author", "first_name": "Katsuiku", "last_name": "Hirokawa", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Uchihara", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Tatebayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-021-02404-7" }, "pmcid": { "normalized": "PMC8282672" }, "pmid": { "normalized": "34267322" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Amyloid beta-Peptides", "descriptor_ui": "D016229", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens", "descriptor_ui": "D000941", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chondroitin Sulfate Proteoglycan 4", "descriptor_ui": "D000099216", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Neural Cell Adhesion Molecules", "descriptor_ui": "D019006", "major_topic": false }, { "descriptor": "Oligodendrocyte Precursor Cells", "descriptor_ui": "D000073637", "major_topic": false }, { "descriptor": "Oligodendroglia", "descriptor_ui": "D009836", "major_topic": false }, { "descriptor": "Peptide Fragments", "descriptor_ui": "D010446", "major_topic": false }, { "descriptor": "Proteoglycans", "descriptor_ui": "D011509", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jul 15", "date_precision": "day", "issue": "1", "normalized_date": "2021-07-15", "pages": "870", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "4", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Essential roles of plexin-B3(+) oligodendrocyte precursor cells in the pathogenesis of Alzheimer's disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We evaluated the effect of high hydrostatic pressure on mouse embryonic fibroblasts (MEFs) and mouse embryonic stem (ES) cells. Hydrostatic pressures of 15, 30, 60, and 90 MPa were applied for 10 min, and changes in gene expression were evaluated. Among genes related to mechanical stimuli, death-associated protein 3 was upregulated in MEF subjected to 90 MPa pressure; however, other genes known to be upregulated by mechanical stimuli did not change significantly. Genes related to cell differentiation did not show a large change in expression. On the other hand, genes related to pluripotency, such as Oct4 and Sox2, showed a twofold increase in expression upon application of 60 MPa hydrostatic pressure for 10 min. Although these changes did not persist after overnight culture, cells that were pressurized to 15 MPa showed an increase in pluripotency genes after overnight culture. When mouse ES cells were pressurized, they also showed an increase in the expression of pluripotency genes. These results show that hydrostatic pressure activates pluripotency genes in mammalian cells. This article has an associated First Person interview with the first author of the paper.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuko", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Yoshie", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/bio.058544" }, "pmcid": { "normalized": "PMC8325925" }, "pmid": { "normalized": "34258610" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Hydrostatic Pressure", "descriptor_ui": "D006874", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Octamer Transcription Factor-3", "descriptor_ui": "D050814", "major_topic": false }, { "descriptor": "SOXB1 Transcription Factors", "descriptor_ui": "D055748", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jul 15", "date_precision": "day", "issue": "7", "normalized_date": "2021-07-15", "pages": "bio058544", "proceedings_title": null, "publisher": "", "title": "Biology open", "volume": "10", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Pressure-induced changes on the morphology and gene expression in mammalian cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Apelin/APJ signalling pathway, involved in multiple physiological and pathological processes, has been attracting increasing interest recently. In our previous study, Apelin overexpression in colon26 tumor cells suppressed tumor growth by inducing vascular maturation. Here, we found that MC38 and LLC tumor growth were greater in the absence of Apelin than in wild-type (WT) mice, suggesting that Apelin acts as a tumor suppressor. Consistent with this, treating WT mice with [Pyr(1)]Apelin-13 inhibited tumor growth. In MC38 tumors, only endothelial cells (ECs) strongly express APJ, a cognate receptor for Apelin, indicating that EC-derived Apelin might regulate tumor formation in an autocrine manner. Comparing with WT mice, larger numbers of vessels with narrower diameters were observed in tumors of Apelin knockout mice and lack of Apelin enhanced tumor hypoxia. Investigating immune cells in the tumor revealed that [Pyr(1)]Apelin-13 infusion induced the accumulation of CD8(+) and CD4(+) T cells in central areas. Moreover, RNA-sequencing analysis showed that Apelin induces chemokine CCL8 expression in ECs. Thus, enhancing anti-tumor immunity might be one of the mechanisms by which Apelin is involved in tumor growth. Our result indicated that increased CCL8 expression might induce CD8( +) T cells infiltration into tumor and tumor inhibition.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Liuying", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-93619-5" }, "pmcid": { "normalized": "PMC8263715" }, "pmid": { "normalized": "34234274" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apelin", "descriptor_ui": "D000073861", "major_topic": false }, { "descriptor": "Apelin Receptors", "descriptor_ui": "D000075244", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Chemokine CCL8", "descriptor_ui": "D054412", "major_topic": false }, { "descriptor": "Chemotaxis, Leukocyte", "descriptor_ui": "D002634", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphocytes, Tumor-Infiltrating", "descriptor_ui": "D016246", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "T-Lymphocyte Subsets", "descriptor_ui": "D016176", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jul 7", "date_precision": "day", "issue": "1", "normalized_date": "2021-07-07", "pages": "14047", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Endothelial cell-derived Apelin inhibits tumor growth by altering immune cell localization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In this study, we present a live-cell-based fluorometric coupled assay system to identify the compounds that can regulate the targeted metabolic pathways in live cells. The assay is established through targeting specific metabolic pathways and using \"input\" and \"output\" metabolite pairs. The changes in the extracellular output that are generated and released into the extracellular media from the input are assessed as the activity of the pathway. The screening for the glycolytic pathway and amino acid metabolism reveals the activities of the present drugs, 6-BIO and regorafenib, that regulate the metabolic fate of tumor cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kouichi", "last_name": "Yanagi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Shusuke", "last_name": "Ogihara", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2021.109311" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34233188" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Biological Assay", "descriptor_ui": "D001681", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Cells", "descriptor_ui": "D002477", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Phenylurea Compounds", "descriptor_ui": "D010671", "major_topic": false }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false }, { "descriptor": "Sorafenib", "descriptor_ui": "D000077157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jul 6", "date_precision": "day", "issue": "1", "normalized_date": "2021-07-06", "pages": "109311", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "36", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Establishment of live-cell-based coupled assay system for identification of compounds to modulate metabolic activities of cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bombesin is a putative antibacterial peptide isolated from the skin of the frog, Bombina bombina. Two related (bombesin-like) peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB) have been found in mammals. The history of GRP/bombesin discovery has caused little attention to be paid to the evolutionary relationship of GRP/bombesin and their receptors in vertebrates. We have classified the peptides and their receptors from the phylogenetic viewpoint using a newly established genetic database and bioinformatics. Here we show, by using a clawed frog (Xenopus tropicalis), that GRP is not a mammalian counterpart of bombesin and also that, whereas the GRP system is widely conserved among vertebrates, the NMB/bombesin system has diversified in certain lineages, in particular in frog species. To understand the derivation of GRP system in the ancestor of mammals, we have focused on the GRP system in Xenopus. Gene expression analyses combined with immunohistochemistry and Western blotting experiments demonstrated that GRP peptides and their receptors are distributed in the brain and stomach of Xenopus. We conclude that GRP peptides and their receptors have evolved from ancestral (GRP-like peptide) homologues to play multiple roles in both the gut and the brain as one of the 'gut-brain peptide' systems.", "classifications": [ { "id": "21H00428", "label": "21H00428", "researcher": "Tatsuya Sakamoto", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Asuka", "last_name": "Hirooka", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Fujiyama", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Takanami", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Oti", "name": null }, { "creator_type": "author", "first_name": "Yukitoshi", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-92528-x" }, "pmcid": { "normalized": "PMC8233351" }, "pmid": { "normalized": "34172791" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anura", "descriptor_ui": "D001001", "major_topic": false }, { "descriptor": "Bombesin", "descriptor_ui": "D001839", "major_topic": false }, { "descriptor": "Gastrin-Releasing Peptide", "descriptor_ui": "D019886", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Neurokinin B", "descriptor_ui": "D015287", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Receptors, Bombesin", "descriptor_ui": "D018004", "major_topic": false }, { "descriptor": "Xenopus laevis", "descriptor_ui": "D014982", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun 25", "date_precision": "day", "issue": "1", "normalized_date": "2021-06-25", "pages": "13315", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "The gastrin-releasing peptide/bombesin system revisited by a reverse-evolutionary study considering Xenopus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nuclear hyperpolarization has emerged as a method to dramatically enhance the sensitivity of NMR spectroscopy. By application of this powerful tool, small molecules with stable isotopes have been used for highly sensitive biomedical molecular imaging. The recent development of molecular probes for hyperpolarized in vivo analysis has demonstrated the ability of this technique to provide unique metabolic and physiological information. This review presents a brief introduction of hyperpolarization technology, approaches to the rational design of molecular probes for hyperpolarized analysis, and examples of molecules that have met with success in vitro or in vivo.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Takakusagi", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Sando", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201915718" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32372551" } }, "mesh": [ { "descriptor": "Magnetic Resonance Spectroscopy", "descriptor_ui": "D009682", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": true }, { "descriptor": "Molecular Probes", "descriptor_ui": "D015335", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun 25", "date_precision": "day", "issue": "27", "normalized_date": "2021-06-25", "pages": "14779-14799", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "60", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Design of Nuclear Magnetic Resonance Molecular Probes for Hyperpolarized Bioimaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Flower opening is an important phenomenon in plant that indicates the readiness of the flower for pollination leading to petal expansion and pigmentation. This phenomenon has great impact on crop yield, which makes researches of its mechanism attractive for both plant physiology study and agriculture. Gene promoters directing the expression in petal during the petal cell wall modification and expansion when flower opens could be a convenient tool to analyze or monitor gene expression targeting this event. However, there are no reports of isolated gene promoters that can direct gene expression in petal or petal limb during the rapid cell wall dynamics when the flower opens. Xyloglucan endotransglucosylase/hydrolase 7 (XTH7), a cell wall modifying enzyme, was reported having up-regulated gene expression in the petal of Arabidopsis thaliana and Petunia hybrida. In this study, we fused a 1,904 bp length P. hybrida XTH7 promoter with a gene encoding a bright bioluminescent protein (Green enhanced Nano-lantern) to report gene expression and observed petal up-regulated bioluminescence activity by means of a consumer-grade camera. More importantly, this novel promoter demonstrated up-regulated activity in the petal limb of P. hybrida matured flower during flower opening. P. hybrida XTH7 promoter would be a useful tool for flowering study, especially for petal expansion research during flower opening.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Quang", "last_name": "Tran", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Osabe", "name": null }, { "creator_type": "author", "first_name": "Tetsuyuki", "last_name": "Entani", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.5511/plantbiotechnology.21.0130a" }, "pmcid": { "normalized": "PMC8329265" }, "pmid": { "normalized": "34393598" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jun 25", "date_precision": "day", "issue": "2", "normalized_date": "2021-06-25", "pages": "197-204", "proceedings_title": null, "publisher": "", "title": "Plant biotechnology (Tokyo, Japan)", "volume": "38", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "A novel petal up-regulated PhXTH7 promoter analysis in Petunia hybrida by using bioluminescence reporter gene.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Here, we present a comprehensive protocol to analyze the roles of disease-related genes in synaptic transmission. We have developed a pipeline of electrophysiological techniques and combined these with optogenetics in the medial prefrontal cortex of mice. This methodology provides a cost-effective, faster, and easier screening approach to elucidate functional aspects of single genes in several regions in the mouse brain such as a specific layer of the mPFC. For complete details on the use and execution of this protocol, please refer to Nagahama et al. (2020) and Sacai et al. (2020).", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Nagahama", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Fujino", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xpro.2021.100469" }, "pmcid": { "normalized": "PMC8079664" }, "pmid": { "normalized": "33937875" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": true }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Pyramidal Cells", "descriptor_ui": "D017966", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Jun 18", "date_precision": "day", "issue": "2", "normalized_date": "2021-06-18", "pages": "100469", "proceedings_title": null, "publisher": "", "title": "STAR protocols", "volume": "2", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Combining electrophysiology and optogenetics for functional screening of pyramidal neurons in the mouse prefrontal cortex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mechanism that mediates the interaction between the contractile ring and the plasma membrane during cytokinesis remains elusive. We previously found that ERM (Ezrin/Radixin/Moesin) proteins, which usually mediate cellular pole contraction, become over-accumulated at the cell equator and support furrow ingression upon the loss of other actin-membrane associated proteins, anillin and supervillin. In this study, we addressed the molecular basis of the exchangeability between ezrin and other actin-membrane associated proteins in mediating cortical contraction during cytokinesis. We found that depletion of anillin and supervillin caused over-accumulation of the membrane-associated FERM domain and actin-binding C-terminal domain (C-term) of ezrin at the cleavage furrow, respectively. This finding suggests that ezrin differentially shares its binding sites with these proteins on the actin cytoskeleton or inner membrane surface. Using chimeric mutants, we found that ezrin C-term, but not the FERM domain, can substitute for the corresponding anillin domains in cytokinesis and cell proliferation. On the other hand, either the membrane-associated or the actin/myosin-binding domains of anillin could not substitute for the corresponding ezrin domains in controlling cortical blebbing at the cell poles. Our results highlight specific designs of actin- or membrane-associated moieties of different actin-membrane associated proteins with limited exchangeability, which enables them to support diverse cortical activities on the shared actin-membrane interface during cytokinesis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Guang", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Hiruma", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Kinjo", "name": null }, { "creator_type": "author", "first_name": "Mithilesh", "last_name": "Mishra", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.yexcr.2021.112600" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33862101" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cytokinesis", "descriptor_ui": "D048749", "major_topic": false }, { "descriptor": "Cytoskeletal Proteins", "descriptor_ui": "D003598", "major_topic": false }, { "descriptor": "Ezrin", "descriptor_ui": "D000099149", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Microfilament Proteins", "descriptor_ui": "D008840", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun 15", "date_precision": "day", "issue": "2", "normalized_date": "2021-06-15", "pages": "112600", "proceedings_title": null, "publisher": "", "title": "Experimental cell research", "volume": "403", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular basis of functional exchangeability between ezrin and other actin-membrane associated proteins during cytokinesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We designed a new caging group that can be photoactivated only in the presence of a non-endogenous enzyme when exposed to 405 nm light. Because cells or tissues can be genetically tagged by an exogenously expressed enzyme, this novel method can serve as a strategy for adding targeting abilities to photocaged compounds.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Akinobu Z.", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Taichi", "last_name": "Sakano", "name": null }, { "creator_type": "author", "first_name": "Hirona", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Watahiki", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Furuta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d1cc01405f" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34018507" } }, "mesh": [ { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Nucleotides, Cyclic", "descriptor_ui": "D009712", "major_topic": false }, { "descriptor": "Photochemical Processes", "descriptor_ui": "D055668", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun 8", "date_precision": "day", "issue": "46", "normalized_date": "2021-06-08", "pages": "5630-5633", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "57", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Design and synthesis of gene-directed caged cyclic nucleotides exhibiting cell type selectivity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The circadian clock controls daily rhythms of physiological processes. The presence of the clock mechanism throughout the body is hampering its local regulation by small molecules. A photoresponsive clock modulator would enable precise and reversible regulation of circadian rhythms using light as a bio-orthogonal external stimulus. Here we show, through judicious molecular design and state-of-the-art photopharmacological tools, the development of a visible light-responsive inhibitor of casein kinase I (CKI) that controls the period and phase of cellular and tissue circadian rhythms in a reversible manner. The dark isomer of photoswitchable inhibitor 9 exhibits almost identical affinity towards the CKIalpha and CKIdelta isoforms, while upon irradiation it becomes more selective towards CKIdelta, revealing the higher importance of CKIdelta in the period regulation. Our studies enable long-term regulation of CKI activity in cells for multiple days and show the reversible modulation of circadian rhythms with a several hour period and phase change through chronophotopharmacology.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Dusan", "last_name": "Kolarski", "name": null }, { "creator_type": "author", "first_name": "Carla", "last_name": "Miro-Vinyals", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Ashutosh", "last_name": "Srivastava", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Mui", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Itami", "name": null }, { "creator_type": "author", "first_name": "Florence", "last_name": "Tama", "name": null }, { "creator_type": "author", "first_name": "Wiktor", "last_name": "Szymanski", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Ben L.", "last_name": "Feringa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-021-23301-x" }, "pmcid": { "normalized": "PMC8155176" }, "pmid": { "normalized": "34039965" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Casein Kinase Ialpha", "descriptor_ui": "D048128", "major_topic": false }, { "descriptor": "Casein Kinase Idelta", "descriptor_ui": "D048148", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Chronobiology Disorders", "descriptor_ui": "D021081", "major_topic": false }, { "descriptor": "Circadian Clocks", "descriptor_ui": "D057906", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Drug Chronotherapy", "descriptor_ui": "D055870", "major_topic": true }, { "descriptor": "Drug Evaluation, Preclinical", "descriptor_ui": "D004353", "major_topic": false }, { "descriptor": "Enzyme Assays", "descriptor_ui": "D057075", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Molecular Docking Simulation", "descriptor_ui": "D062105", "major_topic": false }, { "descriptor": "Photoperiod", "descriptor_ui": "D017440", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": false }, { "descriptor": "Tissue Culture Techniques", "descriptor_ui": "D046509", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May 26", "date_precision": "day", "issue": "1", "normalized_date": "2021-05-26", "pages": "3164", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Reversible modulation of circadian time with chronophotopharmacology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mammalian brain is highly vulnerable to oxygen deprivation, yet the mechanism underlying the brain's sensitivity to hypoxia is incompletely understood. Hypoxia induces accumulation of hydrogen sulfide, a gas that inhibits mitochondrial respiration. Here, we show that, in mice, rats, and naturally hypoxia-tolerant ground squirrels, the sensitivity of the brain to hypoxia is inversely related to the levels of sulfide:quinone oxidoreductase (SQOR) and the capacity to catabolize sulfide. Silencing SQOR increased the sensitivity of the brain to hypoxia, whereas neuron-specific SQOR expression prevented hypoxia-induced sulfide accumulation, bioenergetic failure, and ischemic brain injury. Excluding SQOR from mitochondria increased sensitivity to hypoxia not only in the brain but also in heart and liver. Pharmacological scavenging of sulfide maintained mitochondrial respiration in hypoxic neurons and made mice resistant to hypoxia. These results illuminate the critical role of sulfide catabolism in energy homeostasis during hypoxia and identify a therapeutic target for ischemic brain injury.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Eizo", "last_name": "Marutani", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Kai", "name": null }, { "creator_type": "author", "first_name": "Robert M. H.", "last_name": "Grange", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Lisa", "last_name": "Traeger", "name": null }, { "creator_type": "author", "first_name": "Aurora", "last_name": "Magliocca", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Daniel R.", "last_name": "Flicker", "name": null }, { "creator_type": "author", "first_name": "Benjamin", "last_name": "Corman", "name": null }, { "creator_type": "author", "first_name": "Naohiro", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Annabelle", "last_name": "Batten", "name": null }, { "creator_type": "author", "first_name": "Rebecca", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takamitsu", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Dmitriy N.", "last_name": "Atochin", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Benjamin A.", "last_name": "Olenchock", "name": null }, { "creator_type": "author", "first_name": "Xinggui", "last_name": "Shen", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Christopher G.", "last_name": "Kevil", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Xian", "name": null }, { "creator_type": "author", "first_name": "Donald B.", "last_name": "Bloch", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Allyson G.", "last_name": "Hindle", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Fumito", "last_name": "Ichinose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-021-23363-x" }, "pmcid": { "normalized": "PMC8149856" }, "pmid": { "normalized": "34035265" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Brain Injuries", "descriptor_ui": "D001930", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": false }, { "descriptor": "Hypoxia", "descriptor_ui": "D000860", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Potential, Mitochondrial", "descriptor_ui": "D053078", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred DBA", "descriptor_ui": "D008811", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "NAD", "descriptor_ui": "D009243", "major_topic": false }, { "descriptor": "Quinone Reductases", "descriptor_ui": "D011808", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May 25", "date_precision": "day", "issue": "1", "normalized_date": "2021-05-25", "pages": "3108", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Sulfide catabolism ameliorates hypoxic brain injury.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Elongated tubular endosomes play essential roles in diverse cellular functions. Multiple molecules have been implicated in tubulation of recycling endosomes, but the mechanism of endosomal tubule biogenesis has remained unclear. In this study, we found that JRAB/MICAL-L2 induces endosomal tubulation via activated Rab8A. In association with Rab8A, JRAB/MICAL-L2 adopts its closed form, which functions in the tubulation of recycling endosomes. Moreover, JRAB/MICAL-L2 induces liquid-liquid phase separation, initiating the formation of tubular recycling endosomes upon overexpression. Between its N-terminal and C-terminal globular domains, JRAB/MICAL-L2 contains an intrinsically disordered region, which contributes to the formation of JRAB/MICAL-L2 condensates. Based on our findings, we propose that JRAB/MICAL-L2 plays two sequential roles in the biogenesis of tubular recycling endosomes: first, JRAB/MICAL-L2 organizes phase separation, and then the closed form of JRAB/MICAL-L2 formed by interaction with Rab8A promotes endosomal tubulation.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ayuko", "last_name": "Sakane", "name": null }, { "creator_type": "author", "first_name": "Taka-Aki", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Uchihashi", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Issei", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Shusaku", "last_name": "Kurisu", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Takei", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Sasaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-021-02080-7" }, "pmcid": { "normalized": "PMC8113518" }, "pmid": { "normalized": "33976349" } }, "mesh": [ { "descriptor": "Cytoskeletal Proteins", "descriptor_ui": "D003598", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": false }, { "descriptor": "Endosomes", "descriptor_ui": "D011992", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microfilament Proteins", "descriptor_ui": "D008840", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "rab GTP-Binding Proteins", "descriptor_ui": "D020691", "major_topic": false }, { "descriptor": "Tight Junctions", "descriptor_ui": "D019108", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May 11", "date_precision": "day", "issue": "1", "normalized_date": "2021-05-11", "pages": "551", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "4", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "JRAB/MICAL-L2 undergoes liquid-liquid phase separation to form tubular recycling endosomes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recently, a new wave of synthetic embryo systems (SESs) has been established from cultured cells for efficient and ethical embryonic development research. We recently reported our epiblast stem cell (EPISC) reprogramming SES that generates numerous blastocyst (BC)-like hemispheres (BCLH) with pluripotent and extraembryonic cell features detected by microscopy. Here, we further explored the system over key time points with single-cell RNA-sequencing analysis. We found broad induction of the 2C-like reporter MERVL and RNA velocities diverging to three major cell populations with gene expression profiles resembling those of pluripotent epiblast, primitive endoderm, and trophectoderm. Enrichment of those three induced BC-like cell fates involved key gene-regulatory networks, zygotic genome activation-related genes, and specific RNA splicing, and many cells closely resembled in silico models. This analysis confirms the induction of extraembryonic cell populations during EPISC reprogramming. We anticipate that our unique BCLH SES and rich dataset may uncover new facets of cell potency, improve developmental biology, and advance biomedicine.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kiichiro", "last_name": "Tomoda", "name": null }, { "creator_type": "author", "first_name": "Haiming", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Hashimita", "last_name": "Sanyal", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null }, { "creator_type": "author", "first_name": "Cody", "last_name": "Kime", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2021.03.016" }, "pmcid": { "normalized": "PMC8185450" }, "pmid": { "normalized": "33891866" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blastocyst", "descriptor_ui": "D001755", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": true }, { "descriptor": "Embryo Implantation", "descriptor_ui": "D010064", "major_topic": true }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Germ Layers", "descriptor_ui": "D005855", "major_topic": false }, { "descriptor": "Leukemia Inhibitory Factor", "descriptor_ui": "D053605", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May 11", "date_precision": "day", "issue": "5", "normalized_date": "2021-05-11", "pages": "1197-1209", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "16", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Reprogramming epiblast stem cells into pre-implantation blastocyst cell-like cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In eukaryotes, histone variant distribution within the genome is the key epigenetic feature. To understand how each histone variant is targeted to the genome, we developed a new method, the RhIP (Reconstituted histone complex Incorporation into chromatin of Permeabilized cell) assay, in which epitope-tagged histone complexes are introduced into permeabilized cells and incorporated into their chromatin. Using this method, we found that H3.1 and H3.3 were incorporated into chromatin in replication-dependent and -independent manners, respectively. We further found that the incorporation of histones H2A and H2A.Z mainly occurred at less condensed chromatin (open), suggesting that condensed chromatin (closed) is a barrier for histone incorporation. To overcome this barrier, H2A, but not H2A.Z, uses a replication-coupled deposition mechanism. Our study revealed that the combination of chromatin structure and DNA replication dictates the differential histone deposition to maintain the epigenetic chromatin states.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Tachiwana", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Dacher", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Seto", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurumizaka", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Saitoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.66290" }, "pmcid": { "normalized": "PMC8110306" }, "pmid": { "normalized": "33970102" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Chromatin Assembly and Disassembly", "descriptor_ui": "D042002", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nucleosomes", "descriptor_ui": "D009707", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May 10", "date_precision": "day", "issue": "", "normalized_date": "2021-05-10", "pages": "e66290", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "10", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Chromatin structure-dependent histone incorporation revealed by a genome-wide deposition assay.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the cerebellum of neonatal mice, multiple climbing fibers (CFs) form excitatory synapses on each Purkinje cell (PC). Only one CF is strengthened in each PC from postnatal day 3 (P3) to P7, whereas the other weaker CFs are eliminated progressively from approximately P7 to approximately P11 (early phase of CF elimination) and from approximately P12 to approximately P17 (late phase of CF elimination). Type 1 metabotropic glutamate receptor (mGluR1) triggers a canonical pathway in PCs for the late phase of CF elimination. Among downstream signaling molecules of mGluR1, phospholipase C beta3 (PLCbeta3) and beta4 (PLCbeta4) are expressed complementarily in PCs of aldolase C (Aldoc)-positive (+) and Aldoc-negative (-) cerebellar compartments, respectively. PLCbeta4 is reported to mediate the late phase of CF elimination in the anterior half of the cerebellar vermis which corresponds to the Aldoc (-) region. However, roles of PLCbeta3 and Aldoc in CF synapse elimination are unknown. Here, we investigated CF innervation of PCs in Aldoc-tdTomato knock-in mice that underwent lentivirus-mediated knockdown (KD) of PLCbeta3 in PCs during postnatal development. By recording CF-mediated excitatory postsynaptic currents from PCs and immunostaining CF synaptic terminals, we found that significantly higher percentage of PCs with PLCbeta3-KD remained multiply innervated by CFs in Aldoc (+) compartments after P12, which was accompanied by impaired elimination of somatic CF synapses and reduced dendritic CF translocation. In contrast, deletion of Aldoc had no effect on CF synapse elimination. These results suggest that PLCbeta3 is required for the late phase of CF elimination in Aldoc (+) PCs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yurie", "last_name": "Rai", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Matsuyama", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuroscience.2020.04.035" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32360594" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Fructose-Bisphosphate Aldolase", "descriptor_ui": "D005634", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nerve Fibers", "descriptor_ui": "D009412", "major_topic": true }, { "descriptor": "Phospholipase C beta", "descriptor_ui": "D054799", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May 10", "date_precision": "day", "issue": "", "normalized_date": "2021-05-10", "pages": "36-43", "proceedings_title": null, "publisher": "", "title": "Neuroscience", "volume": "462", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Phospholipase C beta3 is Required for Climbing Fiber Synapse Elimination in Aldolase C-positive Compartments of the Developing Mouse Cerebellum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dynamic tuning of nanoscale coloration by exploiting localized surface plasmon resonance of gold nanoparticles (AuNPs) combined with an interference coloration mechanism is demonstrated experimentally. When interference between the scattering field from AuNPs and the reflected field from the substrate is observed under back-scattering white-light microscopy, the AuNPs exhibit various colors depending on their distance to the substrate. When the numerical aperture of the microscope objective is optimized, much greater coverage of the color space than was achieved with previously reported plasmon-based approaches is attained. Also, color tunability is examined by exploiting the temperature-induced volume change of a temperature-responsive hydrogel with embedded AuNPs to dynamically modify the distance to the substrate.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Bokusui", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Takahito", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Esashika", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Toshiharu", "last_name": "Saiki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/oe.422564" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33985209" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 May 10", "date_precision": "day", "issue": "10", "normalized_date": "2021-05-10", "pages": "15001-15012", "proceedings_title": null, "publisher": "", "title": "Optics express", "volume": "29", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Interference-based wide-range dynamic tuning of the plasmonic color of single gold nanoparticles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Soichi", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Michisuke", "last_name": "Yuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuroscience.2021.02.028" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33892899" } }, "mesh": [ { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": true }, { "descriptor": "Emotions", "descriptor_ui": "D004644", "major_topic": false }, { "descriptor": "Neurosciences", "descriptor_ui": "D009488", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 May 10", "date_precision": "day", "issue": "", "normalized_date": "2021-05-10", "pages": "1-3", "proceedings_title": null, "publisher": "", "title": "Neuroscience", "volume": "462", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Masao Ito-A Visionary Neuroscientist with a Passion for the Cerebellum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Arginine vasopressin (AVP) is synthesized in parvocellular- and magnocellular neuroendocrine neurons in the paraventricular nucleus (PVN) of the hypothalamus. Whereas magnocellular AVP neurons project primarily to the posterior pituitary, parvocellular AVP neurons project to the median eminence (ME) and to extrahypothalamic areas. The AVP gene encodes pre-pro-AVP that comprises the signal peptide, AVP, neurophysin (NPII), and a copeptin glycopeptide. In the present study, we used an N-terminal copeptin antiserum to examine copeptin expression in magnocellular and parvocellular neurons in the hypothalamus in the mouse, rat, and macaque monkey. Although magnocellular NPII-expressing neurons exhibited strong N-terminal copeptin immunoreactivity in all three species, a great majority (~90%) of parvocellular neurons that expressed NPII was devoid of copeptin immunoreactivity in the mouse, and in approximately half (~53%) of them in the rat, whereas in monkey hypothalamus, virtually all NPII-immunoreactive parvocellular neurons contained strong copeptin immunoreactivity. Immunoelectron microscopy in the mouse clearly showed copeptin-immunoreactivity co-localized with NPII-immunoreactivity in neurosecretory vesicles in the internal layer of the ME and posterior pituitary, but not in the external layer of the ME. Intracerebroventricular administration of a prohormone convertase inhibitor, hexa-d-arginine amide resulted in a marked reduction of copeptin-immunoreactivity in the NPII-immunoreactive magnocellular PVN neurons in the mouse, suggesting that low protease activity and incomplete processing of pro-AVP could explain the disproportionally low levels of N-terminal copeptin expression in rodent AVP (NPII)-expressing parvocellular neurons. Physiologic and phylogenetic aspects of copeptin expression among neuroendocrine neurons require further exploration.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Natsuko", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Otubo", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Maejima", "name": null }, { "creator_type": "author", "first_name": "Ashraf H.", "last_name": "Talukder", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Oti", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Takanami", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Itoi", "name": null }, { "creator_type": "author", "first_name": "John F.", "last_name": "Morris", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cne.25026" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32892351" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glycopeptides", "descriptor_ui": "D006020", "major_topic": false }, { "descriptor": "Macaca", "descriptor_ui": "D008251", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Paraventricular Hypothalamic Nucleus", "descriptor_ui": "D010286", "major_topic": false }, { "descriptor": "Protein Precursors", "descriptor_ui": "D011498", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Vasopressins", "descriptor_ui": "D014667", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May 1", "date_precision": "day", "issue": "7", "normalized_date": "2021-05-01", "pages": "1372-1390", "proceedings_title": null, "publisher": "", "title": "The Journal of comparative neurology", "volume": "529", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Variation of pro-vasopressin processing in parvocellular and magnocellular neurons in the paraventricular nucleus of the hypothalamus: Evidence from the vasopressin-related glycopeptide copeptin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Host-microbe interactions orchestrate skin homeostasis, the dysregulation of which has been implicated in chronic inflammatory conditions such as atopic dermatitis and psoriasis. Here, we show that Staphylococcus cohnii is a skin commensal capable of beneficially inhibiting skin inflammation. We find that Tmem79(-/-) mice spontaneously develop interleukin-17 (IL-17)-producing T-cell-driven skin inflammation. Comparative skin microbiome analysis reveals that the disease activity index is negatively associated with S. cohnii. Inoculation with S. cohnii strains isolated from either mouse or human skin microbiota significantly prevents and ameliorates dermatitis in Tmem79(-/-) mice without affecting pathobiont burden. S. cohnii colonization is accompanied by activation of host glucocorticoid-related pathways and induction of anti-inflammatory genes in the skin and is therefore effective at suppressing inflammation in diverse pathobiont-independent dermatitis models, including chemically induced, type 17, and type 2 immune-driven models. As such, S. cohnii strains have great potential as effective live biotherapeutics for skin inflammation.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Youxian", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Tanoue", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Ashwin N.", "last_name": "Skelly", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Okahashi", "name": null }, { "creator_type": "author", "first_name": "Eiichiro", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Shiohama", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Kurokawa", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Hachiro", "last_name": "Iseki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Iwakura", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Shiota", "name": null }, { "creator_type": "author", "first_name": "Liansheng", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Junzo", "last_name": "Hisatsune", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Koseki", "name": null }, { "creator_type": "author", "first_name": "Motoyuki", "last_name": "Sugai", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Ohara", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null }, { "creator_type": "author", "first_name": "Masahira", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Atarashi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Amagai", "name": null }, { "creator_type": "author", "first_name": "Kenya", "last_name": "Honda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2021.109052" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33910010" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Staphylococcus", "descriptor_ui": "D013210", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr 27", "date_precision": "day", "issue": "4", "normalized_date": "2021-04-27", "pages": "109052", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "35", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Staphylococcus cohnii is a potentially biotherapeutic skin commensal alleviating skin inflammation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herpes simplex virus 1 (HSV-1) replicates its genome and packages it into capsids within the nucleus. HSV-1 has evolved a complex mechanism of nuclear egress whereby nascent capsids bud on the inner nuclear membrane to form perinuclear virions that subsequently fuse with the outer nuclear membrane, releasing capsids into the cytosol. The viral-encoded nuclear egress complex (NEC) plays a crucial role in this vesicle-mediated nucleocytoplasmic transport. Nevertheless, similar system mediates the movement of other cellular macromolecular complexes in normal cells. Therefore, HSV-1 may utilize viral proteins to hijack the cellular machinery in order to facilitate capsid transport. However, little is known about the molecular mechanisms underlying this phenomenon. This review summarizes our current understanding of the cellular and viral factors involved in the nuclear egress of HSV-1 capsids.", "classifications": [ { "id": "19H05417", "label": "19H05417", "researcher": "Jun Arii", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/v13050754" }, "pmcid": { "normalized": "PMC8146395" }, "pmid": { "normalized": "33923040" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Host-Pathogen Interactions", "descriptor_ui": "D054884", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Transport Vesicles", "descriptor_ui": "D022161", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virus Release", "descriptor_ui": "D057074", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Apr 25", "date_precision": "day", "issue": "5", "normalized_date": "2021-04-25", "pages": "754", "proceedings_title": null, "publisher": "", "title": "Viruses", "volume": "13", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Host and Viral Factors Involved in Nuclear Egress of Herpes Simplex Virus 1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the mammalian cerebral neocortex, different regions have different cytoarchitecture, neuronal birthdates, and functions. In most regions, neuronal migratory profiles are speculated similar based on observations using thymidine analogs. Few reports have investigated regional migratory differences from mitosis at the ventricular surface. In this study, we applied FlashTag technology, in which dyes are injected intraventricularly, to describe migratory profiles. We revealed a mediolateral regional difference in the migratory profiles of neurons that is dependent on developmental stage; for example, neurons labeled at embryonic day 12.5-15.5 reached their destination earlier dorsomedially than dorsolaterally, even where there were underlying ventricular surfaces, reflecting sojourning below the subplate. This difference was hardly recapitulated by thymidine analogs, which visualize neurogenic gradients, suggesting a biological significance different from the neurogenic gradient. These observations advance our understanding of cortical development and the power of FlashTag in studying migration and are thus resources for future neurodevelopmental studies.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yoshinaga", "name": null }, { "creator_type": "author", "first_name": "Minkyung", "last_name": "Shin", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Kitazawa", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Tanuma", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichiro", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Nakajima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2021.102277" }, "pmcid": { "normalized": "PMC8022222" }, "pmid": { "normalized": "33851097" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Apr 23", "date_precision": "day", "issue": "4", "normalized_date": "2021-04-23", "pages": "102277", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "24", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Comprehensive characterization of migration profiles of murine cerebral cortical neurons during development using FlashTag labeling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Induced pluripotent stem cells (iPSCs) are capable of providing an unlimited source of cells from all three germ layers and germ cells. The derivation and usage of iPSCs from various animal models may facilitate stem cell-based therapy, gene-modified animal production, and evolutionary studies assessing interspecies differences. However, there is a lack of species-wide methods for deriving iPSCs, in particular by means of non-viral and non-transgene-integrating (NTI) approaches. Here, we demonstrate the iPSC derivation from somatic fibroblasts of multiple mammalian species from three different taxonomic orders, including the common marmoset (Callithrix jacchus) in Primates, the dog (Canis lupus familiaris) in Carnivora, and the pig (Sus scrofa) in Cetartiodactyla, by combinatorial usage of chemical compounds and NTI episomal vectors. Interestingly, the fibroblasts temporarily acquired a neural stem cell-like state during the reprogramming. Collectively, our method, robustly applicable to various species, holds a great potential for facilitating stem cell-based research using various animals in Mammalia.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sho", "last_name": "Yoshimatsu", "name": null }, { "creator_type": "author", "first_name": "Mayutaka", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Aozora", "last_name": "Iguchi", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Sanosaka", "name": null }, { "creator_type": "author", "first_name": "Tsukika", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Ryusuke", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Okahara", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Noce", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Erika", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Rudiger", "last_name": "Behr", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Edamura", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Shiozawa", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2021.03.002" }, "pmcid": { "normalized": "PMC8072067" }, "pmid": { "normalized": "33798453" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Callithrix", "descriptor_ui": "D002144", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": false }, { "descriptor": "Germ Layers", "descriptor_ui": "D005855", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "RNA-Seq", "descriptor_ui": "D000081246", "major_topic": false }, { "descriptor": "Species Specificity", "descriptor_ui": "D013045", "major_topic": false }, { "descriptor": "Swine", "descriptor_ui": "D013552", "major_topic": false }, { "descriptor": "Transgenes", "descriptor_ui": "D019076", "major_topic": true }, { "descriptor": "Viruses", "descriptor_ui": "D014780", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr 13", "date_precision": "day", "issue": "4", "normalized_date": "2021-04-13", "pages": "754-770", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "16", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Non-viral Induction of Transgene-free iPSCs from Somatic Fibroblasts of Multiple Mammalian Species.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hematopoietic stem cells (HSCs) in adult bone marrow (BM) are usually maintained in a state of quiescence. The cellular mechanism coordinating the balance between HSC quiescence and differentiation is not fully understood. Here, we report that galactose-binding lectin-3 (galectin-3; Gal-3) is upregulated by Tie2 or Mpl activation to maintain quiescence. Conditional overexpression of Gal-3 in mouse HSCs under the transcriptional control of Tie2 or Vav1 promoters (Gal-3 Tg) causes cell cycle retardation via induction of p21. Conversely, the cell cycle of long-term repopulating HSCs (LT-HSCs) in Gal-3-deficient (Gal-3(-/-)) mice is accelerated, resulting in their exhaustion. Mechanistically, Gal-3 regulates p21 transcription by forming a complex with Sp1, thus blocking cell cycle entry. These results demonstrate that Gal-3 is a negative regulator of cell-cycling in HSCs and plays a crucial role in adult hematopoiesis to prevent HSC exhaustion.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Weizhen", "last_name": "Jia", "name": null }, { "creator_type": "author", "first_name": "Lingyu", "last_name": "Kong", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Han-Yun", "last_name": "Hsieh", "name": null }, { "creator_type": "author", "first_name": "Daishi", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Daniel K.", "last_name": "Hsu", "name": null }, { "creator_type": "author", "first_name": "Fu-Tong", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-021-22346-2" }, "pmcid": { "normalized": "PMC8035175" }, "pmid": { "normalized": "33837181" } }, "mesh": [ { "descriptor": "Adult Stem Cells", "descriptor_ui": "D053687", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p21", "descriptor_ui": "D050759", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Galectin 3", "descriptor_ui": "D037502", "major_topic": false }, { "descriptor": "Hematopoiesis", "descriptor_ui": "D006410", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Models, Animal", "descriptor_ui": "D023421", "major_topic": false }, { "descriptor": "Receptor, TIE-2", "descriptor_ui": "D042787", "major_topic": false }, { "descriptor": "Receptors, Thrombopoietin", "descriptor_ui": "D053628", "major_topic": false }, { "descriptor": "Sp1 Transcription Factor", "descriptor_ui": "D016329", "major_topic": false }, { "descriptor": "Transcriptional Activation", "descriptor_ui": "D015533", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr 9", "date_precision": "day", "issue": "1", "normalized_date": "2021-04-09", "pages": "2118", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Indispensable role of Galectin-3 in promoting quiescence of hematopoietic stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Most patients with coronavirus disease 2019 (COVID-19) experience asymptomatic disease or mild symptoms, but some have critical symptoms requiring intensive care. It is important to determine how patients with asymptomatic or mild COVID-19 react to severe acute respiratory syndrome coronavirus 2 infection and suppress virus spread. Innate immunity is important for evasion from the first virus attack, and it may play an important role in the pathogenesis in these patients. We measured serum cytokine levels in 95 patients with COVID-19 during the infection's acute phase and report that significantly higher interleukin 12 and 2 levels were induced in patients with asymptomatic or mild disease than in those with moderate or severe disease, indicating the key roles of these cytokines in the pathogenesis of asymptomatic or mild COVID-19.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Lidya Handayani", "last_name": "Tjan", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Kiriu", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Sachiyo", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/infdis/jiab005" }, "pmcid": { "normalized": "PMC7928883" }, "pmid": { "normalized": "33411935" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Asymptomatic Infections", "descriptor_ui": "D058345", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": false }, { "descriptor": "COVID-19 Nucleic Acid Testing", "descriptor_ui": "D000087123", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Healthy Volunteers", "descriptor_ui": "D064368", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": true }, { "descriptor": "Interleukin-12", "descriptor_ui": "D018664", "major_topic": false }, { "descriptor": "Interleukin-2", "descriptor_ui": "D007376", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "RNA, Viral", "descriptor_ui": "D012367", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false }, { "descriptor": "Severity of Illness Index", "descriptor_ui": "D012720", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr 8", "date_precision": "day", "issue": "7", "normalized_date": "2021-04-08", "pages": "1145-1149", "proceedings_title": null, "publisher": "", "title": "The Journal of infectious diseases", "volume": "223", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Early Differences in Cytokine Production by Severity of Coronavirus Disease 2019.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Different dynamics of gene expression are observed during cell differentiation. In T cells, genes that are turned on early or turned off and stay off have been thoroughly studied. However, genes that are initially turned off but then turned on again after stimulation has ceased have not been defined; they are obviously important, especially in the context of acute versus chronic inflammation. Using the Th1/Th2 differentiation paradigm, we found that the Cxxc1 subunit of the Trithorax complex directs transcription of genes initially down-regulated by TCR stimulation but up-regulated again in a later phase. The late up-regulation of these genes was impaired either by prolonged TCR stimulation or Cxxc1 deficiency, which led to decreased expression of Trib3 and Klf2 in Th1 and Th2 cells, respectively. Loss of Cxxc1 resulted in enhanced pathogenicity in allergic airway inflammation in vivo. Thus, Cxxc1 plays essential roles in the establishment of a proper CD4+ T cell immune system via epigenetic control of a specific set of genes.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Kiuchi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Onodera", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Kokubo", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Eto", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Koseki", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Hirahara", "name": null }, { "creator_type": "author", "first_name": "Toshinori", "last_name": "Nakayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1084/jem.20201690" }, "pmcid": { "normalized": "PMC7808308" }, "pmid": { "normalized": "33433611" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CD4-Positive T-Lymphocytes", "descriptor_ui": "D015496", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": false }, { "descriptor": "Kruppel-Like Transcription Factors", "descriptor_ui": "D051741", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false }, { "descriptor": "Respiratory Hypersensitivity", "descriptor_ui": "D012130", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Th1 Cells", "descriptor_ui": "D018417", "major_topic": false }, { "descriptor": "Th2 Cells", "descriptor_ui": "D018418", "major_topic": false }, { "descriptor": "Trans-Activators", "descriptor_ui": "D015534", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr 5", "date_precision": "day", "issue": "4", "normalized_date": "2021-04-05", "pages": "e20201690", "proceedings_title": null, "publisher": "", "title": "The Journal of experimental medicine", "volume": "218", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "The Cxxc1 subunit of the Trithorax complex directs epigenetic licensing of CD4+ T cell differentiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Proteoglycans (PGs) are one of the main components in the extracellular matrix of the central nervous system. Chondroitin sulfate (CS) is a glycosaminoglycan (GAG), which is composed of major PGs. Similar to keratin sulfate (KS), another GAG, CS inhibits axon regeneration. However, the influence of these GAGs on the pathogenicity of neuroimmunological diseases is unclear. Here, we induced experimental autoimmune encephalomyelitis (EAE) in mice lacking CS N-acetylgalactosaminyltransferase-1 (CSGalNAcT1-KO), an important enzyme for CS synthesis. In our study, CSGalNAcT1-KO mice showed milder EAE symptoms than those in wild-type (WT) mice. The recall response of antigen-specific lymphocytes showed that CSGalNAcT1-KO-derived lymphocytes had a milder cell proliferation response than that in WT-derived lymphocytes. These results suggest that CS contributes toward the induction phase of EAE. We previously performed EAE experiments in GlcNAc-6-O-sulfotransferase KO (GlcNAc6ST-KO) and C6ST1-KO mice, which had reduced KS and reduced CS-C, respectively. EAE in CSGalNAcT1-KO mice was more similar to that in GlcNAc6ST-KO mice than in C6ST1-KO mice. In conclusion, the distinct GAG sugar chains are associated with severe or mild phenotypes of EAE and are therefore potential new therapeutic targets for neuroimmunological diseases, including multiple sclerosis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Rino", "last_name": "Inada", "name": null }, { "creator_type": "author", "first_name": "Katsuichi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Moriguchi", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kadomatsu", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Kusunoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/glycob/cwaa072" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32839819" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Chondroitin Sulfates", "descriptor_ui": "D002809", "major_topic": false }, { "descriptor": "Encephalomyelitis, Autoimmune, Experimental", "descriptor_ui": "D004681", "major_topic": false }, { "descriptor": "Lymphocytes", "descriptor_ui": "D008214", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "N-Acetylgalactosaminyltransferases", "descriptor_ui": "D017350", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr 1", "date_precision": "day", "issue": "3", "normalized_date": "2021-04-01", "pages": "260-265", "proceedings_title": null, "publisher": "", "title": "Glycobiology", "volume": "31", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Chondroitin sulfate N-acetylgalactosyltransferase-1 knockout shows milder phenotype in experimental autoimmune encephalomyelitis than in wild type.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cladoceran crustacean Daphnia has long been a model of energy allocation studies due to its important position in the trophic cascade of freshwater ecosystems. However, the loci for controlling energy allocation between life history traits still remain unknown. Here, we report CRISPR/Cas-mediated target mutagenesis of DNA methyltransferase 3.1 (DNMT3.1) that is upregulated in response to caloric restriction in Daphnia magna. The resulting biallelic mutant is viable and did not show any change in growth rate, reproduction, and longevity under nutrient rich conditions. In contrast, under starved conditions, the growth rate of this DNMT3.1 mutant was increased but its reproduction was reciprocally reduced compared to the wild type when the growth and reproduction activities competed during a period from instar 4 to 8. The life span of this mutant was significantly shorter than that of the wild type. We also compared transcriptomes between DNMT3.1 mutant and wild type under nutrient-rich and starved conditions. Consistent with the DNMT3.1 mutant phenotypes, the starved condition led to changes in the transcriptomes of the mutant including differential expression of vitellogenin genes. In addition, we found upregulation of the I am not dead yet (INDY) ortholog, which has been known to shorten the life span in Drosophila, explaining the shorter life span of the DNMT3.1 mutant. These results establish DNMT3.1 as a key regulator for life span and energy allocation between growth and reproduction during caloric restriction. Our findings reveal how energy allocation is implemented by selective expression of a DNMT3 ortholog that is widely distributed among animals. We also infer a previously unidentified adaptation of Daphnia that invests more energy for reproduction than growth under starved conditions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Nhan Duc", "last_name": "Nguyen", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-86578-4" }, "pmcid": { "normalized": "PMC8016896" }, "pmid": { "normalized": "33795753" } }, "mesh": [ { "descriptor": "Adaptation, Physiological", "descriptor_ui": "D000222", "major_topic": false }, { "descriptor": "Alleles", "descriptor_ui": "D000483", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Size", "descriptor_ui": "D049628", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "DNA (Cytosine-5-)-Methyltransferases", "descriptor_ui": "D004248", "major_topic": false }, { "descriptor": "DNA Methyltransferase 3A", "descriptor_ui": "D000090205", "major_topic": false }, { "descriptor": "Food Deprivation", "descriptor_ui": "D005508", "major_topic": true }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Life History Traits", "descriptor_ui": "D000071421", "major_topic": false }, { "descriptor": "Longevity", "descriptor_ui": "D008136", "major_topic": true }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false }, { "descriptor": "Molecular Biology", "descriptor_ui": "D008967", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Reproduction", "descriptor_ui": "D012098", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "RNA-Seq", "descriptor_ui": "D000081246", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false }, { "descriptor": "Vitellogenins", "descriptor_ui": "D014819", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr 1", "date_precision": "day", "issue": "1", "normalized_date": "2021-04-01", "pages": "7326", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "DNMT3.1 controls trade-offs between growth, reproduction, and life span under starved conditions in Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Male penis is required to become erect during copulation. In the upper (dorsal) part of penis, the erectile tissue termed corpus cavernosum (CC) plays fundamental roles for erection by regulating the inner blood flow. When blood flows into the CC, the microvascular complex termed sinusoidal space is reported to expand during erection. A novel in vitro explant system to analyze the dynamic erectile responses during contraction/relaxation is established. The current data show regulatory contraction/relaxation processes induced by phenylephrine (PE) and nitric oxide (NO) donor mimicking dynamic erectile responses by in vitro CC explants. Two-photon excitation microscopy (TPEM) observation shows the synchronous movement of sinusoidal space and the entire CC. By taking advantages of the CC explant system, tadalafil (Cialis) was shown to increase sinusoidal relaxation. Histopathological changes have been generally reported associating with erection in several pathological conditions. Various stressed statuses have been suggested to occur in the erectile responses by previous studies. The current CC explant model enables to analyze such conditions through directly manipulating CC in the repeated contraction/relaxation processes. Expression of oxidative stress marker and contraction-related genes, Hypoxia-inducible factor 1-alpha (Hif1a), glutathione peroxidase 1 (Gpx1), Ras homolog family member A (RhoA), and Rho-associated protein kinase (Rock), was significantly increased in such repeated contraction/relaxation. Altogether, it is suggested that the system is valuable for analyzing structural changes and physiological responses to several regulators in the field of penile medicine.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daiki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null }, { "creator_type": "author", "first_name": "Hisao", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Taiju", "last_name": "Hyuga", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Yoshiki", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kuroki", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Morioka", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/biolre/ioab011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33511393" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Erectile Dysfunction", "descriptor_ui": "D007172", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Organ Culture Techniques", "descriptor_ui": "D009924", "major_topic": false }, { "descriptor": "Penile Erection", "descriptor_ui": "D010410", "major_topic": false }, { "descriptor": "Penis", "descriptor_ui": "D010413", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr 1", "date_precision": "day", "issue": "4", "normalized_date": "2021-04-01", "pages": "875-886", "proceedings_title": null, "publisher": "", "title": "Biology of reproduction", "volume": "104", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic erectile responses of a novel penile organ model utilizing TPEMdagger.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Acquired immune reaction is initiated by dendritic cells (DCs), which present Ags to a few naive Ag-specific T cells. Deregulation of gene expression in DCs may alter the outcome of the immune response toward immunodeficiency and/or autoimmune diseases. Expression of TRIM28, a nuclear protein that mediates gene silencing through heterochromatin, decreased in DCs from old mice, suggesting alteration of gene regulation. Mice specifically lacking TRIM28 in DCs show increased DC population in the spleen and enhanced T cell priming toward inflammatory effector T cells, leading to acceleration and exacerbation in experimental autoimmune encephalomyelitis. TRIM28-deficient DCs were found to ectopically transcribe endogenous retrovirus (ERV) elements. Combined genome-wide analysis revealed a strong colocalization among the decreased repressive histone mark H3K9me3-transcribed ERV elements and the derepressed host genes that were related to inflammation in TRIM28-deficient DCs. This suggests that TRIM28 occupancy of ERV elements critically represses expression of proximal inflammatory genes on the genome. We propose that gene silencing through repressive histone modification by TRIM28 plays a role in maintaining the integrity of precise gene regulation in DCs, which prevents aberrant T cell priming to inflammatory effector T cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "So", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Mahoko Takahashi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Hodaka", "last_name": "Hayabuchi", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Tokifuji", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Kanayama", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Arase", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.4049/jimmunol.2001003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33619215" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Encephalomyelitis, Autoimmune, Experimental", "descriptor_ui": "D004681", "major_topic": false }, { "descriptor": "Endogenous Retroviruses", "descriptor_ui": "D020077", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Gene Silencing", "descriptor_ui": "D020868", "major_topic": false }, { "descriptor": "Heterochromatin", "descriptor_ui": "D006570", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Multiple Sclerosis", "descriptor_ui": "D009103", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false }, { "descriptor": "Tripartite Motif-Containing Protein 28", "descriptor_ui": "D000076183", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr 1", "date_precision": "day", "issue": "7", "normalized_date": "2021-04-01", "pages": "1528-1539", "proceedings_title": null, "publisher": "", "title": "Journal of immunology (Baltimore, Md. : 1950)", "volume": "206", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "TRIM28 Expression on Dendritic Cells Prevents Excessive T Cell Priming by Silencing Endogenous Retrovirus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Oxytocin is produced in the hypothalamus and stimulates uterine contraction and milk ejection. While many people consider oxytocin to be a female hormone, it is reported that, in men, the plasma oxytocin level increases markedly after ejaculation. However, this aspect of oxytocin physiology is poorly understood. The spinal ejaculation generator (SEG), which expresses the neuropeptide, gastrin-releasing peptide (GRP), can trigger ejaculation in rats. Therefore, we focused on systemic effects of oxytocin on the GRP/SEG neuron system in the lumbar spinal cord controlling sexual activity in male rats. We found that systemic administration of oxytocin significantly shortened the latency to the first mount, intromission and ejaculation during male copulatory behavior. In addition, the local oxytocin level in the lumbar cord was significantly higher in males than in females. Histological analysis showed that oxytocin-binding is apparent in spinal GRP/SEG neurons. We therefore conclude that oxytocin influences male sexual activity via the SEG.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Oti", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/19420889.2021.1902056" }, "pmcid": { "normalized": "PMC8009111" }, "pmid": { "normalized": "33828638" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Mar 29", "date_precision": "day", "issue": "1", "normalized_date": "2021-03-29", "pages": "55-60", "proceedings_title": null, "publisher": "", "title": "Communicative & integrative biology", "volume": "14", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Systemic effects of oxytocin on male sexual activity via the spinal ejaculation generator in rats.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The spinal ejaculation generator (SEG) is located in the central gray (lamina X) of the rat lumbar spinal cord and plays a pivotal role in the ejaculatory reflex. We recently reported that SEG neurons express the oxytocin receptor and are activated by oxytocin projections from the paraventricular nucleus of hypothalamus (PVH). However, it is unknown whether the SEG responds to oxytocin in vivo. In this study, we analyzed the characteristics of the brain-spinal cord neural circuit that controls male sexual function using a newly developed in vivo electrophysiological technique. Optogenetic stimulation of the PVH of rats expressing channel rhodopsin under the oxytocin receptor promoter increased the spontaneous firing of most lamina X SEG neurons. This is the first demonstration of the in vivo electrical response from the deeper (lamina X) neurons in the spinal cord. Furthermore, we succeeded in the in vivo whole-cell recordings of lamina X neurons. In vivo whole-cell recordings may reveal the features of lamina X SEG neurons, including differences in neurotransmitters and response to stimulation. Taken together, these results suggest that in vivo electrophysiological stimulation can elucidate the neurophysiological response of a variety of spinal neurons during male sexual behavior.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Uta", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Oti", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms22073400" }, "pmcid": { "normalized": "PMC8036474" }, "pmid": { "normalized": "33810239" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Channelrhodopsins", "descriptor_ui": "D000075402", "major_topic": false }, { "descriptor": "Ejaculation", "descriptor_ui": "D004542", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Oxytocin", "descriptor_ui": "D010121", "major_topic": false }, { "descriptor": "Paraventricular Hypothalamic Nucleus", "descriptor_ui": "D010286", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Reflex", "descriptor_ui": "D012018", "major_topic": false }, { "descriptor": "Spinal Cord Ventral Horn", "descriptor_ui": "D066151", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar 26", "date_precision": "day", "issue": "7", "normalized_date": "2021-03-26", "pages": "3400", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "22", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "In Vivo Electrophysiology of Peptidergic Neurons in Deep Layers of the Lumbar Spinal Cord after Optogenetic Stimulation of Hypothalamic Paraventricular Oxytocin Neurons in Rats.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bilirubin in human blood is highly important as a general index of one's physical condition because its concentration changes under the influence of several diseases. In particular, in newborns, jaundice is one of the most common diseases involving unconjugated bilirubin (UCBR), causing serious symptoms such as nuclear jaundice and deafness. Therefore, a frequent measurement of the UCBR levels in the blood is important. Here, we report a ratiometric bioluminescent indicator, BABI (bilirubin assessment with a bioluminescent indicator), that changes the emission color from blue to green depending on the UCBR concentration in a sample. Owing to the use of a bioluminescence signal that has a higher signal-to-noise ratio than the absorption and fluorescence signal, BABI enables highly sensitive and quantitative detection of UCBR for small blood samples using a smartphone camera. The establishment of a UCBR measurement assay using BABI provides the possibility of a simple and rapid method for blood-based diagnosis using bioluminescent indicators and a versatile mobile device.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukino", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Tetsuichi", "last_name": "Wazawa", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acssensors.0c02000" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33443410" } }, "mesh": [ { "descriptor": "Bilirubin", "descriptor_ui": "D001663", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infant, Newborn", "descriptor_ui": "D007231", "major_topic": false }, { "descriptor": "Smartphone", "descriptor_ui": "D000068997", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Mar 26", "date_precision": "day", "issue": "3", "normalized_date": "2021-03-26", "pages": "889-895", "proceedings_title": null, "publisher": "", "title": "ACS sensors", "volume": "6", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Ratiometric Bioluminescent Indicator for Simple and Rapid Diagnosis of Bilirubin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The translocator protein (TSPO) has been identified as a positron emission tomography (PET)-visible biomarker of inflammation and promising immunotherapeutic target for the treatment of Alzheimer's disease (AD). While TSPO ligands have been shown to reduce the accumulation of the toxic Alzheimer's beta-amyloid peptide, their effect on tau pathology has not yet been investigated. To address this, we analyzed the effects of TSPO ligand, Ro5-4864, on the progression of neuropathology in rTg4510 tau transgenic mice (TauTg). METHODS: Brain atrophy, tau accumulation, and neuroinflammation were assessed longitudinally using volumetric magnetic resonance imaging, tau-PET, and TSPO-PET, respectively. In vivo neuroimaging results were confirmed by immunohistochemistry for markers of neuronal survival (NeuN), tauopathy (AT8), and inflammation (TSPO, ionized calcium-binding adaptor molecule 1 or IBA-1, and complement component 1q or C1q) in brain sections from scanned mice. RESULTS: TSPO ligand treatment attenuated brain atrophy and hippocampal neuronal loss in the absence of any detected effect on tau depositions. Atrophy and neuronal loss were strongly associated with in vivo inflammatory signals measured by TSPO-PET, IBA-1, and levels of C1q, a regulator of the complement cascade. In vitro studies confirmed that the TSPO ligand Ro5-4864 reduces C1q expression in a microglial cell line in response to inflammation, reduction of which has been shown in previous studies to protect synapses and neurons in models of tauopathy. CONCLUSIONS: These findings support a protective role for TSPO ligands in tauopathy, reducing neuroinflammation, neurodegeneration, and brain atrophy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Lauren H.", "last_name": "Fairley", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Ichio", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Bin", "last_name": "Ji", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Anna M.", "last_name": "Barron", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12974-021-02122-1" }, "pmcid": { "normalized": "PMC7980620" }, "pmid": { "normalized": "33740987" } }, "mesh": [ { "descriptor": "Amyloid beta-Protein Precursor", "descriptor_ui": "D016564", "major_topic": false }, { "descriptor": "Atrophy", "descriptor_ui": "D001284", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Neuroprotective Agents", "descriptor_ui": "D018696", "major_topic": false }, { "descriptor": "Positron-Emission Tomography", "descriptor_ui": "D049268", "major_topic": false }, { "descriptor": "Receptors, GABA", "descriptor_ui": "D018079", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar 19", "date_precision": "day", "issue": "1", "normalized_date": "2021-03-19", "pages": "76", "proceedings_title": null, "publisher": "", "title": "Journal of neuroinflammation", "volume": "18", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Neuroprotective effect of mitochondrial translocator protein ligand in a mouse model of tauopathy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This protocol uses Nr4a1-GFP Nr4a3-Tocky mice to study T cell receptor (TCR) signaling using flow cytometry. It identifies the optimal mouse transgenic status and fluorochromes compatible with the dual reporter. This protocol has applications in TCR signaling, and we outline how to obtain high-quality datasets. It is not compatible with cellular fixation, and cells should be analyzed immediately after staining. For complete details on the use and execution of this protocol, please refer to Jennings et al., 2020.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Emma K.", "last_name": "Jennings", "name": null }, { "creator_type": "author", "first_name": "David A. J.", "last_name": "Lecky", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Bending", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xpro.2020.100284" }, "pmcid": { "normalized": "PMC7821036" }, "pmid": { "normalized": "33532733" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nuclear Receptor Subfamily 4, Group A, Member 1", "descriptor_ui": "D057105", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar 19", "date_precision": "day", "issue": "1", "normalized_date": "2021-03-19", "pages": "100284", "proceedings_title": null, "publisher": "", "title": "STAR protocols", "volume": "2", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Application of dual Nr4a1-GFP Nr4a3-Tocky reporter mice to study T cell receptor signaling by flow cytometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Adult-born neurons (ABNs) in the dentate gyrus bestow unique cellular plasticity to the mammalian brain. We recently found that the activity of ABNs during sleep is necessary for memory consolidation. Here, we describe our method for Ca(2+) imaging of ABN activity using a miniaturized fluorescent microscope and sleep recordings. As preparatory surgery and post-recording data processing can be major obstacles, we provide detailed descriptions and problem-solving tips. For complete details on the use and execution of this protocol, please refer to Kumar et al. (2020).", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Alvaro", "last_name": "Carrier-Ruiz", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugaya", "name": null }, { "creator_type": "author", "first_name": "Deependra", "last_name": "Kumar", "name": null }, { "creator_type": "author", "first_name": "Pablo", "last_name": "Vergara", "name": null }, { "creator_type": "author", "first_name": "Iyo", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Sakthivel", "last_name": "Srinivasan", "name": null }, { "creator_type": "author", "first_name": "Toshie", "last_name": "Naoi", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Sakaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xpro.2020.100238" }, "pmcid": { "normalized": "PMC7797924" }, "pmid": { "normalized": "33458703" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Dentate Gyrus", "descriptor_ui": "D018891", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Intravital Microscopy", "descriptor_ui": "D000069416", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar 19", "date_precision": "day", "issue": "1", "normalized_date": "2021-03-19", "pages": "100238", "proceedings_title": null, "publisher": "", "title": "STAR protocols", "volume": "2", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Calcium imaging of adult-born neurons in freely moving mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by core symptoms of impaired social behavior and communication. Recent studies have suggested that the oxytocin system, which regulates social behavior in mammals, is potentially involved in ASD. Mouse models of ASD provide a useful system for understanding the associations between an impaired oxytocin system and social behavior deficits. However, limited studies have shown the involvement of the oxytocin system in the behavioral phenotypes in mouse models of ASD. We have previously demonstrated that a mouse model that carries the ASD patient-derived de novo mutation in the pogo transposable element derived with zinc finger domain (POGZ(WT/Q1038R) mice), showed ASD-like social behavioral deficits. Here, we have explored whether oxytocin (OXT) administration improves impaired social behavior in POGZ(WT/Q1038R) mice and found that intranasal oxytocin administration effectively restored the impaired social behavior in POGZ(WT/Q1038R) mice. We also found that the expression level of the oxytocin receptor gene (OXTR) was low in POGZ(WT/Q1038R) mice. However, we did not detect significant changes in the number of OXT-expressing neurons between the paraventricular nucleus of POGZ(WT/Q1038R) mice and that of WT mice. A chromatin immunoprecipitation assay revealed that POGZ binds to the promoter region of OXTR and is involved in the transcriptional regulation of OXTR. In summary, our study demonstrate that the pathogenic mutation in the POGZ, a high-confidence ASD gene, impairs the oxytocin system and social behavior in mice, providing insights into the development of oxytocin-based therapeutics for ASD.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kohei", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Momoka", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13041-021-00769-8" }, "pmcid": { "normalized": "PMC7962304" }, "pmid": { "normalized": "33726803" } }, "mesh": [ { "descriptor": "Administration, Intranasal", "descriptor_ui": "D000281", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autism Spectrum Disorder", "descriptor_ui": "D000067877", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutation, Missense", "descriptor_ui": "D020125", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Oxytocin", "descriptor_ui": "D010121", "major_topic": false }, { "descriptor": "Point Mutation", "descriptor_ui": "D017354", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Receptors, Oxytocin", "descriptor_ui": "D018045", "major_topic": false }, { "descriptor": "Receptors, Vasopressin", "descriptor_ui": "D017483", "major_topic": false }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": true }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false }, { "descriptor": "Transposases", "descriptor_ui": "D019895", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar 16", "date_precision": "day", "issue": "1", "normalized_date": "2021-03-16", "pages": "56", "proceedings_title": null, "publisher": "", "title": "Molecular brain", "volume": "14", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Intranasal oxytocin administration ameliorates social behavioral deficits in a POGZ(WT/Q1038R) mouse model of autism spectrum disorder.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During the developmental processes of embryos, cells undergo massive deformation and division that are regulated by mechanical cues. However, little is known about how embryonic cells change their mechanical properties during different cleavage stages. Here, using atomic force microscopy, we investigated the stiffness of cells in ascidian embryos from the fertilised egg to the stage before gastrulation. In both animal and vegetal hemispheres, we observed a Rho kinase (ROCK)-independent cell stiffening that the cell stiffness exhibited a remarkable increase at the timing of cell division where cortical actin filaments were organized. Furthermore, in the vegetal hemisphere, we observed another mechanical behaviour, i.e., a ROCK-associated cell stiffening, which was retained even after cell division or occurred without division and propagated sequentially toward adjacent cells, displaying a characteristic cell-to-cell mechanical variation. The results indicate that the mechanical properties of embryonic cells are regulated at the single cell level in different germ layers.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "contributor", "first_name": "Yuki", "last_name": "Fujii", "name": null }, { "creator_type": "contributor", "first_name": "Wataru C.", "last_name": "Koizumi", "name": null }, { "creator_type": "contributor", "first_name": "Taichi", "last_name": "Imai", "name": null }, { "creator_type": "contributor", "first_name": "Megumi", "last_name": "Yokobori", "name": null }, { "creator_type": "contributor", "first_name": "Tomohiro", "last_name": "Matsuo", "name": null }, { "creator_type": "contributor", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "contributor", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "contributor", "first_name": "Takaharu", "last_name": "Okajima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-021-01869-w" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Mar 16", "date_precision": "day", "issue": "", "normalized_date": "2021-03-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "", "volume": "4", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatiotemporal dynamics of single cell stiffness in the early developing ascidian chordate embryo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Histone variants (HVs) are a subfamily of epigenetic regulators implicated in embryonic development, but their role in human stem cell fate remains unclear. Here, we reveal that the phosphorylation state of the HV H2A.X (gammaH2A.X) regulates self-renewal and differentiation of human pluripotent stem cells (hPSCs) and leukemic progenitors. As demonstrated by CRISPR-Cas deletion, H2A.X is essential in maintaining normal hPSC behavior. However, reduced levels of gammaH2A.X enhances hPSC differentiation toward the hematopoietic lineage with concomitant inhibition of neural development. In contrast, activation and sustained levels of phosphorylated H2A.X enhance hPSC neural fate while suppressing hematopoiesis. This controlled lineage bias correlates to occupancy of gammaH2A.X at genomic loci associated with ectoderm versus mesoderm specification. Finally, drug modulation of H2A.X phosphorylation overcomes differentiation block of patient-derived leukemic progenitors. Our study demonstrates HVs may serve to regulate pluripotent cell fate and that this biology could be extended to somatic cancer stem cell control.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Luca", "last_name": "Orlando", "name": null }, { "creator_type": "author", "first_name": "Borko", "last_name": "Tanasijevic", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Jennifer C.", "last_name": "Reid", "name": null }, { "creator_type": "author", "first_name": "Juan L.", "last_name": "Garcia-Rodriguez", "name": null }, { "creator_type": "author", "first_name": "Kapil Dev", "last_name": "Chauhan", "name": null }, { "creator_type": "author", "first_name": "Deanna P.", "last_name": "Porras", "name": null }, { "creator_type": "author", "first_name": "Lili", "last_name": "Aslostovar", "name": null }, { "creator_type": "author", "first_name": "Justin D.", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Zoya", "last_name": "Shapovalova", "name": null }, { "creator_type": "author", "first_name": "Ryan R.", "last_name": "Mitchell", "name": null }, { "creator_type": "author", "first_name": "Allison L.", "last_name": "Boyd", "name": null }, { "creator_type": "author", "first_name": "Mickie", "last_name": "Bhatia", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2021.108818" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33691101" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cell Self Renewal", "descriptor_ui": "D000066673", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Ectoderm", "descriptor_ui": "D004475", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia, Myeloid, Acute", "descriptor_ui": "D015470", "major_topic": false }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Nucleosomes", "descriptor_ui": "D009707", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar 9", "date_precision": "day", "issue": "10", "normalized_date": "2021-03-09", "pages": "108818", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "34", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Phosphorylation state of the histone variant H2A.X controls human stem and progenitor cell fate decisions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A notable example of spiral architecture in organs is the mammalian cochlear duct, where the morphology is critical for hearing function. Genetic studies have revealed necessary signaling molecules, but it remains unclear how cellular dynamics generate elongating, bending, and coiling of the cochlear duct. Here, we show that extracellular signal-regulated kinase (ERK) activation waves control collective cell migration during the murine cochlear duct development using deep tissue live-cell imaging, Forster resonance energy transfer (FRET)-based quantitation, and mathematical modeling. Long-term FRET imaging reveals that helical ERK activation propagates from the apex duct tip concomitant with the reverse multicellular flow on the lateral side of the developing cochlear duct, resulting in advection-based duct elongation. Moreover, model simulations, together with experiments, explain that the oscillatory wave trains of ERK activity and the cell flow are generated by mechanochemical feedback. Our findings propose a regulatory mechanism to coordinate the multicellular behaviors underlying the duct elongation during development.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mamoru", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Tateya", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.61092" }, "pmcid": { "normalized": "PMC7935486" }, "pmid": { "normalized": "33667159" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Cochlear Duct", "descriptor_ui": "D003053", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar 5", "date_precision": "day", "issue": "", "normalized_date": "2021-03-05", "pages": "e61092", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "10", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Retrograde ERK activation waves drive base-to-apex multicellular flow in murine cochlear duct morphogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The ever-growing demand for fluorogenic dyes usable in the rapid construction of analyte-responsive fluorescent probes, has recently contributed to a revival of interest in the chemistry of diketopyrrolopyrrole (DPP) pigments. In this context, we have explored the potential of symmetrical and unsymmetrical DPP derivatives bearing two or one 4-pyridyl substituents acting as optically tunable group(s). The unique fluorogenic behavior of these molecules, closely linked to N-substitution/charge state of their pyridine unit (i.e., neutral pyridine or cationic pyridinium), has been used to design DPP-based fluorescent probes for detection of hypoxia-related redox enzymes and penicillin G acylase (PGA). In this paper, we describe synthesis, spectral characterization and bioanalytical validations of these probes. Dramatic differences in terms of aqueous stability and enzymatic fluorescence activation were observed. This systematic study enables to delineate the scope of application of pyridine-flanked DPP fluorophores in the field of enzyme biosensing.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Sebastien", "last_name": "Jenni", "name": null }, { "creator_type": "author", "first_name": "Flavien", "last_name": "Ponsot", "name": null }, { "creator_type": "author", "first_name": "Pierre", "last_name": "Baroux", "name": null }, { "creator_type": "author", "first_name": "Lucile", "last_name": "Collard", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ikeno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Valentin", "last_name": "Quesneau", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Renault", "name": null }, { "creator_type": "author", "first_name": "Anthony", "last_name": "Romieu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.saa.2020.119179" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33248891" } }, "mesh": [ { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Ketones", "descriptor_ui": "D007659", "major_topic": false }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false }, { "descriptor": "Pyrroles", "descriptor_ui": "D011758", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Mar 5", "date_precision": "day", "issue": "", "normalized_date": "2021-03-05", "pages": "119179", "proceedings_title": null, "publisher": "", "title": "Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy", "volume": "248", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Design, synthesis and evaluation of enzyme-responsive fluorogenic probes based on pyridine-flanked diketopyrrolopyrrole dyes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Marine invertebrate larvae are known to begin metamorphosis in response to environmentally derived cues. However, little is known about the relationships between the perception of such cues and internal signalling for metamorphosis. To elucidate the mechanism underlying the initiation of metamorphosis in the ascidian, Ciona intestinalis type A (Ciona robusta), we artificially induced ascidian metamorphosis and investigated Ca(2+) dynamics from pre- to post-metamorphosis. Ca(2+) transients were observed and consisted of two temporally distinct phases with different durations before tail regression which is the early event of metamorphosis. In the first phase, Phase I, the Ca(2+) transient in the papillae (adhesive organ of the anterior trunk) was coupled with the Ca(2+) transient in dorsally localized cells and endoderm cells just after mechanical stimulation. The Ca(2+) transients in Phase I were also observed when applying only short stimulation. In the second phase, Phase II, the Ca(2+) transient in papillae was observed again and lasted for approximately 5-11 min just after the Ca(2+) transient in Phase I continued for a few minutes. The impaired papillae by Foxg-knockdown failed to induce the second Ca(2+) transient in Phase II and tail regression. In Phase II, a wave-like Ca(2+) propagation was also observed across the entire epidermis. Our results indicate that the papillae sense a mechanical cue and two-round Ca(2+) transients in papillae transmits the internal metamorphic signals to different tissues, which subsequently induces tail regression. Our study will help elucidate the internal mechanism of metamorphosis in marine invertebrate larvae in response to environmental cues.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Maiki K.", "last_name": "Wakai", "name": null }, { "creator_type": "author", "first_name": "Mitsuru J.", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1098/rspb.2020.3207" }, "pmcid": { "normalized": "PMC7935057" }, "pmid": { "normalized": "33593191" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": true }, { "descriptor": "Epidermis", "descriptor_ui": "D004817", "major_topic": false }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": false }, { "descriptor": "Metamorphosis, Biological", "descriptor_ui": "D008675", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 24", "date_precision": "day", "issue": "1945", "normalized_date": "2021-02-24", "pages": "20203207", "proceedings_title": null, "publisher": "", "title": "Proceedings. Biological sciences", "volume": "288", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Two-Round Ca(2+) transient in papillae by mechanical stimulation induces metamorphosis in the ascidian Ciona intestinalis type A.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cyclic peptides (CPs) have attracted attention as next-generation drugs because they possess both cell-permeable potential as small molecules and specific affinity similar to antibodies. As intracellular molecules are important targets of CPs, quantitation of the intracellular retention and transmembrane permeability of CPs is necessary for drug development. However, permeated CPs within cells cannot be directly assessed by conventional permeability assays using methods such as artificial membranes and cell monolayers. Here, we propose a new approach using single-cell cytoplasm mass spectrometry (SCC-MS). After cells were incubated with CPs, the cytoplasm was directly collected from a single cell using a microneedle followed by nanoelectrospray ionization mass spectrometry detection of the CPs. The height of the CP peak was plotted against time and fitted with a simple function, y = a(1 – e–bx), to calculate the apparent permeability coefficient (Papp) for both the influx and efflux directions. MCF-7 cells were selected as model cancer cells and cultured with cyclosporin A (CsA) and its demethylated analogs (dmCsA-1, -2, and -3) as model CPs. Papp values (10–6 cm/s) obtained from cells incubated with 50 μM CPs ranged from 0.017 to 0.121 for influx and 0.20 to 1.48 for efflux. The higher efflux ratio was possibly caused by efflux transporters such as P-glycoprotein, a well-known receptor of CsA. The equilibrated intracellular concentration of CPs was estimated to be as low as 4.1–6.8 μM, which showed good consistency with the high efflux ratio. SCC-MS is promising as a reliable permeability assay for next-generation CP-based pharmaceuticals.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takayuki", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Mihara", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Ohkubo", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Asami", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.0c03901" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2021-02-23", "date_precision": "day", "issue": "7", "normalized_date": "2021-02-23", "pages": "3370-3377", "proceedings_title": null, "publisher": "American Chemical Society", "title": "Analytical Chemistry", "volume": "93", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitation of Cell Membrane Permeability of Cyclic Peptides by Single-Cell Cytoplasm Mass Spectrometry", "url": "https://doi.org/10.1021/acs.analchem.0c03901", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown. METHODS: The current study explored metabolites representing the molecular mechanisms of oxytocin's efficacy using high-throughput metabolomics analysis on plasma collected before and after 6-week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N = 106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial. RESULTS: Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (false discovery rate (FDR) corrected P = 0.043, d = 0.74, N = 83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (PFDR = 0.004, d = 1.13, N = 60). The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (PFDR = 0.006, r = - 0.485, N = 43) and deteriorations between 2 and 4 weeks (PFDR = 0.032, r = 0.415, N = 37). LIMITATIONS: The metabolites changes caused by oxytocin administration were quantified using peripheral blood and therefore may not directly reflect central nervous system changes. CONCLUSION: Our findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-methyl-D-aspartate receptor and neural plasticity to the time-course change in oxytocin's efficacy. TRIAL REGISTRATION: A multi-center, parallel-group, placebo-controlled, double-blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders (the date registered: 30 October 2014; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703 ) (UMIN000015264).", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Munesue", "name": null }, { "creator_type": "author", "first_name": "Seico", "last_name": "Benner", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Walid", "last_name": "Yassin", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Eriguchi", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Kameno", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Kiyoto", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Kosaka", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Yamasue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13229-021-00423-z" }, "pmcid": { "normalized": "PMC7903697" }, "pmid": { "normalized": "33622389" } }, "mesh": [ { "descriptor": "Administration, Intranasal", "descriptor_ui": "D000281", "major_topic": false }, { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Autistic Disorder", "descriptor_ui": "D001321", "major_topic": false }, { "descriptor": "Double-Blind Method", "descriptor_ui": "D004311", "major_topic": false }, { "descriptor": "Facial Expression", "descriptor_ui": "D005149", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Oxytocin", "descriptor_ui": "D010121", "major_topic": false }, { "descriptor": "Sarcosine", "descriptor_ui": "D012521", "major_topic": false }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 23", "date_precision": "day", "issue": "1", "normalized_date": "2021-02-23", "pages": "15", "proceedings_title": null, "publisher": "", "title": "Molecular autism", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "C. elegans spe-9 class genes encode sperm proteins with indispensable roles during fertilization. We have previously reported that spe-45 belongs to the spe-9 class, based on the finding that self-sperm of spe-45(tm3715) hermaphrodites were not consumed by fertilization. In this study, we directly observed live fertilization in the spermatheca of fem-1(hc17) females after mating with spe-45(tm3715) males. As expected, it was clearly shown that spe-45 mutant spermatozoa failed to fuse with the oocyte plasma membrane. Thus, our live imaging system for C. elegans fertilization seems to be useful for evaluation of the functions of male and female gametes.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Tajima", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Nishimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.17912/micropub.biology.000372" }, "pmcid": { "normalized": "PMC7900825" }, "pmid": { "normalized": "33644705" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Feb 21", "date_precision": "day", "issue": "", "normalized_date": "2021-02-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "microPublication biology", "volume": "2021", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "C. elegans spermatozoa lacking spe-45 are incapable of fusing with the oocyte plasma membrane.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The somatic haploidy is unstable in diplontic animals, but cellular processes determining haploid stability remain elusive. Here, we found that inhibition of mevalonate pathway by pitavastatin, a widely used cholesterol-lowering drug, drastically destabilized the haploid state in HAP1 cells. Interestingly, cholesterol supplementation did not restore haploid stability in pitavastatin-treated cells, and cholesterol inhibitor U18666A did not phenocopy haploid destabilization. These results ruled out the involvement of cholesterol in haploid stability. Besides cholesterol perturbation, pitavastatin induced endoplasmic reticulum (ER) stress, the suppression of which by a chemical chaperon significantly restored haploid stability in pitavastatin-treated cells. Our data demonstrate the involvement of the mevalonate pathway in the stability of the haploid state in human somatic cells through managing ER stress, highlighting a novel link between ploidy and ER homeostatic control.Key words: haploid, ER stress, Mevalonate pathway.", "classifications": [ { "id": "19H05413", "label": "19H05413", "researcher": "Ryota Uehara", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kan", "last_name": "Yaguchi", "name": null }, { "creator_type": "author", "first_name": "Kimino", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Koya", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Yuyama", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Gabor", "last_name": "Banhegyi", "name": null }, { "creator_type": "author", "first_name": "Eva", "last_name": "Margittai", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1247/csf.20055" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33361684" } }, "mesh": [ { "descriptor": "Cholesterol", "descriptor_ui": "D002784", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": true }, { "descriptor": "Endoplasmic Reticulum Stress", "descriptor_ui": "D059865", "major_topic": true }, { "descriptor": "Haploidy", "descriptor_ui": "D006238", "major_topic": true }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mevalonic Acid", "descriptor_ui": "D008798", "major_topic": true }, { "descriptor": "Quinolines", "descriptor_ui": "D011804", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 19", "date_precision": "day", "issue": "1", "normalized_date": "2021-02-19", "pages": "1-9", "proceedings_title": null, "publisher": "", "title": "Cell structure and function", "volume": "46", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Mevalonate Pathway-mediated ER Homeostasis Is Required for Haploid Stability in Human Somatic Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A new type of thiol probes based on the meso-vinyl-BODIPY (VB) scaffold were developed. The monochloro-substituted VB1Cl exhibited the largest fluorescence enhancement (>200-fold) as well as high selectivity upon biological thiol sensing. VB1Cl was successfully applied for reporting the protein unfolding process under ER stress in living cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Huiying", "last_name": "Mu", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Otsuka", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d0cc08160d" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33480929" } }, "mesh": [ { "descriptor": "Boron Compounds", "descriptor_ui": "D001896", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Protein Folding", "descriptor_ui": "D017510", "major_topic": true }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 19", "date_precision": "day", "issue": "14", "normalized_date": "2021-02-19", "pages": "1818-1821", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "57", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Substituted meso-vinyl-BODIPY as thiol-selective fluorogenic probes for sensing unfolded proteins in the endoplasmic reticulum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Collective cell migration is a fundamental process in embryonic development and tissue homeostasis. This is a macroscopic population-level phenomenon that emerges across hierarchy from microscopic cell-cell interactions; however, the underlying mechanism remains unclear. Here, we addressed this issue by focusing on epithelial collective cell migration, driven by the mechanical force regulated by chemical signals of traveling ERK activation waves, observed in wound healing. We propose a hierarchical mathematical framework for understanding how cells are orchestrated through mechanochemical cell-cell interaction. In this framework, we mathematically transformed a particle-based model at the cellular level into a continuum model at the tissue level. The continuum model described relationships between cell migration and mechanochemical variables, namely, ERK activity gradients, cell density, and velocity field, which could be compared with live-cell imaging data. Through numerical simulations, the continuum model recapitulated the ERK wave-induced collective cell migration in wound healing. We also numerically confirmed a consistency between these two models. Thus, our hierarchical approach offers a new theoretical platform to reveal a causality between macroscopic tissue-level and microscopic cellular-level phenomena. Furthermore, our model is also capable of deriving a theoretical insight on both of mechanical and chemical signals, in the causality of tissue and cellular dynamics.", "classifications": [ { "id": "19H05438", "label": "19H05438", "researcher": "Yohei Kondo", "type": "grant" }, { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Asakura", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Honda", "last_name": "Naoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-83396-6" }, "pmcid": { "normalized": "PMC7892579" }, "pmid": { "normalized": "33603023" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Wound Healing", "descriptor_ui": "D014945", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 18", "date_precision": "day", "issue": "1", "normalized_date": "2021-02-18", "pages": "4069", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [ "ssbd-database-000231" ], "repository": [ "ssbd-repos-000231" ] }, "title": "Hierarchical modeling of mechano-chemical dynamics of epithelial sheets across cells and tissue.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Oocyte quality decreases with aging, thereby increasing errors in fertilization, chromosome segregation, and embryonic cleavage. Oocyte appearance also changes with aging, suggesting a functional relationship between oocyte quality and appearance. However, no methods are available to objectively quantify age-associated changes in oocyte appearance. RESULTS: We show that statistical image processing of Nomarski differential interference contrast microscopy images can be used to quantify age-associated changes in oocyte appearance in the nematode Caenorhabditis elegans. Max-min value (mean difference between the maximum and minimum intensities within each moving window) quantitatively characterized the difference in oocyte cytoplasmic texture between 1- and 3-day-old adults (Day 1 and Day 3 oocytes, respectively). With an appropriate parameter set, the gray level co-occurrence matrix (GLCM)-based texture feature Correlation (COR) more sensitively characterized this difference than the Max-min Value. Manipulating the smoothness of and/or adding irregular structures to the cytoplasmic texture of Day 1 oocyte images reproduced the difference in Max-min Value but not in COR between Day 1 and Day 3 oocytes. Increasing the size of granules in synthetic images recapitulated the age-associated changes in COR. Manual measurements validated that the cytoplasmic granules in oocytes become larger with aging. CONCLUSIONS: The Max-min value and COR objectively quantify age-related changes in C. elegans oocyte in Nomarski DIC microscopy images. Our methods provide new opportunities for understanding the mechanism underlying oocyte aging.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Momoko", "last_name": "Imakubo", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Hatsumi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12859-021-03990-3" }, "pmcid": { "normalized": "PMC7890843" }, "pmid": { "normalized": "33596821" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": true }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": false }, { "descriptor": "Chromosome Segregation", "descriptor_ui": "D020090", "major_topic": false }, { "descriptor": "Oocytes", "descriptor_ui": "D009865", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 17", "date_precision": "day", "issue": "1", "normalized_date": "2021-02-17", "pages": "73", "proceedings_title": null, "publisher": "", "title": "BMC bioinformatics", "volume": "22", "year": 2021 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000158" ] }, "title": "Statistical image processing quantifies the changes in cytoplasmic texture associated with aging in Caenorhabditis elegans oocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human induced pluripotent stem cells (iPSCs) have great potential to elucidate the molecular pathogenesis of neurological/psychiatric diseases. In particular, neurological/psychiatric diseases often display brain region-specific symptoms, and the technology for generating region-specific neural cells from iPSCs has been established for detailed modeling of neurological/psychiatric disease phenotypes in vitro. On the other hand, recent advances in culturing human iPSCs without feeder cells have enabled highly efficient and reproducible neural induction. However, conventional regional control technologies have mainly been developed based on on-feeder iPSCs, and these methods are difficult to apply to feeder-free (ff) iPSC cultures. In this study, we established a novel culture system to generate region-specific neural cells from human ff-iPSCs. This system is the best optimized approach for feeder-free iPSC culture and generates specific neuronal subtypes with high purity and functionality, including forebrain cortical neurons, forebrain interneurons, midbrain dopaminergic neurons, and spinal motor neurons. In addition, the temporal patterning of cortical neuron layer specification in the forebrain was reproduced in our culture system, which enables the generation of layer-specific cortical neurons. Neuronal activity was demonstrated in the present culture system by using multiple electrode array and calcium imaging. Collectively, our ff-iPSC-based culture system would provide a desirable platform for modeling various types of neurological/psychiatric disease phenotypes.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tsukika", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neulet.2021.135676" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33516803" } }, "mesh": [ { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 16", "date_precision": "day", "issue": "", "normalized_date": "2021-02-16", "pages": "135676", "proceedings_title": null, "publisher": "", "title": "Neuroscience letters", "volume": "746", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of region-specific and high-purity neurons from human feeder-free iPSCs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/cid/ciaa694" }, "pmcid": { "normalized": "PMC7314194" }, "pmid": { "normalized": "32474577" } }, "mesh": [ { "descriptor": "Communicable Diseases", "descriptor_ui": "D003141", "major_topic": true }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Health Facilities", "descriptor_ui": "D006268", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 16", "date_precision": "day", "issue": "4", "normalized_date": "2021-02-16", "pages": "723-724", "proceedings_title": null, "publisher": "", "title": "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America", "volume": "72", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Diligent Medical Activities of a Publicly Designated Medical Institution for Infectious Diseases Pave the Way for Overcoming COVID-19: A Positive Message to People Working at the Cutting Edge.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The aberrant expression of dopamine receptors (DRDs) in acute myeloid leukemia (AML) cells has encouraged the repurposing of DRD antagonists such as thioridazine (TDZ) as anti-leukemic agents. Here, we access patient cells from a Phase I dose escalation trial to resolve the cellular and molecular bases of response to TDZ, and we extend these findings to an additional independent cohort of AML patient samples tested preclinically. We reveal that in DRD2(+) AML patients, DRD signaling in leukemic progenitors provides leukemia-exclusive networks of sensitivity that spare healthy hematopoiesis. AML progenitor cell suppression can be increased by the isolation of the positive enantiomer from the racemic TDZ mixture (TDZ(+)), and this is accompanied by reduced cardiac liability. Our study indicates that the development of DRD-directed therapies provides a targeting strategy for a subset of AML patients and potentially other cancers that acquire DRD expression upon transformation from healthy tissue.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Lili", "last_name": "Aslostovar", "name": null }, { "creator_type": "author", "first_name": "Allison L.", "last_name": "Boyd", "name": null }, { "creator_type": "author", "first_name": "Yannick D.", "last_name": "Benoit", "name": null }, { "creator_type": "author", "first_name": "Justin", "last_name": "Di Lu", "name": null }, { "creator_type": "author", "first_name": "Juan Luis", "last_name": "Garcia Rodriguez", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Deanna P.", "last_name": "Porras", "name": null }, { "creator_type": "author", "first_name": "Jennifer C.", "last_name": "Reid", "name": null }, { "creator_type": "author", "first_name": "Ryan R.", "last_name": "Mitchell", "name": null }, { "creator_type": "author", "first_name": "Brian", "last_name": "Leber", "name": null }, { "creator_type": "author", "first_name": "Anargyros", "last_name": "Xenocostas", "name": null }, { "creator_type": "author", "first_name": "Ronan", "last_name": "Foley", "name": null }, { "creator_type": "author", "first_name": "Mickie", "last_name": "Bhatia", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xcrm.2021.100202" }, "pmcid": { "normalized": "PMC7897800" }, "pmid": { "normalized": "33665638" } }, "mesh": [ { "descriptor": "Hematopoiesis", "descriptor_ui": "D006410", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia, Myeloid, Acute", "descriptor_ui": "D015470", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Receptors, Dopamine", "descriptor_ui": "D011954", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Thioridazine", "descriptor_ui": "D013881", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 16", "date_precision": "day", "issue": "2", "normalized_date": "2021-02-16", "pages": "100202", "proceedings_title": null, "publisher": "", "title": "Cell reports. Medicine", "volume": "2", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Abnormal dopamine receptor signaling allows selective therapeutic targeting of neoplastic progenitors in AML patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the pineal organ of zebrafish larvae, the bistable opsin parapinopsin alone generates color opponency between UV and visible light. Our previous study suggested that dark inactivation of the parapinopsin photoproduct, which activates G-proteins, is important for the regulation of the amount of the photoproduct. In turn, the photoproduct is responsible for visible light sensitivity in color opponency. Here, we found that an opsin kinase or a G-protein-coupled receptor kinase (GRK) is involved in inactivation of the active photoproduct of parapinopsin in the pineal photoreceptor cells of zebrafish larvae. We investigated inactivation of the photoproduct in the parapinopsin cells of various knockdown larvae by measuring the light responses of the cells using calcium imaging. We found that GRK7a knockdown slowed recovery of the response of parapinopsin photoreceptor cells, whereas GRK1b knockdown or GRK7b knockdown did not have a remarkable effect, suggesting that GRK7a, a cone-type GRK, is mainly responsible for inactivation of the parapinopsin photoproduct in zebrafish larvae. We also observed a similar knockdown effect on the response of the parapinopsin photoreceptor cells of mutant larvae expressing the opsin SWS1, a UV-sensitive cone opsin, instead of parapinopsin, suggesting that the parapinopsin photoproduct was inactivated in a way similar to that described for cone opsins. We confirmed the immunohistochemical distribution of GRK7a in parapinopsin photoreceptor cells by comparing the immunoreactivity to GRK7 in GRK7a-knockdown and control larvae. These findings suggest that in pineal photoreceptor cells, the cone opsin kinase GRK7a contributes greatly to the inactivation of parapinopsin, which underlies pineal color opponency.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Baoguo", "last_name": "Shen", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Nishioka", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Kawano-Yamashita", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s40851-021-00171-1" }, "pmcid": { "normalized": "PMC7881645" }, "pmid": { "normalized": "33579376" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Feb 12", "date_precision": "day", "issue": "1", "normalized_date": "2021-02-12", "pages": "1", "proceedings_title": null, "publisher": "", "title": "Zoological letters", "volume": "7", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Functional identification of an opsin kinase underlying inactivation of the pineal bistable opsin parapinopsin in zebrafish.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Macrophage recognition and phagocytosis of crystals is critical for the associated fibrosis and cancer. Of note, multi-walled carbon nanotubes (MWCNTs), the highly representative products of nanotechnology, induce macrophage NLRP3 inflammasome activation and cause asbestosis-like pathogenesis. However, it remains largely unknown how macrophages efficiently recognize MWCNTs on their cell surfaces. Here, we identify by a targeted screening of phagocyte receptors the phosphatidylserine receptors T cell immunoglobulin mucin 4 (Tim4) and Tim1 as the pattern-recognition receptors for carbon crystals. Docking simulation studies reveal spatiotemporally stable interfaces between aromatic residues in the extracellular IgV domain of Tim4 and one-dimensional carbon crystals. Further, CRISPR-Cas9-mediated deletion of Tim4 and Tim1 reveals that Tim4, but not Tim1, critically contributes to the recognition of MWCNTs by peritoneal macrophages and to granuloma development in a mouse model of direct mesothelium exposure to MWCNTs. These results suggest that Tim4 recognizes MWCNTs through aromatic interactions and mediates phagocytosis leading to granulomas.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Omori", "name": null }, { "creator_type": "author", "first_name": "Misato", "last_name": "Tsugita", "name": null }, { "creator_type": "author", "first_name": "Yasuto", "last_name": "Hoshikawa", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Qilin", "last_name": "Xie", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Noyori", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Ayato", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Saitoh", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Toyokuni", "name": null }, { "creator_type": "author", "first_name": "Hisaya", "last_name": "Akiba", "name": null }, { "creator_type": "author", "first_name": "Shigekazu", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Nakayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2021.108734" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33567275" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Granuloma", "descriptor_ui": "D006099", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Macrophages, Peritoneal", "descriptor_ui": "D017737", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Nanotubes, Carbon", "descriptor_ui": "D037742", "major_topic": true }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "Phagocytosis", "descriptor_ui": "D010587", "major_topic": true }, { "descriptor": "THP-1 Cells", "descriptor_ui": "D000074084", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 9", "date_precision": "day", "issue": "6", "normalized_date": "2021-02-09", "pages": "108734", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "34", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Tim4 recognizes carbon nanotubes and mediates phagocytosis leading to granuloma formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Many enzymes involved in photosynthesis possess highly conserved cysteine residues that serve as redox switches in chloroplasts. These redox switches function to activate or deactivate enzymes during light-dark transitions and have the function of fine-tuning their activities according to the intensity of light. Accordingly, many studies on chloroplast redox regulation have been conducted under the hypothesis that \"fine regulation of the activities of these enzymes is crucial for efficient photosynthesis.\" However, the impact of the regulatory system on plant metabolism is still unclear. To test this hypothesis, we here studied the impact of the ablation of a redox switch in chloroplast NADP-malate dehydrogenase (MDH). By genome editing, we generated a mutant plant whose MDH lacks one of its redox switches and is active even in dark conditions. Although NADPH consumption by MDH in the dark is expected to be harmful to plant growth, the mutant line did not show any phenotypic differences under standard long-day conditions. In contrast, the mutant line showed severe growth retardation under short-day or fluctuating light conditions. These results indicate that thiol-switch redox regulation of MDH activity is crucial for maintaining NADPH homeostasis in chloroplasts under these conditions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuichi", "last_name": "Yokochi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Florian", "last_name": "Hahn", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Kawai-Yamada", "name": null }, { "creator_type": "author", "first_name": "Andreas P. M.", "last_name": "Weber", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2016903118" }, "pmcid": { "normalized": "PMC8017969" }, "pmid": { "normalized": "33531363" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Chloroplasts", "descriptor_ui": "D002736", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Embryophyta", "descriptor_ui": "D019669", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Malate Dehydrogenase (NADP+)", "descriptor_ui": "D050538", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Photosynthesis", "descriptor_ui": "D010788", "major_topic": false }, { "descriptor": "Thioredoxins", "descriptor_ui": "D013879", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 9", "date_precision": "day", "issue": "6", "normalized_date": "2021-02-09", "pages": "e2016903118", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "118", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Redox regulation of NADP-malate dehydrogenase is vital for land plants under fluctuating light environment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Optogenetic approaches for studying neuronal functions have proven their utility in the neurosciences. However, optogenetic tools capable of inducing synaptic plasticity at the level of single synapses have been lacking. Here, we engineered a photoactivatable (pa)CaMKII by fusing a light-sensitive domain, LOV2, to CaMKIIalpha. Blue light or two-photon excitation reversibly activated paCaMKII. Activation in single spines was sufficient to induce structural long-term potentiation (sLTP) in vitro and in vivo. paCaMKII activation was also sufficient for the recruitment of AMPA receptors and functional LTP in single spines. By combining paCaMKII with protein activity imaging by 2-photon FLIM-FRET, we demonstrate that paCaMKII activation in clustered spines induces robust sLTP via a mechanism that involves the actin-regulatory small GTPase, Cdc42. This optogenetic tool for dissecting the function of CaMKII activation (i.e., the sufficiency of CaMKII rather than necessity) and for manipulating synaptic plasticity will find many applications in neuroscience and other fields.", "classifications": [ { "id": "19H05434", "label": "19H05434", "researcher": "Hideji Murakoshi", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akihiro C. E.", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Hiromi H.", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Eto", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Onda", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tatsuko", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Nabekura", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-021-21025-6" }, "pmcid": { "normalized": "PMC7854602" }, "pmid": { "normalized": "33531495" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinase Type 2", "descriptor_ui": "D054732", "major_topic": false }, { "descriptor": "Electrophysiology", "descriptor_ui": "D004594", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Long-Term Potentiation", "descriptor_ui": "D017774", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Receptors, AMPA", "descriptor_ui": "D018091", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 2", "date_precision": "day", "issue": "1", "normalized_date": "2021-02-02", "pages": "751", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Photoactivatable CaMKII induces synaptic plasticity in single synapses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Patients with coronavirus disease 2019 (COVID-19) exhibit a wide clinical spectrum ranging from mild respiratory symptoms to critical and fatal diseases, and older individuals are known to be more severely affected. The underlying mechanism of this phenomenon is unknown. A neutralizing antibody against viruses is known to be important to eliminate the virus. In addition, this antibody is induced at high levels in patients with severe COVID-19, followed by a termination of virus replication. Severe COVID-19 patients exhibit high levels of cytokines/chemokines, even after the disappearance of the virus. This indicates that cytokines/chemokines play significant roles in disease severity. These findings also suggest that antiviral therapy (monoclonal antibody and/or convalescent plasma therapy) should be administered early to eliminate the virus, followed by steroid treatment after viral genome disappearance, especially in patients with severe symptoms.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Lidya Handayani", "last_name": "Tjan", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Sayo", "last_name": "Fujinaka", "name": null }, { "creator_type": "author", "first_name": "Sachiyo", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Tohma", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.31662/jmaj.2020-0083" }, "pmcid": { "normalized": "PMC7872782" }, "pmid": { "normalized": "33575497" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jan 29", "date_precision": "day", "issue": "1", "normalized_date": "2021-01-29", "pages": "1-7", "proceedings_title": null, "publisher": "", "title": "JMA journal", "volume": "4", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "The Neutralizing Antibody Response against Severe Acute Respiratory Syndrome Coronavirus 2 and the Cytokine/Chemokine Release in Patients with Different Levels of Coronavirus Diseases 2019 Severity: Cytokine Storm Still Persists Despite Viral Disappearance in Critical Patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic is spreading rapidly all over the world. The Japanese government lifted the state of emergency, announced in April 2020, on May 25, but there are still sporadic clusters. Asymptomatic patients who can transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause some of these clusters. It is thus urgent to investigate the seroprevalence of antibodies against SARS-CoV-2 and their neutralizing activity. We conducted a cross-sectional study of >10,000 samples at hospitals in Hyogo Prefecture, Japan. METHODS: Between August 6 and October 1, 2020, we collected samples of residual blood from the patients who visited or were admitted to five hospitals and a foundation in Hyogo. We tested the samples for antibodies against SARS-CoV-2 by electrochemiluminescence immunoassay (ECLIA) and chemiluminescent enzyme immunoassay (CLEIA). Sera that were positive by ECLIA or CLEIA were analyzed by an immunochromatographic (IC) test and neutralizing activity assay. RESULTS: We tested 10,377 samples from patients aged between 0 and 99 years old; 27 cases (0.26%) were positive on the ECLIA, and 51 cases (0.49%) were positive on CLEIA. In the 14 cases that tested positive on both ECLIA and CLEIA, the positive rates on the IC test and for neutralizing activity were high (85% and 92%, respectively). In 50 cases (0.48%) that were positive by either ECLIA or CLEIA, the corresponding rates were low (20% and 6%, respectively). The positive rate of neutralizing antibody was 0.15%. CONCLUSIONS: These results indicate that most Hyogo Prefecture residents still do not have antibodies and should avoid the risk of incurring a SARS-CoV-2 infection. Two or more antibody tests should be required for seroepidemiological studies of the antibody for SARS-CoV-2, and a neutralizing activity assay is also essential.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Koichi", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Lidya Handayani", "last_name": "Tjan", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Lystia Poetranto", "name": null }, { "creator_type": "author", "first_name": "Zhenxiao", "last_name": "Ren", "name": null }, { "creator_type": "author", "first_name": "Salma", "last_name": "Aktar", "name": null }, { "creator_type": "author", "first_name": "Jing Rin", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Sutandhio", "name": null }, { "creator_type": "author", "first_name": "Yukiya", "last_name": "Kurahashi", "name": null }, { "creator_type": "author", "first_name": "Arisa", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Shiho", "last_name": "Shigekuni", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Uto", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Itsuko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Inui", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Kosaka", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Oota", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Saegusa", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.31662/jmaj.2020-0094" }, "pmcid": { "normalized": "PMC7872787" }, "pmid": { "normalized": "33575502" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jan 29", "date_precision": "day", "issue": "1", "normalized_date": "2021-01-29", "pages": "41-49", "proceedings_title": null, "publisher": "", "title": "JMA journal", "volume": "4", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Seroepidemiological Survey of the Antibody for Severe Acute Respiratory Syndrome Coronavirus 2 with Neutralizing Activity at Hospitals: A Cross-sectional Study in Hyogo Prefecture, Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Heart failure (HF) occurs frequently among older individuals, and dysfunction of cardiac mitochondria is often observed. We here show the cardiac-specific downregulation of a certain mitochondrial component during the chronological aging of mice, which is detrimental to the heart. MitoNEET is a mitochondrial outer membrane protein, encoded by CDGSH iron sulfur domain 1 (CISD1). Expression of mitoNEET was specifically downregulated in the heart and kidney of chronologically aged mice. Mice with a constitutive cardiac-specific deletion of CISD1 on the C57BL/6J background showed cardiac dysfunction only after 12 months of age and developed HF after 16 months; whereas irregular morphology and higher levels of reactive oxygen species in their cardiac mitochondria were observed at earlier time points. Our results suggest a possible mechanism by which cardiac mitochondria may gradually lose their integrity during natural aging, and shed light on an uncharted molecular basis closely related to age-associated HF.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takaaki", "last_name": "Furihata", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Kakutani", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Mizushima", "name": null }, { "creator_type": "author", "first_name": "Arata", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Enzan", "name": null }, { "creator_type": "author", "first_name": "Shouji", "last_name": "Matsushima", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Handa", "name": null }, { "creator_type": "author", "first_name": "Yoshizuki", "last_name": "Fumoto", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Nio-Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Iwanaga", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Tsutsui", "name": null }, { "creator_type": "author", "first_name": "Hisataka", "last_name": "Sabe", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Kinugawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-021-01675-4" }, "pmcid": { "normalized": "PMC7846856" }, "pmid": { "normalized": "33514783" } }, "mesh": [ { "descriptor": "Age Factors", "descriptor_ui": "D000367", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": false }, { "descriptor": "Iron-Binding Proteins", "descriptor_ui": "D033862", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mitochondria, Heart", "descriptor_ui": "D008929", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Ventricular Dysfunction, Left", "descriptor_ui": "D018487", "major_topic": false }, { "descriptor": "Ventricular Function, Left", "descriptor_ui": "D016277", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan 29", "date_precision": "day", "issue": "1", "normalized_date": "2021-01-29", "pages": "138", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "4", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Cardiac-specific loss of mitoNEET expression is linked with age-related heart failure.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "T-cells play key roles in immunity to COVID-19 as well as the development of severe disease. T-cell immunity to COVID-19 is mediated through differentiated CD4(+) T-cells and cytotoxic CD8(+) T-cells, although their differentiation is often atypical and ambiguous in COVID-19 and single cell dynamics of key genes need to be characterized. Notably, T-cells are dysregulated in severe COVID-19 patients, although their molecular features are still yet to be fully revealed. Importantly, it is not clear which T-cell activities are beneficial and protective and which ones can contribute to the development of severe COVID-19. In this article, we examine the latest evidence and discuss the key features of T-cell responses in COVID-19, showing how T-cells are dysregulated in severe COVID-19 patients. Particularly, we highlight the impairment of FOXP3 induction in CD4(+) T-cells and how the impaired FOXP3 expression can lead to the differentiation of abnormally activated (hyperactivated) T-cells and the dysregulated T-cell responses in severe patients. Furthermore, we characterise the feature of hyperactivated T-cells, showing their potential contribution to T-cell dysregulation and immune-mediated tissue destruction (immunopathology) in COVID-19.", "classifications": [ { "id": "19H05426", "label": "19H05426", "researcher": "Masahiro Ono", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Bahire", "last_name": "Kalfaoglu", "name": null }, { "creator_type": "author", "first_name": "Jose", "last_name": "Almeida-Santos", "name": null }, { "creator_type": "author", "first_name": "Chanidapa Adele", "last_name": "Tye", "name": null }, { "creator_type": "author", "first_name": "Yorifumi", "last_name": "Satou", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2020.10.079" }, "pmcid": { "normalized": "PMC7648511" }, "pmid": { "normalized": "33220925" } }, "mesh": [ { "descriptor": "CD4-Positive T-Lymphocytes", "descriptor_ui": "D015496", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false }, { "descriptor": "T-Lymphocytes, Cytotoxic", "descriptor_ui": "D013602", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan 29", "date_precision": "day", "issue": "", "normalized_date": "2021-01-29", "pages": "204-210", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "538", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "T-cell dysregulation in COVID-19.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Spermatogenesis, the complex process of male germ cell proliferation, differentiation, and maturation, is the basis of male fertility. In the seminiferous tubules of the testes, spermatozoa are constantly generated from spermatogonial stem cells through a stereotyped sequence of mitotic and meiotic divisions. The basic physiological principles, however, that control both maturation and luminal transport of the still immotile spermatozoa within the seminiferous tubules remain poorly, if at all, defined. Here, we show that coordinated contractions of smooth muscle-like testicular peritubular cells provide the propulsive force for luminal sperm transport toward the rete testis. Using a mouse model for in vivo imaging, we describe and quantify spontaneous tubular contractions and show a causal relationship between peritubular Ca(2+) waves and peristaltic transport. Moreover, we identify P2 receptor-dependent purinergic signaling pathways as physiological triggers of tubular contractions both in vitro and in vivo. When challenged with extracellular ATP, transport of luminal content inside the seminiferous tubules displays stage-dependent directionality. We thus suggest that paracrine purinergic signaling coordinates peristaltic recurrent contractions of the mouse seminiferous tubules to propel immotile spermatozoa to the rete testis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "David", "last_name": "Fleck", "name": null }, { "creator_type": "author", "first_name": "Lina", "last_name": "Kenzler", "name": null }, { "creator_type": "author", "first_name": "Nadine", "last_name": "Mundt", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Strauch", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Moosmann", "name": null }, { "creator_type": "author", "first_name": "Felicitas", "last_name": "Bruentgens", "name": null }, { "creator_type": "author", "first_name": "Annika", "last_name": "Missel", "name": null }, { "creator_type": "author", "first_name": "Artur", "last_name": "Mayerhofer", "name": null }, { "creator_type": "author", "first_name": "Dorit", "last_name": "Merhof", "name": null }, { "creator_type": "author", "first_name": "Jennifer", "last_name": "Spehr", "name": null }, { "creator_type": "author", "first_name": "Marc", "last_name": "Spehr", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.62885" }, "pmcid": { "normalized": "PMC7840184" }, "pmid": { "normalized": "33502316" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Seminiferous Tubules", "descriptor_ui": "D012671", "major_topic": false }, { "descriptor": "Sperm Transport", "descriptor_ui": "D013083", "major_topic": true }, { "descriptor": "Testis", "descriptor_ui": "D013737", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan 27", "date_precision": "day", "issue": "", "normalized_date": "2021-01-27", "pages": "e62885", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "10", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "ATP activation of peritubular cells drives testicular sperm transport.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Colonial tunicates are the only chordate that possess two distinct developmental pathways to produce an adult body: either sexually through embryogenesis or asexually through a stem cell-mediated renewal termed blastogenesis. Using the colonial tunicate Botryllus schlosseri, we combine transcriptomics and microscopy to build an atlas of the molecular and morphological signatures at each developmental stage for both pathways. The general molecular profiles of these processes are largely distinct. However, the relative timing of organogenesis and ordering of tissue-specific gene expression are conserved. By comparing the developmental pathways of B. schlosseri with other chordates, we identify hundreds of putative transcription factors with conserved temporal expression. Our findings demonstrate that convergent morphology need not imply convergent molecular mechanisms but that it showcases the importance that tissue-specific stem cells and transcription factors play in producing the same mature body through different pathways.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mark", "last_name": "Kowarsky", "name": null }, { "creator_type": "author", "first_name": "Chiara", "last_name": "Anselmi", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Paolo", "last_name": "Burighel", "name": null }, { "creator_type": "author", "first_name": "Giovanna", "last_name": "Zaniolo", "name": null }, { "creator_type": "author", "first_name": "Federico", "last_name": "Caicci", "name": null }, { "creator_type": "author", "first_name": "Benyamin", "last_name": "Rosental", "name": null }, { "creator_type": "author", "first_name": "Norma F.", "last_name": "Neff", "name": null }, { "creator_type": "author", "first_name": "Katherine J.", "last_name": "Ishizuka", "name": null }, { "creator_type": "author", "first_name": "Karla J.", "last_name": "Palmeri", "name": null }, { "creator_type": "author", "first_name": "Jennifer", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Tal", "last_name": "Gordon", "name": null }, { "creator_type": "author", "first_name": "Irving L.", "last_name": "Weissman", "name": null }, { "creator_type": "author", "first_name": "Stephen R.", "last_name": "Quake", "name": null }, { "creator_type": "author", "first_name": "Lucia", "last_name": "Manni", "name": null }, { "creator_type": "author", "first_name": "Ayelet", "last_name": "Voskoboynik", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2020.108681" }, "pmcid": { "normalized": "PMC7949349" }, "pmid": { "normalized": "33503429" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Reproduction, Asexual", "descriptor_ui": "D012100", "major_topic": false }, { "descriptor": "Sexual Development", "descriptor_ui": "D046468", "major_topic": false }, { "descriptor": "Urochordata", "descriptor_ui": "D014561", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan 26", "date_precision": "day", "issue": "4", "normalized_date": "2021-01-26", "pages": "108681", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "34", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Sexual and asexual development: two distinct programs producing the same tunicate.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Photoacoustic (PA) imaging is an emerging molecular imaging modality that complements fluorescence imaging and enables high resolution within deep tissue. Fluorescence/PA multimodality imaging would be a powerful technique to extract more comprehensive information from targets than traditional single-modality imaging. In this paper, we developed a new pH-activatable sensor, CypHRGD, which is applicable to both fluorescence and PA detection. CypHRGD was derived from our previous near-infrared pH-sensing platform, in which substitution with a bulky phenyl group and functionalization with a cRGD peptide remarkably improved the sensor's biocompatibility with attenuated dye aggregation. The multimodality imaging applications of CypHRGD were demonstrated in cultured cells and cancer-xenografted mice with rapid kinetics and high sensitivity and specificity, which relies on cRGD-facilitated tumor targeting, probe accumulation and subsequent activation in the acidic organelles after endocytosis.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Huiying", "last_name": "Mu", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kouki", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Nogita", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acssensors.0c01926" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33331765" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Photoacoustic Techniques", "descriptor_ui": "D061088", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Jan 22", "date_precision": "day", "issue": "1", "normalized_date": "2021-01-22", "pages": "123-129", "proceedings_title": null, "publisher": "", "title": "ACS sensors", "volume": "6", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "pH-Activatable Cyanine Dyes for Selective Tumor Imaging Using Near-Infrared Fluorescence and Photoacoustic Modalities.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bioluminescence is a powerful imaging modality for monitoring biological phenomena both in vitro and in vivo. Bioluminescence imagin (BLI) is becoming a seamless imaging technology covering the range from cells to organs of small animals. Long-term imaging at the single cell level would lead to a true understanding of the dynamics of life phenomena. This work presents a long-term single cell bioluminescence imaging technology accomplished with C-3 position protected furimazines (FMZs), a CTZ analogues, which generate intense blue emission when paired with a highly stable engineered luciferase, Nanoluc. Four types of FMZs protected at the C-3 position have been synthesized. The type and steric bulkiness of the protection group strongly contributed to storage stability and the kinetics of the bioluminescence reactions of the analogues in human living cells. In particular, two developed FMZ analogues resulted in significantly longer bioluminescence emission with higher S/N ratio than FMZ at single cell level. Long-term bioluminescence single cell imaging technology with the developed FMZ analogues will lead to seamless imaging in the range from cells to organs of small animals.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Mizui", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yuma", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d0ob02020f" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33140803" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Imidazoles", "descriptor_ui": "D007093", "major_topic": false }, { "descriptor": "Luminescence", "descriptor_ui": "D049449", "major_topic": true }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Pyrazines", "descriptor_ui": "D011719", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan 21", "date_precision": "day", "issue": "3", "normalized_date": "2021-01-21", "pages": "579-586", "proceedings_title": null, "publisher": "", "title": "Organic & biomolecular chemistry", "volume": "19", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Long-term single cell bioluminescence imaging with C-3 position protected coelenterazine analogues.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transfer entropy in information theory was recently demonstrated [Basak et al., Phys. Rev. E 102, 012404 (2020)] to enable us to elucidate the interaction domain among interacting elements solely from an ensemble of trajectories. Therefore, only pairs of elements whose distances are shorter than some distance variable, termed cutoff distance, are taken into account in the computation of transfer entropies. The prediction performance in capturing the underlying interaction domain is subject to the noise level exerted on the elements and the sufficiency of statistics of the interaction events. In this paper, the dependence of the prediction performance is scrutinized systematically on noise level and the length of trajectories by using a modified Vicsek model. The larger the noise level and the shorter the time length of trajectories, the more the derivative of average transfer entropy fluctuates, which makes the identification of the interaction domain in terms of the position of global minimum of the derivative of average transfer entropy difficult. A measure to quantify the degree of strong convexity at the coarse-grained level is proposed. It is shown that the convexity score scheme can identify the interaction distance fairly well even while the position of the global minimum of the derivative of average transfer entropy does not. We also derive an analytical model to explain the relationship between the interaction domain and the change in transfer entropy that supports our cutoff distance technique to elucidate the underlying interaction domain from trajectories.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" }, { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Udoy S.", "last_name": "Basak", "name": null }, { "creator_type": "author", "first_name": "Sulimon", "last_name": "Sattari", "name": null }, { "creator_type": "author", "first_name": "Md Motaleb", "last_name": "Hossain", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/5.0034467" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33499629" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jan 21", "date_precision": "day", "issue": "3", "normalized_date": "2021-01-21", "pages": "034901", "proceedings_title": null, "publisher": "", "title": "The Journal of chemical physics", "volume": "154", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "An information-theoretic approach to infer the underlying interaction domain among elements from finite length trajectories in a noisy environment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "ADP-ribosylation factor (Arf) family consisting of six family members, Arf1-Arf6, belongs to Ras superfamily and orchestrates vesicle trafficking under the control of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins. It is well established that brefeldin A, a potent inhibitor of ArfGEFs, blocks cytokine secretion from activated T cells, suggesting that the Arf pathway plays important roles in T cell functions. In this study, because Arf1 and Arf6 are the best-characterized members among Arf family, we established T lineage-specific Arf1-deficient, Arf6-deficient, and Arf1/6 double-deficient mice to understand physiological roles of the Arf pathway in the immune system. Contrary to our expectation, Arf deficiency had little or no impact on cytokine secretion from the activated T cells. In contrast, the lack of both Arf1 and Arf6, but neither Arf1 nor Arf6 deficiency alone, rendered naive T cells susceptible to apoptosis upon TCR stimulation because of imbalanced expression of Bcl-2 family members. We further demonstrate that Arf1/6 deficiency in T cells alleviates autoimmune diseases like colitis and experimental autoimmune encephalomyelitis, whereas Ab response under Th2-polarizing conditions is seemingly normal. Our findings reveal an unexpected role for the Arf pathway in the survival of T cells during TCR-induced activation and its potential as a therapeutic target in the autoimmune diseases.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mami", "last_name": "Sumiyoshi", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Kotani", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ikuta", "name": null }, { "creator_type": "author", "first_name": "Kazutomo", "last_name": "Suzue", "name": null }, { "creator_type": "author", "first_name": "Madoka", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null }, { "creator_type": "author", "first_name": "Taketo", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Koyasu", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Kanaho", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.4049/jimmunol.2000971" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33310872" } }, "mesh": [ { "descriptor": "ADP-Ribosylation Factor 1", "descriptor_ui": "D020823", "major_topic": false }, { "descriptor": "ADP-Ribosylation Factor 6", "descriptor_ui": "D000089982", "major_topic": false }, { "descriptor": "ADP-Ribosylation Factors", "descriptor_ui": "D020727", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Colitis", "descriptor_ui": "D003092", "major_topic": false }, { "descriptor": "Encephalomyelitis, Autoimmune, Experimental", "descriptor_ui": "D004681", "major_topic": false }, { "descriptor": "Immunotherapy", "descriptor_ui": "D007167", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-bcl-2", "descriptor_ui": "D019253", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan 15", "date_precision": "day", "issue": "2", "normalized_date": "2021-01-15", "pages": "366-375", "proceedings_title": null, "publisher": "", "title": "Journal of immunology (Baltimore, Md. : 1950)", "volume": "206", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Arf1 and Arf6 Synergistically Maintain Survival of T Cells during Activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Viral cell-to-cell spread, a method employed by several viral families for entrance via cell junctions, is highly relevant to the pathogenesis of various viral infections. Cell-to-cell spread of herpes simplex virus 1 (HSV-1) is known to depend greatly on envelope glycoprotein E (gE). However, the molecular mechanism by which gE acts in HSV-1 cell-to-cell spread and the mechanisms of cell-to-cell spread by other herpesviruses remain poorly understood. Here, we describe our identification of prohibitin-1 as a novel gE-interacting host cell protein. Ectopic expression of prohibitin-1 increased gE-dependent HSV-1 cell-to-cell spread. As observed with the gE-null mutation, decreased expression or pharmacological inhibition of prohibitin-1 reduced HSV-1 cell-to-cell spread without affecting the yield of virus progeny. Similar effects were produced by pharmacological inhibition of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway, wherein prohibitin-1 acts as a protein scaffold and is required for induction of this pathway. Furthermore, artificial activation of the MAPK/ERK pathway restored HSV-1 cell-to-cell spread impaired by the gE-null mutation. Notably, pharmacological inhibition of prohibitins or the MAPK/ERK pathway reduced viral cell-to-cell spread of representative members in all herpesvirus subfamilies. Our results suggest that prohibitin-1 contributes to gE-dependent HSV-1 cell-to-cell spread via the MAPK/ERK pathway and that this mechanism is conserved throughout the Herpesviridae, whereas gE is conserved only in the Alphaherpesvirinae subfamily.IMPORTANCE Herpesviruses are ubiquitous pathogens of various animals, including humans. These viruses primarily pass through cell junctions to spread to uninfected cells. This method of cell-to-cell spread is an important pathogenic characteristic of these viruses. Here, we show that the host cell protein prohibitin-1 contributes to HSV-1 cell-to-cell spread via a downstream intracellular signaling cascade, the MAPK/ERK pathway. We also demonstrate that the role of the prohibitin-1-mediated MAPK/ERK pathway in viral cell-to-cell spread is conserved in representative members of every herpesvirus subfamily. This study has revealed a common molecular mechanism of the cell-to-cell spread of herpesviruses.", "classifications": [ { "id": "19H05417", "label": "19H05417", "researcher": "Jun Arii", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mizuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shimojima", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kozuka-Hata", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Minamitani", "name": null }, { "creator_type": "author", "first_name": "Teruhito", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Kosugi", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01413-20" }, "pmcid": { "normalized": "PMC7925112" }, "pmid": { "normalized": "33177205" } }, "mesh": [ { "descriptor": "A549 Cells", "descriptor_ui": "D000072283", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": true }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Junctions", "descriptor_ui": "D007365", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": false }, { "descriptor": "Prohibitins", "descriptor_ui": "D000091402", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Viral Envelope Proteins", "descriptor_ui": "D014759", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan 13", "date_precision": "day", "issue": "3", "normalized_date": "2021-01-13", "pages": "e01413-20", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "95", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Prohibitin-1 Contributes to Cell-to-Cell Transmission of Herpes Simplex Virus 1 via the MAPK/ERK Signaling Pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Angiogenesis contributes to numerous pathological conditions. Understanding the molecular mechanisms of angiogenesis will offer new therapeutic opportunities. Several experimental in vivo models that better represent the pathological conditions have been generated for this purpose in mice, but it is difficult to translate results from mouse to human blood vessels. To understand human vascular biology and translate findings into human research, we need human blood vessel models to replicate human vascular physiology. Here, we show that human tumor tissue transplantation into a cranial window enables engraftment of human blood vessels in mice. An in vivo imaging technique using two-photon microscopy allows continuous observation of human blood vessels until at least 49 days after tumor transplantation. These human blood vessels make connections with mouse blood vessels as shown by the finding that lectin injected into the mouse tail vein reaches the human blood vessels. Finally, this model revealed that formation and/or maintenance of human blood vessels depends on VEGFR2 signaling. This approach represents a useful tool to study molecular mechanisms of human blood vessel formation and to test effects of drugs that target human blood vessels in vivo to show proof of concept in a preclinical model.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Hang", "last_name": "Su", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Iba", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-80497-6" }, "pmcid": { "normalized": "PMC7804448" }, "pmid": { "normalized": "33436931" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Colonic Neoplasms", "descriptor_ui": "D003110", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Mice, SCID", "descriptor_ui": "D016513", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan 12", "date_precision": "day", "issue": "1", "normalized_date": "2021-01-12", "pages": "745", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "An in vivo model allowing continuous observation of human vascular formation in the same animal over time.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Oxytocinergic neurons in the paraventricular nucleus of the hypothalamus that project to extrahypothalamic brain areas and the lumbar spinal cord play an important role in the control of erectile function and male sexual behavior in mammals. The gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord is an important component of the neural circuits that control penile reflexes in rats, circuits that are commonly referred to as the \"spinal ejaculation generator (SEG).\" We have examined the functional interaction between the SEG neurons and the hypothalamo-spinal oxytocin system in rats. Here, we show that SEG/GRP neurons express oxytocin receptors and are activated by oxytocin during male sexual behavior. Intrathecal injection of oxytocin receptor antagonist not only attenuates ejaculation but also affects pre-ejaculatory behavior during normal sexual activity. Electron microscopy of potassium-stimulated acute slices of the lumbar cord showed that oxytocin-neurophysin-immunoreactivity was detected in large numbers of neurosecretory dense-cored vesicles, many of which are located close to the plasmalemma of axonal varicosities in which no electron-lucent microvesicles or synaptic membrane thickenings were visible. These results suggested that, in rats, release of oxytocin in the lumbar spinal cord is not limited to conventional synapses but occurs by exocytosis of the dense-cored vesicles from axonal varicosities and acts by diffusion-a localized volume transmission-to reach oxytocin receptors on GRP neurons and facilitate male sexual function.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Oti", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Uta", "name": null }, { "creator_type": "author", "first_name": "Junta", "last_name": "Nagafuchi", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Tateishi", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Takanami", "name": null }, { "creator_type": "author", "first_name": "Larry J.", "last_name": "Young", "name": null }, { "creator_type": "author", "first_name": "Antony", "last_name": "Galione", "name": null }, { "creator_type": "author", "first_name": "John F.", "last_name": "Morris", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2020.09.089" }, "pmcid": { "normalized": "PMC7855431" }, "pmid": { "normalized": "33125871" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Diffusion", "descriptor_ui": "D004058", "major_topic": false }, { "descriptor": "Ejaculation", "descriptor_ui": "D004542", "major_topic": false }, { "descriptor": "Exocytosis", "descriptor_ui": "D005089", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gastrin-Releasing Peptide", "descriptor_ui": "D019886", "major_topic": false }, { "descriptor": "Heparin-binding EGF-like Growth Factor", "descriptor_ui": "D066257", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Injections, Spinal", "descriptor_ui": "D007278", "major_topic": false }, { "descriptor": "Lumbar Vertebrae", "descriptor_ui": "D008159", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Oxytocin", "descriptor_ui": "D010121", "major_topic": false }, { "descriptor": "Penile Erection", "descriptor_ui": "D010410", "major_topic": false }, { "descriptor": "Penis", "descriptor_ui": "D010413", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Transgenic", "descriptor_ui": "D055647", "major_topic": false }, { "descriptor": "Receptors, Oxytocin", "descriptor_ui": "D018045", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan 11", "date_precision": "day", "issue": "1", "normalized_date": "2021-01-11", "pages": "103-114.e5", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "31", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Oxytocin Influences Male Sexual Activity via Non-synaptic Axonal Release in the Spinal Cord.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alzheimer's disease (AD) is characterized by the accumulation of amyloid-beta (Abeta) as senile plaques and cerebral amyloid angiopathy, and hyperphosphorylated tau (hp-tau) as neurofibrillary tangles in the brain. The AD-related pathology has been reported in several non-human animals, and most animals develop only the Abeta or tau pathology. We herein describe the Abeta and hp-tau pathology in the brains of aged pinniped species (seal, sea lion, and walrus). Molecular analyses revealed that the sequence of pinniped Abeta was identical to that of human Abeta. Histopathological examinations detected argyrophilic plaques composed of Abeta associated with dystrophic neurites in the cerebral cortex of aged pinnipeds. Astrogliosis and microglial infiltration were identified around Abeta plaques. Abeta deposits were observed in the blood vessel walls of the meninges and cerebrum. Pinniped tau protein was physiologically subjected to alternative splicing at exons 2, 3, and 10, and presented as five isoforms: two 3-repeat tau isoforms (1N3R, 2N3R) and three 4-repeat tau isoforms (0N4R, 1N4R, 2N4R); 0N3R tau isoform was absent. Histopathological examinations revealed argyrophilic fibrillar aggregates composed of hp-tau in the neuronal somata and neurites of aged pinniped brains. Few hp-tau aggregates were found in oligodendrocytes and microglia. Biochemically, hp-tau of the 3-repeat and 4-repeat isoforms was detected in brain sarkosyl-insoluble fractions. Abeta and hp-tau both predominantly accumulated in the neocortex, particularly the frontal cortex. Furthermore, the activation of GSK-3beta was detected within cells containing hp-tau aggregates, and activated GSK-3beta was strongly expressed in cases with severe hp-tau pathologies. The present results suggest that, in association with Abeta deposition, the activation of GSK-3beta contributes to hp-tau accumulation in pinniped brains. Here, we report that pinniped species naturally accumulate Abeta and tau with aging, similar to the human AD pathology.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Takaichi", "name": null }, { "creator_type": "author", "first_name": "James K.", "last_name": "Chambers", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Soeda", "name": null }, { "creator_type": "author", "first_name": "Riki", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Katsumata", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Fuko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Haritani", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Uchida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s40478-020-01104-3" }, "pmcid": { "normalized": "PMC7792306" }, "pmid": { "normalized": "33413691" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Amyloid beta-Peptides", "descriptor_ui": "D016229", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Caniformia", "descriptor_ui": "D010872", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Phoca", "descriptor_ui": "D046049", "major_topic": false }, { "descriptor": "Sea Lions", "descriptor_ui": "D046070", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Walruses", "descriptor_ui": "D014856", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan 7", "date_precision": "day", "issue": "1", "normalized_date": "2021-01-07", "pages": "10", "proceedings_title": null, "publisher": "", "title": "Acta neuropathologica communications", "volume": "9", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Amyloid beta and tau pathology in brains of aged pinniped species (sea lion, seal, and walrus).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A panel of radiochemicals has enabled in vivo positron emission tomography (PET) of tau pathologies in Alzheimer's disease (AD), although sensitive detection of frontotemporal lobar degeneration (FTLD) tau inclusions has been unsuccessful. Here, we generated an imaging probe, PM-PBB3, for capturing diverse tau deposits. In vitro assays demonstrated the reactivity of this compound with tau pathologies in AD and FTLD. We could also utilize PM-PBB3 for optical/PET imaging of a living murine tauopathy model. A subsequent clinical PET study revealed increased binding of (18)F-PM-PBB3 in diseased patients, reflecting cortical-dominant AD and subcortical-dominant progressive supranuclear palsy (PSP) tau topologies. Notably, the in vivo reactivity of (18)F-PM-PBB3 with FTLD tau inclusion was strongly supported by neuropathological examinations of brains derived from Pick's disease, PSP, and corticobasal degeneration patients who underwent PET scans. Finally, visual inspection of (18)F-PM-PBB3-PET images was indicated to facilitate individually based identification of diverse clinical phenotypes of FTLD on a neuropathological basis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Tagai", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Takahata", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Takado", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shinotoh", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Yasuharu", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kiwamu", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takuwa", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Shimojo", "name": null }, { "creator_type": "author", "first_name": "Manami", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Hisaomi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Mitsumoto", "last_name": "Onaya", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Kimihito", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Nobutaka", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "John Q.", "last_name": "Trojanowski", "name": null }, { "creator_type": "author", "first_name": "Virginia M. Y.", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Sushil K.", "last_name": "Mishra", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Ichise", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Ming-Rong", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Shigeta", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2020.09.042" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33125873" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzothiazoles", "descriptor_ui": "D052160", "major_topic": false }, { "descriptor": "Carbon Radioisotopes", "descriptor_ui": "D002250", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Positron-Emission Tomography", "descriptor_ui": "D049268", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan 6", "date_precision": "day", "issue": "1", "normalized_date": "2021-01-06", "pages": "42-58.e8", "proceedings_title": null, "publisher": "", "title": "Neuron", "volume": "109", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer's and Non-Alzheimer's Disease Tauopathies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Microglia-mediated neuroinflammation has been implicated in the pathogenesis of Alzheimer's disease (AD). Although microglia in aging and neurodegenerative disease model mice show a loss of homeostatic phenotype and activation of disease-associated microglia (DAM), a correlation between those phenotypes and the degree of neuronal cell loss has not been clarified. In this study, we performed RNA sequencing of microglia isolated from three representative neurodegenerative mouse models, App(NL-G-F/NL-G-F) with amyloid pathology, rTg4510 with tauopathy, and SOD1(G93A) with motor neuron disease by magnetic activated cell sorting. In parallel, gene expression patterns of the human precuneus with early Alzheimer's change (n = 11) and control brain (n = 14) were also analyzed by RNA sequencing. We found that a substantial reduction of homeostatic microglial genes in rTg4510 and SOD1(G93A) microglia, whereas DAM genes were uniformly upregulated in all mouse models. The reduction of homeostatic microglial genes was correlated with the degree of neuronal cell loss. In human precuneus with early AD pathology, reduced expression of genes related to microglia- and oligodendrocyte-specific markers was observed, although the expression of DAM genes was not upregulated. Our results implicate a loss of homeostatic microglial function in the progression of AD and other neurodegenerative diseases. Moreover, analyses of human precuneus also suggest loss of microglia and oligodendrocyte functions induced by early amyloid pathology in human.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akira", "last_name": "Sobue", "name": null }, { "creator_type": "author", "first_name": "Okiru", "last_name": "Komine", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Fumito", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mizoguchi", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takaomi C.", "last_name": "Saido", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Tomoo", "last_name": "Ogi", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Yamanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s40478-020-01099-x" }, "pmcid": { "normalized": "PMC7786928" }, "pmid": { "normalized": "33402227" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Amyloid beta-Protein Precursor", "descriptor_ui": "D016564", "major_topic": false }, { "descriptor": "Amyotrophic Lateral Sclerosis", "descriptor_ui": "D000690", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microglia", "descriptor_ui": "D017628", "major_topic": false }, { "descriptor": "Parietal Lobe", "descriptor_ui": "D010296", "major_topic": false }, { "descriptor": "RNA-Seq", "descriptor_ui": "D000081246", "major_topic": false }, { "descriptor": "Superoxide Dismutase", "descriptor_ui": "D013482", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Jan 5", "date_precision": "day", "issue": "1", "normalized_date": "2021-01-05", "pages": "1", "proceedings_title": null, "publisher": "", "title": "Acta neuropathologica communications", "volume": "9", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Microglial gene signature reveals loss of homeostatic microglia associated with neurodegeneration of Alzheimer's disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "TARM1 is a member of the leukocyte immunoglobulin-like receptor family and stimulates macrophages and neutrophils in vitro by associating with FcRγ. However, the function of this molecule in the regulation of the immune system is unclear. Here, we show that Tarm1 expression is elevated in the joints of rheumatoid arthritis mouse models, and the development of collagen-induced arthritis (CIA) is suppressed in Tarm1(-/-) mice. T cell priming against type 2 collagen is suppressed in Tarm1(-/-) mice and antigen-presenting ability of GM-CSF-induced dendritic cells (GM-DCs) from Tarm1(-/-) mouse bone marrow cells is impaired. We show that type 2 collagen is a functional ligand for TARM1 on GM-DCs and promotes DC maturation. Furthermore, soluble TARM1-Fc and TARM1-Flag inhibit DC maturation and administration of TARM1-Fc blocks the progression of CIA in mice. These results indicate that TARM1 is an important stimulating factor of dendritic cell maturation and could be a good target for the treatment of autoimmune diseases.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Rikio", "last_name": "Yabe", "name": null }, { "creator_type": "author", "first_name": "Soo-Hyun", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Masanori A.", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Akahori", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Akimasa", "last_name": "Seno", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Kaifu", "name": null }, { "creator_type": "author", "first_name": "Shinobu", "last_name": "Saijo", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Iwakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-020-20307-9" }, "pmcid": { "normalized": "PMC7782728" }, "pmid": { "normalized": "33397982" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigen Presentation", "descriptor_ui": "D017951", "major_topic": false }, { "descriptor": "Arthritis, Experimental", "descriptor_ui": "D001169", "major_topic": false }, { "descriptor": "Collagen", "descriptor_ui": "D003094", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": false }, { "descriptor": "Granulocyte-Macrophage Colony-Stimulating Factor", "descriptor_ui": "D016178", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Immunization", "descriptor_ui": "D007114", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Receptors, Immunologic", "descriptor_ui": "D011971", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan 4", "date_precision": "day", "issue": "1", "normalized_date": "2021-01-04", "pages": "94", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "TARM1 contributes to development of arthritis by activating dendritic cells through recognition of collagens.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A still unanswered question is what drives the small fraction of activated germinal center (GC) B cells to become long-lived quiescent memory B cells. We found here that a small population of GC-derived CD38intBcl6hi/intEfnb1+ cells with lower mTORC1 activity favored the memory B cell fate. Constitutively high mTORC1 activity led to defects in formation of the CD38intBcl6hi/intEfnb1+ cells; conversely, decreasing mTORC1 activity resulted in relative enrichment of this memory-prone population over the recycling-prone one. Furthermore, the CD38intBcl6hi/intEfnb1+ cells had higher levels of Bcl2 and surface BCR that, in turn, contributed to their survival and development. We also found that downregulation of Bcl6 resulted in increased expression of both Bcl2 and BCR. Given the positive correlation between the strength of T cell help and mTORC1 activity, our data suggest a model in which weak help from T cells together with provision of an increased survival signal are key for GC B cells to adopt a memory B cell fate.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Shinnakasu", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Ise", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Nicolas", "last_name": "Sax", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Hidehiro", "last_name": "Fukuyama", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kurosaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1084/jem.20200866" }, "pmcid": { "normalized": "PMC7555411" }, "pmid": { "normalized": "33045065" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, Differentiation", "descriptor_ui": "D000943", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": false }, { "descriptor": "Germinal Center", "descriptor_ui": "D018858", "major_topic": false }, { "descriptor": "Immunologic Memory", "descriptor_ui": "D007156", "major_topic": true }, { "descriptor": "Mechanistic Target of Rapamycin Complex 1", "descriptor_ui": "D000076222", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-bcl-2", "descriptor_ui": "D019253", "major_topic": false }, { "descriptor": "Receptors, Antigen, B-Cell", "descriptor_ui": "D011947", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "T-Lymphocytes, Helper-Inducer", "descriptor_ui": "D006377", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan 4", "date_precision": "day", "issue": "1", "normalized_date": "2021-01-04", "pages": "e20200866", "proceedings_title": null, "publisher": "", "title": "The Journal of experimental medicine", "volume": "218", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Exit from germinal center to become quiescent memory B cells depends on metabolic reprograming and provision of a survival signal.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We demonstrate hyperspectral imaging by visible-wavelength two-photon excitation microscopy using line illumination and slit-confocal detection. A femtosecond pulsed laser light at 530 nm was used for the simultaneous excitation of fluorescent proteins with different emission wavelengths. The use of line illumination enabled efficient detection of hyperspectral images and achieved simultaneous detection of three fluorescence spectra in the observation of living HeLa cells with an exposure time of 1 ms per line, which is equivalent to about 2 micros per pixel in point scanning, with 160 data points per spectrum. On combining linear spectral unmixing techniques, localization of fluorescent probes in the cells was achieved. A theoretical investigation of the imaging property revealed high-depth discrimination property attained through the combination of nonlinear excitation and slit detection.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Temma", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Kai", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/ol.413526" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33362007" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jan 1", "date_precision": "day", "issue": "1", "normalized_date": "2021-01-01", "pages": "37-40", "proceedings_title": null, "publisher": "", "title": "Optics letters", "volume": "46", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Hyperspectral two-photon excitation microscopy using visible wavelength.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In many phenomena of biological systems, not a majority, but a minority of cells act on the entire multicellular system causing drastic changes in the system properties. To understand the mechanisms underlying such phenomena, it is essential to observe the spatiotemporal dynamics of a huge population of cells at sub-cellular resolution, which is difficult with conventional tools such as microscopy and flow cytometry. Here, we describe an imaging system named AMATERAS that enables optical imaging with an over-one-centimeter field-of-view and a-few-micrometer spatial resolution. This trans-scale-scope has a simple configuration, composed of a low-power lens for machine vision and a hundred-megapixel image sensor. We demonstrated its high cell-throughput, capable of simultaneously observing more than one million cells. We applied it to dynamic imaging of calcium ions in HeLa cells and cyclic-adenosine-monophosphate in Dictyostelium discoideum, and successfully detected less than 0.01% of rare cells and observed multicellular events induced by these cells.Competing Interest StatementThe authors have declared no competing interest.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "T.", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "T.", "last_name": "Kakizuka", "name": null }, { "creator_type": "author", "first_name": "K.", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "K.", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "A.", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "H.", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "K.", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "T. M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "T.", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/2020.06.29.179044" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2021-01-01", "date_precision": "day", "issue": "", "normalized_date": "2021-01-01", "pages": "2020.06.29.179044", "proceedings_title": null, "publisher": "", "title": "bioRxiv", "volume": "", "year": 2021 }, "ssbd": { "database": [ "ssbd-database-000199" ], "repository": [ "ssbd-repos-000199" ] }, "title": "Exploring rare cellular activity in more than one million cells by a trans-scale-scope", "url": "http://biorxiv.org/content/early/2021/03/02/2020.06.29.179044.abstract", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Elucidating the mechanisms underlying human pain sensation requires the establishment of an in vitro model of pain reception comprising human cells expressing pain-sensing receptors and function properly as neurons. Human dental pulp stem cells (hDPSCs) are mesenchymal stem cells and a promising candidate for producing human neuronal cells, however, the functional properties of differentiated hDPSCs have not yet been fully characterized. In this study, we demonstrated neuronal differentiation of hDPSCs via both their expression of neuronal marker proteins and their neuronal function examined using Ca2+ imaging. Moreover, to confirm the ability of nociception, Ca2+ responses in differentiated hDPSCs were compared to those of rat dorsal root ganglion (DRG) neurons. Those cells showed similar responses to glutamate, ATP and agonists of transient receptor potential (TRP) channels. Since TRP channels are implicated in nociception, differentiated hDPSCs provide a useful in vitro model of human peripheral neuron response to stimuli interpreted as pain.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Arimura", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Taka", "last_name": "Nakahara", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0251356" }, "pmcid": { "normalized": "PMC8101759" }, "pmid": { "normalized": "33956879" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Dental Pulp", "descriptor_ui": "D003782", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mesenchymal Stem Cells", "descriptor_ui": "D059630", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Nociception", "descriptor_ui": "D059225", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "5", "normalized_date": "2021", "pages": "e0251356", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "16", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Peripheral-neuron-like properties of differentiated human dental pulp stem cells (hDPSCs).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Research on endocannabinoid signaling has greatly advanced our understanding of how the excitability of neural circuits is controlled in health and disease. In general, endocannabinoid signaling at excitatory synapses suppresses excitability by inhibiting glutamate release, while that at inhibitory synapses promotes excitability by inhibiting GABA release, although there are some exceptions in genetically epileptic animal models. In the epileptic brain, the physiological distributions of endocannabinoid signaling molecules are disrupted during epileptogenesis, contributing to the occurrence of spontaneous seizures. However, it is still unknown how endocannabinoid signaling changes during seizures and how the redistribution of endocannabinoid signaling molecules proceeds during epileptogenesis. Recent development of cannabinoid sensors has enabled us to investigate endocannabinoid signaling in much greater spatial and temporal details than before. Application of cannabinoid sensors to epilepsy research has elucidated activity-dependent changes in endocannabinoid signaling during seizures. Furthermore, recent endocannabinoid research has paved the way for the clinical use of cannabidiol for the treatment of refractory epilepsy, such as Dravet syndrome, Lennox-Gastaut syndrome and tuberous sclerosis complex. Cannabidiol significantly reduces seizures and is considered to have comparable tolerability to conventional antiepileptic drugs. In this article, we introduce recent advances in research on the roles of endocannabinoid signaling in epileptic seizures and discuss future directions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugaya", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fncir.2021.781113" }, "pmcid": { "normalized": "PMC8762319" }, "pmid": { "normalized": "35046779" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anticonvulsants", "descriptor_ui": "D000927", "major_topic": false }, { "descriptor": "Cannabidiol", "descriptor_ui": "D002185", "major_topic": true }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": false }, { "descriptor": "Epilepsy", "descriptor_ui": "D004827", "major_topic": true }, { "descriptor": "Seizures", "descriptor_ui": "D012640", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "781113", "proceedings_title": null, "publisher": "", "title": "Frontiers in neural circuits", "volume": "15", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Endocannabinoid-Mediated Control of Neural Circuit Excitability and Epileptic Seizures.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP, gene name ADCYAP1) is a multifunctional neuropeptide involved in brain development and synaptic plasticity. With respect to PACAP function, most attention has been given to that mediated by its specific receptor PAC1 (ADCYAP1R1). However, PACAP also binds tightly to the high affinity receptors for vasoactive intestinal peptide (VIP, VIP), called VPAC1 and VPAC2 (VIPR1 and VIPR2, respectively). Depending on innervation patterns, PACAP can thus interact physiologically with any of these receptors. VPAC2 receptors, the focus of this review, are known to have a pivotal role in regulating circadian rhythms and to affect multiple other processes in the brain, including those involved in fear cognition. Accumulating evidence in human genetics indicates that microduplications at 7q36.3, containing VIPR2 gene, are linked to schizophrenia and possibly autism spectrum disorder. Although detailed molecular mechanisms have not been fully elucidated, recent studies in animal models suggest that overactivation of the VPAC2 receptor disrupts cortical circuit maturation. The VIPR2 linkage can thus be potentially explained by inappropriate control of receptor signaling at a time when neural circuits involved in cognition and social behavior are being established. Alternatively, or in addition, VPAC2 receptor overactivity may disrupt ongoing synaptic plasticity during processes of learning and memory. Finally, in vitro data indicate that PACAP and VIP have differential activities on the maturation of neurons via their distinct signaling pathways. Thus perturbations in the balance of VPAC2, VPAC1, and PAC1 receptors and their ligands may have important consequences in brain development and plasticity.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "James A.", "last_name": "Waschek", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2021.717490" }, "pmcid": { "normalized": "PMC8339898" }, "pmid": { "normalized": "34366784" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "717490", "proceedings_title": null, "publisher": "", "title": "Frontiers in neuroscience", "volume": "15", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Probing the VIPR2 Microduplication Linkage to Schizophrenia in Animal and Cellular Models.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "18H05414", "label": "18H05414", "researcher": "Hiroko Bannai", "type": "grant" }, { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Riki", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Takaichi", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Soeda", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.nbas.2021.100022" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36911517" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "", "proceedings_title": null, "publisher": "", "title": "Aging Brain", "volume": "1", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Memory formation in old age requires GSK-3β.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Animal opsin-based pigments are light-activated G-protein-coupled receptors (GPCRs), which drive signal transduction cascades via G-proteins. Thousands of animal opsins have been identified, and molecular phylogenetic and biochemical analyses have revealed the unexpected diversity in selectivity of G-protein activation and photochemical property. Here we discuss the optogenetic potentials of diverse animal opsins, particularly recently well-characterized three non-canonical opsins, parapinopsin, peropsin, and LWS bistable opsin. Unlike canonical opsins such as vertebrate visual opsins that have been conventionally used for optogenetic applications, these opsins are bistable; opsin-based pigments do not release the chromophore retinal after light absorption, and the stable photoproducts revert to their original dark states upon subsequent light absorption. Parapinopsins have a \"complete photoregeneration ability,\" which allows a clear color-dependent regulation of signal transductions. On the other hand, peropsins serve as a \"dark-active and light-inactivated\" GPCR to regulate signal transductions in the opposite way compared with usual opsins. In addition, an LWS bistable opsin from a butterfly was revealed to be the longest wavelength-sensitive animal opsin with its absorption maximum at ~570 nm. The property-dependent optical regulations of signal transductions were demonstrated in mammalian cultured cells, showing potentials of new optogenetic tools.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Tomoka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Kawano-Yamashita", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-981-15-8763-4_8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33398811" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Opsins", "descriptor_ui": "D055355", "major_topic": true }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": true }, { "descriptor": "Vertebrates", "descriptor_ui": "D014714", "major_topic": false }, { "descriptor": "Vision, Ocular", "descriptor_ui": "D014785", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "141-151", "proceedings_title": null, "publisher": "", "title": "Advances in experimental medicine and biology", "volume": "1293", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Optogenetic Potentials of Diverse Animal Opsins: Parapinopsin, Peropsin, LWS Bistable Opsin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The recent development of the bright luciferase NanoLuc (Nluc) has greatly improved the sensitivity of bioluminescence imaging, enabling real-time cellular imaging with high spatial resolution. However, the limited color variants of Nluc have restricted its wider application to multicolor imaging of biological phenomena. To address this issue, we developed five new spectral variants of the bright bioluminescent protein with emissions across the visible spectrum. In this chapter, we describe the following two protocols for single-cell bioluminescence imaging: (a) multicolor bioluminescence imaging of subcellular structures and (b) multicolor calcium imaging in single living cells.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazushi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Md Nadim", "last_name": "Hossain", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-1593-5_14" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34331288" } }, "mesh": [ { "descriptor": "Bioluminescence Resonance Energy Transfer Techniques", "descriptor_ui": "D060807", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence, Multiphoton", "descriptor_ui": "D036641", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "229-237", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2350", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Multicolor Bioluminescence Imaging of Subcellular Structures and Multicolor Calcium Imaging in Single Living Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Membrane receptors play a crucial role in transmitting external signals inside cells. Signal molecule-bound receptors activate multiple downstream pathways, the dynamics of which are modulated by intracellular trafficking. A significant contribution of beta-arrestin to intracellular trafficking has been suggested, but the underlying mechanism is poorly understood. Here, we describe a protocol for manipulating beta-arrestin-regulated membrane receptor trafficking using photo-induced dimerization of cryptochrome-2 from Arabidopsis thaliana and its binding partner CIBN. Additionally, the protocol guides analytical methods to quantify the changes in localization and modification of membrane receptors during trafficking.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Osamu", "last_name": "Takenouchi", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-1258-3_2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34050458" } }, "mesh": [ { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": true }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoprecipitation", "descriptor_ui": "D047468", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Receptors, Adrenergic, beta-2", "descriptor_ui": "D018343", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "15-23", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2274", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative Analysis of Membrane Receptor Trafficking Manipulated by Optogenetic Tools.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer patients with low or absent pre-existing anti-tumour immunity (\"cold\" tumours) respond poorly to treatment with immune checkpoint inhibitors (ICPI). In order to render these patients susceptible to ICPI, initiation of de novo tumour-targeted immune responses is required. This involves triggering of inflammatory signalling, innate immune activation including recruitment and stimulation of dendritic cells (DCs), and ultimately priming of tumour-specific T cells. The ability of tumour localised therapies to trigger these pathways and act as in situ tumour vaccines is being increasingly explored, with the aspiration of developing combination strategies with ICPI that could generate long-lasting responses. In this effort, it is crucial to consider how therapy-induced changes in the tumour microenvironment (TME) act both as immune stimulants but also, in some cases, exacerbate immune resistance mechanisms. Increasingly refined immune monitoring in pre-clinical studies and analysis of on-treatment biopsies from clinical trials have provided insight into therapy-induced biomarkers of response, as well as actionable targets for optimal synergy between localised therapies and ICB. Here, we review studies on the immunomodulatory effects of novel and experimental localised therapies, as well as the re-evaluation of established therapies, such as radiotherapy, as immune adjuvants with a focus on ICPI combinations.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Elizabeth", "last_name": "Appleton", "name": null }, { "creator_type": "author", "first_name": "Jehanne", "last_name": "Hassan", "name": null }, { "creator_type": "author", "first_name": "Charleen", "last_name": "Chan Wah Hak", "name": null }, { "creator_type": "author", "first_name": "Nanna", "last_name": "Sivamanoharan", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Wilkins", "name": null }, { "creator_type": "author", "first_name": "Adel", "last_name": "Samson", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Kevin J.", "last_name": "Harrington", "name": null }, { "creator_type": "author", "first_name": "Alan", "last_name": "Melcher", "name": null }, { "creator_type": "author", "first_name": "Erik", "last_name": "Wennerberg", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2021.754436" }, "pmcid": { "normalized": "PMC8558396" }, "pmid": { "normalized": "34733287" } }, "mesh": [ { "descriptor": "Adjuvants, Immunologic", "descriptor_ui": "D000276", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, Neoplasm", "descriptor_ui": "D000951", "major_topic": false }, { "descriptor": "Cancer Vaccines", "descriptor_ui": "D019496", "major_topic": false }, { "descriptor": "Combined Modality Therapy", "descriptor_ui": "D003131", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": false }, { "descriptor": "Drug Screening Assays, Antitumor", "descriptor_ui": "D004354", "major_topic": false }, { "descriptor": "Drug Synergism", "descriptor_ui": "D004357", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Checkpoint Inhibitors", "descriptor_ui": "D000082082", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": false }, { "descriptor": "Immunomodulating Agents", "descriptor_ui": "D000091369", "major_topic": false }, { "descriptor": "Immunomodulation", "descriptor_ui": "D056747", "major_topic": true }, { "descriptor": "Immunotherapy", "descriptor_ui": "D007167", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Oncolytic Virotherapy", "descriptor_ui": "D050130", "major_topic": false }, { "descriptor": "T-Lymphocyte Subsets", "descriptor_ui": "D016176", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "754436", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Kickstarting Immunity in Cold Tumours: Localised Tumour Therapy Combinations With Immune Checkpoint Blockade.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cytokines are important intercellular communication tools for immunity. Most cytokines utilize the JAK-STAT and Ras-ERK pathways to promote gene transcription and proliferation; however, this signaling is tightly regulated. The suppressor of cytokine signaling (SOCS) family and SPRED family are a representative negative regulators of the JAK-STAT pathway and the Ras-ERK pathway, respectively. The SOCS family regulates the differentiation and function of CD4(+) T cells, CD8(+) T cells, and regulatory T cells, and is involved in immune tolerance, anergy, and exhaustion. SPRED family proteins have been shown to inactivate Ras by recruiting the Ras-GTPase neurofibromatosis type 1 (NF1) protein. Human genetic analysis has shown that SOCS family members are strongly associated with autoimmune diseases, allergies, and tumorigenesis, and SPRED1 is involved in NF1-like syndromes and tumors. We also identified the NR4a family of nuclear receptors as a key transcription factor for immune tolerance that suppresses cytokine expression and induces various immuno-regulatory molecules including SOCS1.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Aki", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.2183/pjab.97.016" }, "pmcid": { "normalized": "PMC8403526" }, "pmid": { "normalized": "34121041" } }, "mesh": [ { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": true }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Tolerance", "descriptor_ui": "D007108", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Suppressor of Cytokine Signaling Proteins", "descriptor_ui": "D050826", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "6", "normalized_date": "2021", "pages": "277-291", "proceedings_title": null, "publisher": "", "title": "Proceedings of the Japan Academy. Series B, Physical and biological sciences", "volume": "97", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "SOCS, SPRED, and NR4a: Negative regulators of cytokine signaling and transcription in immune tolerance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Matrix metalloproteinase-2 (MMP-2), which is one of MMPs family, is known as an extracellular gelatinase controlling cancer cell adhesion, growth, and metastasis. Because of the great interest in MMP-2 activity, the detailed protocols for evaluating MMP-2-responsive contrast agents, especially photoacoustic probes for in vivo use, are helpful for researchers in the field. We here describe the detailed synthetic procedure of MMP-2-activatable photoacoustic probe AlNc-pep-PEG consisting of aluminum naphthalocyanine, MMP-2-responsive peptide sequence, and poly(ethylene glycol), which has recently been developed in our research group. The detailed measurement protocol of photoacoustic signal intensity in vitro and in vivo by using in-house built photoacoustic signal measurement system and photoacoustic imaging apparatus are also summarized.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Nogita", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Oe", "name": null }, { "creator_type": "author", "first_name": "Huiying", "last_name": "Mu", "name": null }, { "creator_type": "author", "first_name": "Wenting", "last_name": "Huo", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/bs.mie.2021.07.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34353500" } }, "mesh": [ { "descriptor": "Aluminum", "descriptor_ui": "D000535", "major_topic": false }, { "descriptor": "Contrast Media", "descriptor_ui": "D003287", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Matrix Metalloproteinase 2", "descriptor_ui": "D020778", "major_topic": true }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "89-109", "proceedings_title": null, "publisher": "", "title": "Methods in enzymology", "volume": "657", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Aluminum naphthalocyanine conjugate as an MMP-2-activatable photoacoustic probe for in vivo tumor imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lymph nodes (LNs) are secondary lymphoid organs that function as the first line of defense against invasive foreign substances. Within the LNs, different types of immune cells are strategically localized to induce immune responses efficiently. Such a sophisticated tissue structure is a complex of functionally specialized niches, constructed by a variety of fibroblastic stromal cells. Elucidating the characteristics and functions of the niches and stromal cells will facilitate comprehension of the immune response induced in the LNs. Three recent studies offered novel insights into specialized stromal cells. In our discussion of these surprisingly diverse stromal cells, we will integrate information from these studies to improve knowledge about the structure and niches of LN.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Arata", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Madoka", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Guangwei", "last_name": "Cui", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ikuta", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-3-030-86016-5_5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34850284" } }, "mesh": [ { "descriptor": "Immunity", "descriptor_ui": "D007109", "major_topic": false }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": true }, { "descriptor": "Stromal Cells", "descriptor_ui": "D017154", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "103-121", "proceedings_title": null, "publisher": "", "title": "Current topics in microbiology and immunology", "volume": "434", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Lymph Node Stromal Cells: Diverse Meshwork Structures Weave Functionally Subdivided Niches.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A split-luciferase-based cell fusion assay enables high-throughput screening of myogenesis-promoting chemicals in chemical libraries. The assay consists of two C2C12 myoblast-derived cell lines (N- and C-cells), each of which stably expresses either an N- or C-terminal split-firefly luciferase (FLuc) fragment fused to a naturally split DnaE intein (N- and C-probes, respectively). The fusion of N- and C-cells during myogenesis induces bioluminescence (BL) in the cytosol due to a stable reconstitution of the split-FLuc. Thus, the myogenesis-promoting effects of a chemical compound can be determined through the enhanced BL intensity. Here, we describe the preparation of N- and C-cells and determination of the myogenesis-promoting effects of imatinib using a 96-well microplate-based assay.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Qiaojing", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-1258-3_8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34050464" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": true }, { "descriptor": "Cell Fusion", "descriptor_ui": "D002459", "major_topic": true }, { "descriptor": "Cytosol", "descriptor_ui": "D003600", "major_topic": false }, { "descriptor": "Imatinib Mesylate", "descriptor_ui": "D000068877", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle Development", "descriptor_ui": "D024510", "major_topic": true }, { "descriptor": "Muscle Fibers, Skeletal", "descriptor_ui": "D018485", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "79-87", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2274", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "A Split-Luciferase-Based Cell Fusion Assay for Evaluating the Myogenesis-Promoting Effects of Bioactive Molecules.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cells respond to a wide range of extracellular stimuli, and process the input information through an intracellular signaling system comprised of biochemical and biophysical reactions, including enzymatic and protein-protein interactions. It is essential to understand the molecular mechanisms underlying intracellular signal transduction in order to clarify not only physiological cellular functions but also pathological processes such as tumorigenesis. Fluorescent proteins have revolutionized the field of life science, and brought the study of intracellular signaling to the single-cell and subcellular levels. Much effort has been devoted to developing genetically encoded fluorescent biosensors based on fluorescent proteins, which enable us to visualize the spatiotemporal dynamics of cell signaling. In addition, optogenetic techniques for controlling intracellular signal transduction systems have been developed and applied in recent years by regulating intracellular signaling in a light-dependent manner. Here, we outline the principles of biosensors for probing intracellular signaling and the optogenetic tools for manipulating them.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuhei", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-981-15-8763-4_13" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33398816" } }, "mesh": [ { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Intracellular Space", "descriptor_ui": "D042541", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "225-234", "proceedings_title": null, "publisher": "", "title": "Advances in experimental medicine and biology", "volume": "1293", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualization and Manipulation of Intracellular Signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Durvalumab (anti-programmed cell death ligand-1) administration after concurrent chemoradiotherapy (cCRT) has improved the survival of patients with unresectable, locally advanced (LA) stage III non-small cell lung cancer (NSCLC). Some patients are unable to complete cCRT and cannot receive immunotherapy due to poor performance status based on adverse events after cCRT. Immunotherapy plays an important role in anti-programmed cell death ligand-1 (PD-L1)-positive advanced NSCLC and is replacing chemotherapy. In addition, radiotherapy and immunotherapy have been reported to have a synergistic effect. This Phase II, multicenter study (DOLPHIN, WJOG11619L, JapicCTI-194840) is designed to assess the efficacy and safety of durvalumab plus concurrent curative radiation therapy for PD-L1-positive unresectable LA-NSCLC without chemotherapy. Unresectable LA stage III NSCLC patients aged 20 years or older with a World Health Organization/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 and PD-L1 positivity are enrolled. The patients will receive curative radiation therapy (60 Gy) plus durvalumab 10 mg/kg every 2 weeks (q2w) for up to 12 months until there is evidence of disease progression (PD) or unacceptable toxicity. The primary endpoint is the 12-month progression-free survival rate as assessed by an independent central review. The secondary endpoints are progression-free survival, overall survival, objective response rate, treatment completion rate, and safety. Recruitment began in September 2019.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Motoko", "last_name": "Tachihara", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Tsujino", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kurata", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Isamu", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Teraoka", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Daga", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kodaira", "name": null }, { "creator_type": "author", "first_name": "Miyako", "last_name": "Satouchi", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Shimokawa", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Nakagawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.2147/cmar.s336262" }, "pmcid": { "normalized": "PMC8684372" }, "pmid": { "normalized": "34934361" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "9167-9173", "proceedings_title": null, "publisher": "", "title": "Cancer management and research", "volume": "13", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Rationale and Design for a Multicenter, Phase II Study of Durvalumab Plus Concurrent Radiation Therapy in Locally Advanced Non-Small Cell Lung Cancer: The DOLPHIN Study (WJOG11619L).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "[This corrects the article DOI: 10.3389/fnins.2021.650154.].", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Sato", "last_name": "Honma", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2021.810796" }, "pmcid": { "normalized": "PMC8689129" }, "pmid": { "normalized": "34949988" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "810796", "proceedings_title": null, "publisher": "", "title": "Frontiers in neuroscience", "volume": "15", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Corrigendum: Roles of Neuropeptides, VIP and AVP, in the Mammalian Central Circadian Clock.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pain in the elbow, shoulder, knee, lower back, and various other joints is relieved by adhesion of pyramidal thorn patches. To elucidate the pain relief mechanism induced by the patches, we established a quantitative method for estimating the pain reduction and investigated the brain regions that change in association with pain relief. We first attempted to quantify the pain relief using transcutaneous electric stimulation (TCES) and a visual analog scale (VAS), and then applied near-infrared spectroscopy (NIRS) to the prefrontal cortex, including the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex (OFC). We also examined the salivary oxytocin levels, which are thought to reflect oxytocin secretion levels from the posterior pituitary in the brain. Application of pyramidal thorn patches to pain regions decreased the pain degree estimated using TCES and VAS. Oxyhemoglobin levels were likely to be decreased in the left DLPFC on the basis of NIRS measurements during patch treatment, suggesting that the left DLPFC is involved in pain relief. On the other hand, the salivary oxytocin levels varied widely. A potential reason for the varying salivary oxytocin levels is its utilization in the pain region as an analgesic agent. Our results suggest that the left DLPFC will become a target brain region for pain therapy.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shun", "last_name": "Miyashiro", "name": null }, { "creator_type": "author", "first_name": "Yurika", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Nagaoka", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Toshizumi", "last_name": "Muta", "name": null }, { "creator_type": "author", "first_name": "Haruyuki", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuri", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Fusako", "last_name": "Koshikawa", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0256626" }, "pmcid": { "normalized": "PMC8382195" }, "pmid": { "normalized": "34424921" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Dorsolateral Prefrontal Cortex", "descriptor_ui": "D000087643", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Oxyhemoglobins", "descriptor_ui": "D010108", "major_topic": true }, { "descriptor": "Oxytocin", "descriptor_ui": "D010121", "major_topic": true }, { "descriptor": "Pain", "descriptor_ui": "D010146", "major_topic": false }, { "descriptor": "Pain Management", "descriptor_ui": "D059408", "major_topic": false }, { "descriptor": "Pain Measurement", "descriptor_ui": "D010147", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Saliva", "descriptor_ui": "D012463", "major_topic": false }, { "descriptor": "Spectroscopy, Near-Infrared", "descriptor_ui": "D019265", "major_topic": true }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "8", "normalized_date": "2021", "pages": "e0256626", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "16", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Pain relief associated with decreased oxyhemoglobin level in left dorsolateral prefrontal cortex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Photoacoustic (PA) imaging is an emerging imaging modality that combines the advantages of optical imaging and ultrasound imaging. In particular, activatable PA probes, which visualize the presence or the activity of target molecules in terms of a change of the PA signal, are useful tools for functional imaging. In this chapter, we describe the development of small-molecule-based activatable PA probes, focusing on the design and synthesis of PA-MMSiNQ, our recently developed activatable PA probe for HOCl. We also describe the protocols used for evaluation of PA-MMSiNQ with a UV-vis spectrometer and a PA imaging microscope.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ikeno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/bs.mie.2021.06.041" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34353483" } }, "mesh": [ { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Photoacoustic Techniques", "descriptor_ui": "D061088", "major_topic": true }, { "descriptor": "Spectrum Analysis", "descriptor_ui": "D013057", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "1-19", "proceedings_title": null, "publisher": "", "title": "Methods in enzymology", "volume": "657", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a small-molecule-based activatable photoacoustic probe.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The green fluorescent protein (GFP) derived from Pacific Ocean jellyfish is an essential tool in biology. GFP-solvent interactions can modulate the fluorescent property of GFP. We previously reported that glycine insertion is an effective mutation in the yellow variant of GFP, yellow fluorescent protein (YFP). Glycine insertion into one of the beta-strands comprising the barrel structure distorts its structure, allowing water molecules to invade near the chromophore, enhancing hydrostatic pressure or solution hydrophobicity sensitivity. However, the underlying mechanism of how glycine insertion imparts environmental sensitivity to YFP has not been elucidated yet. To unveil the relationship between fluorescence and beta-strand distortion, we investigated the effects of glycine insertion on the dependence of the optical properties of GFP variants named enhanced-GFP (eGFP) and its yellow (eYFP) and cyan (eCFP) variants with respect to pH, temperature, pressure, and hydrophobicity. Our results showed that the quantum yield decreased depending on the number of inserted glycines in all variants, and the dependence on pH, temperature, pressure, and hydrophobicity was altered, indicating the invasion of water molecules into the beta-barrel. Peak shifts in the emission spectrum were observed in glycine-inserted eGFP, suggesting a change of the electric state in the excited chromophore. A comparative investigation of the spectral shift among variants under different conditions demonstrated that glycine insertion rearranged the hydrogen bond network between His148 and the chromophore. The present results provide important insights for further understanding the fluorescence mechanism in GFPs and suggest that glycine insertion could be a potent approach for investigating the relationship between water molecules and the intra-protein chromophore.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takamitsu J.", "last_name": "Morikawa", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v18.016" }, "pmcid": { "normalized": "PMC8214926" }, "pmid": { "normalized": "34178565" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "145-158", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "18", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Glycine insertion modulates the fluorescence properties of Aequorea victoria green fluorescent protein and its variants in their ambient environment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Spatiotemporal dynamics of cellular proteins, including protein-protein interactions and conformational changes, is essential for understanding cellular functions such as synaptic plasticity, cell motility, and cell division. One of the best ways to understand the mechanisms of signal transduction is to visualize protein activity with high spatiotemporal resolution in living cells within tissues. Optogenetic probes such as fluorescent proteins, in combination with Forster Resonance Energy Transfer (FRET) techniques, enable the measurement of protein-protein interactions and conformational changes in response to signaling events in living cells. Of the various FRET detection systems, two-photon fluorescence lifetime imaging microscopy (2pFLIM) is one of the methods best suited to monitoring FRET in subcellular compartments of living cells located deep within tissues, such as brain slices. This review will introduce the principle of 2pFLIM-FRET and the use of chromoproteins for imaging intracellular protein activities and protein-protein interactions. Also, we will discuss two examples of 2pFLIM-FRET application: imaging actin polymerization in synapses of hippocampal neurons in brain sections and detecting small GTPase Cdc42 activity in astrocytes.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-981-15-8763-4_18" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33398821" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence, Multiphoton", "descriptor_ui": "D036641", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "295-308", "proceedings_title": null, "publisher": "", "title": "Advances in experimental medicine and biology", "volume": "1293", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Optogenetic Imaging of Protein Activity Using Two-Photon Fluorescence Lifetime Imaging Microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Microglia are the resident phagocytes of the central nervous system, and microglial activation is considered to play an important role in the pathogenesis of neurodegenerative diseases. Recent studies with single-cell RNA analysis of CNS cells in Alzheimer's disease and diverse other neurodegenerative conditions revealed that the transition from homeostatic microglia to disease-associated microglia was defined by changes of gene expression levels, including down-regulation of the P2Y12 receptor gene (P2Y12R). However, it is yet to be clarified in Alzheimer's disease brains whether and when this down-regulation occurs in response to amyloid-beta and tau depositions, which are core pathological processes in the disease etiology. To further evaluate the significance of P2Y12 receptor alterations in the neurodegenerative pathway of Alzheimer's disease and allied disorders, we generated an anti-P2Y12 receptor antibody and examined P2Y12 receptor expressions in the brains of humans and model mice bearing amyloid-beta and tau pathologies. We observed that the brains of both Alzheimer's disease and non-Alzheimer's disease tauopathy patients and tauopathy model mice (rTg4510 and PS19 mouse lines) displayed declined microglial P2Y12 receptor levels in regions enriched with tau inclusions, despite an increase in the total microglial population. Notably, diminution of microglial immunoreactivity with P2Y12 receptor was noticeable prior to massive accumulations of phosphorylated tau aggregates and neurodegeneration in rTg4510 mouse brains, despite a progressive increase of total microglial population. On the other hand, Iba1-positive microglia encompassing compact and dense-cored amyloid-beta plaques expressed P2Y12 receptor at varying levels in amyloid precursor protein (APP) mouse models (APP23 and App(NL-F/NL-F) mice). By contrast, neuritic plaques in Alzheimer's disease brains were associated with P2Y12 receptor-negative microglia. These data suggest that the down-regulation of microglia P2Y12 receptor, which is characteristic of disease-associated microglia, is intimately associated with tau rather than amyloid-beta pathologies from an early stage and could be a sensitive index for neuroinflammatory responses to Alzheimer's disease-related neurodegenerative processes.", "classifications": [ { "id": "19H05437", "label": "19H05437", "researcher": "Naruhiko Sahara", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Minamihisamatsu", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Shimojo", "name": null }, { "creator_type": "author", "first_name": "Xiaoyun", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Matsuba", "name": null }, { "creator_type": "author", "first_name": "Bin", "last_name": "Ji", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Masanao", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Akatsu", "name": null }, { "creator_type": "author", "first_name": "Daita", "last_name": "Kaneda", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "John L.", "last_name": "Robinson", "name": null }, { "creator_type": "author", "first_name": "Virginia M.-Y.", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takaomi C.", "last_name": "Saido", "name": null }, { "creator_type": "author", "first_name": "John Q.", "last_name": "Trojanowski", "name": null }, { "creator_type": "author", "first_name": "Ming-Rong", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/braincomms/fcab011" }, "pmcid": { "normalized": "PMC7901060" }, "pmid": { "normalized": "33644757" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "1", "normalized_date": "2021", "pages": "fcab011", "proceedings_title": null, "publisher": "", "title": "Brain communications", "volume": "3", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Distinct microglial response against Alzheimer's amyloid and tau pathologies characterized by P2Y12 receptor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Schizophrenia is a mental illness that involves both genetic and environmental factors. Clozapine, an atypical antipsychotic, is a well-established therapy for treatment-resistant schizophrenia. In this study, we focused on a set of monozygotic twins with treatment-resistant schizophrenia in which one twin effectively responded to clozapine treatment and the other did not. Our previous study generated neurons from induced pluripotent stem (iPS) cells derived from these patients and compared the transcriptome profiles between mock- and clozapine-treated neurons. In this study, we performed genome-wide DNA methylation profiling to investigate the mechanisms underlying gene expression changes. First, we extracted the differentially methylated sites from each twin based on statistical analysis. Then, we combined the DNA methylation profiling with transcriptome profiling from our previous RNA-seq data. Among the genes with altered methylation and expression, we found the different proportions of the genes related to neuronal and synaptic functions between the clozapine responder and non-responder (35.7 and 6.7%, respectively). This trend was observed even when the basal differences between the responder and non-responder was excluded. These results suggest that effective clozapine action may correct the abnormalities of neuronal and synapse functions in schizophrenia via changes in methylation.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masataka", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Hidenaga", "last_name": "Yamamori", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Shusuke", "last_name": "Numata", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fpsyt.2021.734606" }, "pmcid": { "normalized": "PMC8488120" }, "pmid": { "normalized": "34616320" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "734606", "proceedings_title": null, "publisher": "", "title": "Frontiers in psychiatry", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Methylation Analysis in Monozygotic Twins With Treatment-Resistant Schizophrenia and Discordant Responses to Clozapine.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The application of smartphones as detectors is essential to achieve ubiquitous measurement targeting biomolecules. Because bioluminescence (BL), as a tag for a target sample, does not require an excitation light source, it can be combined with a smartphone to constitute a compact and mobile measurement system. A method was recently established to detect the spectral change of ratiometric indicators based on bioluminescence resonance energy transfer with a smartphone camera. For example, it was possible to detect changes in the BL color of the Ca(2+) indicator quantitatively and easily calculate the concentration of free Ca(2+) by setting appropriate image acquisition conditions in a smartphone application. In this paper, we describe techniques to obtain scientifically relevant and reliable BL data with such a convenient instrument. This protocol expands the potential of the smartphone as a personal imaging device with high mobility that can be used anywhere.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-1258-3_25" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34050481" } }, "mesh": [ { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Escherichia coli Proteins", "descriptor_ui": "D029968", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Smartphone", "descriptor_ui": "D000068997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "295-304", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2274", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Method for Detecting Emission Spectral Change of Bioluminescent Ratiometric Indicators by a Smartphone.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cellular signaling is regulated by the spatiotemporal dynamics and kinetics of molecular behavior. To investigate the mechanisms at the molecular level, fluorescence single-molecule analysis is an effective method owing to the direct observation of individual molecules in situ in cells and the results in quantitative information about the behavior. The integration of machine learning into this analysis modality enables the acquisition of behavioral features at all time points of all molecules. As a case study, we described a hidden Markov model-based approach to infer the molecular states of mobility and clustering for epidermal growth factor receptor (EGFR) along a single-molecule trajectory. We reveal a scheme of the receptor signaling through the dynamic coupling of the mobility and clustering states under the influence of a local membrane structure. As the activation process progressed, EGFR generally converged to an immobile cluster. This state exhibited high affinity with a specific cytoplasmic protein, shown by two-color single-molecule analysis, and could be a platform for downstream signaling. The method was effective for elucidating the biophysical mechanisms of signaling regulation when comprehensive analysis is possible for a huge number and multiple molecular species in the signaling pathway. Thus, a fully automated system for single-molecule analysis, in which indispensable expertise was replicated using artificial intelligence, has been developed to enable in-cell large-scale analysis. This system opens new single-molecule approaches for pharmacological applications as well as the basic sciences.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-981-33-6064-8_3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33834432" } }, "mesh": [ { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": true }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Single Molecule Imaging", "descriptor_ui": "D000072760", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "59-80", "proceedings_title": null, "publisher": "", "title": "Advances in experimental medicine and biology", "volume": "1310", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "In-Cell Single-Molecule Analysis of Molecular State and Reaction Kinetics Coupling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In mammals, the central circadian clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Individual SCN cells exhibit intrinsic oscillations, and their circadian period and robustness are different cell by cell in the absence of cellular coupling, indicating that cellular coupling is important for coherent circadian rhythms in the SCN. Several neuropeptides such as arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) are expressed in the SCN, where these neuropeptides function as synchronizers and are important for entrainment to environmental light and for determining the circadian period. These neuropeptides are also related to developmental changes of the circadian system of the SCN. Transcription factors are required for the formation of neuropeptide-related neuronal networks. Although VIP is critical for synchrony of circadian rhythms in the neonatal SCN, it is not required for synchrony in the embryonic SCN. During postnatal development, the clock genes cryptochrome (Cry)1 and Cry2 are involved in the maturation of cellular networks, and AVP is involved in SCN networks. This mini-review focuses on the functional roles of neuropeptides in the SCN based on recent findings in the literature.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Sato", "last_name": "Honma", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2021.650154" }, "pmcid": { "normalized": "PMC8081951" }, "pmid": { "normalized": "33935635" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "650154", "proceedings_title": null, "publisher": "", "title": "Frontiers in neuroscience", "volume": "15", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Roles of Neuropeptides, VIP and AVP, in the Mammalian Central Circadian Clock.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "HIV-1 infectivity is achieved through virion maturation. Virus particles undergo structural changes via cleavage of the Gag polyprotein mediated by the viral protease, causing the transition from an uninfectious to an infectious status. The majority of proviruses in people living with HIV-1 treated with combination antiretroviral therapy are defective with large internal deletions. Defective proviral DNA frequently preserves intact sequences capable of expressing viral structural proteins to form virus-like particles whose maturation status is an important factor for chronic antigen-mediated immune stimulation and inflammation. Thus, novel methods to study the maturation capability of defective virus particles are needed to characterize their immunogenicity. To build a quantitative tool to study virion maturation in vitro, we developed a novel single virion visualization technique based on fluorescence resonance energy transfer (FRET). We inserted an optimized intramolecular CFP-YPF FRET donor-acceptor pair bridged with an HIV-1 protease cleavage sequence between the Gag MA-CA domains. This system allowed us to microscopically distinguish mature and immature virions via their FRET signal when the FRET donor and acceptor proteins were separated by the viral protease during maturation. We found that approximately 80% of the FRET labeled virus particles were mature with equivalent infectivity to wild type. The proportion of immature virions was increased by treatment of virus producer cells with a protease inhibitor in a dose-dependent manner, which corresponded to a relative decrease in infectivity. Potential areas of application for this tool are assessing maturation efficiency in different cell type settings of intact or deficient proviral DNA integrated cells. We believe that this FRET-based single-virion imaging platform will facilitate estimating the impact on the immune system of both extracellular intact and defective viruses by quantifying the Gag maturation status.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Anamaria D.", "last_name": "Sarca", "name": null }, { "creator_type": "author", "first_name": "Luca", "last_name": "Sardo", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Shirakawa", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Takaori-Kondo", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Izumi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fmicb.2021.647452" }, "pmcid": { "normalized": "PMC7985248" }, "pmid": { "normalized": "33767685" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "647452", "proceedings_title": null, "publisher": "", "title": "Frontiers in microbiology", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "FRET-Based Detection and Quantification of HIV-1 Virion Maturation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: We aimed to explore the associations of musculoskeletal inflammation patterns with peripheral blood innate lymphoid cell (ILC) populations, serum cytokines/chemokines, and treatment response to methotrexate in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: We enrolled 100 patients with either RA or SpA and performed ultrasound to evaluate power Doppler signals for synovitis (52 joint regions), tenosynovitis (20 tendons), and enthesitis (44 sites). We performed clustering analysis using unsupervised random forest based on the multi-axis ultrasound information and classified the patients into groups. We identified and counted ILC1-3 populations in the peripheral blood by flow cytometry and also measured the serum levels of 20 cytokines/chemokines. We also determined ACR20 response at 3 months in 38 patients who began treatment with methotrexate after study assessment. RESULTS: Synovitis was more prevalent and severe in RA than in SpA, whereas tenosynovitis and enthesitis were comparable between RA and SpA. Patients were classified into two groups which represented synovitis-dominant and synovitis-nondominant inflammation patterns. While peripheral ILC counts were not significantly different between RA and SpA, they were significantly higher in the synovitis-nondominant group than in the synovitis-dominant group (ILC1-3: p = 0.0007, p = 0.0061, and p = 0.0002, respectively). On the other hand, clustering of patients based on serum cytokines/chemokines did not clearly correspond either to clinical diagnoses or to synovitis-dominant/nondominant patterns. The synovitis-dominant pattern was the most significant factor that predicted clinical response to methotrexate (p = 0.0065). CONCLUSIONS: Musculoskeletal inflammation patterns determined by ultrasound are associated with peripheral ILC counts and could predict treatment response to methotrexate.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Manami", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Suga", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Norihiro", "last_name": "Mimura", "name": null }, { "creator_type": "author", "first_name": "Tadamichi", "last_name": "Kasuya", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Furuya", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Arifumi", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Furuta", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Suto", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nakajima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0252116" }, "pmcid": { "normalized": "PMC8139502" }, "pmid": { "normalized": "34019595" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Arthritis, Rheumatoid", "descriptor_ui": "D001172", "major_topic": false }, { "descriptor": "Chemokines", "descriptor_ui": "D018925", "major_topic": false }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Lymphocytes", "descriptor_ui": "D008214", "major_topic": false }, { "descriptor": "Methotrexate", "descriptor_ui": "D008727", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Spondylarthritis", "descriptor_ui": "D025241", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "5", "normalized_date": "2021", "pages": "e0252116", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "16", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Associations of ultrasound-based inflammation patterns with peripheral innate lymphoid cell populations, serum cytokines/chemokines, and treatment response to methotrexate in rheumatoid arthritis and spondyloarthritis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Whereas adenosine 5'-triphosphate (ATP) is the major energy source in cells, extracellular ATP (eATP) released from activated/damaged cells is widely thought to represent a potent damage-associated molecular pattern that promotes inflammatory responses. Here, we provide suggestive evidence that eATP is constitutively produced in the uninflamed lymph node (LN) paracortex by naive T cells responding to C-C chemokine receptor type 7 (CCR7) ligand chemokines. Consistently, eATP was markedly reduced in naive T cell-depleted LNs, including those of nude mice, CCR7-deficient mice, and mice subjected to the interruption of the afferent lymphatics in local LNs. Stimulation with a CCR7 ligand chemokine, CCL19, induced ATP release from LN cells, which inhibited CCR7-dependent lymphocyte migration in vitro by a mechanism dependent on the purinoreceptor P2X7 (P2X7R), and P2X7R inhibition enhanced T cell retention in LNs in vivo. These results collectively indicate that paracortical eATP is produced by naive T cells in response to constitutively expressed chemokines, and that eATP negatively regulates CCR7-mediated lymphocyte migration within LNs via a specific subtype of ATP receptor, demonstrating its fine-tuning role in homeostatic cell migration within LNs.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Daichi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Umemoto", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Ueta", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Hayasaka", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Matsuzaki", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Hamachi", "name": null }, { "creator_type": "author", "first_name": "Gennady G.", "last_name": "Yegutkin", "name": null }, { "creator_type": "author", "first_name": "Marko", "last_name": "Salmi", "name": null }, { "creator_type": "author", "first_name": "Sirpa", "last_name": "Jalkanen", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Miyasaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2021.786595" }, "pmcid": { "normalized": "PMC8728011" }, "pmid": { "normalized": "35003105" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Intravital Microscopy", "descriptor_ui": "D000069416", "major_topic": false }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Animal", "descriptor_ui": "D023421", "major_topic": false }, { "descriptor": "Purinergic P2X Receptor Antagonists", "descriptor_ui": "D058920", "major_topic": false }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Receptors, CCR7", "descriptor_ui": "D054400", "major_topic": false }, { "descriptor": "Receptors, Purinergic P2X7", "descriptor_ui": "D058486", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false }, { "descriptor": "Tetrazoles", "descriptor_ui": "D013777", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "786595", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Extracellular ATP Limits Homeostatic T Cell Migration Within Lymph Nodes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Heart failure is a complex clinical syndrome characterized by insufficient cardiac function. Heart-resident and infiltrated macrophages have been shown to play important roles in the cardiac remodeling that occurs in response to cardiac pressure overload. However, the possible roles of T cells in this process, have not been well characterized. Here we show that T cell depletion conferred late-stage heart protection but induced cardioprotective hypertrophy at an early stage of heart failure caused by cardiac pressure overload. Single-cell RNA sequencing analysis revealed that CD8(+)T cell depletion induced cardioprotective hypertrophy characterized with the expression of mitochondrial genes and growth factor receptor genes. CD8(+)T cells regulated the conversion of both cardiac-resident macrophages and infiltrated macrophages into cardioprotective macrophages expressing growth factor genes such as Areg, Osm, and Igf1, which have been shown to be essential for the myocardial adaptive response after cardiac pressure overload. Our results demonstrate a dynamic interplay between cardiac CD8(+)T cells and macrophages that is necessary for adaptation to cardiac stress, highlighting the homeostatic functions of resident and infiltrated macrophages in the heart.", "classifications": [ { "id": "21H00432", "label": "21H00432", "researcher": "Minako Ito", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kyoko", "last_name": "Komai", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Seitaro", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Shichino", "name": null }, { "creator_type": "author", "first_name": "Manami", "last_name": "Katoh", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Ko", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Iizuka-Koga", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Nakatsukasa", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2021.763647" }, "pmcid": { "normalized": "PMC8564148" }, "pmid": { "normalized": "34745139" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cardiomegaly", "descriptor_ui": "D006332", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "763647", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-Cell Analysis Revealed the Role of CD8(+) Effector T Cells in Preventing Cardioprotective Macrophage Differentiation in the Early Phase of Heart Failure.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "21H00422", "label": "21H00422", "researcher": "Daisuke Ono", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jihwan", "last_name": "Myung", "name": null }, { "creator_type": "author", "first_name": "Takahiro J.", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Jeff R.", "last_name": "Jones", "name": null }, { "creator_type": "author", "first_name": "Rae", "last_name": "Silver", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2021.735007" }, "pmcid": { "normalized": "PMC8380925" }, "pmid": { "normalized": "34434086" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "735007", "proceedings_title": null, "publisher": "", "title": "Frontiers in neuroscience", "volume": "15", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Editorial: Development of Circadian Clock Functions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "All living tissues and organs have their respective sizes, critical to various biological functions, such as development, growth, and homeostasis. As tissues and organs generally converge to a certain size, intrinsic regulatory mechanisms may be involved in the maintenance of size regulation. In recent years, important findings regarding size regulation have been obtained from diverse disciplines at the molecular and cellular levels. Here, I briefly review the size regulation of biological tissues from the perspective of control systems. This minireview focuses on how feedback systems engage in tissue size maintenance through the mechanical interactions of constituent cell collectives through intracellular signaling. I introduce a general framework of a feedback control system for tissue size regulation, followed by two examples: maintenance of epithelial tissue volume and epithelial tube diameter. The examples deliver the idea of how cellular mechano-response works for maintaining tissue size.", "classifications": [ { "id": "21H00426", "label": "21H00426", "researcher": "Tsuyoshi Hirashima", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2021.820391" }, "pmcid": { "normalized": "PMC8795865" }, "pmid": { "normalized": "35096843" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "820391", "proceedings_title": null, "publisher": "", "title": "Frontiers in cell and developmental biology", "volume": "9", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Mechanical Feedback Control for Multicellular Tissue Size Maintenance: A Minireview.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Channelrhodopsins (ChRs) are the light-gated ion channels that have opened the research field of optogenetics. They were originally identified in the green alga Chlamydomonas reinhardtii, a biciliated unicellular alga that inhabits in freshwater, swims with the cilia, and undergoes photosynthesis. It has various advantages as an experimental organism and is used in a wide range of research fields including photosynthesis, cilia, and sexual reproduction. ChRs function as the primary photoreceptor for the cell's photo-behavioral responses, seen as changes in the manner of swimming after photoreception. In this chapter, we will introduce C. reinhardtii as an experimental organism and explain our current understanding of how the cell senses light and shows photo-behavioral responses.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Isu", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Ueki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-981-15-8763-4_2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33398805" } }, "mesh": [ { "descriptor": "Channelrhodopsins", "descriptor_ui": "D000075402", "major_topic": false }, { "descriptor": "Chlamydomonas reinhardtii", "descriptor_ui": "D016825", "major_topic": false }, { "descriptor": "Cilia", "descriptor_ui": "D002923", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": true }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Photosynthesis", "descriptor_ui": "D010788", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "21-33", "proceedings_title": null, "publisher": "", "title": "Advances in experimental medicine and biology", "volume": "1293", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Channelrhodopsin-Dependent Photo-Behavioral Responses in the Unicellular Green Alga Chlamydomonas reinhardtii.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Integrin regulation by Rap1 is indispensable for lymphocyte recirculation. In mice having B-cell-specific Rap1a/b double knockouts (DKO), the number of B cells in lymph nodes decreased to approximately 4% of that of control mice, and B cells were present in the spleen and blood. Upon the immunization with NP-CGG, DKO mice demonstrated the defective GC formation in the spleen, and the reduced NP-specific antibody production. In vitro, Rap1 deficiency impaired the movement of activated B cells along the gradients of chemoattractants known to be critical for their localization in the follicles. Furthermore, B-1a cells were almost completely absent in the peritoneal cavity, spleen and blood of adult DKO mice, and the number of B-cell progenitor/precursor (B-p) were reduced in neonatal and fetal livers. However, DKO B-ps normally proliferated, and differentiated into IgM(+) cells in the presence of IL-7. CXCL12-dependent migration of B-ps on the VCAM-1 was severely impaired by Rap1 deficiency. Immunostaining study of fetal livers revealed defects in the co-localization of DKO B-ps and IL-7-producing stromal cells. This study proposes that the profound effects of Rap1-deficiency on humoral responses and B-1a cell generation may be due to or in part caused by impairments of the chemoattractant-dependent positioning and the contact with stromal cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Sayaka", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Risa", "last_name": "Sugioka", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Miwa", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hidehiro", "last_name": "Fukuyama", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Kotani", "name": null }, { "creator_type": "author", "first_name": "Koko", "last_name": "Katagiri", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2021.624419" }, "pmcid": { "normalized": "PMC8203927" }, "pmid": { "normalized": "34140948" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Chemokine CXCL12", "descriptor_ui": "D054377", "major_topic": false }, { "descriptor": "Chemotaxis, Leukocyte", "descriptor_ui": "D002634", "major_topic": true }, { "descriptor": "gamma-Globulins", "descriptor_ui": "D005719", "major_topic": false }, { "descriptor": "Germinal Center", "descriptor_ui": "D018858", "major_topic": false }, { "descriptor": "Immunity, Humoral", "descriptor_ui": "D056724", "major_topic": false }, { "descriptor": "Immunization", "descriptor_ui": "D007114", "major_topic": false }, { "descriptor": "Intercellular Adhesion Molecule-1", "descriptor_ui": "D018799", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Precursor Cells, B-Lymphoid", "descriptor_ui": "D054448", "major_topic": false }, { "descriptor": "rap GTP-Binding Proteins", "descriptor_ui": "D020668", "major_topic": false }, { "descriptor": "rap1 GTP-Binding Proteins", "descriptor_ui": "D020827", "major_topic": false }, { "descriptor": "Spleen", "descriptor_ui": "D013154", "major_topic": false }, { "descriptor": "Vascular Cell Adhesion Molecule-1", "descriptor_ui": "D019010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "624419", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Rap1 Is Essential for B-Cell Locomotion, Germinal Center Formation and Normal B-1a Cell Population.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masahito", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fncir.2021.703300" }, "pmcid": { "normalized": "PMC8261147" }, "pmid": { "normalized": "34248506" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "703300", "proceedings_title": null, "publisher": "", "title": "Frontiers in neural circuits", "volume": "15", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Editorial: Neuroscience and Neurotechnology of Neuronal Cell Surface Molecules in Neural Circuits.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In addition to simple on/off switches for molecular activity, spatiotemporal dynamics are also thought to be important for the regulation of cellular function. However, their physiological significance and in vivo importance remain largely unknown. Fluorescence imaging technology is a powerful technique that can reveal the spatiotemporal dynamics of molecular activity. In addition, because imaging detects the correlations between molecular activity and biological phenomena, the technique of molecular manipulation is also important to analyze causal relationships. Recent advances in optical manipulation techniques that artificially perturb molecules and cells via light can address this issue to elucidate the causality between manipulated target and its physiological function. The use of light enables the manipulation of molecular activity in microspaces, such as organelles and nerve spines. In this review, we describe the chromophore-assisted light inactivation method, which is an optical manipulation technique that has been attracting attention in recent years.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kiwamu", "last_name": "Takemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.2183/pjab.97.011" }, "pmcid": { "normalized": "PMC8062263" }, "pmid": { "normalized": "33840676" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromophore-Assisted Light Inactivation", "descriptor_ui": "D061885", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "4", "normalized_date": "2021", "pages": "197-209", "proceedings_title": null, "publisher": "", "title": "Proceedings of the Japan Academy. Series B, Physical and biological sciences", "volume": "97", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Optical manipulation of molecular function by chromophore-assisted light inactivation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neuroligin is a postsynaptic cell-adhesion molecule that is involved in synapse formation and maturation by interacting with presynaptic neurexin. Mutations in neuroligin genes, including the arginine to cystein substitution at the 451st amino acid residue (R451C) of neuroligin-3 (NLGN3), have been identified in patients with autism spectrum disorder (ASD). Functional magnetic resonance imaging and examination of post-mortem brain in ASD patients implicate alteration of cerebellar morphology and Purkinje cell (PC) loss. In the present study, we examined possible association between the R451C mutation in NLGN3 and synaptic development and function in the mouse cerebellum. In NLGN3-R451C mutant mice, the expression of NLGN3 protein in the cerebellum was reduced to about 10% of the level of wild-type mice. Elimination of redundant climbing fiber (CF) to PC synapses was impaired from postnatal day 10-15 (P10-15) in NLGN3-R451C mutant mice, but majority of PCs became mono-innervated as in wild-type mice after P16. In NLGN3-R451C mutant mice, selective strengthening of a single CF relative to the other CFs in each PC was impaired from P16, which persisted into juvenile stage. Furthermore, the inhibition to excitation (I/E) balance of synaptic inputs to PCs was elevated, and calcium transients in the soma induced by strong and weak CF inputs were reduced in NLGN3-R451C mutant mice. These results suggest that a single point mutation in NLGN3 significantly influences the synapse development and refinement in cerebellar circuitry, which might be related to the pathogenesis of ASD.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Esther Suk King", "last_name": "Lai", "name": null }, { "creator_type": "author", "first_name": "Hisako", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Tabuchi", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fncir.2021.676891" }, "pmcid": { "normalized": "PMC8273702" }, "pmid": { "normalized": "34262438" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autism Spectrum Disorder", "descriptor_ui": "D000067877", "major_topic": true }, { "descriptor": "Autistic Disorder", "descriptor_ui": "D001321", "major_topic": true }, { "descriptor": "Cell Adhesion Molecules, Neuronal", "descriptor_ui": "D015816", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "676891", "proceedings_title": null, "publisher": "", "title": "Frontiers in neural circuits", "volume": "15", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "An Autism-Associated Neuroligin-3 Mutation Affects Developmental Synapse Elimination in the Cerebellum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In some types of meditation, such as mindfulness and Zen, breathing is the focus of attention, whereas during an excessive, short-period of anaerobic exercise, the muscles become the focus of attention. Thus, during both efforts, one's attention is focused on a certain feature of the body. Both meditation and exercise generally provide mental refreshment to humans. We hypothesized that the same brain regions are activated by both efforts in humans. To examine this hypothesis, we engaged participants in 3 tasks: meditation, exercise, and a control task. After each task, the participants underwent a 2-back test to concentrate their thoughts, while changes in their blood hemoglobin levels were simultaneously monitored using near-infrared spectroscopy (NIRS). Seventeen participants (20-24 years of age; 11 men, 6 women) were enrolled. We applied a fast-Fourier transform (FFT) analysis to the NIRS wave data and calculated the correlation coefficients of the FFT data between (1) meditation and control, (2) exercise and control, and (3) meditation and exercise, at the orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC), brain areas that are generally involved in mental refreshment. A significant difference in the correlation coefficients between the OFC and DLPFC was detected in the meditation and exercise analysis, and signal source analysis confirmed that the NIRS waves spread from the right and left OFC edges (i.e., right and left temples) toward the center. Our results suggest that both meditation and exercise activate the OFC, which is involved in emotional reactions and motivation behavior, resulting in mental refreshment.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shun", "last_name": "Miyashiro", "name": null }, { "creator_type": "author", "first_name": "Yurika", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Toshizumi", "last_name": "Muta", "name": null }, { "creator_type": "author", "first_name": "Haruyuki", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuri", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Fusako", "last_name": "Koshikawa", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0247685" }, "pmcid": { "normalized": "PMC7901739" }, "pmid": { "normalized": "33621250" } }, "mesh": [ { "descriptor": "Attention", "descriptor_ui": "D001288", "major_topic": false }, { "descriptor": "Brain Mapping", "descriptor_ui": "D001931", "major_topic": false }, { "descriptor": "Exercise", "descriptor_ui": "D015444", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Meditation", "descriptor_ui": "D019122", "major_topic": true }, { "descriptor": "Mindfulness", "descriptor_ui": "D064866", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Spectroscopy, Near-Infrared", "descriptor_ui": "D019265", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "2", "normalized_date": "2021", "pages": "e0247685", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "16", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Activation of the orbitofrontal cortex by both meditation and exercise: A near-infrared spectroscopy study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP) display psychomotor abnormalities, most of which are ameliorated by atypical antipsychotics with serotonin (5-HT) 2A receptor (5-HT2A) antagonism. Heterozygous Pacap mutant mice show a significantly higher hallucinogenic response than wild-type mice to a 5-HT2A agonist. Endogenous PACAP may, therefore, affect 5-HT2A signaling; however, the underlying neurobiological mechanism for this remains unclear. Here, we examined whether PACAP modulates 5-HT2A signaling by addressing cellular protein localization. PACAP induced an increase in internalization of 5-HT2A but not 5-HT1A, 5-HT2C, dopamine D2 receptors or metabotropic glutamate receptor 2 in HEK293T cells. This PACAP action was inhibited by protein kinase C inhibitors, beta-arrestin2 silencing, the PACAP receptor PAC1 antagonist PACAP6-38, and PAC1 silencing. In addition, the levels of endogenous 5-HT2A were decreased on the cell surface of primary cultured cortical neurons after PACAP stimulation and were increased in frontal cortex cell membranes of Pacap(-/-) mice. Finally, intracerebroventricular PACAP administration suppressed 5-HT2A agonist-induced head twitch responses in mice. These results suggest that PACAP-PAC1 signaling increases 5-HT2A internalization resulting in attenuation of 5-HT2A-mediated signaling, although further study is necessary to determine the relationship between behavioral abnormalities in Pacap(-/-) mice and PACAP-induced 5-HT2A internalization.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Moriguchi", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Encho", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fendo.2021.732456" }, "pmcid": { "normalized": "PMC8574227" }, "pmid": { "normalized": "34759890" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Receptor, Serotonin, 5-HT2A", "descriptor_ui": "D044402", "major_topic": false }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I", "descriptor_ui": "D051237", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "732456", "proceedings_title": null, "publisher": "", "title": "Frontiers in endocrinology", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "PACAP-PAC1 Signaling Regulates Serotonin 2A Receptor Internalization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Photo-induced behavioral responses (photobehaviors) are crucial to the survival of motile phototrophic organisms in changing light conditions. Volvocine green algae are excellent model organisms for studying the regulatory mechanisms of photobehavior. We recently reported that unicellular Chlamydomonas reinhardtii and multicellular Volvox rousseletii exhibit similar photobehaviors, such as phototactic and photoshock responses, via different ciliary regulations. To clarify how the regulatory systems have changed during the evolution of multicellularity, we investigated the photobehaviors of four-celled Tetrabaena socialis. Surprisingly, unlike C. reinhardtii and V. rousseletii, T. socialis did not exhibit immediate photobehaviors after light illumination. Electrophysiological analysis revealed that the T. socialis eyespot does not function as a photoreceptor. Instead, T. socialis exhibited slow accumulation toward the light source in a photosynthesis-dependent manner. Our assessment of photosynthetic activities showed that T. socialis chloroplasts possess higher photoprotection abilities against strong light than C. reinhardtii. These data suggest that C. reinhardtii and T. socialis employ different strategies to avoid high-light stress (moving away rapidly and gaining photoprotection, respectively) despite their close phylogenetic relationship.", "classifications": [ { "id": "21H00420", "label": "21H00420", "researcher": "Ken-ichi Wakabayashi", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Asuka", "last_name": "Tanno", "name": null }, { "creator_type": "author", "first_name": "Ryutaro", "last_name": "Tokutsu", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Arakaki", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Ueki", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Minagawa", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null }, { "creator_type": "author", "first_name": "Hisayoshi", "last_name": "Nozaki", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0259138" }, "pmcid": { "normalized": "PMC8547699" }, "pmid": { "normalized": "34699573" } }, "mesh": [ { "descriptor": "Chlorophyta", "descriptor_ui": "D000460", "major_topic": false }, { "descriptor": "Photic Stimulation", "descriptor_ui": "D010775", "major_topic": false }, { "descriptor": "Phototropism", "descriptor_ui": "D018524", "major_topic": false }, { "descriptor": "Volvox", "descriptor_ui": "D044446", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "10", "normalized_date": "2021", "pages": "e0259138", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "16", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "The four-celled Volvocales green alga Tetrabaena socialis exhibits weak photobehavior and high-photoprotection ability.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent extensive studies revealed that the intracellular concentration of magnesium ions (Mg(2+)) is one of the important factors to regulate cellular functions. To evaluate the impact of Mg(2+) concentration changes on intracellular signals or events, simultaneous imaging of Mg(2+) with those phenomena is a powerful technique. The present protocol describes the synthesis and evaluation of near-infrared (NIR) fluorescent Mg(2+)-selective probes, named KMG-500 series, and the application to simultaneous imaging of the corresponding intracellular signal transductions and molecular events. The present protocol for multicolor imaging using fluorescent probes in the NIR and visible ranges is highly useful to reveal how multiple molecular events are correlated each other in each single cell.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Yuma", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-1258-3_19" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34050475" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Membrane Potential, Mitochondrial", "descriptor_ui": "D053078", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Spectroscopy, Near-Infrared", "descriptor_ui": "D019265", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "217-235", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2274", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of Near-Infrared Fluorescent Mg(2+) Probe and Application to Multicolor Imaging of Intracellular Signals.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Oligodendrocytes (OLs) form a myelin sheath around neuronal axons to increase conduction velocity of action potential. Although both large and small diameter axons are intermingled in the central nervous system (CNS), the number of myelin wrapping is related to the axon diameter, such that the ratio of the diameter of the axon to that of the entire myelinated-axon unit is optimal for each axon, which is required for exerting higher brain functions. This indicates there are unknown axon diameter-dependent factors that control myelination. We tried to investigate physical factors to clarify the mechanisms underlying axon diameter-dependent myelination. To visualize OL-generating forces during myelination, a tension sensor based on fluorescence resonance energy transfer (FRET) was used. Polystyrene nanofibers with varying diameters similar to neuronal axons were prepared to investigate biophysical factors regulating the OL-axon interactions. We found that higher tension was generated at OL processes contacting larger diameter fibers compared with smaller diameter fibers. Additionally, OLs formed longer focal adhesions (FAs) on larger diameter axons and shorter FAs on smaller diameter axons. These results suggest that OLs respond to the fiber diameter and activate mechanotransduction initiated at FAs, which controls their cytoskeletal organization and myelin formation. This study leads to the novel and interesting idea that physical factors are involved in myelin formation in response to axon diameter.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Ichino", "name": null }, { "creator_type": "author", "first_name": "Atsunori", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Akimasa", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Tajiri", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Hida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fncel.2021.685044" }, "pmcid": { "normalized": "PMC8364977" }, "pmid": { "normalized": "34408628" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "685044", "proceedings_title": null, "publisher": "", "title": "Frontiers in cellular neuroscience", "volume": "15", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Tension Sensor Based on Fluorescence Resonance Energy Transfer Reveals Fiber Diameter-Dependent Mechanical Factors During Myelination.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The dopamine system plays an important role in regulating many brain functions, including the motor function. The blockade of dopamine receptors results in a serious motor dysfunction, such as catalepsy and Parkinsonism. However, the neuronal mechanism underlying the drug-induced motor dysfunction is not well understood. Here, we examine brain-wide activation patterns in Fos-enhanced green fluorescent protein reporter mice that exhibit cataleptic behavior induced by SCH39166, a dopamine D1-like receptor antagonist, and raclopride, a dopamine D2-like receptor antagonist. Support vector classifications showed that the orbital cortex (ORB) and striatum including the caudoputamen (CP) and nucleus accumbens (ACB), prominently contribute to the discrimination between brains of the vehicle-treated and both SCH39166- and raclopride-treated mice. Interregional correlations indicated that the increased functional connectivity of functional networks, including the ORB, CP, and ACB, is the common mechanism underlying SCH39166- and raclopride-induced cataleptic behavior. Moreover, the distinct mechanisms in the SCH39166- and raclopride-induced cataleptic behaviors are the decreased functional connectivity between three areas above and the cortical amygdala, and between three areas above and the anterior cingulate cortex, respectively. Thus, the alterations of functional connectivity in diverse brain regions, including the ORB, provide new insights on the mechanism underlying drug-induced movement disorders.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Misaki", "last_name": "Niu", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Misuzu", "last_name": "Hayashida", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Tanuma", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Hirato", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1248/bpb.b20-01006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33642553" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzazepines", "descriptor_ui": "D001552", "major_topic": false }, { "descriptor": "Catalepsy", "descriptor_ui": "D002375", "major_topic": false }, { "descriptor": "Corpus Striatum", "descriptor_ui": "D003342", "major_topic": false }, { "descriptor": "Dopamine Antagonists", "descriptor_ui": "D018492", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Raclopride", "descriptor_ui": "D020891", "major_topic": false }, { "descriptor": "Receptors, Dopamine D1", "descriptor_ui": "D017447", "major_topic": false }, { "descriptor": "Receptors, Dopamine D2", "descriptor_ui": "D017448", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "3", "normalized_date": "2021", "pages": "442-447", "proceedings_title": null, "publisher": "", "title": "Biological & pharmaceutical bulletin", "volume": "44", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Altered Functional Connectivity of the Orbital Cortex and Striatum Associated with Catalepsy Induced by Dopamine D1 and D2 Antagonists.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Synchronized movement of (both unicellular and multicellular) systems can be observed almost everywhere. Understanding of how organisms are regulated to synchronized behavior is one of the challenging issues in the field of collective motion. It is hypothesized that one or a few agents in a group regulate(s) the dynamics of the whole collective, known as leader(s). The identification of the leader (influential) agent(s) is very crucial. This article reviews different mathematical models that represent different types of leadership. We focus on the improvement of the leader-follower classification problem. It was found using a simulation model that the use of interaction domain information significantly improves the leader-follower classification ability using both linear schemes and information-theoretic schemes for quantifying influence. This article also reviews different schemes that can be used to identify the interaction domain using the motion data of agents.", "classifications": [ { "id": "18H05413", "label": "18H05413", "researcher": "Tamiki Komatsuzaki", "type": "grant" }, { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" }, { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Udoy S.", "last_name": "Basak", "name": null }, { "creator_type": "author", "first_name": "Sulimon", "last_name": "Sattari", "name": null }, { "creator_type": "author", "first_name": "Motaleb", "last_name": "Hossain", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v18.015" }, "pmcid": { "normalized": "PMC8214925" }, "pmid": { "normalized": "34178564" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "131-144", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "18", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Transfer entropy dependent on distance among agents in quantifying leader-follower relationships.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An organoid, a self-organizing organ-like tissue developed from stem cells, can exhibit a miniaturized three-dimensional (3D) structure and part of the physiological functions of the original organ. Due to the reproducibility of tissue complexity and ease of handling, organoids have replaced real organs and animals for a variety of uses, such as investigations of the mechanisms of organogenesis and disease onset, and screening of drug effects and/or toxicity. The recent advent of tissue clearing and 3D imaging techniques have great potential contributions to organoid studies by allowing the collection and analysis of 3D images of whole organoids with a reasonable throughput and thus can expand the means of examining the 3D architecture, cellular components, and variability among organoids. Genetic and histological cell-labeling methods, together with organoid clearing, also allow visualization of critical structures and cellular components within organoids. The collected 3D data may enable image analysis to quantitatively assess structures within organoids and sensitively/effectively detect abnormalities caused by perturbations. These capabilities of tissue/organoid clearing and 3D imaging techniques not only extend the utility of organoids in basic biology but can also be applied for quality control of clinical organoid production and large-scale drug screening.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Etsuo A.", "last_name": "Susaki", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2021.679226" }, "pmcid": { "normalized": "PMC8236633" }, "pmid": { "normalized": "34195197" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "679226", "proceedings_title": null, "publisher": "", "title": "Frontiers in cell and developmental biology", "volume": "9", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Perspective: Extending the Utility of Three-Dimensional Organoids by Tissue Clearing Technologies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "With the rapid increase in aging populations worldwide, there has been an increase in demand for preventive and therapeutic measures for age-related cognitive decline and dementia. Epidemiological studies show that consumption of dairy products reduces the risk for cognitive decline and dementia in the elderly. We have previously demonstrated in randomized trials that the consumption of beta-lactolin, a whey-derived Gly-Thr-Trp-Tyr lactotetrapeptide, improves cognitive function in older adults. Orally administered beta-lactolin is delivered to the brain and inhibits monoamine oxidase, resulting in alleviation of memory impairment. However, there is currently no evidence of the effects of long-term beta-lactolin intake on aging. Here, we found that the discrimination index in the novel object recognition test for object recognition memory was reduced in mice aged 20 months compared with that in young mice, indicating that age-related cognitive decline was induced in the aged mice; in aged mice fed beta-lactolin for 3 months, memory impairment was subsequently alleviated. In aged mice, impairment of light/dark activity cycles was found to be induced, which was subsequently alleviated by beta-lactolin consumption. Additionally, the number of activated microglia in the hippocampus and cortex and the production of cytokines (tumor necrosis factor-alpha, macrophage inflammatory protein-1alpha, and macrophage chemoattractant protein-1) were increased in aged mice compared with those in young mice but were reduced in aged mice fed beta-lactolin. The age-related hippocampal atrophy was improved in aged mice fed beta-lactolin. Cytochrome c levels in the hippocampus and cortex were increased in aged mice compared with those in young mice but were also reduced by beta-lactolin consumption. These results suggest that beta-lactolin consumption prevents neural inflammation and alleviates aging-related cognitive decline.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Ano", "name": null }, { "creator_type": "author", "first_name": "Rena", "last_name": "Ohya", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nakayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnut.2021.724134" }, "pmcid": { "normalized": "PMC8419277" }, "pmid": { "normalized": "34497823" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "724134", "proceedings_title": null, "publisher": "", "title": "Frontiers in nutrition", "volume": "8", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "beta-Lactolin Reduces Age-Related Inflammation and Cognitive Decline.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Conditions that resemble osteoarthritis (OA) were produced by injection of sodium monoiodoacetate (MIA) into the knee joints of mice. Bone marrow derived mast cells (BMMCs) injected into the OA knee joints enhanced spontaneous pain. Since no spontaneous pain was observed when BMMCs were injected into the knee joints of control mice that had not been treated with MIA, BMMCs should be activated within the OA knee joints and release some pain-inducible factors. Protease activated receptor-2 (PAR2) antagonist (FSLLRY-NH2) almost abolished the pain-enhancing effects of BMMCs injected into the OA knee joints, suggesting that tryptase, a mast cell protease that is capable of activating PAR2, should be released from the injected BMMCs and enhance pain through activation of PAR2. When PAR2 agonist (SLIGKV-NH2) instead of BMMCs was injected into the OA knee joints, it was also enhanced pain. Apyrase, an ATP degrading enzyme, injected into the OA knee joints before BMMCs suppressed the pain enhanced by BMMCs. We showed that purinoceptors (P2X4 and P2X7) were expressed in BMMCs and that extracellular ATP stimulated the release of tryptase from BMMCs. These observations suggest that ATP may stimulate degranulation of BMMCs and thereby enhanced pain. BMMCs injected into the OA knee joints stimulated expression of IL-1beta, IL-6, TNF-alpha, CCL2, and MMP9 genes in the infrapatellar fat pads, and PAR2 antagonist suppressed the stimulatory effects of BMMCs. Our study suggests that intermittent pain frequently observed in OA knee joints may be due, at least partly, to mast cells through activation of PAR2 and action of ATP, and that intraarticular injection of BMMCs into the OA knee joints may provide a useful experimental system for investigating molecular mechanisms by which pain is induced in OA knee joints.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Habuchi", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Junpei", "last_name": "Dan", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Ushida", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Ikeuchi", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Osami", "last_name": "Habuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0252590" }, "pmcid": { "normalized": "PMC8177436" }, "pmid": { "normalized": "34086763" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arthritis, Experimental", "descriptor_ui": "D001169", "major_topic": false }, { "descriptor": "Bone Marrow Cells", "descriptor_ui": "D001854", "major_topic": false }, { "descriptor": "Chemokine CXCL2", "descriptor_ui": "D054426", "major_topic": false }, { "descriptor": "Chenodeoxycholic Acid", "descriptor_ui": "D002635", "major_topic": false }, { "descriptor": "Chronic Pain", "descriptor_ui": "D059350", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Knee Joint", "descriptor_ui": "D007719", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mast Cells", "descriptor_ui": "D008407", "major_topic": false }, { "descriptor": "Matrix Metalloproteinase 9", "descriptor_ui": "D020780", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Oligopeptides", "descriptor_ui": "D009842", "major_topic": false }, { "descriptor": "Receptor, PAR-2", "descriptor_ui": "D044464", "major_topic": false }, { "descriptor": "Receptors, Purinergic", "descriptor_ui": "D011983", "major_topic": false }, { "descriptor": "Synovial Fluid", "descriptor_ui": "D013582", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "6", "normalized_date": "2021", "pages": "e0252590", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "16", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Bone marrow derived mast cells injected into the osteoarthritic knee joints of mice induced by sodium monoiodoacetate enhanced spontaneous pain through activation of PAR2 and action of extracellular ATP.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ascidiella aspersa is an ascidian in the class of chordates-the closest relatives of vertebrates. A. aspersa is a potential model organism for bio-imaging studies due to its extremely transparent embryos as well as is a globally distributed cosmopolitan species. However, there is no standard developmental table for this organism. Here, as a first step to establish A. aspersa as a model organism, we report a standard developmental table as a web-based digital image resource. This resource used confocal laser scanning microscopy to scan more than 3,000 cross-sectional images and 3D-reconstructed images of A. aspersa embryos during embryogenesis. With reference to the standardized developmental table of Ciona intestinalis type A, 26 different developmental stages (Stages 1-26) from fertilized eggs to hatched larvae were redefined for A. aspersa. Cell lineages up to the cleavage period were annotated: The cleavage patterns, the embryonic morphology, and the developmental time were then compared with Ciona. We found that the cleavage patterns and developmental time up to the neurula period in A. aspersa were extremely conserved versus. Ciona. The ratio of the trunk and tail length in the tailbud period were smaller than Ciona indicating a relatively short tail. In addition, the timing of the bending of the tail is earlier than Ciona. This A. aspersa standard 3D digital resource is essential for connecting different omics data to different spatiotemporal hierarchies and is useful for a system-level understanding of chordate development and evolution.", "classifications": [ { "id": "21H00440", "label": "21H00440", "researcher": "Kohji Hotta", "type": "grant" }, { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Haruka M.", "last_name": "Funakoshi", "name": null }, { "creator_type": "author", "first_name": "Takumi T.", "last_name": "Shito", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2021.789046" }, "pmcid": { "normalized": "PMC8718802" }, "pmid": { "normalized": "34977032" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "789046", "proceedings_title": null, "publisher": "", "title": "Frontiers in cell and developmental biology", "volume": "9", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Developmental Table and Three-Dimensional Embryological Image Resource of the Ascidian Ascidiella aspersa.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sleep and wakefulness are regulated by both the homeostatic mechanism and circadian clock. In mammals, the central circadian clock, the suprachiasmatic nucleus, in the hypothalamus plays a crucial role in the timing of physiology and behavior. Recently, we found that the circadian regulation of wakefulness was transmitted via corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus of the hypothalamus to orexin neurons in the lateral hypothalamus. However, it is still unclear how the molecular clock in the CRF neurons contributes to the regulation of sleep and wakefulness. In the present study, we established CRF neuron-specific Bmal1-deficient mice and measured locomotor activity or electroencephalography and electromyography. We found that these mice showed normal circadian locomotor activity rhythms in both light-dark cycle and constant darkness. Furthermore, they showed normal daily patterns of sleep and wakefulness. These results suggest that Bmal1 in CRF neurons has no effect on either circadian locomotor activity or sleep and wakefulness.", "classifications": [ { "id": "21H00422", "label": "21H00422", "researcher": "Daisuke Ono", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Chi Jung", "last_name": "Hung", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2021.808754" }, "pmcid": { "normalized": "PMC8894318" }, "pmid": { "normalized": "35250437" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "808754", "proceedings_title": null, "publisher": "", "title": "Frontiers in neuroscience", "volume": "15", "year": 2021 }, "ssbd": { "database": [ "ssbd-database-000246" ], "repository": [ "ssbd-repos-000246" ] }, "title": "Conditional Knockout of Bmal1 in Corticotropin-Releasing Factor Neurons Does Not Alter Sleep-Wake Rhythm in Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The locomotor system is highly bilateral at the macroscopic level. Homochirality of biological molecules is fully compatible with the bilateral body. However, whether and how single-handed cells contribute to the bilateral locomotor system is obscure. Here, exploiting the small number of cells in the swimming tadpole larva of the ascidian Ciona, we analyzed morphology of the tail at cellular and subcellular scales. Quantitative phase-contrast X-ray tomographic microscopy revealed a high-density midline structure ventral to the notochord in the tail. Muscle cell nuclei on each side of the notochord were roughly bilaterally aligned. However, fluorescence microscopy detected left-right asymmetry of myofibril inclination relative to the longitudinal axis of the tail. Zernike phase-contrast X-ray tomographic microscopy revealed the presence of left-handed helices of myofibrils in muscle cells on both sides. Therefore, the locomotor system of ascidian larvae harbors symmetry-breaking left-handed helical cells, while maintaining bilaterally symmetrical cell alignment. These results suggest that bilateral animals can override cellular homochirality to generate the bilateral locomotor systems at the supracellular scale.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koichi", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Mayu", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yanlin", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Koh", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Momose", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Nishino", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2021.800455" }, "pmcid": { "normalized": "PMC8688927" }, "pmid": { "normalized": "34950666" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "800455", "proceedings_title": null, "publisher": "", "title": "Frontiers in cell and developmental biology", "volume": "9", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Bilaterally Asymmetric Helical Myofibrils in Ascidian Tadpole Larvae.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "There are several paths when excited molecules return to the ground state. In the case of fluorescent molecules, the dominant path is fluorescence emission that is greatly contributing to bioimaging. Meanwhile, photosensitizers transfer electron or energy from chromophore to the surrounding molecules, including molecular oxygen. Generated reactive oxygen species has potency to attack other molecules by oxidation. In this chapter, we introduce the chromophore-assisted light inactivation (CALI) method using a photosensitizer to inactivate proteins in a spatiotemporal manner and development of CALI tools, which is useful for investigation of protein functions and dynamics, by inactivation of the target molecules. Moreover, photosensitizers with high efficiency make it possible optogenetic control of cell ablation in living organisms and photodynamic therapy. Further development of photosensitizers with different excitation wavelengths will contribute to the investigation of multiple proteins or cell functions through inactivation in the different positions and timings.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yemima Dani", "last_name": "Riani", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-981-15-8763-4_16" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33398819" } }, "mesh": [ { "descriptor": "Cell Physiological Phenomena", "descriptor_ui": "D002468", "major_topic": false }, { "descriptor": "Chromophore-Assisted Light Inactivation", "descriptor_ui": "D061885", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Photochemotherapy", "descriptor_ui": "D010778", "major_topic": false }, { "descriptor": "Photosensitizing Agents", "descriptor_ui": "D017319", "major_topic": true }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "265-279", "proceedings_title": null, "publisher": "", "title": "Advances in experimental medicine and biology", "volume": "1293", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetically Encoded Photosensitizer for Destruction of Protein or Cell Function.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Gene manipulation is a useful approach for understanding functions of genes and is important for investigating basic mechanisms of brain function on the level of single neurons and circuits. Despite the development and the wide range of applications of CRISPR-Cas9 and base editors (BEs), their implementation for an analysis of individual neurons in vivo remained limited. In fact, conventional gene manipulations are generally achieved only on the population level. Here, we combined either CRISPR-Cas9 or BEs with the targeted single-cell electroporation technique as a proof-of-concept test for gene manipulation in single neurons in vivo. Our assay consisted of CRISPR-Cas9- or BEs-induced gene knockout in single Purkinje cells in the cerebellum. Our results demonstrate the feasibility of both gene editing and base editing in single cells in the intact brain, providing a tool through which molecular perturbations of individual neurons can be used for analysis of circuits and, ultimately, behaviors.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Beomjong", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Chan Young", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Jun Hee", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Arthur", "last_name": "Konnerth", "name": null }, { "creator_type": "author", "first_name": "Sangsu", "last_name": "Bae", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.csbj.2021.04.051" }, "pmcid": { "normalized": "PMC8113754" }, "pmid": { "normalized": "34025938" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "2477-2485", "proceedings_title": null, "publisher": "", "title": "Computational and structural biotechnology journal", "volume": "19", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "In vivo genome editing in single mammalian brain neurons through CRISPR-Cas9 and cytosine base editors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Schizophrenia is characterized by positive symptoms, negative symptoms and cognitive dysfunction. Although the abnormal neuronal development, impaired synaptic functions and impaired neural circuit functions are suggested to be the causes of psychiatric disorders, the molecular and cellular etiology of schizophrenia remains largely unclear. iPS-related technologies can be powerful for not only understanding the molecular and cellular etiology of schizophrenia but also drug discovery research. In 2011, the first iPS cells derived from patients with schizophrenia harboring a DISC1 mutation were generated. Subsequently, many iPS cells from patients with schizophrenia were established for understanding the molecular and cellular disease phenotypes of the differentiated neuronal cells. For replicating disease phenotypes with iPSC-derived neuronal cells, it is important to develop the differentiation strategies for generating cell-type specific cultures of various types of neurons, astrocytes and oligodendrocytes. Especially, scalable cultures of iPSC-derived neuronal cells are valuable platforms for drug discovery research. In this review, the focus has been made on the iPSC differentiation technology, pharmacological and drug discovery studies with iPSC-derived neurons from patients with schizophrenia. Continued advancement of the iPSC-related technologies and research will help the success in central nervous system drug discovery and development.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/fpj.21003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34193699" } }, "mesh": [ { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Schizophrenia", "descriptor_ui": "D012559", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "4", "normalized_date": "2021", "pages": "220-223", "proceedings_title": null, "publisher": "", "title": "Nihon yakurigaku zasshi. Folia pharmacologica Japonica", "volume": "156", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "[Pharmacological studies using iPSC-derived neurons from patients with schizophrenia].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vision of sharks embraces various biological and ecological themes ranging from predation and adaptation to deep-sea life. However, behavioural and genetic studies have been limited by their elusive lifestyles, repeatedly reported declines of wild populations, and their unique life-history traits including low fecundity and enhanced longevity. Sharks have also not been actively studied on the cellular and molecular levels, because of additional difficulties in cell culture, tissue collection and genome sequencing. A recent study circumvented some of these obstacles by means of genome informatics thereby portrayed the variation of visual opsin gene repertoires among elasmobranchs (sharks and rays) and spectral shifts of the rhodopsin pigment. Comprehensive surveys in whole-genome sequences are also revealing the repertoires of nonvisual opsins with unknown functions. This review is aimed to summarize existing studies on shark opsins with an emphasis on genomic investigation of gene repertoires and to provide insights into the better understanding of underwater ecology of marine megafauna with in vitro experimentation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Kuraku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/jeb.13730" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33135271" } }, "mesh": [ { "descriptor": "Adaptation, Biological", "descriptor_ui": "D000220", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ecosystem", "descriptor_ui": "D017753", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "Opsins", "descriptor_ui": "D055355", "major_topic": false }, { "descriptor": "Sharks", "descriptor_ui": "D012754", "major_topic": false }, { "descriptor": "Vision, Ocular", "descriptor_ui": "D014785", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "968-976", "proceedings_title": null, "publisher": "", "title": "Journal of evolutionary biology", "volume": "34", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Visual and nonvisual opsin genes of sharks and other nonosteichthyan vertebrates: Genomic exploration of underwater photoreception.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We previously reported that ROR1 is a crucial downstream gene for the TTF-1/NKX2-1 lineage-survival oncogene in lung adenocarcinoma, while others have found altered expression of ROR1 in multiple cancer types. Accumulated evidence therefore indicates ROR1 as an attractive molecular target, though it has yet to be determined whether targeting Ror1 can inhibit tumor development and growth in vivo. To this end, genetically engineered mice carrying homozygously floxed Ror1 alleles and an SP-C promoter-driven human mutant EGFR transgene were generated. Ror1 ablation resulted in marked retardation of tumor development and progression in association with reduced malignant characteristics and significantly better survival. Interestingly, gene set enrichment analysis identified a hypoxia-induced gene set (HALLMARK_HYPOXIA) as most significantly downregulated by Ror1 ablation in vivo, which led to findings showing that ROR1 knockdown diminished HIF-1alpha expression under normoxia and clearly hampered HIF-1alpha induction in response to hypoxia in human lung adenocarcinoma cell lines. The present results directly demonstrate the importance of Ror1 for in vivo development and progression of lung adenocarcinoma, and also identify Ror1 as a novel regulator of Hif-1alpha. Thus, a future study aimed at the development of a novel therapeutic targeting ROR1 for treatment of solid tumors such as seen in lung cancer, which are frequently accompanied with a hypoxic tumor microenvironment, is warranted.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hisanori", "last_name": "Isomura", "name": null }, { "creator_type": "author", "first_name": "Ayumu", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kajino", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Asai", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakatochi", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Motoshi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Teruaki", "last_name": "Fujishita", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.14825" }, "pmcid": { "normalized": "PMC8019194" }, "pmid": { "normalized": "33506575" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypoxia", "descriptor_ui": "D000860", "major_topic": false }, { "descriptor": "Hypoxia-Inducible Factor 1, alpha Subunit", "descriptor_ui": "D051795", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Oncogenes", "descriptor_ui": "D009857", "major_topic": false }, { "descriptor": "Receptor Tyrosine Kinase-like Orphan Receptors", "descriptor_ui": "D057050", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Thyroid Nuclear Factor 1", "descriptor_ui": "D000074482", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "1614-1623", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "112", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Conditional Ror1 knockout reveals crucial involvement in lung adenocarcinoma development and identifies novel HIF-1alpha regulator.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mammalian central circadian clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN contains multiple circadian oscillators which synchronize with each other via several neurotransmitters. Importantly, an inhibitory neurotransmitter, gamma-amino butyric acid (GABA), is expressed in almost all SCN neurons. In this review, we discuss how GABA influences circadian rhythms in the SCN. Excitatory and inhibitory effects of GABA may depend on intracellular Cl(-) concentration, in which several factors such as day-length, time of day, development, and region in the SCN may be involved. GABA also mediates oscillatory coupling of the circadian rhythms in the SCN. Recent genetic approaches reveal that GABA refines circadian output rhythms, but not circadian oscillations in the SCN. Since several efferent projections of the SCN have been suggested, GABA might work downstream of neuronal pathways from the SCN which regulate the temporal order of physiology and behavior.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Sato", "last_name": "Honma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/jnc.15012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32198942" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Period Circadian Proteins", "descriptor_ui": "D056950", "major_topic": false }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "31-41", "proceedings_title": null, "publisher": "", "title": "Journal of neurochemistry", "volume": "157", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "GABAergic mechanisms in the suprachiasmatic nucleus that influence circadian rhythm.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although the field of antibody drugs has grown larger, the antibody production still faces several challenges. Effective antibody purification is required, but the conventional purification method for antibodies is cost intensive and often causes aggregation problems, indicating the need for new alternative antibody purification methods. In the present study, a constant temperature antibody purification system for use with a thermo-responsive polymer column was developed based on switching of anion species in eluents. By adjusting the temperature for each antibody, the developed column enabled separation of the therapeutic monoclonal antibodies, rituximab and trastuzumab, from contaminants without changing salt concentration or pH of the eluents. The thermo-responsive hydrogel-modified column packing material was synthesized by introducing n-butyl methacrylate, acrylic acid, N,N'-methylenebisacrylamide and N-isopropylacrylamide to the surface of silica beads with an initiator by a graft-from approach. Elution behavior of antibodies with three types of anions, such as citrate, phosphate, and chloride were tested under three different temperature conditions. It was demonstrated that the thermo-responsive hydrogel grafted column showed a switchable antibody retention behavior at constant temperature and salt concentration, with antibody adsorption by NaCl eluent and desorption by citric acid buffer eluent.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daiki", "last_name": "Nomoto", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nagase", "name": null }, { "creator_type": "author", "first_name": "Yubuki", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hideko", "last_name": "Kanazawa", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.colsurfb.2021.111890" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34089966" } }, "mesh": [ { "descriptor": "Adsorption", "descriptor_ui": "D000327", "major_topic": false }, { "descriptor": "Anions", "descriptor_ui": "D000838", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": true }, { "descriptor": "Silicon Dioxide", "descriptor_ui": "D012822", "major_topic": true }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "111890", "proceedings_title": null, "publisher": "", "title": "Colloids and surfaces. B, Biointerfaces", "volume": "205", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Anion species-triggered antibody separation system utilizing a thermo-responsive polymer column under optimized constant temperature.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tough double network (DN) hydrogels are promising substitutes of soft supporting tissues such as cartilage and ligaments. For such applications, it is indispensable to robustly fix the hydrogels to bones with medically feasible methods. Recently, robustly bonding the DN hydrogels to defected bones of rabbits in vivo has been proved successful. The low crystalline hydroxyapatite (HAp) of calcium-phosphate-hydroxide salt coated on the surface layer of the DN hydrogels induced spontaneous osteogenesis penetrating into the semi-permeable hydrogels to form a gel/bone composite layer. In this work, the (44) Ca isotope-doped HAp/DN hydrogel is implanted in a defect of rabbit femoral bone and the dynamic osteogenesis process at the gel/bone interface is analyzed by tracing the calcium isotope ratio using isotope microscopy. The synthetic HAp hybridized on the surface layer of DN gel dissolves rapidly in the first two weeks by inflammation, and then the immature bone with a gradient structure starts to form in the gel region, reutilizing the dissolved Ca ions. These results reveal, for the first time, that synthetic HAp is reutilized for osteogenesis. These facts help to understand the lifetime of bone absorbable materials and to elucidate the mechanism of spontaneous, non-toxic, but strong fixation of hydrogels to bones.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takayuki", "last_name": "Nonoyama", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Kiyama", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kousuke", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Hisayoshi", "last_name": "Yurimoto", "name": null }, { "creator_type": "author", "first_name": "Jian Ping", "last_name": "Gong", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/adhm.202001731" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33191665" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone and Bones", "descriptor_ui": "D001842", "major_topic": false }, { "descriptor": "Durapatite", "descriptor_ui": "D017886", "major_topic": false }, { "descriptor": "Hydrogels", "descriptor_ui": "D020100", "major_topic": true }, { "descriptor": "Isotopes", "descriptor_ui": "D007554", "major_topic": false }, { "descriptor": "Osteogenesis", "descriptor_ui": "D010012", "major_topic": true }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "e2001731", "proceedings_title": null, "publisher": "", "title": "Advanced healthcare materials", "volume": "10", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Isotope Microscopic Observation of Osteogenesis Process Forming Robust Bonding of Double Network Hydrogel to Bone.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41590-021-01008-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34426689" } }, "mesh": [ { "descriptor": "Autoimmunity", "descriptor_ui": "D015551", "major_topic": true }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "1080-1082", "proceedings_title": null, "publisher": "", "title": "Nature immunology", "volume": "22", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Restoring control over autoimmunity by inducing Foxp3.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human immune systems are very complex, and the basis for individual differences in immune phenotypes is largely unclear. One reason is that the phenotype of the immune system is so complex that it is very difficult to describe its features and quantify differences between samples. To identify the genetic factors that cause individual differences in whole lymphocyte profiles and their changes after vaccination without having to rely on biological assumptions, we performed a genome-wide association study (GWAS), using cytometry data. Here, we applied computational analysis to the cytometry data of 301 people before receiving an influenza vaccine, and 1, 7, and 90 days after the vaccination to extract the feature statistics of the lymphocyte profiles in a nonparametric and data-driven manner. We analyzed two types of cytometry data: measurements of six markers for B cell classification and seven markers for T cell classification. The coordinate values calculated by this method can be treated as feature statistics of the lymphocyte profile. Next, we examined the genetic basis of individual differences in human immune phenotypes with a GWAS for the feature statistics, and we newly identified seven significant and 36 suggestive single-nucleotide polymorphisms associated with the individual differences in lymphocyte profiles and their change after vaccination. This study provides a new workflow for performing combined analyses of cytometry data and other types of genomics data.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Daigo", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Setoh", "name": null }, { "creator_type": "author", "first_name": "Takahisa", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Higasa", "name": null }, { "creator_type": "author", "first_name": "Yasuharu", "last_name": "Tabara", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s10038-020-00874-x" }, "pmcid": { "normalized": "PMC8144016" }, "pmid": { "normalized": "33230199" } }, "mesh": [ { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Data Mining", "descriptor_ui": "D057225", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune System", "descriptor_ui": "D007107", "major_topic": false }, { "descriptor": "Influenza Vaccines", "descriptor_ui": "D007252", "major_topic": false }, { "descriptor": "Influenza, Human", "descriptor_ui": "D007251", "major_topic": false }, { "descriptor": "Lymphocytes", "descriptor_ui": "D008214", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false }, { "descriptor": "Vaccination", "descriptor_ui": "D014611", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "557-567", "proceedings_title": null, "publisher": "", "title": "Journal of human genetics", "volume": "66", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Genome-wide association study of individual differences of human lymphocyte profiles using large-scale cytometry data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) plays an essential role in the modulation of astrocyte functions. Although lactate secretion from astrocytes contributes to many forms of neuronal plasticity in the central nervous system, including fear learning and memory, the role of PACAP in lactate secretion from astrocytes is unclear. METHODS: The amygdala and hippocampus of PACAP (+ / +) and PACAP (-/-) mice were acquired 1 h after memory acquisition and recall in the passive avoidance test. The concentration of glycogen and lactate in these regions was measured. The concentration of lactate in the hippocampus's extracellular fluid was also measured by microdialysis during memory acquisition or intracerebroventricular administration of PACAP. RESULTS: We observed that memory acquisition caused a significant decrease in glycogen concentration and increased lactate concentration in the PACAP (+ / +) mice's hippocampus. However, memory acquisition did not increase in the lactate concentration in PACAP (-/-) mice's hippocampus. Further, memory retrieval evoked lactate production in the amygdala and the hippocampus of PACAP (+ / +) mice. Still, there was no significant increase in lactate concentration in the same regions of PACAP (-/-) mice. In vivo microdialysis in rats revealed that the hippocampus's extracellular lactate concentration increased after a single PACAP intracerebroventricular injection. Additionally, the hippocampus's extracellular lactate concentration increased with the memory acquisition in PACAP (+ / +) mice, but not in PACAP (-/-) mice. CONCLUSIONS: PACAP may enhance lactate production and secretion in astrocytes during the acquisition and recall of fear memories.", "classifications": [ { "id": "18H05416", "label": "18H05416", "researcher": "Hitoshi Hashimoto", "type": "grant" }, { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Kambe", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Trung", "last_name": "Thanh Nguyen", "name": null }, { "creator_type": "author", "first_name": "Thu", "last_name": "Thi Nguyen", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Shimako", "last_name": "Yoshitake", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yoshitake", "name": null }, { "creator_type": "author", "first_name": "Jan", "last_name": "Kehr", "name": null }, { "creator_type": "author", "first_name": "Namiko", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Goro", "last_name": "Katsuura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Atsuro", "last_name": "Miyata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s43440-021-00222-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33835466" } }, "mesh": [ { "descriptor": "Amygdala", "descriptor_ui": "D000679", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Fear", "descriptor_ui": "D005239", "major_topic": false }, { "descriptor": "Glycogen", "descriptor_ui": "D006003", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Lactic Acid", "descriptor_ui": "D019344", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "1109-1121", "proceedings_title": null, "publisher": "", "title": "Pharmacological reports : PR", "volume": "73", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "The pivotal role of pituitary adenylate cyclase-activating polypeptide for lactate production and secretion in astrocytes during fear memory.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ugis", "last_name": "Sarkans", "name": null }, { "creator_type": "author", "first_name": "Wah", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Lucy", "last_name": "Collinson", "name": null }, { "creator_type": "author", "first_name": "Michele C.", "last_name": "Darrow", "name": null }, { "creator_type": "author", "first_name": "Jan", "last_name": "Ellenberg", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Grunwald", "name": null }, { "creator_type": "author", "first_name": "Jean-Karim", "last_name": "Heriche", "name": null }, { "creator_type": "author", "first_name": "Andrii", "last_name": "Iudin", "name": null }, { "creator_type": "author", "first_name": "Gabriel G.", "last_name": "Martins", "name": null }, { "creator_type": "author", "first_name": "Terry", "last_name": "Meehan", "name": null }, { "creator_type": "author", "first_name": "Kedar", "last_name": "Narayan", "name": null }, { "creator_type": "author", "first_name": "Ardan", "last_name": "Patwardhan", "name": null }, { "creator_type": "author", "first_name": "Matthew Robert Geoffrey", "last_name": "Russell", "name": null }, { "creator_type": "author", "first_name": "Helen R.", "last_name": "Saibil", "name": null }, { "creator_type": "author", "first_name": "Caterina", "last_name": "Strambio-De-Castillia", "name": null }, { "creator_type": "author", "first_name": "Jason R.", "last_name": "Swedlow", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Tischer", "name": null }, { "creator_type": "author", "first_name": "Virginie", "last_name": "Uhlmann", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Verkade", "name": null }, { "creator_type": "author", "first_name": "Mary", "last_name": "Barlow", "name": null }, { "creator_type": "author", "first_name": "Omer", "last_name": "Bayraktar", "name": null }, { "creator_type": "author", "first_name": "Ewan", "last_name": "Birney", "name": null }, { "creator_type": "author", "first_name": "Cesare", "last_name": "Catavitello", "name": null }, { "creator_type": "author", "first_name": "Christopher", "last_name": "Cawthorne", "name": null }, { "creator_type": "author", "first_name": "Stephan", "last_name": "Wagner-Conrad", "name": null }, { "creator_type": "author", "first_name": "Elizabeth", "last_name": "Duke", "name": null }, { "creator_type": "author", "first_name": "Perrine", "last_name": "Paul-Gilloteaux", "name": null }, { "creator_type": "author", "first_name": "Emmanuel", "last_name": "Gustin", "name": null }, { "creator_type": "author", "first_name": "Maria", "last_name": "Harkiolaki", "name": null }, { "creator_type": "author", "first_name": "Pasi", "last_name": "Kankaanpaa", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Lemberger", "name": null }, { "creator_type": "author", "first_name": "Jo", "last_name": "McEntyre", "name": null }, { "creator_type": "author", "first_name": "Josh", "last_name": "Moore", "name": null }, { "creator_type": "author", "first_name": "Andrew W.", "last_name": "Nicholls", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Helen", "last_name": "Parkinson", "name": null }, { "creator_type": "author", "first_name": "Maddy", "last_name": "Parsons", "name": null }, { "creator_type": "author", "first_name": "Marina", "last_name": "Romanchikova", "name": null }, { "creator_type": "author", "first_name": "Nicholas", "last_name": "Sofroniew", "name": null }, { "creator_type": "author", "first_name": "Jim", "last_name": "Swoger", "name": null }, { "creator_type": "author", "first_name": "Nadine", "last_name": "Utz", "name": null }, { "creator_type": "author", "first_name": "Lenard M.", "last_name": "Voortman", "name": null }, { "creator_type": "author", "first_name": "Frances", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Peijun", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Gerard J.", "last_name": "Kleywegt", "name": null }, { "creator_type": "author", "first_name": "Alvis", "last_name": "Brazma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41592-021-01166-8" }, "pmcid": { "normalized": "PMC8606015" }, "pmid": { "normalized": "34021280" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Congresses as Topic", "descriptor_ui": "D003226", "major_topic": false }, { "descriptor": "Cryoelectron Microscopy", "descriptor_ui": "D020285", "major_topic": false }, { "descriptor": "Data Mining", "descriptor_ui": "D057225", "major_topic": false }, { "descriptor": "Databases, Factual", "descriptor_ui": "D016208", "major_topic": false }, { "descriptor": "Diagnostic Imaging", "descriptor_ui": "D003952", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Metadata", "descriptor_ui": "D000071253", "major_topic": true }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1418-1422", "proceedings_title": null, "publisher": "", "title": "Nature methods", "volume": "18", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "REMBI: Recommended Metadata for Biological Images-enabling reuse of microscopy data in biology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The freshwater crustacean Daphnia magna has traditionally been a model for ecotoxicological studies owing to its sensitivity to many xenobiotics. Because it is used in many toxicity assessments, its detoxification mechanism for xenobiotics is important and requires further study. However, studies related to detoxification genes are limited to transcriptomic profiling, and there are no D. magna mutants for use in the understanding of xenobiotic metabolism in vivo. We report the generation of a D. magna CYP360A8 mutant-the gene is a cytochrome P450 (CYP) clan 3 gene. Based on RNA sequencing of adult D. magna, we found that CYP360A8 has the highest expression level among all CYP genes. At ovarian maturation, its expression level is up-regulated 6-fold compared to the juvenile stages and is maintained thereafter. Using the CRISPR/CRISPR-associated 9 (Cas9) system, we disrupted CYP360A8 by coinjecting CYP360A8-targeting guide RNA and Cas9 proteins into D. magna eggs and established one monoallelic CYP360A8 mutant line. This CYP360A8 mutant had a higher sensitivity to the herbicide paraquat compared to the wild type. We confirmed the up-regulation of CYP360A8 by paraquat. The results demonstrate the role of CYP360A8 in paraquat detoxification. The present study establishes a CYP mutant of D. magna, and this strategy can be a basic platform to document a range of CYP gene-xenobiotic relationships in this species. Environ Toxicol Chem 2021;40:1279-1288. (c) 2020 SETAC.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Pijar", "last_name": "Religia", "name": null }, { "creator_type": "author", "first_name": "Nhan Duc", "last_name": "Nguyen", "name": null }, { "creator_type": "author", "first_name": "Quang Dang", "last_name": "Nong", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/etc.4970" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33338286" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cytochrome P-450 Enzyme System", "descriptor_ui": "D003577", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Paraquat", "descriptor_ui": "D010269", "major_topic": false }, { "descriptor": "Water Pollutants, Chemical", "descriptor_ui": "D014874", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "1279-1288", "proceedings_title": null, "publisher": "", "title": "Environmental toxicology and chemistry", "volume": "40", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Mutation of the Cytochrome P450 CYP360A8 Gene Increases Sensitivity to Paraquat in Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: IL-31 is a major pruritogen associated with atopic dermatitis (AD). Although a specific antibody for IL-31 receptor has been shown to alleviate pruritus in patients with AD, therapeutic approaches to inhibition of IL-31 production remain unexploited. IL-31 production by TH cells critically depends on the transcription factor EPAS1, which mediates IL31 promoter activation in collaboration with SP1. OBJECTIVE: We aimed at developing small-molecule inhibitors that selectively block IL-31 production by TH cells. METHODS: We generated the reporter cell line that inducibly expressed EPAS1 in the presence of doxycycline to mediate Il31 promoter activation, and we screened 9600 chemical compounds. The selected compounds were further examined by using TH cells from a spontaneous mouse model of AD and TH cells from patients with AD. RESULTS: We have identified 4-(2-(4-isopropylbenzylidene)hydrazineyl)benzoic acid (IPHBA) as an inhibitor of IL31 induction. Although IPHBA did not affect nonspecific T-cell proliferation, IPHBA inhibited antigen-induced IL-31 production by TH cells from both an AD mouse model and patients with AD without affecting other cytokine production and hypoxic responses. In line with this, itch responses induced by adoptive transfer of IL-31-producing TH cells were attenuated when mice were orally treated with IPHBA. Mechanistically, IPHBA inhibited the association between EPAS1 and SP1, resulting in defective recruitment of both transcription factors to the specific sites of the IL31 promoter. We also determined the structure-activity relationship of IPHBA by synthesizing and analyzing 201 analogous compounds. CONCLUSION: IPHBA could be a potential drug leading to inhibition of EPAS1-driven IL-31 production.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Kamikaseda", "name": null }, { "creator_type": "author", "first_name": "Takehito", "last_name": "Uruno", "name": null }, { "creator_type": "author", "first_name": "Kazufumi", "last_name": "Kunimura", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Saiki", "name": null }, { "creator_type": "author", "first_name": "Kounosuke", "last_name": "Oisaki", "name": null }, { "creator_type": "author", "first_name": "Daiji", "last_name": "Sakata", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nakahara", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Kido-Nakahara", "name": null }, { "creator_type": "author", "first_name": "Motomu", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Masutaka", "last_name": "Furue", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Fukui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jaci.2021.03.029" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33819507" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Dermatitis, Atopic", "descriptor_ui": "D003876", "major_topic": false }, { "descriptor": "Doxycycline", "descriptor_ui": "D004318", "major_topic": false }, { "descriptor": "Endothelial PAS Domain-Containing Protein 1", "descriptor_ui": "D000099162", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Interleukins", "descriptor_ui": "D007378", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "T-Lymphocytes, Helper-Inducer", "descriptor_ui": "D006377", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "633-638", "proceedings_title": null, "publisher": "", "title": "The Journal of allergy and clinical immunology", "volume": "148", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Targeted inhibition of EPAS1-driven IL-31 production by a small-molecule compound.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Accurate diagnosis of peritoneal metastasis in gastric cancer (GC) is important to determine the appropriate treatment. This study aimed to examine whether matrix metalloprotease-14 (MMP-14) was a candidate enzyme in fluorescence imaging for the diagnosis of peritoneal metastasis in GC. METHODS: GC and normal peritoneal (NP) tissues from 96 and 20 patients, respectively were evaluated for MMP-14 expression. Live cell imaging of GC cell lines (NUGC4, MKN45, MKN74, HGC-27, and Kato-III) was performed using the MMP-14-activatable fluorescence probe; BODIPY-MMP. Furthermore, the overall survival (OS) was calculated in all patients (n = 96). RESULTS: MMP-14 expression was significantly higher in GC tissues (median: 3.57 ng/mg protein; range:0.64-24.4 ng/mg protein) than in NP tissues (median: 1.34 ng/mg protein; median: 0.53-3.09 ng/mg protein) (P < 0.01). Receiver operating characteristic curves showed that the area under the curve, sensitivity, and specificity were 0.907, 84.4%, and 90.0%, respectively. In live cell imaging using the BODIPY-MMP, fluorescence was observed in five GC cell lines. In the analysis of OS, the high expression of the MMP-14 group had a significantly poorer OS rate than the low expression of the MMP-14 group (P = 0.02). In the multivariate analyses, MMP-14 expression was an independent risk factor for OS (hazard ratio: 2.33; 95 % confidence interval: 1.05-5.45; P = 0.04). CONCLUSION: MMP-14 is a promising enzyme in intraoperative fluorescence imaging for peritoneal metastasis in GC, especially in patients with poor prognosis.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Soichiro", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Hidemasa", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Yasutoshi", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yubakami", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yugo", "last_name": "Kuriki", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Eigo", "last_name": "Otsuji", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.pdpdt.2021.102420" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34242818" } }, "mesh": [ { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Matrix Metalloproteinase 14", "descriptor_ui": "D053511", "major_topic": false }, { "descriptor": "Peritoneal Neoplasms", "descriptor_ui": "D010534", "major_topic": true }, { "descriptor": "Photochemotherapy", "descriptor_ui": "D010778", "major_topic": true }, { "descriptor": "Photosensitizing Agents", "descriptor_ui": "D017319", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Sep", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "102420", "proceedings_title": null, "publisher": "", "title": "Photodiagnosis and photodynamic therapy", "volume": "35", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Matrix metalloprotease-14 is a target enzyme for detecting peritoneal metastasis in gastric cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer burden has been increasing worldwide, making cancer the second leading cause of death in the world. Over the past decades, various experimental models have provided important insights into the nature of cancer. Among them, the fruit fly Drosophila as a whole-animal toolkit has made a decisive contribution to our understanding of fundamental mechanisms of cancer development including loss of cell polarity. In recent years, scalable Drosophila platforms have proven useful also in developing anti-cancer regimens that are effective not only in mammalian models but also in patients. Here, we review studies using Drosophila as a tool to advance cancer study by complementing other traditional research systems.", "classifications": [ { "id": "19H05412", "label": "19H05412", "researcher": "Masahiro Sonoshita", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryodai", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Ooshio", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.14747" }, "pmcid": { "normalized": "PMC7893992" }, "pmid": { "normalized": "33275812" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "505-514", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "112", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Tiny Drosophila makes giant strides in cancer research.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Newly emerging transformed cells are often eliminated from the epithelium via cell competition with the surrounding normal cells. A number of recent studies using mammalian cell competition systems have demonstrated that cells with various types of oncogenic insults are extruded from the tissue in a cell death-dependent or -independent manner. Cell competition-mediated elimination of transformed cells, called EDAC (epithelial defense against cancer), represents an intrinsic anti-tumor activity within the epithelial cell society to reduce the risk of oncogenesis. Here we delineate roles and molecular mechanisms of this homeostatic process, especially focusing on mammalian models.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kon", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2021.03.015" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33774012" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Competition", "descriptor_ui": "D000084502", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "112-116", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "476", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell competition-induced apical elimination of transformed cells, EDAC, orchestrates the cellular homeostasis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Navigation of fast migrating cells such as amoeba Dictyostelium and immune cells are tightly associated with their morphologies that range from steady polarized forms that support high directionality to those more complex and variable when making frequent turns. Model simulations are essential for quantitative understanding of these features and their origins, however systematic comparisons with real data are underdeveloped. Here, by employing deep-learning-based feature extraction combined with phase-field modeling framework, we show that a low dimensional feature space for 2D migrating cell morphologies obtained from the shape stereotype of keratocytes, Dictyostelium and neutrophils can be fully mapped by an interlinked signaling network of cell-polarization and protrusion dynamics. Our analysis links the data-driven shape analysis to the underlying causalities by identifying key parameters critical for migratory morphologies both normal and aberrant under genetic and pharmacological perturbations. The results underscore the importance of deciphering self-organizing states and their interplay when characterizing morphological phenotypes.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Nen", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Motohiko", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Toyoko", "last_name": "Sugita", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Koko", "last_name": "Katagiri", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Okimura", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Iwadate", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1009237" }, "pmcid": { "normalized": "PMC8360578" }, "pmid": { "normalized": "34383753" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": false }, { "descriptor": "Cell Surface Extensions", "descriptor_ui": "D022081", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cichlids", "descriptor_ui": "D023681", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "HL-60 Cells", "descriptor_ui": "D018922", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "e1009237", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "17", "year": 2021 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000167" ] }, "title": "Comparative mapping of crawling-cell morphodynamics in deep learning-based feature space.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stem cell (SC) proliferation and differentiation organize tissue homeostasis. However, how SCs regulate coordinate tissue scaling in dynamic organs remain unknown. Here, we delineate SC regulations in dynamic skin. We found that interfollicular epidermal SCs (IFESCs) shape basal epidermal proliferating clusters (EPCs) in expanding abdominal epidermis of pregnant mice and proliferating plantar epidermis. EPCs consist of IFESC-derived Tbx3(+)-basal cells (Tbx3(+)-BCs) and their neighboring cells where Adam8-extracellular signal-regulated kinase signaling is activated. Clonal lineage tracing revealed that Tbx3(+)-BC clones emerge in the abdominal epidermis during pregnancy, followed by differentiation after parturition. In the plantar epidermis, Tbx3(+)-BCs are sustained as long-lived SCs to maintain EPCs invariably. We showed that Tbx3(+)-BCs are vasculature-dependent IFESCs and identified mechanical stretch as an external cue for the vasculature-driven EPC formation. Our results uncover vasculature-mediated IFESC regulations, which explain how the epidermis adjusts its size in orchestration with dermal constituents in dynamic skin.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Ichijo", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kabata", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Riki", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Tsutsui", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Iizuka", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Sada", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abd2575" }, "pmcid": { "normalized": "PMC7875541" }, "pmid": { "normalized": "33568475" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Feb", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "eabd2575", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "7", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Vasculature-driven stem cell population coordinates tissue scaling in dynamic organs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Single-cell RNA-sequencing analysis is one of the most effective tools for understanding specific cellular states. The use of single cells or pooled cells in RNA-seq analysis requires the isolation of cells from a tissue or culture. Although trypsin or more recently cold-active protease (CAP) has been used for cell dissociation, the extent to which the gene expression changes are suppressed has not been clarified. To this end, we conducted detailed profiling of the enzyme-dependent gene expression changes in mouse skeletal muscle progenitor cells, focusing on the enzyme treatment time, amount and temperature. We found that the genes whose expression was changed by the enzyme treatment could be classified in a time-dependent manner and that there were genes whose expression was changed independently of the enzyme treatment time, amount and temperature. This study will be useful as reference data for genes that should be excluded or considered for RNA-seq analysis using enzyme isolation methods.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Atsuko", "last_name": "Miyawaki-Kuwakado", "name": null }, { "creator_type": "author", "first_name": "Qianmei", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Tomimatsu", "name": null }, { "creator_type": "author", "first_name": "Takeru", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.12870" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33987903" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myoblasts", "descriptor_ui": "D032446", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "RNA-Seq", "descriptor_ui": "D000081246", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true }, { "descriptor": "Trypsin", "descriptor_ui": "D014357", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "530-540", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "26", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Transcriptome analysis of gene expression changes upon enzymatic dissociation in skeletal myoblasts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reactive oxygen species are key factors that strongly affect the cellular redox state and regulate various physiological and cellular phenomena. To monitor changes in the redox state, we previously developed fluorescent redox sensors named Re-Q, the emissions of which are quenched under reduced conditions. However, such fluorescent probes are unsuitable for use in the cells of photosynthetic organisms because they require photoexcitation that may change intracellular conditions and induce autofluorescence, primarily in chlorophylls. In addition, the presence of various chromophore pigments may interfere with fluorescence-based measurements because of their strong absorbance. To overcome these problems, we adopted the bioluminescence resonance energy transfer (BRET) mechanism for the sensor and developed two BRET-based redox sensors by fusing cyan fluorescent protein-based or yellow fluorescent protein-based Re-Q with the luminescent protein Nluc. We named the resulting redox-sensitive BRET-based indicator probes \"ROBINc\" and \"ROBINy.\" ROBINc is pH insensitive, which is especially vital for observation in photosynthetic organisms. By using these sensors, we successfully observed dynamic redox changes caused by an anticancer agent in HeLa cells and light/dark-dependent redox changes in the cells of photosynthetic cyanobacterium Synechocystis sp. PCC 6803. Since the newly developed sensors do not require excitation light, they should be especially useful for visualizing intracellular phenomena caused by redox changes in cells containing colored pigments.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Nae", "last_name": "Fu", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Shungo", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbc.2021.101186" }, "pmcid": { "normalized": "PMC8487062" }, "pmid": { "normalized": "34517006" } }, "mesh": [ { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": true }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Synechocystis", "descriptor_ui": "D046939", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Oct", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "101186", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "297", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Monitoring cellular redox dynamics using newly developed BRET-based redox sensor proteins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent advances in genome-wide technologies have enabled analyses using small cell numbers of even single cells. However, obtaining tissue epigenomes with cell-type resolution from large organs and tissues still remains challenging, especially when the available material is limited. Here, we present a ChIL-based approach for analyzing the diverse cellular dynamics at the tissue level using high-depth epigenomic data. \"ChIL for tissues\" allows the analysis of a single tissue section and can reproducibly generate epigenomic profiles from several tissue types, based on the distribution of target epigenomic states, tissue morphology, and number of cells. The proposed method enabled the independent evaluation of changes in cell populations and gene activation in cells from regenerating skeletal muscle tissues, using a statistical model of RNA polymerase II distribution on gene loci. Thus, the integrative analyses performed using ChIL can elucidate in vivo cell-type dynamics of tissues.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Tomimatsu", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Fukuoka", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Handa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurumizaka", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Saitoh", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.15252/msb.202110323" }, "pmcid": { "normalized": "PMC8564819" }, "pmid": { "normalized": "34730297" } }, "mesh": [ { "descriptor": "Epigenome", "descriptor_ui": "D000081122", "major_topic": true }, { "descriptor": "Epigenomics", "descriptor_ui": "D057890", "major_topic": true }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "Population Density", "descriptor_ui": "D011156", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "e10323", "proceedings_title": null, "publisher": "", "title": "Molecular systems biology", "volume": "17", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Modeling population size independent tissue epigenomes by ChIL-seq with single thin sections.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The food-entrainable oscillator, which underlies the prefeeding activity peak developed by restricted daily feeding (RF) in rodents, does not depend on the circadian pacemaker in the suprachiasmatic nucleus (SCN) or on the known clock genes. In the present study, to clarify the roles of SCN circadian pacemaker and nutrient conditions on the development of prefeeding activity peak, RF of 3-h daily feeding was imposed on four groups of adult male mice for 10 cycles at different circadian times, zeitgeber time (ZT)2, ZT8, ZT14, and ZT20, where ZT0 is the time of lights-on in LD12:12. Seven days after the termination of RF session with ad libitum feeding in between, total food deprivation (FD) for 72 h was imposed. Wheel-running activity and core body temperature were measured throughout the experiment. Immediately after the RF or FD session, the PER2::LUC rhythms were measured in the cultured SCN slices and peripheral tissues. Not only the buildup process and magnitude of the prefeeding activity peak, but also the percentages of nocturnal activity and hypothermia developed under RF were significantly different among the four groups, indicating the involvement of light entrained circadian pacemaker. The buildup of prefeeding activity peak was accomplished by either phase-advance or phase-delay shifts (or both) of activity bouts comprising a nocturnal band. Hypothermia under FD was less prominent in RF-exposed mice than in naive counterparts, indicating that restricted feeding increases tolerance to caloric restriction as well as to the heat loss mechanism. RF phase-shifted the peripheral clocks but FD did not affect the clocks in any tissue examined. These findings are better understood by assuming multiple bout oscillators, which are located outside the SCN and directly drive activity bouts uncoupled from the circadian pacemaker by RF or hypothermia.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinya", "last_name": "Nishide", "name": null }, { "creator_type": "author", "first_name": "Yohko", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Sato", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Honma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1177/07487304211047937" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34634956" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": true }, { "descriptor": "Feeding Behavior", "descriptor_ui": "D005247", "major_topic": false }, { "descriptor": "Food", "descriptor_ui": "D005502", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "575-588", "proceedings_title": null, "publisher": "", "title": "Journal of biological rhythms", "volume": "36", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "The Food-entrainable Oscillator Is a Complex of Non-SCN Activity Bout Oscillators Uncoupled From the SCN Circadian Pacemaker.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have previously identified receptor tyrosine kinase-like orphan receptor 1 (ROR1) as a direct transcriptional target of TTF-1/NKX2-1, a lineage-survival oncogene in lung adenocarcinoma. ROR1 sustains prosurvival signaling from multiple receptor tyrosine kinases including epidermal growth factor receptor, MET, and insulin-like growth factor 1 receptor in part by maintaining the caveolae structure as a scaffold protein of cavin-1 and caveolin-1. In this study, a high throughput screening of the natural product library containing 2560 compounds was undertaken using a cell-based FluoPPI assay detecting ROR1-cavin-1 interaction. As a result, geldanamycin (GA), a known inhibitor of heat shock protein 90 (HSP90), was identified as a potential inhibitor of ROR1. Geldanamycin, as well as two GA derivatives tested in the clinic, 17-allylamino-17-demethoxygeldanamycin (17-AAG) and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), decreased ROR1 protein expression. We found that ROR1 physically interacted with HSP90alpha, but not with other HSP90 paralogs, HSP90beta or GRP94. Geldanamycin in turn destabilized and degraded ROR1 protein in a dose- and time-dependent manner through the ubiquitin/proteasome pathway, resulting in a significant suppression of cell proliferation in lung adenocarcinoma cell lines, for which the kinase domain of ROR1, but not its kinase activity or N-glycosylation, was required. Our findings indicate that HSP90 is required to sustain expression of ROR1 crucial for lung adenosarcoma survival, suggesting that inhibition of HSP90 could be a promising therapeutic strategy in ROR1-positive lung adenocarcinoma.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Behnoush", "last_name": "Khaledian", "name": null }, { "creator_type": "author", "first_name": "Ayumu", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Shin-Ya", "name": null }, { "creator_type": "author", "first_name": "Lisa", "last_name": "Kondo-Ida", "name": null }, { "creator_type": "author", "first_name": "Noritaka", "last_name": "Kagaya", "name": null }, { "creator_type": "author", "first_name": "Motoshi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kajino", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.14786" }, "pmcid": { "normalized": "PMC7935804" }, "pmid": { "normalized": "33370472" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": false }, { "descriptor": "Antibiotics, Antineoplastic", "descriptor_ui": "D000903", "major_topic": false }, { "descriptor": "Benzoquinones", "descriptor_ui": "D016227", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Drug Screening Assays, Antitumor", "descriptor_ui": "D004354", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "High-Throughput Screening Assays", "descriptor_ui": "D057166", "major_topic": false }, { "descriptor": "HSP90 Heat-Shock Proteins", "descriptor_ui": "D018841", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lactams, Macrocyclic", "descriptor_ui": "D047029", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Proteasome Endopeptidase Complex", "descriptor_ui": "D046988", "major_topic": false }, { "descriptor": "Proteolysis", "descriptor_ui": "D059748", "major_topic": false }, { "descriptor": "Receptor Tyrosine Kinase-like Orphan Receptors", "descriptor_ui": "D057050", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "1225-1234", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "112", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Inhibition of heat shock protein 90 destabilizes receptor tyrosine kinase ROR1 in lung adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The JIPANG study is a randomized phase III study of pemetrexed/cisplatin (Pem/Cis) versus vinorelbine/cisplatin (Vnr/Cis) for completely resected stage II-IIIA non-squamous non-small cell lung cancer (Ns-NSCLC). This study did not meet the primary endpoint (recurrence-free survival, RFS) but Pem/Cis had a similar efficacy to Vnr/Cis with a better tolerability. Tumor mutation burden (TMB) is thought to have a predictive value of immune checkpoint inhibitors. However, the relevance of TMB to cytotoxic chemotherapy remains unknown. This exploratory study investigates the relationship between tumor mutation profiles and clinical outcome of Pem/Cis. Formalin-fixed, paraffin-embedded tumor tissues (n = 389) were obtained from the patients. Mutation status of tissue DNA was analyzed by targeted deep sequencing. Epidermal growth factor receptor (EGFR) mutations were detected frequently in Ns-NSCLC (139/374). Patients without any EGFR mutations experienced longer RFS in the Pem/Cis arm versus Vnr/Cis arms. Pem/Cis in patients with high TMB (≥12-16 mut/Mb) tended to have improved survival. In patients with wild-type EGFR, TMB ≥ 12 mut/Mb was significantly associated with improved RFS with Pem/Cis versus Vnr/Cis (not reached vs 52.5 months; hazard ratio (HR) 0.477). It could be proposed that TMB was predictive of RFS benefit with Pem/Cis versus Vnr/Cis in Ns-NSCLC. Further investigation is required to determine whether TMB combined with EGFR mutation status could be used as a predictive biomarker.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuko", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Hirotsugu", "last_name": "Kenmotsu", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Daga", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Ohira", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Hosomi", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Takiguchi", "name": null }, { "creator_type": "author", "first_name": "Akimasa", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Haruki", "name": null }, { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Akamatsu", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Seto", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Saeki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sugio", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Nishio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.14730" }, "pmcid": { "normalized": "PMC7780021" }, "pmid": { "normalized": "33185928" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Cisplatin", "descriptor_ui": "D002945", "major_topic": false }, { "descriptor": "DNA Mutational Analysis", "descriptor_ui": "D004252", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Pemetrexed", "descriptor_ui": "D000068437", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "388-396", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "112", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Tumor mutation burden as a biomarker for lung cancer patients treated with pemetrexed and cisplatin (the JIPANG-TR).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "pH is one of the most critical physiological parameters determining vital cellular activities, such as photosynthetic performance. Fluorescent sensor proteins capable of measuring in situ pH in animal cells have been reported. However, these proteins require an excitation laser for pH measurement that may affect photosynthetic performance and induce autofluorescence from chlorophyll. As a result, it is not possible to measure the intracellular or intraorganelle pH changes in plants. To overcome this problem, we developed a luminescent pH sensor by fusing the luminescent protein Nanoluc to a uniquely designed pH-sensitive GFP variant protein. In this system, an excitation laser is unnecessary because the fused GFP variant reports on the luminescent signal by bioluminescence resonance energy transfer from Nanoluc. The ratio of two luminescent peaks from the sensor protein was approximately linear with respect to pH in the range of 7.0 to 8.5. We designated this sensor protein as \"luminescent pH indicator protein\" (Luphin). We applied Luphin to the in situ pH measurement of a photosynthetic organism under fluctuating light conditions, allowing us to successfully observe the cytosolic pH changes associated with photosynthetic electron transfer in the cyanobacterium Synechocystis sp. PCC 6803. Detailed analyses of the mechanisms of the observed estimated pH changes in the cytosol in this alga suggested that the photosynthetic electron transfer is suppressed by the reduced plastoquinone pool under light conditions. These results indicate that Luphin may serve as a helpful tool to further illuminate pH-dependent processes throughout the photosynthetic organisms.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shungo", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Nae", "last_name": "Fu", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sugiura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.ra120.016847" }, "pmcid": { "normalized": "PMC7948502" }, "pmid": { "normalized": "33268379" } }, "mesh": [ { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chlorophyll", "descriptor_ui": "D002734", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Photosynthesis", "descriptor_ui": "D010788", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Synechocystis", "descriptor_ui": "D046939", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan-Jun", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "100134", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "296", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "A luminescent Nanoluc-GFP fusion protein enables readout of cellular pH in photosynthetic organisms.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Immune checkpoint inhibitor (ICI) programmed death (PD)-1/PD-ligand 1 (PD-L1) blockade has been approved for various cancers. However, the underlying antitumor mechanisms mediated by ICIs and the predictive biomarkers remain unclear. We report the effects of anti-PD-L1/PD-1 Ab in tumor angiogenesis. In syngeneic mouse models, anti-PD-L1 Ab inhibited tumor angiogenesis and induces net-like hypoxia only in ICI-sensitive cell lines. In tumor tissue and serum of ICI-sensitive cell line-bearing mice, interferon-gamma (IFN-gamma) inducible angiostatic chemokines CXCL10/11 were upregulated by PD-L1 blockade. In vitro, CXCL10/11 gene upregulation by IFN-gamma stimulation in tumor cell lines correlated with the sensitivity of PD-L1 blockade. The CXCL10/11 receptor CXCR3-neutralizing Ab or CXCL11 silencing in tumor cells inhibited the antiangiogenic effect of PD-L1 blockade in vivo. In pretreatment serum of lung carcinoma patients receiving anti-PD-1 Ab, the concentration of CXCL10/11 significantly correlated with the clinical outcome. Our results indicate the antiangiogenic function of PD-1/PD-L1 blockade and identify tumor-derived CXCL10/11 as a potential circulating biomarker of therapeutic sensitivity.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mitsuhashi", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Kondoh", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Na Thi", "last_name": "Nguyen", "name": null }, { "creator_type": "author", "first_name": "Tania", "last_name": "Afroj", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Yoneda", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Otsuka", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Ogino", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nokihara", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Shinohara", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Nishioka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.15161" }, "pmcid": { "normalized": "PMC8645761" }, "pmid": { "normalized": "34628702" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Chemokine CXCL10", "descriptor_ui": "D054357", "major_topic": false }, { "descriptor": "Chemokine CXCL11", "descriptor_ui": "D054371", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Checkpoint Inhibitors", "descriptor_ui": "D000082082", "major_topic": false }, { "descriptor": "Interferon-gamma", "descriptor_ui": "D007371", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred CBA", "descriptor_ui": "D008808", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Neoplasms, Experimental", "descriptor_ui": "D009374", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "4853-4866", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "112", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Programmed death (PD)-1/PD-ligand 1 blockade mediates antiangiogenic effects by tumor-derived CXCL10/11 as a potential predictive biomarker.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Accurate recognition of antigens by specific T cells is crucial for adaptive immunity to work properly. The activation of a T-cell antigen-specific response by an antigen-presenting cell (APC) has not been clearly measured at a single T-cell level. It is also unknown whether the cell-extrinsic environment alters antigen recognition by a T cell. To measure the activation probability of a single T cell by an APC, we performed a single-cell live imaging assay and found that the activation probability changes depending not only on the antigens but also on the interactions of other T cells with the APC. We found that the specific reactivity of single naive T cells was poor. However, their antigen-specific reactivity increased drastically when attached to an APC interacting with activated T cells. Activation of T cells was suppressed when regulatory T cells interacted with the APC. These findings suggest that although the ability of APCs to activate an antigen-specific naive T cell is low at a single-cell level, the surrounding environment of APCs improves the specificity of the bulk response.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Machiyama", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Yanagida", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/1873-3468.14082" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33826750" } }, "mesh": [ { "descriptor": "Adaptive Immunity", "descriptor_ui": "D056704", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigen Presentation", "descriptor_ui": "D017951", "major_topic": true }, { "descriptor": "Antigen-Presenting Cells", "descriptor_ui": "D000938", "major_topic": false }, { "descriptor": "Biological Assay", "descriptor_ui": "D001681", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ion Transport", "descriptor_ui": "D017136", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Probability", "descriptor_ui": "D011336", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Spleen", "descriptor_ui": "D013154", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "1512-1524", "proceedings_title": null, "publisher": "", "title": "FEBS letters", "volume": "595", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Activation probability of a single naive T cell upon TCR ligation is controlled by T cells interacting with the same antigen-presenting cell.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Naotaka", "last_name": "Nitta", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Hachiya", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10396-021-01159-2" }, "pmcid": { "normalized": "PMC8578076" }, "pmid": { "normalized": "34669074" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Oct", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "415", "proceedings_title": null, "publisher": "", "title": "Journal of medical ultrasonics (2001)", "volume": "48", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Correction to: A review of physical and engineering factors potentially affecting shear wave elastography.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sleep is affected by the environment. In rodents, changes in the amount of rapid eye movement sleep (REMS) can precede those of other sleep/wake stages. The molecular mechanism underlying the dynamic regulation of REMS remains poorly understood. Here, we focused on the sublaterodorsal nucleus (SLD), located in the pontine tegmental area, which plays a crucial role in the regulation of REMS. We searched for genes selectively expressed in the SLD and identified copine-7 (Cpne7), whose involvement in sleep was totally unknown. We generated Cpne7-Cre knock-in mice, which enabled both the knockout (KO) of Cpne7 and the genetic labeling of Cpne7-expressing cells. While Cpne7-KO mice exhibited normal sleep under basal conditions, the amount of REMS in Cpne7-KO mice was larger compared to wildtype mice following cage change or water immersion and restraint stress, both of which are conditions that acutely reduce REMS. Thus, it was suggested that copine-7 is involved in negatively regulating REMS under certain conditions. In addition, chemogenetically activating Cpne7-expressing neurons in the SLD reduced the amount of REMS, suggesting that these neurons negatively regulate REMS. These results identify copine-7 and Cpne7-expressing neurons in the SLD as candidate molecular or neuronal components of the regulatory system that controls REMS.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Chih-Yao", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Chia-Jung", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Yasugaki", "name": null }, { "creator_type": "author", "first_name": "Nanae", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Isotani", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2020.04.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32283105" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Immersion", "descriptor_ui": "D007101", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": false }, { "descriptor": "Sleep, REM", "descriptor_ui": "D012895", "major_topic": true }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Apr", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "14-25", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "165", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Copine-7 is required for REM sleep regulation following cage change or water immersion and restraint stress in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Daigo", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Setoh", "name": null }, { "creator_type": "author", "first_name": "Takahisa", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Higasa", "name": null }, { "creator_type": "author", "first_name": "Yasuharu", "last_name": "Tabara", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s10038-020-00890-x" }, "pmcid": { "normalized": "PMC8414790" }, "pmid": { "normalized": "33446886" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "643", "proceedings_title": null, "publisher": "", "title": "Journal of human genetics", "volume": "66", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Publisher Correction: Genome-wide association study of individual differences of human lymphocyte profiles using large-scale cytometry data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Metformin (Met) is the first-line treatment for type 2 diabetes mellitus and plays an effective role in treating various diseases, such as cardiovascular disease, neurodegenerative disease, cancer, and aging. However, the underlying mechanism of Met-dependent antitumor immunity remains to be elucidated. METHODS: MitoTEMPO, a scavenger of mitochondrial superoxide, abolished the antitumor effect of Met, but not antiprogrammed cell death (PD-1) antibody (Ab) treatment. Consequently, we studied the mechanism of the Met-induced antitumor effect. Expressions of glucose transporter (Glut)-1, mitochondrial reactive oxygen species (mtROS), interferon (IFN)-gamma, Ki67, autophagy markers, activation markers for NF-E2-related factor 2 (Nrf2), and mammalian target of rapamaycin complex 1 (mTORC1) in CD8(+) tumor-infiltrating T lymphocytes (CD8TILs) were examined by flow cytometry analysis. In addition, conditional knockout mice for Nrf2 and p62 were used to detect these markers, together with the monitoring of in vivo tumor growth. RNA sequencing was performed for CD8TILs and tumor cells. Melanoma cells containing an IFN-gamma receptor (IFNgammaR) cytoplasmic domain deletion mutant was overexpressed and used for characterization of the metabolic profile of those tumor cells using a Seahorse Flux Analyzer. RESULTS: Met administration elevates mtROS and cell surface Glut-1, resulting in the production of IFN-gamma in CD8TILs. mtROS activates Nrf2 in a glycolysis-dependent manner, inducing activation of autophagy, glutaminolysis, mTORC1, and p62/SQSTM1. mTORC1-dependent phosphorylation of p62 at serine 351 (p-p62(S351)) is also involved in activation of Nrf2. Conditional deletion of Nrf2 in CD8TILs abrogates mTORC1 activation and antitumor immunity by Met. In synergy with the effect of anti-PD-1 Ab, Met boosts CD8TIL proliferation and IFN-gamma secretion, resulting in decreased glycolysis and oxidative phosphorylation in tumor cells. Consequently, Glut-1 is elevated in CD8TILs, together with the expansion of activated dendritic cells. Moreover, tumor cells lacking in IFNgammaR signaling abolish IFN-gamma production and proliferation of CD8TILs. CONCLUSIONS: We found that Met stimulates production of mtROS, which triggers Glut-1 elevation and Nrf2 activation in CD8TILs. Nrf2 activates mTORC1, whereas mTORC1 activates Nrf2 in a p-p62(S351)-dependent manner, thus creating a feedback loop that ensures CD8TILs' proliferation. In combination with anti-PD-1 Ab, Met stimulates robust proliferation of CD8TILs and IFN-gamma secretion, resulting in an IFN-gamma-dependent reprogramming of the tumor microenvironment.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mikako", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Nahoko", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Taisaku", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Koseki", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Warabi", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Ohue", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Kakimi", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null }, { "creator_type": "author", "first_name": "Heiichiro", "last_name": "Udono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1136/jitc-2021-002954" }, "pmcid": { "normalized": "PMC8449974" }, "pmid": { "normalized": "34531248" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphocytes, Tumor-Infiltrating", "descriptor_ui": "D016246", "major_topic": false }, { "descriptor": "Metformin", "descriptor_ui": "D008687", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "NF-E2-Related Factor 2", "descriptor_ui": "D051267", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "e002954", "proceedings_title": null, "publisher": "", "title": "Journal for immunotherapy of cancer", "volume": "9", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Mitochondrial reactive oxygen species trigger metformin-dependent antitumor immunity via activation of Nrf2/mTORC1/p62 axis in tumor-infiltrating CD8T lymphocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The ABC transporter, Scarlet, and its binding partner, White are involved in pigment synthesis in the insect eye and mutations in these genes are used as genetic markers. Recent studies have suggested that these transporters also have additional functions in the neuronal system. In our previous study, we generated scarlet mutant in the small crustacean, Daphnia magna and showed that the mutant lacked the eye pigment in the mutant. Here, we show that the scarlet mutant exhibits spinning behavior. This phenotype is partly associated with the presence of light. Metabolomic analysis of a juvenile mutant revealed that the scarlet mutant has approximately one-tenth of the histamine content of the wild type. Application of histamine to the scarlet mutant rescued the spinning behavior in juveniles, suggesting that the spinning behavior of the mutant is caused by the reduction of histamine. However, the altered behavior was not rescued in the adult mutant by the addition of histamine, suggesting that Scarlet plays an irreversible role in the development of histaminergic neurons. These results suggest that Scarlet plays an important role in histaminergic signaling, which might be related to control the spinning behavior, in addition to its role in eye pigmentation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Nur Izzatur Binti", "last_name": "Ismail", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Cristian", "last_name": "Gomez-Canela", "name": null }, { "creator_type": "author", "first_name": "Carlos", "last_name": "Barata", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/dvg.23403" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33348442" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "ATP-Binding Cassette Transporters", "descriptor_ui": "D018528", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "Eye Proteins", "descriptor_ui": "D005136", "major_topic": false }, { "descriptor": "Histamine", "descriptor_ui": "D006632", "major_topic": false }, { "descriptor": "Insect Proteins", "descriptor_ui": "D019476", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Pigmentation", "descriptor_ui": "D010858", "major_topic": false }, { "descriptor": "Pigments, Biological", "descriptor_ui": "D010860", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "e23403", "proceedings_title": null, "publisher": "", "title": "Genesis (New York, N.Y. : 2000)", "volume": "59", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Reduction of histamine and enhanced spinning behavior of Daphnia magna caused by scarlet mutant.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Small, soluble metabolites not only are essential intermediates in intracellular biochemical processes, but can also influence neighbouring cells when released into the extracellular milieu(1-3). Here we identify the metabolite and neurotransmitter GABA as a candidate signalling molecule synthesized and secreted by activated B cells and plasma cells. We show that B cell-derived GABA promotes monocyte differentiation into anti-inflammatory macrophages that secrete interleukin-10 and inhibit CD8(+) T cell killer function. In mice, B cell deficiency or B cell-specific inactivation of the GABA-generating enzyme GAD67 enhances anti-tumour responses. Our study reveals that, in addition to cytokines and membrane proteins, small metabolites derived from B-lineage cells have immunoregulatory functions, which may be pharmaceutical targets allowing fine-tuning of immune responses.", "classifications": [ { "id": "18H05411", "label": "18H05411", "researcher": "Katsuyuki Shiroguchi", "type": "grant" }, { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Baihao", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Alexis", "last_name": "Vogelzang", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Miyajima", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Yibo", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Chamoto", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Ryusuke", "last_name": "Hatae", "name": null }, { "creator_type": "author", "first_name": "Rosemary J.", "last_name": "Menzies", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Sonomura", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Hojo", "name": null }, { "creator_type": "author", "first_name": "Taisaku", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Wakana", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Tsutsui", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Mikako", "last_name": "Maruya", "name": null }, { "creator_type": "author", "first_name": "Seiko", "last_name": "Narushima", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sugiya", "name": null }, { "creator_type": "author", "first_name": "Kosaku", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Motomu", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Katsuhiro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Honjo", "name": null }, { "creator_type": "author", "first_name": "Sidonia", "last_name": "Fagarasan", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41586-021-04082-1" }, "pmcid": { "normalized": "PMC8599023" }, "pmid": { "normalized": "34732892" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": false }, { "descriptor": "Glutamate Decarboxylase", "descriptor_ui": "D005968", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Interleukin-10", "descriptor_ui": "D016753", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "T-Lymphocytes, Cytotoxic", "descriptor_ui": "D013602", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Nov", "date_precision": "unknown", "issue": "7885", "normalized_date": null, "pages": "471-476", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "599", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "B cell-derived GABA elicits IL-10(+) macrophages to limit anti-tumour immunity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: To expand the recent description of a new neurodevelopmental syndrome related to alterations in CDK19. METHODS: Individuals were identified through international collaboration. Functional studies included autophosphorylation assays for CDK19 Gly28Arg and Tyr32His variants and in vivo zebrafish assays of the CDK19(G28R) and CDK19(Y32H). RESULTS: We describe 11 unrelated individuals (age range: 9 months to 14 years) with de novo missense variants mapped to the kinase domain of CDK19, including two recurrent changes at residues Tyr32 and Gly28. In vitro autophosphorylation and substrate phosphorylation assays revealed that kinase activity of protein was lower for p.Gly28Arg and higher for p.Tyr32His substitutions compared with that of the wild-type protein. Injection of CDK19 messenger RNA (mRNA) with either the Tyr32His or the Gly28Arg variants using in vivo zebrafish model significantly increased fraction of embryos with morphological abnormalities. Overall, the phenotype of the now 14 individuals with CDK19-related disorder includes universal developmental delay and facial dysmorphism, hypotonia (79%), seizures (64%), ophthalmologic anomalies (64%), and autism/autistic traits (56%). CONCLUSION: CDK19 de novo missense variants are responsible for a novel neurodevelopmental disorder. Both kinase assay and zebrafish experiments showed that the pathogenetic mechanism may be more diverse than previously thought.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuri A.", "last_name": "Zarate", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Oginuma", "name": null }, { "creator_type": "author", "first_name": "Sora", "last_name": "Harako", "name": null }, { "creator_type": "author", "first_name": "Shizuka", "last_name": "Ishitani", "name": null }, { "creator_type": "author", "first_name": "Anna-Elina", "last_name": "Lehesjoki", "name": null }, { "creator_type": "author", "first_name": "Tatjana", "last_name": "Bierhals", "name": null }, { "creator_type": "author", "first_name": "Katja", "last_name": "Kloth", "name": null }, { "creator_type": "author", "first_name": "Nadja", "last_name": "Ehmke", "name": null }, { "creator_type": "author", "first_name": "Denise", "last_name": "Horn", "name": null }, { "creator_type": "author", "first_name": "Manuel", "last_name": "Holtgrewe", "name": null }, { "creator_type": "author", "first_name": "Katherine", "last_name": "Anderson", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Viskochil", "name": null }, { "creator_type": "author", "first_name": "Courtney L.", "last_name": "Edgar-Zarate", "name": null }, { "creator_type": "author", "first_name": "Maria J. Guillen", "last_name": "Sacoto", "name": null }, { "creator_type": "author", "first_name": "Rhonda E.", "last_name": "Schnur", "name": null }, { "creator_type": "author", "first_name": "Michelle M.", "last_name": "Morrow", "name": null }, { "creator_type": "author", "first_name": "Amarilis", "last_name": "Sanchez-Valle", "name": null }, { "creator_type": "author", "first_name": "John", "last_name": "Pappas", "name": null }, { "creator_type": "author", "first_name": "Rachel", "last_name": "Rabin", "name": null }, { "creator_type": "author", "first_name": "Mikko", "last_name": "Muona", "name": null }, { "creator_type": "author", "first_name": "Anna-Kaisa", "last_name": "Anttonen", "name": null }, { "creator_type": "author", "first_name": "Konrad", "last_name": "Platzer", "name": null }, { "creator_type": "author", "first_name": "Johannes", "last_name": "Luppe", "name": null }, { "creator_type": "author", "first_name": "Janina", "last_name": "Gburek-Augustat", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Kaname", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Yusaku", "last_name": "Kaido", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Ohkuma", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Ishitani", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Kosaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41436-020-01091-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33495529" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinases", "descriptor_ui": "D018844", "major_topic": false }, { "descriptor": "Gain of Function Mutation", "descriptor_ui": "D000073659", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infant", "descriptor_ui": "D007223", "major_topic": false }, { "descriptor": "Intellectual Disability", "descriptor_ui": "D008607", "major_topic": true }, { "descriptor": "Mutation, Missense", "descriptor_ui": "D020125", "major_topic": false }, { "descriptor": "Neurodevelopmental Disorders", "descriptor_ui": "D065886", "major_topic": true }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "1050-1057", "proceedings_title": null, "publisher": "", "title": "Genetics in medicine : official journal of the American College of Medical Genetics", "volume": "23", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "CDK19-related disorder results from both loss-of-function and gain-of-function de novo missense variants.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Jason R.", "last_name": "Swedlow", "name": null }, { "creator_type": "author", "first_name": "Pasi", "last_name": "Kankaanpaa", "name": null }, { "creator_type": "author", "first_name": "Ugis", "last_name": "Sarkans", "name": null }, { "creator_type": "author", "first_name": "Wojtek", "last_name": "Goscinski", "name": null }, { "creator_type": "author", "first_name": "Graham", "last_name": "Galloway", "name": null }, { "creator_type": "author", "first_name": "Leonel", "last_name": "Malacrida", "name": null }, { "creator_type": "author", "first_name": "Ryan P.", "last_name": "Sullivan", "name": null }, { "creator_type": "author", "first_name": "Steffen", "last_name": "Hartel", "name": null }, { "creator_type": "author", "first_name": "Claire M.", "last_name": "Brown", "name": null }, { "creator_type": "author", "first_name": "Christopher", "last_name": "Wood", "name": null }, { "creator_type": "author", "first_name": "Antje", "last_name": "Keppler", "name": null }, { "creator_type": "author", "first_name": "Federica", "last_name": "Paina", "name": null }, { "creator_type": "author", "first_name": "Ben", "last_name": "Loos", "name": null }, { "creator_type": "author", "first_name": "Sara", "last_name": "Zullino", "name": null }, { "creator_type": "author", "first_name": "Dario Livio", "last_name": "Longo", "name": null }, { "creator_type": "author", "first_name": "Silvio", "last_name": "Aime", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41592-021-01113-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33948027" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Databases, Factual", "descriptor_ui": "D016208", "major_topic": false }, { "descriptor": "Diagnostic Imaging", "descriptor_ui": "D003952", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Information Storage and Retrieval", "descriptor_ui": "D016247", "major_topic": false }, { "descriptor": "Metadata", "descriptor_ui": "D000071253", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Societies, Scientific", "descriptor_ui": "D012958", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "User-Computer Interface", "descriptor_ui": "D014584", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1440-1446", "proceedings_title": null, "publisher": "", "title": "Nature methods", "volume": "18", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "A global view of standards for open image data formats and repositories.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Growth factors regulate cell fates, including their proliferation, differentiation, survival, and death, according to the cell type. Even when the response to a specific growth factor is deterministic for collective cell behavior, significant levels of fluctuation are often observed between single cells. Statistical analyses of single-cell responses provide insights into the mechanism of cell fate decisions but very little is known about the distributions of the internal states of cells responding to growth factors. Using multi-color immunofluorescent staining, we have here detected the phosphorylation of seven elements in the early response of the ERBB-RAS-MAPK system to two growth factors. Among these seven elements, five were analyzed simultaneously in distinct combinations in the same single cells. Although principle component analysis suggested cell-type and input specific phosphorylation patterns, cell-to-cell fluctuation was large. Mutual information analysis suggested that each cell type uses multitrack (bush-like) signal transduction pathways under conditions in which clear fate changes have been reported. The clustering of single-cell response patterns indicated that the fate change in a cell population correlates with the large entropy of the response, suggesting a bet-hedging strategy is used in decision making. A comparison of true and randomized datasets further indicated that this large variation is not produced by simple reaction noise, but is defined by the properties of the signal-processing network.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiraku", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.biosystems.2020.104293" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33221378" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "MCF-7 Cells", "descriptor_ui": "D061986", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Principal Component Analysis", "descriptor_ui": "D025341", "major_topic": false }, { "descriptor": "ras Proteins", "descriptor_ui": "D018631", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "104293", "proceedings_title": null, "publisher": "", "title": "Bio Systems", "volume": "199", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell-to-cell diversification in ERBB-RAS-MAPK signal transduction that produces cell-type specific growth factor responses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Memory is initially labile but can be consolidated into stable long-term memory (LTM) that is stored in the brain for extended periods. Despite recent progress, the molecular and cellular mechanisms underlying the intriguing neurobiological processes of LTM remain incompletely understood. Using the Drosophila courtship conditioning assay as a memory paradigm, here, we show that the LIM homeodomain (LIM-HD) transcription factor Apterous (Ap), which is known to regulate various developmental events, is required for both the consolidation and maintenance of LTM. Interestingly, Ap is involved in these 2 memory processes through distinct mechanisms in different neuronal subsets in the adult brain. Ap and its cofactor Chip (Chi) are indispensable for LTM maintenance in the Drosophila memory center, the mushroom bodies (MBs). On the other hand, Ap plays a crucial role in memory consolidation in a Chi-independent manner in pigment dispersing factor (Pdf)-containing large ventral-lateral clock neurons (l-LNvs) that modulate behavioral arousal and sleep. Since disrupted neurotransmission and electrical silencing in clock neurons impair memory consolidation, Ap is suggested to contribute to the stabilization of memory by ensuring the excitability of l-LNvs. Indeed, ex vivo imaging revealed that a reduced function of Ap, but not Chi, results in exaggerated Cl- responses to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in l-LNvs, indicating that wild-type (WT) Ap maintains high l-LNv excitability by suppressing the GABA response. Consistently, enhancing the excitability of l-LNvs by knocking down GABAA receptors compensates for the impaired memory consolidation in ap null mutants. Overall, our results revealed unique dual functions of the developmental regulator Ap for LTM consolidation in clock neurons and LTM maintenance in MBs.", "classifications": [ { "id": "21H00434", "label": "21H00434", "researcher": "Takaomi Sakai", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Show", "last_name": "Inami", "name": null }, { "creator_type": "author", "first_name": "Tomohito", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Kurata", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kitamoto", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pbio.3001459" }, "pmcid": { "normalized": "PMC8641882" }, "pmid": { "normalized": "34860826" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Clocks", "descriptor_ui": "D001683", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Heterozygote", "descriptor_ui": "D006579", "major_topic": false }, { "descriptor": "LIM-Homeodomain Proteins", "descriptor_ui": "D060850", "major_topic": false }, { "descriptor": "Memory Consolidation", "descriptor_ui": "D000069077", "major_topic": false }, { "descriptor": "Memory, Long-Term", "descriptor_ui": "D057567", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Mushroom Bodies", "descriptor_ui": "D024521", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "e3001459", "proceedings_title": null, "publisher": "", "title": "PLoS biology", "volume": "19", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Consolidation and maintenance of long-term memory involve dual functions of the developmental regulator Apterous in clock neurons and mushroom bodies in the Drosophila brain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Acute lymphoblastic leukaemia with mixed lineage leukaemia gene rearrangement (MLL-ALL) frequently affects infants and is associated with a poor prognosis. Primary refractory and relapsed disease due to resistance to glucocorticoids (GCs) remains a substantial hurdle to improving clinical outcomes. In this study, we aimed to overcome GC resistance of MLL-ALL. METHODS: Using leukaemia patient specimens, we performed bioinformatic analyses to identify target genes/pathways. To test inhibition of target pathways in vivo, we created pre-clinical therapeutic mouse patient-derived xenograft (PDX)-models by transplanting human MLL-ALL leukaemia initiating cells (LIC) into immune-deficient NSG mice. Finally, we conducted B-cell lymphoma-2 (BCL-2) homology domain 3 (BH3) profiling to identify BH3 peptides responsible for treatment resistance in MLL-leukaemia. FINDINGS: Src family kinases (SFKs) and Fms-like tyrosine kinase 3 (FLT3) signaling pathway were over-represented in MLL-ALL cells. PDX-models of infant MLL- ALL recapitulated GC-resistance in vivo but RK-20449, an inhibitor of SFKs and FLT3 eliminated human MLL-ALL cells in vivo, overcoming GC-resistance. Further, we identified BCL-2 dependence as a mechanism of treatment resistance in MLL-ALL through BH3 profiling. Furthermore, MLL-ALL cells resistant to RK-20449 treatment were dependent on the anti-apoptotic BCL-2 protein for their survival. Combined inhibition of SFKs/FLT3 by RK-20449 and of BCL-2 by ABT-199 led to substantial elimination of MLL-ALL cells in vitro and in vivo. Triple treatment combining GCs, RK-20449 and ABT-199 resulted in complete elimination of MLL-ALL cells in vivo. INTERPRETATION: SFKs/FLT3 signaling pathways are promising targets for treatment of treatment-resistant MLL-ALL. Combined inhibition of these kinase pathways and anti-apoptotic BCL-2 successfully eliminated highly resistant MLL-ALL and demonstrated a new treatment strategy for treatment-resistant poor-outcome MLL-ALL. FUNDING: This study was supported by RIKEN (RIKEN President's Discretionary Grant) for FI, Japan Agency for Medical Research and Development (the Basic Science and Platform Technology Program for Innovative Biological Medicine for FI and by NIH CA034196 for LDS. The funders had no role in the study design, data collection, data analysis, interpretation nor writing of the report.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Anne P.", "last_name": "de Groot", "name": null }, { "creator_type": "author", "first_name": "Yoriko", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Rintaro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Ikuko", "last_name": "Ogahara", "name": null }, { "creator_type": "author", "first_name": "Saera", "last_name": "Fujiki", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kajita", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Tomizawa", "name": null }, { "creator_type": "author", "first_name": "Katsuyoshi", "last_name": "Koh", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Ohara", "name": null }, { "creator_type": "author", "first_name": "Leonard D.", "last_name": "Shultz", "name": null }, { "creator_type": "author", "first_name": "Shuki", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Ishikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ebiom.2021.103235" }, "pmcid": { "normalized": "PMC7878180" }, "pmid": { "normalized": "33581643" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Drug Synergism", "descriptor_ui": "D004357", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Leukemic", "descriptor_ui": "D015973", "major_topic": false }, { "descriptor": "Gene Rearrangement", "descriptor_ui": "D015321", "major_topic": true }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Myeloid-Lymphoid Leukemia Protein", "descriptor_ui": "D051788", "major_topic": false }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": false }, { "descriptor": "Pyrroles", "descriptor_ui": "D011758", "major_topic": false }, { "descriptor": "Steroids", "descriptor_ui": "D013256", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "103235", "proceedings_title": null, "publisher": "", "title": "EBioMedicine", "volume": "64", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Targeting critical kinases and anti-apoptotic molecules overcomes steroid resistance in MLL-rearranged leukaemia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Methylglyoxal (MG) is a reactive and cytotoxic alpha-dicarbonyl byproduct of glycolysis. Our bodies have several bio-defense systems to detoxify MG, including an enzymatic system by glyoxalase (GLO) 1 and GLO2. We identified a subtype of schizophrenia patients with novel mutations in the GLO1 gene that results in reductions of enzymatic activity. Moreover, we found that vitamin B6 (VB6) levels in peripheral blood of the schizophrenia patients with GLO1 dysfunction are significantly lower than that of healthy controls. However, the effects of GLO1 dysfunction and VB6 deficiency on the pathophysiology of schizophrenia remains poorly understood. Here, we generated a novel mouse model for this subgroup of schizophrenia patients by feeding Glo1 knockout mice VB6-deficent diets (KO/VB6(-)) and evaluated the combined effects of GLO1 dysfunction and VB6 deficiency on brain function. KO/VB6(-) mice accumulated homocysteine in plasma and MG in the prefrontal cortex (PFC), hippocampus, and striatum, and displayed behavioral deficits, such as impairments of social interaction and cognitive memory and a sensorimotor deficit in the prepulse inhibition test. Furthermore, we found aberrant gene expression related to mitochondria function in the PFC of the KO/VB6(-) mice by RNA-sequencing and weighted gene co-expression network analysis (WGCNA). Finally, we demonstrated abnormal mitochondrial respiratory function and subsequently enhanced oxidative stress in the PFC of KO/VB6(-) mice in the PFC. These findings suggest that the combination of GLO1 dysfunction and VB6 deficiency may cause the observed behavioral deficits via mitochondrial dysfunction and oxidative stress in the PFC.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuya", "last_name": "Toriumi", "name": null }, { "creator_type": "author", "first_name": "Stefano", "last_name": "Berto", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Noriyoshi", "last_name": "Usui", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Dan", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Miyashita", "name": null }, { "creator_type": "author", "first_name": "Yasue", "last_name": "Horiuchi", "name": null }, { "creator_type": "author", "first_name": "Akane", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Asakura", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Nagahama", "name": null }, { "creator_type": "author", "first_name": "Hsiao-Chun", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugaya", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ogasawara", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Masanari", "last_name": "Itokawa", "name": null }, { "creator_type": "author", "first_name": "Genevieve", "last_name": "Konopka", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Arai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.redox.2021.102057" }, "pmcid": { "normalized": "PMC8253914" }, "pmid": { "normalized": "34198071" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lactoylglutathione Lyase", "descriptor_ui": "D007791", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Schizophrenia", "descriptor_ui": "D012559", "major_topic": true }, { "descriptor": "Vitamin B 6 Deficiency", "descriptor_ui": "D026681", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Sep", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "102057", "proceedings_title": null, "publisher": "", "title": "Redox biology", "volume": "45", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Combined glyoxalase 1 dysfunction and vitamin B6 deficiency in a schizophrenia model system causes mitochondrial dysfunction in the prefrontal cortex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the management of patients with type 1 von Willebrand disease, supplementation with Con Facto F(®) as well as hemodynamic stabilization with appropriate analgesia and sedation may be important to reduce the risk of bleeding.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Aiji", "last_name": "Sato Boku", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Miyamoro", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Furuno", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Shibuya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/ccr3.4755" }, "pmcid": { "normalized": "PMC8405533" }, "pmid": { "normalized": "34484779" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "e04755", "proceedings_title": null, "publisher": "", "title": "Clinical case reports", "volume": "9", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Perioperative management of von Willebrand patients at the time of implant placement: Case report.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Age-related regeneration failure in the central nervous system can occur as a result of a decline in remyelination efficacy. The responsiveness of myelin-forming cells to signals for remyelination is affected by aging-related epigenetic modification; however, the molecular mechanism is not fully clarified. In the present study, we report that the apelin receptor (APJ) mediates remyelination efficiency with age. APJ expression in myelin-forming cells is correlated with age-associated changes in remyelination efficiency, and the activation of APJ promotes remyelination through the translocation of myelin regulatory factor. APJ signaling activation promoted remyelination in both aged mice with toxin-induced demyelination and mice with experimental autoimmune encephalomyelitis. In human cells, APJ activation enhanced the expression of remyelination markers. Impaired oligodendrocyte function in aged animals can be reversibly reactivated; thus, the results demonstrate that dysfunction of the apelin-APJ system mediates remyelination failure in aged animals, and that their myelinating function can be reactivated by APJ activation.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masumi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Rieko", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Bikram", "last_name": "Sharma", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Uyeda", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Harutoshi", "last_name": "Fujimura", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Kawahara", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Takao", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Fukamizu", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Yamashita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s43587-021-00041-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37118408" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apelin", "descriptor_ui": "D000073861", "major_topic": false }, { "descriptor": "Apelin Receptors", "descriptor_ui": "D000075244", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myelin Sheath", "descriptor_ui": "D009186", "major_topic": false }, { "descriptor": "Remyelination", "descriptor_ui": "D000074586", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "284-294", "proceedings_title": null, "publisher": "", "title": "Nature aging", "volume": "1", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Age-dependent decline in remyelination capacity is mediated by apelin-APJ signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stem cell-based products have clinical and industrial applications. Thus, there is a need to develop quality control methods to standardize stem cell manufacturing. Here, we report a deep learning-based automated cell tracking (DeepACT) technology for noninvasive quality control and identification of cultured human stem cells. The combination of deep learning-based cascading cell detection and Kalman filter algorithm-based tracking successfully tracked the individual cells within the densely packed human epidermal keratinocyte colonies in the phase-contrast images of the culture. DeepACT rapidly analyzed the motion of individual keratinocytes, which enabled the quantitative evaluation of keratinocyte dynamics in response to changes in culture conditions. Furthermore, DeepACT can distinguish keratinocyte stem cell colonies from non-stem cell-derived colonies by analyzing the spatial and velocity information of cells. This system can be widely applied to stem cell cultures used in regenerative medicine and provides a platform for developing reliable and noninvasive quality control technology.", "classifications": [ { "id": "19H05418", "label": "19H05418", "researcher": "Daisuke Nanba", "type": "grant" }, { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takuya", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Jun'ichi", "last_name": "Kotoku", "name": null }, { "creator_type": "author", "first_name": "Fujio", "last_name": "Toki", "name": null }, { "creator_type": "author", "first_name": "Emi K.", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Nanba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/stem.3371" }, "pmcid": { "normalized": "PMC8359832" }, "pmid": { "normalized": "33783921" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Tracking", "descriptor_ui": "D058948", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Epidermal Cells", "descriptor_ui": "D000078404", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": false }, { "descriptor": "Quality Control", "descriptor_ui": "D011786", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "1091-1100", "proceedings_title": null, "publisher": "", "title": "Stem cells (Dayton, Ohio)", "volume": "39", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-free quality control and identification of human keratinocyte stem cells by deep learning-based automated cell tracking.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The analysis of gene expression regulation, or the epigenome analysis, at the single-cell level is at the forefront of genomics research. To elucidate the mechanisms that regulate gene expression, chromatin immunoprecipitation has been conventionally used for determining the binding sites of DNA-binding proteins, such as histones and transcription factors. Now several new approaches have been emerged to reveal epigenome states at the single-cell level. Instead of using immunoprecipitation of fragmented chromatin, in situ reactions using cells or nuclei, combining with transposase tagging and other methods, have enabled single-cell analysis. Furthermore, single-cell multiomics techniques to simultaneously profiling transcriptome and open chromatin or histone modification have been developed. These single-cell analyses have the potential to identify different cell types in a cell population and reveal the dynamic changes of gene regulation, although those technologies have not yet reached a level for general application.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.sbi.2021.06.010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34303078" } }, "mesh": [ { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": true }, { "descriptor": "Chromatin Immunoprecipitation", "descriptor_ui": "D047369", "major_topic": false }, { "descriptor": "Epigenomics", "descriptor_ui": "D057890", "major_topic": true }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "116-122", "proceedings_title": null, "publisher": "", "title": "Current opinion in structural biology", "volume": "71", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Recent advances in single-cell epigenomics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "FoxP3(+) regulatory T cells (Tregs) play crucial roles in peripheral immune tolerance. In addition, Tregs that reside or accumulate in nonlymphoid tissues, called tissue Tregs, exhibit tissue-specific functions and contribute to the maintenance of tissue homeostasis and repair. In an experimental mouse model of crescentic glomerulonephritis induced by an anti-glomerular basement membrane antibody, Tregs started to accumulate in the kidney on day 10 of disease onset and remained at high levels (~30-35% of CD4(+) T cells) during the late stage (days 21-90), which correlated with stable disease control. Treg depletion on day 21 resulted in the relapse of renal dysfunction and an increase in Th1 cells, suggesting that Tregs are essential for disease control during the convalescence stage. The Tregs that accumulated in the kidney showed tissue Treg phenotypes, including high expression of GATA3, ST2 (the IL33 receptor subunit), amphiregulin (Areg), and PPARgamma. Although T-bet(+) Tregs and RORgammat(+) Tregs were observed in the kidney, GATA3(+) Tregs were predominant during the convalescence stage, and a PPARgamma agonist enhanced the accumulation of GATA3(+) Tregs in the kidney. To understand the function of specific genes in kidney Tregs, we developed a novel T cell transfer system to T cell-deficient mice. This experiment demonstrates that ST2, Areg, and CCR4 in Tregs play important roles in the accumulation of GATA3(+) Tregs in the kidney and in the amelioration of renal injury. Our data suggest that GATA3 is important for the recruitment of Tregs into the kidney, which is necessary for convalescence after renal tissue destruction.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryota", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Komai", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Iizuka-Koga", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Yoshie", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nishimasu", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Nureki", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41423-020-00547-x" }, "pmcid": { "normalized": "PMC8093306" }, "pmid": { "normalized": "32917984" } }, "mesh": [ { "descriptor": "Amphiregulin", "descriptor_ui": "D066258", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies", "descriptor_ui": "D000906", "major_topic": false }, { "descriptor": "Convalescence", "descriptor_ui": "D003289", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "GATA3 Transcription Factor", "descriptor_ui": "D050990", "major_topic": false }, { "descriptor": "Glomerulonephritis", "descriptor_ui": "D005921", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Interleukin-1 Receptor-Like 1 Protein", "descriptor_ui": "D000072179", "major_topic": false }, { "descriptor": "Interleukin-33", "descriptor_ui": "D000067596", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Lymphocyte Subsets", "descriptor_ui": "D016131", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "PPAR gamma", "descriptor_ui": "D047495", "major_topic": false }, { "descriptor": "Receptors, CCR4", "descriptor_ui": "D054398", "major_topic": false }, { "descriptor": "Receptors, Chemokine", "descriptor_ui": "D019707", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "1249-1261", "proceedings_title": null, "publisher": "", "title": "Cellular & molecular immunology", "volume": "18", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Kidney GATA3(+) regulatory T cells play roles in the convalescence stage after antibody-mediated renal injury.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Specific interaction between the start codon, 5'-AUG-3', and the anticodon, 5'-CAU-3', ensures accurate initiation of translation. Recent studies show that several near-cognate start codons (e.g. GUG and CUG) can play a role in initiating translation in eukaryotes. However, the mechanism allowing initiation through mismatched base-pairs at the ribosomal decoding site is still unclear at an atomic level. In this work, we propose an extended simulation-based method to evaluate free energy profiles, through computing the distance between each base-pair of the triplet interactions involved in recognition of start codons in eukaryotic translation pre-initiation complex. Our method provides not only the free energy penalty for mismatched start codons relative to the AUG start codon, but also the preferred pathways of transitions between bound and unbound states, which has not been described by previous studies. To verify the method, the binding dynamics of cognate (AUG) and near-cognate start codons (CUG and GUG) were simulated. Evaluated free energy profiles agree with experimentally observed changes in initiation frequencies from respective codons. This work proposes for the first time how a G:U mismatch at the first position of codon (GUG)-anticodon base-pairs destabilizes the accommodation in the initiating eukaryotic ribosome and how initiation at a CUG codon is nearly as strong as, or sometimes stronger than, that at a GUG codon. Our method is expected to be applied to study the affinity changes for various mismatched base-pairs.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takeru", "last_name": "Kameda", "name": null }, { "creator_type": "author", "first_name": "Katsura", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Togashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1009068" }, "pmcid": { "normalized": "PMC8224888" }, "pmid": { "normalized": "34125830" } }, "mesh": [ { "descriptor": "Anticodon", "descriptor_ui": "D000926", "major_topic": false }, { "descriptor": "Base Pairing", "descriptor_ui": "D020029", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Codon, Initiator", "descriptor_ui": "D018387", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Eukaryotic Cells", "descriptor_ui": "D005057", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": false }, { "descriptor": "Nucleic Acid Conformation", "descriptor_ui": "D009690", "major_topic": false }, { "descriptor": "Peptide Chain Initiation, Translational", "descriptor_ui": "D010442", "major_topic": true }, { "descriptor": "Ribosomes", "descriptor_ui": "D012270", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Thermodynamics", "descriptor_ui": "D013816", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "e1009068", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "17", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Free energy landscape of RNA binding dynamics in start codon recognition by eukaryotic ribosomal pre-initiation complex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The bending of epithelial tubes is a fundamental process in organ morphogenesis, driven by various multicellular behaviours. The cochlea in the mammalian inner ear is a representative example of spiral tissue architecture where the continuous bending of the duct is a fundamental component of its morphogenetic process. Although the cochlear duct morphogenesis has been studied by genetic approaches extensively, it is still unclear how the cochlear duct morphology is physically formed. Here, we report that nuclear behaviour changes are associated with the curvature of the pseudostratified epithelium during murine cochlear development. Two-photon live-cell imaging reveals that the nuclei shuttle between the luminal and basal edges of the cell is in phase with cell-cycle progression, known as interkinetic nuclear migration, in the flat region of the pseudostratified epithelium. However, the nuclei become stationary on the luminal side following mitosis in the curved region. Mathematical modelling together with perturbation experiments shows that this nuclear stalling facilitates luminal-basal differential growth within the epithelium, suggesting that the nuclear stalling would contribute to the bending of the pseudostratified epithelium during the cochlear duct development. The findings suggest a possible scenario of differential growth which sculpts the tissue shape, driven by collective nuclear dynamics.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mamoru", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Tateya", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1098/rsos.211024" }, "pmcid": { "normalized": "PMC8652271" }, "pmid": { "normalized": "34909216" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "211024", "proceedings_title": null, "publisher": "", "title": "Royal Society open science", "volume": "8", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Stalling interkinetic nuclear migration in curved pseudostratified epithelium of developing cochlea.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A substantial and constitutive expression of translocator protein (TSPO) in cerebral blood vessels hampers the sensitive detection of neuroinflammation characterized by greatly induced TSPO expression in activated glia. Here, we conducted in vivo positron emission tomography (PET) and in vitro autoradiographic imaging of normal and TSPO-deficient mouse brains to compare the binding properties of (18)F-FEBMP, a relatively novel TSPO radioligand developed for human studies based on its insensitivity to a common polymorphism, with (11)C-PK11195, as well as other commonly used TSPO radioligands including (11)C-PBR28, (11)C-Ac5216 and (18)F-FEDAA1106. TSPO in cerebral vessels of normal mice was found to provide a major binding site for (11)C-PK11195, (11)C-PBR28 and (18)F-FEDAA1106, in contrast to no overt specific binding of (18)F-FEBMP and (11)C-Ac5216 to this vascular component. In addition, (18)F-FEBMP yielded PET images of microglial TSPO with a higher contrast than (11)C-PK11195 in a tau transgenic mouse modeling Alzheimer's disease (AD) and allied neurodegenerative tauopathies. Moreover, TSPO expression examined by immunoblotting was significantly increased in AD brains compared with healthy controls, and was well correlated with the autoradiographic binding of (18)F-FEBMP but not (11)C-PK11195. Our findings support the potential advantage of comparatively glial TSPO-selective radioligands such as (18)F-FEBMP for PET imaging of inflammatory glial cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Bin", "last_name": "Ji", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Tomoteru", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Fujinaga", "name": null }, { "creator_type": "author", "first_name": "Ming-Rong", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Ichio", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Kito", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Sawada", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1177/0271678x21992457" }, "pmcid": { "normalized": "PMC8327108" }, "pmid": { "normalized": "33557690" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": true }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microglia", "descriptor_ui": "D017628", "major_topic": false }, { "descriptor": "Positron-Emission Tomography", "descriptor_ui": "D049268", "major_topic": false }, { "descriptor": "Radiopharmaceuticals", "descriptor_ui": "D019275", "major_topic": false }, { "descriptor": "Receptors, GABA", "descriptor_ui": "D018079", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "2076-2089", "proceedings_title": null, "publisher": "", "title": "Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism", "volume": "41", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Detection of Alzheimer's disease-related neuroinflammation by a PET ligand selective for glial versus vascular translocator protein.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reactive sulfur species, including hydrogen sulfide, hydropersulfide, and polysulfide, have many roles in biological systems. For example, hydrogen sulfide is involved in the relaxation of vascular smooth muscles and mediation of neurotransmission, while sulfane sulfur, which exists in cysteine persulfide/polysulfide, and glutathione persulfide/polysulfide, is involved in physiological antioxidation and cytoprotection mechanisms. Fluorescence imaging is well suited for real-time monitoring of reactive sulfur species in living cells, and many fluorescent probes for reactive sulfur species have been reported. In such probes, the choice of detection chemistry is extremely important, not only to achieve effective fluorescence switching and high selectivity, but also because the reactions may be applicable to develop other chemical tools, such as reactive sulfur species donors/scavengers. Here, we present an overview of both widely used and recently developed fluorescent probes for reactive sulfur species, focusing especially on the chemical reactions employed in them for fluorescence switching. We also briefly introduce some applications of fluorescent probes for hydrogen sulfide and sulfane sulfur.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Honami", "last_name": "Echizen", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.3164/jcbn.20-18" }, "pmcid": { "normalized": "PMC7844667" }, "pmid": { "normalized": "33536707" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "9-17", "proceedings_title": null, "publisher": "", "title": "Journal of clinical biochemistry and nutrition", "volume": "68", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Recent advances in probe design to detect reactive sulfur species and in the chemical reactions employed for fluorescence switching.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "It has been recognized that tissue stiffness provides useful diagnostic information, as with palpation as a screening for diseases such as cancer. In recent years, shear wave elastography (SWE), a technique for evaluating and imaging tissue elasticity quantitatively and objectively in diagnostic imaging, has been put into practical use, and the amount of clinical knowledge about SWE has increased. In addition, some guidelines and review papers regarding technology and clinical applications have been published, and the status as a diagnostic technology is in the process of being established. However, there are still unclear points about the interpretation of shear wave speed (SWS) and converted elastic modulus in SWE. To clarify these, it is important to investigate the factors that affect the SWS and elastic modulus. Therefore, physical and engineering factors that potentially affect the SWS and elastic modulus are discussed in this review paper, based on the principles of SWE and a literature review. The physical factors include the propagation properties of shear waves, mechanical properties (viscoelasticity, nonlinearity, and anisotropy), and size and shape of target tissues. The engineering factors include the region of interest depth and signal processing. The aim of this review paper is not to provide an answer to the interpretation of SWS. It is to provide information for readers to formulate and verify the hypothesis for the interpretation. Therefore, methods to verify the hypothesis for the interpretation are also reviewed. Finally, studies on the safety of SWE are discussed.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Naotaka", "last_name": "Nitta", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Hachiya", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10396-021-01127-w" }, "pmcid": { "normalized": "PMC8578095" }, "pmid": { "normalized": "34453649" } }, "mesh": [ { "descriptor": "Elastic Modulus", "descriptor_ui": "D055119", "major_topic": false }, { "descriptor": "Elasticity Imaging Techniques", "descriptor_ui": "D054459", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Oct", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "403-414", "proceedings_title": null, "publisher": "", "title": "Journal of medical ultrasonics (2001)", "volume": "48", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "A review of physical and engineering factors potentially affecting shear wave elastography.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Thyroglossal duct on the dorsum of the tongue in the pediatric patient can cause a difficult airway due to the large mass and risk of airway obstruction associated with a swollen tongue after surgery.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Aiji", "last_name": "Sato Boku", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Kako", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Okuni", "name": null }, { "creator_type": "author", "first_name": "Nobuyoshi", "last_name": "Kusama", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kamimura", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sento", "name": null }, { "creator_type": "author", "first_name": "MinHye", "last_name": "So", "name": null }, { "creator_type": "author", "first_name": "Motoshi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Shibuya", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Sobue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/ccr3.3607" }, "pmcid": { "normalized": "PMC7869400" }, "pmid": { "normalized": "33598223" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "673-676", "proceedings_title": null, "publisher": "", "title": "Clinical case reports", "volume": "9", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Perioperative management of thyroglossal duct cystectomy in a pediatric patient: A case report.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yang", "last_name": "Shi", "name": null }, { "creator_type": "author", "first_name": "Alexey G.", "last_name": "Murzin", "name": null }, { "creator_type": "author", "first_name": "Benjamin", "last_name": "Falcon", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Epstein", "name": null }, { "creator_type": "author", "first_name": "Jonathan", "last_name": "Machin", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Tempest", "name": null }, { "creator_type": "author", "first_name": "Kathy L.", "last_name": "Newell", "name": null }, { "creator_type": "author", "first_name": "Ruben", "last_name": "Vidal", "name": null }, { "creator_type": "author", "first_name": "Holly J.", "last_name": "Garringer", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Bernardino", "last_name": "Ghetti", "name": null }, { "creator_type": "author", "first_name": "Ming-Kuei", "last_name": "Jang", "name": null }, { "creator_type": "author", "first_name": "Sjors H. W.", "last_name": "Scheres", "name": null }, { "creator_type": "author", "first_name": "Michel", "last_name": "Goedert", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00401-021-02303-5" }, "pmcid": { "normalized": "PMC8496564" }, "pmid": { "normalized": "33830331" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "983", "proceedings_title": null, "publisher": "", "title": "Acta neuropathologica", "volume": "141", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Correction to: Cryo-EM structures of tau filaments from Alzheimer's disease with PET ligand APN-1607.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The excretion and reabsorption of uric acid both to and from urine are tightly regulated by uric acid transporters. Metabolic syndrome conditions, such as obesity, hypercholesterolemia, and insulin resistance, are believed to regulate the expression of uric acid transporters and decrease the excretion of uric acid. However, the mechanisms driving cholesterol impacts on uric acid transporters have been unknown. Here, we show that cholesterol metabolite 27-hydroxycholesterol (27HC) upregulates the uric acid reabsorption transporter URAT1 encoded by SLC22A12 via estrogen receptors (ER). Transcriptional motif analysis showed that the SLC22A12 gene promoter has more estrogen response elements (EREs) than other uric acid reabsorption transporters such as SLC22A11 and SLC22A13, and 27HC-activated SLC22A12 gene promoter via ER through EREs. Furthermore, 27HC increased SLC22A12 gene expression in human kidney organoids. Our results suggest that in hypercholesterolemic conditions, elevated levels of 27HC derived from cholesterol induce URAT1/SLC22A12 expression to increase uric acid reabsorption, and thereby, could increase serum uric acid levels.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masaya", "last_name": "Matsubayashi", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko M.", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Hitoki", "last_name": "Nanaura", "name": null }, { "creator_type": "author", "first_name": "Sotaro", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Arvand", "last_name": "Asghari", "name": null }, { "creator_type": "author", "first_name": "Linh", "last_name": "Bui", "name": null }, { "creator_type": "author", "first_name": "Shinko", "last_name": "Kobashigawa", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Riko", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Takeshi K.", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Genro", "last_name": "Kashino", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Eriguchi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Tsuruya", "name": null }, { "creator_type": "author", "first_name": "Shushi", "last_name": "Nagamori", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Sugie", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null }, { "creator_type": "author", "first_name": "Michihisa", "last_name": "Umetani", "name": null }, { "creator_type": "author", "first_name": "Eiichiro", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1096/fj.202002077r" }, "pmcid": { "normalized": "PMC7771643" }, "pmid": { "normalized": "33368618" } }, "mesh": [ { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydroxycholesterols", "descriptor_ui": "D006888", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Organic Anion Transporters", "descriptor_ui": "D027361", "major_topic": false }, { "descriptor": "Organic Cation Transport Proteins", "descriptor_ui": "D027701", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "Receptors, Estrogen", "descriptor_ui": "D011960", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "e21262", "proceedings_title": null, "publisher": "", "title": "FASEB journal : official publication of the Federation of American Societies for Experimental Biology", "volume": "35", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "27-Hydroxycholesterol regulates human SLC22A12 gene expression through estrogen receptor action.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In vertebrate embryos, the kidney primordium metanephros is formed from two distinct cell lineages, Wolffian duct and metanephric mesenchyme, which were classically grouped as intermediate mesoderm. Whereas the reciprocal interactions between these two cell populations in kidney development have been studied extensively, the mechanisms generating them remain elusive. Here, we show that the mouse cell lineage that forms nephric mesenchyme develops as a subpopulation of Tbx6-expressing mesodermal precursor derivatives of neuro-mesodermal progenitors (NMPs) under the condition of bone morphogenetic protein (BMP)-signal-dependent Osr1 expression. The Osr1-expressing nephric mesenchyme precursors were confirmed as descendants of NMPs because they were labeled by Sox2 N1 enhancer-EGFP. In Tbx6 mutant embryos, nephric mesenchyme changed its fate into neural tissues, which reflected its NMP origin. In Osr1 mutant embryos, the specific region of the Tbx6-expressing mesoderm precursor, which normally expresses Osr1 and develops into the nephric mesenchyme, instead expressed the somite marker FoxC2. BMP signaling activated Osr1 expression in a region of TBX6-expressing mesoderm and elicited nephric mesenchyme development. This study suggested a new model of cell lineage segregation during gastrulation.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shinichi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2021.07.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34256037" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Morphogenetic Proteins", "descriptor_ui": "D019485", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Gastrulation", "descriptor_ui": "D054262", "major_topic": true }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Mesenchymal Stem Cells", "descriptor_ui": "D059630", "major_topic": false }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Somites", "descriptor_ui": "D019170", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "T-Box Domain Proteins", "descriptor_ui": "D020825", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Oct", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "155-162", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "478", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "The nephric mesenchyme lineage of intermediate mesoderm is derived from Tbx6-expressing derivatives of neuro-mesodermal progenitors via BMP-dependent Osr1 function.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Light-responsive regulation of ciliary motility is known to be conducted through modulation of dyneins, but the mechanism is not fully understood. Here, we report a novel subunit of the two-headed f/I1 inner arm dynein, named DYBLUP, in animal spermatozoa and a unicellular green alga. This subunit contains a BLUF (sensors of blue light using FAD) domain that appears to directly modulate dynein activity in response to light. DYBLUP (dynein-associated BLUF protein) mediates the connection between the f/I1 motor domain and the tether complex that links the motor to the doublet microtubule. Chlamydomonas lacking the DYBLUP ortholog shows both positive and negative phototaxis but becomes acclimated and attracted to high-intensity blue light. These results suggest a mechanism to avoid toxic strong light via direct photoregulation of dyneins.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Osamu", "last_name": "Kutomi", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Katsutoshi", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Yuuhei", "last_name": "Nakagiri", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Noga", "name": null }, { "creator_type": "author", "first_name": "Jagan Mohan", "last_name": "Obbineni", "name": null }, { "creator_type": "author", "first_name": "Noemi", "last_name": "Zimmermann", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Misa", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Kogiku", "last_name": "Shiba", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Kigoshi", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Yuma", "last_name": "Asahina", "name": null }, { "creator_type": "author", "first_name": "Chihong", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Mia", "last_name": "Nakachi", "name": null }, { "creator_type": "author", "first_name": "Lixy", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Shiori", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Sawada", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Mitsuoka", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Takahide", "last_name": "Kon", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Inaba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abf3621" }, "pmcid": { "normalized": "PMC7909887" }, "pmid": { "normalized": "33637535" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Feb", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "eabf3621", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "7", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "A dynein-associated photoreceptor protein prevents ciliary acclimation to blue light.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "DNA methylation is associated with a number of biological phenomena, and plays crucial roles in epigenetic regulation of eukaryotic gene expression. It is also suggested that DNA methylation alters the mechanical properties of DNA molecules, which is likely to affect epigenetic regulation. However, it has not been systematically investigated how methylation changes the structural and dynamic features of DNA. In this research, to elucidate the effects of methylation on DNA mechanics, a fully atomic molecular dynamics simulation of double-stranded DNA with several methylation patterns was performed. Through the analysis of the relative positioning of the nucleotides (base-step variables), characteristic changes in terms of local flexibility were observed, which further affected the overall DNA geometry and stiffness. These findings may serve as a basis for a discussion on methylation-dependent DNA dynamics in physiological conditions.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takeru", "last_name": "Kameda", "name": null }, { "creator_type": "author", "first_name": "Miho M.", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Awazu", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Togashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.103.012404" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33601517" } }, "mesh": [ { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": true }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": true }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": true }, { "descriptor": "Nucleic Acid Conformation", "descriptor_ui": "D009690", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Jan", "date_precision": "unknown", "issue": "1-1", "normalized_date": null, "pages": "012404", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "103", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Structural dynamics of DNA depending on methylation pattern.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hair follicles, mammalian mini-organs that grow hair, miniaturize during aging, leading to hair thinning and loss. Here we report that hair follicle stem cells (HFSCs) lose their regenerative capabilities during aging owing to the adoption of an atypical cell division program. Cell fate tracing and cell division axis analyses revealed that while HFSCs in young mice undergo typical symmetric and asymmetric cell divisions to regenerate hair follicles, upon aging or stress, they adopt an atypical 'stress-responsive' type of asymmetric cell division. This type of division is accompanied by the destabilization of hemidesmosomal protein COL17A1 and cell polarity protein aPKClambda and generates terminally differentiating epidermal cells instead of regenerating the hair follicle niche. With the repetition of these atypical divisions, HFSCs detach from the basal membrane causing their exhaustion, elimination and organ aging. The experimentally induced stabilization of COL17A1 rescued organ homeostasis through aPKClambda stabilization. These results demonstrate that distinct stem cell division programs may govern tissue and organ aging.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Nan", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Nanba", "name": null }, { "creator_type": "author", "first_name": "Shizuko", "last_name": "Ichinose", "name": null }, { "creator_type": "author", "first_name": "Aki", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Sotaro", "last_name": "Kurata", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Morinaga", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Mohri", "name": null }, { "creator_type": "author", "first_name": "Adele", "last_name": "De Arcangelis", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Emi K.", "last_name": "Nishimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s43587-021-00033-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37118636" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Hair", "descriptor_ui": "D006197", "major_topic": false }, { "descriptor": "Hair Follicle", "descriptor_ui": "D018859", "major_topic": true }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "190-204", "proceedings_title": null, "publisher": "", "title": "Nature aging", "volume": "1", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Distinct types of stem cell divisions determine organ regeneration and aging in hair follicles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide having trophic and protective functions in neural tissues, including the retina. Previously, we have shown that intravitreal PACAP administration can maintain retinal structure in the animal model of retinopathy of prematurity (ROP). The purpose of this study is to examine the development of ROP in PACAP-deficient and wild-type mice to reveal the function of endogenous PACAP. Wild-type and PACAP-knockout (KO) mouse pups at postnatal day (PD) 7 were maintained at 75% oxygen for 5 consecutive days then returned to room air on PD12 to develop oxygen-induced retinopathy (OIR). On PD15, animals underwent electroretinography (ERG) to assess visual function. On PD16, eyes were harvested for either immunohistochemistry to determine the percentage of the central avascular retinal area or molecular analysis to assess angiogenesis proteins by array kit and anti-apoptotic protein kinase B (Akt) change by western blot. Retinas of PACAP-deficient OIR mice showed a greater central avascular area than that of the wild types. ERG revealed significantly decreased b-wave amplitude in PACAP KO compared to their controls. Several angiogenic proteins were upregulated due to OIR, and 11 different proteins markedly increased in PACAP-deficient mice, whereas western blot analysis revealed a reduction in Akt phosphorylation, suggesting an advanced cell death in the lack of PACAP. This is the first study to examine the endogenous effect of PACAP in the OIR model. Previously, we have shown the beneficial effect of exogenous local PACAP treatment in the rat OIR model. Together with the present findings, we suggest that PACAP could be a novel retinoprotective agent in ROP.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Timea", "last_name": "Kvarik", "name": null }, { "creator_type": "author", "first_name": "Dora", "last_name": "Reglodi", "name": null }, { "creator_type": "author", "first_name": "Dora", "last_name": "Werling", "name": null }, { "creator_type": "author", "first_name": "Alexandra", "last_name": "Vaczy", "name": null }, { "creator_type": "author", "first_name": "Petra", "last_name": "Kovari", "name": null }, { "creator_type": "author", "first_name": "Edina", "last_name": "Szabo", "name": null }, { "creator_type": "author", "first_name": "Krisztina", "last_name": "Kovacs", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Tibor", "last_name": "Ertl", "name": null }, { "creator_type": "author", "first_name": "Judit", "last_name": "Gyarmati", "name": null }, { "creator_type": "author", "first_name": "Tamas", "last_name": "Atlasz", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12031-021-01846-2" }, "pmcid": { "normalized": "PMC8602170" }, "pmid": { "normalized": "33895966" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Retinopathy of Prematurity", "descriptor_ui": "D012178", "major_topic": false }, { "descriptor": "Vision, Ocular", "descriptor_ui": "D014785", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "2546-2557", "proceedings_title": null, "publisher": "", "title": "Journal of molecular neuroscience : MN", "volume": "71", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "The Protective Effects of Endogenous PACAP in Oxygen-Induced Retinopathy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated , quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist's experiments, while more than half have even failed to reproduce their own experiments. One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique. Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g. DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility. In April 2020, the QUality Assessment and REProducibility for instruments and images in Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models and tools, including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper (1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; (2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists, bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers and observers of such; (3) outlines the current actions of the QUAREP-LiMi initiative and (4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Glyn", "last_name": "Nelson", "name": null }, { "creator_type": "author", "first_name": "Ulrike", "last_name": "Boehm", "name": null }, { "creator_type": "author", "first_name": "Steve", "last_name": "Bagley", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Bajcsy", "name": null }, { "creator_type": "author", "first_name": "Johanna", "last_name": "Bischof", "name": null }, { "creator_type": "author", "first_name": "Claire M.", "last_name": "Brown", "name": null }, { "creator_type": "author", "first_name": "Aurelien", "last_name": "Dauphin", "name": null }, { "creator_type": "author", "first_name": "Ian M.", "last_name": "Dobbie", "name": null }, { "creator_type": "author", "first_name": "John E.", "last_name": "Eriksson", "name": null }, { "creator_type": "author", "first_name": "Orestis", "last_name": "Faklaris", "name": null }, { "creator_type": "author", "first_name": "Julia", "last_name": "Fernandez-Rodriguez", "name": null }, { "creator_type": "author", "first_name": "Alexia", "last_name": "Ferrand", "name": null }, { "creator_type": "author", "first_name": "Laurent", "last_name": "Gelman", "name": null }, { "creator_type": "author", "first_name": "Ali", "last_name": "Gheisari", "name": null }, { "creator_type": "author", "first_name": "Hella", "last_name": "Hartmann", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Kukat", "name": null }, { "creator_type": "author", "first_name": "Alex", "last_name": "Laude", "name": null }, { "creator_type": "author", "first_name": "Miso", "last_name": "Mitkovski", "name": null }, { "creator_type": "author", "first_name": "Sebastian", "last_name": "Munck", "name": null }, { "creator_type": "author", "first_name": "Alison J.", "last_name": "North", "name": null }, { "creator_type": "author", "first_name": "Tobias M.", "last_name": "Rasse", "name": null }, { "creator_type": "author", "first_name": "Ute", "last_name": "Resch-Genger", "name": null }, { "creator_type": "author", "first_name": "Lucas C.", "last_name": "Schuetz", "name": null }, { "creator_type": "author", "first_name": "Arne", "last_name": "Seitz", "name": null }, { "creator_type": "author", "first_name": "Caterina", "last_name": "Strambio-De-Castillia", "name": null }, { "creator_type": "author", "first_name": "Jason R.", "last_name": "Swedlow", "name": null }, { "creator_type": "author", "first_name": "Ioannis", "last_name": "Alexopoulos", "name": null }, { "creator_type": "author", "first_name": "Karin", "last_name": "Aumayr", "name": null }, { "creator_type": "author", "first_name": "Sergiy", "last_name": "Avilov", "name": null }, { "creator_type": "author", "first_name": "Gert-Jan", "last_name": "Bakker", "name": null }, { "creator_type": "author", "first_name": "Rodrigo R.", "last_name": "Bammann", "name": null }, { "creator_type": "author", "first_name": "Andrea", "last_name": "Bassi", "name": null }, { "creator_type": "author", "first_name": "Hannes", "last_name": "Beckert", "name": null }, { "creator_type": "author", "first_name": "Sebastian", "last_name": "Beer", "name": null }, { "creator_type": "author", "first_name": "Yury", "last_name": "Belyaev", "name": null }, { "creator_type": "author", "first_name": "Jakob", "last_name": "Bierwagen", "name": null }, { "creator_type": "author", "first_name": "Konstantin A.", "last_name": "Birngruber", "name": null }, { "creator_type": "author", "first_name": "Manel", "last_name": "Bosch", "name": null }, { "creator_type": "author", "first_name": "Juergen", "last_name": "Breitlow", "name": null }, { "creator_type": "author", "first_name": "Lisa A.", "last_name": "Cameron", "name": null }, { "creator_type": "author", "first_name": "Joe", "last_name": "Chalfoun", "name": null }, { "creator_type": "author", "first_name": "James J.", "last_name": "Chambers", "name": null }, { "creator_type": "author", "first_name": "Chieh-Li", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Eduardo", "last_name": "Conde-Sousa", "name": null }, { "creator_type": "author", "first_name": "Alexander D.", "last_name": "Corbett", "name": null }, { "creator_type": "author", "first_name": "Fabrice P.", "last_name": "Cordelieres", "name": null }, { "creator_type": "author", "first_name": "Elaine Del", "last_name": "Nery", "name": null }, { "creator_type": "author", "first_name": "Ralf", "last_name": "Dietzel", "name": null }, { "creator_type": "author", "first_name": "Frank", "last_name": "Eismann", "name": null }, { "creator_type": "author", "first_name": "Elnaz", "last_name": "Fazeli", "name": null }, { "creator_type": "author", "first_name": "Andreas", "last_name": "Felscher", "name": null }, { "creator_type": "author", "first_name": "Hans", "last_name": "Fried", "name": null }, { "creator_type": "author", "first_name": "Nathalie", "last_name": "Gaudreault", "name": null }, { "creator_type": "author", "first_name": "Wah Ing", "last_name": "Goh", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Guilbert", "name": null }, { "creator_type": "author", "first_name": "Roland", "last_name": "Hadleigh", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Hemmerich", "name": null }, { "creator_type": "author", "first_name": "Gerhard A.", "last_name": "Holst", "name": null }, { "creator_type": "author", "first_name": "Michelle S.", "last_name": "Itano", "name": null }, { "creator_type": "author", "first_name": "Claudia B.", "last_name": "Jaffe", "name": null }, { "creator_type": "author", "first_name": "Helena K.", "last_name": "Jambor", "name": null }, { "creator_type": "author", "first_name": "Stuart C.", "last_name": "Jarvis", "name": null }, { "creator_type": "author", "first_name": "Antje", "last_name": "Keppler", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Kirchenbuechler", "name": null }, { "creator_type": "author", "first_name": "Marcel", "last_name": "Kirchner", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Gabriel", "last_name": "Krens", "name": null }, { "creator_type": "author", "first_name": "Susanne", "last_name": "Kunis", "name": null }, { "creator_type": "author", "first_name": "Judith", "last_name": "Lacoste", "name": null }, { "creator_type": "author", "first_name": "Marco", "last_name": "Marcello", "name": null }, { "creator_type": "author", "first_name": "Gabriel G.", "last_name": "Martins", "name": null }, { "creator_type": "author", "first_name": "Daniel J.", "last_name": "Metcalf", "name": null }, { "creator_type": "author", "first_name": "Claire A.", "last_name": "Mitchell", "name": null }, { "creator_type": "author", "first_name": "Joshua", "last_name": "Moore", "name": null }, { "creator_type": "author", "first_name": "Tobias", "last_name": "Mueller", "name": null }, { "creator_type": "author", "first_name": "Michael S.", "last_name": "Nelson", "name": null }, { "creator_type": "author", "first_name": "Stephen", "last_name": "Ogg", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Alexandra L.", "last_name": "Palmer", "name": null }, { "creator_type": "author", "first_name": "Perrine", "last_name": "Paul-Gilloteaux", "name": null }, { "creator_type": "author", "first_name": "Jaime A.", "last_name": "Pimentel", "name": null }, { "creator_type": "author", "first_name": "Laure", "last_name": "Plantard", "name": null }, { "creator_type": "author", "first_name": "Santosh", "last_name": "Podder", "name": null }, { "creator_type": "author", "first_name": "Elton", "last_name": "Rexhepaj", "name": null }, { "creator_type": "author", "first_name": "Arnaud", "last_name": "Royon", "name": null }, { "creator_type": "author", "first_name": "Markku A.", "last_name": "Saari", "name": null }, { "creator_type": "author", "first_name": "Damien", "last_name": "Schapman", "name": null }, { "creator_type": "author", "first_name": "Vincent", "last_name": "Schoonderwoert", "name": null }, { "creator_type": "author", "first_name": "Britta", "last_name": "Schroth-Diez", "name": null }, { "creator_type": "author", "first_name": "Stanley", "last_name": "Schwartz", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Shaw", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Spitaler", "name": null }, { "creator_type": "author", "first_name": "Martin T.", "last_name": "Stoeckl", "name": null }, { "creator_type": "author", "first_name": "Damir", "last_name": "Sudar", "name": null }, { "creator_type": "author", "first_name": "Jeremie", "last_name": "Teillon", "name": null }, { "creator_type": "author", "first_name": "Stefan", "last_name": "Terjung", "name": null }, { "creator_type": "author", "first_name": "Roland", "last_name": "Thuenauer", "name": null }, { "creator_type": "author", "first_name": "Christian D.", "last_name": "Wilms", "name": null }, { "creator_type": "author", "first_name": "Graham D.", "last_name": "Wright", "name": null }, { "creator_type": "author", "first_name": "Roland", "last_name": "Nitschke", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/jmi.13041" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34214188" } }, "mesh": [ { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": true }, { "descriptor": "Reference Standards", "descriptor_ui": "D012015", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Oct", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "56-73", "proceedings_title": null, "publisher": "", "title": "Journal of microscopy", "volume": "284", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pluripotent stem cells (PSCs) can differentiate into all cell types in the body, and their differentiation procedures recapitulate the developmental processes of embryogenesis. Focusing on neurodevelopment, we describe here the application of knowledge gained from embryology to the neural induction of PSCs. Furthermore, PSC-based neural modeling provides novel insights into neurodevelopmental processes. In particular, human PSC cultures are a powerful tool for the study of human-specific neurodevelopmental processes and could even enable the elucidation of the mechanisms of human brain evolution. We also discuss challenges and potential future directions in further improving PSC-based neural modeling.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12699" }, "pmcid": { "normalized": "PMC7984205" }, "pmid": { "normalized": "33141454" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "18-25", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "63", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Modeling neurodevelopment in a dish with pluripotent stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tau and Abeta assemblies of Alzheimer's disease (AD) can be visualized in living subjects using positron emission tomography (PET). Tau assemblies comprise paired helical and straight filaments (PHFs and SFs). APN-1607 (PM-PBB3) is a recently described PET ligand for AD and other tau proteinopathies. Since it is not known where in the tau folds PET ligands bind, we used electron cryo-microscopy (cryo-EM) to determine the binding sites of APN-1607 in the Alzheimer fold. We identified two major sites in the beta-helix of PHFs and SFs and a third major site in the C-shaped cavity of SFs. In addition, we report that tau filaments from posterior cortical atrophy (PCA) and primary age-related tauopathy (PART) are identical to those from AD. In support, fluorescence labelling showed binding of APN-1607 to intraneuronal inclusions in AD, PART and PCA. Knowledge of the binding modes of APN-1607 to tau filaments may lead to the development of new ligands with increased specificity and binding activity. We show that cryo-EM can be used to identify the binding sites of small molecules in amyloid filaments.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yang", "last_name": "Shi", "name": null }, { "creator_type": "author", "first_name": "Alexey G.", "last_name": "Murzin", "name": null }, { "creator_type": "author", "first_name": "Benjamin", "last_name": "Falcon", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Epstein", "name": null }, { "creator_type": "author", "first_name": "Jonathan", "last_name": "Machin", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Tempest", "name": null }, { "creator_type": "author", "first_name": "Kathy L.", "last_name": "Newell", "name": null }, { "creator_type": "author", "first_name": "Ruben", "last_name": "Vidal", "name": null }, { "creator_type": "author", "first_name": "Holly J.", "last_name": "Garringer", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Bernardino", "last_name": "Ghetti", "name": null }, { "creator_type": "author", "first_name": "Ming-Kuei", "last_name": "Jang", "name": null }, { "creator_type": "author", "first_name": "Sjors H. W.", "last_name": "Scheres", "name": null }, { "creator_type": "author", "first_name": "Michel", "last_name": "Goedert", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00401-021-02294-3" }, "pmcid": { "normalized": "PMC8043864" }, "pmid": { "normalized": "33723967" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Benzothiazoles", "descriptor_ui": "D052160", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Cryoelectron Microscopy", "descriptor_ui": "D020285", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorine Radioisotopes", "descriptor_ui": "D005462", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Positron-Emission Tomography", "descriptor_ui": "D049268", "major_topic": false }, { "descriptor": "Radiopharmaceuticals", "descriptor_ui": "D019275", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "697-708", "proceedings_title": null, "publisher": "", "title": "Acta neuropathologica", "volume": "141", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Cryo-EM structures of tau filaments from Alzheimer's disease with PET ligand APN-1607.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: As of March 2021, Japan is facing a fourth wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To prevent further spread of infection, sera cross-neutralizing activity of patients previously infected with conventional SARS-CoV-2 against novel variants is important but has not been firmly established. METHODS: We investigated the neutralizing potency of 81 coronavirus disease 2019 (COVID-19) patients' sera from the first to fourth waves of the pandemic against SARS-CoV-2 D614G, B.1.1.7, P.1, and B.1.351 variants using their authentic viruses. RESULTS: Most sera had neutralizing activity against all variants, showing similar activity against B.1.1.7 and D614G, but lower activity especially against B.1.351. In the fourth wave, sera-neutralizing activity against B.1.1.7 was significantly higher than that against any other variants, including D614G. The sera-neutralizing activity in less severe patients was lower than that of more severe patients for all variants. CONCLUSIONS: The cross-neutralizing activity of convalescent sera was effective against all variants but was potentially weaker for B.1.351. The high neutralizing activity specific to B.1.1.7 in the fourth wave suggests that mutations in the virus might cause conformational change of its spike protein, which affects immune recognition of D614G. Our results indicate that individuals who recover from COVID-19 could be protected from the severity caused by infection with newly emerging variants.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Koichi", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Lidya Handayani", "last_name": "Tjan", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Sutandhio", "name": null }, { "creator_type": "author", "first_name": "Yukiya", "last_name": "Kurahashi", "name": null }, { "creator_type": "author", "first_name": "Sachiyo", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Tohma", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Kiriu", "name": null }, { "creator_type": "author", "first_name": "Masatsugu", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/ofid/ofab430" }, "pmcid": { "normalized": "PMC8496759" }, "pmid": { "normalized": "34631915" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "ofab430", "proceedings_title": null, "publisher": "", "title": "Open forum infectious diseases", "volume": "8", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Cross-Neutralizing Activity Against SARS-CoV-2 Variants in COVID-19 Patients: Comparison of 4 Waves of the Pandemic in Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mutations in the presenilin genes (PS1, PS2) have been linked to the majority of familial Alzheimer's disease (AD). Although great efforts have been made to investigate pathogenic PS mutations, which ultimately cause an increase in the toxic form of beta-amyloid (Abeta), the intrinsic physiological functions of PS in human neurons remain to be determined. In this study, to investigate the physiological roles of PS in human neurons, we generated PS1 conditional knock-out (KO) induced pluripotent stem cells (iPSCs), in which PS1 can be selectively abrogated under Cre transduction with or without additional PS2 KO. We showed that iPSC-derived neural progenitor cells (NPCs) do not confer a maintenance ability in the absence of both PS1 and PS2, showing the essential role of PS in Notch signaling. We then generated PS-null human cortical neurons, where PS1 was intact until full neuronal differentiation occurred. Abeta40 production was reduced exclusively in human PS1/PS2-null neurons along with a concomitant accumulation of amyloid beta precursor protein (APP)-C-terminal fragments CTFs, whereas Abeta42 was decreased in neurons devoid of PS2 Unlike previous studies in mice, in which APP cleavage is largely attributable to PS1, gamma-secretase activity seemed to be comparable between PS1 and PS2. In contrast, cleavage of another substrate, N-cadherin, was impaired only in neurons devoid of PS1 Moreover, PS2/gamma-secretase exists largely in late endosomes/lysosomes, as measured by specific antibody against the gamma-secretase complex, in which Abeta42 species are supposedly produced. Using this novel stem cell-based platform, we assessed important physiological PS1/PS2 functions in mature human neurons, the dysfunction of which could underlie AD pathogenesis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Cai", "name": null }, { "creator_type": "author", "first_name": "Zhi", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/eneuro.0500-20.2021" }, "pmcid": { "normalized": "PMC7932187" }, "pmid": { "normalized": "33608391" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": true }, { "descriptor": "Amyloid beta-Peptides", "descriptor_ui": "D016229", "major_topic": false }, { "descriptor": "Amyloid beta-Protein Precursor", "descriptor_ui": "D016564", "major_topic": false }, { "descriptor": "Amyloid Precursor Protein Secretases", "descriptor_ui": "D053829", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Presenilin-1", "descriptor_ui": "D053764", "major_topic": false }, { "descriptor": "Presenilin-2", "descriptor_ui": "D053766", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar-Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "ENEURO.0500-20.2021", "proceedings_title": null, "publisher": "", "title": "eNeuro", "volume": "8", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Flexible and Accurate Substrate Processing with Distinct Presenilin/gamma-Secretases in Human Cortical Neurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Long noncoding RNAs (lncRNAs) are vastly transcribed and extensively studied but lncRNAs overlapping with the sense orientation of mRNA have been poorly studied. We analyzed the lncRNA DAPALR overlapping with the 5 UTR of the Doublesex1 (Dsx1), the male determining gene in Daphnia magna. By affinity purification, we identified an RNA binding protein, Shep as a DAPALR binding protein. Shep also binds to Dsx1 5 UTR by recognizing the overlapping sequence and suppresses translation of the mRNA. In vitro and in vivo analyses indicated that DAPALR increased Dsx1 translation efficiency by sequestration of Shep. This regulation was impaired when the Shep binding site in DAPALR was deleted. These results suggest that Shep suppresses the unintentional translation of Dsx1 by setting a threshold; and when the sense lncRNA DAPALR is expressed, DAPALR cancels the suppression caused by Shep. This mechanism may be important to show dimorphic gene expressions such as sex determination and it may account for the binary expression in various developmental processes.", "classifications": [ { "id": "19H05423", "label": "19H05423", "researcher": "Yasuhiko Kato", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Christelle Alexa Garcia", "last_name": "Perez", "name": null }, { "creator_type": "author", "first_name": "Shungo", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Quang Dang", "last_name": "Nong", "name": null }, { "creator_type": "author", "first_name": "Nikko", "last_name": "Adhitama", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Natsume", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pgen.1009683" }, "pmcid": { "normalized": "PMC8351930" }, "pmid": { "normalized": "34319983" } }, "mesh": [ { "descriptor": "5' Untranslated Regions", "descriptor_ui": "D020121", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "RNA, Long Noncoding", "descriptor_ui": "D062085", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false }, { "descriptor": "Sex Determination Processes", "descriptor_ui": "D019849", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "e1009683", "proceedings_title": null, "publisher": "", "title": "PLoS genetics", "volume": "17", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Sense-overlapping lncRNA as a decoy of translational repressor protein for dimorphic gene expression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Determination of cellular ATP levels, a key indicator of metabolic status, is essential for the quantitative analysis of metabolism. The biciliate green alga Chlamydomonas reinhardtii is an excellent experimental organism to study ATP production pathways, including photosynthesis and respiration, particularly because it can be cultured either photoautotrophically or heterotrophically. Additionally, its cellular ATP concentration, [ATP], is reflected in the beating of its cilia. However, the methods currently used for quantifying the cellular ATP levels are time consuming or invasive. In this study, we established a rapid method for estimating cytosolic [ATP] from the ciliary beating frequency in C. reinhardtii. Using an improved method of motility reactivation in demembranated cell models, we obtained calibration curves for [ATP]-ciliary beating frequency over a physiological range of ATP concentrations. These curves allowed rapid estimation of the cytosolic [ATP] in live wild-type cells to be approximately 2.0 mM in the light and approximately 1.5 mM in the dark: values comparable to those obtained by other methods. Furthermore, we used this method to assess the effects of genetic mutations or inhibitors of photosynthesis or respiration quantitatively and noninvasively. This sensor-free method is a convenient tool for quickly estimating cytosolic [ATP] and studying the mechanism of ATP production in C. reinhardtii or other ciliated organisms.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Wakako", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.ra120.015263" }, "pmcid": { "normalized": "PMC7857514" }, "pmid": { "normalized": "33273011" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Axoneme", "descriptor_ui": "D054468", "major_topic": false }, { "descriptor": "Biological Assay", "descriptor_ui": "D001681", "major_topic": true }, { "descriptor": "Chlamydomonas reinhardtii", "descriptor_ui": "D016825", "major_topic": false }, { "descriptor": "Cilia", "descriptor_ui": "D002923", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Oxidative Phosphorylation", "descriptor_ui": "D010085", "major_topic": false }, { "descriptor": "Photosynthesis", "descriptor_ui": "D010788", "major_topic": false }, { "descriptor": "Rotenone", "descriptor_ui": "D012402", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan-Jun", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "100156", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "296", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Rapid estimation of cytosolic ATP concentration from the ciliary beating frequency in the green alga Chlamydomonas reinhardtii.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Zebra finch (Taeniopygia guttata) is a songbird species in which males sing their unique songs to attract females who then select their preferred male. Acoustic features in the songs of individual males are important features for female auditory perception. While the male of this species is a classic model of vocal production, it has been little known about auditory processing in female. In the higher auditory brain regions, the caudomedial mesopallium (CMM) and nidopallium (NCM) contribute to female's sound recognition, we, therefore, extracted acoustic features that induce neural activities with high detection power on both regions in female finches. A multiple linear regression analysis revealed that neurons were sensitive to mean frequency and Wiener entropy. In addition, we performed an experiment with modified artificial songs and harmonic songs to directly investigate neural responsiveness for deriving further evidence for the contribution of these two acoustic features. Finally, we illustrated a specific ratio combining these two acoustic features that showed highest sensitivity to neural responsiveness, and we found that properties of sensitivity are different between CMM and NCM. Our results indicate that the mixture of the two acoustic features with the specific ratio is important in the higher auditory regions of female songbirds, and these two regions have differences in encoding for sensitivity to these acoustic features.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Inda", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/ejn.15047" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33205482" } }, "mesh": [ { "descriptor": "Acoustic Stimulation", "descriptor_ui": "D000161", "major_topic": false }, { "descriptor": "Acoustics", "descriptor_ui": "D000162", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Auditory Perception", "descriptor_ui": "D001307", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Finches", "descriptor_ui": "D046369", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Vocalization, Animal", "descriptor_ui": "D014828", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Mar", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "1412-1427", "proceedings_title": null, "publisher": "", "title": "The European journal of neuroscience", "volume": "53", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "High responsiveness of auditory neurons to specific combination of acoustic features in female songbirds.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "T cells with a stem cell memory (T(SCM)) phenotype provide long-term and potent antitumor effects for T-cell transfer therapies. Although various methods for the induction of T(SCM)-like cells in vitro have been reported, few methods generate T(SCM)-like cells from effector/exhausted T cells. We have reported that coculture with the Notch ligand-expressing OP9 stromal cells induces T(SCM)-like (iT(SCM)) cells. Here, we established a feeder-free culture system to improve iT(SCM) cell generation from expanded chimeric antigen receptor (CAR)-expressing T cells; culturing CAR T cells in the presence of IL7, CXCL12, IGF-I, and the Notch ligand, hDLL1. Feeder-free CAR-iT(SCM) cells showed the expression of cell surface markers and genes similar to that of OP9-hDLL1 feeder cell-induced CAR-iT(SCM) cells, including the elevated expression of SCM-associated genes, TCF7, LEF1, and BCL6, and reduced expression of exhaustion-associated genes like LAG3, TOX, and NR4A1. Feeder-free CAR-iT(SCM) cells showed higher proliferative capacity depending on oxidative phosphorylation and exhibited higher IL2 production and stronger antitumor activity in vivo than feeder cell-induced CAR-iT(SCM) cells. Our feeder-free culture system represents a way to rejuvenate effector/exhausted CAR T cells to SCM-like CAR T cells. SIGNIFICANCE: Resting CAR T cells with our defined factors reprograms exhausted state to SCM-like state and enables development of improved CAR T-cell therapy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Tomisato", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Shichino", "name": null }, { "creator_type": "author", "first_name": "Tanakorn", "last_name": "Srirat", "name": null }, { "creator_type": "author", "first_name": "Setsuko", "last_name": "Mise-Omata", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Nakagawara", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/2767-9764.crc-21-0034" }, "pmcid": { "normalized": "PMC9973402" }, "pmid": { "normalized": "36860911" } }, "mesh": [ { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Immunotherapy, Adoptive", "descriptor_ui": "D016219", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": true }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Oct", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "41-55", "proceedings_title": null, "publisher": "", "title": "Cancer research communications", "volume": "1", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Rejuvenating Effector/Exhausted CAR T Cells to Stem Cell Memory-Like CAR T Cells By Resting Them in the Presence of CXCL12 and the NOTCH Ligand.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alport syndrome (AS) is a progressive inherited kidney disease characterized by hearing loss and ocular abnormalities. There are three forms of AS depending on inheritance mode: X-linked Alport syndrome (XLAS), autosomal recessive AS (ARAS), and autosomal dominant AS (ADAS). XLAS is caused by pathogenic variants in COL4A5, which encodes type IV collagen alpha5 chain, while ADAS and ARAS are caused by variants in COL4A3 or COL4A4, which encode type IV collagen alpha3 or alpha4 chain, respectively. In male XLAS or ARAS cases, end-stage kidney disease (ESKD) develops around a median age of 20 to 30 years old, while female XLAS or ADAS cases develop ESKD around a median age of 60 to 70 years old. The diagnosis of AS is dependent on either genetic or pathological findings. However, determining the pathogenicity of the variants detected by gene tests can be difficult. Recently, we applied the following molecular investigation tools to determine pathogenicity: 1) in silico and in vitro trimer formation assay of alpha345 chains to assess triple helix formation ability, 2) kidney organoids constructed from patients' induced pluripotent stem cells to identify alpha5 chain expression on the glomerular basement membrane, and 3) in vitro splicing assay to detect aberrant splicing to determine the pathogenicity of variants. In this review article, we discuss the genetic background and novel assays for determining the pathogenicity of variants. We also discuss the current treatment approaches and introduce exon skipping therapy as one potential treatment option.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kandai", "last_name": "Nozu", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Takaoka", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Kai", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Yabuuchi", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Nana", "last_name": "Sakakibara", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ninchoji", "name": null }, { "creator_type": "author", "first_name": "China", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Kazumoto", "last_name": "Iijima", "name": null } ], "identifiers": { "doi": { "normalized": "10.23876/j.krcp.20.111" }, "pmcid": { "normalized": "PMC7771000" }, "pmid": { "normalized": "33214343" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Dec 31", "date_precision": "day", "issue": "4", "normalized_date": "2020-12-31", "pages": "402-413", "proceedings_title": null, "publisher": "", "title": "Kidney research and clinical practice", "volume": "39", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetic background, recent advances in molecular biology, and development of novel therapy in Alport syndrome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In recent years, it has been realized that the tau protein is a key player in multiple neurodegenerative diseases. Positron emission tomography (PET) radiotracers that bind to tau filaments in Alzheimer's disease (AD) are in common use, but PET tracers binding to tau filaments of rarer, age-related dementias, such as Pick's disease, have not been widely explored. To design disease-specific and tau-selective PET tracers, it is important to determine where and how PET tracers bind to tau filaments. In this paper, we present the first molecular modelling study on PET probe binding to the structured core of tau filaments from a patient with Pick's disease (Tau(PiD)). We have used docking, molecular dynamics simulations, binding-affinity and tunnel calculations to explore Tau(PiD) binding sites, binding modes, and binding energies of PET probes (AV-1451, MK-6240, PBB3, PM-PBB3, THK-5351 and PiB) with Tau(PiD). The probes bind to Tau(PiD) at multiple surface binding sites as well as in a cavity binding site. The probes show unique surface binding patterns, and, out of them all, PM-PBB3 proves to bind the strongest. The findings suggest that our computational workflow of structural and dynamic details of the tau filaments has potential for the rational design of Tau(PiD) specific PET tracers.", "classifications": [ { "id": "19H05437", "label": "19H05437", "researcher": "Naruhiko Sahara", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sushil K.", "last_name": "Mishra", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms22010349" }, "pmcid": { "normalized": "PMC7796283" }, "pmid": { "normalized": "33396273" } }, "mesh": [ { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Pick Disease of the Brain", "descriptor_ui": "D020774", "major_topic": false }, { "descriptor": "Positron-Emission Tomography", "descriptor_ui": "D049268", "major_topic": false }, { "descriptor": "Radiopharmaceuticals", "descriptor_ui": "D019275", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Dec 31", "date_precision": "day", "issue": "1", "normalized_date": "2020-12-31", "pages": "E349", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "22", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Pick's Tau Fibril Shows Multiple Distinct PET Probe Binding Sites: Insights from Computational Modelling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The smallest arenavirus gene product, Z protein, plays critical roles in the virus life cycle. Z is the major driving force of budding and particle production because of a unique property that defines self-assembly. In addition to the roles in budding, Z also participates in the suppression of type I interferon production to evade host antiviral immunity. Therefore, Z and its assembled form are an attractive drug target for arenaviral hemorrhagic fever, such as Lassa fever. Here, we developed a biosensor that enabled the evaluation of the prototype arenavirus, lymphocytic choriomeningitis virus (LCMV), Z assembly using the principle of Forster resonance energy transfer (FRET). This FRET biosensor consisted of three tandem Z that were sandwiched between super-enhanced cyan-emitting fluorescent protein and variant of a yellow-emitting mutant of green fluorescent protein so that Z-Z intermolecular binding via the really interesting new gene finger domain increased the emission ratio. To identify novel anti-arenavirus compounds, the FRET biosensor was employed to screen the PathogenBox400 for inhibitors of Z assembly in a 96-well plate format. The assay performed well, with a Z'-factor of 0.89, and identified two compounds that decreased the emission ratio of the FRET biosensor in a dose-dependent manner. Of them, the compound, 5,6,7,8-tetrahydro-7-(benzyl)-pyrido[4',3':4,5]thieno[2,3-d]pyrimidin-2,4-diamine , was found to significantly inhibit LCMV propagation in infected cells. Thereby, the present study demonstrated that a novel FRET biosensor incorporating Z assembly built on FRET and named Zabton, was a valuable screening tool to identify anti-arenavirus compounds in the context of inhibition of Z assembly.Key words: Arenavirus, Forster resonance energy transfer, anti-viral drugs, Z protein.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuaki", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Mizuta", "name": null }, { "creator_type": "author", "first_name": "Jiro", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Shuzo", "last_name": "Urata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1247/csf.20030" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33191384" } }, "mesh": [ { "descriptor": "Antiviral Agents", "descriptor_ui": "D000998", "major_topic": true }, { "descriptor": "Arenavirus", "descriptor_ui": "D018050", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": true }, { "descriptor": "Drug Evaluation, Preclinical", "descriptor_ui": "D004353", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": true }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virus Assembly", "descriptor_ui": "D019065", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Dec 25", "date_precision": "day", "issue": "2", "normalized_date": "2020-12-25", "pages": "155-163", "proceedings_title": null, "publisher": "", "title": "Cell structure and function", "volume": "45", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "An Antiviral Drug Screening Platform with a FRET Biosensor for Measurement of Arenavirus Z Assembly.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Autism susceptibility candidate 2 (AUTS2), a risk gene for autism spectrum disorders (ASDs), is implicated in telencephalon development. Because AUTS2 is also expressed in the cerebellum where defects have been linked to ASDs, we investigated AUTS2 functions in the cerebellum. AUTS2 is specifically localized in Purkinje cells (PCs) and Golgi cells during postnatal development. Auts2 conditional knockout (cKO) mice exhibited smaller and deformed cerebella containing immature-shaped PCs with reduced expression of Cacna1a. Auts2 cKO and knock-down experiments implicated AUTS2 participation in elimination and translocation of climbing fiber synapses and restriction of parallel fiber synapse numbers. Auts2 cKO mice exhibited behavioral impairments in motor learning and vocal communications. Because Cacna1a is known to regulate synapse development in PCs, it suggests that AUTS2 is required for PC maturation to elicit normal development of PC synapses and thus the impairment of AUTS2 may cause cerebellar dysfunction related to psychiatric illnesses such as ASDs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kunihiko", "last_name": "Yamashiro", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Esther S. K.", "last_name": "Lai", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Shimaoka", "name": null }, { "creator_type": "author", "first_name": "Nariko", "last_name": "Arimura", "name": null }, { "creator_type": "author", "first_name": "Saki F.", "last_name": "Egusa", "name": null }, { "creator_type": "author", "first_name": "Asami", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Mikio", "last_name": "Hoshino", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2020.101820" }, "pmcid": { "normalized": "PMC7708818" }, "pmid": { "normalized": "33305180" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Dec 18", "date_precision": "day", "issue": "12", "normalized_date": "2020-12-18", "pages": "101820", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "23", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "AUTS2 Governs Cerebellar Development, Purkinje Cell Maturation, Motor Function and Social Communication.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent developments of molecular biology have revealed diverse mechanisms of skin diseases, and precision medicine considering these mechanisms requires the frequent objective evaluation of skin phenotypes. Transepidermal water loss (TEWL) is commonly used for evaluating skin barrier function; however, direct measurement of TEWL is time-consuming and is not convenient for daily clinical practice. Here, we propose a new skin barrier assessment method using skin images with topological data analysis (TDA). TDA enabled efficient identification of structural features from a skin image taken by a microscope. These features reflected the regularity of the skin texture. We found a significant correlation between the topological features and TEWL. Moreover, using the features as input, we trained machine-learning models to predict TEWL and obtained good accuracy (R(2) = 0.524). Our results suggest that assessment of skin barrier function by topological image analysis is promising.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Keita", "last_name": "Koseki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Atsugi", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Naru", "name": null }, { "creator_type": "author", "first_name": "Tamotsu", "last_name": "Ebihara", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Amagai", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41540-020-00160-8" }, "pmcid": { "normalized": "PMC7749164" }, "pmid": { "normalized": "33339832" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Data Analysis", "descriptor_ui": "D000078332", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": true }, { "descriptor": "Skin Physiological Phenomena", "descriptor_ui": "D012879", "major_topic": false }, { "descriptor": "Water Loss, Insensible", "descriptor_ui": "D014870", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Dec 18", "date_precision": "day", "issue": "1", "normalized_date": "2020-12-18", "pages": "40", "proceedings_title": null, "publisher": "", "title": "NPJ systems biology and applications", "volume": "6", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Assessment of skin barrier function using skin images with topological data analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Current smartphones equipped with high-sensitivity and high-resolution sensors in the camera can respond to the needs of low-light imaging, streaming acquisition, targets of various scales, etc. Therefore, a smartphone has great potential as an imaging device even in the scientific field and has already been introduced into biomolecular imaging using fluorescence tags. However, owing to the necessity of an excitation light source, fluorescence methods impair its mobility. Bioluminescence does not require illumination; therefore, imaging with a smartphone camera is compact and requires minimal devices, thus making it suitable for personal and portable imaging devices. Here, we report smartphone-based methods to observe biological targets in various scales using bioluminescence. In particular, we demonstrate, for the first time, that bioluminescence can be observed in an organelle in a single living cell using a smartphone camera by attaching a detachable objective lens. Through capturing color changes with the camera, changes in the amount of target molecules was detected using bioluminescent indicators. The combination of bioluminescence and a mobile phone makes possible a compact imaging system without an external light source and expands the potential of portable devices.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Sumito", "last_name": "Shirane", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Kuniaki", "last_name": "Nagayama", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/s20247166" }, "pmcid": { "normalized": "PMC7764933" }, "pmid": { "normalized": "33327525" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": true }, { "descriptor": "Cell Phone", "descriptor_ui": "D040421", "major_topic": false }, { "descriptor": "Lighting", "descriptor_ui": "D008029", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Organelles", "descriptor_ui": "D015388", "major_topic": true }, { "descriptor": "Smartphone", "descriptor_ui": "D000068997", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Dec 14", "date_precision": "day", "issue": "24", "normalized_date": "2020-12-14", "pages": "E7166", "proceedings_title": null, "publisher": "", "title": "Sensors (Basel, Switzerland)", "volume": "20", "year": 2020 }, "ssbd": { "database": [ "ssbd-database-000235" ], "repository": [ "ssbd-repos-000235" ] }, "title": "Smartphone-Based Portable Bioluminescence Imaging System Enabling Observation at Various Scales from Whole Mouse Body to Organelle.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Induced pluripotent stem cell (iPSC)-based disease modeling has a great potential for uncovering the mechanisms of pathogenesis, especially in the case of neurodegenerative diseases where disease-susceptible cells can usually not be obtained from patients. So far, the iPSC-based modeling of neurodegenerative diseases has mainly focused on neurons because the protocols for generating astrocytes from iPSCs have not been fully established. The growing evidence of astrocytes' contribution to neurodegenerative diseases has underscored the lack of iPSC-derived astrocyte models. In the present study, we established a protocol to efficiently generate iPSC-derived astrocytes (iPasts), which were further characterized by RNA and protein expression profiles as well as functional assays. iPasts exhibited calcium dynamics and glutamate uptake activity comparable to human primary astrocytes. Moreover, when co-cultured with neurons, iPasts enhanced neuronal synaptic maturation. Our protocol can be used for modeling astrocyte-related disease phenotypes in vitro and further exploring the contribution of astrocytes to neurodegenerative diseases.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Nicolas", "last_name": "Leventoux", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Mashima", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Iki", "last_name": "Sonn", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cells9122680" }, "pmcid": { "normalized": "PMC7763297" }, "pmid": { "normalized": "33322219" } }, "mesh": [ { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Embryoid Bodies", "descriptor_ui": "D058732", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Neurodegenerative Diseases", "descriptor_ui": "D019636", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Principal Component Analysis", "descriptor_ui": "D025341", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Dec 13", "date_precision": "day", "issue": "12", "normalized_date": "2020-12-13", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cells", "volume": "9", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Human Astrocytes Model Derived from Induced Pluripotent Stem Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Studies on induced pluripotent stem (iPS) cells highly rely on the investigation of their gene expression which requires normalization by housekeeping genes. Whether the housekeeping genes are stable during the iPS reprogramming, a transition of cell state known to be associated with profound changes, has been overlooked. In this study we analyzed the expression patterns of the most comprehensive list to date of housekeeping genes during iPS reprogramming of a mouse neural stem cell line N31. Our results show that housekeeping genes' expression fluctuates significantly during the iPS reprogramming. Clustering analysis shows that ribosomal genes' expression is rising, while the expression of cell-specific genes, such as vimentin (Vim) or elastin (Eln), is decreasing. To ensure the robustness of the obtained data, we performed a correlative analysis of the genes. Overall, all 70 genes analyzed changed the expression more than two-fold during the reprogramming. The scale of this analysis, that takes into account 70 previously known and newly suggested genes, allowed us to choose the most stable of all genes. We highlight the fact of fluctuation of housekeeping genes during iPS reprogramming, and propose that, to ensure robustness of qPCR experiments in iPS cells, housekeeping genes should be used together in combination, and with a prior testing in a specific line used in each study. We suggest that the longest splice variants of Rpl13a, Rplp1 and Rps18 can be used as a starting point for such initial testing as the most stable candidates.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yulia", "last_name": "Panina", "name": null }, { "creator_type": "author", "first_name": "Arno", "last_name": "Germond", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-78863-5" }, "pmcid": { "normalized": "PMC7728746" }, "pmid": { "normalized": "33303957" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Genes, Essential", "descriptor_ui": "D020043", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Ribosomal Proteins", "descriptor_ui": "D012269", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Dec 10", "date_precision": "day", "issue": "1", "normalized_date": "2020-12-10", "pages": "21711", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Analysis of the stability of 70 housekeeping genes during iPS reprogramming.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIM2 is a cytosolic DNA sensor of the inflammasome, which induces critical innate immune responses against various invading pathogens. Earlier biochemical studies showed that the binding of AIM2 to DNA triggered the self-oligomerization of AIM2, which is essential for AIM2 inflammasome activation. We recently reported that VP22, a virion tegument protein of herpes simplex virus 1 (HSV-1), inhibited activation of the AIM2 inflammasome in HSV-1-infected cells by preventing AIM2 oligomerization. VP22 binds non-specifically to DNA; however, its role in HSV-1 replication is unclear. We investigated the role of VP22 DNA binding activity in the VP22-mediated inhibition of AIM2 inflammasome activation. We identified a VP22 domain encoded by amino acids 227 to 258 as the minimal domain required for its binding to DNA in vitro Consecutive alanine substitutions in this domain substantially impaired the DNA binding activity of VP22 in vitro and attenuated the inhibitory effect of VP22 on AIM2 inflammasome activation in an AIM2 inflammasome reconstitution system. The inhibitory effect of VP22 on AIM2 inflammasome activation was completely abolished in macrophages infected with a recombinant virus harboring VP22 with one of the consecutive alanine substitutions, similar to the effect of a VP22-null mutant virus. These results suggested that the DNA binding activity of VP22 is critical for VP22-mediated AIM2 inflammasome activation in HSV1-infected cells.IMPORTANCE VP22, a major component of the HSV-1 virion tegument, is conserved in alphaherpesviruses and has structural similarity to ORF52, a component of the virion tegument that is well-conserved in gammaherpesviruses. Although the potential DNA binding activity of VP22 was discovered decades ago, its significance in the HSV-1 life cycle is poorly understood. Here, we show that the DNA binding activity of VP22 is critical for the inhibition of AIM2 inflammasome activation induced in HSV-1-infected cells. This is the first report to show a role for the DNA binding activity of VP22 in the HSV-1 life cycle, allowing the virus to evade AIM2 inflammasome activation, which is critical for its replication in vivo.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.02172-20" }, "pmcid": { "normalized": "PMC8092817" }, "pmid": { "normalized": "33298538" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Dec 9", "date_precision": "day", "issue": "", "normalized_date": "2020-12-09", "pages": "JVI.02172-20", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of the DNA Binding Activity of Herpes Simplex Virus 1 VP22 in Evading AIM2-Dependent Inflammasome Activation Induced by the Virus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human herpesvirus 6A (HHV-6A) and HHV-6B use different cellular receptors, human CD46 and CD134, respectively and have different cell tropisms although they have 90% similarity at the nucleotide level. An important feature that characterizes HHV-6A/6B is the glycoprotein H (gH)/gL/gQ1/gQ2 complex (a tetramer) that each virus has specifically on its envelope. Here, to determine which molecules in the tetramer contribute to the specificity for each receptor, we developed a cell-cell fusion assay system for HHV-6A and HHV-6B that uses the cells expressing CD46 or CD134. With this system, when we replaced the gQ1 or gQ2 of HHV-6A with that of HHV-6B in the tetramer, the cell fusion activity mediated by glycoproteins via CD46 was lower than that done with the original-type tetramer. When we replaced the gQ1 or the gQ2 of HHV-6A with that of HHV-6B in the tetramer, the cell fusion mediated by glycoproteins via CD134 was not seen. In addition, we generated two types of C-terminal truncation mutants of HHV-6A gQ2 (AgQ2) to examine the interaction domains of HHV-6A gQ1 (AgQ1) and AgQ2. We found that amino acid residues 163 to 185 in AgQ2 are important for interaction of AgQ1 and AgQ2. Finally, to investigate whether HHV-6B gQ2 (BgQ2) can complement AgQ2, an HHV-6A genome harboring BgQ2 was constructed. The mutant could not produce an infectious virus, indicating that BgQ2 cannot work for the propagation of HHV-6A. These results suggest that gQ2 supports the tetramer's function, and the combination of gQ1 and gQ2 is critical for virus propagation.IMPORTANCE Glycoprotein Q2 (gQ2), an essential gene for virus propagation, forms a heterodimer with gQ1. The gQ1/gQ2 complex has a critical role in receptor recognition in the gH/gL/gQ1/gQ2 complex (a tetramer). We investigated whether gQ2 regulates the specific interaction between the HHV-6A or -6B tetramer and CD46 or CD134. We established a cell-cell fusion assay system for HHV-6A/6B and switched the gQ1 or gQ2 of HHV-6A with that of HHV-6B in the tetramer. Although cell fusion was induced via CD46 when gQ1 or gQ2 was switched between HHV-6A and -6B, the activity was lower than that of the original combination. When gQ1 or gQ2 was switched in HHV-6A and -6B, no cell fusion was observed via CD134. HHV-6B gQ2 could not complement the function of HHV-6A's gQ2 in HHV-6A propagation, suggesting that the combination of gQ1 and gQ2 is critical to regulate the specificity of the tetramer's function for virus entry.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Aika", "last_name": "Wakata", "name": null }, { "creator_type": "author", "first_name": "Lidya Handayani", "last_name": "Tjan", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Kawabata", "name": null }, { "creator_type": "author", "first_name": "Anna Lystia", "last_name": "Poetranto", "name": null }, { "creator_type": "author", "first_name": "Chisato", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01638-20" }, "pmcid": { "normalized": "PMC8092820" }, "pmid": { "normalized": "33298543" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Dec 9", "date_precision": "day", "issue": "", "normalized_date": "2020-12-09", "pages": "JVI.01638-20", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "The Combination of gQ1 and gQ2 in Human Herpesvirus 6A and 6B Regulates the Viral Tetramer Function for Their Receptor Recognition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Aquatic heavy metal pollution is a growing concern. To facilitate heavy metal monitoring in water, we developed transgenic Daphnia that are highly sensitive to heavy metals and respond to them rapidly. Metallothionein A, which was a metal response gene, and its promoter region was obtained from Daphnia magna. A chimeric gene fusing the promoter region with a green fluorescent protein (GFP) gene was integrated into D. magna using the TALEN technique and transgenic Daphnia named D. magna MetalloG were produced. When D. magna MetalloG was exposed to heavy metal solutions for 1 h, GFP expression was induced only in their midgut and hepatopancreas. The lowest concentrations of heavy metals that activated GFP expression were 1.2 microM Zn(2+), 130 nM Cu(2+), and 70 nM Cd(2+). Heavy metal exposure for 24 h could lower the thresholds even further. D. magna MetalloG facilitates aqueous heavy metal detection and might enhance water quality monitoring.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takuto", "last_name": "Arao", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Quang Dang", "last_name": "Nong", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Haruna", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Norihisa", "last_name": "Tatarazako", "name": null }, { "creator_type": "author", "first_name": "Kazune", "last_name": "Tani", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Takeru", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-78572-z" }, "pmcid": { "normalized": "PMC7722880" }, "pmid": { "normalized": "33293611" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "Environmental Monitoring", "descriptor_ui": "D004784", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Genetic Engineering", "descriptor_ui": "D005818", "major_topic": false }, { "descriptor": "Metallothionein", "descriptor_ui": "D008668", "major_topic": false }, { "descriptor": "Metals, Heavy", "descriptor_ui": "D019216", "major_topic": false }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": false }, { "descriptor": "Water Pollutants, Chemical", "descriptor_ui": "D014874", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Dec 8", "date_precision": "day", "issue": "1", "normalized_date": "2020-12-08", "pages": "21490", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Production of genome-edited Daphnia for heavy metal detection by fluorescence.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Currently an in vitro model that fully recapitulates the human embryonic gonad is lacking. Here we describe a fully defined feeder-free protocol to generate early testis-like cells with the ability to be cultured as an organoid, from human induced pluripotent stem cells. This stepwise approach uses small molecules to mimic embryonic development, with upregulation of bipotential gonad markers (LHX9, EMX2, GATA4, and WT1) at day 10 of culture, followed by induction of testis Sertoli cell markers (SOX9, WT1, and AMH) by day 15. Aggregation into 3D structures and extended culture on Transwell filters yielded organoids with defined tissue structures and distinct Sertoli cell marker expression. These studies provide insight into human gonadal development, suggesting that a population of precursor cells may originate from a more lateral region of the mesoderm. Our protocol represents a significant advance toward generating a much-needed human gonad organoid for studying disorders/differences of sex development.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ingrid M.", "last_name": "Knarston", "name": null }, { "creator_type": "author", "first_name": "Svenja", "last_name": "Pachernegg", "name": null }, { "creator_type": "author", "first_name": "Gorjana", "last_name": "Robevska", "name": null }, { "creator_type": "author", "first_name": "Irene", "last_name": "Ghobrial", "name": null }, { "creator_type": "author", "first_name": "Pei Xuan", "last_name": "Er", "name": null }, { "creator_type": "author", "first_name": "Elizabeth", "last_name": "Georges", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null }, { "creator_type": "author", "first_name": "Alexander N.", "last_name": "Combes", "name": null }, { "creator_type": "author", "first_name": "Anne", "last_name": "Jorgensen", "name": null }, { "creator_type": "author", "first_name": "Melissa H.", "last_name": "Little", "name": null }, { "creator_type": "author", "first_name": "Andrew H.", "last_name": "Sinclair", "name": null }, { "creator_type": "author", "first_name": "Katie L.", "last_name": "Ayers", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2020.10.009" }, "pmcid": { "normalized": "PMC7724470" }, "pmid": { "normalized": "33217324" } }, "mesh": [ { "descriptor": "Antigens, Differentiation", "descriptor_ui": "D000943", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Sertoli Cells", "descriptor_ui": "D012708", "major_topic": false }, { "descriptor": "Tissue Culture Techniques", "descriptor_ui": "D046509", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Dec 8", "date_precision": "day", "issue": "6", "normalized_date": "2020-12-08", "pages": "1377-1391", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "15", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "An In Vitro Differentiation Protocol for Human Embryonic Bipotential Gonad and Testis Cell Development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fast-scan cyclic voltammetry (FSCV) is a powerful technique for studying the local dynamics of neurotransmitters and neuromodulators. FSCV is attractive to researchers employing electrophysiological techniques because it can be performed using an electrophysiological voltage-clamp amplifier. However, the narrow test potential range of electrophysiological amplifiers (typically, +/-1 V) limits testable species of analytes. Here we devised a booster that extends the test potential range. Using the booster, we could detect the oxidation current of adenosine peaking near a test potential of +1.5 V. The booster should promote combined electrophysiological and electrochemical studies of synaptic release and neural secretion.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Haruki", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Taichi", "last_name": "Yokoi", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Tabata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ab.2020.113934" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32891595" } }, "mesh": [ { "descriptor": "Adenosine", "descriptor_ui": "D000241", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Electrochemical Techniques", "descriptor_ui": "D055664", "major_topic": false }, { "descriptor": "Microelectrodes", "descriptor_ui": "D008839", "major_topic": false }, { "descriptor": "Neurotransmitter Agents", "descriptor_ui": "D018377", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Dec 1", "date_precision": "day", "issue": "", "normalized_date": "2020-12-01", "pages": "113934", "proceedings_title": null, "publisher": "", "title": "Analytical biochemistry", "volume": "610", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "A test potential booster for fast-scan cyclic voltammetry with an electrophysiological amplifier.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Abstract\n The mechanism that mediates the interaction between the contractile ring and the plasma membrane during cytokinesis remains elusive. We previously found that ERM (Ezrin/Radixin/Moesin) proteins, which usually mediate cellular pole contraction, become over-accumulated at the cell equator and support furrow ingression upon the loss of other actin-membrane associated proteins, anillin and supervillin. In this study, we addressed the molecular basis of the semi-compatibility between ezrin and other actin-membrane associated proteins in mediating cortical contraction during cytokinesis. We found that depletion of supervillin and anillin caused over-accumulation of the membrane-associated FERM domain and actin-binding C-terminal domain (C-term) of ezrin at the cleavage furrow, respectively. This finding suggests that ezrin differentially shares its binding sites with these proteins on the actin cytoskeleton or inner membrane surface. Using chimeric mutants, we found that ezrin C-term, but not the FERM domain, can substitute for the corresponding anillin domains in cytokinesis and cell proliferation. On the other hand, either the membrane-associated or the actin/myosin-binding domains of anillin could not substitute for the corresponding ezrin domains in controlling cortical blebbing at the cell poles. Our results highlight specific designs of actin- or membrane-associated moieties of different actin-membrane associated proteins with limited compatibility, which enables them to support diverse cortical activities on the shared actin-membrane interface during cytokinesis.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Guang", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Hiruma", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Kinjo", "name": null }, { "creator_type": "author", "first_name": "Mithilesh", "last_name": "Mishra", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/2020.11.30.403253" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2020-11-30", "date_precision": "day", "issue": null, "normalized_date": "2020-11-30", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular basis of functional compatibility between ezrin and other actin-membrane associated proteins during cytokinesis", "url": "http://biorxiv.org/lookup/doi/10.1101/2020.11.30.403253", "zotero": { "item_type": "preprint" } }, { "abstract": "The transparency of animals is an important biological feature. Ascidian eggs have various degrees of transparency, but this characteristic has not yet been measured quantitatively and comprehensively. In this study, we established a method for evaluating the transparency of eggs to first characterize the transparency of ascidian eggs across different species and to infer a phylogenetic relationship among multiple taxa in the class Ascidiacea. We measured the transmittance of 199 eggs from 21 individuals using a hyperspectral camera. The spectrum of the visual range of wavelengths (400-760 nm) varied among individuals and we calculated each average transmittance of the visual range as bio-transparency. When combined with phylogenetic analysis based on the nuclear 18S rRNA and the mitochondrial cytochrome c oxidase subunit I gene sequences, the bio-transparencies of 13 species were derived from four different families: Ascidiidae, Cionidae, Pyuridae, and Styelidae. The bio-transparency varied 10-90% and likely evolved independently in each family. Ascidiella aspersa showed extremely high (88.0 +/- 1.6%) bio-transparency in eggs that was maintained in the \"invisible\" larva. In addition, it was indicated that species of the Ascidiidae family may have a phylogenetic constraint of egg transparency.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takumi T.", "last_name": "Shito", "name": null }, { "creator_type": "author", "first_name": "Naohiro", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-77585-y" }, "pmcid": { "normalized": "PMC7709464" }, "pmid": { "normalized": "33257720" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Eggs", "descriptor_ui": "D004531", "major_topic": true }, { "descriptor": "Photography", "descriptor_ui": "D010781", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Pigmentation", "descriptor_ui": "D010858", "major_topic": false }, { "descriptor": "Species Specificity", "descriptor_ui": "D013045", "major_topic": false }, { "descriptor": "Spectrum Analysis", "descriptor_ui": "D013057", "major_topic": false }, { "descriptor": "Urochordata", "descriptor_ui": "D014561", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 30", "date_precision": "day", "issue": "1", "normalized_date": "2020-11-30", "pages": "20829", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Phylogenetic comparison of egg transparency in ascidians by hyperspectral imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Temperature governs states and dynamics of all biological molecules, and several cellular processes are often heat sources and/or sinks. Technical achievement of intracellular thermometry enables us to measure intracellular temperature, and it can offer novel perspectives in biology and medicine. However, little is known that changes of intracellular temperature throughout the cell-cycle and the manner of which cells regulates their thermogenesis in response to fluctuation of the environmental temperature. Here, cell-cycle-dependent changes of intracellular temperature were reconstructed from the snapshots of cell population at single-cell resolution using ergodic analysis for asynchronously cultured HeLa cells expressing a genetically encoded thermometry. Intracellular temperature is highest at G1 phase, and it gradually decreases along cell-cycle progression and increases abruptly during mitosis. Cells easily heated up are harder to cool down and vice versa, especially at G1/S phases. Together, intracellular thermogenesis depends on cell-cycle phases and it maintains intracellular temperature through compensating environmental temperature fluctuations.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryu", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Hiroi", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2020.08.110" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32928506" } }, "mesh": [ { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": true }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "G1 Phase", "descriptor_ui": "D016193", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false }, { "descriptor": "S Phase", "descriptor_ui": "D016196", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false }, { "descriptor": "Thermogenesis", "descriptor_ui": "D022722", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 26", "date_precision": "day", "issue": "1", "normalized_date": "2020-11-26", "pages": "70-76", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "533", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Cellular thermogenesis compensates environmental temperature fluctuations for maintaining intracellular temperature.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Glycerophospholipids are major components of cell membranes. Phosphatidylethanolamine (PE) is a glycerophospholipid that is involved in multiple cellular processes, such as membrane fusion, the cell cycle, autophagy, and apoptosis. In this study, we investigated the role of PE biosynthesis in herpes simplex virus 1 (HSV-1) infection by knocking out the host cell gene encoding phosphate cytidylyltransferase 2, ethanolamine (Pcyt2), which is a key rate-limiting enzyme in one of the two major pathways for PE biosynthesis. Pcyt2 knockout reduced HSV-1 replication and caused an accumulation of unenveloped and partially enveloped nucleocapsids in the cytoplasm of an HSV-1-infected cell culture. A similar phenotype was observed when infected cells were treated with meclizine, which is an inhibitor of Pcyt2. In addition, treatment of HSV-1-infected mice with meclizine significantly reduced HSV-1 replication in the mouse brains and improved their survival rates. These results indicated that PE biosynthesis mediated by Pcyt2 was required for efficient HSV-1 envelopment in the cytoplasm of infected cells and for viral replication and pathogenicity in vivo The results also identified the PE biosynthetic pathway as a possible novel target for antiviral therapy of HSV-associated diseases and raised an interesting possibility for meclizine repositioning for treatment of these diseases, since it is an over-the-counter drug that has been used for decades against nausea and vertigo in motion sickness.IMPORTANCE Glycerophospholipids in cell membranes and virus envelopes often affect viral entry and budding. However, the role of glycerophospholipids in membrane-associated events in viral replication in herpesvirus-infected cells has not been reported to date. In this study, we have presented data showing that cellular PE biosynthesis mediated by Pcyt2 is important for HSV-1 envelopment in the cytoplasm, as well as for viral replication and pathogenicity in vivo This is the first report showing the importance of PE biosynthesis in herpesvirus infections. Our results showed that inhibition of Pcyt2, a key cell enzyme for PE synthesis, significantly inhibited HSV-1 replication and pathogenicity in mice. This suggested that the PE biosynthetic pathway, as well as the HSV-1 virion maturation pathway, can be a target for the development of novel anti-HSV drugs.", "classifications": [ { "id": "19H05417", "label": "19H05417", "researcher": "Jun Arii", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Shimanaka", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Kono", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01572-20" }, "pmcid": { "normalized": "PMC7925202" }, "pmid": { "normalized": "32999028" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Nucleocapsid", "descriptor_ui": "D019251", "major_topic": false }, { "descriptor": "Phosphatidylethanolamines", "descriptor_ui": "D010714", "major_topic": false }, { "descriptor": "RNA Nucleotidyltransferases", "descriptor_ui": "D012316", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Virion", "descriptor_ui": "D014771", "major_topic": false }, { "descriptor": "Virulence", "descriptor_ui": "D014774", "major_topic": false }, { "descriptor": "Virus Internalization", "descriptor_ui": "D053586", "major_topic": false }, { "descriptor": "Virus Release", "descriptor_ui": "D057074", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 23", "date_precision": "day", "issue": "24", "normalized_date": "2020-11-23", "pages": "e01572-20", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "94", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of Phosphatidylethanolamine Biosynthesis in Herpes Simplex Virus 1-Infected Cells in Progeny Virus Morphogenesis in the Cytoplasm and in Viral Pathogenicity In Vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ca2+ is one of the most important second messengers in cells. A far-red to near-infrared (NIR) Ca2+ fluorescent probe is useful for multi-color imaging in GFP or YFP-expressing biosamples. Here we developed a cytosolically localized far-red to NIR rhodamine-based fluorescent probe for Ca2+, CaSiR-2 AM, while rhodamine dyes are basically localized to mitochondria or lysosomes in cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Numasawa", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ikeno", "name": null }, { "creator_type": "author", "first_name": "Honami", "last_name": "Echizen", "name": null }, { "creator_type": "author", "first_name": "Tomoe", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Ikegaya", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d0an01739f" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33000768" } }, "mesh": [ { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": true }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Ions", "descriptor_ui": "D007477", "major_topic": false }, { "descriptor": "Lysosomes", "descriptor_ui": "D008247", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 23", "date_precision": "day", "issue": "23", "normalized_date": "2020-11-23", "pages": "7736-7740", "proceedings_title": null, "publisher": "", "title": "The Analyst", "volume": "145", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "A cytosolically localized far-red to near-infrared rhodamine-based fluorescent probe for calcium ions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The nuclear lamina plays an important role in the regulation of chromatin organization and gene positioning in animals. CROWDED NUCLEI (CRWN) is a strong candidate for the plant nuclear lamina protein in Arabidopsis thaliana but its biological function was largely unknown. Here, we show that CRWNs localize at the nuclear lamina and build the meshwork structure. Fluorescence in situ hybridization and RNA-seq analyses revealed that CRWNs regulate chromatin distribution and gene expression. More than 2000 differentially expressed genes were identified in the crwn1crwn4 double mutant. Copper-associated (CA) genes that form a gene cluster on chromosome 5 were among the downregulated genes in the double mutant exhibiting low tolerance to excess copper. Our analyses showed this low tolerance to copper was associated with the suppression of CA gene expression and that CRWN1 interacts with the CA gene locus, enabling the locus to localize at the nuclear lamina under excess copper conditions.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Chieko", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Kiminori", "last_name": "Toyooka", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Ikuko", "last_name": "Hara-Nishimura", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Sachihiro", "last_name": "Matsunaga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-020-19621-z" }, "pmcid": { "normalized": "PMC7679404" }, "pmid": { "normalized": "33219233" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Copper", "descriptor_ui": "D003300", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "In Situ Hybridization, Fluorescence", "descriptor_ui": "D017404", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Nuclear Lamina", "descriptor_ui": "D034881", "major_topic": true }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": true }, { "descriptor": "Plant Proteins", "descriptor_ui": "D010940", "major_topic": false }, { "descriptor": "RNA-Seq", "descriptor_ui": "D000081246", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 20", "date_precision": "day", "issue": "1", "normalized_date": "2020-11-20", "pages": "5914", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Subnuclear gene positioning through lamina association affects copper tolerance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Optogenetics is a powerful technique using photoresponsive proteins, and the light-inducible dimerization (LID) system, an optogenetic tool, allows to manipulate intracellular signaling pathways. One of the red/far-red responsive LID systems, phytochrome B (PhyB)-phytochrome interacting factor (PIF), has a unique property of controlling both association and dissociation by light on the second time scale, but PhyB requires a linear tetrapyrrole chromophore such as phycocyanobilin (PCB), and such chromophores are present only in higher plants and cyanobacteria. Here, we report that we further improved our previously developed PCB synthesis system (SynPCB) and successfully established a stable cell line containing a genetically encoded PhyB-PIF LID system. First, four genes responsible for PCB synthesis, namely, PcyA, HO1, Fd, and Fnr, were replaced with their counterparts derived from thermophilic cyanobacteria. Second, Fnr was truncated, followed by fusion with Fd to generate a chimeric protein, tFnr-Fd. Third, these genes were concatenated with P2A peptide cDNAs for polycistronic expression, resulting in an approximately 4-fold increase in PCB synthesis compared with the previous version. Finally, we incorporated the PhyB, PIF, and SynPCB system into drug inducible lentiviral and transposon vectors, which enabled us to induce PCB synthesis and the PhyB-PIF LID system by doxycycline treatment. These tools provide a new opportunity to advance our understanding of the causal relationship between intracellular signaling and cellular functions.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Youichi", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Mii", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acschembio.0c00477" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33164485" } }, "mesh": [ { "descriptor": "Biosynthetic Pathways", "descriptor_ui": "D053898", "major_topic": true }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Genes, Bacterial", "descriptor_ui": "D005798", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Phycobilins", "descriptor_ui": "D052980", "major_topic": false }, { "descriptor": "Phycocyanin", "descriptor_ui": "D010798", "major_topic": false }, { "descriptor": "Synechocystis", "descriptor_ui": "D046939", "major_topic": false }, { "descriptor": "Thermosynechococcus", "descriptor_ui": "D000086325", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 20", "date_precision": "day", "issue": "11", "normalized_date": "2020-11-20", "pages": "2896-2906", "proceedings_title": null, "publisher": "", "title": "ACS chemical biology", "volume": "15", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Improvement of Phycocyanobilin Synthesis for Genetically Encoded Phytochrome-Based Optogenetics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The prevention of age-related cognitive decline and dementia is becoming a high priority because of the rapid growth of aging populations. We have previously shown that hop bitter acids such as iso-alpha-acids (IAAs) and matured hop bitter acids (MHBAs) activate the vagus nerve and improve memory impairment. Moreover, supplements with MHBAs were shown to improve memory retrieval in older adults. However, the underlying mechanisms have not been entirely elucidated. We aimed to investigate the effects of MHBAs and the common beta-tricarbonyl moiety on memory impairment induced by the activation of microglia and the loss of the noradrenergic system. MHBAs and a model compound with beta-tricarbonyl moiety were administered to LPS-inoculated mice and 5 x FAD Alzheimer's disease (AD) model mice, following the evaluation in behavioral tests and microglial activation. To evaluate the association of noradrenaline with MHBAs effects, mice treated with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a noradrenergic neurotoxin that selectively damages noradrenergic projections from the locus coeruleus, were subjected to the behavioral evaluation. MHBAs reduced brain inflammation and improved LPS-induced memory impairment. A model compound possessing the beta-tricarbonyl moiety improved the LPS-induced memory impairment and neuronal loss via the vagus nerve. Additionally, the protective effects of MHBAs on memory impairment were attenuated by noradrenaline depletion using DSP-4. MHBAs suppressed the activation of microglia and improved the memory impairment in 5 x FAD mice, which was also attenuated by noradrenaline depletion. Treatment with MHBAs increased cholecystokinin production from the intestinal cells. Generally, cholecystokinin activates the vagal nerve, which stimulate the noradrenergic neuron in the locus ceruleus. Taken together, our results reveal that food ingredients such as hop bitter acids with a beta-tricarbonyl moiety suppress microglial activation and improve memory impairment induced by inflammation or AD pathology via the activation of the gut-brain axis and noradrenergic system. Supplements with hop bitter acids, including MHBAs, might be a novel approach for the prevention of cognitive decline and dementia.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Ano", "name": null }, { "creator_type": "author", "first_name": "Rena", "last_name": "Ohya", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yoshimasa", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nakayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-77034-w" }, "pmcid": { "normalized": "PMC7674441" }, "pmid": { "normalized": "33208787" } }, "mesh": [ { "descriptor": "Acids", "descriptor_ui": "D000143", "major_topic": false }, { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cognitive Dysfunction", "descriptor_ui": "D060825", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory Disorders", "descriptor_ui": "D008569", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Norepinephrine", "descriptor_ui": "D009638", "major_topic": false }, { "descriptor": "Vagus Nerve", "descriptor_ui": "D014630", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 18", "date_precision": "day", "issue": "1", "normalized_date": "2020-11-18", "pages": "20028", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Hop bitter acids containing a beta-carbonyl moiety prevent inflammation-induced cognitive decline via the vagus nerve and noradrenergic system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dietary phosphate overload induces chronic kidney disease (CKD), and calciprotein particles (CPPs), a form of nanoparticle comprising calcium phosphate and serum proteins, has been proposed to cause renal toxicity. However, the mechanism of CPP cytotoxicity in renal tubular cells is unknown. Here we show that in renal proximal tubular epithelial HK-2 cells, endocytosed CPPs accumulate in late endosomes/lysosomes (LELs) and increase their luminal pH by ~ 1.0 unit. This results in a decrease in lysosomal hydrolase activity and autophagic flux blockage without lysosomal rupture and reactive oxygen species generation. CPP treatment led to vulnerability to H2O2-induced oxidative stress and plasma membrane injury, probably because of autophagic flux blockage and decreased plasma membrane cholesterol, respectively. CPP-induced disruption of lysosomal homeostasis, autophagy flux and plasma membrane integrity might trigger a vicious cycle, leading to progressive nephron loss.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Rina", "last_name": "Kunishige", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Mizoguchi", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Tsubouchi", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kurosu", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kuro-O", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Murata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-77308-3" }, "pmcid": { "normalized": "PMC7676272" }, "pmid": { "normalized": "33208865" } }, "mesh": [ { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Leucine Zipper Transcription Factors", "descriptor_ui": "D051778", "major_topic": false }, { "descriptor": "Calcifying Nanoparticles", "descriptor_ui": "D059587", "major_topic": false }, { "descriptor": "Calcium Phosphates", "descriptor_ui": "D002130", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Membrane Permeability", "descriptor_ui": "D002463", "major_topic": false }, { "descriptor": "Cholesterol", "descriptor_ui": "D002784", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Kidney Tubules, Proximal", "descriptor_ui": "D007687", "major_topic": false }, { "descriptor": "Lysosomes", "descriptor_ui": "D008247", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 18", "date_precision": "day", "issue": "1", "normalized_date": "2020-11-18", "pages": "20125", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Calciprotein particle-induced cytotoxicity via lysosomal dysfunction and altered cholesterol distribution in renal epithelial HK-2 cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Monitoring cell-state transition in pluripotent cells is invaluable for application and basic research. In this study, we demonstrate the pertinence of noninvasive, label-free Raman spectroscopy to monitor and characterize the cell-state transition of mouse stem cells undergoing reprogramming. Using an isogenic cell line of mouse stem cells, reprogramming from neuronal cells was performed, and we showcase a comparative analysis of living single-cell spectral data of the original stem cells, their neuronal progenitors, and reprogrammed cells. Neural network, regression models, and ratiometric analyses were used to discriminate the cell states and extract several important biomarkers specific to differentiation or reprogramming. Our results indicated that the Raman spectrum allowed us to build a low-dimensional space allowing us to monitor and characterize the dynamics of cell-state transition at a single-cell level, scattered in heterogeneous populations. The ability of monitoring pluripotency by Raman spectroscopy and distinguishing differences between ES and reprogrammed cells is also discussed.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Arno", "last_name": "Germond", "name": null }, { "creator_type": "author", "first_name": "Yulia", "last_name": "Panina", "name": null }, { "creator_type": "author", "first_name": "Mikio", "last_name": "Shiga", "name": null }, { "creator_type": "author", "first_name": "Hirohiko", "last_name": "Niioka", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.0c01800" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33112148" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": true }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Nov 17", "date_precision": "day", "issue": "22", "normalized_date": "2020-11-17", "pages": "14915-14923", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "92", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Following Embryonic Stem Cells, Their Differentiated Progeny, and Cell-State Changes During iPS Reprogramming by Raman Spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cytoskeleton-associated protein 4 (CKAP4) is a palmitoylated type II transmembrane protein localized to the endoplasmic reticulum (ER). Here, we found that knockout (KO) of CKAP4 in HeLaS3 cells induces the alteration of mitochondrial structures and increases the number of ER-mitochondria contact sites. To understand the involvement of CKAP4 in mitochondrial functions, the binding proteins of CKAP4 were explored, enabling identification of the mitochondrial porin voltage-dependent anion-selective channel protein 2 (VDAC2), which is localized to the outer mitochondrial membrane. Palmitoylation at Cys(100) of CKAP4 was required for the binding between CKAP4 and VDAC2. In CKAP4 KO cells, the binding of inositol trisphosphate receptor (IP3R) and VDAC2 was enhanced, the intramitochondrial Ca(2+) concentration increased and the mitochondrial membrane potential decreased. In addition, CKAP4 KO decreased the oxidative consumption rate, in vitro cancer cell proliferation under low-glucose conditions and in vivo xenograft tumor formation. The phenotypes were not rescued by expression of a palmitoylation-deficient CKAP4 mutant. These results suggest that CKAP4 plays a role in maintaining mitochondrial functions through the binding to VDAC2 at ER-mitochondria contact sites and that palmitoylation is required for this novel function of CKAP4.This article has an associated First Person interview with the first author of the paper.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Sada", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Osugi", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Mitsuko", "last_name": "Hayashi-Nishino", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kikuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/jcs.249045" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33067255" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": true }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lipoylation", "descriptor_ui": "D054878", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": true }, { "descriptor": "Mitochondrial Membranes", "descriptor_ui": "D051336", "major_topic": false }, { "descriptor": "Voltage-Dependent Anion Channel 2", "descriptor_ui": "D050996", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 10", "date_precision": "day", "issue": "21", "normalized_date": "2020-11-10", "pages": "jcs249045", "proceedings_title": null, "publisher": "", "title": "Journal of cell science", "volume": "133", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Palmitoylated CKAP4 regulates mitochondrial functions through an interaction with VDAC2 at ER-mitochondria contact sites.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Spontaneously blinking fluorophores are powerful tools for live-cell super-resolution imaging under physiological conditions. Here we show that quantum-chemical calculations can predict key parameters for fluorophore design. We applied this methodology to develop a spontaneously blinking fluorophore with yellow fluorescence for super-resolution imaging of microtubules in living cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Morozumi", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Hiroyoshi", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Aika", "last_name": "Nanjo", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Toshitada", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Tobita", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d0cc05126h" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33020769" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Nov 7", "date_precision": "day", "issue": "86", "normalized_date": "2020-11-07", "pages": "13173-13176", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "56", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Design of spontaneously blinking fluorophores for live-cell super-resolution imaging based on quantum-chemical calculations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cardiac plexus, which contains parasympathetic ganglia, plays an important role in regulating cardiac function. Histamine is known to excite intracardiac ganglion neurons, but the underlying mechanism is obscure. In the present study, therefore, the effect of histamine on rat intracardiac ganglion neurons was investigated using perforated patch-clamp recordings. Histamine depolarized acutely isolated neurons with a half-maximal effective concentration of 4.5 muM. This depolarization was markedly inhibited by the H(1) receptor antagonist triprolidine and mimicked by the H(1) receptor agonist 2-pyridylethylamine, thus implicating histamine H(1) receptors. Consistently, reverse transcription-PCR (RT-PCR) and Western blot analyses confirmed H(1) receptor expression in the intracardiac ganglia. Under voltage-clamp conditions, histamine evoked an inward current that was potentiated by extracellular Ca(2+) removal and attenuated by extracellular Na(+) replacement with N-methyl-D-glucamine. This implicated the involvement of non-selective cation channels, which given the link between H(1) receptors and G(q/11)-protein-phospholipase C signalling, were suspected to be transient receptor potential canonical (TRPC) channels. This was confirmed by the marked inhibition of the inward current through the pharmacological disruption of either G(q/11) signalling or intracellular Ca(2+) release and by the application of the TRPC blockers Pyr3, Gd(3+) and ML204. Consistently, RT-PCR analysis revealed the expression of several TRPC subtypes in the intracardiac ganglia. Whilst histamine was also separately found to inhibit the M-current, the histamine-induced depolarization was only significantly inhibited by the TRPC blockers Gd(3+) and ML204, and not by the M-current blocker XE991. These results suggest that TRPC channels serve as the predominant mediator of neuronal excitation by histamine.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Aya", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shiho", "last_name": "Arichi", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Tatsuko", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Dennis Lawrence", "last_name": "Cheung", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Eto", "name": null }, { "creator_type": "author", "first_name": "Madoka", "last_name": "Narushima", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Maruo", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Kadoya", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Nabekura", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Ishibashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ejphar.2020.173536" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32896550" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Ganglia", "descriptor_ui": "D005724", "major_topic": false }, { "descriptor": "Heart", "descriptor_ui": "D006321", "major_topic": false }, { "descriptor": "Histamine", "descriptor_ui": "D006632", "major_topic": false }, { "descriptor": "Histamine Agonists", "descriptor_ui": "D017442", "major_topic": false }, { "descriptor": "Histamine H1 Antagonists", "descriptor_ui": "D006634", "major_topic": false }, { "descriptor": "Ion Channels", "descriptor_ui": "D007473", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Meglumine", "descriptor_ui": "D008536", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Potassium Channels", "descriptor_ui": "D015221", "major_topic": false }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Triprolidine", "descriptor_ui": "D014311", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false }, { "descriptor": "Type C Phospholipases", "descriptor_ui": "D010738", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 5", "date_precision": "day", "issue": "", "normalized_date": "2020-11-05", "pages": "173536", "proceedings_title": null, "publisher": "", "title": "European journal of pharmacology", "volume": "886", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Histamine depolarizes rat intracardiac ganglion neurons through the activation of TRPC non-selective cation channels.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We developed a new class of turn-on fluorescent probes for an esterase. After the esterase-mediated hydrolysis produced carboxylate (as a fluorescence activator), the fluorescence intensity was markedly increased through the detachment of a quencher moiety from the quenched Cy5 fluorophore. Because the probes based on this new activator-induced quencher-detachment (AiQd) adopt a non-immolative linker between the cleavable site and the fluorophore, the rate of the enzymatic reaction is greatly improved, without the generation of any by-products.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Oe", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d0ob00899k" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32832959" } }, "mesh": [ { "descriptor": "Carbocyanines", "descriptor_ui": "D002232", "major_topic": false }, { "descriptor": "Carboxylic Acids", "descriptor_ui": "D002264", "major_topic": true }, { "descriptor": "Esterases", "descriptor_ui": "D004950", "major_topic": true }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Hydrolysis", "descriptor_ui": "D006868", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 4", "date_precision": "day", "issue": "42", "normalized_date": "2020-11-04", "pages": "8620-8624", "proceedings_title": null, "publisher": "", "title": "Organic & biomolecular chemistry", "volume": "18", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "An enzyme-triggered turn-on fluorescent probe based on carboxylate-induced detachment of a fluorescence quencher.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nr4a receptors are activated by T cell receptor (TCR) signaling and play key roles in T cell differentiation. Which TCR signaling pathways regulate Nr4a receptors and their sensitivities to TCR signal strength and duration remains unclear. Using Nr4a1/Nur77-GFP and Nr4a3-Timer of cell kinetics and activity (Tocky) mice, we elucidate the signaling pathways governing Nr4a receptor expression. We reveal that Nr4a1-Nr4a3 are Src family kinase dependent. Moreover, Nr4a2 and Nr4a3 are attenuated by calcineurin inhibitors and bind nuclear factor of activated T cells 1 (NFAT1), highlighting a necessary and sufficient role for NFAT1 in the control of Nr4a2 and Nr4a3, but redundancy for Nr4a1. Nr4a1-GFP is activated by tonic and cognate signals during T cell development, whereas Nr4a3-Tocky requires cognate peptide:major histocompatibility complex (MHC) interactions for expression. Compared to Nr4a3-Tocky, Nr4a1-GFP is approximately 2- to 3-fold more sensitive to TCR signaling and is detectable by shorter periods of TCR signaling. These findings suggest that TCR signal duration may be an underappreciated aspect influencing the developmental fate of T cells in vivo.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Emma", "last_name": "Jennings", "name": null }, { "creator_type": "author", "first_name": "Thomas A. E.", "last_name": "Elliot", "name": null }, { "creator_type": "author", "first_name": "Natasha", "last_name": "Thawait", "name": null }, { "creator_type": "author", "first_name": "Shivani", "last_name": "Kanabar", "name": null }, { "creator_type": "author", "first_name": "Juan Carlos", "last_name": "Yam-Puc", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Kai-Michael", "last_name": "Toellner", "name": null }, { "creator_type": "author", "first_name": "David C.", "last_name": "Wraith", "name": null }, { "creator_type": "author", "first_name": "Graham", "last_name": "Anderson", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Bending", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2020.108328" }, "pmcid": { "normalized": "PMC7653457" }, "pmid": { "normalized": "33147449" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcineurin", "descriptor_ui": "D019703", "major_topic": false }, { "descriptor": "CD4-Positive T-Lymphocytes", "descriptor_ui": "D015496", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "NFATC Transcription Factors", "descriptor_ui": "D050778", "major_topic": false }, { "descriptor": "Nuclear Receptor Subfamily 4, Group A, Member 1", "descriptor_ui": "D057105", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false }, { "descriptor": "Receptors, Steroid", "descriptor_ui": "D011987", "major_topic": false }, { "descriptor": "Receptors, Thyroid Hormone", "descriptor_ui": "D011988", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Nov 3", "date_precision": "day", "issue": "5", "normalized_date": "2020-11-03", "pages": "108328", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "33", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Nr4a1 and Nr4a3 Reporter Mice Are Differentially Sensitive to T Cell Receptor Signal Strength and Duration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder, caused by mutation in the gene encoding lamin A/C, which produces a truncated protein called progerin. In cells from HGPS patients, progerin accumulates at the nuclear membrane (NM), where it causes NM deformations. In this study, we investigated whether progerin-induced NM deformation involved ESCRT-III, a protein complex that remodels nuclear and cytoplasmic membranes. The ESCRT-III protein CHMP4B was recruited to sites of aberrant NM proliferation in human cells ectopically expressing progerin and in patient-derived HGPS fibroblasts. Derepression of NM deformation in these cells was observed following depletion of CHMP4B or an ESCRT-III adaptor, ALIX. Treatment with rapamycin (which induce autophagic clearance of progerin and reverse progerin-induced cellular phenotypes) down-regulated progerin-induced NM deformation, whereas treatment with bafilomycin A1 (an inhibitor of autophagy and lysosome-based degradation) or CHMP4B depletion antagonized the effects of rapamycin. These results indicate that the ALIX-mediated ESCRT-III pathway plays a suppressive role in progerin-induced NM deformation and suggest that autophagy down-regulates progerin-induced NM deformation in a manner dependent on ESCRT-III machinery.", "classifications": [ { "id": "19H05417", "label": "19H05417", "researcher": "Jun Arii", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-75852-6" }, "pmcid": { "normalized": "PMC7606583" }, "pmid": { "normalized": "33139753" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Calcium-Binding Proteins", "descriptor_ui": "D002135", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Endosomal Sorting Complexes Required for Transport", "descriptor_ui": "D056827", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lamin Type A", "descriptor_ui": "D034904", "major_topic": false }, { "descriptor": "Macrolides", "descriptor_ui": "D018942", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Nuclear Envelope", "descriptor_ui": "D009685", "major_topic": false }, { "descriptor": "Progeria", "descriptor_ui": "D011371", "major_topic": false }, { "descriptor": "Sirolimus", "descriptor_ui": "D020123", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 2", "date_precision": "day", "issue": "1", "normalized_date": "2020-11-02", "pages": "18877", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "ESCRT-III controls nuclear envelope deformation induced by progerin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The activity of the molecular motor enzyme, chloroplast ATP synthase, is regulated in a redox-dependent manner. The gamma subunit, CF1-gamma, is the central shaft of this enzyme complex and possesses the redox-active cysteine pair, which is reduced by thioredoxin (Trx). In light conditions, Trx transfers the reducing equivalent obtained from the photosynthetic electron transfer system to the CF1-gamma. Previous studies showed that the light-dependent reduction of CF1-gamma is more rapid than those of other Trx target proteins in the stroma. Although there are multiple Trx isoforms in chloroplasts, it is not well understood as to which chloroplast Trx isoform primarily contributes to the reduction of CF1-gamma, especially under physiological conditions. We therefore performed direct assessment of the CF1-gamma reduction capacity of each of the Trx isoforms. The kinetic analysis of the reduction process showed no significant difference in the reduction efficiency between two major chloroplast Trxs, namely Trx-f and Trx-m. Based on the thorough analyses of the CF1-gamma redox dynamics in Arabidopsis thaliana Trx mutant plants, we found that lack of Trx-f or Trx-m had no significant impact on the in vivo light-dependent reduction of CF1-gamma. The results showed that CF1-gamma can accept the reducing power from both Trx-f and Trx-m in chloroplasts.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takatoshi", "last_name": "Sekiguchi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Okegawa", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbabio.2020.148261" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32659266" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Chloroplast Proton-Translocating ATPases", "descriptor_ui": "D025222", "major_topic": false }, { "descriptor": "Chloroplast Thioredoxins", "descriptor_ui": "D054479", "major_topic": false }, { "descriptor": "Chloroplasts", "descriptor_ui": "D002736", "major_topic": false }, { "descriptor": "Electron Transport", "descriptor_ui": "D004579", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Photosynthesis", "descriptor_ui": "D010788", "major_topic": true }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 1", "date_precision": "day", "issue": "11", "normalized_date": "2020-11-01", "pages": "148261", "proceedings_title": null, "publisher": "", "title": "Biochimica et biophysica acta. Bioenergetics", "volume": "1861", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Chloroplast ATP synthase is reduced by both f-type and m-type thioredoxins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ciona robusta (Ciona intestinalis type A), a model organism for biological studies, belongs to ascidians, the main class of tunicates, which are the closest relatives of vertebrates. In Ciona, a project on the ontology of both development and anatomy is ongoing for several years. Its goal is to standardize a resource relating each anatomical structure to developmental stages. Today, the ontology is codified until the hatching larva stage. Here, we present its extension throughout the swimming larva stages, the metamorphosis, until the juvenile stages. For standardizing the developmental ontology, we acquired different time-lapse movies, confocal microscope images and histological serial section images for each developmental event from the hatching larva stage (17.5 h post fertilization) to the juvenile stage (7 days post fertilization). Combining these data, we defined 12 new distinct developmental stages (from Stage 26 to Stage 37), in addition to the previously defined 26 stages, referred to embryonic development. The new stages were grouped into four Periods named: Adhesion, Tail Absorption, Body Axis Rotation, and Juvenile. To build the anatomical ontology, 203 anatomical entities were identified, defined according to the literature, and annotated, taking advantage from the high resolution and the complementary information obtained from confocal microscopy and histology. The ontology describes the anatomical entities in hierarchical levels, from the cell level (cell lineage) to the tissue/organ level. Comparing the number of entities during development, we found two rounds on entity increase: in addition to the one occurring after fertilization, there is a second one during the Body Axis Rotation Period, when juvenile structures appear. Vice versa, one-third of anatomical entities associated with the embryo/larval life were significantly reduced at the beginning of metamorphosis. Data was finally integrated within the web-based resource \"TunicAnatO\", which includes a number of anatomical images and a dictionary with synonyms. This ontology will allow the standardization of data underpinning an accurate annotation of gene expression and the comprehension of mechanisms of differentiation. It will help in understanding the emergence of elaborated structures during both embryogenesis and metamorphosis, shedding light on tissue degeneration and differentiation occurring at metamorphosis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Delphine", "last_name": "Dauga", "name": null }, { "creator_type": "author", "first_name": "Lucia", "last_name": "Manni", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-73544-9" }, "pmcid": { "normalized": "PMC7578030" }, "pmid": { "normalized": "33087765" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": false }, { "descriptor": "Metamorphosis, Biological", "descriptor_ui": "D008675", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Urochordata", "descriptor_ui": "D014561", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Oct 21", "date_precision": "day", "issue": "1", "normalized_date": "2020-10-21", "pages": "17916", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "The ontology of the anatomy and development of the solitary ascidian Ciona: the swimming larva and its metamorphosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Two-photon imaging is a major recording technique used in neuroscience. However, it suffers from several limitations, including a low sampling rate, the nonlinearity of calcium responses, the slow dynamics of calcium dyes and a low SNR, all of which severely limit the potential of two-photon imaging to elucidate neuronal dynamics with high temporal resolution. We developed a hyperacuity algorithm (HA_time) based on an approach that combines a generative model and machine learning to improve spike detection and the precision of spike time inference. Bayesian inference was performed to estimate the calcium spike model, assuming constant spike shape and size. A support vector machine using this information and a jittering method maximizing the likelihood of estimated spike times enhanced spike time estimation precision approximately fourfold (range, 2-7; mean, 3.5-4.0; 2SEM, 0.1-0.25) compared to the sampling interval. Benchmark scores of HA_time for biological data from three different brain regions were among the best of the benchmark algorithms. Simulation of broader data conditions indicated that our algorithm performed better than others with high firing rate conditions. Furthermore, HA_time exhibited comparable performance for conditions with and without ground truths. Thus HA_time is a useful tool for spike reconstruction from two-photon imaging.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Huu", "last_name": "Hoang", "name": null }, { "creator_type": "author", "first_name": "Masa-Aki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Shinomoto", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Tomoe", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Ikegaya", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Mitsuo", "last_name": "Kawato", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Toyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-74672-y" }, "pmcid": { "normalized": "PMC7576127" }, "pmid": { "normalized": "33082425" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Oct 20", "date_precision": "day", "issue": "1", "normalized_date": "2020-10-20", "pages": "17844", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Improved hyperacuity estimation of spike timing from calcium imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cryptococcus deneoformans is an opportunistic fungal pathogen that frequently causes fatal meningoencephalitis in patients with impaired cell-mediated immune responses such as AIDS. Caspase-associated recruitment domain 9 (CARD9) plays a critical role in the host defense against cryptococcal infection, suggesting the involvement of one or more C-type lectin receptors (CLRs). In the present study, we analyzed the role of macrophage-inducible C-type lectin (Mincle), one of the CLRs, in the host defense against C. deneoformans infection. Mincle expression in the lungs of wild-type (WT) mice was increased in the early stage of cryptococcal infection in a CARD9-dependent manner. In Mincle gene-disrupted (Mincle KO) mice, the clearance of this fungus, pathological findings, Th1/Th2 response, and antimicrobial peptide production in the infected lungs were nearly comparable to those in WT mice. However, the production of interleukin-22 (IL-22), tumor necrosis factor alpha (TNF-alpha), and IL-6 and the expression of AhR were significantly decreased in the lungs of Mincle KO mice compared to those of WT mice. In in vitro experiments, TNF-alpha production by bone marrow-derived dendritic cells was significantly decreased in Mincle KO mice. In addition, the disrupted lysates of C. deneoformans, but not those of whole yeast cells, activated Mincle-triggered signaling in an assay with a nuclear factor of activated T cells (NFAT)-green fluorescent protein (GFP) reporter cells expressing this receptor. These results suggest that Mincle may be involved in the production of Th22-related cytokines at the early stage of cryptococcal infection, although its role may be limited in the host defense against infection with C. deneoformans.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Tomomitsu", "last_name": "Miyasaka", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Tanno", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Miyahara", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Kagesawa", "name": null }, { "creator_type": "author", "first_name": "Akiho", "last_name": "Oniyama", "name": null }, { "creator_type": "author", "first_name": "Kotone", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Rin", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kitai", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Umeki", "name": null }, { "creator_type": "author", "first_name": "Shigenari", "last_name": "Ishizuka", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Ryuhei", "last_name": "Shiroma", "name": null }, { "creator_type": "author", "first_name": "Nana", "last_name": "Nakahata", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Kanno", "name": null }, { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Tanno", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Hiromitsu", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/iai.00400-20" }, "pmcid": { "normalized": "PMC7573449" }, "pmid": { "normalized": "32868343" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cryptococcosis", "descriptor_ui": "D003453", "major_topic": false }, { "descriptor": "Cryptococcus neoformans", "descriptor_ui": "D003455", "major_topic": false }, { "descriptor": "Lectins, C-Type", "descriptor_ui": "D037181", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Oct 19", "date_precision": "day", "issue": "11", "normalized_date": "2020-10-19", "pages": "e00400-20", "proceedings_title": null, "publisher": "", "title": "Infection and immunity", "volume": "88", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Limited Role of Mincle in the Host Defense against Infection with Cryptococcus deneoformans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cyclin-dependent kinase 8 (CDK8) is a member of the CDK/Cyclin module of the mediator complex. A recent study reported that heterozygous missense CDK8 mutations cause a neurodevelopmental disorder in humans. The mechanistic basis of CDK8-related disorder has yet to be delineated. Here, we report 2 patients with de novo missense mutations within the kinase domain of CDK8 along with the results of in vitro and in vivo functional analyses using a zebrafish model. Patient 1 and Patient 2 had intellectual disabilities and congenital anomalies. Exome analyses showed that patient 1 had a heterozygous de novo missense p.G28A variant in the CDK8 (NM_001260.3) gene and patient 2 had a heterozygous de novo missense p.N156S variant in the CDK8 gene. We assessed the pathogenicity of these two variants using cultured-cells and zebrafish model. An in vitro kinase assay of human CDK8 showed that enzymes with a p.G28A or p.N156S substitution showed decreased kinase activity. An in vivo assays of zebrafish overexpression analyses also showed that the p.G28A and p.N156S alleles were hypomorphic alleles. Importantly, the inhibition of CDK8 kinase activity in zebrafish embryos using a specific chemical inhibitor induced craniofacial and heart defects similar to the patients' phenotype. Taken together, zebrafish studies showed that non-synonymous variants in the kinase domain of CDK8 act as hypomorphic alleles causing human congenital disorder.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tomoko", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Oginuma", "name": null }, { "creator_type": "author", "first_name": "Shizuka", "last_name": "Ishitani", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshihashi", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Takenouchi", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Kosaki", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Ishitani", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-74642-4" }, "pmcid": { "normalized": "PMC7567849" }, "pmid": { "normalized": "33067521" } }, "mesh": [ { "descriptor": "Abnormalities, Multiple", "descriptor_ui": "D000015", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Child", "descriptor_ui": "D002648", "major_topic": false }, { "descriptor": "Craniofacial Abnormalities", "descriptor_ui": "D019465", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase 8", "descriptor_ui": "D056850", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinases", "descriptor_ui": "D018844", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Heart Defects, Congenital", "descriptor_ui": "D006330", "major_topic": false }, { "descriptor": "Heterozygote", "descriptor_ui": "D006579", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infant", "descriptor_ui": "D007223", "major_topic": false }, { "descriptor": "Intellectual Disability", "descriptor_ui": "D008607", "major_topic": false }, { "descriptor": "Loss of Function Mutation", "descriptor_ui": "D000073658", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mutation, Missense", "descriptor_ui": "D020125", "major_topic": true }, { "descriptor": "Neurodevelopmental Disorders", "descriptor_ui": "D065886", "major_topic": false }, { "descriptor": "Point Mutation", "descriptor_ui": "D017354", "major_topic": true }, { "descriptor": "Protein Domains", "descriptor_ui": "D000072417", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Quinazolines", "descriptor_ui": "D011799", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false }, { "descriptor": "Zebrafish Proteins", "descriptor_ui": "D029961", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Oct 16", "date_precision": "day", "issue": "1", "normalized_date": "2020-10-16", "pages": "17575", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Pathogenesis of CDK8-associated disorder: two patients with novel CDK8 variants and in vitro and in vivo functional analyses of the variants.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Autism spectrum disorder (ASD) is thought to result from deviation from normal development of neural circuits and synaptic function. Many genes with mutation in ASD patients have been identified. Here we report that two molecules associated with ASD susceptibility, contactin associated protein-like 2 (CNTNAP2) and Abelson helper integration site-1 (AHI1), are required for synaptic function and ASD-related behavior in mice. Knockdown of CNTNAP2 or AHI1 in layer 2/3 pyramidal neurons of the developing mouse prefrontal cortex (PFC) reduced excitatory synaptic transmission, impaired social interaction and induced mild vocalization abnormality. Although the causes of reduced excitatory transmission were different, pharmacological enhancement of AMPA receptor function effectively restored impaired social behavior in both CNTNAP2- and AHI1-knockdown mice. We conclude that reduced excitatory synaptic transmission in layer 2/3 pyramidal neurons of the PFC leads to impaired social interaction and mild vocalization abnormality in mice.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Sacai", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Sakoori", "name": null }, { "creator_type": "author", "first_name": "Kohtarou", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Nagahama", "name": null }, { "creator_type": "author", "first_name": "Honoka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-020-18861-3" }, "pmcid": { "normalized": "PMC7552417" }, "pmid": { "normalized": "33046712" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Vesicular Transport", "descriptor_ui": "D033942", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autism Spectrum Disorder", "descriptor_ui": "D000067877", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Pyramidal Cells", "descriptor_ui": "D017966", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Oct 12", "date_precision": "day", "issue": "1", "normalized_date": "2020-10-12", "pages": "5140", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Autism spectrum disorder-like behavior caused by reduced excitatory synaptic transmission in pyramidal neurons of mouse prefrontal cortex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We previously showed that mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP) exhibit attenuated light-induced phase shift. To explore the underlying mechanisms, we performed gene expression analysis of laser capture microdissected suprachiasmatic nuclei (SCNs) and found that lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is involved in the impaired response to light stimulation in the late subjective night in PACAP-deficient mice. L-PGDS-deficient mice also showed impaired light-induced phase advance, but normal phase delay and nonvisual light responses. Then, we examined the receptors involved in the response and observed that mice deficient for type 2 PGD2 receptor DP2/CRTH2 (chemoattractant receptor homologous molecule expressed on Th2 cells) show impaired light-induced phase advance. Concordant results were observed using the selective DP2/CRTH2 antagonist CAY10471. These results indicate that L-PGDS is involved in a mechanism of light-induced phase advance via DP2/CRTH2 signaling.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Chihiro", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Michiyoshi", "last_name": "Hatanaka", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Kuromi", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Yamano", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Soken", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okuno", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Urade", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Kin-Ya", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Shuh", "last_name": "Narumiya", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-020-01281-w" }, "pmcid": { "normalized": "PMC7544906" }, "pmid": { "normalized": "33033338" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Genes", "descriptor_ui": "D005796", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Intramolecular Oxidoreductases", "descriptor_ui": "D019746", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Lipocalins", "descriptor_ui": "D054834", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Oct 8", "date_precision": "day", "issue": "1", "normalized_date": "2020-10-08", "pages": "557", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "3", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Lipocalin-type prostaglandin D synthase regulates light-induced phase advance of the central circadian rhythm in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Kuraku", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1017/s0952523820000073" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33028447" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Oct 8", "date_precision": "day", "issue": "", "normalized_date": "2020-10-08", "pages": "E009", "proceedings_title": null, "publisher": "", "title": "Visual neuroscience", "volume": "37", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Letter to the editor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Antibodies produced by plasma cells are critical for protection from infection. It has been demonstrated that global epigenetic modification, such as changes in DNA methylation, occurs during differentiation of plasma cells from B cells. However, the precise mechanisms by which DNA methylation controls plasma cell differentiation are not fully understood. We examined the effect of deficiency of DNA demethylases, Tet2 and Tet3, on B-cell activation and plasma cell differentiation, by generating conditional Tet2/3 double-KO (Tet dKO) B cells. We found that Tet dKO B cells failed to differentiate into plasma cells upon immunization with antigens. Tet dKO B cells proliferated normally and were capable of generating cells with IRF4int, but not with IRF4hi, the majority of which were CD138+ plasma cells. IRF4 overexpression rescued the defect of Tet dKO B cells in plasma cell differentiation, suggesting that Tet2/3-dependent high IRF4 expression is required for plasma cell differentiation. We identified CpG sites in the Irf4 locus that were demethylated specifically in plasma cells and in a Tet2/3-dependent manner. Our results suggest that Tet2/3-dependent demethylation of these CpG sites is dispensable for initial IRF4 expression but is essential for high IRF4 expression which is prerequisite for plasma cell differentiation.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kentaro", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Narazaki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kumanogoh", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Koseki", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kurosaki", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Ise", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/intimm/dxaa042" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32583857" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "DNA-Directed DNA Polymerase", "descriptor_ui": "D004259", "major_topic": false }, { "descriptor": "Interferon Regulatory Factor-4", "descriptor_ui": "D000099218", "major_topic": false }, { "descriptor": "Interferon Regulatory Factors", "descriptor_ui": "D050835", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Plasma Cells", "descriptor_ui": "D010950", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Sep 30", "date_precision": "day", "issue": "10", "normalized_date": "2020-09-30", "pages": "683-690", "proceedings_title": null, "publisher": "", "title": "International immunology", "volume": "32", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Tet DNA demethylase is required for plasma cell differentiation by controlling expression levels of IRF4.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Identification of the complete set of translated genes of viruses is important to understand viral replication and pathogenesis as well as for therapeutic approaches to control viral infection. Here, we use chemical proteomics, integrating bio-orthogonal non-canonical amino acid tagging and high-resolution mass spectrometry, to characterize the newly synthesized herpes simplex virus 1 (HSV-1) proteome in infected cells. In these infected cells, host cellular protein synthesis is shut-off, increasing the chance to preferentially detect viral proteomes. We identify nine previously cryptic orphan protein coding sequences whose translated products are expressed in HSV-1-infected cells. Functional characterization of one identified protein, designated piUL49, shows that it is critical for HSV-1 neurovirulence in vivo by regulating the activity of virally encoded dUTPase, a key enzyme that maintains accurate DNA replication. Our results demonstrate that cryptic orphan protein coding genes of HSV-1, and probably other large DNA viruses, remain to be identified.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Shungo", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Kousuke", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Shinobu", "last_name": "Kitazume", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Kusano", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Tomohisa", "last_name": "Hatta", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Natsume", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-020-18718-9" }, "pmcid": { "normalized": "PMC7524712" }, "pmid": { "normalized": "32994400" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "DNA Replication", "descriptor_ui": "D004261", "major_topic": false }, { "descriptor": "Encephalitis, Herpes Simplex", "descriptor_ui": "D020803", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genes, Viral", "descriptor_ui": "D005814", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Protein Biosynthesis", "descriptor_ui": "D014176", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Pyrophosphatases", "descriptor_ui": "D011755", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virulence Factors", "descriptor_ui": "D037521", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Sep 29", "date_precision": "day", "issue": "1", "normalized_date": "2020-09-29", "pages": "4894", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of a herpes simplex virus 1 gene encoding neurovirulence factor by chemical proteomics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We scrutinize the length dependency of the binding affinity of bacterial repressor TrpR protein to trpO (specific site) on DNA. A footprinting experiment shows that the longer the DNA length, the larger the affinity of TrpR to the specific site on DNA. This effect termed \"antenna effect\" might be interpreted as follows: longer DNA provides higher probability for TrpR to access to the specific site aided by one-dimensional diffusion along the nonspecific sites of DNA. We show that, however, the antenna effect cannot be explained while detailed balance holds among three kinetic states, that is, free protein/DNA, nonspecific complexes, and specific complex. We propose a working hypothesis that slow degree(s) of freedom in the system switch(es) different potentials of mean force causing transitions among the three states. This results in a deviation from detailed balance on the switching timescale. We then derive a simple reaction diffusion/binding model that describes the antenna effect on TrpR binding to its target operator. Possible scenarios for such slow degree(s) of freedom in TrpR-DNA complex are addressed.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Nobuo", "last_name": "Shimamoto", "name": null }, { "creator_type": "author", "first_name": "Mikito", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Shigetoshi", "last_name": "Nara", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null }, { "creator_type": "author", "first_name": "Kiyoto", "last_name": "Kamagata", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kinebuchi", "name": null }, { "creator_type": "author", "first_name": "Jun-Ichi", "last_name": "Tomizawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-71598-3" }, "pmcid": { "normalized": "PMC7518442" }, "pmid": { "normalized": "32973254" } }, "mesh": [ { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "DNA, Bacterial", "descriptor_ui": "D004269", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Escherichia coli Proteins", "descriptor_ui": "D029968", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": true }, { "descriptor": "Operator Regions, Genetic", "descriptor_ui": "D009875", "major_topic": true }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Sep 24", "date_precision": "day", "issue": "1", "normalized_date": "2020-09-24", "pages": "15624", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Dependence of DNA length on binding affinity between TrpR and trpO of DNA.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "G protein-coupled receptors (GPCRs) transduce extracellular signals into cells by interacting with G proteins and arrestins. Emerging evidence suggests that GPCRs on the plasma membrane are in a dynamic equilibrium among monomers, dimers, and larger oligomers. Nevertheless, the role of the oligomer formation in the GPCR signal transduction remains unclear. Using multicolor single-molecule live-cell imaging, we show a dynamic interconversion between small and large oligomer states of a chemoattractant GPCR, Formyl Peptide Receptor 1 (FPR1), and its binding affinity with G protein. Full agonist stimulation increased a fraction of large FPR1 oligomers, which allowed for prolonged FPR1-G protein interaction. The G protein interaction with FPR1 was most stabilized at the full agonist-bound large FPR1 oligomers. Based on these results, we propose that G protein-mediated signal transduction may be regulated synergistically by the ligand-binding and FPR1 oligomerization. Cooperative signal control induced by receptor oligomerization is anticipated as a target for drug discovery.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "contributor", "first_name": "Tomoki", "last_name": "Nishiguchi", "name": null }, { "creator_type": "contributor", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "contributor", "first_name": "Rinshi S.", "last_name": "Kasai", "name": null }, { "creator_type": "contributor", "first_name": "Takahiro K.", "last_name": "Fujiwara", "name": null }, { "creator_type": "contributor", "first_name": "Takeaki", "last_name": "Ozawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acschembio.0c00631" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Sep 18", "date_precision": "day", "issue": "", "normalized_date": "2020-09-18", "pages": "", "proceedings_title": null, "publisher": "", "title": "", "volume": "15", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Synergetic Roles of Formyl Peptide Receptor 1 Oligomerization in Ligand-Induced Signal Transduction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dendritic spines function as microcompartments that can modify the efficiency of their associated synapses. Here, we analyzed stimulus-dependent molecular changes in spines. The F-actin capping protein CapZ accumulates in parts of dendritic spines within regions where long-term potentiation has been induced. We produced a transgenic mouse line, AiCE-Tg, in which CapZ tagged with enhanced green fluorescence protein (EGFP-CapZ) is expressed. Twenty minutes after unilateral visual or somatosensory stimulation in AiCE-Tg mice, relative EGFP-CapZ signal intensification was seen in a subset of dendritic spines selectively in stimulated-side cortices; this right-left difference was abolished by NMDA receptor blockade. Immunolabeling of alpha-actinin, a PSD-95 binding protein that can recruit AMPA receptors, showed that the alpha-actinin signals colocalized more frequently in spines with the brightest EGFP-CapZ signals (top 100) than in spines with more typical EGFP-CapZ signal strength (top 1,000). This stimulus-dependent in vivo redistribution of EGFP-CapZ represents a novel molecular event with plasticity-like characteristics, and bright EGFP-CapZ in AiCE-Tg mice make high-CapZ spines traceable in vivo and ex vivo. This mouse line has the potential to be used to reveal sequential molecular events, including synaptic tagging, and to relate multiple types of plasticity in these spines, extending knowledge related to memory mechanisms.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuya", "last_name": "Kuboyama", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hashimotodani", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Tohsuke", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Tetsuzawa", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Ohtsuka", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Ren", "last_name": "Takara", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Miyazawa", "name": null }, { "creator_type": "author", "first_name": "Pooja", "last_name": "Gusain", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Maki K.", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-72248-4" }, "pmcid": { "normalized": "PMC7499203" }, "pmid": { "normalized": "32943708" } }, "mesh": [ { "descriptor": "Actinin", "descriptor_ui": "D000185", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Disks Large Homolog 4 Protein", "descriptor_ui": "D000076122", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Receptors, AMPA", "descriptor_ui": "D018091", "major_topic": false }, { "descriptor": "Receptors, N-Methyl-D-Aspartate", "descriptor_ui": "D016194", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Sep 17", "date_precision": "day", "issue": "1", "normalized_date": "2020-09-17", "pages": "15266", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Traceable stimulus-dependent rapid molecular changes in dendritic spines in the brain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We established a methodology for initiating cross-linking of antibodies selectively on the cell surface through intermolecular copper-free click reactions facilitated by increased effective concentrations of antibodies binding to target antigens. Upon cross-linking of tetrazine- and bicyclononyne-modified trastuzumab on the surface of HER2-overexpressing cells, increased antibody uptake and activation of intracellular signaling were observed. Our findings demonstrate that the cross-linking reaction can significantly alter the biophysical properties of proteins, activating their unique functionalities on targeted cells to realize an increased cargo delivery and synthetic manipulation of cellular signaling.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Etsu", "last_name": "Kyo", "name": null }, { "creator_type": "author", "first_name": "Haruki", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Kyoji", "last_name": "Tsuchikama", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.0c05331" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32897068" } }, "mesh": [ { "descriptor": "3T3 Cells", "descriptor_ui": "D016475", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aza Compounds", "descriptor_ui": "D001372", "major_topic": false }, { "descriptor": "Bridged Bicyclo Compounds", "descriptor_ui": "D001643", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cross-Linking Reagents", "descriptor_ui": "D003432", "major_topic": false }, { "descriptor": "Erb-b2 Receptor Tyrosine Kinases", "descriptor_ui": "D018719", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Surface Properties", "descriptor_ui": "D013499", "major_topic": false }, { "descriptor": "Trastuzumab", "descriptor_ui": "D000068878", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Sep 16", "date_precision": "day", "issue": "37", "normalized_date": "2020-09-16", "pages": "15644-15648", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "142", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Antibody Clicking as a Strategy to Modify Antibody Functionalities on the Surface of Targeted Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Frequent mutation of the tumour suppressor RNF43 is observed in many cancers, particularly colon malignancies. RNF43, an E3 ubiquitin ligase, negatively regulates Wnt signalling by inducing degradation of the Wnt receptor Frizzled. In this study, we discover that RNF43 activity requires phosphorylation at a triplet of conserved serines. This phospho-regulation of RNF43 is required for zebrafish development and growth of mouse intestinal organoids. Cancer-associated mutations that abrogate RNF43 phosphorylation cooperate with active Ras to promote tumorigenesis by abolishing the inhibitory function of RNF43 in Wnt signalling while maintaining its inhibitory function in p53 signalling. Our data suggest that RNF43 mutations cooperate with KRAS mutations to promote multi-step tumorigenesis via the Wnt-Ras-p53 axis in human colon cancers. Lastly, phosphomimetic substitutions of the serine trio restored the tumour suppressive activity of extracellular oncogenic mutants. Therefore, harnessing phospho-regulation of RNF43 might be a potential therapeutic strategy for tumours with RNF43 mutations.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tadasuke", "last_name": "Tsukiyama", "name": null }, { "creator_type": "author", "first_name": "Juqi", "last_name": "Zou", "name": null }, { "creator_type": "author", "first_name": "Jihoon", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Ogamino", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shino", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Alessandra", "last_name": "Merenda", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Sayuri", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Hidehisa", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Ishitani", "name": null }, { "creator_type": "author", "first_name": "Keiichi I.", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Bon-Kyoung", "last_name": "Koo", "name": null }, { "creator_type": "author", "first_name": "Shigetsugu", "last_name": "Hatakeyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-020-18257-3" }, "pmcid": { "normalized": "PMC7492264" }, "pmid": { "normalized": "32934222" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Oncogene Protein p21(ras)", "descriptor_ui": "D015689", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Proteolysis", "descriptor_ui": "D059748", "major_topic": false }, { "descriptor": "Receptors, Wnt", "descriptor_ui": "D060490", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false }, { "descriptor": "Ubiquitin-Protein Ligases", "descriptor_ui": "D044767", "major_topic": false }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Sep 15", "date_precision": "day", "issue": "1", "normalized_date": "2020-09-15", "pages": "4586", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "A phospho-switch controls RNF43-mediated degradation of Wnt receptors to suppress tumorigenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "SETD1A encodes a histone methyltransferase whose de novo mutations are identified in schizophrenia (SCZ) patients and confer a large increase in disease risk. Here, we generate Setd1a mutant mice carrying the frameshift mutation that closely mimics a loss-of-function variant of SCZ. Our Setd1a (+/-) mice display various behavioral abnormalities relevant to features of SCZ, impaired excitatory synaptic transmission in layer 2/3 (L2/3) pyramidal neurons of the medial prefrontal cortex (mPFC), and altered expression of diverse genes related to neurodevelopmental disorders and synaptic functions in the mPFC. RNAi-mediated Setd1a knockdown (KD) specifically in L2/3 pyramidal neurons of the mPFC only recapitulates impaired sociality among multiple behavioral abnormalities of Setd1a (+/-) mice. Optogenetics-assisted selective stimulation of presynaptic neurons combined with Setd1a KD reveals that Setd1a at postsynaptic site is essential for excitatory synaptic transmission. Our findings suggest that reduced SETD1A may attenuate excitatory synaptic function and contribute to the pathophysiology of SCZ.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Nagahama", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Sakoori", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kishi", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Kawaji", "name": null }, { "creator_type": "author", "first_name": "Michinori", "last_name": "Koebis", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Gotoh", "name": null }, { "creator_type": "author", "first_name": "Atsu", "last_name": "Aiba", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2020.108126" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32937141" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": true }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neurodevelopmental Disorders", "descriptor_ui": "D065886", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Presynaptic Terminals", "descriptor_ui": "D017729", "major_topic": false }, { "descriptor": "Pyramidal Cells", "descriptor_ui": "D017966", "major_topic": false }, { "descriptor": "Schizophrenia", "descriptor_ui": "D012559", "major_topic": false }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Sep 15", "date_precision": "day", "issue": "11", "normalized_date": "2020-09-15", "pages": "108126", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "32", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Setd1a Insufficiency in Mice Attenuates Excitatory Synaptic Function and Recapitulates Schizophrenia-Related Behavioral Abnormalities.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Some fish have acquired the ability to breathe air, but these fish can no longer flush their gills effectively when out of water. Hence, they have developed characteristic means for defense against external stressors, including thirst (osmolarity/ions) and toxicity. Amphibious fish, extant air-breathing fish emerged from water, may serve as models to examine physiological responses to these stressors. Some of these fish, including mudskipper gobies such as Periophthalmodon schlosseri, Boleophthalmus boddarti and our Periophthalmus modestus, display distinct adaptational behaviors to these factors compared with fully aquatic fish. In this review, we introduce the mudskipper goby as a unique model to study the behaviors and the neuro/endocrine mechanisms of behavioral responses to the stressors. Our studies have shown that a local sensation of thirst in the buccal cavity-this being induced by dipsogenic hormones-motivates these fish to move to water through a forebrain response. The corticosteroid system, which is responsive to various stressors, also stimulates migration, possibly via the receptors in the brain. We suggest that such fish are an important model to deepen insights into the stress-related neuro/endocrine-behavioral effects.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yukitoshi", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms21186748" }, "pmcid": { "normalized": "PMC7555618" }, "pmid": { "normalized": "32938015" } }, "mesh": [ { "descriptor": "Adrenal Cortex Hormones", "descriptor_ui": "D000305", "major_topic": false }, { "descriptor": "Amphibians", "descriptor_ui": "D000663", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cheek", "descriptor_ui": "D002610", "major_topic": false }, { "descriptor": "Fishes", "descriptor_ui": "D005399", "major_topic": false }, { "descriptor": "Models, Animal", "descriptor_ui": "D023421", "major_topic": false }, { "descriptor": "Neurosecretory Systems", "descriptor_ui": "D009490", "major_topic": false }, { "descriptor": "Sensation", "descriptor_ui": "D012677", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Sep 14", "date_precision": "day", "issue": "18", "normalized_date": "2020-09-14", "pages": "E6748", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "21", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Introducing the Amphibious Mudskipper Goby as a Unique Model to Evaluate Neuro/Endocrine Regulation of Behaviors Mediated by Buccal Sensation and Corticosteroids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The wide spread of smartphones and QR codes for various end-user applications has had an impact beyond traditional fields of use, recently also reaching point-of-care testing (POCT). This work presents the integration of QR code recognition into paper-based analytical devices (PADs) with \"distance-based\" colorimetric signalling, resulting in semiquantitative readout fully relying on straightforward barcode reader solutions. PADs consist of an array of QR codes arranged in series inside a paperfluidic channel. A mask dye concept has been developed, which enables utilisation of colour changing indicators by initially hiding QR codes. The colour change of the indicator induced by the presence of an analyte of interest results in gradual unmasking of QR codes, which become recognisable by the smartphone barcode reader app. To reproducibly fabricate devices, all fabrication steps were performed by commercial desktop solid ink and inkjet printing. The QR code masking function was optimised by controlling the amount of printed mask dye through adjusting the opacity of printing patterns during the inkjet deposition process. For proof-of-concept, a model assay in the form of colorimetric copper ion (Cu2+) detection in the concentration range of 0.4 mM to 3.2 mM was evaluated. Consistent results independent of the smartphone model and environmental light condition were achieved with a free barcode reader app. To the best of our knowledge, this work is the first demonstration of a semiquantitative assay approach fully relying on QR code readout without digital colour analysis, customised app or hardware modification.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Aya", "last_name": "Katoh", "name": null }, { "creator_type": "author", "first_name": "Kento", "last_name": "Maejima", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d0an00955e" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32812544" } }, "mesh": [ { "descriptor": "Colorimetry", "descriptor_ui": "D003124", "major_topic": true }, { "descriptor": "Smartphone", "descriptor_ui": "D000068997", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Sep 14", "date_precision": "day", "issue": "18", "normalized_date": "2020-09-14", "pages": "6071-6078", "proceedings_title": null, "publisher": "", "title": "The Analyst", "volume": "145", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "All-printed semiquantitative paper-based analytical devices relying on QR code array readout.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Magnesium plays important roles in the nervous system. An increase in the Mg(2+) concentration in cerebrospinal fluid enhances neural functions, while Mg(2+) deficiency is implicated in neuronal diseases in the central nervous system. We have previously demonstrated that high concentrations of glutamate induce excitotoxicity and elicit a transient increase in the intracellular concentration of Mg(2+) due to the release of Mg(2+) from mitochondria, followed by a decrease to below steady-state levels. Since Mg(2+) deficiency is involved in neuronal diseases, this decrease presumably affects neuronal survival under excitotoxic conditions. However, the mechanism of the Mg(2+) decrease and its effect on the excitotoxicity process have not been elucidated. In this study, we demonstrated that inhibitors of Mg(2+) extrusion, quinidine and amiloride, attenuated glutamate excitotoxicity in cultured rat hippocampal neurons. A toxic concentration of glutamate induced both Mg(2+) release from mitochondria and Mg(2+) extrusion from cytosol, and both quinidine and amiloride suppressed only the extrusion. This resulted in the maintenance of a higher Mg(2+) concentration in the cytosol than under steady-state conditions during the ten-minute exposure to glutamate. These inhibitors also attenuated the glutamate-induced depression of cellular energy metabolism. Our data indicate the importance of Mg(2+) regulation in neuronal survival under excitotoxicity.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/nu12092768" }, "pmcid": { "normalized": "PMC7551965" }, "pmid": { "normalized": "32927908" } }, "mesh": [ { "descriptor": "Amiloride", "descriptor_ui": "D000584", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cytosol", "descriptor_ui": "D003600", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Quinidine", "descriptor_ui": "D011802", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Sep 10", "date_precision": "day", "issue": "9", "normalized_date": "2020-09-10", "pages": "E2768", "proceedings_title": null, "publisher": "", "title": "Nutrients", "volume": "12", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Inhibition of Mg(2+) Extrusion Attenuates Glutamate Excitotoxicity in Cultured Rat Hippocampal Neurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Aiming at the evaluation of the viscosity of the interfacial solidlike structure of ionic liquids (ILs), we performed total internal reflection fluorescence (TIRF) spectroscopy for N,N-diethyl-N'-phenyl-rhodamine (Ph-DER), a fluorescent probe that is sensitive to viscosity in a high-viscosity range. TIRF spectra at the glass interface of trioctylmethylammonium bis(nonafluorobutanesulfonyl)amide (TOMAC4C4N), a hydrophobic IL, showed that the fluorescence intensity of Ph-DER increases with the decrease of the evanescence penetration depth, suggesting that there exists a high-viscosity region at the interface. In contrast, glycerol, which is a molecular liquid with a bulk viscosity similar to that of TOMAC4C4N, did not show such a fluorescence increase, supporting that the formation of a highly viscous solidlike structure at the interface is intrinsic to ILs. A model analysis suggested that the high viscous region at the glass interface of TOMAC4C4N is at least twice thicker than the ionic multilayers at the air interface, implying that the solid substrate enhances the ordering of the interfacial structure of ILs. The viscosity at the glass interface of TOMAC4C4N was found to be at least 40 times higher than that of the liquid bulk.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Naoya", "last_name": "Nishi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yamazawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Sakka", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ikeno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.langmuir.0c01528" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32787009" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Sep 8", "date_precision": "day", "issue": "35", "normalized_date": "2020-09-08", "pages": "10397-10403", "proceedings_title": null, "publisher": "", "title": "Langmuir : the ACS journal of surfaces and colloids", "volume": "36", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "How Viscous Is the Solidlike Structure at the Interface of Ionic Liquids? A Study Using Total Internal Reflection Fluorescence Spectroscopy with a Fluorescent Molecular Probe Sensitive to High Viscosity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The transplantation of neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs) has beneficial effects on spinal cord injury (SCI). However, while there are many subtypes of NPCs with different regional identities, the subtype of iPSC-derived NPCs that is most appropriate for cell therapy for SCI has not been identified. Here, we generated forebrain- and spinal cord-type NPCs from human iPSCs and grafted them onto the injured spinal cord in mice. These two types of NPCs retained their regional identities after transplantation and exhibited different graft-host interconnection properties. NPCs with spinal cord regional identity but not those with forebrain identity resulted in functional improvement in SCI mice, especially in those with mild-to-moderate lesions. This study highlights the importance of the regional identity of human iPSC-derived NPCs used in cell therapy for SCI.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Keita", "last_name": "Kajikawa", "name": null }, { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Munehisa", "last_name": "Shinozaki", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Reo", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kamata", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Narihito", "last_name": "Nagoshi", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13041-020-00662-w" }, "pmcid": { "normalized": "PMC7650268" }, "pmid": { "normalized": "32883317" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell- and Tissue-Based Therapy", "descriptor_ui": "D064987", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Mice, SCID", "descriptor_ui": "D016513", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Organ Specificity", "descriptor_ui": "D009928", "major_topic": true }, { "descriptor": "Recovery of Function", "descriptor_ui": "D020127", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false }, { "descriptor": "Spinal Cord Injuries", "descriptor_ui": "D013119", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Sep 3", "date_precision": "day", "issue": "1", "normalized_date": "2020-09-03", "pages": "120", "proceedings_title": null, "publisher": "", "title": "Molecular brain", "volume": "13", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell therapy for spinal cord injury by using human iPSC-derived region-specific neural progenitor cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: Lung transplantation is the only effective therapy for patients with end-stage lung disease but an organ shortage crisis necessitates the development of alternative therapies. Recent studies have highlighted the potential of foetal tissue transplantation to facilitate the regeneration of vital organs such as liver that have been damaged by lethal diseases. Herein, with the aim of restoring pulmonary function, we hypothesized that allogenic foetal lung tissue implantation would attenuate severe respiratory failure. METHODS: Lung tissue from the foetuses of pregnant green fluorescent protein-C57BL/6 mice at 13.5 days of gestation was injected into the left lungs of recipient mice. Severe lung injury was induced by paraquat, and we analysed the survival rate and pathohistological findings after 1 month. RESULTS: The survival rate of the therapy group was 39%, which was significantly higher than the vehicle group at 5.9% (P = 0.034). Immunochemical staining showed that positive cytoplasmic stained cells with anti-interleukin-10 antibody were identified in the gland-like structure of embryonic day 13.5 foetal lung. At 4 weeks after orthotopic implantation, haematoxylin and eosin staining showed reduced lung inflammatory cells, reduced lung oedema and increased active cell proliferation of foetal lung cells. Lung injury score showed that the airway septal thickening revealed statistically significant differences between vehicle and foetal lung therapy (P < 0.001). CONCLUSIONS: Immature foetal lungs improved the survival rate of mice with paraquat-induced severe lung injury, establishing the need for systematic follow-up studies. The anti-inflammatory cytokine in the tissue from embryonic day 13.5 foetal lung might suppress severe lung injury.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Toyofumi F.", "last_name": "Chen-Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Date", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Takebe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/ejcts/ezaa091" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32259837" } }, "mesh": [ { "descriptor": "Acute Lung Injury", "descriptor_ui": "D055371", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fetus", "descriptor_ui": "D005333", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infant, Newborn", "descriptor_ui": "D007231", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Lung Injury", "descriptor_ui": "D055370", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Paraquat", "descriptor_ui": "D010269", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Sep 1", "date_precision": "day", "issue": "3", "normalized_date": "2020-09-01", "pages": "638-645", "proceedings_title": null, "publisher": "", "title": "European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery", "volume": "58", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Orthotopic foetal lung tissue direct injection into lung showed a preventive effect against paraquat-induced acute lung injury in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Us3 proteins of herpes simplex virus 1 (HSV-1) and HSV-2 are multifunctional serine-threonine protein kinases. Here, we identified an HSV-2 tegument protein, UL7, as a novel physiological substrate of HSV-2 Us3. Mutations in HSV-2 UL7, which precluded Us3 phosphorylation of the viral protein, significantly reduced mortality, viral replication in the vagina, and development of vaginal disease in mice following vaginal infection. These results indicated that Us3 phosphorylation of UL7 in HSV-2 was required for efficient viral replication and pathogenicity in vivo Of note, this phosphorylation was conserved in UL7 of chimpanzee herpesvirus (ChHV), which phylogenetically forms a monophyletic group with HSV-2 and the resurrected last common ancestral UL7 for HSV-2 and ChHV. In contrast, the phosphorylation was not conserved in UL7s of HSV-1, which belongs to a sister clade of the monophyletic group, the resurrected last common ancestor for HSV-1, HSV-2, and ChHV, and other members of the genus Simplexvirus that are phylogenetically close to these viruses. Thus, evolution of Us3 phosphorylation of UL7 coincided with the phylogeny of simplex viruses. Furthermore, artificially induced Us3 phosphorylation of UL7 in HSV-1, in contrast to phosphorylation in HSV-2, had no effect on viral replication and pathogenicity in mice. Our results suggest that HSV-2 and ChHV have acquired and maintained Us3 phosphoregulation of UL7 during their evolution because the phosphoregulation had an impact on viral fitness in vivo, whereas most other simplex viruses have not because the phosphorylation was not necessary for efficient fitness of the viruses in vivo IMPORTANCE It has been hypothesized that the evolution of protein phosphoregulation drives phenotypic diversity across species of organisms, which impacts fitness during their evolution. However, there is a lack of information regarding linkage between the evolution of viral phosphoregulation and the phylogeny of virus species. In this study, we clarified the novel HSV-2 Us3 phosphoregulation of UL7 in infected cells, which is important for viral replication and pathogenicity in vivo We also showed that the evolution of Us3 phosphoregulation of UL7 was linked to the phylogeny of viruses that are phylogenetically close to HSV-2 and to the phosphorylation requirements for the efficient in vivo viral fitness of HSV-2 and HSV-1, which are representative of viruses that have and have not evolved phosphoregulation, respectively. This study reports the first evidence showing that evolution of viral phosphoregulation coincides with phylogeny of virus species and supports the hypothesis regarding the evolution of viral phosphoregulation during viral evolution.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Misato", "last_name": "Shibazaki", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Suganami", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01055-20" }, "pmcid": { "normalized": "PMC7459551" }, "pmid": { "normalized": "32611749" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Viral", "descriptor_ui": "D015967", "major_topic": true }, { "descriptor": "Genetic Fitness", "descriptor_ui": "D056084", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Herpes Genitalis", "descriptor_ui": "D006558", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Herpesvirus 2, Human", "descriptor_ui": "D018258", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Sequence Alignment", "descriptor_ui": "D016415", "major_topic": false }, { "descriptor": "Sequence Homology, Amino Acid", "descriptor_ui": "D017386", "major_topic": false }, { "descriptor": "Vagina", "descriptor_ui": "D014621", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Matrix Proteins", "descriptor_ui": "D014763", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Viral Structural Proteins", "descriptor_ui": "D015678", "major_topic": false }, { "descriptor": "Virulence", "descriptor_ui": "D014774", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Aug 31", "date_precision": "day", "issue": "18", "normalized_date": "2020-08-31", "pages": "e01055-20", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "94", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Phosphoregulation of a Conserved Herpesvirus Tegument Protein by a Virally Encoded Protein Kinase in Viral Pathogenicity and Potential Linkage between Its Evolution and Viral Phylogeny.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neuronal synapses undergo structural and functional changes throughout life, which are essential for nervous system physiology. However, these changes may also perturb the excitatory-inhibitory neurotransmission balance and trigger neuropsychiatric and neurological disorders. Molecular tools to restore this balance are highly desirable. Here, we designed and characterized CPTX, a synthetic synaptic organizer combining structural elements from cerebellin-1 and neuronal pentraxin-1. CPTX can interact with presynaptic neurexins and postsynaptic AMPA-type ionotropic glutamate receptors and induced the formation of excitatory synapses both in vitro and in vivo. CPTX restored synaptic functions, motor coordination, spatial and contextual memories, and locomotion in mouse models for cerebellar ataxia, Alzheimer's disease, and spinal cord injury, respectively. Thus, CPTX represents a prototype for structure-guided biologics that can efficiently repair or remodel neuronal circuits.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kunimichi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Jonathan", "last_name": "Elegheert", "name": null }, { "creator_type": "author", "first_name": "Inseon", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Sasakura", "name": null }, { "creator_type": "author", "first_name": "Oleg", "last_name": "Senkov", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Kakegawa", "name": null }, { "creator_type": "author", "first_name": "Amber J.", "last_name": "Clayton", "name": null }, { "creator_type": "author", "first_name": "Veronica T.", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Maura", "last_name": "Ferrer-Ferrer", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Rahul", "last_name": "Kaushik", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Ikeno", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Morioka", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Otsuka", "name": null }, { "creator_type": "author", "first_name": "Stoyan", "last_name": "Stoyanov", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Dityatev", "name": null }, { "creator_type": "author", "first_name": "A. Radu", "last_name": "Aricescu", "name": null }, { "creator_type": "author", "first_name": "Michisuke", "last_name": "Yuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.abb4853" }, "pmcid": { "normalized": "PMC7116145" }, "pmid": { "normalized": "32855309" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "C-Reactive Protein", "descriptor_ui": "D002097", "major_topic": false }, { "descriptor": "Cerebellar Ataxia", "descriptor_ui": "D002524", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Mutant Strains", "descriptor_ui": "D008817", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Pentraxins", "descriptor_ui": "D000099153", "major_topic": false }, { "descriptor": "Protein Domains", "descriptor_ui": "D000072417", "major_topic": false }, { "descriptor": "Protein Precursors", "descriptor_ui": "D011498", "major_topic": false }, { "descriptor": "Receptors, AMPA", "descriptor_ui": "D018091", "major_topic": false }, { "descriptor": "Receptors, Glutamate", "descriptor_ui": "D017470", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Spine", "descriptor_ui": "D013131", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Aug 28", "date_precision": "day", "issue": "6507", "normalized_date": "2020-08-28", "pages": "eabb4853", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "369", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "A synthetic synaptic organizer protein restores glutamatergic neuronal circuits.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The occurrence of dreaming during rapid eye movement (REM) sleep prompts interest in the role of REM sleep in hippocampal-dependent episodic memory. Within the mammalian hippocampus, the dentate gyrus (DG) has the unique characteristic of exhibiting neurogenesis persisting into adulthood. Despite their small numbers and sparse activity, adult-born neurons (ABNs) in the DG play critical roles in memory; however, their memory function during sleep is unknown. Here, we investigate whether young ABN activity contributes to memory consolidation during sleep using Ca(2+) imaging in freely moving mice. We found that contextual fear learning recruits a population of young ABNs that are reactivated during subsequent REM sleep against a backdrop of overall reduced ABN activity. Optogenetic silencing of this sparse ABN activity during REM sleep alters the structural remodeling of spines on ABN dendrites and impairs memory consolidation. These findings provide a causal link between ABN activity during REM sleep and memory consolidation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "contributor", "first_name": "Deependra", "last_name": "Kumar", "name": null }, { "creator_type": "contributor", "first_name": "Iyo", "last_name": "Koyanagi", "name": null }, { "creator_type": "contributor", "first_name": "Alvaro", "last_name": "Carrier-Ruiz", "name": null }, { "creator_type": "contributor", "first_name": "Pablo", "last_name": "Vergara", "name": null }, { "creator_type": "contributor", "first_name": "Sakthivel", "last_name": "Srinivasan", "name": null }, { "creator_type": "contributor", "first_name": "Yuki", "last_name": "Sugaya", "name": null }, { "creator_type": "contributor", "first_name": "Masatoshi", "last_name": "Kasuya", "name": null }, { "creator_type": "contributor", "first_name": "Tzong-Shiue", "last_name": "Yu", "name": null }, { "creator_type": "contributor", "first_name": "Kaspar E.", "last_name": "Vogt", "name": null }, { "creator_type": "contributor", "first_name": "Masafumi", "last_name": "Muratani", "name": null }, { "creator_type": "contributor", "first_name": "Takaaki", "last_name": "Ohnishi", "name": null }, { "creator_type": "contributor", "first_name": "Sima", "last_name": "Singh", "name": null }, { "creator_type": "contributor", "first_name": "Catia M.", "last_name": "Teixeira", "name": null }, { "creator_type": "contributor", "first_name": "Yoan", "last_name": "Cherasse", "name": null }, { "creator_type": "contributor", "first_name": "Toshie", "last_name": "Naoi", "name": null }, { "creator_type": "contributor", "first_name": "Szu-Han", "last_name": "Wang", "name": null }, { "creator_type": "contributor", "first_name": "Pimpimon", "last_name": "Nondhalee", "name": null }, { "creator_type": "contributor", "first_name": "Boran A. H.", "last_name": "Osman", "name": null }, { "creator_type": "contributor", "first_name": "Naoko", "last_name": "Kaneko", "name": null }, { "creator_type": "contributor", "first_name": "Kazunobu", "last_name": "Sawamoto", "name": null }, { "creator_type": "contributor", "first_name": "Steven G.", "last_name": "Kernie", "name": null }, { "creator_type": "contributor", "first_name": "Takeshi", "last_name": "Sakurai", "name": null }, { "creator_type": "contributor", "first_name": "Thomas J.", "last_name": "McHugh", "name": null }, { "creator_type": "contributor", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "contributor", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "contributor", "first_name": "Masanori", "last_name": "Sakaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2020.05.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Aug 5", "date_precision": "day", "issue": "", "normalized_date": "2020-08-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "", "volume": "107", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Sparse Activity of Hippocampal Adult-Born Neurons during REM Sleep Is Necessary for Memory Consolidation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cells inside the body are subjected to various mechanical stress, such as stretch or compression provided by surrounding cells, shear stresses by blood or lymph flows, and normal stresses by luminal liquids. Force loading to the biological tissues is a fundamental method to better understand cellular responses to such mechanical stimuli. There have been many studies on compression or stretch experiments that target culture cells attached to a flexible extensible material including polydimethylsiloxane (PDMS); however, the know-how of those targeting to tissues is still incomplete. Here we present the protocol for mechanical tissue compression and image-based analysis by focusing on developing murine epididymis as an example. We show a series of steps including tissue dissection from murine embryos, hydrogel-based compression method using a manual device, and non-destructive volumetric tissue imaging. This protocol is useful for quantifying and exploring the biological mechanoresponse system at tissue level.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.21769/bioprotoc.3694" }, "pmcid": { "normalized": "PMC7842499" }, "pmid": { "normalized": "33659362" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Aug 5", "date_precision": "day", "issue": "15", "normalized_date": "2020-08-05", "pages": "e3694", "proceedings_title": null, "publisher": "", "title": "Bio-protocol", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Mechanical Tissue Compression and Whole-mount Imaging at Single CellResolution for Developing Murine Epididymal Tubules.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Influenza virus M2 and PB1-F2 proteins have been proposed to activate the Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome in macrophages by altering intracellular ionic balance or mitochondrial reactive oxygen species (ROS) production. However, the precise mechanism by which these viral proteins trigger the NLRP3 inflammasome activation remains unclear. Here we show that influenza virus stimulates oxidized DNA release from macrophages. Ion channel activity of the M2 protein or mitochondrial localization of the PB1-F2 protein was required for oxidized DNA release. The oxidized DNA enhanced influenza virus-induced IL-1beta secretion, whereas inhibition of mitochondrial ROS production by antioxidant Mito-TEMPO decreased the virus-induced IL-1beta secretion. In addition, we show that influenza virus stimulates IL-1beta secretion from macrophages in an AIM2-dependent manner. These results provide a missing link between influenza viral proteins and the NLRP3 inflammasome activation and reveal the importance of influenza virus-induced oxidized DNA in inflammasomes activation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Miyu", "last_name": "Moriyama", "name": null }, { "creator_type": "author", "first_name": "Minami", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Koshiba", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ichinohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2020.101270" }, "pmcid": { "normalized": "PMC7293844" }, "pmid": { "normalized": "32592999" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Jul 24", "date_precision": "day", "issue": "7", "normalized_date": "2020-07-24", "pages": "101270", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "23", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Influenza Virus-Induced Oxidized DNA Activates Inflammasomes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This work describes a colorimetric signaling approach for competitive lateral flow immunoassays (LFIAs) enabling sensitive and semiquantitative direct visual result readout in the form of \"text\", demonstrated on the example of 8-hydroxy-2'-deoxyguanosine (8-OHdG) detection. The distinctive feature of the developed text-displaying LFIA (TD-LFIA) is the test zone system consisting of a combination of two types of inkjet-deposited capture molecules referred to as \"mask antigen\" and \"text antibody\", allowing for sensitive turn-on signaling as opposed to the inverse response of conventional competitive LFIAs. The user operation is limited to sample application, followed by direct reading of assay results written in text after approximately 10 min. TD-LFIAs enabled the visual detection of 8-OHdG at concentrations down to 3 ng/mL, which is a 2-3 orders of magnitude lower visual detection limit than that achieved with the corresponding conventional design and is comparable to the existing LFIAs relying on external signal readout equipment. Highly reproducible observer-independent assay performance was confirmed, and the result interpretation is not influenced by sample color and readout timing. Making use of customizable threshold settings for text appearance, a device for semiquantitative assays was developed and successfully applied to the detection of 8-OHdG at four concentration levels (trace, low, medium, and high) in 54 human urine samples within the clinically relevant concentration range. The sensitive and intuitive signaling method of the developed system offers great potential for an alternative competitive LFIA platform suitable for real-world point-of-care testing applications.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazushi", "last_name": "Misawa", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acssensors.0c00637" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32575982" } }, "mesh": [ { "descriptor": "Colorimetry", "descriptor_ui": "D003124", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoassay", "descriptor_ui": "D007118", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jul 24", "date_precision": "day", "issue": "7", "normalized_date": "2020-07-24", "pages": "2076-2085", "proceedings_title": null, "publisher": "", "title": "ACS sensors", "volume": "5", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Text-Displaying Semiquantitative Competitive Lateral Flow Immunoassay Relying on Inkjet-Printed Patterns.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Regulatory T cells (Tregs) play essential roles in maintaining immunological self-tolerance and preventing autoimmunity. The adoptive transfer of antigen-specific Tregs has been expected to be a potent therapeutic method for autoimmune diseases, severe allergy, and rejection in organ transplantation. However, effective Treg therapy has not yet been established because of the difficulty in preparing a limited number of antigen-specific Tregs. Chimeric antigen receptor (CAR) T cells have been shown to be a powerful therapeutic method for treating B cell lymphomas, but application of CAR to Treg-mediated therapy has not yet been established. Here, we generated CD19-targeted CAR (CD19-CAR) Tregs from human PBMCs (hPBMCs) and optimized the fraction of the Treg source as CD4+CD25+CD127loCD45RA+CD45RO-. CD19-CAR Tregs could be expanded in vitro while maintaining Treg properties, including high expression of the latent form of TGF-beta. CD19-CAR Tregs suppressed IgG antibody production and differentiation of B cells via a TGF-beta-dependent mechanism. Unlike conventional CD19-CAR CD8+ T cells, CD19-CAR Tregs suppressed antibody production in immunodeficient mice that were reconstituted with hPBMCs, reducing the risk of graft-versus-host disease. Therefore, the adoptive transfer of CD19-CAR Tregs may provide a novel therapeutic method for treating autoantibody-mediated autoimmune diseases.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Imura", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci.insight.136185" }, "pmcid": { "normalized": "PMC7453900" }, "pmid": { "normalized": "32525846" } }, "mesh": [ { "descriptor": "Adoptive Transfer", "descriptor_ui": "D019264", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, CD19", "descriptor_ui": "D018941", "major_topic": false }, { "descriptor": "Autoimmunity", "descriptor_ui": "D015551", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Epitopes", "descriptor_ui": "D000939", "major_topic": false }, { "descriptor": "Graft vs Host Disease", "descriptor_ui": "D006086", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Tolerance", "descriptor_ui": "D007108", "major_topic": false }, { "descriptor": "Immunoglobulin G", "descriptor_ui": "D007074", "major_topic": false }, { "descriptor": "Lymphoma, B-Cell", "descriptor_ui": "D016393", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Receptors, Chimeric Antigen", "descriptor_ui": "D000076962", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jul 23", "date_precision": "day", "issue": "14", "normalized_date": "2020-07-23", "pages": "136185", "proceedings_title": null, "publisher": "", "title": "JCI insight", "volume": "5", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "CD19-targeted CAR regulatory T cells suppress B cell pathology without GvHD.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pathogenic bacteria of the genus Bartonella can induce vasoproliferative lesions during infection. The underlying mechanisms are unclear, but involve secretion of an unidentified mitogenic factor. Here, we use functional transposon-mutant screening in Bartonella henselae to identify such factor as a pro-angiogenic autotransporter, called BafA. The passenger domain of BafA induces cell proliferation, tube formation and sprouting of microvessels, and drives angiogenesis in mice. BafA interacts with vascular endothelial growth factor (VEGF) receptor-2 and activates the downstream signaling pathway, suggesting that BafA functions as a VEGF analog. A BafA homolog from a related pathogen, Bartonella quintana, is also functional. Our work unveils the mechanistic basis of vasoproliferative lesions observed in bartonellosis, and we propose BafA as a key pathogenic factor contributing to bacterial spread and host adaptation.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kentaro", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Naoaki", "last_name": "Shinzawa", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Hisateru", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Kameyama", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kurahashi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Horiguchi", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Doi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-020-17391-2" }, "pmcid": { "normalized": "PMC7366657" }, "pmid": { "normalized": "32678094" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacterial Outer Membrane Proteins", "descriptor_ui": "D001425", "major_topic": false }, { "descriptor": "Bartonella", "descriptor_ui": "D001473", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Human Umbilical Vein Endothelial Cells", "descriptor_ui": "D061307", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Protein Domains", "descriptor_ui": "D000072417", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Type V Secretion Systems", "descriptor_ui": "D000069320", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor Receptor-2", "descriptor_ui": "D040301", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factors", "descriptor_ui": "D042442", "major_topic": false }, { "descriptor": "Virulence Factors", "descriptor_ui": "D037521", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jul 16", "date_precision": "day", "issue": "1", "normalized_date": "2020-07-16", "pages": "3571", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "The Bartonella autotransporter BafA activates the host VEGF pathway to drive angiogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Zinc finger protein St18 was initially reported as candidate tumor suppressor gene, and also suggested that fibroblast St18 positively regulates NF-kappaB activation. Despite the pleiotropic functions of St18, little is known about its roles in macrophages. Here, we report that myeloid St18 is a potent inhibitor of VEGF-A. Mice lacking St18 in myeloid lineages exhibit increased retinal vasculature with enhanced serum VEGF-A concentrations. Despite the normal activation of NF-kappaB target genes, these mice are highly susceptible to LPS-induced shock, polymicrobial sepsis, and experimental colitis, accompanied by enhanced vascular and intestinal leakage. Pharmacological inhibition of VEGF signaling rescued the high mortality rate of myeloid-specific St18-deficient mice in response to inflammation. Mechanistically, St18 directly binds to Sp1 and attenuates its activity, leading to the suppression of Sp1 target gene VEGF-A. Using mouse genetic and pharmacological models, we reveal myeloid St18 as a critical septic death protector.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kenta", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Takemura", "name": null }, { "creator_type": "author", "first_name": "Erika", "last_name": "Sugisawa", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Mohammed Mansour Abbas", "last_name": "Eid", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Mikael M.", "last_name": "Martino", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Shizuo", "last_name": "Akira", "name": null }, { "creator_type": "author", "first_name": "Alexis", "last_name": "Vandenbon", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Kumagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2020.107906" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32668247" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cecum", "descriptor_ui": "D002432", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Colitis", "descriptor_ui": "D003092", "major_topic": false }, { "descriptor": "Dextran Sulfate", "descriptor_ui": "D016264", "major_topic": false }, { "descriptor": "Disease Susceptibility", "descriptor_ui": "D004198", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Ligation", "descriptor_ui": "D008026", "major_topic": false }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Myeloid Cells", "descriptor_ui": "D022423", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Punctures", "descriptor_ui": "D011677", "major_topic": false }, { "descriptor": "RAW 264.7 Cells", "descriptor_ui": "D000067996", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Sepsis", "descriptor_ui": "D018805", "major_topic": false }, { "descriptor": "Shock, Septic", "descriptor_ui": "D012772", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sp1 Transcription Factor", "descriptor_ui": "D016329", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor A", "descriptor_ui": "D042461", "major_topic": false }, { "descriptor": "Zinc Fingers", "descriptor_ui": "D016335", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Jul 14", "date_precision": "day", "issue": "2", "normalized_date": "2020-07-14", "pages": "107906", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "32", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Zinc Finger Protein St18 Protects against Septic Death by Inhibiting VEGF-A from Macrophages.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "For eradication of HIV-1 infection, it is important to elucidate the detailed features and heterogeneity of HIV-1-infected cells in vivo. To reveal multiple characteristics of HIV-1-producing cells in vivo, we use a hematopoietic-stem-cell-transplanted humanized mouse model infected with GFP-encoding replication-competent HIV-1. We perform multiomics experiments using recently developed technology to identify the features of HIV-1-infected cells. Genome-wide HIV-1 integration-site analysis reveals that productive HIV-1 infection tends to occur in cells with viral integration into transcriptionally active genomic regions. Bulk transcriptome analysis reveals that a high level of viral mRNA is transcribed in HIV-1-infected cells. Moreover, single-cell transcriptome analysis shows the heterogeneity of HIV-1-infected cells, including CXCL13(high) cells and a subpopulation with low expression of interferon-stimulated genes, which can contribute to efficient viral spread in vivo. Our findings describe multiple characteristics of HIV-1-producing cells in vivo, which could provide clues for the development of an HIV-1 cure.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Aso", "name": null }, { "creator_type": "author", "first_name": "Shumpei", "last_name": "Nagaoka", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Saiful", "last_name": "Islam", "name": null }, { "creator_type": "author", "first_name": "Benjy Jek Yang", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Nakaoka", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ashizaki", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yorifumi", "last_name": "Satou", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2020.107887" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32668246" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HIV Infections", "descriptor_ui": "D015658", "major_topic": false }, { "descriptor": "HIV-1", "descriptor_ui": "D015497", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jul 14", "date_precision": "day", "issue": "2", "normalized_date": "2020-07-14", "pages": "107887", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "32", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Multiomics Investigation Revealing the Characteristics of HIV-1-Infected Cells In Vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Adenosine 5' triphosphate (ATP) is a ubiquitous extracellular signaling messenger. Here, we describe a method for in-vivo imaging of extracellular ATP with high spatiotemporal resolution. We prepared a comprehensive set of cysteine-substitution mutants of ATP-binding protein, Bacillus FoF1-ATP synthase epsilon subunit, labeled with small-molecule fluorophores at the introduced cysteine residue. Screening revealed that the Cy3-labeled glutamine-105 mutant (Q105C-Cy3; designated ATPOS) shows a large fluorescence change in the presence of ATP, with submicromolar affinity, pH-independence, and high selectivity for ATP over ATP metabolites and other nucleotides. To enable in-vivo validation, we introduced BoNT/C-Hc for binding to neuronal plasma membrane and Alexa Fluor 488 for ratiometric measurement. The resulting ATPOS complex binds to neurons in cerebral cortex of living mice, and clearly visualized a concentrically propagating wave of extracellular ATP release in response to electrical stimulation. ATPOS should be useful to probe the extracellular ATP dynamics of diverse biological processes in vivo.", "classifications": [ { "id": "19H05414", "label": "19H05414", "researcher": "Kenjiro Hanaoka", "type": "grant" }, { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Nami", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Takikawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Kaname", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Asanuma", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Shodai", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Namiki", "name": null }, { "creator_type": "author", "first_name": "Masamitsu", "last_name": "Iino", "name": null }, { "creator_type": "author", "first_name": "Kenzo", "last_name": "Hirose", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.57544" }, "pmcid": { "normalized": "PMC7398694" }, "pmid": { "normalized": "32648544" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Functional Neuroimaging", "descriptor_ui": "D059907", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jul 10", "date_precision": "day", "issue": "", "normalized_date": "2020-07-10", "pages": "e57544", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "9", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Real-time in vivo imaging of extracellular ATP in the brain with a hybrid-type fluorescent sensor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Two types of nuclear estrogen receptors, ERalpha and ERbeta, have been shown to be differentially involved in the regulation of various types of behaviors. Due to a lack of tools for identifying ERbeta expression, detailed anatomical distribution and neurochemical characteristics of ERbeta expressing cells and cellular co-expression with ERalpha remain unclear. We have generated transgenic mice ERbeta-RFP(tg), in which RFP was inserted downstream of ERbeta BAC promotor. We verified RFP signals as ERbeta by confirming: (1) high ERbeta mRNA levels in RFP-expressing cells collected by fluorescence-activated cell sorting; and (2) co-localization of ERbeta mRNA and RFP proteins in the paraventricular nucleus (PVN). Strong ERbeta-RFP signals were found in the PVN, medial preoptic area (MPOA), bed nucleus of the stria terminalis, medial amygdala (MeA), and dorsal raphe nucleus (DRN). In the MPOA and MeA, three types of cell populations were identified; those expressing both ERalpha and ERbeta, and those expressing exclusively either ERalpha or ERbeta. The majority of PVN and DRN cells expressed only ERbeta-RFP. Further, ERbeta-RFP positive cells co-expressed oxytocin in the PVN, and tryptophan hydroxylase 2 and progesterone receptors in the DRN. In the MeA, some ERbeta-RFP positive cells co-expressed oxytocin receptors. These findings collectively suggest that ERbeta-RFP(tg) mice can be a powerful tool for future studies on ERbeta function in the estrogenic regulation of social behaviors.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shoko", "last_name": "Sagoshi", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Maejima", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takenawa", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Otubo", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Takanami", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Tsukahara", "name": null }, { "creator_type": "author", "first_name": "Sonoko", "last_name": "Ogawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuroscience.2020.04.047" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32387645" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Estrogen Receptor alpha", "descriptor_ui": "D047628", "major_topic": true }, { "descriptor": "Estrogen Receptor beta", "descriptor_ui": "D047629", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Paraventricular Hypothalamic Nucleus", "descriptor_ui": "D010286", "major_topic": false }, { "descriptor": "Receptors, Estrogen", "descriptor_ui": "D011960", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jul 1", "date_precision": "day", "issue": "", "normalized_date": "2020-07-01", "pages": "182-197", "proceedings_title": null, "publisher": "", "title": "Neuroscience", "volume": "438", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Detection and Characterization of Estrogen Receptor Beta Expression in the Brain with Newly Developed Transgenic Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Lymphocytes circulate between peripheral lymphoid tissues via blood and lymphatic systems, and chemokine-induced migration is important in trafficking lymphocytes to distant sites. The small GTPase Rap1 is important in mediating lymphocyte motility, and Rap1-GEFs are involved in chemokine-mediated Rap1 activation. Here, we describe the roles and mechanisms of Rap1-GEFs in lymphocyte trafficking. RESULTS: In this study, we show that RA-GEF-1 and 2 (also known as Rapgef2 and 6) are key guanine nucleotide exchange factors (GEF) for Rap1 in lymphocyte trafficking. Mice harboring T cell-specific knockouts of Rapgef2/6 demonstrate defective homing and egress of T cells. Sphingosine-1-phosphate (S1P) as well as chemokines activates Rap1 in a RA-GEF-1/2-dependent manner, and their deficiency in T cells impairs Mst1 phosphorylation, cell polarization, and chemotaxis toward S1P gradient. On the other hand, B cell-specific knockouts of Rapgef2/6 impair chemokine-dependent retention of B cells in the bone marrow and passively facilitate egress. Phospholipase D2-dependent production of phosphatidic acid by these chemotactic factors determines spatial distribution of Rap1-GTP subsequent to membrane localization of RA-GEFs and induces the development of front membrane. On the other hand, basal de-phosphorylation of RA-GEFs is necessary for chemotactic factor-dependent increase in GEF activity for Rap1. CONCLUSIONS: We demonstrate here that subcellular distribution and activation of RA-GEFs are key factors for a directional movement of lymphocytes and that phosphatidic acid is critical for membrane translocation of RA-GEFs with chemokine stimulation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Sayaka", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Guangwei", "last_name": "Du", "name": null }, { "creator_type": "author", "first_name": "Daniele", "last_name": "Guardavaccaro", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Koko", "last_name": "Katagiri", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12915-020-00809-0" }, "pmcid": { "normalized": "PMC7325102" }, "pmid": { "normalized": "32600317" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Guanine Nucleotide Exchange Factors", "descriptor_ui": "D020662", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphocytes", "descriptor_ui": "D008214", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phosphatidic Acids", "descriptor_ui": "D010712", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jun 29", "date_precision": "day", "issue": "1", "normalized_date": "2020-06-29", "pages": "75", "proceedings_title": null, "publisher": "", "title": "BMC biology", "volume": "18", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Phosphatidic acid-dependent localization and basal de-phosphorylation of RA-GEFs regulate lymphocyte trafficking.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Antibodies are important biomarkers in clinical diagnostics in addition to being increasingly used for therapeutic purposes. Although numerous methods for their detection and quantification exist, they predominantly require benchtop instruments operated by specialists. To enable the detection of antibodies at point-of-care (POC), the development of simple and rapid assay methods independent of laboratory equipment is of high relevance. In this study, we demonstrate microfluidic thread-based analytical devices (muTADs) as a new platform for antibody detection by means of bioluminescence resonance energy-transfer (BRET) switching sensor proteins. The devices consist of vertically assembled layers including a blood separation membrane and a plastic film with a sewn-in cotton thread, onto which the BRET sensor proteins together with the substrate furimazine have been predeposited. In contrast to intensity-based signaling, the BRET mechanism enables time-independent, ratiometric readout of bioluminescence signals with a digital camera in a darkroom or a smartphone camera with a 3D-printed lens adapter. The device design allows spatially separated deposition of multiple bioluminescent proteins on a single sewn thread, enabling quantification of multiple antibodies in 5 muL of whole blood within 5 min. The bioluminescence response is independent of the applied sample volume within the range of 5-15 muL. Therefore, muTADs in combination with BRET-based sensor proteins represent user-friendly analytical tools for POC quantification of antibodies without any laboratory equipment in a finger prick (5 muL) of whole blood.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Tomimuro", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Tenda", "name": null }, { "creator_type": "author", "first_name": "Yan", "last_name": "Ni", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Maarten", "last_name": "Merkx", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acssensors.0c00564" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32441095" } }, "mesh": [ { "descriptor": "Antibodies", "descriptor_ui": "D000906", "major_topic": true }, { "descriptor": "Lab-On-A-Chip Devices", "descriptor_ui": "D056656", "major_topic": true }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Point-of-Care Systems", "descriptor_ui": "D019095", "major_topic": false }, { "descriptor": "Smartphone", "descriptor_ui": "D000068997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jun 26", "date_precision": "day", "issue": "6", "normalized_date": "2020-06-26", "pages": "1786-1794", "proceedings_title": null, "publisher": "", "title": "ACS sensors", "volume": "5", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Thread-Based Bioluminescent Sensor for Detecting Multiple Antibodies in a Single Drop of Whole Blood.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Peripheral nerve injury induces functional and structural remodeling of neural circuits along the somatosensory pathways, forming the basis for somatotopic reorganization and ectopic sensations, such as referred phantom pain. However, the mechanisms underlying that remodeling remain largely unknown. Whisker sensory nerve injury drives functional remodeling in the somatosensory thalamus: the number of afferent inputs to each thalamic neuron increases from one to many. Here, we report that extrasynaptic gamma-aminobutyric acid-type A receptor (GABAAR)-mediated tonic inhibition is necessary for that remodeling. Extrasynaptic GABAAR currents were potentiated rapidly after nerve injury in advance of remodeling. Pharmacological activation of the thalamic extrasynaptic GABAARs in intact mice induced similar remodeling. Notably, conditional deletion of extrasynaptic GABAARs in the thalamus rescued both the injury-induced remodeling and the ectopic mechanical hypersensitivity. Together, our results reveal a molecular basis for injury-induced remodeling of neural circuits and may provide a new pharmacological target for referred phantom sensations after peripheral nerve injury.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Nagumo", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Ueta", "name": null }, { "creator_type": "author", "first_name": "Hisako", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Miyata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2020.107797" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32579924" } }, "mesh": [ { "descriptor": "Afferent Pathways", "descriptor_ui": "D000344", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nerve Tissue", "descriptor_ui": "D009417", "major_topic": false }, { "descriptor": "Neural Inhibition", "descriptor_ui": "D009433", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Protein Subunits", "descriptor_ui": "D021122", "major_topic": false }, { "descriptor": "Receptors, GABA-A", "descriptor_ui": "D011963", "major_topic": false }, { "descriptor": "Sensation", "descriptor_ui": "D012677", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Thalamus", "descriptor_ui": "D013788", "major_topic": false }, { "descriptor": "Ventral Thalamic Nuclei", "descriptor_ui": "D020651", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jun 23", "date_precision": "day", "issue": "12", "normalized_date": "2020-06-23", "pages": "107797", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "31", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Tonic GABAergic Inhibition Is Essential for Nerve Injury-Induced Afferent Remodeling in the Somatosensory Thalamus and Ectopic Sensations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The velvet belly lanternshark, Etmopterus spinax, uses counterillumination to disappear in the surrounding blue light of its marine environment. This shark displays hormonally controlled bioluminescence in which melatonin (MT) and prolactin (PRL) trigger light emission, while alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH) play an inhibitory role. The extraocular encephalopsin (Es-Opn3) was also hypothesized to act as a luminescence regulator. The majority of these compounds (MT, alpha-MSH, ACTH, opsin) are members of the rapid physiological colour change that regulates the pigment motion within chromatophores in metazoans. Interestingly, the lanternshark photophore comprises a specific iris-like structure (ILS), partially composed of melanophore-like cells, serving as a photophore shutter. Here, we investigated the role of (i) Es-Opn3 and (ii) actors involved in both MT and alpha-MSH/ACTH pathways on the shark bioluminescence and ILS cell pigment motions. Our results reveal the implication of Es-Opn3, MT, inositol triphosphate (IP3), intracellular calcium, calcium-dependent calmodulin and dynein in the ILS cell pigment aggregation. Conversely, our results highlighted the implication of the alpha-MSH/ACTH pathway, involving kinesin, in the dispersion of the ILS cell pigment. The lanternshark luminescence then appears to be controlled by the balanced bidirectional motion of ILS cell pigments within the photophore. This suggests a functional link between photoreception and photoemission in the photogenic tissue of lanternsharks and gives precious insights into the bioluminescence control of these organisms.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Laurent", "last_name": "Duchatelet", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sugihara", "name": null }, { "creator_type": "author", "first_name": "Jerome", "last_name": "Delroisse", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Rene", "last_name": "Rezsohazy", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null }, { "creator_type": "author", "first_name": "Jerome", "last_name": "Mallefet", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-67287-w" }, "pmcid": { "normalized": "PMC7311519" }, "pmid": { "normalized": "32576969" } }, "mesh": [ { "descriptor": "Adrenocorticotropic Hormone", "descriptor_ui": "D000324", "major_topic": false }, { "descriptor": "alpha-MSH", "descriptor_ui": "D000521", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Luminescence", "descriptor_ui": "D049449", "major_topic": false }, { "descriptor": "Melatonin", "descriptor_ui": "D008550", "major_topic": false }, { "descriptor": "Movement", "descriptor_ui": "D009068", "major_topic": false }, { "descriptor": "Opsins", "descriptor_ui": "D055355", "major_topic": false }, { "descriptor": "Photoreceptor Cells", "descriptor_ui": "D010786", "major_topic": false }, { "descriptor": "Pigmentation", "descriptor_ui": "D010858", "major_topic": false }, { "descriptor": "Prolactin", "descriptor_ui": "D011388", "major_topic": false }, { "descriptor": "Sharks", "descriptor_ui": "D012754", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jun 23", "date_precision": "day", "issue": "1", "normalized_date": "2020-06-23", "pages": "10195", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "From extraocular photoreception to pigment movement regulation: a new control mechanism of the lanternshark luminescence.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During collective migration of epithelial cells, the migration direction is aligned over a tissue-scale expanse. Although the collective cell migration is known to be directed by mechanical forces transmitted via cell-cell junctions, it remains elusive how the intercellular force transmission is coordinated with intracellular biochemical signaling to achieve collective movements. Here, we show that intercellular coupling of extracellular signal-regulated kinase (ERK)-mediated mechanochemical feedback yields long-distance transmission of guidance cues. Mechanical stretch activates ERK through epidermal growth factor receptor (EGFR) activation, and ERK activation triggers cell contraction. The contraction of the activated cell pulls neighboring cells, evoking another round of ERK activation and contraction in the neighbors. Furthermore, anisotropic contraction based on front-rear polarization guarantees unidirectional propagation of ERK activation, and in turn, the ERK activation waves direct multicellular alignment of the polarity, leading to long-range ordered migration. Our findings reveal that mechanical forces mediate intercellular signaling underlying sustained transmission of guidance cues for collective cell migration.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naoya", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Leone", "last_name": "Rossetti", "name": null }, { "creator_type": "author", "first_name": "Ariadna", "last_name": "Marin-Llaurado", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Xavier", "last_name": "Trepat", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2020.05.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32497487" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": true }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": true }, { "descriptor": "Mechanotransduction, Cellular", "descriptor_ui": "D040542", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Jun 22", "date_precision": "day", "issue": "6", "normalized_date": "2020-06-22", "pages": "646-660.e8", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "53", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "ERK-Mediated Mechanochemical Waves Direct Collective Cell Polarization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurodegenerative diseases are characterized by the accumulation of specific phosphorylated protein aggregates in the brain, such as hyperphosphorylated tau (hp-tau) in tauopathies and phosphorylated alpha-synuclein (p-alphaSyn) in alpha-synucleinopathies. The simultaneous accumulation of different proteins is a common event in many neurodegenerative diseases. We herein describe the detection of the phosphorylation and dimerization of alphaSyn and activation of GSK-3beta, a major kinase known to phosphorylate tau and alphaSyn, in the brains of rTg4510 mice that overexpress human P301L mutant tau. Immunohistochemistry showed p-alphaSyn aggregates in rTg4510 mice, which were suppressed by doxycycline-mediated decreases in mutant tau expression levels. A semi-quantitative analysis revealed a regional correlation between hp-tau and p-alphaSyn accumulation in rTg4510 mice. Furthermore, proteinase K-resistant alphaSyn aggregates were found in the region with excessive hp-tau accumulation in rTg4510 mice, and these aggregates were morphologically different from proteinase K-susceptible p-alphaSyn aggregates. Western blotting revealed decreases in p-alphaSyn monomers in TBS- and sarkosyl-soluble fractions and increases in ubiquitinated p-alphaSyn dimers in sarkosyl-soluble and insoluble fractions in rTg4510 mice. Furthermore, an activated form of GSK-3beta was immunohistochemically detected within cells containing both hp-tau and p-alphaSyn aggregates. A semi-quantitative analysis revealed that increased GSK-3beta activity strongly correlated with hp-tau and p-alphaSyn accumulation in rTg4510 mice. Collectively, the present results suggest that the overexpression of human P301L mutant tau promoted the phosphorylation and dimerization of endogenous alphaSyn by activating GSK-3beta in rTg4510 mice. This synergic effect between tau, alphaSyn, and GSK-3beta may be involved in the pathophysiology of several neurodegenerative diseases that show the accumulation of both tau and alphaSyn.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Takaichi", "name": null }, { "creator_type": "author", "first_name": "James K.", "last_name": "Chambers", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Ano", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Uchida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s40478-020-00969-8" }, "pmcid": { "normalized": "PMC7304163" }, "pmid": { "normalized": "32560668" } }, "mesh": [ { "descriptor": "alpha-Synuclein", "descriptor_ui": "D051844", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Glycogen Synthase Kinase 3 beta", "descriptor_ui": "D000071679", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Aggregation, Pathological", "descriptor_ui": "D066263", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jun 19", "date_precision": "day", "issue": "1", "normalized_date": "2020-06-19", "pages": "86", "proceedings_title": null, "publisher": "", "title": "Acta neuropathologica communications", "volume": "8", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Phosphorylation and oligomerization of alpha-synuclein associated with GSK-3beta activation in the rTg4510 mouse model of tauopathy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In lower vertebrates, brain photoreceptor cells express vertebrate-specific non-visual opsins. We previously revealed that a pineal-related organ-specific opsin, parapinopsin, is UV-sensitive and allows pineal wavelength discrimination in lampreys and teleost. The Australian pouched lamprey was recently reported as having two parapinopsin-related genes. We demonstrate that a parapinopsin-like opsin from the Japanese river lamprey exhibits different molecular properties and distribution than parapinopsin. This opsin activates Gi-type G protein in a mammalian cell culture assay in a light-dependent manner. Heterologous action spectroscopy revealed that the opsin forms a violet to blue-sensitive pigment. Interestingly, the opsin is co-localised with green-sensitive P-opsin in the cells of the M5 nucleus of Schober (M5NS) in the mesencephalon of the river and brook lamprey. Some opsins-containing cells of the river lamprey have cilia and others an axon projecting to the retina. The opsins of the brook lamprey are co-localised in the cilia of centrifugal neurons projecting to the retina, suggesting that cells expressing the parapinopsin-like opsin and P-opsin are sensitive to violet to green light. Moreover, we found neural connections between M5NS cells expressing the opsins and the retina. These findings suggest that the retinal activity might be modulated by brain photoreception.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Emi", "last_name": "Kawano-Yamashita", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Tomoka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sugihara", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Tamotsu", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-66679-2" }, "pmcid": { "normalized": "PMC7295746" }, "pmid": { "normalized": "32541666" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "Fish Proteins", "descriptor_ui": "D029941", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "GTP-Binding Protein alpha Subunits", "descriptor_ui": "D044385", "major_topic": false }, { "descriptor": "Lampreys", "descriptor_ui": "D007798", "major_topic": false }, { "descriptor": "Mesencephalon", "descriptor_ui": "D008636", "major_topic": false }, { "descriptor": "Opsins", "descriptor_ui": "D055355", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Tissue Distribution", "descriptor_ui": "D014018", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jun 15", "date_precision": "day", "issue": "1", "normalized_date": "2020-06-15", "pages": "9669", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "The non-visual opsins expressed in deep brain neurons projecting to the retina in lampreys.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Water hardness (WH) is a useful parameter for testing household water, such as drinking, cooking, and washing water. Many countries around the world use pipeline water in their houses, but there is a need to monitor the WH because hard water has a negative impact on appliances. Currently, WH is often measured using chemical dye-based WH indicators, and these techniques require expensive equipment, and trained personnel. Therefore, a low-cost and simple measurement method has been desired. Here, we report LOTUS-W, which consists of a luciferase, Nanoluc, a yellow fluorescent protein Venus, and a Ca(2+)/Mg(2+) detection domain of human centrin 3. The binding of Ca(2+)/Mg(2+) to this indicator changes the conformation of human centrin 3, and induces bioluminescence resonance energy transfer (BRET) from Nanoluc to Venus, which changes its emission spectrum about 140%. The dissociation constants of LOTUS-W for Ca(2+)/Mg(2+) are approximately several mM, making it suitable for measuring WH in the household water. With this indicator in combination with a smartphone, we have demonstrated that it is possible to evaluate WH easily and quickly. This novel indicator has the potential to be used for measuring not only household water but also water used in the food industry, etc.", "classifications": [ { "id": "18H05410", "label": "18H05410", "researcher": "Takeharu Nagai", "type": "grant" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Md Nadim", "last_name": "Hossain", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/s20113164" }, "pmcid": { "normalized": "PMC7308811" }, "pmid": { "normalized": "32498467" } }, "mesh": [ { "descriptor": "Calcium-Binding Proteins", "descriptor_ui": "D002135", "major_topic": false }, { "descriptor": "Drinking Water", "descriptor_ui": "D060766", "major_topic": false }, { "descriptor": "Energy Transfer", "descriptor_ui": "D004735", "major_topic": false }, { "descriptor": "Hardness", "descriptor_ui": "D006244", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": true }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jun 2", "date_precision": "day", "issue": "11", "normalized_date": "2020-06-02", "pages": "E3164", "proceedings_title": null, "publisher": "", "title": "Sensors (Basel, Switzerland)", "volume": "20", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Bioluminescent Ratiometric Indicator for Analysis of Water Hardness in Household Water.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Currently, there are no treatments for Alport syndrome, which is the second most commonly inherited kidney disease. Here we report the development of an exon-skipping therapy using an antisense-oligonucleotide (ASO) for severe male X-linked Alport syndrome (XLAS). We targeted truncating variants in exon 21 of the COL4A5 gene and conducted a type IV collagen alpha3/alpha4/alpha5 chain triple helix formation assay, and in vitro and in vivo treatment efficacy evaluation. We show that exon skipping enabled trimer formation, leading to remarkable clinical and pathological improvements including expression of the alpha5 chain on glomerular and the tubular basement membrane. In addition, the survival period was clearly prolonged in the ASO treated mice group. This data suggests that exon skipping may represent a promising therapeutic approach for treating severe male XLAS cases.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Terakawa", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Takaoka", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Omachi", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null }, { "creator_type": "author", "first_name": "Kiyosumi", "last_name": "Takaishi", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Shoji", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Onishi", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kanazawa", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Tomono", "name": null }, { "creator_type": "author", "first_name": "Aki", "last_name": "Sugano", "name": null }, { "creator_type": "author", "first_name": "Akemi", "last_name": "Shono", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Minamikawa", "name": null }, { "creator_type": "author", "first_name": "China", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Nana", "last_name": "Sakakibara", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Ishiko", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Aoto", "name": null }, { "creator_type": "author", "first_name": "Misato", "last_name": "Kamura", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Harita", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Shoichiro", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Morisada", "name": null }, { "creator_type": "author", "first_name": "Rini", "last_name": "Rossanti", "name": null }, { "creator_type": "author", "first_name": "Ming Juan", "last_name": "Ye", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Nozu", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Kai", "name": null }, { "creator_type": "author", "first_name": "Kazumoto", "last_name": "Iijima", "name": null }, { "creator_type": "author", "first_name": "Kandai", "last_name": "Nozu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-020-16605-x" }, "pmcid": { "normalized": "PMC7265383" }, "pmid": { "normalized": "32488001" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Collagen Type IV", "descriptor_ui": "D024141", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Drug Delivery Systems", "descriptor_ui": "D016503", "major_topic": false }, { "descriptor": "Exons", "descriptor_ui": "D005091", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kidney Glomerulus", "descriptor_ui": "D007678", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Nephritis, Hereditary", "descriptor_ui": "D009394", "major_topic": false }, { "descriptor": "Renal Insufficiency, Chronic", "descriptor_ui": "D051436", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jun 2", "date_precision": "day", "issue": "1", "normalized_date": "2020-06-02", "pages": "2777", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of an exon skipping therapy for X-linked Alport syndrome with truncating variants in COL4A5.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The relationships between depression and gut microbiota, particularly those involving the immune system, have become a major focus of recent research. Here, we analyzed changes in gut microbiota and their sulfur metabolites in the feces of a depression rat model using the modified 14-day social defeat stress (SDS) paradigm. Our results showed that SDS increased fecal Lactobacillus reuteri in correlation with ergothioneine levels at around day 11, which continued for at least 1 month following SDS administration. In vitro study further revealed that L. reuteri is capable of producing ergothioneine. Although the known anti-inflammatory and anti-oxidative actions of ergothioneine suggested that the increased fecal ergothioneine levels may be related to intestinal anti-inflammatory defense mechanisms, no change was observed in the plasma ergothioneine levels during the same observation period, indicating that the defense mechanisms may not be sufficiently reflected in the body. As ergothioneine is a natural ingredient that is absorbed mainly from the upper gastrointestinal tract, we hypothesized that oral ergothioneine may exert antidepressant effects. As expected, oral administration of ergothioneine prior to and during the SDS paradigm had a preventative effect on SDS-induced depressive behaviors, such as social avoidance and depression-like sleep abnormalities, particularly those of rapid eye movement sleep. These findings indicate that ergothioneine, a metabolite of L. reuteri, may be a common substance in the microbiota-gut-brain axis that prevents stress-induced sleep disturbances, especially those associated with depression.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Takiko", "last_name": "Shinozaki", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Iwao", "last_name": "Ohtsu", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Tatebayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41398-020-0855-1" }, "pmcid": { "normalized": "PMC7256047" }, "pmid": { "normalized": "32467627" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": false }, { "descriptor": "Ergothioneine", "descriptor_ui": "D004880", "major_topic": true }, { "descriptor": "Gastrointestinal Microbiome", "descriptor_ui": "D000069196", "major_topic": true }, { "descriptor": "Limosilactobacillus reuteri", "descriptor_ui": "D052200", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 May 28", "date_precision": "day", "issue": "1", "normalized_date": "2020-05-28", "pages": "170", "proceedings_title": null, "publisher": "", "title": "Translational psychiatry", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Ergothioneine, a metabolite of the gut bacterium Lactobacillus reuteri, protects against stress-induced sleep disturbances.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The pyrophosphate ion (P2O7(4-), PPi) plays a critical role in various biological processes and acts as an essential indicator for physiological mechanism investigations and disease control monitoring. However, most of the currently available approaches for PPi species detection for practical usage still lack appropriate indicator generation, straightforward detection requirements, and operation convenience. In this study, a highly sensitive and selective PPi detection approach via the use of nanozymatic carbon dots (CDs) is introduced. This strategy eliminates the common need for metal ions in the detection process, where a direct indicator-PPi interaction is adopted to provide straightforward signal reports, and importantly, through a green indicator preparation. The preparation of this nanozymatic CDs' indicator utilizes an aqueous solution refluxing, employing galactose and histidine as the precursor materials. The mild conditions of the solution refluxing produce fluorescent CDs exhibiting peroxidase-mimic properties, which can catalyze the o-phenylenediamine oxidation under the presence of H2O2. The introduction of PPi species, interestingly, inhibits this process very efficiently, the extent of which can be colorimetrically monitored by the generated yellow product 2,3-diaminophenazine. Spectroscopic results point to CD surface functional groups' selective binding toward PPi species, which severely interferes with the electron transfer process in the enzymatic catalysis. Relying on this CD peroxidase-mimetic property inhibition, sensitive and selective recognition of PPi reaches a detection limit of 4.29 nM, enabling practical usage in complex matrixes. Owing to the superior compatibility and high stability of nanozymatic CDs, they can also be inkjet-printed on paper-based devices to create a portable and convenient platform for PPi detection. Both the solution and the paper-device-based selective recognitions confirm this unique and robust metal-free inhibitive PPi detection, which is supported by a convenient green preparation of nanozymatic CDs.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Chong-You", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Ying Zi", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Ping-Hsuan", "last_name": "Hsieh", "name": null }, { "creator_type": "author", "first_name": "Chang-Ming", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Kento", "last_name": "Maejima", "name": null }, { "creator_type": "author", "first_name": "Ting-Yi", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Wei-Ssu", "last_name": "Liao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acssensors.9b02486" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32323526" } }, "mesh": [ { "descriptor": "Carbon", "descriptor_ui": "D002244", "major_topic": true }, { "descriptor": "Colorimetry", "descriptor_ui": "D003124", "major_topic": false }, { "descriptor": "Diphosphates", "descriptor_ui": "D011756", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": false }, { "descriptor": "Quantum Dots", "descriptor_ui": "D045663", "major_topic": true }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 May 22", "date_precision": "day", "issue": "5", "normalized_date": "2020-05-22", "pages": "1314-1324", "proceedings_title": null, "publisher": "", "title": "ACS sensors", "volume": "5", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Metal-Free Colorimetric Detection of Pyrophosphate Ions by Inhibitive Nanozymatic Carbon Dots.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Keita", "last_name": "Ashida", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Shidara", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuroscience.2020.03.028" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32240648" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 May 10", "date_precision": "day", "issue": "", "normalized_date": "2020-05-10", "pages": "212-213", "proceedings_title": null, "publisher": "", "title": "Neuroscience", "volume": "434", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Corrigendum to \"Optical dissection of synaptic plasticity for early adaptation in Caenorhabditis elegans\" [Neuroscience 428C (2020) 112-121].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The one-dimensional information of genomic DNA is hierarchically packed inside the eukaryotic cell nucleus and organized in a three-dimensional (3D) space. Genome-wide chromosome conformation capture (Hi-C) methods have uncovered the 3D genome organization and revealed multiscale chromatin domains of compartments and topologically associating domains (TADs). Moreover, single-nucleosome live-cell imaging experiments have revealed the dynamic organization of chromatin domains caused by stochastic thermal fluctuations. However, the mechanism underlying the dynamic regulation of such hierarchical and structural chromatin units within the microscale thermal medium remains unclear. Microrheology is a way to measure dynamic viscoelastic properties coupling between thermal microenvironment and mechanical response. Here, we propose a new, to our knowledge, microrheology for Hi-C data to analyze the dynamic compliance property as a measure of rigidness and flexibility of genomic regions along with the time evolution. Our method allows the conversion of an Hi-C matrix into the spectrum of the dynamic rheological property along the genomic coordinate of a single chromosome. To demonstrate the power of the technique, we analyzed Hi-C data during the neural differentiation of mouse embryonic stem cells. We found that TAD boundaries behave as more rigid nodes than the intra-TAD regions. The spectrum clearly shows the dynamic viscoelasticity of chromatin domain formation at different timescales. Furthermore, we characterized the appearance of synchronous and liquid-like intercompartment interactions in differentiated cells. Together, our microrheology data derived from Hi-C data provide physical insights into the dynamics of the 3D genome organization.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Hiratani", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpj.2020.02.020" }, "pmcid": { "normalized": "PMC7203008" }, "pmid": { "normalized": "32191860" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": true }, { "descriptor": "Chromosomes", "descriptor_ui": "D002875", "major_topic": true }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mouse Embryonic Stem Cells", "descriptor_ui": "D000066450", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 May 5", "date_precision": "day", "issue": "9", "normalized_date": "2020-05-05", "pages": "2220-2228", "proceedings_title": null, "publisher": "", "title": "Biophysical journal", "volume": "118", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Microrheology for Hi-C Data Reveals the Spectrum of the Dynamic 3D Genome Organization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This paper introduces the concept of \"Drawing-PADs\" (Drawing paper-based microfluidic analytical devices) allowing to intuitively evaluate the urinary albumin (Alb) index, a clinically important parameter used for the early detection of renal deficiencies related to diabetes, among others. To enable regular monitoring of the Alb index, a simple examination method suitable for self-diagnosis is highly desirable. The Drawing-PADs rely on the simultaneous naked eye detection of Alb and creatinine (Cre) on a single device according to the distance-based microfluidic PAD (muPAD) approach. The Alb index is visualized by simply drawing a straight line connecting the top of two color-changed assay channel sections (Alb and Cre channels), followed by visually confirming the position of the intercept of the drawn straight line. The semiquantitative Alb index evaluation performed with Drawing-PADs does not require any equipment such as a camera, software, or a color reference chart. The obtained results are independent of the sample volume and are not influenced by changes in the absolute Alb and Cre concentrations caused by urine excretion variations, making spot urine assays possible. Classification of Alb index values according to clinically relevant criteria (normoalbuminuria, microalbuminuria, and macroalbuminuria) is readily achieved within 15 min and has been validated for 15 human urine samples including diabetic patients and healthy volunteers.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryuya", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Kento", "last_name": "Kuwahara", "name": null }, { "creator_type": "author", "first_name": "Yun-Chiao", "last_name": "Wen", "name": null }, { "creator_type": "author", "first_name": "Tzung-Hai", "last_name": "Yen", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Chao-Min", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acssensors.0c00050" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32186370" } }, "mesh": [ { "descriptor": "Albumins", "descriptor_ui": "D000418", "major_topic": false }, { "descriptor": "Creatinine", "descriptor_ui": "D003404", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microfluidic Analytical Techniques", "descriptor_ui": "D046210", "major_topic": false }, { "descriptor": "Urinalysis", "descriptor_ui": "D016482", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Apr 24", "date_precision": "day", "issue": "4", "normalized_date": "2020-04-24", "pages": "1110-1118", "proceedings_title": null, "publisher": "", "title": "ACS sensors", "volume": "5", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Paper-Based Device for Naked Eye Urinary Albumin/Creatinine Ratio Evaluation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Predicting of chemical compounds is one of the fundamental tasks in bioinformatics and chemoinformatics, because it contributes to various applications in metabolic engineering and drug discovery. The recent rapid growth of the amount of available data has enabled applications of computational approaches such as statistical modeling and machine learning method. Both a set of chemical interactions and chemical compound structures are represented as graphs, and various graph-based approaches including graph convolutional neural networks have been successfully applied to chemical network prediction. However, there was no efficient method that can consider the two different types of graphs in an end-to-end manner. RESULTS: We give a new formulation of the chemical network prediction problem as a link prediction problem in a graph of graphs (GoG) which can represent the hierarchical structure consisting of compound graphs and an inter-compound graph. We propose a new graph convolutional neural network architecture called dual graph convolutional network that learns compound representations from both the compound graphs and the inter-compound network in an end-to-end manner. CONCLUSIONS: Experiments using four chemical networks with different sparsity levels and degree distributions shows that our dual graph convolution approach achieves high prediction performance in relatively dense networks, while the performance becomes inferior on extremely-sparse networks.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shonosuke", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Akita", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Tsubaki", "name": null }, { "creator_type": "author", "first_name": "Yukino", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Yamanishi", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Kashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12859-020-3378-0" }, "pmcid": { "normalized": "PMC7178944" }, "pmid": { "normalized": "32321421" } }, "mesh": [ { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Computer Graphics", "descriptor_ui": "D003196", "major_topic": true }, { "descriptor": "Drug Discovery", "descriptor_ui": "D055808", "major_topic": false }, { "descriptor": "Models, Chemical", "descriptor_ui": "D008956", "major_topic": true }, { "descriptor": "Neural Networks, Computer", "descriptor_ui": "D016571", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Apr 23", "date_precision": "day", "issue": "Suppl 3", "normalized_date": "2020-04-23", "pages": "94", "proceedings_title": null, "publisher": "", "title": "BMC bioinformatics", "volume": "21", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Dual graph convolutional neural network for predicting chemical networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Synaptic dysfunction provoking dysregulated cortical neural circuits is currently hypothesized as a key pathophysiological process underlying clinical manifestations in Alzheimer's disease and related neurodegenerative tauopathies. Here, we conducted PET along with postmortem assays to investigate time course changes of excitatory and inhibitory synaptic constituents in an rTg4510 mouse model of tauopathy, which develops tau pathologies leading to noticeable brain atrophy at 5-6 months of age. Both male and female mice were analyzed in this study. We observed that radiosignals derived from [(11)C]flumazenil, a tracer for benzodiazepine receptor, in rTg4510 mice were significantly lower than the levels in nontransgenic littermates at 2-3 months of age. In contrast, retentions of (E)-[(11)C]ABP688, a tracer for mGluR5, were unaltered relative to controls at 2 months of age but then gradually declined with aging in parallel with progressive brain atrophy. Biochemical and immunohistochemical assessment of postmortem brain tissues demonstrated that inhibitory, but not excitatory, synaptic constituents selectively diminished without overt loss of somas of GABAergic interneurons in the neocortex and hippocampus of rTg4510 mice at 2 months of age, which was concurrent with enhanced immunoreactivity of cFos, a well-characterized immediate early gene, suggesting that impaired inhibitory neurotransmission may cause hyperexcitability of cortical circuits. Our findings indicate that tau-induced disruption of the inhibitory synapse may be a critical trigger of progressive neurodegeneration, resulting in massive neuronal loss, and PET assessments of inhibitory versus excitatory synapses potentially offer in vivo indices for hyperexcitability and excitotoxicity early in the etiologic pathway of neurodegenerative tauopathies.SIGNIFICANCE STATEMENT In this study, we examined the in vivo status of excitatory and inhibitory synapses in the brain of the rTg4510 tauopathy mouse model by PET imaging with (E)-[(11)C]ABP688 and [(11)C]flumazenil, respectively. We identified inhibitory synapse as being significantly dysregulated before brain atrophy at 2 months of age, while excitatory synapse stayed relatively intact at this stage. In line with this observation, postmortem assessment of brain tissues demonstrated selective attenuation of inhibitory synaptic constituents accompanied by the upregulation of cFos before the formation of tau pathology in the forebrain at young ages. Our findings indicate that selective degeneration of inhibitory synapse with hyperexcitability in the cortical circuit constitutes the critical early pathophysiology of tauopathy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masafumi", "last_name": "Shimojo", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takuwa", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Takado", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Minatohara", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Urushihata", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Minamihisamatsu", "name": null }, { "creator_type": "author", "first_name": "Ichio", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Ming-Rong", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.2880-19.2020" }, "pmcid": { "normalized": "PMC7178904" }, "pmid": { "normalized": "32265258" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "GABAergic Neurons", "descriptor_ui": "D059330", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neocortex", "descriptor_ui": "D019579", "major_topic": false }, { "descriptor": "Neural Inhibition", "descriptor_ui": "D009433", "major_topic": false }, { "descriptor": "Positron-Emission Tomography", "descriptor_ui": "D049268", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Apr 22", "date_precision": "day", "issue": "17", "normalized_date": "2020-04-22", "pages": "3491-3501", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "40", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Selective Disruption of Inhibitory Synapses Leading to Neuronal Hyperexcitability at an Early Stage of Tau Pathogenesis in a Mouse Model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Orexin/hypocretin-producing and melanin-concentrating hormone-producing (MCH) neurons are co-extensive in the hypothalamus and project throughout the brain to regulate sleep/wakefulness. Ablation of orexin neurons decreases wakefulness and results in a narcolepsy-like phenotype, whereas ablation of MCH neurons increases wakefulness. Since it is unclear how orexin and MCH neurons interact to regulate sleep/wakefulness, we generated transgenic mice in which both orexin and MCH neurons could be ablated. Double-ablated mice exhibited increased wakefulness and decreased both rapid eye movement (REM) and non-REM (NREM) sleep. Double-ablated mice showed severe cataplexy compared with orexin neuron-ablated mice, suggesting that MCH neurons normally suppress cataplexy. Double-ablated mice also showed frequent sleep attacks with elevated spectral power in the delta and theta range, a unique state that we call 'delta-theta sleep'. Together, these results indicate a functional interaction between orexin and MCH neurons in vivo that suggests the synergistic involvement of these neuronal populations in the sleep/wakefulness cycle.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Chi Jung", "last_name": "Hung", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Thomas S.", "last_name": "Kilduff", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.54275" }, "pmcid": { "normalized": "PMC7173968" }, "pmid": { "normalized": "32314734" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cataplexy", "descriptor_ui": "D002385", "major_topic": false }, { "descriptor": "Hypothalamic Hormones", "descriptor_ui": "D007028", "major_topic": true }, { "descriptor": "Melanins", "descriptor_ui": "D008543", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Orexins", "descriptor_ui": "D000068797", "major_topic": true }, { "descriptor": "Pituitary Hormones", "descriptor_ui": "D010907", "major_topic": true }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": false }, { "descriptor": "Wakefulness", "descriptor_ui": "D014851", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Apr 21", "date_precision": "day", "issue": "", "normalized_date": "2020-04-21", "pages": "e54275", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "9", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Dual orexin and MCH neuron-ablated mice display severe sleep attacks and cataplexy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The tailbud stage is part of the organogenesis period-an evolutionarily conserved developmental period among chordates that is essential for determining the characteristics of the chordate body plan. When the volume of the egg is artificially decreased by cutting, ascidians produce a normal-looking but miniature (dwarf) tailbud embryo. Although cell lineages during ascidian embryogenesis are invariant, the number of cell divisions in the dwarf embryo is altered by a different mechanism in each tissue (Yamada and Nishida, 1999). Here, to elucidate the size-regulation strategies of the Ciona robusta dwarf tailbud embryo, we compared anatomical structure, developmental speed, and cell number/volume in each tissue between dwarf and wild type (WT) embryos. To do this, we constructed a 3D virtual mid-tailbud embryo (Nakamura et al., 2012). We could make a Ciona dwarf tailbud embryo from eggs with a diameter over 108 mum (correspond to > 40% of the wild type egg volume). The timings of cleavage (~St. 12) and subsequent morphogenesis were nearly the same but blastomeres of animal hemisphere slightly delayed the timing of mitosis in the early cleavage period. Intriguingly, the tissue-to-tissue volume ratios of dwarf tailbud embryos were similar to those of wild type embryos suggesting that the ratio of tissue volumes is essential for maintaining the proper shape of the tailbud embryo. The number of cells in the epidermis, nervous system, and mesenchyme was significantly reduced in the dwarf embryos whereas the cell volume distribution of these tissues was similar in the dwarf and wild type. In contrast, the number of cells in the notochord, muscle, heart, and endoderm were maintained in the dwarf embryos; cell volumes were significantly reduced. Neither parameter changed in germline precursors. These results indicate that each tissue uses different scaling strategies to coordinate cell number and cell volume in accordance with the embryo size.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kaoru D.", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Mitsuru J.", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Wataru C.", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2020.01.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31981562" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ciona", "descriptor_ui": "D000077262", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": true }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Apr 15", "date_precision": "day", "issue": "2", "normalized_date": "2020-04-15", "pages": "215-223", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "460", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Different strategies for tissue scaling in dwarf tailbud embryos revealed by single-cell analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In this review, we focus on the applications of machine learning methods for analyzing image data acquired in imaging flow cytometry technologies. We propose that the analysis approaches can be categorized into two groups based on the type of data, raw imaging signals or features explicitly extracted from images, being analyzed by a trained model. We hope that this categorization is helpful for understanding uniqueness, differences and opportunities when the machine learning-based analysis is implemented in recently developed 'imaging' cell sorters.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Issei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Horisaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jmicro/dfaa005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32115658" } }, "mesh": [ { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Apr 8", "date_precision": "day", "issue": "2", "normalized_date": "2020-04-08", "pages": "61-68", "proceedings_title": null, "publisher": "", "title": "Microscopy (Oxford, England)", "volume": "69", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Implementing machine learning methods for imaging flow cytometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Single-molecule imaging analysis has been applied to study the dynamics and kinetics of molecular behaviors and interactions in living cells. In spite of its high potential as a technique to investigate the molecular mechanisms of cellular phenomena, single-molecule imaging analysis has not been extended to a large scale of molecules in cells due to the low measurement throughput as well as required expertise. To overcome these problems, we have automated the imaging processes by using computer operations, robotics and artificial intelligence (AI). AI is an ideal substitute for expertise to obtain high-quality images for quantitative analysis. Our automated in-cell single-molecule imaging system, AiSIS, could analyze 1600 cells in 1 day, which corresponds to approximately 100-fold higher efficiency than manual analysis. The large-scale analysis revealed cell-to-cell heterogeneity in the molecular behavior, which had not been recognized in previous studies. An analysis of the receptor behavior and downstream signaling was accomplished within a significantly reduced time frame and revealed the detailed activation scheme of signal transduction, advancing cell biology research. Furthermore, by combining the high-throughput analysis with our previous finding that a receptor changes its behavioral dynamics depending on the presence of a ligand/agonist or inhibitor/antagonist, we show that AiSIS is applicable to comprehensive pharmacological analysis such as drug screening. This AI-aided automation has wide applications for single-molecule analysis.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jmicro/dfz116" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32090254" } }, "mesh": [ { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": true }, { "descriptor": "Automation", "descriptor_ui": "D001331", "major_topic": false }, { "descriptor": "Drug Evaluation, Preclinical", "descriptor_ui": "D004353", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Pharmacology", "descriptor_ui": "D010600", "major_topic": false }, { "descriptor": "Single Molecule Imaging", "descriptor_ui": "D000072760", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Apr 8", "date_precision": "day", "issue": "2", "normalized_date": "2020-04-08", "pages": "69-78", "proceedings_title": null, "publisher": "", "title": "Microscopy (Oxford, England)", "volume": "69", "year": 2020 }, "ssbd": { "database": [ "ssbd-database-000192" ], "repository": [ "ssbd-repos-000192" ] }, "title": "Large-scale single-molecule imaging aided by artificial intelligence.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Distance-based readout is one of the most user-friendly and simple colorimetric signaling methods widely applied for paper-based analytical devices (PADs). This work presents the integration of distance readout PADs into a centrifugal platform enabling affordable, rapid, and sample volume-independent colorimetric assays. Centrifugally assisted distance-based PADs (CD-PADs) eliminate the requirement to use micropipets for sample introduction and reduce the overall time for distance-based assays. All device fabrication steps were performed through computer-controlled print, cut, and laminate (PCL) techniques oriented toward mass production. The inexpensive centrifugal platform was built on a recycled DVD player combined with an open source microcomputer (Arduino). Assay protocols, including rotational velocity and rotation time, were optimized to obtain a maximum dynamic range and reproducible results for sample volume metering (coefficient of variation 3.62%). A colorimetric Ni(2+) assay chosen to demonstrate measurements on CD-PADs allowed the detection of nickel ions (Ni(2+)) with naked-eye interpretation within 1.5 min and a limit of detection (LOD) of 44.1 ng of Ni(2+), which to the best of our knowledge is the lowest value reported for a distance-based Ni(2+) assay.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kento", "last_name": "Maejima", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.9b05782" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32174103" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Apr 7", "date_precision": "day", "issue": "7", "normalized_date": "2020-04-07", "pages": "4749-4754", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "92", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Centrifugal Paperfluidic Platform for Accelerated Distance-Based Colorimetric Signal Readout.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Folate receptors (FRs) are membrane proteins involved in folic acid uptake, and the alpha isoform (FR-alpha) is overexpressed in ovarian and endometrial cancer cells. For fluorescence imaging of FRs in vivo, the near-infrared (NIR) region (650-900 nm), in which tissue penetration is high and autofluorescence is low, is optimal, but existing NIR fluorescent probes targeting FR-alpha show high non-specific tissue adsorption, and require prolonged washout to visualize tumors. We have designed and synthesized a new NIR fluorescent probe, FolateSiR-1, utilizing a Si-rhodamine fluorophore having a carboxy group at the benzene moiety, coupled to a folate ligand moiety through a negatively charged tripeptide linker. This probe exhibits very low background fluorescence and afforded a tumor-to-background ratio (TBR) of up to 83 in FR-expressing tumor-bearing mice within 30 min. Thus, FolateSiR-1 has the potential to contribute to the research in the field of biology and the clinical medicine.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Numasawa", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ikeno", "name": null }, { "creator_type": "author", "first_name": "Honami", "last_name": "Echizen", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yasunaga", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201914826" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31984590" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Folate Receptors, GPI-Anchored", "descriptor_ui": "D058973", "major_topic": false }, { "descriptor": "Folic Acid", "descriptor_ui": "D005492", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": false }, { "descriptor": "Signal-To-Noise Ratio", "descriptor_ui": "D059629", "major_topic": true }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Apr 6", "date_precision": "day", "issue": "15", "normalized_date": "2020-04-06", "pages": "6015-6020", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "59", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "A Fluorescent Probe for Rapid, High-Contrast Visualization of Folate-Receptor-Expressing Tumors In Vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescent protein-based reporter systems are used to track gene expression in cells. Here, we propose a modified bioluminescence resonance energy transfer (BRET) reporter as a maturation-less reporter that utilizes a peptide-assisted complementation strategy. Using effective dimerized peptides obtained from library-versus-library screening with more than 4000 candidates, rapid activation of the reporter was achieved.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taishi", "last_name": "Kakizuka", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Takai", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c9cc08664a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32104841" } }, "mesh": [ { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Bioluminescence Resonance Energy Transfer Techniques", "descriptor_ui": "D060807", "major_topic": true }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 28", "date_precision": "day", "issue": "25", "normalized_date": "2020-03-28", "pages": "3625-3628", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "56", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "An improved fluorescent protein-based expression reporter system that utilizes bioluminescence resonance energy transfer and peptide-assisted complementation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Based on the type-I cannabinoid receptor (CB1) content of hypophysiotropic axons and the involvement of tanycytes in the regulation of the hypothalamic-pituitary-thyroid (HPT) axis, we hypothesized that endocannabinoids are involved in the tanycyte-induced regulation of TRH release in the median eminence (ME). We demonstrated that CB1-immunoreactive TRH axons were associated to DAGLα-immunoreactive tanycyte processes in the external zone of ME and showed that endocannabinoids tonically inhibit the TRH release in this tissue. We showed that glutamate depolarizes the tanycytes, increases their intracellular Ca2+ level and the 2-AG level of the ME via AMPA and kainite receptors and glutamate transport. Using optogenetics, we demonstrated that glutamate released from TRH neurons influences the tanycytes in the ME.In summary, tanycytes regulate TRH secretion in the ME via endocannabinoid release, whereas TRH axons regulate tanycytes by glutamate, suggesting the existence of a reciprocal microcircuit between tanycytes and TRH terminals that controls TRH release.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Erzsébet", "last_name": "Farkas", "name": null }, { "creator_type": "author", "first_name": "Edina", "last_name": "Varga", "name": null }, { "creator_type": "author", "first_name": "Balázs", "last_name": "Kovács", "name": null }, { "creator_type": "author", "first_name": "Anett", "last_name": "Szilvásy-Szabó", "name": null }, { "creator_type": "author", "first_name": "Antonieta", "last_name": "Cote-Vélez", "name": null }, { "creator_type": "author", "first_name": "Zoltán", "last_name": "Péterfi", "name": null }, { "creator_type": "author", "first_name": "Magdalini", "last_name": "Matziari", "name": null }, { "creator_type": "author", "first_name": "Mónika", "last_name": "Tóth", "name": null }, { "creator_type": "author", "first_name": "Dóra", "last_name": "Zelena", "name": null }, { "creator_type": "author", "first_name": "Zsolt", "last_name": "Mezriczky", "name": null }, { "creator_type": "author", "first_name": "Andrea", "last_name": "Kádár", "name": null }, { "creator_type": "author", "first_name": "Dóra", "last_name": "Kővári", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Mackie", "name": null }, { "creator_type": "author", "first_name": "Balázs", "last_name": "Rózsa", "name": null }, { "creator_type": "author", "first_name": "Yvette", "last_name": "Ruska", "name": null }, { "creator_type": "author", "first_name": "Blanka", "last_name": "Tóth", "name": null }, { "creator_type": "author", "first_name": "Zoltán", "last_name": "Máté", "name": null }, { "creator_type": "author", "first_name": "Ferenc", "last_name": "Erdélyi", "name": null }, { "creator_type": "author", "first_name": "Gábor", "last_name": "Szabó", "name": null }, { "creator_type": "author", "first_name": "Balázs", "last_name": "Gereben", "name": null }, { "creator_type": "author", "first_name": "Ronald M.", "last_name": "Lechan", "name": null }, { "creator_type": "author", "first_name": "Jean-Louis", "last_name": "Charli", "name": null }, { "creator_type": "author", "first_name": "Patricia", "last_name": "Joseph-Bravo", "name": null }, { "creator_type": "author", "first_name": "Csaba", "last_name": "Fekete", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2020.100921" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32143135" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Mar 27", "date_precision": "day", "issue": "3", "normalized_date": "2020-03-27", "pages": "", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "23", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "A Glial-Neuronal Circuit in the Median Eminence Regulates Thyrotropin-Releasing Hormone-Release via the Endocannabinoid System.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Detailed spatial information of low-molecular weight compound distribution, especially in the brain, is crucial to understanding their mechanism of actions. Imaging techniques that can directly visualize drugs in the brain at a high resolution will complement existing tools for drug distribution analysis. Here, we performed surface-enhanced Raman scattering (SERS) imaging using a bioorthogonal alkyne tag to visualize drugs directly in situ at a high resolution. Focusing on the selective serotonin reuptake inhibitor S-citalopram (S-Cit), which possesses a nitrile group, we substituted an alkynyl group into its structure and synthesized alkynylated S-Cit (Alk-S-Cit). The brain transitivity and the serotonin reuptake inhibition of Alk-S-Cit were not significantly different as compared with S-Cit. Alk-S-Cit was visualized in the coronal mouse brain section using SERS imaging with silver nanoparticles. Furthermore, SERS imaging combined with fluorescence microscopy allowed Alk-S-Cit to be visualized in the adjacent neuronal membranes, as well as in the brain vessel and parenchyma. Therefore, our multimodal imaging technique is an effective method for detecting low-molecular weight compounds in their original tissue environment and can potentially offer additional information regarding the precise spatial distribution of such drugs.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masato", "last_name": "Tanuma", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Kotoku", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Minoshima", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Higashino", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kimishima", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci.insight.133348" }, "pmcid": { "normalized": "PMC7213792" }, "pmid": { "normalized": "32125287" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antidepressive Agents, Second-Generation", "descriptor_ui": "D018687", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Citalopram", "descriptor_ui": "D015283", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Multimodal Imaging", "descriptor_ui": "D064847", "major_topic": false }, { "descriptor": "Neuroimaging", "descriptor_ui": "D059906", "major_topic": false }, { "descriptor": "Selective Serotonin Reuptake Inhibitors", "descriptor_ui": "D017367", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 26", "date_precision": "day", "issue": "6", "normalized_date": "2020-03-26", "pages": "133348", "proceedings_title": null, "publisher": "", "title": "JCI insight", "volume": "5", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Direct visualization of an antidepressant analog using surface-enhanced Raman scattering in the brain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "HIF-1alpha, an essential transcription factor under hypoxic condition, is indispensable for chondrocytes during skeletal development but its expression and roles in articular chondrocytes are yet to be revealed. We examined HIF-1alpha protein expression and the hypoxic condition during mouse osteoarthritis (OA) development using state of the art hypoxic probes and found that its expression decreased as OA progressed, coinciding with the change in hypoxic conditions in articular cartilage. Gain- and loss-of-function of HIF-1alpha in cell culture experiments showed that HIF-1alpha suppressed catabolic genes such as Mmp13 and Hif2a. We confirmed these anticatabolic effects by measuring glycosaminoglycan release from wild type and conditional knock-out mice femoral heads cultured ex vivo. We went on to surgically induce OA in mice with chondrocyte-specific deletion of Hif1a and found that the development of OA was exacerbated. Increased expression of catabolic factors and activation of NF-kappaB signalling was clearly evident in the knock-out mice. By microarray analysis, C1qtnf3 was identified as a downstream molecule of HIF-1alpha, and experiments showed it exerted anti-catabolic effects through suppression of NF-kappaB. We conclude that HIF-1alpha has an anti-catabolic function in the maintenance of articular cartilage through suppression of NF-kappaB signalling.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Keita", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yuma", "last_name": "Makii", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Nakamoto", "name": null }, { "creator_type": "author", "first_name": "Yasutaka", "last_name": "Murahashi", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Song Ho", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Semba", "name": null }, { "creator_type": "author", "first_name": "Norihiko", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Wen", "last_name": "Piao", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Sakae", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-62463-4" }, "pmcid": { "normalized": "PMC7096515" }, "pmid": { "normalized": "32214220" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Cartilage, Articular", "descriptor_ui": "D002358", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chondrocytes", "descriptor_ui": "D019902", "major_topic": false }, { "descriptor": "Hypoxia-Inducible Factor 1, alpha Subunit", "descriptor_ui": "D051795", "major_topic": false }, { "descriptor": "Matrix Metalloproteinase 13", "descriptor_ui": "D053509", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Osteoarthritis", "descriptor_ui": "D010003", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 25", "date_precision": "day", "issue": "1", "normalized_date": "2020-03-25", "pages": "5425", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Hypoxia-inducible factor-1 alpha maintains mouse articular cartilage through suppression of NF-kappaB signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Classical transection studies suggest that, in addition to the hypothalamus, the brainstem is essential for non-rapid eye movement (NREM) sleep. The circuits underlying this function, however, have remained largely unknown. We identified a circuit distributed in the midbrain, pons, and medulla that promotes NREM sleep in mice. We focused on the sublaterodorsal tegmentum, an area implicated in dual regulation of REM and NREM sleep. Transcriptomic and genetic analyses revealed that neurons positive for the neuropeptide neurotensin promote NREM sleep. Further analyses identified downstream NREM sleep-promoting neurons in the dorsal deep mesencephalic nucleus, the lateral part of the periaqueductal gray, and the medial vestibular nucleus that were also neurotensinergic. Infusion of neurotensin into the fourth ventricle induced NREM sleep-like cortical activity, whereas mice deficient for neurotensin exhibited increased REM sleep, implicating the involvement of the neuropeptide itself. These findings identify a widely distributed NREM sleep-regulating circuit in the brainstem with a common molecular property.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuaki", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Kanuka", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Tatsuzawa", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Kaeko", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Taizo", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Jay W.", "last_name": "Shin", "name": null }, { "creator_type": "author", "first_name": "Harukazu", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shigeyoshi", "last_name": "Itohara", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2020.01.047" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32032507" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain Stem", "descriptor_ui": "D001933", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neurotensin", "descriptor_ui": "D009496", "major_topic": false }, { "descriptor": "Sleep, Slow-Wave", "descriptor_ui": "D000077310", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 23", "date_precision": "day", "issue": "6", "normalized_date": "2020-03-23", "pages": "1002-1010.e4", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "30", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Widely Distributed Neurotensinergic Neurons in the Brainstem Regulate NREM Sleep in Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Firefly bioluminescence is broadly applied as a noninvasive imaging modality in the biomedical research field. One limitation in firefly bioluminescence imaging is the limited variety of luciferins emitting in the near-infrared (NIR) region (650-900 nm), where tissue penetration is high. Herein, we describe a series of structure-inherent NIR emitting firefly luciferin analogues, NIRLucs, designed through a ring fusion strategy. This strategy resulted in pH-independent structure-inherent NIR emission with a native firefly luciferase, which was theoretically supported by quantum chemical calculations of the oxidized form of each luciferin. When applied to cells, NIRLucs displayed dose-independent improved NIR emission even at low concentrations where the native d-luciferin substrate does not emit. Additionally, excellent blood retention and brighter photon flux (7-fold overall, 16-fold in the NIR spectral range) than in the case of d-luciferin have been observed with one of the NIRLucs in mice bearing subcutaneous tumors. We believe that these synthetic luciferins provide a solution to the longstanding limitation in the variety of NIR emitting luciferins and pave the way to the further development of NIR bioluminescence imaging platforms.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuma", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Nomoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.9b04562" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31971368" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Firefly Luciferin", "descriptor_ui": "D049454", "major_topic": false }, { "descriptor": "Infrared Rays", "descriptor_ui": "D007259", "major_topic": false }, { "descriptor": "Luminescent Agents", "descriptor_ui": "D049408", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 17", "date_precision": "day", "issue": "6", "normalized_date": "2020-03-17", "pages": "4235-4243", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "92", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Ring-Fused Firefly Luciferins: Expanded Palette of Near-Infrared Emitting Bioluminescent Substrates.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Leucine-rich repeat kinase 2 (LRRK2) is the causal molecule of familial Parkinson's disease. Although the characteristics of LRRK2 have gradually been revealed, its true physiological functions remain unknown. LRRK2 is highly expressed in immune cells such as B2 cells and macrophages, suggesting that it plays important roles in the immune system. In the present study, we investigate the roles of LRRK2 in the immune functions of dendritic cells (DCs). Bone marrow-derived DCs from both C57BL/6 wild-type (WT) and LRRK2 knockout (KO) mice were induced by culture with granulocyte/macrophage-colony stimulating factor (GM/CSF) in vitro. We observed the differentiation of DCs, the phosphorylation of the transcriptional factors NF-kappaB, Erk1/2, and p-38 after lipopolysaccharide (LPS) stimulation and antigen-presenting ability by flow cytometry. We also analyzed the production of inflammatory cytokines by ELISA. During the observation period, there was no difference in DC differentiation between WT and LRRK2-KO mice. After LPS stimulation, phosphorylation of NF-kappaB was significantly increased in DCs from the KO mice. Large amounts of inflammatory cytokines were produced by DCs from KO mice after both stimulation with LPS and infection with Leishmania. CD4(+) T-cells isolated from antigen-immunized mice proliferated to a significantly greater degree upon coculture with antigen-stimulated DCs from KO mice than upon coculture with DCs from WT mice. These results suggest that LRRK2 may play important roles in signal transduction and antigen presentation by DCs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Mitsue", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Eshima", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Hirotomo", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Obata", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms21051890" }, "pmcid": { "normalized": "PMC7084871" }, "pmid": { "normalized": "32164260" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigen Presentation", "descriptor_ui": "D017951", "major_topic": false }, { "descriptor": "Bone Marrow Cells", "descriptor_ui": "D001854", "major_topic": false }, { "descriptor": "CD4-Positive T-Lymphocytes", "descriptor_ui": "D015496", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": false }, { "descriptor": "Granulocyte-Macrophage Colony-Stimulating Factor", "descriptor_ui": "D016178", "major_topic": false }, { "descriptor": "Leucine-Rich Repeat Serine-Threonine Protein Kinase-2", "descriptor_ui": "D000071158", "major_topic": false }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 10", "date_precision": "day", "issue": "5", "normalized_date": "2020-03-10", "pages": "E1890", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "21", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Leucine-Rich Repeat Kinase 2 Controls Inflammatory Cytokines Production through NF-kappaB Phosphorylation and Antigen Presentation in Bone Marrow-Derived Dendritic Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This study aimed to reveal a new dimension of allergy profiles in the general population by using machine learning to explore complex relationships among various cytokines/chemokines and allergic diseases (asthma and atopic dermatitis; AD). We examined the symptoms related to asthma and AD and the plasma levels of 72 cytokines/chemokines obtained from a general population of 161 children at 6 years of age who participated in a pilot birth cohort study of the Japan Environment and Children's Study (JECS). The children whose signs and symptoms fulfilled the criteria of AD, which are mostly based on questionnaire including past symptoms, tended to have higher levels of the two chemokine ligands, CCL17 and CCL27, which are used for diagnosis of AD. On the other hand, another AD-related chemokine CCL22 level in plasma was higher only in children with visible flexural eczema, which is one of AD diagnostic criteria but was judged on the same day of blood examination unlike other criteria. Here, we also developed an innovative method of machine learning for elucidating the complex cytokine/chemokine milieu related to symptoms of allergic diseases by using clustering analysis based on the random forest dissimilarity measure that relies on artificial intelligence (AI) technique. To our surprise, the majority of children showing at least any asthma-related symptoms during the last month were divided by AI into the two clusters, either cluster-2 having elevated levels of IL-33 (related to eosinophil activation) or cluster-3 having elevated levels of CXCL7/NAP2 (related to neutrophil activation), among the total three clusters. Future studies will clarify better approach for allergic diseases by endotype classification.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kiwako", "last_name": "Yamamoto-Hanada", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Mayako", "last_name": "Saito-Abe", "name": null }, { "creator_type": "author", "first_name": "Miori", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Mitsubuchi", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Katoh", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Sanefuji", "name": null }, { "creator_type": "author", "first_name": "Shouichi", "last_name": "Ohga", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Kuwajima", "name": null }, { "creator_type": "author", "first_name": "Nathan", "last_name": "Mise", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Ikegami", "name": null }, { "creator_type": "author", "first_name": "Fujio", "last_name": "Kayama", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Senju", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shimono", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Kusuhara", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Shoji F.", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Hirohisa", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Ohya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cyto.2020.155051" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32151964" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Mar 6", "date_precision": "day", "issue": "", "normalized_date": "2020-03-06", "pages": "155051", "proceedings_title": null, "publisher": "", "title": "Cytokine", "volume": "130", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Exploratory analysis of plasma cytokine/chemokine levels in 6-year-old children from a birth cohort study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Targeted blockade of programmed cell death 1 (PD-1), an immune-checkpoint receptor that inhibits T cell activation, provides clinical benefits in various cancers. However, how PD-1 modulates gene expression in T cells remains enigmatic. Here we investigated how PD-1 affects transcriptome changes induced by T cell receptor (TCR) activation. Intriguingly, we identified a huge variance in PD-1 sensitivity among TCR-inducible genes. When we quantified the half maximal effective concentration (EC50) as the relationship between change in gene expression and TCR signal strength, we found that genes associated with survival and proliferation were efficiently expressed upon TCR activation and resistant to PD-1-mediated inhibition. Conversely, genes encoding cytokines and effector molecules were expressed less efficiently and sensitive to PD-1-mediated inhibition. We further demonstrated that transcription factor binding motifs and CpG frequency in the promoter region affect EC50 and thus the PD-1 sensitivity of genes. Our findings explain how PD-1, dependent on the TCR signal strength, calibrates cellular transcriptomes to shape functional properties of T cell populations.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Il-Mi", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Yujiro", "last_name": "Takegami", "name": null }, { "creator_type": "author", "first_name": "Chaoyang", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Soichi", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Okazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.molcel.2019.12.012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31926851" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "CpG Islands", "descriptor_ui": "D018899", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Genes, T-Cell Receptor", "descriptor_ui": "D019672", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Jurkat Cells", "descriptor_ui": "D019169", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": true }, { "descriptor": "Lymphocytes, Tumor-Infiltrating", "descriptor_ui": "D016246", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcriptional Activation", "descriptor_ui": "D015533", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Mar 5", "date_precision": "day", "issue": "5", "normalized_date": "2020-03-05", "pages": "937-950.e6", "proceedings_title": null, "publisher": "", "title": "Molecular cell", "volume": "77", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "PD-1 Imposes Qualitative Control of Cellular Transcriptomes in Response to T Cell Activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We investigated the detailed photophysical properties of a series of bis-metal (Zn and Cu) dioxohexaphyrin complexes as potential second near-infrared (NIR-II)-light responsive dyes. A cisoid-configured 28pi-electron-conjugated dioxohexaphyrin analogue (c-3a) containing two peculiar \"confused pyrrole\" moieties in the framework is identified as a reduced isomer derivative of a transoid 26pi-dioxohexaphyrin (t-2a). The symmetry-altered structure of c-3a affords a heteroleptic inner environment within the NNNN/NNOO donor core, which imparts its highly flexible electronic features and nonplanar geometry. The macrocycle c-3a can be transformed into the corresponding 26pi-electron congener (c-2a) having a coplanar rectangular structure by unique solvent-mediated redox reactivity. Furthermore, upon metal complexation, saddle-distorted bis-metal complexes (c-M2-2a) were formed as the 26pi-conjugated structural isomer of the trans-dioxohexaphyrin species (i.e., t-M2-2a). These isoelectronic dioxohexaphyrins demonstrate precise geometry-dependent photophysical properties. Broad tailing NIR-II absorption, weak emissive character, and rapid-decay of the S1 state are observed for c-Zn2-2a. In contrast, the coplanar t-M2-2a exhibits efficient photoacoustic response upon laser excitation with NIR-II light (lambda > 1000 nm). To the best of our knowledge, this is the first example of an expanded porphyrin-based photoacoustic contrast agent responsive to NIR-II light.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Keito", "last_name": "Shimomura", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Kai", "name": null }, { "creator_type": "author", "first_name": "Yuma", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yongseok", "last_name": "Hong", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Notsuka", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Yamaoka", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Dongho", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Furuta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.9b13475" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32036651" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Mar 4", "date_precision": "day", "issue": "9", "normalized_date": "2020-03-04", "pages": "4429-4437", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "142", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Bis-Metal Complexes of Doubly N-Confused Dioxohexaphyrins as Potential Near-Infrared-II Photoacoustic Dyes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mediator is a coregulatory complex that regulates transcription of Pol II-dependent genes. Previously, we showed that human Mediator subunit MED26 plays a role in the recruitment of Super Elongation Complex (SEC) or Little Elongation Complex (LEC) to regulate the expression of certain genes. MED26 plays a role in recruiting SEC to protein-coding genes including c-myc and LEC to small nuclear RNA (snRNA) genes. However, how MED26 engages SEC or LEC to regulate distinct genes is unclear. Here, we provide evidence that MED26 recruits LEC to modulate transcription termination of non-polyadenylated transcripts including snRNAs and mRNAs encoding replication-dependent histone (RDH) at Cajal bodies. Our findings indicate that LEC recruited by MED26 promotes efficient transcription termination by Pol II through interaction with CBC-ARS2 and NELF/DSIF, and promotes 3' end processing by enhancing recruitment of Integrator or Heat Labile Factor to snRNA or RDH genes, respectively.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hidehisa", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Amol", "last_name": "Ranjan", "name": null }, { "creator_type": "author", "first_name": "Shiyuan", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Hidefumi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Kai", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yanfeng", "last_name": "He", "name": null }, { "creator_type": "author", "first_name": "Ying", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null }, { "creator_type": "author", "first_name": "Tadasuke", "last_name": "Tsukiyama", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Midori", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Keiichi I.", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Michael P.", "last_name": "Washburn", "name": null }, { "creator_type": "author", "first_name": "Anita", "last_name": "Saraf", "name": null }, { "creator_type": "author", "first_name": "Laurence", "last_name": "Florens", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Chieri", "last_name": "Tomomori-Sato", "name": null }, { "creator_type": "author", "first_name": "Ronald C.", "last_name": "Conaway", "name": null }, { "creator_type": "author", "first_name": "Joan W.", "last_name": "Conaway", "name": null }, { "creator_type": "author", "first_name": "Shigetsugu", "last_name": "Hatakeyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-020-14849-1" }, "pmcid": { "normalized": "PMC7044329" }, "pmid": { "normalized": "32102997" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "HCT116 Cells", "descriptor_ui": "D045325", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mediator Complex", "descriptor_ui": "D056892", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "RNA Cap-Binding Proteins", "descriptor_ui": "D039381", "major_topic": false }, { "descriptor": "RNA Polymerase II", "descriptor_ui": "D012319", "major_topic": false }, { "descriptor": "RNA, Small Nuclear", "descriptor_ui": "D012342", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcription Termination, Genetic", "descriptor_ui": "D061806", "major_topic": false }, { "descriptor": "Transcriptional Elongation Factors", "descriptor_ui": "D035602", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Feb 26", "date_precision": "day", "issue": "1", "normalized_date": "2020-02-26", "pages": "1063", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "The role of Mediator and Little Elongation Complex in transcription termination.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Angle-strained alkyne-containing pi-conjugated macrocycles are attractive compounds both in functional materials chemistry and biochemistry. Their interesting reactivity as well as photophysical and supramolecular properties have been revealed in the past three decades. This review highlights the recent advances in angle-strained alkyne-containing pi-conjugated macrocycles, especially their synthetic methods, the bond angles of alkynes ( anglesp at C identical withC-C), and their functions. The theoretical and experimental research on cyclo[n]carbons and para-cyclophynes consisting of ethynylenes and para-phenylenes are mainly summarized. Related macrocycles bearing other linkers, such as ortho-phenylenes, meta-phenylenes, heteroaromatics, biphenyls, extended aromatics, are also overviewed. Bond angles of strained alkynes in pi-conjugated macrocycles, which are generable, detectable, and isolable, are summarized at the end of this review.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/chem.201904114" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31647144" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Feb 26", "date_precision": "day", "issue": "12", "normalized_date": "2020-02-26", "pages": "2529-2575", "proceedings_title": null, "publisher": "", "title": "Chemistry (Weinheim an der Bergstrasse, Germany)", "volume": "26", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "pi-Conjugated Macrocycles Bearing Angle-Strained Alkynes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "When oncogenic transformation or apoptosis occurs within epithelia, the harmful or dead cells are apically extruded from tissues to maintain epithelial homeostasis. However, the underlying molecular mechanism still remains elusive. In this study, we first show, using mammalian cultured epithelial cells and zebrafish embryos, that prior to apical extrusion of RasV12-transformed cells, calcium wave occurs from the transformed cell and propagates across the surrounding cells. The calcium wave then triggers and facilitates the process of extrusion. IP3 receptor, gap junction, and mechanosensitive calcium channel TRPC1 are involved in calcium wave. Calcium wave induces the polarized movement of the surrounding cells toward the extruding transformed cells. Furthermore, calcium wave facilitates apical extrusion, at least partly, by inducing actin rearrangement in the surrounding cells. Moreover, comparable calcium propagation also promotes apical extrusion of apoptotic cells. Thus, calcium wave is an evolutionarily conserved, general regulatory mechanism of cell extrusion.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuto", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Rika", "last_name": "Narumi", "name": null }, { "creator_type": "author", "first_name": "Ryutaro", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Elisa", "last_name": "Vitiello", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Tanimura", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Kuromiya", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Mihoko", "last_name": "Kajita", "name": null }, { "creator_type": "author", "first_name": "Masazumi", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Yukinari", "last_name": "Haraoka", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Akieda", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Ishitani", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Sohei", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Yoichiroh", "last_name": "Hosokawa", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2019.11.089" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32004455" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Feb 24", "date_precision": "day", "issue": "4", "normalized_date": "2020-02-24", "pages": "670-681.e6", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "30", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Calcium Wave Promotes Cell Extrusion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cellular durotaxis has been extensively studied in the field of mechanobiology. In principle, asymmetric mechanical field of a stiffness gradient generates motile polarity in a cell, which is a driving factor of durotaxis. However, the actual process by which the motile polarity in durotaxis develops is still unclear. In this study, to clarify the details of the kinetics of the development of durotactic polarity, we investigated the dynamics of both cell-shaping and the microscopic turnover of focal adhesions (FAs) for Venus-paxillin-expressing fibroblasts just crossing an elasticity boundary prepared on microelastically patterned gels. The Fourier mode analysis of cell-shaping based on a persistent random deformation model revealed that motile polarity at a cell-body scale was established within the first few hours after the leading edges of a moving cell passed through the boundary from the soft to the stiff regions. A fluorescence recovery after photobleaching (FRAP) analysis showed that the mobile fractions of paxillin at FAs in the anterior part of the cells exhibited an asymmetric increase within several tens of minutes after cells entered the stiff region. The results demonstrated that motile polarity in durotactic cells is established through the hierarchical step-wise development of different types of asymmetricity in the kinetics of FAs activity and cell-shaping with a several-hour time lag.Key words: Microelasticity patterned gel, durotaxis, cell polarity, focal adhesions, paxillin.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Thasaneeya", "last_name": "Kuboki", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Ebata", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Kidoaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1247/csf.19040" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31902938" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Elasticity", "descriptor_ui": "D004548", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Focal Adhesions", "descriptor_ui": "D022001", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Feb 22", "date_precision": "day", "issue": "1", "normalized_date": "2020-02-22", "pages": "33-43", "proceedings_title": null, "publisher": "", "title": "Cell structure and function", "volume": "45", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Hierarchical Development of Motile Polarity in Durotactic Cells Just Crossing an Elasticity Boundary.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Molecular networks containing various proteins mediate many types of cellular processes. Elucidation of how the proteins interact will improve our understanding of the molecular integration and physiological and pharmacological propensities of the network. One of the most complicated and unexplained interactions between proteins is the inter-G protein-coupled receptor (GPCR) interaction. Recently, many studies have suggested that an interaction between neurotransmitter GPCRs may mediate diverse modalities of neural responses. The B-type gamma-aminobutyric acid (GABA) receptor (GBR) and type-1 metabotropic glutamate receptor (mGluR1) are GPCRs for GABA and glutamate, respectively, and each plays distinct roles in controlling neurotransmission. We have previously reported the possibility of their functional interaction in central neurons. Here, we examined the interaction of these GPCRs using stable cell lines and rat cerebella. Cell-surface imaging and coimmunoprecipitation analysis revealed that these GPCRs interact on the cell surface. Furthermore, fluorometry revealed that these GPCRs mutually modulate signal transduction. These findings provide solid evidence that mGluR1 and GBR have intrinsic abilities to form complexes and to mutually modulate signaling. These findings indicate that synaptic plasticity relies on a network of proteins far more complex than previously assumed.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hakushun", "last_name": "Sakairi", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kamikubo", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Arata", "last_name": "Ichiki", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Sakurai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acschemneuro.9b00599" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31977183" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Central Nervous System", "descriptor_ui": "D002490", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Neurotransmitter Agents", "descriptor_ui": "D018377", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Receptors, GABA", "descriptor_ui": "D018079", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Feb 19", "date_precision": "day", "issue": "4", "normalized_date": "2020-02-19", "pages": "567-578", "proceedings_title": null, "publisher": "", "title": "ACS chemical neuroscience", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "G Protein-Coupled Glutamate and GABA Receptors Form Complexes and Mutually Modulate Their Signals.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescence imaging in the near-infrared (NIR) region (650-900 nm) is useful for bioimaging because background autofluorescence is low and tissue penetration is high in this range. In addition, NIR fluorescence is useful as a complementary color window to green and red for multicolor imaging. Here, we compared the photoinduced electron transfer (PeT)-mediated fluorescence quenching of silicon- and phosphorus-substituted rhodamines (SiRs and PRs) in order to guide the development of improved far-red to NIR fluorescent dyes. The results of density functional theory calculations and photophysical evaluation of a series of newly synthesized PRs confirmed that the fluorescence of PRs was more susceptible than that of SiRs to quenching via PeT. Based on this, we designed and synthesized a NIR fluorescence probe for Ca(2+) , CaPR-1, and its membrane-permeable acetoxymethyl derivative, CaPR-1 AM, which is distributed to the cytosol, in marked contrast to our previously reported Ca(2+) far-red to NIR fluorescence probe based on the SiR scaffold, CaSiR-1 AM, which is mainly localized in lysosomes as well as cytosol in living cells. CaPR-1 showed longer-wavelength absorption and emission (up to 712 nm) than CaSiR-1. The new probe was able to image Ca(2+) at dendrites and spines in brain slices, and should be a useful tool in neuroscience research.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shodai", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Honami", "last_name": "Echizen", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ikeno", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kenzo", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Masamitsu", "last_name": "Iino", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/asia.201901689" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31909880" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Feb 17", "date_precision": "day", "issue": "4", "normalized_date": "2020-02-17", "pages": "524-530", "proceedings_title": null, "publisher": "", "title": "Chemistry, an Asian journal", "volume": "15", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Rational Design of a Near-infrared Fluorescence Probe for Ca(2+) Based on Phosphorus-substituted Rhodamines Utilizing Photoinduced Electron Transfer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Photoacoustic (PA) tomography can be useful to measure the hemoglobin concentration in blood vessels and tissues, and provide important information to determine the course of treatment for hypoxic malignant cancer which possesses the resistance to treatment. To image the hemoglobin concentration and oxygen saturation, the reconstruction of absorption coefficients at multiple wavelengths is required to correct the penetration depths of the multiple wavelengths of light. In this study, the authors tried the image reconstruction of the absorption coefficient for various concentration of photon absorber. Additionally, the effects of the regularizations minimizing 1-norm and p-norm (0<p<1) were compared to examine the improvement of the spatial resolution limited by the characteristics and configurations of the ultrasound transducer and illumination. The PA pressure waves were measured by the probe consisted of the optical fiber and the focused ultrasound transducer. The absorption coefficients of the tubes containing black ink in the phantom made of aqueous solution of Intralipid were from 0.2 to 1.0 mm-1 at a wavelength of 755 nm, corresponding to the range from normoxic to hypoxic condition of the whole blood. Although the tubes with various absorption coefficients were reconstructed with 1-norm regularization, the tube was reconstructed broadly. On the other hand, the regularization technique minimizing p-norm (0<p<1) localized the tube better than 1-norm regularization. The regularization minimizing p-norm (0<p<1) will improve the spatial resolution of the PA tomography.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": null, "last_name": null, "name": "Shinpei Okawa" }, { "creator_type": "author", "first_name": null, "last_name": null, "name": "Takeshi Hirasawa" }, { "creator_type": "author", "first_name": null, "last_name": null, "name": "Toshihiro Kushibiki" }, { "creator_type": "author", "first_name": null, "last_name": null, "name": "Masanori Fujita" }, { "creator_type": "author", "first_name": null, "last_name": null, "name": "Miya Ishihara" } ], "identifiers": { "doi": { "normalized": "10.1117/12.2551478" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": "Proc.SPIE", "date": "2020-02-17", "date_precision": "day", "issue": "", "normalized_date": "2020-02-17", "pages": "112403N", "proceedings_title": "", "publisher": "", "title": null, "volume": "11240", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Photoacoustic tomography reconstructing absorption coefficient and effect of regularization minimizing p-norm", "url": "https://doi.org/10.1117/12.2551478", "zotero": { "item_type": "conferencePaper" } }, { "abstract": "Long-term memory (LTM) is stored as functional modifications of relevant neural circuits in the brain. A large body of evidence indicates that the initial establishment of such modifications through the process known as memory consolidation requires learning-dependent transcriptional activation and de novo protein synthesis. However, it remains poorly understood how the consolidated memory is maintained for a long period in the brain, despite constant turnover of molecular substrates. Using the Drosophila courtship conditioning assay of adult males as a memory paradigm, here, we show that in Drosophila, environmental light plays a critical role in LTM maintenance. LTM is impaired when flies are kept in constant darkness (DD) during the memory maintenance phase. Because light activates the brain neurons expressing the neuropeptide pigment-dispersing factor (Pdf), we examined the possible involvement of Pdf neurons in LTM maintenance. Temporal activation of Pdf neurons compensated for the DD-dependent LTM impairment, whereas temporal knockdown of Pdf during the memory maintenance phase impaired LTM in light/dark cycles. Furthermore, we demonstrated that the transcription factor cAMP response element-binding protein (CREB) is required in the memory center, namely, the mushroom bodies (MBs), for LTM maintenance, and Pdf signaling regulates light-dependent transcription via CREB. Our results demonstrate for the first time that universally available environmental light plays a critical role in LTM maintenance by activating the evolutionarily conserved memory modulator CREB in MBs via the Pdf signaling pathway.SIGNIFICANCE STATEMENT Temporary memory can be consolidated into long-term memory (LTM) through de novo protein synthesis and functional modifications of neuronal circuits in the brain. Once established, LTM requires continual maintenance so that it is kept for an extended period against molecular turnover and cellular reorganization that may disrupt memory traces. How is LTM maintained mechanistically? Despite the critical importance of LTM maintenance, its molecular and cellular underpinnings remain elusive. This study using Drosophila is significant because it revealed for the first time in any organism that universally available environmental light plays an essential role in LTM maintenance. Interestingly, light does so by activating the evolutionarily conserved transcription factor cAMP response element-binding protein via peptidergic signaling.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Show", "last_name": "Inami", "name": null }, { "creator_type": "author", "first_name": "Shoma", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shu", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Hiromu", "last_name": "Tanimoto", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kitamoto", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.1282-19.2019" }, "pmcid": { "normalized": "PMC7044726" }, "pmid": { "normalized": "31932417" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Conditioning, Classical", "descriptor_ui": "D003214", "major_topic": false }, { "descriptor": "Courtship", "descriptor_ui": "D003380", "major_topic": false }, { "descriptor": "Cyclic AMP Response Element-Binding Protein", "descriptor_ui": "D017362", "major_topic": false }, { "descriptor": "Darkness", "descriptor_ui": "D003624", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory Consolidation", "descriptor_ui": "D000069077", "major_topic": false }, { "descriptor": "Memory, Long-Term", "descriptor_ui": "D057567", "major_topic": false }, { "descriptor": "Mushroom Bodies", "descriptor_ui": "D024521", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Sleep Deprivation", "descriptor_ui": "D012892", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Feb 12", "date_precision": "day", "issue": "7", "normalized_date": "2020-02-12", "pages": "1427-1439", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "40", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Environmental Light Is Required for Maintenance of Long-Term Memory in Drosophila.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the anterior foregut (AFG) of mouse embryos, the transcription factor SOX2 is expressed in the epithelia of the esophagus and proximal branches of respiratory organs comprising the trachea and bronchi, whereas NKX2.1 is expressed only in the epithelia of respiratory organs. Previous studies using hypomorphic Sox2 alleles have indicated that reduced SOX2 expression causes the esophageal epithelium to display some respiratory organ characteristics. In the present study, we produced mouse embryos with AFG-specific SOX2 deficiency. In the absence of SOX2 expression, a single NKX2.1-expressing epithelial tube connected the pharynx and the stomach, and a pair of bronchi developed in the middle of the tube. Expression patterns of NKX2.1 and SOX9 revealed that the anterior and posterior halves of SOX2-deficient AFG epithelial tubes assumed the characteristics of the trachea and bronchus, respectively. In addition, we found that mesenchymal tissues surrounding the SOX2-deficient NKX2.1-expressing epithelial tube changed to those surrounding the trachea and bronchi in the anterior and posterior halves, as indicated by the arrangement of smooth muscle cells and SOX9-expressing cells and by the expression of Wnt4 (esophagus specific), Tbx4 (respiratory organ specific), and Hoxb6 (distal bronchus specific). The impact of mesenchyme-derived signaling on the early stage of AFG epithelial specification has been indicated. Our study demonstrated an opposite trend where epithelial tissue specification causes concordant changes in mesenchymal tissues, indicating a reciprocity of epithelial-mesenchymal interactions.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Machiko", "last_name": "Teramoto", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Katsura", "last_name": "Minegishi", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Uchikawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kuroiwa", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Kondoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/bio.048728" }, "pmcid": { "normalized": "PMC7044460" }, "pmid": { "normalized": "31988094" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Endoderm", "descriptor_ui": "D004707", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Esophagus", "descriptor_ui": "D004947", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": false }, { "descriptor": "Gastrointestinal Tract", "descriptor_ui": "D041981", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": false }, { "descriptor": "SOXB1 Transcription Factors", "descriptor_ui": "D055748", "major_topic": false }, { "descriptor": "Trachea", "descriptor_ui": "D014132", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Feb 7", "date_precision": "day", "issue": "2", "normalized_date": "2020-02-07", "pages": "bio048728", "proceedings_title": null, "publisher": "", "title": "Biology open", "volume": "9", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "The absence of SOX2 in the anterior foregut alters the esophagus into trachea and bronchi in both epithelial and mesenchymal components.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The 22q11.2 deletion syndrome (22q11.2DS) is associated with an increased risk for psychiatric disorders. Although most of the 22q11.2DS patients have a 3.0-Mb deletion, existing mouse models only mimic a minor mutation of 22q11.2DS, a 1.5-Mb deletion. The role of the genes existing outside the 1.5-Mb deletion in psychiatric symptoms of 22q11.2DS is unclear. In this study, we generated a mouse model that reproduced the 3.0-Mb deletion of the 22q11.2DS (Del(3.0 Mb)/ +) using the CRISPR/Cas9 system. Ethological and physiological phenotypes of adult male mutants were comprehensively evaluated by visual-evoked potentials, circadian behavioral rhythm, and a series of behavioral tests, such as measurement of locomotor activity, prepulse inhibition, fear-conditioning memory, and visual discrimination learning. As a result, Del(3.0 Mb)/ + mice showed reduction of auditory prepulse inhibition and attenuated cue-dependent fear memory, which is consistent with the phenotypes of existing 22q11.2DS models. In addition, Del(3.0 Mb)/ + mice displayed an impaired early visual processing that is commonly seen in patients with schizophrenia. Meanwhile, unlike the existing models, Del(3.0 Mb)/ + mice exhibited hypoactivity over several behavioral tests, possibly reflecting the fatigability of 22q11.2DS patients. Lastly, Del(3.0 Mb)/ + mice displayed a faster adaptation to experimental jet lag as compared with wild-type mice. Our results support the validity of Del(3.0 Mb)/ + mice as a schizophrenia animal model and suggest that our mouse model is a useful resource to understand pathogenic mechanisms of schizophrenia and other psychiatric disorders associated with 22q11.2DS.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Michinori", "last_name": "Koebis", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Kimiko", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Jingzhu", "last_name": "Liao", "name": null }, { "creator_type": "author", "first_name": "Bolati", "last_name": "Wulaer", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugaya", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Nagahama", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Kushima", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Kiyofumi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Fukada", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Atsu", "last_name": "Aiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41398-020-0723-z" }, "pmcid": { "normalized": "PMC7026107" }, "pmid": { "normalized": "32066675" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DiGeorge Syndrome", "descriptor_ui": "D004062", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Schizophrenia", "descriptor_ui": "D012559", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Feb 5", "date_precision": "day", "issue": "1", "normalized_date": "2020-02-05", "pages": "35", "proceedings_title": null, "publisher": "", "title": "Translational psychiatry", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Comprehensive analysis of a novel mouse model of the 22q11.2 deletion syndrome: a model with the most common 3.0-Mb deletion at the human 22q11.2 locus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary develops from oral ectoderm in contact with adjacent ventral hypothalamus. Impairment in this process results in congenital pituitary hypoplasia (CPH); however, there have been no human disease models for CPH thus far, prohibiting the elucidation of the underlying mechanisms. In this study, we established a disease model of CPH using patient-derived induced pluripotent stem cells (iPSCs) and 3D organoid technique, in which oral ectoderm and hypothalamus develop simultaneously. Interestingly, patient iPSCs with a heterozygous mutation in the orthodenticle homeobox 2 (OTX2) gene showed increased apoptosis in the pituitary progenitor cells, and the differentiation into pituitary hormone-producing cells was severely impaired. As an underlying mechanism, OTX2 in hypothalamus, not in oral ectoderm, was essential for progenitor cell maintenance by regulating LHX3 expression in oral ectoderm via FGF10 expression in the hypothalamus. Convincingly, the phenotype was reversed by the correction of the mutation, and the haploinsufficiency of OTX2 in control iPSCs revealed a similar phenotype, demonstrating that this mutation was responsible. Thus, we established an iPSC-based congenital pituitary disease model, which recapitulated interaction between hypothalamus and oral ectoderm and demonstrated the essential role of hypothalamic OTX2.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryusaku", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Hidetaka", "last_name": "Suga", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Aoi", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Fukuoka", "name": null }, { "creator_type": "author", "first_name": "Genzo", "last_name": "Iguchi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Narumi", "name": null }, { "creator_type": "author", "first_name": "Tomonobu", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci127378" }, "pmcid": { "normalized": "PMC6994153" }, "pmid": { "normalized": "31845906" } }, "mesh": [ { "descriptor": "Fibroblast Growth Factor 10", "descriptor_ui": "D051526", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Haploinsufficiency", "descriptor_ui": "D057895", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Otx Transcription Factors", "descriptor_ui": "D051857", "major_topic": false }, { "descriptor": "Pituitary Diseases", "descriptor_ui": "D010900", "major_topic": false }, { "descriptor": "Pituitary Gland", "descriptor_ui": "D010902", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Feb 3", "date_precision": "day", "issue": "2", "normalized_date": "2020-02-03", "pages": "641-654", "proceedings_title": null, "publisher": "", "title": "The Journal of clinical investigation", "volume": "130", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Congenital pituitary hypoplasia model demonstrates hypothalamic OTX2 regulation of pituitary progenitor cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We study a bad arm existence checking problem in a stochastic K-armed bandit setting, in which a player’s task is to judge whether a positive arm exists or all the arms are negative among given K arms by drawing as small number of arms as possible. Here, an arm is positive if its expected loss suffered by drawing the arm is at least a given threshold $$\theta _U$$, and it is negative if that is less than another given threshold $$\theta _L(\\le \theta _U)$$. This problem is a formalization of diagnosis of disease or machine failure. An interesting structure of this problem is the asymmetry of positive and negative arms’ roles; finding one positive arm is enough to judge positive existence while all the arms must be discriminated as negative to judge whole negativity. In the case with $$ arDelta =\theta _U-\theta _L>0$$, we propose elimination algorithms with arm selection policy (policy to determine the next arm to draw) and decision condition (condition to conclude positive arm’s existence or the drawn arm’s negativity) utilizing this asymmetric problem structure and prove its effectiveness theoretically and empirically.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Atsuyoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10994-019-05854-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2020-02-01", "date_precision": "day", "issue": "2", "normalized_date": "2020-02-01", "pages": "327-372", "proceedings_title": null, "publisher": "", "title": "Machine Learning", "volume": "109", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "A bad arm existence checking problem: How to utilize asymmetric problem structure?", "url": "https://doi.org/10.1007/s10994-019-05854-7", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Grazing-incidence small-angle X-ray scattering (GISAXS) coupled with computed tomography (CT) has enabled the visualization of the spatial distribution of nanostructures in thin films. 2D GISAXS images are obtained by scanning along the direction perpendicular to the X-ray beam at each rotation angle. Because the intensities at the q positions contain nanostructural information, the reconstructed CT images individually represent the spatial distributions of this information (e.g. size, shape, surface, characteristic length). These images are reconstructed from the intensities acquired at angular intervals over 180 degrees , but the total measurement time is prolonged. This increase in the radiation dosage can cause damage to the sample. One way to reduce the overall measurement time is to perform a scanning GISAXS measurement along the direction perpendicular to the X-ray beam with a limited interval angle. Using filtered back-projection (FBP), CT images are reconstructed from sinograms with limited interval angles from 3 to 48 degrees (FBP-CT images). However, these images are blurred and have a low image quality. In this study, to optimize the CT image quality, total variation (TV) regularization is introduced to minimize sinogram image noise and artifacts. It is proposed that the TV method can be applied to downsampling of sinograms in order to improve the CT images in comparison with the FBP-CT images.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Taizo", "last_name": "Kabe", "name": null }, { "creator_type": "author", "first_name": "Mikihito", "last_name": "Takenaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1107/s1600576719016558" }, "pmcid": { "normalized": "PMC6998772" }, "pmid": { "normalized": "32047408" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Feb 1", "date_precision": "day", "issue": "Pt 1", "normalized_date": "2020-02-01", "pages": "140-147", "proceedings_title": null, "publisher": "", "title": "Journal of applied crystallography", "volume": "53", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Improving grazing-incidence small-angle X-ray scattering-computed tomography images by total variation minimization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent studies have shown that stem cell memory T (TSCM) cell-like properties are important for successful adoptive immunotherapy by the chimeric antigen receptor-engineered-T (CAR-T) cells. We previously reported that both human and murine-activated T cells are converted into stem cell memory-like T (iTSCM) cells by coculture with stromal OP9 cells expressing the NOTCH ligand. However, the mechanism of NOTCH-mediated iTSCM reprogramming remains to be elucidated. Here, we report that the NOTCH/OP9 system efficiently converted conventional human CAR-T cells into TSCM-like CAR-T, \"CAR-iTSCM\" cells, and that mitochondrial metabolic reprogramming played a key role in this conversion. NOTCH signaling promoted mitochondrial biogenesis and fatty acid synthesis during iTSCM formation, which are essential for the properties of iTSCM cells. Forkhead box M1 (FOXM1) was identified as a downstream target of NOTCH, which was responsible for these metabolic changes and the subsequent iTSCM differentiation. Like NOTCH-induced CAR-iTSCM cells, FOXM1-induced CAR-iTSCM cells possessed superior antitumor potential compared with conventional CAR-T cells. We propose that NOTCH- or FOXM1-driven CAR-iTSCM formation is an effective strategy for improving cancer immunotherapy. SIGNIFICANCE: Manipulation of signaling and metabolic pathways important for directing production of stem cell memory-like T cells may enable development of improved CAR-T cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Tomisato", "name": null }, { "creator_type": "author", "first_name": "Tanakorn", "last_name": "Srirat", "name": null }, { "creator_type": "author", "first_name": "Binbin", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Setsuko", "last_name": "Mise-Omata", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nishimasu", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Nureki", "name": null }, { "creator_type": "author", "first_name": "Mitsuyo", "last_name": "Ohmura", "name": null }, { "creator_type": "author", "first_name": "Noriyo", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Hishiki", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Uchibori", "name": null }, { "creator_type": "author", "first_name": "Keiya", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/0008-5472.can-19-1196" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31767627" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Forkhead Box Protein M1", "descriptor_ui": "D000072278", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunologic Memory", "descriptor_ui": "D007156", "major_topic": false }, { "descriptor": "Immunotherapy, Adoptive", "descriptor_ui": "D016219", "major_topic": false }, { "descriptor": "Leukemia", "descriptor_ui": "D007938", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Mice, SCID", "descriptor_ui": "D016513", "major_topic": false }, { "descriptor": "Organelle Biogenesis", "descriptor_ui": "D001678", "major_topic": true }, { "descriptor": "Receptors, Chimeric Antigen", "descriptor_ui": "D000076962", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Stromal Cells", "descriptor_ui": "D017154", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Feb 1", "date_precision": "day", "issue": "3", "normalized_date": "2020-02-01", "pages": "471-483", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "80", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "The NOTCH-FOXM1 Axis Plays a Key Role in Mitochondrial Biogenesis in the Induction of Human Stem Cell Memory-like CAR-T Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Interfering with mitosis is a potential cancer therapy strategy. However, the lack of controllability of antimitotic drugs in cell growth suppression causes severe side effects and limits their clinical utility. Herein, we developed an azobenzene-based photoswitchable inhibitor of CENP-E, a mitotic kinesin required for chromosome transportation. The new inhibitor enabled reversible photoswitching of CENP-E activity with approximately 10-fold change in IC50 between cis and trans photoisomerization states both in vitro and in living cells. It also enabled repeatable photoswitching of CENP-E-dependent chromosome congression and hence mitotic progression with UV/vis light illumination cycles. Using this technique, we could specify the exact process of mitotic progression in which CENP-E plays an indispensable role. Our data demonstrate the power of a photochemical approach for highly controllable mitotic interference as well as for discovery of precise molecular functions in dynamic cellular processes.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Noushaba Nusrat", "last_name": "Mafy", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Hiruma", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Tamaoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.9b12782" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31927956" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Jan 29", "date_precision": "day", "issue": "4", "normalized_date": "2020-01-29", "pages": "1763-1767", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "142", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Photoswitchable CENP-E Inhibitor Enabling the Dynamic Control of Chromosome Movement and Mitotic Progression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Highly sensitive protein quantification enables the detection of a small number of protein molecules that serve as markers/triggers for various biological phenomena, such as cancer. Here, we describe the development of a highly sensitive protein quantification system called HaloTag protein barcoding. The method involves covalent linking of a target protein to a unique molecule counting oligonucleotide at a 1:1 conjugation ratio based on an azido-cycloalkyne click reaction. The sensitivity of the HaloTag-based barcoding was remarkably higher than that of a conventional luciferase assay. The HaloTag system was successfully validated by analyzing a set of protein-protein interactions, with the identification rate of 44% protein interactions between positive reference pairs reported in the literature. Desmoglein 3, the target antigen of pemphigus vulgaris, an IgG-mediated autoimmune blistering disease, was used in a HaloTag protein barcode assay to detect the anti-DSG3 antibody. The dynamic range of the assay was over 104-times wider than that of a conventional enzyme-linked immunosorbent assay (ELISA). The technology was used to detect anti-DSG3 antibody in patient samples with much higher sensitivity compared to conventional ELISA. Our detection system, with its superior sensitivity, enables earlier detection of diseases possibly allowing the initiation of care/treatment at an early disease stage.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Junshi", "last_name": "Yazaki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Taisaku", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Mayu", "last_name": "Okoshi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Kii", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Egami", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Amagai", "name": null }, { "creator_type": "author", "first_name": "Takamitsu", "last_name": "Hosoya", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Ohara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nar/gkz1086" }, "pmcid": { "normalized": "PMC6954424" }, "pmid": { "normalized": "31752022" } }, "mesh": [ { "descriptor": "Antibodies, Anti-Idiotypic", "descriptor_ui": "D000888", "major_topic": false }, { "descriptor": "Autoimmune Diseases", "descriptor_ui": "D001327", "major_topic": false }, { "descriptor": "Click Chemistry", "descriptor_ui": "D057930", "major_topic": false }, { "descriptor": "Cycloparaffins", "descriptor_ui": "D003516", "major_topic": false }, { "descriptor": "Desmoglein 3", "descriptor_ui": "D051184", "major_topic": false }, { "descriptor": "Enzyme-Linked Immunosorbent Assay", "descriptor_ui": "D004797", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoglobulin G", "descriptor_ui": "D007074", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Oligonucleotides", "descriptor_ui": "D009841", "major_topic": false }, { "descriptor": "Protein Interaction Domains and Motifs", "descriptor_ui": "D054730", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jan 24", "date_precision": "day", "issue": "2", "normalized_date": "2020-01-24", "pages": "e8", "proceedings_title": null, "publisher": "", "title": "Nucleic acids research", "volume": "48", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "HaloTag-based conjugation of proteins to barcoding-oligonucleotides.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We investigated the capability of simple microfluidic devices with trenches having vertical sidewalls for live-cell fluorescence imaging of adherent cells. An epithelial cell line that forms a two-dimensional (2D) sheet was cultured to adhere to the vertical sidewall so that its vertical section can be imaged directly using ordinal inverted-type laser-scanning microscopy. The material and the structure of the device were characterized. We show that the detailed distribution of intracellular organelles, such as microtubules and mitochondria, and of intercellular apparatus, such as claudin and zonula occludens, can be imaged with high spatio-temporal resolution with a single scan.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "contributor", "first_name": "Seigo", "last_name": "Araki", "name": null }, { "creator_type": "contributor", "first_name": "Masayoshi", "last_name": "Nakano", "name": null }, { "creator_type": "contributor", "first_name": "Mamiko", "last_name": "Tsugane", "name": null }, { "creator_type": "contributor", "first_name": "Fumiko", "last_name": "Sunaga", "name": null }, { "creator_type": "contributor", "first_name": "Mitsuru", "last_name": "Hattori", "name": null }, { "creator_type": "contributor", "first_name": "Masahiro", "last_name": "Nakano", "name": null }, { "creator_type": "contributor", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "contributor", "first_name": "Hiroaki", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c9an02165e" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Jan 21", "date_precision": "day", "issue": "", "normalized_date": "2020-01-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "", "volume": "145", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "A simple microfluidic device for live-imaging of the vertical section of epithelial cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To understand neuronal information processing, it is essential to investigate the input-output relationship and its modulation via detailed dissections of synaptic transmission between pre- and postsynaptic neurons. In Caenorhabditis elegans, pre-exposure to an odorant for five minutes reduces chemotaxis (early adaptation). AWC sensory neurons and AIY interneurons are crucial for this adaptation; AWC neurons sense volatile odors, and AIY interneurons receive glutamatergic inputs from AWC neurons. However, modulations via early adaptation of the input-output relationship between AWC and AIY are not well characterized. Here we use a variety of fluorescent imaging techniques to show that reduced synaptic-vesicle release without Ca(2+) modulation in AWC neurons suppresses the Ca(2+) response in AIY neurons via early adaptation. First, early adaptation modulates the Ca(2+) response in AIY but not AWC neurons. Adaptation in the Ca(2+) signal measured in AIY neurons is caused by adaptation in glutamate release from AWC neurons. Further, we found that a G protein gamma-subunit, GPC-1, is related to modulation of glutamate input to AIY. Our results dissect the modulation of the pre- and postsynaptic relationship in vivo based on optical methods, and demonstrate the importance of neurotransmitter-release modulation in presynaptic neurons without Ca(2+) modulation.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Keita", "last_name": "Ashida", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Shidara", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuroscience.2019.12.026" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31917348" } }, "mesh": [ { "descriptor": "Adaptation, Physiological", "descriptor_ui": "D000222", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Sensory Receptor Cells", "descriptor_ui": "D011984", "major_topic": false }, { "descriptor": "Smell", "descriptor_ui": "D012903", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jan 21", "date_precision": "day", "issue": "", "normalized_date": "2020-01-21", "pages": "112-121", "proceedings_title": null, "publisher": "", "title": "Neuroscience", "volume": "428", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Optical Dissection of Synaptic Plasticity for Early Adaptation in Caenorhabditis elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In addition to helper and regulatory potential, CD4(+) T cells also acquire cytotoxic activity marked by granzyme B (GzmB) expression and the ability to promote rejection of established tumors. Here, we examined the molecular and cellular mechanisms underpinning the differentiation of cytotoxic CD4(+) T cells following immunotherapy. CD4(+) transfer into lymphodepleted animals or regulatory T (Treg) cell depletion promoted GzmB expression by tumor-infiltrating CD4(+), and this was prevented by interleukin-2 (IL-2) neutralization. Transcriptional analysis revealed a polyfunctional helper and cytotoxic phenotype characterized by the expression of the transcription factors T-bet and Blimp-1. While T-bet ablation restricted interferon-gamma (IFN-gamma) production, loss of Blimp-1 prevented GzmB expression in response to IL-2, suggesting two independent programs required for polyfunctionality of tumor-reactive CD4(+) T cells. Our findings underscore the role of Treg cells, IL-2, and Blimp-1 in controlling the differentiation of cytotoxic CD4(+) T cells and offer a pathway to enhancement of anti-tumor activity through their manipulation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Anna", "last_name": "Sledzinska", "name": null }, { "creator_type": "author", "first_name": "Maria", "last_name": "Vila de Mucha", "name": null }, { "creator_type": "author", "first_name": "Katharina", "last_name": "Bergerhoff", "name": null }, { "creator_type": "author", "first_name": "Alastair", "last_name": "Hotblack", "name": null }, { "creator_type": "author", "first_name": "Dafne Franz", "last_name": "Demane", "name": null }, { "creator_type": "author", "first_name": "Ehsan", "last_name": "Ghorani", "name": null }, { "creator_type": "author", "first_name": "Ayse U.", "last_name": "Akarca", "name": null }, { "creator_type": "author", "first_name": "Maria A. V.", "last_name": "Marzolini", "name": null }, { "creator_type": "author", "first_name": "Isabelle", "last_name": "Solomon", "name": null }, { "creator_type": "author", "first_name": "Frederick Arce", "last_name": "Vargas", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Pule", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Benedict", "last_name": "Seddon", "name": null }, { "creator_type": "author", "first_name": "George", "last_name": "Kassiotis", "name": null }, { "creator_type": "author", "first_name": "Charlotte E.", "last_name": "Ariyan", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Korn", "name": null }, { "creator_type": "author", "first_name": "Teresa", "last_name": "Marafioti", "name": null }, { "creator_type": "author", "first_name": "Graham M.", "last_name": "Lord", "name": null }, { "creator_type": "author", "first_name": "Hans", "last_name": "Stauss", "name": null }, { "creator_type": "author", "first_name": "Richard G.", "last_name": "Jenner", "name": null }, { "creator_type": "author", "first_name": "Karl S.", "last_name": "Peggs", "name": null }, { "creator_type": "author", "first_name": "Sergio A.", "last_name": "Quezada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.immuni.2019.12.007" }, "pmcid": { "normalized": "PMC7369640" }, "pmid": { "normalized": "31924474" } }, "mesh": [ { "descriptor": "Adoptive Transfer", "descriptor_ui": "D019264", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Granzymes", "descriptor_ui": "D053804", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interferon-gamma", "descriptor_ui": "D007371", "major_topic": false }, { "descriptor": "Interleukin-2", "descriptor_ui": "D007376", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Positive Regulatory Domain I-Binding Factor 1", "descriptor_ui": "D000074462", "major_topic": false }, { "descriptor": "T-bet Transcription Factor", "descriptor_ui": "D000098815", "major_topic": false }, { "descriptor": "T-Box Domain Proteins", "descriptor_ui": "D020825", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jan 14", "date_precision": "day", "issue": "1", "normalized_date": "2020-01-14", "pages": "151-166.e6", "proceedings_title": null, "publisher": "", "title": "Immunity", "volume": "52", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Regulatory T Cells Restrain Interleukin-2- and Blimp-1-Dependent Acquisition of Cytotoxic Function by CD4(+) T Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Microfold cells (M cells) are responsible for antigen uptake to initiate immune responses in the gut-associated lymphoid tissue (GALT). Receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for M cell differentiation. Follicle-associated epithelium (FAE) covers the GALT and is continuously exposed to RANKL from stromal cells underneath the FAE, yet only a subset of FAE cells undergoes differentiation into M cells. Here, we show that M cells express osteoprotegerin (OPG), a soluble inhibitor of RANKL, which suppresses the differentiation of adjacent FAE cells into M cells. Notably, OPG deficiency increases M cell number in the GALT and enhances commensal bacterium-specific immunoglobulin production, resulting in the amelioration of disease symptoms in mice with experimental colitis. By contrast, OPG-deficient mice are highly susceptible to Salmonella infection. Thus, OPG-dependent self-regulation of M cell differentiation is essential for the balance between the infectious risk and the ability to perform immunosurveillance at the mucosal surface.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Nobuhide", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Mutoh", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Takahashi-Iwanaga", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Meri", "last_name": "Hisamoto", "name": null }, { "creator_type": "author", "first_name": "Midori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Udagawa", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tsuneyasu", "last_name": "Kaisho", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Iwanaga", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Hase", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-019-13883-y" }, "pmcid": { "normalized": "PMC6957684" }, "pmid": { "normalized": "31932605" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Bacterial", "descriptor_ui": "D000907", "major_topic": false }, { "descriptor": "Cecum", "descriptor_ui": "D002432", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Colitis", "descriptor_ui": "D003092", "major_topic": false }, { "descriptor": "Dextran Sulfate", "descriptor_ui": "D016264", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Gastrointestinal Microbiome", "descriptor_ui": "D000069196", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Immunity, Mucosal", "descriptor_ui": "D018928", "major_topic": false }, { "descriptor": "Immunoglobulin G", "descriptor_ui": "D007074", "major_topic": false }, { "descriptor": "Intestinal Mucosa", "descriptor_ui": "D007413", "major_topic": false }, { "descriptor": "Lymphoid Tissue", "descriptor_ui": "D008221", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Osteoprotegerin", "descriptor_ui": "D053244", "major_topic": false }, { "descriptor": "RANK Ligand", "descriptor_ui": "D053245", "major_topic": false }, { "descriptor": "Receptor Activator of Nuclear Factor-kappa B", "descriptor_ui": "D053246", "major_topic": false }, { "descriptor": "Salmonella Infections", "descriptor_ui": "D012480", "major_topic": false }, { "descriptor": "Salmonella typhimurium", "descriptor_ui": "D012486", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jan 13", "date_precision": "day", "issue": "1", "normalized_date": "2020-01-13", "pages": "234", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Osteoprotegerin-dependent M cell self-regulation balances gut infection and immunity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Methyl transfer reactions play important roles in many biological phenomena, wherein the methylation cofactor S-adenosyl-l-methionine (SAM) serves as the important currency to orchestrate those reactions. We have developed a fluorescent-probe-based high-throughput screening (HTS) system to search for the compounds that control cellular SAM levels. HTS with a drug repositioning library revealed the importance of catechol-O-methyltransferase (COMT) and its substrates in controlling the SAM concentrations and histone methylation levels in colorectal tumor cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shusuke", "last_name": "Ogihara", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Yanagi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.9b08698" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31869215" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Catechol O-Methyltransferase", "descriptor_ui": "D002394", "major_topic": false }, { "descriptor": "Catechols", "descriptor_ui": "D002396", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": true }, { "descriptor": "HT29 Cells", "descriptor_ui": "D019073", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "S-Adenosylmethionine", "descriptor_ui": "D012436", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jan 8", "date_precision": "day", "issue": "1", "normalized_date": "2020-01-08", "pages": "21-26", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "142", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolic-Pathway-Oriented Screening Targeting S-Adenosyl-l-methionine Reveals the Epigenetic Remodeling Activities of Naturally Occurring Catechols.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The magnesium ion (Mg(2+)) is an essential cation to maintain proper cellular activities. To visualize the dynamics and functions of Mg(2+), there is a great need for the development of Mg(2+)-selective fluorescent probes. However, conventional Mg(2+) fluorescent probes are falling behind in low selectivity and poor fluorescence color variation. In this report, to make available a distinct color window for multi-color imaging, we designed and synthesized highly Mg(2+)-selective and near-infrared (NIR) fluorescent probes, the KMG-500 series consisting of a charged beta-diketone as a selective binding site for Mg(2+) and a Si-rhodamine residue as the NIR fluorophore, which showed photoinduced electron transfer (PeT)-type OFF-ON response to the concentration of Mg(2+). Two types of KMG-500 series probes, tetramethyl substituted Si-rhodamine KMG-501 and tetraethyl substituted Si-rhodamine KMG-502, were synthesized for the evaluation of cell permeability. For intracellular application, the membrane-permeable acetoxymethyl derivative KMG-501 (KMG-501AM) was synthesized and allowed to stably stain cultured rat hippocampal neurons during imaging of intracellular Mg(2+). On the other hand, KMG-502 was cell membrane permeable without AM modification, preventing the probe from staying inside cells during imaging. KMG-501 distributed mainly in the cytoplasm and partially localized in lysosomes and mitochondria in cultured rat hippocampal neurons. Mg(2+) increase in response to the FCCP uncoupler inducing depolarization of the mitochondrial inner membrane potential was detected in the KMG-501 stained neurons. For the first time, KMG-501 succeeded in imaging intracellular Mg(2+) dynamics with NIR fluorescence. Moreover, it allows one to simultaneously visualize changes in Mg(2+) and ATP concentration and also mitochondrial inner membrane potential and their interactions. This probe is expected to be a strong tool for multi-color imaging of intracellular Mg(2+).", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "contributor", "first_name": "Osamu", "last_name": "Murata", "name": null }, { "creator_type": "contributor", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "contributor", "first_name": "Yuma", "last_name": "Ikeda", "name": null }, { "creator_type": "contributor", "first_name": "Naoko", "last_name": "Iwasawa", "name": null }, { "creator_type": "contributor", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "contributor", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "contributor", "first_name": "Yuki", "last_name": "Hiruta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.9b03872" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Jan 7", "date_precision": "day", "issue": "", "normalized_date": "2020-01-07", "pages": "", "proceedings_title": null, "publisher": "", "title": "", "volume": "92", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Near-Infrared Fluorescent Probes for Imaging of Intracellular Mg(2+) and Application to Multi-Color Imaging of Mg(2+), ATP, and Mitochondrial Membrane Potential.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The spiral wave is a commonly observed spatio-temporal order in diverse signal relaying systems. Although properties of generated spirals have been well studied, the mechanisms for their spontaneous generation in living systems remain elusive. By the newly developed imaging system for trans-scale observation of the intercellular communication among ∼130,000 cells of social amoeba, we investigated the onset dynamics of cAMP signaling and identified mechanisms for the self-organization of the spiral wave at three distinct scalings: At the population-level, the structured heterogeneity of excitability fragments traveling waves at its high/low boundary, that becomes the generic source of the spiral wave. At the cell-level, both the pacemaking leaders and pulse-amplifying followers regulate the heterogeneous growth of the excitability. At the intermediate-scale, the essence of the spontaneous wave fragmentation is the asymmetric positioning of the pacemakers in the high-excitability territories, whose critical controls are operated by a small number of cells, pulse counts, and pulse amounts.Competing Interest StatementThe authors have declared no competing interest.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taishi", "last_name": "Kakizuka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Yusaku", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Mukai", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Ichiraku", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/2020.06.29.176891" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2020-01-01", "date_precision": "day", "issue": "", "normalized_date": "2020-01-01", "pages": "2020.06.29.176891", "proceedings_title": null, "publisher": "", "title": "bioRxiv", "volume": "", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Cellular logics bringing the symmetry breaking in spiral nucleation revealed by trans-scale imaging", "url": "http://biorxiv.org/content/early/2020/06/29/2020.06.29.176891.abstract", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The prevention of age-related memory decline and dementia has been becoming a high priority because of the rapid growth in aging populations. Accumulating epidemiological and clinical studies indicate that intake of fermented dairy products rich in beta-lactolin improves memory retrieval and executive function and attenuates cognitive decline in the elderly. However, the effects of long-term consumption of beta-lactolin on Alzheimer's disease (AD) pathologies have not been investigated. In the present study, we examined the effects of beta-lactolin and whey digestion rich in beta-lactolin on AD pathology in 5xFAD transgenic mice and PS19 tauopathy mice. Intake of beta-lactolin and whey digestion rich in beta-lactolin reduced the levels of inflammatory cytokines, suppressed the infiltration of activated microglia, decreased the levels of amyloid-beta, ameliorated impaired long-term object memory, and attenuated decreased synaptophysin, dopamine, brain-derived neurotrophic factor, and insulin-like growth factor 1 levels in the cortex in 5xFAD transgenic mice. In addition, intake of beta-lactolin and whey digestion rich in beta-lactolin improved behavioral abnormality and reduced the ratio of phosphorylated tau to total tau in the cortex in PS19 tauopathy mice. These findings indicate that consumption with beta-lactolin and whey digestion rich in beta-lactolin suppresses inflammation and attenuates AD pathology and cognitive impairment.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Ano", "name": null }, { "creator_type": "author", "first_name": "Rena", "last_name": "Ohya", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Takaichi", "name": null }, { "creator_type": "author", "first_name": "Terukatsu", "last_name": "Washinuma", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nakayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.3233/jad-190997" }, "pmcid": { "normalized": "PMC7081097" }, "pmid": { "normalized": "31929163" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Amyloid beta-Peptides", "descriptor_ui": "D016229", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Cognitive Dysfunction", "descriptor_ui": "D060825", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Macrophage Activation", "descriptor_ui": "D008262", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microglia", "descriptor_ui": "D017628", "major_topic": false }, { "descriptor": "Neurotransmitter Agents", "descriptor_ui": "D018377", "major_topic": false }, { "descriptor": "Oligopeptides", "descriptor_ui": "D009842", "major_topic": false }, { "descriptor": "Psychomotor Performance", "descriptor_ui": "D011597", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": false }, { "descriptor": "Whey Proteins", "descriptor_ui": "D000067816", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "4", "normalized_date": "2020", "pages": "1331-1342", "proceedings_title": null, "publisher": "", "title": "Journal of Alzheimer's disease : JAD", "volume": "73", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "beta-Lactolin, a Whey-Derived Lacto-Tetrapeptide, Prevents Alzheimer's Disease Pathologies and Cognitive Decline.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tracheal cartilage provides architectural integrity to the respiratory airway, and defects in this structure during embryonic development cause severe congenital anomalies. Previous genetic studies have revealed genes that are critical for the development of tracheal cartilage. However, it is still unclear how crosstalk between these proteins regulates tracheal cartilage formation. Here we show a core regulatory network underlying murine tracheal chondrogenesis from embryonic day (E) 12.5 to E15.5, by combining volumetric imaging of fluorescence reporters, inhibitor assays, and mathematical modeling. We focused on SRY-box transcription factor 9 (Sox9) and extracellular signal-regulated kinase (ERK) in the tracheal mesenchyme, and observed a synchronous, inverted U-shaped temporal change in both Sox9 expression and ERK activity with a peak at E14.5, whereas the expression level of downstream cartilage matrix genes, such as collagen II alpha 1 (Col2a1) and aggrecan (Agc1), monotonically increased. Inhibitor assays revealed that the ERK signaling pathway functions as an inhibitory regulator of tracheal cartilage differentiation during this period. These results suggest that expression of the cartilage matrix genes is controlled by an incoherent feedforward loop via Sox9 and ERK, which is supported by a mathematical model. Furthermore, the modeling analysis suggests that a Sox9-ERK incoherent feedforward regulation augments the robustness against the variation of upstream factors. The present study provides a better understanding of the regulatory network underlying the tracheal development and will be helpful for efficient induction of tracheal organoids.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2020.585640" }, "pmcid": { "normalized": "PMC7642454" }, "pmid": { "normalized": "33195234" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "585640", "proceedings_title": null, "publisher": "", "title": "Frontiers in cell and developmental biology", "volume": "8", "year": 2020 }, "ssbd": { "database": [ "ssbd-database-000172" ], "repository": [ "ssbd-repos-000172" ] }, "title": "Incoherent Feedforward Regulation via Sox9 and ERK Underpins Mouse Tracheal Cartilage Development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: Tocilizumab (TCZ) is a humanised anti-interleukin (IL)-6 receptor (IL-6R) monoclonal antibody that is a promising agent to treat various autoimmune diseases. However, the mechanism of TCZ efficacy is unclear. This study aims to elucidate the relationship between Tregs and IL-6R blockade in autoimmunity-mediated renal disease based on a TCZ-treated cohort of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and in an experimental model of crescentic glomerulonephritis (cGN). METHODS: We examined multiple serum levels of cytokines and chemokines and peripheral blood mononuclear cells in patients with AAV who received TCZ monotherapy and achieved drug-free remission. Moreover, we investigated the mechanistic role of IL-6R blockade in accelerated cGN model to analyse the local sites of inflammation. RESULTS: Serum chemokines CCL22 and CCL17, in addition to the CCR4(+)Foxp3(+) Treg population, increased in patients who demonstrated drug-free remission after the cessation of TCZ. In the cGN model, IL-6R blockade ameliorated the disease, elevated CCL22/17 in CD206(+)CD11b(+)CD11c(+) kidney M2-like type macrophages, and increased the migration of Tregs into the kidney and regional lymph nodes. The local administration of CCL22 in the kidney facilitated Treg accumulation and reduced glomerular crescent formation. CONCLUSIONS: This study revealed a new mechanism whereby effector Tregs migrate into the inflammatory kidney via the CCL22/17-CCR4 axis that is facilitated by M2-like type macrophages that are induced by IL-6R blockade.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryota", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Kurasawa", "name": null }, { "creator_type": "author", "first_name": "Tsuneo", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cti2.1203" }, "pmcid": { "normalized": "PMC7596393" }, "pmid": { "normalized": "33163184" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "11", "normalized_date": "2020", "pages": "e1203", "proceedings_title": null, "publisher": "", "title": "Clinical & translational immunology", "volume": "9", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Tocilizumab monotherapy uncovered the role of the CCL22/17-CCR4(+) Treg axis during remission of crescentic glomerulonephritis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Gas vesicle nanoparticles (GVs) are gas-containing protein assemblies expressed in bacteria and archaea. Recently, GVs have gained considerable attention for biotechnological applications as genetically encodable contrast agents for MRI and ultrasonography. However, at present, the practical use of GVs is hampered by a lack of robust methodology for their induction into mammalian cells. Here, we demonstrate the genetic reconstitution of protein nanoparticles with characteristic bicone structures similar to natural GVs in a human breast cancer cell line KPL-4 and genetic control of their size and shape through expression of reduced sets of humanized gas vesicle genes cloned into Tol2 transposon vectors, referencing the natural gas vesicle gene clusters of the cyanobacteria planktothrix rubescens/agardhii. We then report the utility of these nanoparticles as multiplexed, sensitive, and genetically encoded contrast agents for hyperpolarized xenon chemical exchange saturation transfer (HyperCEST) MRI.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ryota", "last_name": "Mizushima", "name": null }, { "creator_type": "author", "first_name": "Kanako", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Atsuko H.", "last_name": "Iwane", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Atsuomi", "last_name": "Kimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1155/2020/5425934" }, "pmcid": { "normalized": "PMC7091528" }, "pmid": { "normalized": "32256252" } }, "mesh": [ { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": true }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Xenon Isotopes", "descriptor_ui": "D014979", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "5425934", "proceedings_title": null, "publisher": "", "title": "Contrast media & molecular imaging", "volume": "2020", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Multiplexed (129)Xe HyperCEST MRI Detection of Genetically Reconstituted Bacterial Protein Nanoparticles in Human Cancer Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Microtubule-associated protein tau is characterized by the fact that it is an intrinsically disordered protein due to its lack of a stable conformation and high flexibility. Intracellular inclusions of fibrillar forms of tau with a beta-sheet structure accumulate in the brain of patients with Alzheimer's disease and other tauopathies. Accordingly, detachment of tau from microtubules and transition of tau from a disordered state to an abnormally aggregated state are essential events preceding the onset of tau-related diseases. Many reports have shown that this transition is caused by post-translational modifications, including hyperphosphorylation and acetylation. The misfolded tau is self-assembled and forms a tau oligomer before the appearance of tau inclusions. Animal and pathological studies using human samples have demonstrated that tau oligomer formation contributes to neuronal loss. During the progression of tauopathies, tau seeds are released from cells and incorporated into other cells, leading to the propagation of pathological tau aggregation. Accumulating evidence suggests several potential approaches for blocking tau-mediated toxicity: (1) direct inhibition of pathological tau aggregation and (2) inhibition of tau post-translational modifications that occur prior to pathological tau aggregation, (3) inhibition of tau propagation and (4) stabilization of microtubules. In addition to traditional low-molecular-weight compounds, newer drug discovery approaches such as the development of medium-molecular-weight drugs (peptide- or oligonucleotide-based drugs) and high-molecular-weight drugs (antibody-based drugs) provide alternative pathways to preventing the formation of abnormal tau. Of particular interest are recent studies suggesting that tau droplet formation by liquid-liquid phase separation may be the initial step in aberrant tau aggregation, as well results that implicate roles for tau in dendritic and nuclear functions. Here, we review the mechanisms through which drugs can target tau and consider recent clinical trials for the treatment of tauopathies. In addition, we discuss the utility of these newer strategies and propose future directions for research on tau-targeted therapeutics.", "classifications": [ { "id": "18H05414", "label": "18H05414", "researcher": "Hiroko Bannai", "type": "grant" }, { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Soeda", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnmol.2020.590896" }, "pmcid": { "normalized": "PMC7744460" }, "pmid": { "normalized": "33343298" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "590896", "proceedings_title": null, "publisher": "", "title": "Frontiers in molecular neuroscience", "volume": "13", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "New Insights Into Drug Discovery Targeting Tau Protein.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Michael", "last_name": "Lazarus", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Sakiko", "last_name": "Honjoh", "name": null }, { "creator_type": "author", "first_name": "Kaspar E.", "last_name": "Vogt", "name": null }, { "creator_type": "author", "first_name": "Ada", "last_name": "Eban-Rothschild", "name": null }, { "creator_type": "author", "first_name": "Qinghua", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Sakurai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2020.00773" }, "pmcid": { "normalized": "PMC7431517" }, "pmid": { "normalized": "32848553" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "773", "proceedings_title": null, "publisher": "", "title": "Frontiers in neuroscience", "volume": "14", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Editorial: The Gating and Maintenance of Sleep and Wake: New Circuits and Insights.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The CRISPR/Cas9 system is a powerful tool for generation of genetically modified mice. In conventional protocols, Cas9 protein (or mRNA) and sgRNA are introduced into zygotes by microinjection. However, microinjection requires special skill and is too time-consuming to treat zygotes on a large scale. Recently, we have developed a simple electroporation method which generates genetically modified mice with high efficiency. Here, we describe our method GEEP (genome editing by electroporation of Cas9 protein). This method facilitates high-throughput genetic analysis of the mouse. This chapter describes the GEEP method to generate genetically modified mice.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4939-9740-4_13" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31468486" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "CRISPR-Associated Protein 9", "descriptor_ui": "D000076987", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Electroporation", "descriptor_ui": "D018274", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "RNA, Guide, CRISPR-Cas Systems", "descriptor_ui": "D000094704", "major_topic": false }, { "descriptor": "Zygote", "descriptor_ui": "D015053", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "121-126", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2050", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Zygote Electroporation for CRISPR/Cas9 Delivery to Generate Genetically Modified Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bsj-2020018" }, "pmcid": { "normalized": "PMC7610062" }, "pmid": { "normalized": "33194511" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "98-99", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "17", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Detection of singularity in immunity and cancer by novel imaging techniques.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Severe COVID-19 patients show various immunological abnormalities including T-cell reduction and cytokine release syndrome, which can be fatal and is a major concern of the pandemic. However, it is poorly understood how T-cell dysregulation can contribute to the pathogenesis of severe COVID-19. Here we show single cell-level mechanisms for T-cell dysregulation in severe COVID-19, demonstrating new pathogenetic mechanisms of T-cell activation and differentiation underlying severe COVID-19. By in silico sorting CD4+ T-cells from a single cell RNA-seq dataset, we found that CD4+ T-cells were highly activated and showed unique differentiation pathways in the lung of severe COVID-19 patients. Notably, those T-cells in severe COVID-19 patients highly expressed immunoregulatory receptors and CD25, whilst repressing the expression of FOXP3. Furthermore, we show that CD25(+) hyperactivated T-cells differentiate into multiple helper T-cell lineages, showing multifaceted effector T-cells with Th1 and Th2 characteristics. Lastly, we show that CD25-expressing hyperactivated T-cells produce the protease Furin, which facilitates the viral entry of SARS-CoV-2. Collectively, CD4(+) T-cells from severe COVID-19 patients are hyperactivated and FOXP3-mediated negative feedback mechanisms are impaired in the lung, which may promote immunopathology. Therefore, our study proposes a new model of T-cell hyperactivation and paralysis that drives immunopathology in severe COVID-19.", "classifications": [ { "id": "19H05426", "label": "19H05426", "researcher": "Masahiro Ono", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Bahire", "last_name": "Kalfaoglu", "name": null }, { "creator_type": "author", "first_name": "Jose", "last_name": "Almeida-Santos", "name": null }, { "creator_type": "author", "first_name": "Chanidapa Adele", "last_name": "Tye", "name": null }, { "creator_type": "author", "first_name": "Yorifumi", "last_name": "Satou", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2020.589380" }, "pmcid": { "normalized": "PMC7596772" }, "pmid": { "normalized": "33178221" } }, "mesh": [ { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": false }, { "descriptor": "Databases, Genetic", "descriptor_ui": "D030541", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Furin", "descriptor_ui": "D045683", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interleukin-2 Receptor alpha Subunit", "descriptor_ui": "D053645", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Paralysis", "descriptor_ui": "D010243", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false }, { "descriptor": "RNA-Seq", "descriptor_ui": "D000081246", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false }, { "descriptor": "Severity of Illness Index", "descriptor_ui": "D012720", "major_topic": true }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false }, { "descriptor": "Virus Internalization", "descriptor_ui": "D053586", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "589380", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "T-Cell Hyperactivation and Paralysis in Severe COVID-19 Infection Revealed by Single-Cell Analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescence microscopy is currently one of the more powerful and versatile techniques available for biological studies. With conventional biological immunofluorescence microscopy, caveolin-1 (CAV1) is visualized as numerous small dots, which are often distributed as a linear array or along the edge of the cell. Although its presence, as well as that of other proteins, can be detected by conventional immunofluorescence microscopy, those results do not clarify whether two different proteins exist in the plasma membrane of a specimen or how they are distributed two-dimensionally. Here, we describe an unroofing procedure that clearly reveals CAV1 localization in a single plane of the plasma membrane and also demonstrate a super-resolution structured illumination microscopy technique for observation of CAV1 in the plasma membrane.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tomoya", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Toyoshi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-0732-9_4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32548817" } }, "mesh": [ { "descriptor": "Caveolin 1", "descriptor_ui": "D051242", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "43-52", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2169", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Method for Efficient Observation of Caveolin-1 in Plasma Membrane by Microscopy Imaging Analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Crustacean reproduction has been hypothesized to be under complex endocrinological regulation by peptide hormones. To further improve our understanding of the mechanisms underlying this complex regulation, knowledge is needed regarding the hormones not only of the central nervous system (CNS) such as the X-organ/sinus gland (XOSG), brain, and thoracic ganglia, but also the peripheral gonadal tissues. For example, in vertebrates, some gonadal peptide hormones including activin, inhibin, follistatin, and relaxin are known to be involved in the reproductive physiology. Therefore, it is highly likely that some peptide factors from the ovary are serving as the signals among peripheral tissues and central nervous tissues in crustaceans. In this work, we sought to find gonadal peptide hormones and peptide hormone receptors by analyzing the transcriptome of the ovary of the kuruma prawn Marsupenaeus japonicus. The generated ovarian transcriptome data led to the identification of five possible peptide hormones, including bursicon-alpha and -beta, the crustacean hyperglycemic hormone (CHH)-like peptide, insulin-like peptide (ILP), and neuroparsin-like peptide (NPLP). Dominant gene expressions for the bursicons were observed in the thoracic ganglia and the ovary, in the CNS for the CHH-like peptide, in the heart for NPLP, and in the ovary for ILP. Since the gene expressions of CHH-like peptide and NPLP were affected by a CHH (Penaeus japonicus sinus gland peptide-I) from XOSG, we produced recombinant peptides for CHH-like peptide and NPLP using Escherichia coli expression system to examine their possible peripheral regulation. As a result, we found that the recombinant NPLP increased vitellogenin gene expression in incubated ovarian tissue fragments. Moreover, contigs encoding putative receptors for insulin-like androgenic gland factor, insulin, neuroparsin, and neuropeptide Y/F, as well as several contigs encoding orphan G-protein coupled receptors and receptor-type guanylyl cyclases were also identified in the ovarian transcriptome. These results suggest that reproductive physiology in crustaceans is regulated by various gonadal peptide hormones, akin to vertebrates.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naoaki", "last_name": "Tsutsui", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Izumikawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fendo.2020.00541" }, "pmcid": { "normalized": "PMC7466434" }, "pmid": { "normalized": "32973675" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arthropod Proteins", "descriptor_ui": "D060829", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Organ Specificity", "descriptor_ui": "D009928", "major_topic": false }, { "descriptor": "Ovary", "descriptor_ui": "D010053", "major_topic": false }, { "descriptor": "Penaeidae", "descriptor_ui": "D033561", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "541", "proceedings_title": null, "publisher": "", "title": "Frontiers in endocrinology", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Transcriptomic Analysis of the Kuruma Prawn Marsupenaeus japonicus Reveals Possible Peripheral Regulation of the Ovary.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mammalian haploid somatic cells are unstable and prone to diploidize, but the cause of haploid instability remains largely unknown. Previously, we found that mammalian haploid somatic cells suffer chronic centrosome loss stemming from the uncoupling of DNA replication and centrosome duplication cycles. However, the lack of methodology to restore the coupling between DNA replication and centrosome duplication has precluded us from investigating the potential contribution of the haploidy-linked centrosome loss to haploid instability. In this study, we developed an experimental method that allows the re-coupling of DNA and centrosome cycles through the chronic extension of the G1/S phase without compromising cell proliferation using thymidine treatment/release cycles. Chronic extension of G1/S restored normal mitotic centrosome number and mitotic control, substantially improving the stability of the haploid state in HAP1 cells. Stabilization of the haploid state was compromised when cdk2 was inhibited during the extended G1/S, or when early G1 was chronically extended instead of G1/S, showing that the coupling of DNA and centrosome cycles rather than a general extension of the cell cycle is required for haploid stability. Our data indicate the chronic centriole loss arising from the uncoupling of centrosome and DNA cycles as a direct cause of genome instability in haploid somatic cells, and also demonstrate the feasibility of modulation of haploid stability through artificial coordination between DNA and centrosome cycles in mammalian somatic cells.", "classifications": [ { "id": "19H05413", "label": "19H05413", "researcher": "Ryota Uehara", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Koya", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Yaguchi", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2020.00721" }, "pmcid": { "normalized": "PMC7408703" }, "pmid": { "normalized": "32850837" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "721", "proceedings_title": null, "publisher": "", "title": "Frontiers in cell and developmental biology", "volume": "8", "year": 2020 }, "ssbd": { "database": [ "ssbd-database-000240" ], "repository": [ "ssbd-repos-000240" ] }, "title": "Uncoupling of DNA Replication and Centrosome Duplication Cycles Is a Primary Cause of Haploid Instability in Mammalian Somatic Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pathological aggregates of tau proteins accumulate in the brains of neurodegenerative tauopathies including Alzheimer's disease and frontotemporal lobar degeneration (FTLD-tau). Although immunotherapies of these disorders against tau are emerging, it is unknown whether nasal delivery, which offers many benefits over traditional approaches to vaccine administration, is effective or not for tauopathy. Here, we developed vaccination against a secreted form of pathological tau linked to FTLD-tau using a Sendai virus (SeV) vector infectious to host nasal mucosa, a key part of the immune system. Tau vaccines given as nasal drops induced tissue tau-immunoreactive antibody production and ameliorated cognitive impairment in FTLD-tau model mice. In vivo imaging and postmortem neuropathological assays demonstrated the suppression of phosphorylated tau accumulation, neurotoxic gliosis, and neuronal loss in the hippocampus of immunized mice. These findings suggest that nasal vaccine delivery may provide a therapeutic opportunity for a broad range of populations with human tauopathy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Bin", "last_name": "Ji", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Tsukita", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Enami", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Takao", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Miyakawa", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Nobuhisa", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Tabira", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "John Q.", "last_name": "Trojanowski", "name": null }, { "creator_type": "author", "first_name": "Virginia M.-Y.", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Haruhisa", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41541-020-0172-y" }, "pmcid": { "normalized": "PMC7096417" }, "pmid": { "normalized": "32219000" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "1", "normalized_date": "2020", "pages": "28", "proceedings_title": null, "publisher": "", "title": "NPJ vaccines", "volume": "5", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Nasal vaccine delivery attenuates brain pathology and cognitive impairment in tauopathy model mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The ecdysteroid and sesquiterpenoid pathways control growth, developmental transition, and embryogenesis in insects. However, the function of orthologous genes and the cross-talk between both pathways remain largely uncharacterized in non-insect arthropods. Spook (Spo) and Juvenile hormone acid o-methyltransferase (Jhamt) have been suggested to function as rate-limiting factors in ecdysteroid and sesquiterpenoid biosynthesis, respectively, in insects. In this study, we report on the functions of Spo and Jhamt and the cross-talk between them in embryos of the branchiopod crustacean Daphnia magna. Spo expression was activated at the onset of gastrulation, with the depletion of Spo transcript by RNAi resulting in developmental arrest at this stage. This phenotype could be partially rescued by supplementation with 20-hydroxyecdysone, indicating that Spo may play the same role in ecdysteroid biosynthesis in early embryos, as reported in insects. After hatching, Spo expression was repressed, while Jhamt expression was activated transiently, despite its silencing during other embryonic stages. Jhamt RNAi showed little effect on survival, but shortened the embryonic period. Exposure to the sesquiterpenoid analog Fenoxycarb extended the embryonic period and rescued the Jhamt RNAi phenotype, demonstrating a previously unidentified role of sesquiterpenoid in the repression of precocious embryogenesis. Interestingly, the knockdown of Jhamt resulted in the derepression of ecdysteroid biosynthesis genes, including Spo, similar to regulation during insect hormonal biosynthesis. Sesquiterpenoid signaling via the Methoprene-tolerant gene was found to be responsible for the repression of ecdysteroid biosynthesis genes. It upregulated an ortholog of CYP18a1 that degrades ecdysteroid in insects. These results illuminate the conserved and specific functions of the ecdysteroid and sesquiterpenoid pathways in Daphnia embryos. We also infer that the common ancestor of branchiopod crustaceans and insects exhibited antagonism between the two endocrine hormones before their divergence 400 million years ago.", "classifications": [ { "id": "19H05423", "label": "19H05423", "researcher": "Yasuhiko Kato", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Nikko", "last_name": "Adhitama", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0239893" }, "pmcid": { "normalized": "PMC7546464" }, "pmid": { "normalized": "33035251" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "Ecdysteroids", "descriptor_ui": "D026461", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Methyltransferases", "descriptor_ui": "D008780", "major_topic": false }, { "descriptor": "Sesquiterpenes", "descriptor_ui": "D012717", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "10", "normalized_date": "2020", "pages": "e0239893", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "15", "year": 2020 }, "ssbd": { "database": [ "ssbd-database-000247" ], "repository": [ "ssbd-repos-000247" ] }, "title": "Roles of and cross-talk between ecdysteroid and sesquiterpenoid pathways in embryogenesis of branchiopod crustacean Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Tagami", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null }, { "creator_type": "author", "first_name": "Yo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12658" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "3", "normalized_date": "2020", "pages": "149-149", "proceedings_title": null, "publisher": "", "title": "Development, Growth & Differentiation", "volume": "62", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Control and design of biosystems", "url": "https://onlinelibrary.wiley.com/doi/abs/10.1111/dgd.12658", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pogo transposable element derived with ZNF domain (POGZ) has been identified as one of the most recurrently de novo mutated genes in patients with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), intellectual disability and White-Sutton syndrome; however, the neurobiological basis behind these disorders remains unknown. Here, we show that POGZ regulates neuronal development and that ASD-related de novo mutations impair neuronal development in the developing mouse brain and induced pluripotent cell lines from an ASD patient. We also develop the first mouse model heterozygous for a de novo POGZ mutation identified in a patient with ASD, and we identify ASD-like abnormalities in the mice. Importantly, social deficits can be treated by compensatory inhibition of elevated cell excitability in the mice. Our results provide insight into how de novo mutations on high-confidence ASD genes lead to impaired mature cortical network function, which underlies the cellular pathogenesis of NDDs, including ASD.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kensuke", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Nagase", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Ayabe", "name": null }, { "creator_type": "author", "first_name": "Ikuko", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Tamio", "last_name": "Furuse", "name": null }, { "creator_type": "author", "first_name": "Hirotoshi", "last_name": "Shibuya", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Hidenaga", "last_name": "Yamamori", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Nanaka", "last_name": "Gotoda-Nishimura", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Misuzu", "last_name": "Hayashida", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Momoka", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Ueshima", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Tokuichi", "last_name": "Iguchi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Shigeharu", "last_name": "Wakana", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Yoshiki", "name": null }, { "creator_type": "author", "first_name": "Ayako M.", "last_name": "Watabe", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-020-14697-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32103003" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autistic Disorder", "descriptor_ui": "D001321", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Heterozygote", "descriptor_ui": "D006579", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intellectual Disability", "descriptor_ui": "D008607", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Malformations of Cortical Development", "descriptor_ui": "D054220", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Neurodevelopmental Disorders", "descriptor_ui": "D065886", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": true }, { "descriptor": "Transposases", "descriptor_ui": "D019895", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "11", "year": 2020 }, "ssbd": { "database": [ "ssbd-database-000226" ], "repository": [ "ssbd-repos-000226" ] }, "title": "Pathogenic POGZ mutation causes impaired cortical development and reversible autism-like phenotypes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BD5 is a new binary data format based on HDF5 (hierarchical data format version 5). It can be used for representing quantitative biological dynamics data obtained from bioimage informatics techniques and mechanobiological simulations. Biological Dynamics Markup Language (BDML) is an XML (Extensible Markup Language)-based open format that is also used to represent such data; however, it becomes difficult to access quantitative data in BDML files when the file size is large because parsing XML-based files requires large computational resources to first read the whole file sequentially into computer memory. BD5 enables fast random (i.e., direct) access to quantitative data on disk without parsing the entire file. Therefore, it allows practical reuse of data for understanding biological mechanisms underlying the dynamics.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Kenneth H. L.", "last_name": "Ho", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Tohsato", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Itoga", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0237468" }, "pmcid": { "normalized": "PMC7423140" }, "pmid": { "normalized": "32785254" } }, "mesh": [ { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Databases, Factual", "descriptor_ui": "D016208", "major_topic": false }, { "descriptor": "Programming Languages", "descriptor_ui": "D011381", "major_topic": true }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false }, { "descriptor": "Software Design", "descriptor_ui": "D012985", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "8", "normalized_date": "2020", "pages": "e0237468", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "15", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "BD5: An open HDF5-based data format to represent quantitative biological dynamics data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In recent years, the binary definition of sex is being challenged by repetitive reports about individuals with ambiguous sexual identity from various animal groups. This has created an urge to decode the molecular mechanism underlying sexual development. However, sexual ambiguities are extremely uncommon in nature, limiting their experimental value. Here, we report the establishment of a genetically modified clone of Daphnia magna from which intersex daphniids can be readily generated. By mutating the conserved central sex determining factor Doublesex1, body-wide feminization of male daphniid could be achieved. Comparative transcriptomic analysis also revealed a genetic network correlated with Doublesex1 activity which may account for the establishment of sexual identity in D. magna. We found that Dsx1 repressed genes related to growth and promoted genes related to signaling. We infer that different intersex phenotypes are the results of fluctuation in activity of these Dsx1 downstream factors. Our results demonstrated that the D. magna genome is capable of expressing sex in a continuous array, supporting the idea that sex is actually a spectrum.", "classifications": [ { "id": "19H05423", "label": "19H05423", "researcher": "Yasuhiko Kato", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Quang Dang", "last_name": "Nong", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0238256" }, "pmcid": { "normalized": "PMC7458346" }, "pmid": { "normalized": "32866176" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "Disorders of Sex Development", "descriptor_ui": "D012734", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Sexual Development", "descriptor_ui": "D046468", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "8", "normalized_date": "2020", "pages": "e0238256", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "15", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Two Doublesex1 mutants revealed a tunable gene network underlying intersexuality in Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Signaling through the B cell receptor (BCR) plays a critical role at multiple checkpoints of B cell biology. BCR acts as a gatekeeper of the progression of their early development in bone marrow (BM). It is also essential in triggering mechanisms such as clonal deletion and receptor editing to eliminate autoreactive B cells. In the periphery, it most importantly functions as a receptor that recognizes various extracellular antigens in response to bacterial and viral infections for conferring host defense. The recognition of antigens by BCR is the first step to receive T cell help for the functional differentiation of naive B cells toward plasma cells, germinal center (GC) B cells and memory B cells. In addition, similar to the role of BCR in the early stages of B cell development, BCR signaling plays a crucial role in the prevention of dysregulated activation of autoreactive B cells which can induce autoimmunity in the secondary lymphoid organs. Thus, since BCR is essential for the proper elicitation of immune responses by B cells, signaling through the BCR is tightly controlled by the intracellular positive and negative regulators. In this chapter, the mechanisms of activation and repression of BCR signaling are reviewed on the basis of the recent findings.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-981-15-3532-1_2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32323266" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autoimmunity", "descriptor_ui": "D015551", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Receptors, Antigen, B-Cell", "descriptor_ui": "D011947", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "23-36", "proceedings_title": null, "publisher": "", "title": "Advances in experimental medicine and biology", "volume": "1254", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "B Cell Receptor Signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The three-dimensional (3D) genome organization and its role in biological activities have been investigated for over a decade in the field of cell biology. Recent studies using live-imaging and polymer simulation have suggested that the higher-order chromatin structures are dynamic; the stochastic fluctuations of nucleosomes and genomic loci cannot be captured by bulk-based chromosome conformation capture techniques (Hi-C). In this review, we focus on the physical nature of the 3D genome architecture. We first describe how to decode bulk Hi-C data with polymer modeling. We then introduce our recently developed PHi-C method, a computational tool for modeling the fluctuations of the 3D genome organization in the presence of stochastic thermal noise. We also present another new method that analyzes the dynamic rheology property (represented as microrheology spectra) as a measure of the flexibility and rigidity of genomic regions over time. By applying these methods to real Hi-C data, we highlighted a temporal hierarchy embedded in the 3D genome organization; chromatin interaction boundaries are more rigid than the boundary interior, while functional domains emerge as dynamic fluctuations within a particular time interval. Our methods may bridge the gap between live-cell imaging and Hi-C data and elucidate the nature of the dynamic 3D genome organization.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Ryuichiro", "last_name": "Nakato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.csbj.2020.08.014" }, "pmcid": { "normalized": "PMC7484532" }, "pmid": { "normalized": "32952939" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "2259-2269", "proceedings_title": null, "publisher": "", "title": "Computational and structural biotechnology journal", "volume": "18", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Toward understanding the dynamic state of 3D genome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Munehito", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null }, { "creator_type": "author", "first_name": "Haruki", "last_name": "Nakamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bsj-2020030" }, "pmcid": { "normalized": "PMC7781791" }, "pmid": { "normalized": "33447497" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "155", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "17", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Editorial.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Modern society characterized by a 24/7 lifestyle leads to misalignment between environmental cycles and endogenous circadian rhythms. Persisting circadian misalignment leads to deleterious effects on health and healthspan. However, the underlying mechanism remains not fully understood. Here, we subjected adult, wild-type mice to distinct chronic jet-lag paradigms, which showed that long-term circadian misalignment induced significant early mortality. Non-biased RNA sequencing analysis using liver and kidney showed marked activation of gene regulatory pathways associated with the immune system and immune disease in both organs. In accordance, we observed enhanced steatohepatitis with infiltration of inflammatory cells. The investigation of senescence-associated immune cell subsets from the spleens and mesenteric lymph nodes revealed an increase in PD-1+CD44high CD4 T cells as well as CD95+GL7+ germinal center B cells, indicating that the long-term circadian misalignment exacerbates immune senescence and consequent chronic inflammation. Our results underscore immune homeostasis as a pivotal interventional target against clock-related disorders.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Inokawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Umemura", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Shimba", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Nobuya", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Munehiro", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Guangwei", "last_name": "Cui", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Asahi", "name": null }, { "creator_type": "author", "first_name": "Ryutaro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Sasawaki", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Seung-Hee", "last_name": "Yoo", "name": null }, { "creator_type": "author", "first_name": "Zheng", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Teramukai", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ikuta", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Yagita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-59541-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32054990" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hyaluronan Receptors", "descriptor_ui": "D018960", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Jet Lag Syndrome", "descriptor_ui": "D020179", "major_topic": false }, { "descriptor": "Longevity", "descriptor_ui": "D008136", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Chronic circadian misalignment accelerates immune senescence and abbreviates lifespan in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Clinical studies have shown that microduplications at 7q36.3, containing VIPR2, confer significant risk for schizophrenia and autism spectrum disorder (ASD). VIPR2 gene encodes the VPAC2 receptor for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP). Lymphocytes from patients with these mutations exhibited higher VIPR2 gene expression and VIP-induced cAMP responsiveness, but mechanisms by which overactive VPAC2 signaling may lead to these psychiatric disorders are unknown. We have previously found that repeated administration of a selective VPAC2 receptor agonist Ro25-1553 in the mouse during early postnatal development caused synaptic alterations in the prefrontal cortex and sensorimotor gating deficits. In this study, we aimed to clarify the effects of VPAC2 receptor activation on neurite outgrowth in cultured primary mouse cortical neurons. Ro25-1553 and VIP caused reductions in total numbers and lengths of both neuronal dendrites and axons, while PACAP38 facilitated elongation of dendrites, but not axons. These effects of Ro25-1553 and VIP were blocked by a VPAC2 receptor antagonist PG99-465 and abolished in VPAC2 receptor-deficient mice. Additionally, Ro25-1553-induced decreases in axon and dendritic outgrowth in wild-type mice were blocked by a protein kinase A (PKA) inhibitor H89, but not by a PKC inhibitor GF109203X or a mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor U0126. PACAP38- induced facilitation of dendritic outgrowth was blocked by U0126. These results suggest that activation of the VPAC2 receptor impairs neurite outgrowth and decreases branching of cortical neurons by a PKA-dependent mechanism. These findings also imply that the VIPR2-linkage to mental health disorders may be due in part to deficits in neuronal maturation induced by VPAC2 receptor overactivation.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shuto", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Kawanai", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Lu", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Miyaoka", "name": null }, { "creator_type": "author", "first_name": "Mei", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Naotaka", "last_name": "Horiguchi", "name": null }, { "creator_type": "author", "first_name": "Shinsaku", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "James A.", "last_name": "Waschek", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2020.00521" }, "pmcid": { "normalized": "PMC7287155" }, "pmid": { "normalized": "32581681" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "521", "proceedings_title": null, "publisher": "", "title": "Frontiers in neuroscience", "volume": "14", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Activation of the VPAC2 Receptor Impairs Axon Outgrowth and Decreases Dendritic Arborization in Mouse Cortical Neurons by a PKA-Dependent Mechanism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Surgery remains one of the main treatments of cancer and both precise pre- and intraoperative diagnoses are crucial in order to guide the operation. We consider that using an identical probe for both pre- and intra-operative diagnoses would bridge the gap between surgical planning and image-guided resection. Therefore, in this study, we developed gold nanorods (AuNRs) conjugated with radiolabeled anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody, and investigated their feasibility as novel HER2-targeted dual-imaging probes for both single photon emission computed tomography (SPECT) (preoperative diagnosis) and photoacoustic (PA) imaging (intraoperative diagnosis). To achieve the purpose, AuNRs conjugated with different amount of trastuzumab (Tra) were prepared, and Tra-AuNRs were labeled with indium-111. After the evaluation of binding affinity to HER2, cell binding assay and biodistribution studies were carried out for optimization. AuNRs with moderate trastuzumab conjugation (Tra2-AuNRs) were proposed as the novel probe and demonstrated significantly higher accumulation in NCI-N87 (HER2 high-expression) tumors than in SUIT2 (low-expression) tumors 96 h post-injection along with good affinity towards HER2. Thereafter, in vitro PA imaging and in vivo SPECT imaging studies were performed. In in vitro PA imaging, Tra2-AuNRs-treated N87 cells exhibited significant PA signal increase than SUIT2 cells. In in vivo SPECT, signal increase in N87 tumors was more notable than that in SUIT2 tumors. Herein, we report that the Tra2-AuNRs enabled HER2-specific imaging, suggesting the potential as a robust HER2-targeted SPECT and PA dual-imaging probe.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ning", "last_name": "Ding", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Namita", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Saji", "name": null } ], "identifiers": { "doi": { "normalized": "10.1248/bpb.b20-00385" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33268703" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Drug Delivery Systems", "descriptor_ui": "D016503", "major_topic": false }, { "descriptor": "Drug Development", "descriptor_ui": "D000076722", "major_topic": false }, { "descriptor": "Erb-b2 Receptor Tyrosine Kinases", "descriptor_ui": "D018719", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gold", "descriptor_ui": "D006046", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Nanotubes", "descriptor_ui": "D043942", "major_topic": true }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Photoacoustic Techniques", "descriptor_ui": "D061088", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Tomography, Emission-Computed, Single-Photon", "descriptor_ui": "D015899", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "12", "normalized_date": "2020", "pages": "1859-1866", "proceedings_title": null, "publisher": "", "title": "Biological & pharmaceutical bulletin", "volume": "43", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of Gold Nanorods Conjugated with Radiolabeled Anti-human Epidermal Growth Factor Receptor 2 (HER2) Monoclonal Antibody as Single-Photon Emission Computed Tomography/Photoacoustic Dual-Imaging Probes Targeting HER2-Positive Tumors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "As human-origin cells, human dental pulp stem cells (hDPSCs) are thought to be potentially useful for biological and medical experiments. They are easily obtained from lost primary teeth or extracted wisdom teeth, and they are mesenchymal stem cells that are known to differentiate into osteoblasts, chondrocytes, and adipocytes. Although hDPSCs originate from neural crest cells, it is difficult to induce hDPSCs to differentiate into neuron-like cells. To facilitate their differentiation into neuron-like cells, we evaluated various differentiation conditions. Activation of K(+) channels is thought to regulate the intracellular Ca(2+) concentration, allowing for manipulation of the cell cycle to induce the differentiation of hDPSCs. Therefore, in addition to a conventional neural cell differentiation protocol, we activated K(+) channels in hDPSCs. Immunocyto-chemistry and real-time PCR revealed that applying a combination of 3 stimuli (high K(+) solution, epigenetic reprogramming solution, and neural differentiation solution) to hDPSCs increased their expression of neuronal markers, such as beta3-tubulin, postsynaptic density protein 95, and nestin within 5 days, which led to their rapid differentiation into neuron-like cells. Our findings indicate that epigenetic reprogramming along with cell cycle regulation by stimulation with high K(+) accelerated the differentiation of hDPSCs into neuron-like cells. Therefore, hDPSCs can be used in various ways as neuron-like cells by manipulating their cell cycle.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Kogo", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Seto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Totani", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Taka", "last_name": "Nakahara", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bsj-2020023" }, "pmcid": { "normalized": "PMC7671740" }, "pmid": { "normalized": "33240740" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "132-139", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "17", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Rapid differentiation of human dental pulp stem cells to neuron-like cells by high K(+) stimulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND PURPOSE: Chronic inflammation is involved in the formation and enlargement of cerebral aneurysms (CAs), with macrophages playing a key role in the process. The present study evaluated visualization of macrophages present in CAs using an activatable fluorescent probe (IONP-ICG) comprising an iron oxide nanoparticles (IONPs) conjugated with indocyanine green (ICG). METHODS: IONP-ICG was intravenously administered to 15-week-old CA model rats (n = 8), and ex vivo near-infrared fluorescence (NIRF) imaging and histological assessment of exposed CAs and cerebral arteries were performed 48 h later. Similar evaluations were performed in the control group, which included CA model rats given IONPs or ICG (n = 8 each). RESULTS: ICG-derived NIRF signals were detected in three IONP-ICG group rats but not in IONP or ICG control groups. Among the three rats that exhibited signals, NIRF signal accumulation was observed in the CA of two rats and at the site of hemodynamic stress in the left posterior cerebral artery in one rat. Histologically, NIRF signals correlated strongly with macrophage localization. A total of 13 CAs formed in the IONP-ICG group. The number of macrophages in the CA wall was significantly greater in the two CAs that exhibited NIRF signals compared to the remaining 11 CAs that did not (P = 0.037). Moreover, all 11 CAs that did not exhibit NIRF signals were iron-negative, while the two CAs that exhibited NIRF signals were both iron-positive (P = 0.013). CONCLUSION: NIRF imaging using an activatable IONP-ICG probe is feasible for detecting the macrophage-rich regions in CAs and the cerebral artery wall, which is considered an early lesion in the process of CA formation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Chihara", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Abekura", "name": null }, { "creator_type": "author", "first_name": "Hidehisa", "last_name": "Nishi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Saji", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Miyamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2020.00370" }, "pmcid": { "normalized": "PMC7189773" }, "pmid": { "normalized": "32390794" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "370", "proceedings_title": null, "publisher": "", "title": "Frontiers in neuroscience", "volume": "14", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Activatable Fluorescence Imaging of Macrophages in Cerebral Aneurysms Using Iron Oxide Nanoparticles Conjugated With Indocyanine Green.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sleep is mandatory in most animals that have the nervous system and is universally observed in model organisms ranging from the nematodes, zebrafish, to mammals. However, it is unclear whether different sleep states fulfill common functions and are driven by shared mechanisms in these different animal species. Mammals and birds exhibit two obviously distinct states of sleep, i.e., non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep, but it is unknown why sleep should be so segregated. Studying sleep in other animal models might give us clues that help solve this puzzle. Recent studies suggest that REM sleep, or ancestral forms of REM sleep might be found in non-mammalian or -avian species such as reptiles. These observations suggest that REM sleep and NREM sleep evolved earlier than previously thought. In this review, we discuss the evolutionary origin of the distinct REM/NREM sleep states to gain insight into the mechanistic and functional reason for these two different types of sleep.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Risa", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Paul-Antoine", "last_name": "Libourel", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Kaspar E.", "last_name": "Vogt", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Sakurai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fpsyg.2020.567618" }, "pmcid": { "normalized": "PMC7767968" }, "pmid": { "normalized": "33381062" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "567618", "proceedings_title": null, "publisher": "", "title": "Frontiers in psychology", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Evolutionary Origin of Distinct NREM and REM Sleep.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Various artificial cells and artificial tissues can be generated from induced pluripotent stem cells (iPS cells). There is now an urgent need to standardize the quality evaluation and management of iPS cells. Recently, artificial intelligence (AI) technology such as machine learning is providing evaluation method for the quality of iPS cells and iPS cell-derived somatic cells based on optical microscopy. Light, which is the principle of optical microscopy, has an interesting and important feature. There are various kinds of interaction between light and molecule, and the scattered light includes internal information of the molecule. Raman scattering inheres all the vibration mode of molecular bonds composing a molecule, and second harmonic generation (SHG) light, which is one of second-order non-linear scattering light, is derived from electric polarizations in the molecule, in other words, carries structural information within the protein. While states of a cell are usually defined by protein/gene expression patterns, we have proposed to apply Raman spectra for cellular fingerprinting as an alternative for identifying the cell state, and now succeeded in predicting gene-expression of antibiotic resistant bacteria in combination with machine learning technology. Meanwhile, SHG microscopy has been used to visualize fiber structures in living specimens, such as collagen, and microtubules as a label-free modality. By utilizing the feature that SHG senses protein structure change, we developed a new method to measure actomyosin activity in cardiac cells. The most important advantage of the use of the scattering light is their non-labeling and non-invasive capability.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Kaneshiro", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/fpj.20042" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32879172" } }, "mesh": [ { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": false }, { "descriptor": "Collagen", "descriptor_ui": "D003094", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "5", "normalized_date": "2020", "pages": "312-318", "proceedings_title": null, "publisher": "", "title": "Nihon yakurigaku zasshi. Folia pharmacologica Japonica", "volume": "155", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "[Application of scattering microscopy for evaluation of iPS cell and its differentiated cells].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Imaging flow cytometry shows significant potential for increasing our understanding of heterogeneous and complex life systems and is useful for biomedical applications. Ghost cytometry is a recently proposed approach for directly analyzing compressively measured signals of cells, thereby relieving a computational bottleneck for real-time data analysis in high-throughput imaging cytometry. In our previous work, we demonstrated that this image-free approach could distinguish cells from two cell lines prepared with the same fluorescence staining method. However, the demonstration using different cell lines could not exclude the possibility that classification was based on non-morphological factors such as the speed of cells in flow, which could be encoded in the compressed signals. In this study, we show that GC can classify cells from the same cell line but with different fluorescence distributions in space, supporting the strength of our image-free approach for accurate morphological cell analysis. (c) 2020 International Society for Advancement of Cytometry.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Horisaki", "name": null }, { "creator_type": "author", "first_name": "Issei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Katsuhito", "last_name": "Fujiu", "name": null }, { "creator_type": "author", "first_name": "Kayo", "last_name": "Waki", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Noji", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cyto.a.23989" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32115874" } }, "mesh": [ { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Image Cytometry", "descriptor_ui": "D019044", "major_topic": true }, { "descriptor": "Staining and Labeling", "descriptor_ui": "D013194", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "415-422", "proceedings_title": null, "publisher": "", "title": "Cytometry. Part A : the journal of the International Society for Analytical Cytology", "volume": "97", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Use of Ghost Cytometry to Differentiate Cells with Similar Gross Morphologic Characteristics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Leucine-rich repeat kinase 2 (LRRK2) is the causal gene of the autosomal dominant hereditary form of Parkinson's disease (PD), PARK8. We have previously reported that induced pluripotent stem cells (iPSCs) from a PARK8 patient with I2020T LRRK2 mutation replicated to some extent the pathologic phenotype evident in the brain of PD patients. In the present study, we generated gene-corrected iPSCs line, KEIUi001-A, using TALEN-mediated genome editing. KEIUi001-A retained a normal karyotype and pluripotency, i.e. the capacity to differentiate into cell types of the three germ layers. This iPSCs will be valuable for clarifying various aspects of LRRK2-related pathology.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Takefumi", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Ukai", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Hisamatsu", "name": null }, { "creator_type": "author", "first_name": "Tokiko", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Hiroki R.", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Obata", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.scr.2020.102073" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33181472" } }, "mesh": [ { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Leucine-Rich Repeat Serine-Threonine Protein Kinase-2", "descriptor_ui": "D000071158", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Parkinson Disease", "descriptor_ui": "D010300", "major_topic": true }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Dec", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "102073", "proceedings_title": null, "publisher": "", "title": "Stem cell research", "volume": "49", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of gene-corrected iPSCs line (KEIUi001-A) from a PARK8 patient iPSCs with familial Parkinson's disease carrying the I2020T mutation in LRRK2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Aizawa", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Demura", "name": null }, { "creator_type": "author", "first_name": "Kazutoshi", "last_name": "Gohara", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Haga", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Ishimori", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Kinjo", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Maenaka", "name": null }, { "creator_type": "author", "first_name": "Min", "last_name": "Yao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12551-020-00649-w" }, "pmcid": { "normalized": "PMC7242605" }, "pmid": { "normalized": "32347462" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "233-236", "proceedings_title": null, "publisher": "", "title": "Biophysical reviews", "volume": "12", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Biophysical research in Hokkaido University, Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A contribution of epigenetic modifications to B cell tolerance has been proposed but not directly tested. Here we report that deficiency of ten-eleven translocation (Tet) DNA demethylase family members Tet2 and Tet3 in B cells led to hyperactivation of B and T cells, autoantibody production and lupus-like disease in mice. Mechanistically, in the absence of Tet2 and Tet3, downregulation of CD86, which normally occurs following chronic exposure of self-reactive B cells to self-antigen, did not take place. The importance of dysregulated CD86 expression in Tet2- and Tet3-deficient B cells was further demonstrated by the restriction, albeit not complete, on aberrant T and B cell activation following anti-CD86 blockade. Tet2- and Tet3-deficient B cells had decreased accumulation of histone deacetylase 1 (HDAC1) and HDAC2 at the Cd86 locus. Thus, our findings suggest that Tet2- and Tet3-mediated chromatin modification participates in repression of CD86 on chronically stimulated self-reactive B cells, which contributes, at least in part, to preventing autoimmunity.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Ise", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Chisato", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yoshihito", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Sakakibara", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Ikuo", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Jafar", "last_name": "Sharif", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Koseki", "name": null }, { "creator_type": "author", "first_name": "Pandelakis A.", "last_name": "Koni", "name": null }, { "creator_type": "author", "first_name": "Indu", "last_name": "Raman", "name": null }, { "creator_type": "author", "first_name": "Quan-Zhen", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Katsunori", "last_name": "Fujiki", "name": null }, { "creator_type": "author", "first_name": "Ryuichiro", "last_name": "Nakato", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Shirahige", "name": null }, { "creator_type": "author", "first_name": "Hiromitsu", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Fumihito", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kurosaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41590-020-0700-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32572241" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autoimmune Diseases", "descriptor_ui": "D001327", "major_topic": false }, { "descriptor": "Autoimmunity", "descriptor_ui": "D015551", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "B7-2 Antigen", "descriptor_ui": "D051940", "major_topic": false }, { "descriptor": "Dioxygenases", "descriptor_ui": "D049308", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "950-961", "proceedings_title": null, "publisher": "", "title": "Nature immunology", "volume": "21", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Tet2 and Tet3 in B cells are required to repress CD86 and prevent autoimmunity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND/AIM: Malignant peripheral nerve sheath tumor (MPNST) is a rare soft-tissue tumor, and its diagnosis is usually made histopathologically. The effectiveness of chemotherapy and radiotherapy has not been established. We elucidated prognostic factors, diagnostic markers, and therapeutic targets. MATERIALS AND METHODS: Cases of MPNST were studied using next-generation sequencing. A total of 24 tumor samples, 11 from von Recklinghausen's disease-associated MPNST (vRH-MPNST), 11 from sporadic non-vRH MPNST, and two neurofibroma (NF) cases were retrieved, on which next-generation sequencing and survival analysis were performed. RESULTS: We identified NF1 gene mutations, including three mutations in two NFs, and 10 mutations in eight MPNSTs (five vRH-MPNSTs and three sporadic MPNSTs). Meningioma 1 (MN1) gene alteration was detected in six cases of vRH-MPNST. It is considered that MN1 gene alteration is related to the tumorigenesis of vRH-MPNST. CONCLUSION: MN1 gene mutation was detected in more than half of our cases, it may have potential for use as a therapeutic target in vRH-MPNST.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Izumi", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Kohashi", "name": null }, { "creator_type": "author", "first_name": "Hidetaka", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Y. U.", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yousuke", "last_name": "Susuki", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Ichiki", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masutaka", "last_name": "Furue", "name": null }, { "creator_type": "author", "first_name": "Yasuharu", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Yoshinao", "last_name": "Oda", "name": null } ], "identifiers": { "doi": { "normalized": "10.21873/anticanres.14642" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33109559" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Genes, Neurofibromatosis 1", "descriptor_ui": "D016514", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Nerve Sheath Neoplasms", "descriptor_ui": "D018317", "major_topic": false }, { "descriptor": "Neurofibroma", "descriptor_ui": "D009455", "major_topic": false }, { "descriptor": "Neurofibromatosis 1", "descriptor_ui": "D009456", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-bcl-2", "descriptor_ui": "D019253", "major_topic": false }, { "descriptor": "Survival Analysis", "descriptor_ui": "D016019", "major_topic": false }, { "descriptor": "Trans-Activators", "descriptor_ui": "D015534", "major_topic": false }, { "descriptor": "Tumor Suppressor Proteins", "descriptor_ui": "D025521", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "6221-6228", "proceedings_title": null, "publisher": "", "title": "Anticancer research", "volume": "40", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Frequent MN1 Gene Mutations in Malignant Peripheral Nerve Sheath Tumor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null }, { "creator_type": "author", "first_name": "Haruki", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Jeremy", "last_name": "Tame", "name": null }, { "creator_type": "author", "first_name": "Saeko", "last_name": "Yanaka", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Kuniaki", "last_name": "Nagayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12551-020-00691-8" }, "pmcid": { "normalized": "PMC7242520" }, "pmid": { "normalized": "32212057" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "183-185", "proceedings_title": null, "publisher": "", "title": "Biophysical reviews", "volume": "12", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Editorial for the Special Issue of Biophysical Reviews focused on the Biophysical Society of Japan with select scientific content from the 57th BSJ annual meeting, Miyazaki, Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Motility often plays a decisive role in the survival of species. Five systems of motility have been studied in depth: those propelled by bacterial flagella, eukaryotic actin polymerization and the eukaryotic motor proteins myosin, kinesin and dynein. However, many organisms exhibit surprisingly diverse motilities, and advances in genomics, molecular biology and imaging have showed that those motilities have inherently independent mechanisms. This makes defining the breadth of motility nontrivial, because novel motilities may be driven by unknown mechanisms. Here, we classify the known motilities based on the unique classes of movement-producing protein architectures. Based on this criterion, the current total of independent motility systems stands at 18 types. In this perspective, we discuss these modes of motility relative to the latest phylogenetic Tree of Life and propose a history of motility. During the ~4 billion years since the emergence of life, motility arose in Bacteria with flagella and pili, and in Archaea with archaella. Newer modes of motility became possible in Eukarya with changes to the cell envelope. Presence or absence of a peptidoglycan layer, the acquisition of robust membrane dynamics, the enlargement of cells and environmental opportunities likely provided the context for the (co)evolution of novel types of motility.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Robert C.", "last_name": "Robinson", "name": null }, { "creator_type": "author", "first_name": "Taro Q. P.", "last_name": "Uyeda", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Fukumori", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Haruta", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Homma", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Chikara", "last_name": "Kaito", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Kenri", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kinosita", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Minamino", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Nakane", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Shimabukuro", "name": null }, { "creator_type": "author", "first_name": "Masatada", "last_name": "Tamakoshi", "name": null }, { "creator_type": "author", "first_name": "Azuma", "last_name": "Taoka", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Tashiro", "name": null }, { "creator_type": "author", "first_name": "Isil", "last_name": "Tulum", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.12737" }, "pmcid": { "normalized": "PMC7004002" }, "pmid": { "normalized": "31957229" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": false }, { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Dyneins", "descriptor_ui": "D004398", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Flagella", "descriptor_ui": "D005407", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kinesins", "descriptor_ui": "D016547", "major_topic": false }, { "descriptor": "Myosins", "descriptor_ui": "D009218", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "6-21", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "25", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Tree of motility - A proposed history of motility systems in the tree of life.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Arginine vasopressin (AVP), when released into portal capillaries with corticotrophin-releasing factor (CRF) from terminals of parvocellular neurones of the hypothalamic paraventricular nucleus (PVH), facilitates the secretion of adrenocorticotrophic hormone (ACTH) in stressed rodents. The AVP gene encodes a propeptide precursor containing AVP, AVP-associated neurophysin II (NPII), and a glycopeptide copeptin, although it is currently unclear whether copeptin is always cleaved from the neurophysin and whether the NPII and/or copeptin have any functional role in the pituitary. Furthermore, for primates, it is unknown whether CRF, AVP, NPII and copeptin are all colocalised in neurosecretory vesicles in the terminal region of the paraventricular CRF neurone axons. Therefore, we investigated, by fluorescence and immunogold immunocytochemistry, the cellular and subcellular relationships of these peptides in the CRF- and AVP-producing cells in unstressed Japanese macaque monkeys (Macaca fuscata). Reverse transcription-polymerase chain reaction analysis showed the expression of both CRF and AVP mRNAs in the monkey PVH. As expected, in the magnocellular neurones of the PVH and supraoptic nucleus, essentially no CRF immunoreactivity could be detected in NPII-immunoreactive (AVP-producing) neurones. Immunofluorescence showed that, in the parvocellular part of the PVH, NPII was detectable in a subpopulation (approximately 39%) of the numerous CRF-immunoreactive neuronal perikarya, whereas, in the outer median eminence, NPII was more prominent (approximately 52%) in the CRF varicosities. Triple immunoelectron microscopy in the median eminence demonstrated the presence of both NPII and copeptin immunoreactivity in dense-cored vesicles of CRF-containing axons. The results are consistent with an idea that the AVP propeptide is processed and NPII and copeptin are colocalised in hypothalamic-pituitary CRF axons in the median eminence of a primate. The CRF, AVP and copeptin are all co-packaged in neurosecretory vesicles in monkeys and are thus likely to be co-released into the portal capillary blood to amplify ACTH release from the primate anterior pituitary.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akito", "last_name": "Otubo", "name": null }, { "creator_type": "author", "first_name": "Natsuko", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Maejima", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "John F.", "last_name": "Morris", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/jne.12875" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32715549" } }, "mesh": [ { "descriptor": "Adrenocorticotropic Hormone", "descriptor_ui": "D000324", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Corticotropin-Releasing Hormone", "descriptor_ui": "D003346", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Macaca fuscata", "descriptor_ui": "D000080527", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Median Eminence", "descriptor_ui": "D008473", "major_topic": false }, { "descriptor": "Neurosecretory Systems", "descriptor_ui": "D009490", "major_topic": false }, { "descriptor": "Secretory Vesicles", "descriptor_ui": "D022142", "major_topic": false }, { "descriptor": "Tissue Distribution", "descriptor_ui": "D014018", "major_topic": false }, { "descriptor": "Vasopressins", "descriptor_ui": "D014667", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "e12875", "proceedings_title": null, "publisher": "", "title": "Journal of neuroendocrinology", "volume": "32", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Vasopressin gene products are colocalised with corticotrophin-releasing factor within neurosecretory vesicles in the external zone of the median eminence of the Japanese macaque monkey (Macaca fuscata).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alzheimer's disease (AD) patients often suffer from sleep disturbances. Alterations in sleep, especially rapid eye movement sleep (REMS), can precede the onset of dementia. To accurately characterize the sleep impairments accompanying AD and their underlying mechanisms using animal models, it is crucial to use models in which brain areas are affected in a manner similar to that observed in the actual patients. Here, we focused on App(NL-G-F) mice, in which expression levels and patterns of mutated amyloid precursor protein (APP) follow the endogenous patterns. We characterized the sleep architecture of male App(NL-G-F) homozygous and heterozygous mice at two ages (six and 12 months). At six months, homozygous mice exhibited reduced REMS, which was further reduced at 12 months together with a slight reduction in non-REMS (NREMS). By contrast, heterozygous mice exhibited an overall normal sleep architecture. Homozygous mice also exhibited decreased electroencephalogram gamma to delta power ratio during REMS from six months, resembling the electroencephalogram slowing phenomenon observed in preclinical or early stages of AD. In addition, homozygous mice showed learning and memory impairments in the trace fear conditioning (FC) at both ages, and task performance strongly correlated with REMS amount at 12 months. Finally, histologic analyses revealed that amyloid-beta accumulation in the pontine tegmental area and ventral medulla followed a course similar to that of the REMS reduction. These findings support the notion that changes in REMS are an early marker of AD and provide a starting point to address the mechanism of sleep deficits in AD and the effects on cognition.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sakura Eri B.", "last_name": "Maezono", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Kanuka", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Tatsuzawa", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Taizo", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Mitsuaki", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Pimpimon", "last_name": "Nondhalee", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takaomi C.", "last_name": "Saido", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/eneuro.0093-20.2020" }, "pmcid": { "normalized": "PMC7196722" }, "pmid": { "normalized": "32321771" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": true }, { "descriptor": "Amyloid beta-Peptides", "descriptor_ui": "D016229", "major_topic": true }, { "descriptor": "Amyloid beta-Protein Precursor", "descriptor_ui": "D016564", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar/Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "ENEURO.0093-20.2020", "proceedings_title": null, "publisher": "", "title": "eNeuro", "volume": "7", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Progressive Changes in Sleep and Its Relations to Amyloid-beta Distribution and Learning in Single App Knock-In Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Zebra finches (Taeniopygia guttata) use their voices for communication. Song structures in the songs of individual males are important for sound recognition in females. The caudomedial mesopallium (CMM) and nidopallium (NCM) are known to be essential higher auditory regions for sound recognition. These two regions have also been discussed with respect to their fundamental functions and song selectivity. To clarify their functions and selectivity, we investigated latencies and spiking patterns and also developed a novel correlation analysis to evaluate the relationship between neural activity and the characteristics of acoustic factors. We found that the latencies and spiking patterns in response to song stimuli differed between the CMM and NCM. In addition, our correlation analysis revealed that amplitude and frequency structures were important temporal acoustic factors for both regions. Although the CMM and NCM have different fundamental functions, they share similar encoding systems for acoustic factors.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Inda", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/ejn.14616" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31705589" } }, "mesh": [ { "descriptor": "Acoustic Stimulation", "descriptor_ui": "D000161", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Auditory Cortex", "descriptor_ui": "D001303", "major_topic": true }, { "descriptor": "Auditory Perception", "descriptor_ui": "D001307", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Finches", "descriptor_ui": "D046369", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Vocalization, Animal", "descriptor_ui": "D014828", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Apr", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "1770-1783", "proceedings_title": null, "publisher": "", "title": "The European journal of neuroscience", "volume": "51", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Neural properties of fundamental function encoding of sound selectivity in the female avian auditory cortex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Formation of the body of vertebrate embryos proceeds sequentially by posterior addition of tissues from the tail bud. Cells of the tail bud and the posterior presomitic mesoderm, which control posterior elongation(1), exhibit a high level of aerobic glycolysis that is reminiscent of the metabolic status of cancer cells experiencing the Warburg effect(2,3). Glycolytic activity downstream of fibroblast growth factor controls WNT signalling in the tail bud(3). In the neuromesodermal precursors of the tail bud(4), WNT signalling promotes the mesodermal fate that is required for sustained axial elongation, at the expense of the neural fate(3,5). How glycolysis regulates WNT signalling in the tail bud is currently unknown. Here we used chicken embryos and human tail bud-like cells differentiated in vitro from induced pluripotent stem cells to show that these cells exhibit an inverted pH gradient, with the extracellular pH lower than the intracellular pH, as observed in cancer cells(6). Our data suggest that glycolysis increases extrusion of lactate coupled to protons via the monocarboxylate symporters. This contributes to elevating the intracellular pH in these cells, which creates a favourable chemical environment for non-enzymatic beta-catenin acetylation downstream of WNT signalling. As acetylated beta-catenin promotes mesodermal rather than neural fate(7), this ultimately leads to activation of mesodermal transcriptional WNT targets and specification of the paraxial mesoderm in tail bud precursors. Our work supports the notion that some tumour cells reactivate a developmental metabolic programme.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masayuki", "last_name": "Oginuma", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Harima", "name": null }, { "creator_type": "author", "first_name": "Oscar A.", "last_name": "Tarazona", "name": null }, { "creator_type": "author", "first_name": "Margarete", "last_name": "Diaz-Cuadros", "name": null }, { "creator_type": "author", "first_name": "Arthur", "last_name": "Michaut", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Ishitani", "name": null }, { "creator_type": "author", "first_name": "Fengzhu", "last_name": "Xiong", "name": null }, { "creator_type": "author", "first_name": "Olivier", "last_name": "Pourquie", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41586-020-2428-0" }, "pmcid": { "normalized": "PMC8278564" }, "pmid": { "normalized": "32581357" } }, "mesh": [ { "descriptor": "Acetylation", "descriptor_ui": "D000107", "major_topic": false }, { "descriptor": "Amnion", "descriptor_ui": "D000650", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "beta Catenin", "descriptor_ui": "D051176", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": false }, { "descriptor": "Chick Embryo", "descriptor_ui": "D002642", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Lactic Acid", "descriptor_ui": "D019344", "major_topic": false }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": false }, { "descriptor": "Wnt Proteins", "descriptor_ui": "D051153", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Aug", "date_precision": "unknown", "issue": "7819", "normalized_date": null, "pages": "98-101", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "584", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Intracellular pH controls WNT downstream of glycolysis in amniote embryos.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Madoka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12551-020-00624-5" }, "pmcid": { "normalized": "PMC7242534" }, "pmid": { "normalized": "32006252" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "301-302", "proceedings_title": null, "publisher": "", "title": "Biophysical reviews", "volume": "12", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "BSJ 2019 \"Single-cell PRESTO\" session.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The molecular mechanism responsible for hyperphosphorylated tau accumulation in dendrites of Alzheimer's disease (AD) neurons has not been fully clarified. Recently, we reported that tau mRNA is distributed into dendrites, and that translation and phosphorylation of tau protein are immediately enhanced in response to glutamatergic stimulation. Here, we focused on dendritic glycogen synthase kinase 3beta (GSK3beta), a key enzyme for tau phosphorylation, and investigated the mechanism responsible for the neural stimulation-induced hyperphosphorylation of the newly translated dendritic tau protein. We found that GSK3beta mRNA was also distributed into dendrites of cultured hippocampal neurons, and that a glutamate-dependent slight increase of translation occurred in a short time. Concomitantly, dephosphorylation at the Ser9 residue of the preexisting GSK3beta, which reactivates this kinase, was strongly induced without an increase of its phosphatase PP1 or a decrease of the PP1 inhibitor I-2. Instead, I-2 phosphorylation was observed, suggesting disinhibition of PP1. This glutamate-dependent phosphorylation of I-2 and the dephosphorylation of preexisting GSK3beta were abolished in the presence of GSK3beta inhibitors. Interestingly, translational obstruction of GSK3beta mRNA also canceled these reactions. These results indicate that dendrites exhibit a glutamate-responsive cycle for amplification of reactivated preexisting GSK3beta operating via PP1 disinhibition, whose activation requires neural activity-dependent translation of dendritic GSK3beta mRNA. This would explain why a slight increase of dendritic GSK3beta is sufficient to trigger hyperphosphorylation of significantly increased tau protein.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Toru", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Sachiyo", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuint.2020.104808" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32711020" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Glycogen Synthase Kinase 3 beta", "descriptor_ui": "D000071679", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Biosynthesis", "descriptor_ui": "D014176", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Oct", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "104808", "proceedings_title": null, "publisher": "", "title": "Neurochemistry international", "volume": "139", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Glutamate-responsive translation of dendritic GSK3beta mRNA triggers a cycle for amplification of reactivated preexisting GSK3beta that is indispensable for tau hyperphosphorylation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To prevent the destruction of tissues owing to excessive and/or inappropriate immune responses, immune cells are under strict check by various regulatory mechanisms at multiple points. Inhibitory coreceptors, including programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), serve as critical checkpoints in restricting immune responses against self-tissues and tumor cells. Immune checkpoint inhibitors that block PD-1 and CTLA-4 pathways significantly improved the outcomes of patients with diverse cancer types and have revolutionized cancer treatment. However, response rates to such therapies are rather limited, and immune-related adverse events are also observed in a substantial patient population, leading to the urgent need for novel therapeutics with higher efficacy and lower toxicity. In addition to PD-1 and CTLA-4, a variety of stimulatory and inhibitory coreceptors are involved in the regulation of T cell activation. Such coreceptors are listed as potential drug targets, and the competition to develop novel immunotherapies targeting these coreceptors has been very fierce. Among such coreceptors, lymphocyte activation gene-3 (LAG-3) is expected as the foremost target next to PD-1 in the development of cancer therapy, and multiple clinical trials testing the efficacy of LAG-3-targeted therapy are underway. LAG-3 is a type I transmembrane protein with structural similarities to CD4. Accumulating evidence indicates that LAG-3 is an inhibitory coreceptor and plays pivotal roles in autoimmunity, tumor immunity, and anti-infection immunity. In this review, we summarize the current understanding of LAG-3, ranging from its discovery to clinical application.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Il-Mi", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Okazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1136/jitc-2020-001014" }, "pmcid": { "normalized": "PMC7488795" }, "pmid": { "normalized": "32929051" } }, "mesh": [ { "descriptor": "Adaptive Immunity", "descriptor_ui": "D056704", "major_topic": false }, { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunotherapy", "descriptor_ui": "D007167", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Sep", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "e001014", "proceedings_title": null, "publisher": "", "title": "Journal for immunotherapy of cancer", "volume": "8", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "LAG-3: from molecular functions to clinical applications.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Missense mutations of the RET gene have been identified in both multiple endocrine neoplasia (MEN) type 2A/B and Hirschsprung disease (HSCR: congenital absence of the enteric nervous system, ENS). Current consensus holds that MEN2A/B and HSCR are caused by activating and inactivating RET mutations, respectively. However, the biological significance of RET missense mutations in vivo has not been fully elucidated. In the present study, we introduced one MEN2B-associated (M918T) and two HSCR-associated (N394K and Y791F) RET missense mutations into the corresponding regions of the mouse Ret gene by genome editing (Ret(M919T) , Ret(N396K) and Ret(Y792F) ) and performed histological examinations of Ret-expressing tissues to understand the pathogenetic impact of each mutant in vivo. Ret(M919T/+) mice displayed MEN2B-related phenotypes, including C-cell hyperplasia and abnormal enlargement of the primary sympathetic ganglia. Similar sympathetic phenotype was observed in Ret(M919T/-) mice, demonstrating a strong pathogenetic effect of the Ret M918T by a single-allele expression. In contrast, no abnormality was found in the ENS of mice harboring the Ret N394K or Y791F mutation. Most surprisingly, single-allele expression of RET N394K or Y791F was sufficient for normal ENS development, indicating that these RET mutants exert largely physiological function in vivo. This study reveals contrasting pathogenetic effects between MEN2B- and HSCR-associated RET missense mutations, and suggests that some of HSCR-associated RET missense mutations are by themselves neither inactivating nor pathogenetic and require involvement of other gene mutations for disease expressivity.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taichi", "last_name": "Nakatani", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Atsuhiro", "last_name": "Yamamichi", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Bitoh", "name": null }, { "creator_type": "author", "first_name": "Kosaku", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Fukumoto", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12664" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32275061" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hirschsprung Disease", "descriptor_ui": "D006627", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Multiple Endocrine Neoplasia Type 2b", "descriptor_ui": "D018814", "major_topic": false }, { "descriptor": "Mutation, Missense", "descriptor_ui": "D020125", "major_topic": true }, { "descriptor": "Point Mutation", "descriptor_ui": "D017354", "major_topic": true }, { "descriptor": "Proto-Oncogene Proteins c-ret", "descriptor_ui": "D051096", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 May", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "214-222", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "62", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Point mutagenesis in mouse reveals contrasting pathogenetic effects between MEN2B- and Hirschsprung disease-associated missense mutations of the RET gene.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cerebellum is a brain region located in the dorsal part of the anterior hindbrain, composed of a highly stereotyped neural circuit structure with small sets of neurons. The cerebellum is involved in a wide variety of functions such as motor control, learning, cognition and others. Damage to the cerebellum often leads to impairments in motor skills (cerebellar ataxia). Cerebellar ataxia can occur as a result of neurodegenerative diseases such as spinocerebellar ataxia. Recent advances in technologies related to pluripotent stem cells and their neural differentiation has enabled researchers to investigate the mechanisms of development and of disease in the human brain. Here, we review recent applications of leading-edge stem cell technologies to the mechanistic investigation of human cerebellar development and neurological diseases affecting the cerebellum.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tamada", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.mcn.2020.103530" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32693017" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nervous System Diseases", "descriptor_ui": "D009422", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Sep", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "103530", "proceedings_title": null, "publisher": "", "title": "Molecular and cellular neurosciences", "volume": "107", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Investigating developmental and disease mechanisms of the cerebellum with pluripotent stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Two-photon excitation microscopy is one of the key techniques used to observe three-dimensional (3-D) structures in biological samples. We utilized a visible-wavelength laser beam for two-photon excitation in a multifocus confocal scanning system to improve the spatial resolution and image contrast in 3-D live-cell imaging. Experimental and numerical analyses revealed that the axial resolution has improved for a wide range of pinhole sizes used for confocal detection. We observed the 3-D movements of the Golgi bodies in living HeLa cells with an imaging speed of 2 s per volume. We also confirmed that the time-lapse observation up to 8 min did not cause significant cell damage in two-photon excitation experiments using wavelengths in the visible light range. These results demonstrate that multifocus, two-photon excitation microscopy with the use of a visible wavelength can constitute a simple technique for 3-D visualization of living cells with high spatial resolution and image contrast.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Oketani", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Uegaki", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1117/1.jbo.25.1.014502" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31691550" } }, "mesh": [ { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Golgi Apparatus", "descriptor_ui": "D006056", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence, Multiphoton", "descriptor_ui": "D036641", "major_topic": false }, { "descriptor": "Movement", "descriptor_ui": "D009068", "major_topic": false }, { "descriptor": "Optical Phenomena", "descriptor_ui": "D055620", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of Biomedical Optics", "volume": "25", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Visible-wavelength two-photon excitation microscopy with multifocus scanning for volumetric live-cell imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: The calcineurin-NFAT (nuclear factor for activated T cells)-DSCR (Down syndrome critical region)-1 pathway plays a crucial role as the downstream effector of VEGF (vascular endothelial growth factor)-mediated tumor angiogenesis in endothelial cells. A role for DSCR-1 in different organ microenvironment such as the cornea and its role in ocular diseases is not well understood. Corneal changes can be indicators of various disease states and are easily detected through ocular examinations. Approach and Results: The presentation of a corneal arcus or a corneal opacity due to lipid deposition in the cornea often indicates hyperlipidemia and in most cases, hypercholesterolemia. Although the loss of Apo (apolipoprotein) E has been well characterized and is known to lead to elevated serum cholesterol levels, there are few corneal changes observed in ApoE(-/-) mice. In this study, we show that the combined loss of ApoE and DSCR-1 leads to a dramatic increase in serum cholesterol levels and severe corneal opacity with complete penetrance. The cornea is normally maintained in an avascular state; however, loss of Dscr-1 is sufficient to induce hyper-inflammatory and -oxidative condition, increased corneal neovascularization, and lymphangiogenesis. Furthermore, immunohistological analysis and genome-wide screening revealed that loss of Dscr-1 in mice triggers increased immune cell infiltration and upregulation of SDF (stromal derived factor)-1 and its receptor, CXCR4 (C-X-C motif chemokine ligand receptor-4), potentiating this signaling axis in the cornea, thereby contributing to pathological corneal angiogenesis and opacity. CONCLUSIONS: This study is the first demonstration of the critical role for the endogenous inhibitor of calcineurin, DSCR-1, and pathological corneal angiogenesis in hypercholesterolemia induced corneal opacity.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Osawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Toyono", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Usui", "name": null }, { "creator_type": "author", "first_name": "Sandra", "last_name": "Ryeom", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Minami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1161/atvbaha.120.315003" }, "pmcid": { "normalized": "PMC7518298" }, "pmid": { "normalized": "32787520" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium-Binding Proteins", "descriptor_ui": "D002135", "major_topic": false }, { "descriptor": "Chemokine CXCL12", "descriptor_ui": "D054377", "major_topic": false }, { "descriptor": "Chemotaxis, Leukocyte", "descriptor_ui": "D002634", "major_topic": false }, { "descriptor": "Corneal Neovascularization", "descriptor_ui": "D016510", "major_topic": false }, { "descriptor": "Corneal Opacity", "descriptor_ui": "D003318", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Endothelium, Corneal", "descriptor_ui": "D004728", "major_topic": false }, { "descriptor": "Eye Infections, Fungal", "descriptor_ui": "D015821", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypercholesterolemia", "descriptor_ui": "D006937", "major_topic": false }, { "descriptor": "Lymphangiogenesis", "descriptor_ui": "D042583", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout, ApoE", "descriptor_ui": "D000074085", "major_topic": false }, { "descriptor": "Muscle Proteins", "descriptor_ui": "D009124", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Receptors, CXCR4", "descriptor_ui": "D019718", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stevens-Johnson Syndrome", "descriptor_ui": "D013262", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor A", "descriptor_ui": "D042461", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "2425-2439", "proceedings_title": null, "publisher": "", "title": "Arteriosclerosis, thrombosis, and vascular biology", "volume": "40", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Loss of Down Syndrome Critical Region-1 Mediated-Hypercholesterolemia Accelerates Corneal Opacity Via Pathological Neovessel Formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The transcription factor (TF) SOX2 regulates various stem cells and tissue progenitors via functional interactions with cell type-specific partner TFs that co-bind to enhancer sequences. Neural progenitors are the major embryonic tissues where SOX2 assumes central regulatory roles. In order to characterize the partner TFs of SOX2 in neural progenitors, we investigated the regulation of the D1 enhancer of the Sox2 gene, which is activated in the embryonic neural tube (NT) and neural crest (NC), using chicken embryo electroporation. We identified essential TF binding sites for a SOX, and two ZIC TFs in the activation of the D1 enhancer. By comparison of dorso-ventral and antero-posterior patterns of D1 enhancer activation, and the effect of mutations on the enhancer activation patterns with TF expression patterns, we determined SOX2 and ZIC2 as the major D1 enhancer-activating TFs. Binding of these TFs to the D1 enhancer sequence was confirmed by chromatin immunoprecipitation analysis. The combination of SOX2 and ZIC2 TFs activated the enhancer in both the NT and NC. These results indicate that SOX2 and ZIC2, which have been known to play major regulatory roles in neural progenitors, do functionally cooperate. In addition, the recently demonstrated SOX2 expression during the NC development is accounted for at least partly by the D1 enhancer activity. Deletion of the D1 enhancer sequence from the mouse genome, however, did not affect the mouse development, indicating functional redundancies of other enhancers.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hideaki", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Machiko", "last_name": "Teramoto", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Uchikawa", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Kondoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.12753" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31997540" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chick Embryo", "descriptor_ui": "D002642", "major_topic": false }, { "descriptor": "Chickens", "descriptor_ui": "D002645", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Enhancer Elements, Genetic", "descriptor_ui": "D004742", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neural Crest", "descriptor_ui": "D009432", "major_topic": false }, { "descriptor": "Neural Tube", "descriptor_ui": "D054259", "major_topic": false }, { "descriptor": "SOXB1 Transcription Factors", "descriptor_ui": "D055748", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "242-256", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "25", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Sox2 gene regulation via the D1 enhancer in embryonic neural tube and neural crest by the combined action of SOX2 and ZIC2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: We evaluated the association between survival and bystandercardiopulmonary resuscitation (CPR) with or without dispatcher instructions (DI) considering the time from emergency call receipt by the dispatch center to emergency medical services (EMS) personnel's contact with the patient (i.e. time to EMS arrival). METHODS: This prospective study conducted in Osaka City, Japan, from 2009 to 2015 included patients with medical cause-related out-of-hospital cardiac arrest who were >/=18 years old. The primary outcome was one-month favorable neurological survival. Using multiple logistic regression models, the adjusted odds ratios (AOR) of independent and DI-dependent CPR for the primary outcome were compared with no CPR. Adjustments were made for patients' age, sex, activities of daily living before the cardiac arrest, year of cardiac arrest, location, presence or absence of witnesses, etiology of cardiac arrest, and the time from EMS contact with the patient to patient's arrival at the hospital. The effective estimated \"time to EMS arrival\" was also calculated. RESULTS: For analyses 10,925 individuals were eligible. Independent CPR had a significantly higher one-month favorable neurological survival than no CPR whereas there was no significant difference between DI-dependent CPR and no CPR (AOR, 1.90 [1.47-2.46] and 1.16 [0.91-1.47], respectively). The estimated \"time to EMS arrival\" for a one-month favorable neurological survival after independent CPR was 99%, respectively, and a molar activity of 100+/-13GBq/mumol (n=3). The overall synthesis time from the end of the bombardment to pharmaceutical formulation was 48min. A preliminary preclinical PET study in a rat demonstrated the potential of the radioligand for the evaluation of the penetration of (R,S)-isoproterenol in human brain.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ikenuma", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Kajino", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Junichiro", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kawasumi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bmcl.2019.07.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31311732" } }, "mesh": [ { "descriptor": "Acetone", "descriptor_ui": "D000096", "major_topic": false }, { "descriptor": "Alkylation", "descriptor_ui": "D000478", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood-Brain Barrier", "descriptor_ui": "D001812", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Carbon Radioisotopes", "descriptor_ui": "D002250", "major_topic": false }, { "descriptor": "Isoproterenol", "descriptor_ui": "D007545", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Norepinephrine", "descriptor_ui": "D009638", "major_topic": false }, { "descriptor": "Positron-Emission Tomography", "descriptor_ui": "D049268", "major_topic": false }, { "descriptor": "Radiopharmaceuticals", "descriptor_ui": "D019275", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Aug 15", "date_precision": "day", "issue": "16", "normalized_date": "2019-08-15", "pages": "2107-2111", "proceedings_title": null, "publisher": "", "title": "Bioorganic & medicinal chemistry letters", "volume": "29", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis of (R,S)-isoproterenol, an inhibitor of tau aggregation, as an (11)C-labeled PET tracer via reductive alkylation of (R,S)-norepinephrine with [2-(11)C]acetone.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "SAD kinases regulate presynaptic vesicle clustering and neuronal polarization. A previous report demonstrated that Sada-/- and Sadb-/- double-mutant mice showed perinatal lethality with a severe defect in axon/dendrite differentiation, but their single mutants did not. These results indicated that they were functionally redundant. Surprisingly, we show that on a C57BL/6N background, SAD-A is essential for cortical development whereas SAD-B is dispensable. Sada-/- mice died within a few days after birth. Their cortical lamination pattern was disorganized and radial migration of cortical neurons was perturbed. Birth date analyses with BrdU and in utero electroporation using pCAG-EGFP vector showed a delayed migration of cortical neurons to the pial surface in Sada-/- mice. Time-lapse imaging of these mice confirmed slow migration velocity in the cortical plate. While the neurites of hippocampal neurons in Sada-/- mice could ultimately differentiate in culture to form axons and dendrites, the average length of their axons was shorter than that of the wild type. Thus, analysis on a different genetic background than that used initially revealed a nonredundant role for SAD-A in neuronal migration and differentiation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Niida", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Madoka", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Johmura", "name": null }, { "creator_type": "author", "first_name": "Chisato", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Koh-Ichi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Nobuaki", "last_name": "Wakamatsu", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Kishi", "name": null }, { "creator_type": "author", "first_name": "Y. Albert", "last_name": "Pan", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Ugawa", "name": null }, { "creator_type": "author", "first_name": "Shoichi", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Joshua R.", "last_name": "Sanes", "name": null }, { "creator_type": "author", "first_name": "Yujiro", "last_name": "Higashi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Nakanishi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/cercor/bhy253" }, "pmcid": { "normalized": "PMC7335017" }, "pmid": { "normalized": "30307479" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Isoenzymes", "descriptor_ui": "D007527", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Aug 14", "date_precision": "day", "issue": "9", "normalized_date": "2019-08-14", "pages": "3738-3751", "proceedings_title": null, "publisher": "", "title": "Cerebral cortex (New York, N.Y. : 1991)", "volume": "29", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Isozyme-Specific Role of SAD-A in Neuronal Migration During Development of Cerebral Cortex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescence probes that can detect pH are useful tools for biological research and clinical diagnosis. Here we report pH-activatable near-infrared fluorescence probes, based on hydroxymethyl germanium-rhodamine (HMGeR), that are suitable for a range of biological applications. The pKa, the ratio of the fluorescent form in an acidic environment, and the absorption/emission wavelengths can all be conveniently optimized. The most promising probe, 2-HM IGeR, offers significant advantages over currently available near-infrared pH probes, notably high quantum efficiency, appropriate pKa value for biological applications, and high photostability. Further, our molecular design strategy allows easy conjugation of the probes to biomolecules without loss of functionality. We illustrate the value of this strategy by developing probe-Herceptin® and probe-avidin conjugates to visualize pH change in cellular vesicles during endocytosis, and to visualize tumors in a mouse model, respectively. We believe 2-HM IGeR is currently among the best-in-class pH-activatable near-infrared probes for biological and medical research.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Koide", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Numasawa", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Hisataka", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42004-019-0194-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2019-08-09", "date_precision": "day", "issue": "1", "normalized_date": "2019-08-09", "pages": "94", "proceedings_title": null, "publisher": "", "title": "Communications Chemistry", "volume": "2", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Design strategy for germanium-rhodamine based pH-activatable near-infrared fluorescence probes suitable for biological applications", "url": "https://doi.org/10.1038/s42004-019-0194-4", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We developed a biomineral-inspired hybrid material composed of CaCO3 and an organic polymer as a column packing material for HPLC. This material combines a hierarchical mesoporous structure and the functionality of the polymer. The surface of monodispersed mesoporous CaCO3 microspheres was modified with poly(maleic acid-alt-1-octadecene) (PMAcO) comprising hydrophobic alkyl chains and anionic carboxylate groups. PMAcO adsorbed onto the surface of CaCO3 through electrostatic interaction between Ca2+ sites and carboxylate groups, resulting in an octadecene coated microsphere interface. These microspheres were applied as a HPLC column and exhibited reversed-phase retention behavior in the separation of alkylbenzenes. This column showed high alkaline mobile phase resistance compared with the conventionally applied ODS column packing material. Quantitative analysis of the basic antidepressants clomipramine and imipramine spiked into whole blood was achieved with an alkaline mobile phase, demonstrating the potential of the biomineral-inspired material as a HPLC stationary phase for practical applications in routine analyses of basic drugs requiring alkaline mobile phases.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mai", "last_name": "Mochida", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c9tb01014a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31389963" } }, "mesh": [ { "descriptor": "Adsorption", "descriptor_ui": "D000327", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antidepressive Agents", "descriptor_ui": "D000928", "major_topic": false }, { "descriptor": "Benzene Derivatives", "descriptor_ui": "D001555", "major_topic": false }, { "descriptor": "Biomimetic Materials", "descriptor_ui": "D040761", "major_topic": false }, { "descriptor": "Calcium Carbonate", "descriptor_ui": "D002119", "major_topic": false }, { "descriptor": "Chromatography, High Pressure Liquid", "descriptor_ui": "D002851", "major_topic": false }, { "descriptor": "Chromatography, Reverse-Phase", "descriptor_ui": "D056148", "major_topic": false }, { "descriptor": "Clomipramine", "descriptor_ui": "D002997", "major_topic": false }, { "descriptor": "Imipramine", "descriptor_ui": "D007099", "major_topic": false }, { "descriptor": "Maleic Anhydrides", "descriptor_ui": "D008299", "major_topic": false }, { "descriptor": "Microspheres", "descriptor_ui": "D008863", "major_topic": true }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Porosity", "descriptor_ui": "D016062", "major_topic": false }, { "descriptor": "Proof of Concept Study", "descriptor_ui": "D000075082", "major_topic": false }, { "descriptor": "Swine", "descriptor_ui": "D013552", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Aug 7", "date_precision": "day", "issue": "31", "normalized_date": "2019-08-07", "pages": "4771-4777", "proceedings_title": null, "publisher": "", "title": "Journal of materials chemistry. B", "volume": "7", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "A biomimetic hybrid material consisting of CaCO3 mesoporous microspheres and an alternating copolymer for reversed-phase HPLC.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "There is a high demand for sensitive biothiol probes targeting cysteine, glutathione, and homocysteine. These biothiols are known as playing essential roles to maintain homeostasis and work as indicators of many diseases. This work presents a bioluminescent probe (named AMCM) to detect biothiols in live mammalian cells and in vivo with a limit of detection of 0.11 muM for cysteine in solution and high selectivity for biothiols, making it suitable for real-time biothiol detection in biological systems. Upon application to live cells, AMCM showed low cytotoxicity and sensitively reported bioluminescence in response to changes of biothiol levels. Furthermore, a bioluminescence resonance energy transfer system consisting of AMCM combined with the near-infrared fluorescent protein iRFP713 was applied to in vivo imaging, with emitted tissue-permeable luminescence in living mice. In summary, this work demonstrates that AMCM is of high practical value for the detection of biothiols in living cells and for deep tissue imaging in living animals.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Nanako", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Nishihara", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Sung Bae", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Iwasawa", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Moritoshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.9b00694" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31291724" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Imidazoles", "descriptor_ui": "D007093", "major_topic": false }, { "descriptor": "Luminescent Agents", "descriptor_ui": "D049408", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Pyrazines", "descriptor_ui": "D011719", "major_topic": false }, { "descriptor": "Sensilla", "descriptor_ui": "D058618", "major_topic": false }, { "descriptor": "Sulfhydryl Compounds", "descriptor_ui": "D013438", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Aug 6", "date_precision": "day", "issue": "15", "normalized_date": "2019-08-06", "pages": "9546-9553", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "91", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Biothiol-Activatable Bioluminescent Coelenterazine Derivative for Molecular Imaging in Vitro and in Vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null }, { "creator_type": "author", "first_name": "Steve", "last_name": "Presse", "name": null }, { "creator_type": "author", "first_name": "Patrick", "last_name": "Senet", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jpcb.9b05382" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31366205" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells", "descriptor_ui": "D002477", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Thermodynamics", "descriptor_ui": "D013816", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Aug 1", "date_precision": "day", "issue": "30", "normalized_date": "2019-08-01", "pages": "6387-6388", "proceedings_title": null, "publisher": "", "title": "The journal of physical chemistry. B", "volume": "123", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Deciphering Molecular Complexity in Dynamics and Kinetics-From the Single Molecule to the Single Cell Level.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Food exploration is an essential survival behavior in organisms. To find food efficiently, many organisms use a foraging strategy called area-restricted search (ARS) wherein individuals first turn more frequently, restricting their search to one area, then turn less frequently, moving along a straight path to widen the search area. Previous research suggests that the nematode Caenorhabditis elegans shows ARS behavior by changing turn frequency, and that dopamine is a crucial determinant. However, the effects of dopamine on multiple behavioral parameters have remained unknown. Here, we evaluated turn (pirouette) frequency, moving velocity, and specific area occupancy (cell occupancy) over time by using a multiple-worms tracking system. In the control (mock) experiments, all parameters changed over time, but no changes were observed in experiments with dopamine pre-exposed and dopamine-deficient animals. In inverse reinforcement learning analysis, the value function for specific velocity was found to modulate over time in mock animals only. These results demonstrate that dopamine regulates ARS via changes not only to pirouette frequency change but also to velocity.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Keita", "last_name": "Ashida", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neulet.2019.05.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31082452" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Appetitive Behavior", "descriptor_ui": "D001070", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Reinforcement, Psychology", "descriptor_ui": "D012054", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jul 27", "date_precision": "day", "issue": "", "normalized_date": "2019-07-27", "pages": "68-74", "proceedings_title": null, "publisher": "", "title": "Neuroscience letters", "volume": "706", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Multiple tracking and machine learning reveal dopamine modulation for area-restricted foraging behaviors via velocity change in Caenorhabditis elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tau is a microtubule-associated protein expressed in neuronal axons. Hyperphosphorylated tau is a major component of neurofibrillary tangles, a pathological hallmark of Alzheimer's disease (AD). Hyperphosphorylated tau aggregates are also found in many neurodegenerative diseases, collectively referred to as \"tauopathies,\" and tau mutations are associated with familial frontotemporal lobar degeneration (FTLD). Previous studies have generated transgenic mice with mutant tau as tauopathy models, but nonhuman primates, which are more similar to humans, may be a better model to study tauopathies. For example, the common marmoset is poised as a nonhuman primate model for investigating the etiology of age-related neurodegenerative diseases. However, no biochemical studies of tau have been conducted in marmoset brains. Here, we investigated several important aspects of tau, including expression of different tau isoforms and its phosphorylation status, in the marmoset brain. We found that marmoset tau does not possess the \"primate-unique motif\" in its N-terminal domain. We also discovered that the tau isoform expression pattern in marmosets is more similar to that of mice than that of humans, with adult marmoset brains expressing only four-repeat tau isoforms as in adult mice but unlike in adult human brains. Of note, tau in brains of marmoset newborns was phosphorylated at several sites associated with AD pathology. However, in adult marmoset brains, much of this phosphorylation was lost, except for Ser-202 and Ser-404 phosphorylation. These results reveal key features of tau expression and phosphorylation in the marmoset brain, a potentially useful nonhuman primate model of neurodegenerative diseases.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Govinda", "last_name": "Sharma", "name": null }, { "creator_type": "author", "first_name": "Anni", "last_name": "Huo", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Shiozawa", "name": null }, { "creator_type": "author", "first_name": "Reona", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Minaka", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Ishigaki", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Kanae", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Sobue", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Hisanaga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.ra119.008415" }, "pmcid": { "normalized": "PMC6663862" }, "pmid": { "normalized": "31171723" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Callithrix", "descriptor_ui": "D002144", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "DNA, Complementary", "descriptor_ui": "D018076", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jul 26", "date_precision": "day", "issue": "30", "normalized_date": "2019-07-26", "pages": "11433-11444", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "294", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Tau isoform expression and phosphorylation in marmoset brains.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescent and bioluminescent genetically encoded Ca(2+) indicators (GECIs) are an indispensable tool for monitoring Ca(2+) dynamics in numerous cellular events. Although fluorescent GECIs have a high spatiotemporal resolution, their application is often confined to short-term imaging due to the external illumination that causes phototoxicity and autofluorescence from specimens. Bioluminescent GECIs overcome these pitfalls with enhanced compatibility to optogenetic manipulation and photophysiological processes; however, they are compromised for spatiotemporal resolution. Therefore, there has been a push toward the use of Ca(2+) indicators that possess the advantages of both fluorescent and bioluminescent GECI for a wide range of applications. To address this, we developed a high-affinity bimodal GECI, GLICO, using a single fluorescent protein-based GECI combined with a split luciferase. Through this novel design, the fusion protein becomes bimodal and possesses Ca(2+) sensing properties similar to those of its fluorescent ancestor and confers bioluminescence-based Ca(2+) imaging. GLICO in bioluminescence mode has the highest dynamic range (2200%) of all bioluminescent GECIs. We demonstrated the performance of GLICO in studying cytosolic Ca(2+) dynamics in different cultured cells in each mode. With the purpose of Ca(2+) imaging in high Ca(2+) content organelle, we also created a low-affinity variant, ReBLICO and performed Ca(2+) imaging of the ER in both fluorescence and bioluminescence modes. The ability to switch between fluorescence and bioluminescence modes with a single indicator would benefit transgenic applications by presenting an opportunity for a wide range of live Ca(2+) imaging in physiological and pathophysiological conditions.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Israt", "last_name": "Farhana", "name": null }, { "creator_type": "author", "first_name": "Md Nadim", "last_name": "Hossain", "name": null }, { "creator_type": "author", "first_name": "Kazushi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acssensors.9b00531" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31276380" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calmodulin", "descriptor_ui": "D002147", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Channelrhodopsins", "descriptor_ui": "D000075402", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Protein Engineering", "descriptor_ui": "D015202", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jul 26", "date_precision": "day", "issue": "7", "normalized_date": "2019-07-26", "pages": "1825-1834", "proceedings_title": null, "publisher": "", "title": "ACS sensors", "volume": "4", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetically Encoded Fluorescence/Bioluminescence Bimodal Indicators for Ca(2+) Imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Both glutamine (Gln) and glutamate (Glu) are known to exist in plasma and brain. However, despite the assumed relationship between brain and plasma, no studies have clarified the association between them. Proton magnetic resonance spectroscopy (MRS) was sequentially performed twice, with a 60-min interval, on 10 males and 10 females using a 3T scanner. Blood samples for liquid chromatography-mass spectrometry (LC/MS) to measure Gln and Glu concentrations in plasma were collected during the time interval between the two MRS sessions. MRS voxels of interest were localized at the posterior cingulate cortex (PCC) and cerebellum (Cbll) and measured by the SPECIAL sequence. Spearman's correlation coefficient was used to examine the association between brain and plasma metabolites. The Gln concentrations in PCC (mean of two measurements) were positively correlated with Gln concentrations in plasma (p < 0.01, r = 0.72). However, the Glu concentrations in the two regions were not correlated with those in plasma. Consideration of the different dynamics of Gln and Glu between plasma and brain is crucial when addressing the pathomechanism and therapeutic strategies for brain disorders such as Alzheimer's disease and hepatic encephalopathy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuhei", "last_name": "Takado", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Kanbe", "name": null }, { "creator_type": "author", "first_name": "Moyoko", "last_name": "Tomiyasu", "name": null }, { "creator_type": "author", "first_name": "Lijing", "last_name": "Xin", "name": null }, { "creator_type": "author", "first_name": "Jamie", "last_name": "Near", "name": null }, { "creator_type": "author", "first_name": "Kohki", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Higashi", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Obata", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/nu11071649" }, "pmcid": { "normalized": "PMC6682979" }, "pmid": { "normalized": "31330962" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Brain Chemistry", "descriptor_ui": "D001923", "major_topic": true }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Glutamine", "descriptor_ui": "D005973", "major_topic": false }, { "descriptor": "Gyrus Cinguli", "descriptor_ui": "D006179", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Proton Magnetic Resonance Spectroscopy", "descriptor_ui": "D066244", "major_topic": true }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jul 19", "date_precision": "day", "issue": "7", "normalized_date": "2019-07-19", "pages": "E1649", "proceedings_title": null, "publisher": "", "title": "Nutrients", "volume": "11", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Association between Brain and Plasma Glutamine Levels in Healthy Young Subjects Investigated by MRS and LC/MS.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Photoacoustic (PA) imaging is a novel imaging modality that combines the high contrast of optical imaging and the deep tissue penetration of ultrasound. PA imaging contrast agents targeting various biological phenomena have been reported, but the development of activatable PA probes, which show a PA signal only in the presence of target molecules, remains challenging in spite of their potential usefulness for real-time PA imaging of specific biomolecules in vivo. To establish a simple design strategy for activatable PA probes, we first designed and synthesized a silicon-rhodamine based near-infrared nonfluorescent dye, wsSiNQ660 (water-soluble SiNQ660), as a scaffold and demonstrated that it offers a high conversion efficiency from light to ultrasound compared to typical near-infrared fluorescent dyes. Importantly, absorption off/on strategies previously established for rhodamine-based fluorescent probes are also applicable to this nonfluorescent dye scaffold. We validated this approach by synthesizing an activatable PA probe for hypochlorous acid (HOCl) and confirmed that it enables three-dimensional imaging of HOCl in mouse subcutis.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ikeno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Shimpei", "last_name": "Iwaki", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Myochin", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Ohde", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.9b01529" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31265237" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drug Design", "descriptor_ui": "D015195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypochlorous Acid", "descriptor_ui": "D006997", "major_topic": false }, { "descriptor": "Infrared Rays", "descriptor_ui": "D007259", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Organosilicon Compounds", "descriptor_ui": "D017646", "major_topic": false }, { "descriptor": "Photoacoustic Techniques", "descriptor_ui": "D061088", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": false }, { "descriptor": "Subcutaneous Tissue", "descriptor_ui": "D040521", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jul 16", "date_precision": "day", "issue": "14", "normalized_date": "2019-07-16", "pages": "9086-9092", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "91", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Design and Synthesis of an Activatable Photoacoustic Probe for Hypochlorous Acid.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During the nuclear export of nascent nucleocapsids of herpes simplex virus 1 (HSV-1), the nucleocapsids acquire a primary envelope by budding through the inner nuclear membrane into the perinuclear space between the inner and outer nuclear membranes. This unique budding process, termed primary envelopment, is initiated by the nuclear egress complex (NEC), composed of the HSV-1 UL31 and UL34 proteins. Earlier biochemical approaches have shown that the NEC has an intrinsic ability to vesiculate membranes through the formation of a hexagonal lattice structure. The significance of intrahexamer interactions of the NEC in the primary envelopment of HSV-1-infected cells has been reported. In contrast, the contribution of lattice formation of the NEC hexamer to primary envelopment in HSV-1-infected cells remains to be elucidated. Therefore, we constructed and characterized a recombinant HSV-1 strain carrying an amino acid substitution in a UL31 residue that is an interhexamer contact site for the lattice formation of the NEC hexamer. This mutation was reported to destabilize the interhexamer interactions of the HSV-1 NEC. Here, we demonstrate that the mutation causes the aberrant accumulation of nucleocapsids in the nucleus and reduces viral replication in Vero and HeLa cells. Thus, the ability of HSV-1 to form the hexagonal lattice structure of the NEC was linked to an increase in primary envelopment and viral replication. Our results suggest that the lattice formation of the NEC hexamer has an important role in HSV-1 replication by regulating primary envelopment.IMPORTANCE The scaffolding proteins of several envelope viruses required for virion assembly form high-order lattice structures. However, information on the significance of their lattice formation in infected cells is limited. Herpesviruses acquire envelopes twice during their viral replication. The first envelop acquisition (primary envelopment) is one of the steps in the vesicle-mediated nucleocytoplasmic transport of nascent nucleocapsids, which is unique in biology. HSV-1 NEC, thought to be conserved in all members of the Herpesviridae family, is critical for primary envelopment and was shown to form a hexagonal lattice structure. Here, we investigated the significance of the interhexamer contact site for hexagonal lattice formation of the NEC in HSV-1-infected cells and present evidence suggesting that the lattice formation of the NEC hexamer has an important role in HSV-1 replication by regulating primary envelopment. Our results provide insights into the mechanisms of the envelopment of herpesviruses and other envelope viruses.", "classifications": [ { "id": "19H05417", "label": "19H05417", "researcher": "Jun Arii", "type": "grant" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00498-19" }, "pmcid": { "normalized": "PMC6600192" }, "pmid": { "normalized": "31043535" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Multiprotein Complexes", "descriptor_ui": "D046912", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jul 15", "date_precision": "day", "issue": "14", "normalized_date": "2019-07-15", "pages": "e00498-19", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "93", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Roles of the Interhexamer Contact Site for Hexagonal Lattice Formation of the Herpes Simplex Virus 1 Nuclear Egress Complex in Viral Primary Envelopment and Replication.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Current clinically approved biomarkers for the PD-1 blockade cancer immunotherapy are based entirely on the properties of tumour cells. With increasing awareness of clinical responses, more precise biomarkers for the efficacy are required based on immune properties. In particular, expression levels of immune checkpoint-associated molecules such as PD-1, PD-L1, and CTLA-4 would be critical to evaluate the immune state of individuals. Although quantification of their soluble form leased from the membrane will provide quick evaluation of patients' immune status, available methods such as enzyme-linked immunosorbent assays to measure these soluble factors have limitations in sensitivity and reproducibility for clinical use. To overcome these problems, we developed a rapid and sensitive immunoassay system based on chemiluminescent magnetic technology. The system is fully automated, providing high reproducibility. Application of this system to plasma of patients with several types of tumours demonstrated that soluble PD-1, PD-L1, and CTLA-4 levels were increased compared to those of healthy controls and varied among tumour types. The sensitivity and detection range were sufficient for evaluating plasma concentrations before and after the surgical ablation of cancers. Therefore, our newly developed system shows potential for accurate detection of soluble PD-1, PD-L1, and CTLA-4 levels in the clinical practice.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Megumi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Chamoto", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Saya", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Iino", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Toshinari", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Sonobe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Date", "name": null }, { "creator_type": "author", "first_name": "Junzo", "last_name": "Hamanishi", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Mandai", "name": null }, { "creator_type": "author", "first_name": "Yoshimasa", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Ryusuke", "last_name": "Hatae", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Muto", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Minamiguchi", "name": null }, { "creator_type": "author", "first_name": "Nagahiro", "last_name": "Minato", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Honjo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-019-46548-3" }, "pmcid": { "normalized": "PMC6626008" }, "pmid": { "normalized": "31300681" } }, "mesh": [ { "descriptor": "Automation, Laboratory", "descriptor_ui": "D057205", "major_topic": false }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Carcinoma, Renal Cell", "descriptor_ui": "D002292", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "CTLA-4 Antigen", "descriptor_ui": "D060908", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoassay", "descriptor_ui": "D007118", "major_topic": false }, { "descriptor": "Kidney Neoplasms", "descriptor_ui": "D007680", "major_topic": false }, { "descriptor": "Luminescence", "descriptor_ui": "D049449", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Multiple Myeloma", "descriptor_ui": "D009101", "major_topic": false }, { "descriptor": "Ovarian Neoplasms", "descriptor_ui": "D010051", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jul 12", "date_precision": "day", "issue": "1", "normalized_date": "2019-07-12", "pages": "10144", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "9", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Analytical performance of a new automated chemiluminescent magnetic immunoassays for soluble PD-1, PD-L1, and CTLA-4 in human plasma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Carbon-based double helicates consisting of two anthracene-containing oligo(p-phenyleneethynylene) units and two flexible chiral 1,1'-binaphthyl units or two rigid chiral 9,9'-spirobifluorene units were developed. The curved oligo(p-phenyleneethynylene) fragments in the double helicates were successfully constructed by tin-mediated reductive aromatization. Helical oligo(p-phenyleneethynylene) double strands fixed by two rigid spirobifluorene units showed little structural change under photoirradiation, thereby emitting circularly polarized luminescence (CPL) in the visible region with a high quantum yield (PhiPL =0.93). In contrast, flexible binaphthyl units induced dynamic structural change of the oligo(p-phenyleneethynylene) luminophores under photoirradiation, leading to strong CPL (|glum |=1.1x10(-2) ) in the near-infrared (NIR) region. UV/Vis, circular dichroism (CD), CPL and NMR spectroscopic analyses of the binaphthyl-hinged double helicate suggested excimer formation between two pi-conjugated strands in the excited state. Theoretical calculations highlight the importance of the tightly interlocked excimer structure of the carbon-based double helicate in controlling the angle between the electric and magnetic transition dipole moments for strong NIR CPL generation.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Takeru", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Gon", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Chujo", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Mizuhata", "name": null }, { "creator_type": "author", "first_name": "Norihiro", "last_name": "Tokitoh", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/chem.201901467" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30980553" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 Jul 11", "date_precision": "day", "issue": "39", "normalized_date": "2019-07-11", "pages": "9211-9216", "proceedings_title": null, "publisher": "", "title": "Chemistry (Weinheim an der Bergstrasse, Germany)", "volume": "25", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Near-Infrared Circularly Polarized Luminescence through Intramolecular Excimer Formation of Oligo(p-phenyleneethynylene)-Based Double Helicates.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hedgehog (Hh) proteins regulate development and tissue homeostasis, but their role in atopic dermatitis (AD) remains unknown. We found that on induction of mouse AD, Sonic Hedgehog (Shh) expression in skin, and Hh pathway action in skin T cells were increased. Shh signaling reduced AD pathology and the levels of Shh expression determined disease severity. Hh-mediated transcription in skin T cells in AD-induced mice increased Treg populations and their suppressive function through increased active transforming growth factor-beta (TGF-beta) in Tregs signaling to skin T effector populations to reduce disease progression and pathology. RNA sequencing of skin CD4+ T cells from AD-induced mice demonstrated that Hh signaling increased expression of immunoregulatory genes and reduced expression of inflammatory and chemokine genes. Addition of recombinant Shh to cultures of naive human CD4+ T cells in iTreg culture conditions increased FOXP3 expression. Our findings establish an important role for Shh upregulation in preventing AD, by increased Gli-driven Treg cell-mediated immune suppression, paving the way for a potential new therapeutic strategy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Eleftheria", "last_name": "Papaioannou", "name": null }, { "creator_type": "author", "first_name": "Diana C.", "last_name": "Yanez", "name": null }, { "creator_type": "author", "first_name": "Susan", "last_name": "Ross", "name": null }, { "creator_type": "author", "first_name": "Ching-In", "last_name": "Lau", "name": null }, { "creator_type": "author", "first_name": "Anisha", "last_name": "Solanki", "name": null }, { "creator_type": "author", "first_name": "Mira Manilal", "last_name": "Chawda", "name": null }, { "creator_type": "author", "first_name": "Alex", "last_name": "Virasami", "name": null }, { "creator_type": "author", "first_name": "Ismael", "last_name": "Ranz", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Ryan F. L.", "last_name": "O'Shaughnessy", "name": null }, { "creator_type": "author", "first_name": "Tessa", "last_name": "Crompton", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci125170" }, "pmcid": { "normalized": "PMC6668675" }, "pmid": { "normalized": "31264977" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dermatitis, Atopic", "descriptor_ui": "D003876", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Hedgehog Proteins", "descriptor_ui": "D053823", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false }, { "descriptor": "Zinc Finger Protein Gli2", "descriptor_ui": "D000075746", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jul 2", "date_precision": "day", "issue": "8", "normalized_date": "2019-07-02", "pages": "3153-3170", "proceedings_title": null, "publisher": "", "title": "The Journal of clinical investigation", "volume": "129", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Sonic Hedgehog signaling limits atopic dermatitis via Gli2-driven immune regulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cyanobacteria possess a sophisticated photosynthesis-based metabolism with admirable plasticity. This plasticity is possible via the deep regulation network, the thiol-redox regulations operated by thioredoxin (hereafter, Trx). In this context, we characterized the Trx-m1-deficient mutant strain of Anabaena sp., PCC 7120 (shortly named A.7120), cultivated under nitrogen limitation. Trx-m1 appears to coordinate the nitrogen response and its absence induces large changes in the proteome. Our data clearly indicate that Trx-m1 is crucial for the diazotrophic growth of A.7120. The lack of Trx-m1 resulted in a large differentiation of heterocysts (>20% of total cells), which were barely functional probably due to a weak expression of nitrogenase. In addition, heterocysts of the mutant strain did not display the usual cellular structure of nitrogen-fixative cells. This unveiled why the mutant strain was not able to grow under nitrogen starvation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Fri Di Ric", "last_name": "Deschoenmaeker", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Mihara", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Jiro", "last_name": "Nomata", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pcp/pcz056" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31038682" } }, "mesh": [ { "descriptor": "Anabaena", "descriptor_ui": "D017033", "major_topic": false }, { "descriptor": "Antioxidants", "descriptor_ui": "D000975", "major_topic": false }, { "descriptor": "Chlorophyll", "descriptor_ui": "D002734", "major_topic": false }, { "descriptor": "Chloroplast Thioredoxins", "descriptor_ui": "D054479", "major_topic": false }, { "descriptor": "Chloroplasts", "descriptor_ui": "D002736", "major_topic": false }, { "descriptor": "Genes, Bacterial", "descriptor_ui": "D005798", "major_topic": false }, { "descriptor": "Microscopy, Electron, Transmission", "descriptor_ui": "D046529", "major_topic": false }, { "descriptor": "Nitrogen", "descriptor_ui": "D009584", "major_topic": false }, { "descriptor": "Photosynthesis", "descriptor_ui": "D010788", "major_topic": false }, { "descriptor": "Proteome", "descriptor_ui": "D020543", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jul 1", "date_precision": "day", "issue": "7", "normalized_date": "2019-07-01", "pages": "1504-1513", "proceedings_title": null, "publisher": "", "title": "Plant & cell physiology", "volume": "60", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Disruption of the Gene trx-m1 Impedes the Growth of Anabaena sp. PCC 7120 under Nitrogen Starvation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An amendment to this paper has been published and can be accessed via a link at the top of the paper.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shoko", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Matsuba", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Kamano", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Mihira", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Jiro", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Takaomi C.", "last_name": "Saido", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-019-10990-8" }, "pmcid": { "normalized": "PMC6603009" }, "pmid": { "normalized": "31263162" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 Jul 1", "date_precision": "day", "issue": "1", "normalized_date": "2019-07-01", "pages": "2964", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Author Correction: Tau binding protein CAPON induces tau aggregation and neurodegeneration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "ATP hydrolysis activity catalyzed by chloroplast and proteobacterial ATP synthase is inhibited by their ϵ subunits. To clarify the function of the ϵ subunit from phototrophs, here we analyzed the ϵ subunit–mediated inhibition (ϵ-inhibition) of cyanobacterial F1-ATPase, a subcomplex of ATP synthase obtained from the thermophilic cyanobacterium Thermosynechococcus elongatus BP-1. We generated three C-terminal α-helix null ϵ-mutants; one lacked the C-terminal α-helices, and in the other two, the C-terminal conformation could be locked by a disulfide bond formed between two α-helices or an α-helix and a β-sandwich structure. All of these ϵ-mutants maintained ATPase-inhibiting competency. We then used single-molecule observation techniques to analyze the rotary motion of F1-ATPase in the presence of these ϵ-mutants. The stop angular position of the γ subunit in the presence of the ϵ-mutant was identical to that in the presence of the WT ϵ. Using magnetic tweezers, we examined recovery from the inhibited rotation and observed restoration of rotation by 80° forcing of the γ subunit in the case of the ADP-inhibited form, but not when the rotation was inhibited by the ϵ-mutants or by the WT ϵ subunit. These results imply that the C-terminal α-helix domain of the ϵ subunit of cyanobacterial enzyme does not directly inhibit ATP hydrolysis and that its N-terminal domain alone can inhibit the hydrolysis activity. Notably, this property differed from that of the proteobacterial ϵ, which could not tightly inhibit rotation. We conclude that phototrophs and heterotrophs differ in the ϵ subunit–mediated regulation of ATP synthase.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Inabe", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.ra118.007131" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31068416" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Cyanobacteria", "descriptor_ui": "D000458", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Protein Subunits", "descriptor_ui": "D021122", "major_topic": false }, { "descriptor": "Proton-Translocating ATPases", "descriptor_ui": "D006180", "major_topic": false }, { "descriptor": "Sequence Homology", "descriptor_ui": "D017385", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jun 28", "date_precision": "day", "issue": "26", "normalized_date": "2019-06-28", "pages": "10094-10103", "proceedings_title": null, "publisher": "", "title": "The Journal of Biological Chemistry", "volume": "294", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "The N-terminal region of the ϵ subunit from cyanobacterial ATP synthase alone can inhibit ATPase activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The gamma-subunit of cyanobacterial and chloroplast ATP synthase, the rotary shaft of F(1)-ATPase, equips a specific insertion region that is only observed in photosynthetic organisms. This region plays a physiologically pivotal role in enzyme regulation, such as in ADP inhibition and redox response. Recently solved crystal structures of the gamma-subunit of F(1)-ATPase from photosynthetic organisms revealed that the insertion region forms a beta-hairpin structure, which is positioned along the central stalk. The structure-function relationship of this specific region was studied by constraining the expected conformational change in this region caused by the formation of a disulfide bond between Cys residues introduced on the central stalk and this beta-hairpin structure. This fixation of the beta-hairpin region in the alpha(3)beta(3)gamma complex affects both ADP inhibition and the binding of the epsilon-subunit to the complex, indicating the critical role that the beta-hairpin region plays as a regulator of the enzyme. This role must be important for the maintenance of the intracellular ATP levels in photosynthetic organisms.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kentaro", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Inabe", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1042/bcj20190242" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31164401" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Cyanobacteria", "descriptor_ui": "D000458", "major_topic": false }, { "descriptor": "Protein Structure, Secondary", "descriptor_ui": "D017433", "major_topic": false }, { "descriptor": "Proton-Translocating ATPases", "descriptor_ui": "D006180", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jun 26", "date_precision": "day", "issue": "12", "normalized_date": "2019-06-26", "pages": "1771-1780", "proceedings_title": null, "publisher": "", "title": "The Biochemical journal", "volume": "476", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "The beta-hairpin region of the cyanobacterial F(1)-ATPase gamma-subunit plays a regulatory role in the enzyme activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Long-term synaptic plasticity requires a mechanism that converts short Ca(2+) pulses into persistent biochemical signaling to maintain changes in the synaptic structure and function. Here, we present a novel mechanism of a positive feedback loop, formed by a reciprocally activating kinase-effector complex (RAKEC) in dendritic spines, enabling the persistence and confinement of a molecular memory. We found that stimulation of a single spine causes the rapid formation of a RAKEC consisting of CaMKII and Tiam1, a Rac-GEF. This interaction is mediated by a pseudo-autoinhibitory domain on Tiam1, which is homologous to the CaMKII autoinhibitory domain itself. Therefore, Tiam1 binding results in constitutive CaMKII activation, which in turn persistently phosphorylates Tiam1. Phosphorylated Tiam1 promotes stable actin-polymerization through Rac1, thereby maintaining the structure of the spine during LTP. The RAKEC can store biochemical information in small subcellular compartments, thus potentially serving as a general mechanism for prolonged and compartmentalized signaling.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takeo", "last_name": "Saneyoshi", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Matsuno", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Nathan G.", "last_name": "Hedrick", "name": null }, { "creator_type": "author", "first_name": "Emily", "last_name": "Agnello", "name": null }, { "creator_type": "author", "first_name": "Rory", "last_name": "O'Connell", "name": null }, { "creator_type": "author", "first_name": "Margaret M.", "last_name": "Stratton", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2019.04.012" }, "pmcid": { "normalized": "PMC6669903" }, "pmid": { "normalized": "31078368" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinase Type 2", "descriptor_ui": "D054732", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Feedback, Physiological", "descriptor_ui": "D025461", "major_topic": false }, { "descriptor": "Guanine Nucleotide Exchange Factors", "descriptor_ui": "D020662", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Long-Term Potentiation", "descriptor_ui": "D017774", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Polymerization", "descriptor_ui": "D058105", "major_topic": false }, { "descriptor": "Pyrones", "descriptor_ui": "D011753", "major_topic": false }, { "descriptor": "Quinolines", "descriptor_ui": "D011804", "major_topic": false }, { "descriptor": "rac1 GTP-Binding Protein", "descriptor_ui": "D020830", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "T-Lymphoma Invasion and Metastasis-inducing Protein 1", "descriptor_ui": "D000075684", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jun 19", "date_precision": "day", "issue": "6", "normalized_date": "2019-06-19", "pages": "1199-1210.e6", "proceedings_title": null, "publisher": "", "title": "Neuron", "volume": "102", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Reciprocal Activation within a Kinase-Effector Complex Underlying Persistence of Structural LTP.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sleep/wakefulness cycle is regulated by coordinated interactions between sleep- and wakefulness-regulating neural circuitry. However, the detailed mechanism is far from understood. Here, we found that glutamic acid decarboxylase 67-positive GABAergic neurons in the ventral tegmental area (VTAGad67+) are a key regulator of non-rapid eye movement (NREM) sleep in mice. VTAGad67+ project to multiple brain areas implicated in sleep/wakefulness regulation such as the lateral hypothalamus (LH). Chemogenetic activation of VTAGad67+ promoted NREM sleep with higher delta power whereas optogenetic inhibition of these induced prompt arousal from NREM sleep, even under highly somnolescent conditions, but not from REM sleep. VTAGad67+ showed the highest activity in NREM sleep and the lowest activity in REM sleep. Moreover, VTAGad67+ directly innervated and inhibited wake-promoting orexin/hypocretin neurons by releasing GABA. As such, optogenetic activation of VTAGad67+ terminals in the LH promoted NREM sleep. Taken together, we revealed that VTAGad67+ play an important role in the regulation of NREM sleep.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Srikanta", "last_name": "Chowdhury", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Toh", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Fukatsu", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.44928" }, "pmcid": { "normalized": "PMC6548506" }, "pmid": { "normalized": "31159923" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arousal", "descriptor_ui": "D001143", "major_topic": false }, { "descriptor": "GABAergic Neurons", "descriptor_ui": "D059330", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Sleep, Slow-Wave", "descriptor_ui": "D000077310", "major_topic": true }, { "descriptor": "Ventral Tegmental Area", "descriptor_ui": "D017557", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jun 4", "date_precision": "day", "issue": "", "normalized_date": "2019-06-04", "pages": "e44928", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "8", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "GABA neurons in the ventral tegmental area regulate non-rapid eye movement sleep in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Near-infrared (NIR) imaging techniques have attracted significant attention for biological and medicinal applications due to the ability of NIR to penetrate deeply into tissues. However, there are very few stable, activatable molecular probes that can utilize NIR light in the wavelength range beyond 800 nm. Herein, we report a new activatable NIR system for photoacoustic imaging based on tautomeric benziphthalocyanines (BPcs). We found that the existence of a free hydroxyl group is crucial for NIR absorption of BPcs. Synthesized water-soluble hydroxy BPcs exhibited high photostability and no fluorescence, which are desirable features for photoacoustic imaging. We synthesized BPcs in which the free hydroxyl group was masked by an esterase-labile or an H(2) O(2) -labile group. The photoacoustic signals of these hydroxy-masked BPcs were increased upon NIR excitation at 880 nm in the presence of esterase or H(2) O(2) , respectively. These are rare examples of activatable probes utilizing NIR light at around 900 nm.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Toriumi", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ikeno", "name": null }, { "creator_type": "author", "first_name": "Atsuya", "last_name": "Muranaka", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Uchiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201903303" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30957388" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 Jun 3", "date_precision": "day", "issue": "23", "normalized_date": "2019-06-03", "pages": "7788-7791", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "58", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Design of Photostable, Activatable Near-Infrared Photoacoustic Probes Using Tautomeric Benziphthalocyanine as a Platform.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To understand the molecular processes that link Abeta amyloidosis, tauopathy and neurodegeneration, we screened for tau-interacting proteins by immunoprecipitation/LC-MS. We identified the carboxy-terminal PDZ ligand of nNOS (CAPON) as a novel tau-binding protein. CAPON is an adaptor protein of neuronal nitric oxide synthase (nNOS), and activated by the N-methyl-D-aspartate receptor. We observed accumulation of CAPON in the hippocampal pyramidal cell layer in the App(NL-G-F) -knock-in (KI) brain. To investigate the effect of CAPON accumulation on Alzheimer's disease (AD) pathogenesis, CAPON was overexpressed in the brain of App(NL-G-F) mice crossbred with MAPT (human tau)-KI mice. This produced significant hippocampal atrophy and caspase3-dependent neuronal cell death in the CAPON-expressing hippocampus, suggesting that CAPON accumulation increases neurodegeneration. CAPON expression also induced significantly higher levels of phosphorylated, oligomerized and insoluble tau. In contrast, CAPON deficiency ameliorated the AD-related pathological phenotypes in tauopathy model. These findings suggest that CAPON could be a druggable AD target.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shoko", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Matsuba", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Kamano", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Mihira", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Jiro", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Takaomi C.", "last_name": "Saido", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-019-10278-x" }, "pmcid": { "normalized": "PMC6546774" }, "pmid": { "normalized": "31160584" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Amyloid beta-Protein Precursor", "descriptor_ui": "D016564", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Atrophy", "descriptor_ui": "D001284", "major_topic": false }, { "descriptor": "Caspase 3", "descriptor_ui": "D053148", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoprecipitation", "descriptor_ui": "D047468", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Protein Aggregation, Pathological", "descriptor_ui": "D066263", "major_topic": false }, { "descriptor": "Pyramidal Cells", "descriptor_ui": "D017966", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jun 3", "date_precision": "day", "issue": "1", "normalized_date": "2019-06-03", "pages": "2394", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Tau binding protein CAPON induces tau aggregation and neurodegeneration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The real-time quantitative polymerase chain reaction (qPCR) is routinely used for quantification of nucleic acids and is considered the gold standard in the field of relative nucleic acid measurements. The efficiency of the qPCR reaction is one of the most important parameters in data analysis in qPCR experiments. The Minimum Information for publication of Quantitative real-time PCR Experiments (MIQE) guidelines recommends the calibration curve as the method of choice for estimation of qPCR efficiency. The precision of this method has been reported to be between SD = 0.007 (three replicates) and SD = 0.022 (no replicates). RESULTS: In this article, we present a novel approach to the analysis of qPCR data which has been obtained by running a dilution series. Unlike previously developed methods, our method, Pairwise Efficiency, involves a new formula that describes pairwise relationships between data points on separate amplification curves and thus enables extensive statistics. The comparison of Pairwise Efficiency with the calibration curve by Monte Carlo simulation shows the two-folds improvement in the precision of estimations of efficiency and gene expression ratios on the same dataset. CONCLUSIONS: The Pairwise Efficiency nearly doubles the precision in qPCR efficiency determinations compared to standard calibration curve method. This paper demonstrates that applications of combinatorial treatment of data provide the improvement of the determination.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yulia", "last_name": "Panina", "name": null }, { "creator_type": "author", "first_name": "Arno", "last_name": "Germond", "name": null }, { "creator_type": "author", "first_name": "Brit G.", "last_name": "David", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12859-019-2911-5" }, "pmcid": { "normalized": "PMC6543629" }, "pmid": { "normalized": "31146686" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calibration", "descriptor_ui": "D002138", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Data Analysis", "descriptor_ui": "D000078332", "major_topic": false }, { "descriptor": "Indicator Dilution Techniques", "descriptor_ui": "D007201", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Monte Carlo Method", "descriptor_ui": "D009010", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May 30", "date_precision": "day", "issue": "1", "normalized_date": "2019-05-30", "pages": "295", "proceedings_title": null, "publisher": "", "title": "BMC bioinformatics", "volume": "20", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Pairwise efficiency: a new mathematical approach to qPCR data analysis increases the precision of the calibration curve assay.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alterations in pituitary adenylate cyclase-activating polypeptide (PACAP), a multifunctional neuropeptide, and its receptors have been identified as risk factors for certain psychiatric disorders, including schizophrenia. Increasing evidence from human genetic and animal model studies suggest an association between various psychiatric disorders and altered dendritic spine morphology. In the present study, we investigated the role of exogenous and endogenous PACAP in spine formation and maturation. PACAP modified the density and morphology of PSD-95-positive spines in primary cultured hippocampal neurons. Notably, PACAP increased the levels of microRNA (miR)-132 and decreased expression of corresponding miR-132 target genes and protein expression of p250GAP, a miR-132 effector known to be involved in spine morphology regulation. In corroboration, PSD-95-positive spines were reduced in PACAP-deficient (PACAP(-/-)) mice versus WT mice. Golgi staining of hippocampal CA1 neurons revealed a reduced spine densities and atypical morphologies in the male PACAP(-/-) mice. Furthermore, viral miR-132 overexpression reversed the reduction in hippocampal spinal density in the male PACAP(-/-) mice. These results indicate that PACAP signaling plays a critical role in spine morphogenesis possibly via miR-132. We suggest that dysfunction of PACAP signaling may contribute to the pathogenesis of neuropsychiatric disorders, at least partly through its effects on spine formation.SIGNIFICANCE STATEMENT Pituitary adenylate cyclase-activating polypeptide (PACAP) signaling dysfunction and dendritic spine morphology alterations have recently been suggested as important pathophysiological mechanisms underlying several psychiatric and neurological disorders. In this study, we investigated whether PACAP regulates dendritic spine morphogenesis. In a combination of pharmacological and viral gain- and loss-of-function approaches in vitro and in vivo experiments, we found PACAP to increase the size and density of dendritic spines via miR-132 upregulation. Together, our data suggest that a dysfunction of PACAP signaling may contribute to the pathogenesis of neuropsychiatric disorders, at least partly through abnormal spine formation.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Kamo", "name": null }, { "creator_type": "author", "first_name": "Harui", "last_name": "Kijima", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Higashino", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "James A.", "last_name": "Waschek", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.2468-18.2019" }, "pmcid": { "normalized": "PMC6538856" }, "pmid": { "normalized": "30886013" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May 29", "date_precision": "day", "issue": "22", "normalized_date": "2019-05-29", "pages": "4208-4220", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "39", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Pituitary Adenylate Cyclase-Activating Polypeptide Modulates Dendritic Spine Maturation and Morphogenesis via MicroRNA-132 Upregulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Heart failure, which is a major global health problem, is often preceded by pathological cardiac hypertrophy. The expansion of the cardiac vasculature, to maintain adequate supply of oxygen and nutrients, is a key determinant of whether the heart grows in a physiological compensated manner or a pathological decompensated manner. Bidirectional endothelial cell (EC)-cardiomyocyte (CMC) cross talk via cardiokine and angiocrine signaling plays an essential role in the regulation of cardiac growth and homeostasis. Currently, the mechanisms involved in the EC-CMC interaction are not fully understood, and very little is known about the EC-derived signals involved. Understanding how an excess of angiogenesis induces cardiac hypertrophy and how ECs regulate CMC homeostasis could provide novel therapeutic targets for heart failure. METHODS: Genetic mouse models were used to delete vascular endothelial growth factor (VEGF) receptors, adeno-associated viral vectors to transduce the myocardium, and pharmacological inhibitors to block VEGF and ErbB signaling in vivo. Cell culture experiments were used for mechanistic studies, and quantitative polymerase chain reaction, microarrays, ELISA, and immunohistochemistry were used to analyze the cardiac phenotypes. RESULTS: Both EC deletion of VEGF receptor (VEGFR)-1 and adeno-associated viral vector-mediated delivery of the VEGFR1-specific ligands VEGF-B or placental growth factor into the myocardium increased the coronary vasculature and induced CMC hypertrophy in adult mice. The resulting cardiac hypertrophy was physiological, as indicated by preserved cardiac function and exercise capacity and lack of pathological gene activation. These changes were mediated by increased VEGF signaling via endothelial VEGFR2, because the effects of VEGF-B and placental growth factor on both angiogenesis and CMC growth were fully inhibited by treatment with antibodies blocking VEGFR2 or by endothelial deletion of VEGFR2. To identify activated pathways downstream of VEGFR2, whole-genome transcriptomics and secretome analyses were performed, and the Notch and ErbB pathways were shown to be involved in transducing signals for EC-CMC cross talk in response to angiogenesis. Pharmacological or genetic blocking of ErbB signaling also inhibited part of the VEGF-B-induced effects in the heart. CONCLUSIONS: This study reveals that cross talk between the EC VEGFR2 and CMC ErbB signaling pathways coordinates CMC hypertrophy with angiogenesis, contributing to physiological cardiac growth.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Riikka", "last_name": "Kivela", "name": null }, { "creator_type": "author", "first_name": "Karthik Amudhala", "last_name": "Hemanthakumar", "name": null }, { "creator_type": "author", "first_name": "Katri", "last_name": "Vaparanta", "name": null }, { "creator_type": "author", "first_name": "Marius", "last_name": "Robciuc", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Izumiya", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Xuyang", "last_name": "Peng", "name": null }, { "creator_type": "author", "first_name": "Douglas B.", "last_name": "Sawyer", "name": null }, { "creator_type": "author", "first_name": "Klaus", "last_name": "Elenius", "name": null }, { "creator_type": "author", "first_name": "Kenneth", "last_name": "Walsh", "name": null }, { "creator_type": "author", "first_name": "Kari", "last_name": "Alitalo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1161/circulationaha.118.036099" }, "pmcid": { "normalized": "PMC6553980" }, "pmid": { "normalized": "30922063" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cardiomegaly", "descriptor_ui": "D006332", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Heparin-binding EGF-like Growth Factor", "descriptor_ui": "D066257", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Neovascularization, Physiologic", "descriptor_ui": "D018919", "major_topic": true }, { "descriptor": "Paracrine Communication", "descriptor_ui": "D019899", "major_topic": true }, { "descriptor": "Receptor Cross-Talk", "descriptor_ui": "D020239", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Vascular Endothelial Growth Factor B", "descriptor_ui": "D042561", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor Receptor-1", "descriptor_ui": "D040281", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor Receptor-2", "descriptor_ui": "D040301", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May 28", "date_precision": "day", "issue": "22", "normalized_date": "2019-05-28", "pages": "2570-2584", "proceedings_title": null, "publisher": "", "title": "Circulation", "volume": "139", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Endothelial Cells Regulate Physiological Cardiomyocyte Growth via VEGFR2-Mediated Paracrine Signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The rapid growth in aging populations has made prevention of age-related memory decline and dementia a high priority. Several epidemiological and clinical studies have concluded that fermented dairy products can help prevent cognitive decline; furthermore, intake of Camembert cheese prevents microglial inflammation and Alzheimer's pathology in mouse models. To elucidate the molecular mechanisms underlying the preventive effects of fermented dairy products, we screened peptides from digested milk protein for their potential to regulate the activation of microglia. We identified dipeptides of tryptophan-tyrosine (WY) and tryptophan-methionine that suppressed the microglial inflammatory response and enhanced the phagocytosis of amyloid-beta (Abeta). Various fermented dairy products and food materials contain the WY peptide. Orally administered WY peptide was smoothly absorbed into blood, delivered to the brain, and improved the cognitive decline induced by lipopolysaccharide via the suppression of inflammation. Intake of the WY peptide prevented microglial inflammation, hippocampal long-term potential deficit, and memory impairment in aged mice. In an Alzheimer's model using 5xFAD mice, intake of the WY peptide also suppressed microglial inflammation and accumulation of Abeta, which improved cognitive decline. The identified dipeptides regulating microglial activity could potentially be used to prevent cognitive decline and dementia related to inflammation.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Ano", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Yoshino", "name": null }, { "creator_type": "author", "first_name": "Toshiko", "last_name": "Kutsukake", "name": null }, { "creator_type": "author", "first_name": "Rena", "last_name": "Ohya", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nakayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.18632/aging.101909" }, "pmcid": { "normalized": "PMC6555451" }, "pmid": { "normalized": "31121563" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cognitive Dysfunction", "descriptor_ui": "D060825", "major_topic": false }, { "descriptor": "Cultured Milk Products", "descriptor_ui": "D043302", "major_topic": true }, { "descriptor": "Dipeptides", "descriptor_ui": "D004151", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Microglia", "descriptor_ui": "D017628", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May 23", "date_precision": "day", "issue": "10", "normalized_date": "2019-05-23", "pages": "2949-2967", "proceedings_title": null, "publisher": "", "title": "Aging", "volume": "11", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Tryptophan-related dipeptides in fermented dairy products suppress microglial activation and prevent cognitive decline.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We use Raman microscopic images with high spatial and spectral resolution to investigate differences between human follicular thyroid (Nthy-ori 3-1) and follicular thyroid carcinoma (FTC-133) cells, a well-differentiated thyroid cancer. Through comparison to classification of single-cell Raman spectra, the importance of subcellular information in the Raman images is emphasized. Subcellular information is extracted through a coarse-graining of the spectra at high spatial resolution ( approximately 1.7 mum(2)), producing a set of characteristic spectral groups representing locations having similar biochemical compositions. We develop a cell classifier based on the frequencies at which the characteristic spectra appear within each of the single cells. Using this classifier, we obtain a more accurate (89.8%) distinction of FTC-133 and Nthy-ori 3-1, in comparison to single-cell spectra (77.6%). We also infer which subcellular components are important to cellular distinction; we find that cancerous FTC-133 cells contain increased populations of lipid-containing components and decreased populations of cytochrome-containing components relative to Nthy-ori 3-1, and that the regions containing these contributions are largely outside the cell nuclei. In addition to increased classification accuracy, this approach provides rich subcellular information about biochemical differences and cellular locations associated with the distinction of the normal and cancerous follicular thyroid cells.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "J. Nicholas", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jpcb.9b01159" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31035762" } }, "mesh": [ { "descriptor": "Adenocarcinoma, Follicular", "descriptor_ui": "D018263", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Thyroid Neoplasms", "descriptor_ui": "D013964", "major_topic": false }, { "descriptor": "Unsupervised Machine Learning", "descriptor_ui": "D000069558", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019 May 23", "date_precision": "day", "issue": "20", "normalized_date": "2019-05-23", "pages": "4358-4372", "proceedings_title": null, "publisher": "", "title": "The journal of physical chemistry. B", "volume": "123", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "High-Resolution Raman Microscopic Detection of Follicular Thyroid Cancer Cells with Unsupervised Machine Learning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To decipher dynamic brain information processing, current genetically encoded calcium indicators (GECIs) are limited in single action potential (AP) detection speed, combinatorial spectral compatibility, and two-photon imaging depth. To address this, here, we rationally engineered a next-generation quadricolor GECI suite, XCaMPs. Single AP detection was achieved within 3-10 ms of spike onset, enabling measurements of fast-spike trains in parvalbumin (PV)-positive interneurons in the barrel cortex in vivo and recording three distinct (two inhibitory and one excitatory) ensembles during pre-motion activity in freely moving mice. In vivo paired recording of pre- and postsynaptic firing revealed spatiotemporal constraints of dendritic inhibition in layer 1 in vivo, between axons of somatostatin (SST)-positive interneurons and apical tufts dendrites of excitatory pyramidal neurons. Finally, non-invasive, subcortical imaging using red XCaMP-R uncovered somatosensation-evoked persistent activity in hippocampal CA1 neurons. Thus, the XCaMPs offer a critical enhancement of solution space in studies of complex neuronal circuit dynamics. VIDEO ABSTRACT.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Atsuya", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Manita", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Horigane", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Kazushi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kouhei", "last_name": "Otomo", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Ryang", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Tatsushi", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Takemoto-Kimura", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Yayoi", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Sean", "last_name": "Quirin", "name": null }, { "creator_type": "author", "first_name": "Charu", "last_name": "Ramakrishnan", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Nemoto", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Karl", "last_name": "Deisseroth", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Bito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cell.2019.04.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31080068" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Interneurons", "descriptor_ui": "D007395", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Pyramidal Cells", "descriptor_ui": "D017966", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May 16", "date_precision": "day", "issue": "5", "normalized_date": "2019-05-16", "pages": "1346-1360.e24", "proceedings_title": null, "publisher": "", "title": "Cell", "volume": "177", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Rational Engineering of XCaMPs, a Multicolor GECI Suite for In Vivo Imaging of Complex Brain Circuit Dynamics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have developed a platform for activatable fluorescent substrates of glucose transporters (GLUTs). We firstly conjugated fluorescein to glucosamine via an amide or methylene linker at the C-2 position of d-glucosamine, but the resulting compounds, FLG1 and FLG2, showed no uptake into MIN6 cells. So, we changed the fluorophore moiety to a fluorescein analogue, 2-Me TokyoGreen, which is less negatively charged. TokyoGreen-conjugated glucosamines TGG1 and TGG2 were successfully taken up into cells via GLUT. We further derivatized TGG1 and TGG2, and among the synthesized compounds, 2-Me-4-OMe TGG showed weak fluorescence under the acidic conditions of the extracellular environment inside tumors and in gastric cancers, and strong fluorescence at the intracellular physiological pH, under the control of a photoinduced electron transfer (PeT) process. This fluorogenic platform should be useful for developing a range of activatable fluorescent substrates targeting GLUTs, as well as derivatives that would be fluorescently activated by various intracellular enzymes, such as esterases, beta-galactosidase and bioreductases.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Takasugi", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ikeno", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bmc.2019.02.055" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30935790" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Fluorescein", "descriptor_ui": "D019793", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Glucosamine", "descriptor_ui": "D005944", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Glucose Transport Proteins, Facilitative", "descriptor_ui": "D051246", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May 15", "date_precision": "day", "issue": "10", "normalized_date": "2019-05-15", "pages": "2122-2126", "proceedings_title": null, "publisher": "", "title": "Bioorganic & medicinal chemistry", "volume": "27", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a platform for activatable fluorescent substrates of glucose transporters (GLUTs).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: We aimed to develop an ovarian cancer-specific predictive framework for clinical stage, histotype, residual tumor burden, and prognosis using machine learning methods based on multiple biomarkers. EXPERIMENTAL DESIGN: Overall, 334 patients with epithelial ovarian cancer (EOC) and 101 patients with benign ovarian tumors were randomly assigned to \"training\" and \"test\" cohorts. Seven supervised machine learning classifiers, including Gradient Boosting Machine (GBM), Support Vector Machine, Random Forest (RF), Conditional RF (CRF), Naive Bayes, Neural Network, and Elastic Net, were used to derive diagnostic and prognostic information from 32 parameters commonly available from pretreatment peripheral blood tests and age. RESULTS: Machine learning techniques were superior to conventional regression-based analyses in predicting multiple clinical parameters pertaining to EOC. Ensemble methods combining weak decision trees, such as GBM, RF, and CRF, showed the best performance in EOC prediction. The values for the highest accuracy and area under the ROC curve (AUC) for segregating EOC from benign ovarian tumors with RF were 92.4% and 0.968, respectively. The highest accuracy and AUC for predicting clinical stages with RF were 69.0% and 0.760, respectively. High-grade serous and mucinous histotypes of EOC could be preoperatively predicted with RF. An ordinal RF classifier could distinguish complete resection from others. Unsupervised clustering analysis identified subgroups among early-stage EOC patients with significantly worse survival. CONCLUSIONS: Machine learning systems can provide critical diagnostic and prognostic prediction for patients with EOC before initial intervention, and the use of predictive algorithms may facilitate personalized treatment options through pretreatment stratification of patients.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Yanaihara", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Koseki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Misato", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Komazaki", "name": null }, { "creator_type": "author", "first_name": "Jason S.", "last_name": "Shapiro", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Motoaki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Hirokuni", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Kyosuke", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Aikou", "last_name": "Okamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/1078-0432.ccr-18-3378" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30979733" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": true }, { "descriptor": "Bayes Theorem", "descriptor_ui": "D001499", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinoma, Ovarian Epithelial", "descriptor_ui": "D000077216", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Grading", "descriptor_ui": "D060787", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Neural Networks, Computer", "descriptor_ui": "D016571", "major_topic": false }, { "descriptor": "Ovarian Neoplasms", "descriptor_ui": "D010051", "major_topic": false }, { "descriptor": "Preoperative Care", "descriptor_ui": "D011300", "major_topic": true }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "ROC Curve", "descriptor_ui": "D012372", "major_topic": false }, { "descriptor": "Support Vector Machine", "descriptor_ui": "D060388", "major_topic": true }, { "descriptor": "Survival Rate", "descriptor_ui": "D015996", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May 15", "date_precision": "day", "issue": "10", "normalized_date": "2019-05-15", "pages": "3006-3015", "proceedings_title": null, "publisher": "", "title": "Clinical cancer research : an official journal of the American Association for Cancer Research", "volume": "25", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Application of Artificial Intelligence for Preoperative Diagnostic and Prognostic Prediction in Epithelial Ovarian Cancer Based on Blood Biomarkers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Targeted blockade of PD-1 with immune checkpoint inhibitors can activate T cells to destroy tumors. PD-1 is believed to function mainly at the effector, but not in the activation, phase of T cell responses, yet how PD-1 function is restricted at the activation stage is currently unknown. Here we demonstrate that CD80 interacts with PD-L1 in cis on antigen-presenting cells (APCs) to disrupt PD-L1/PD-1 binding. Subsequently, PD-L1 cannot engage PD-1 to inhibit T cell activation when APCs express substantial amounts of CD80. In knock-in mice in which cis-PD-L1/CD80 interactions do not occur, tumor immunity and autoimmune responses were greatly attenuated by PD-1. These findings indicate that CD80 on APCs limits the PD-1 coinhibitory signal, while promoting CD28-mediated costimulation, and highlight critical components for induction of optimal immune responses.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" }, { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Il-Mi", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Takeo K.", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Okazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.aav7062" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31000591" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autoimmunity", "descriptor_ui": "D015551", "major_topic": false }, { "descriptor": "B7-1 Antigen", "descriptor_ui": "D018122", "major_topic": false }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "CD28 Antigens", "descriptor_ui": "D018106", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunotherapy", "descriptor_ui": "D007167", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Mutant Strains", "descriptor_ui": "D008817", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May 10", "date_precision": "day", "issue": "6440", "normalized_date": "2019-05-10", "pages": "558-566", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "364", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Restriction of PD-1 function by cis-PD-L1/CD80 interactions is required for optimal T cell responses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Abstract Monte Carlo tree search (MCTS) has received considerable interest due to its spectacular success in the difficult problem of computer Go and also proved beneficial in a range of other domains. A major issue that has received little attention in the MCTS literature is the fact that, in most games, different actions can lead to the same state, that may lead to a high degree of redundancy in tree representation and unnecessary additional computational cost. We extend MCTS to single rooted directed acyclic graph (SR-DAG), and consider the Best Arm Identification (BAI) and the Best Leaf Identification (BLI) problem of an expanding SR-DAG of arbitrary depth. We propose algorithms that are (?, σ)-correct in the fixed confidence setting, and prove an asymptotic upper bounds of sample complexity for our BAI algorithm. As a major application for our BLI algorithm, a novel approach for Feature Selection is proposed by representing the feature set space as a SR-DAG and repeatedly evaluating feature subsets until a candidate for the best leaf is returned, a proof of concept is shown on benchmark data sets.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Aurélien", "last_name": "Pélissier", "name": null }, { "creator_type": "author", "first_name": "Atsuyoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tabata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1137/1.9781611975673.51" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2019-05-06", "date_precision": "day", "issue": null, "normalized_date": "2019-05-06", "pages": "450-458", "proceedings_title": null, "publisher": "Society for Industrial and Applied Mathematics", "title": null, "volume": "", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Feature selection as Monte-Carlo Search in Growing Single Rooted Directed Acyclic Graph by Best Leaf Identification", "url": "https://doi.org/10.1137/1.9781611975673.51", "zotero": { "item_type": "bookSection" } }, { "abstract": "The assembly of organized colonies is the earliest manifestation in the derivation or induction of pluripotency in vitro. However, the necessity and origin of this assemblance is unknown. Here, we identify human pluripotent founder cells (hPFCs) that initiate, as well as preserve and establish, pluripotent stem cell (PSC) cultures. PFCs are marked by N-cadherin expression (NCAD(+)) and reside exclusively at the colony boundary of primate PSCs. As demonstrated by functional analysis, hPFCs harbor the clonogenic capacity of PSC cultures and emerge prior to commitment events or phenotypes associated with pluripotent reprogramming. Comparative single-cell analysis with pre- and post-implantation primate embryos revealed hPFCs share hallmark properties with primitive endoderm (PrE) and can be regulated by non-canonical Wnt signaling. Uniquely informed by primate embryo organization in vivo, our study defines a subset of founder cells critical to the establishment pluripotent state.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mio", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Ryan R.", "last_name": "Mitchell", "name": null }, { "creator_type": "author", "first_name": "Yannick D.", "last_name": "Benoit", "name": null }, { "creator_type": "author", "first_name": "Luca", "last_name": "Orlando", "name": null }, { "creator_type": "author", "first_name": "Jennifer C.", "last_name": "Reid", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Kathryn C.", "last_name": "Davidson", "name": null }, { "creator_type": "author", "first_name": "Zoya", "last_name": "Shapovalova", "name": null }, { "creator_type": "author", "first_name": "Tony J.", "last_name": "Collins", "name": null }, { "creator_type": "author", "first_name": "Andras", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Mickie", "last_name": "Bhatia", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cell.2019.03.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30982595" } }, "mesh": [ { "descriptor": "Antigens, CD", "descriptor_ui": "D015703", "major_topic": false }, { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Endoderm", "descriptor_ui": "D004707", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May 2", "date_precision": "day", "issue": "4", "normalized_date": "2019-05-02", "pages": "910-924.e22", "proceedings_title": null, "publisher": "", "title": "Cell", "volume": "177", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Human Pluripotency Is Initiated and Preserved by a Unique Subset of Founder Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Here, we describe an optimized and detailed protocol for block-face serial microscopy tomography (FAST). FAST enables high-speed serial section fluorescence imaging of fixed brains at an axonal spatial resolution and subsequent image data processing. It renders brain-wide anatomical and functional analyses, including structural profiling of nuclear-stained brain at the single-cell level, cell-type-specific mapping with reporter animal brains and neuronal tracing with anterograde/retrograde labeling. Light-sheet fluorescence microscopy of cleared brains is advantageous in regard to imaging speed, but its spatial resolution is generally limited, whereas the opposite is true for conventional confocal microscopy. FAST offers a solution to overcome these technical limitations. This protocol describes detailed procedures for assembling the FAST hardware, sample preparation, imaging and image processing. A single imaging session takes as little as 2.4 h per mouse brain, and sample preparation requires 1 to several days, depending on pretreatments; however, multiple samples can be prepared simultaneously. We anticipate that FAST will contribute to unbiased and hypothesis-free approaches for a better understanding of brain systems.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Misaki", "last_name": "Niu", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Naka", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Tanuma", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Yamaura", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41596-019-0148-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30962606" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Brain Chemistry", "descriptor_ui": "D001923", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Tomography", "descriptor_ui": "D014054", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019-05", "date_precision": "month", "issue": "5", "normalized_date": "2019-05", "pages": "1509-1529", "proceedings_title": null, "publisher": "", "title": "Nature Protocols", "volume": "14", "year": 2019 }, "ssbd": { "database": [ "ssbd-database-000225" ], "repository": [ "ssbd-repos-000225" ] }, "title": "Whole-brain block-face serial microscopy tomography at subcellular resolution using FAST", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ten-eleven translocation (TET) proteins regulate DNA methylation and gene expression by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Although Tet2/Tet3 deficiency has been reported to lead to myeloid cell, B-cell and invariant natural killer T (iNKT) cell malignancy, the effect of TET on regulatory T cells (Tregs) has not been elucidated. We found that Tet2/Tet3 deficiency in Tregs led to lethal hyperproliferation of CD4+Foxp3+ T cells in the spleen and mesenteric lymph nodes after 5 months of age. Additionally, in aged Treg-specific Tet2/Tet3-deficient mice, serum IgG1, IgG3, IgM and IgE levels were markedly elevated. High IL-17 expression was observed in both Foxp3+ and Fopx3- CD4+ T cells, and adoptive transfer of Tet2/Tet3-deficient Tregs into lymphopenic mice inhibited Foxp3 expression and caused conversion into IL-17-producing cells. However, the conserved non-coding DNA sequence-2 (CNS2) region of the Foxp3 gene locus, which has been shown to be particularly important for stable Foxp3 expression, was only partly methylated. We identified novel TET-dependent demethylation sites in the Foxp3 upstream enhancer, which may contribute to stable Foxp3 expression. Together, these data indicate that Tet2 and Tet3 are involved in Treg stability and immune homeostasis in mice.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Nakatsukasa", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Jinghua", "last_name": "Yin", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Koga-Iizuka", "name": null }, { "creator_type": "author", "first_name": "Kazue", "last_name": "Someya", "name": null }, { "creator_type": "author", "first_name": "Yohko", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Naganari", "last_name": "Ohkura", "name": null }, { "creator_type": "author", "first_name": "Shimon", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Ikuko", "last_name": "Koya", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Sanosaka", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Kohyama", "name": null }, { "creator_type": "author", "first_name": "Yu-Ichi", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Takeji", "last_name": "Takamura-Enya", "name": null }, { "creator_type": "author", "first_name": "Qianjin", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/intimm/dxz008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30726915" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Dioxygenases", "descriptor_ui": "D049308", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Interleukin-17", "descriptor_ui": "D020381", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr 26", "date_precision": "day", "issue": "5", "normalized_date": "2019-04-26", "pages": "335-347", "proceedings_title": null, "publisher": "", "title": "International immunology", "volume": "31", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Loss of TET proteins in regulatory T cells promotes abnormal proliferation, Foxp3 destabilization and IL-17 expression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Endocytosis mediates the internalization and ingestion of a variety of endogenous or exogenous substances, including virus particles, under the control of intracellular signaling pathways. We have previously reported that the complex formed between the small GTPase Ras and phosphoinositide 3-kinase (PI3K) translocates from the plasma membrane to endosomes, signaling from which thereby regulates clathrin-independent endocytosis, endosome maturation, influenza virus internalization, and infection. However, the molecular mechanism by which the Ras-PI3K complex is recruited to endosomes remains unclear. Here, we have identified the amino acid sequence responsible for endosomal localization of the Ras-PI3K complex. PI3K lacking this sequence failed to translocate to endosomes, and expression of the peptide comprising this PI3K-derived sequence inhibited clathrin-independent endocytosis, influenza virus internalization, and infection. Moreover, treatment of cells with this peptide in an arginine-rich, cell-penetrating form successfully suppressed influenza virus infection in vitro and ex vivo, making this peptide a potential therapeutic agent against influenza virus infection.Key words: signal transduction, endocytosis, endosome, imaging, influenza virus.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Aya O.", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Kosui", "last_name": "Horiuchi", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Prabha", "last_name": "Nepal", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Sarad", "last_name": "Paudel", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Nishide", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Nanbo", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1247/csf.19001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30905923" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": false }, { "descriptor": "Endosomes", "descriptor_ui": "D011992", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Orthomyxoviridae", "descriptor_ui": "D009975", "major_topic": false }, { "descriptor": "Peptide Fragments", "descriptor_ui": "D010446", "major_topic": false }, { "descriptor": "Phosphatidylinositol 3-Kinase", "descriptor_ui": "D058539", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "ras Proteins", "descriptor_ui": "D018631", "major_topic": false }, { "descriptor": "Virus Internalization", "descriptor_ui": "D053586", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr 25", "date_precision": "day", "issue": "1", "normalized_date": "2019-04-25", "pages": "61-74", "proceedings_title": null, "publisher": "", "title": "Cell structure and function", "volume": "44", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "A Peptide Derived from Phosphoinositide 3-kinase Inhibits Endocytosis and Influenza Virus Infection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Parkinson's disease (PD) is the second most common neurodegenerative disease. Lewy bodies and pale bodies in dopaminergic neurons in the substantia nigra are pathological hallmarks of PD. A number of neurodegenerative diseases demonstrate aggregate formation, but how these aggregates are associated with their pathogenesis remains unknown. It has been reported that repressor element-1 silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is induced in the nuclei of aged neurons, preserves neuronal function, and protects against neurodegeneration during aging through the repression of cell death-inducing genes. The loss of REST is associated with Alzheimer's disease pathology. However, its function in dopaminergic neurons remains unknown. Here we demonstrated that REST enters the nucleus of aged dopaminergic neurons. On the other hand, REST is partially sequestrated in Lewy bodies and is mostly absent from the nucleus of neurons in brains with PD and dementia with Lewy bodies (DLB). Dopaminergic neuron-specific autophagy-deficient mice exhibit REST accumulation in aggregates. Defects in the protein quality control system induce REST mRNA expression; its gene product mainly appears in aggregates. Our results suggest that Lewy pathology disturbs normal aging processes in dopaminergic neurons by sequestering REST and the loss of REST may associate with the PD pathology.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Miwako", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Shigeto", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Kahori", "last_name": "Shiba-Fukushima", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Takanashi", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Nobutaka", "last_name": "Hattori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neulet.2019.01.042" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30684677" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": true }, { "descriptor": "Dopaminergic Neurons", "descriptor_ui": "D059290", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lewy Bodies", "descriptor_ui": "D016631", "major_topic": false }, { "descriptor": "Lewy Body Disease", "descriptor_ui": "D020961", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Parkinson Disease", "descriptor_ui": "D010300", "major_topic": false }, { "descriptor": "RE1-Silencing Transcription Factor", "descriptor_ui": "D000099229", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Tyrosine 3-Monooxygenase", "descriptor_ui": "D014446", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr 23", "date_precision": "day", "issue": "", "normalized_date": "2019-04-23", "pages": "59-63", "proceedings_title": null, "publisher": "", "title": "Neuroscience letters", "volume": "699", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Loss of nuclear REST/NRSF in aged-dopaminergic neurons in Parkinson's disease patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have developed an activatable red fluorescence probe for dipeptidylpeptidase-IV (DPP-IV) by precisely controlling the photoinduced electron transfer (PeT) process of a red fluorescent scaffold, SiR600. The developed probe exhibited an extremely low background signal and showed significant fluorescence activation upon reaction with DPP-IV, enabling sensitive detection of esophageal cancer in clinical specimens from cancer patients.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akira", "last_name": "Ogasawara", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Yugo", "last_name": "Kuriki", "name": null }, { "creator_type": "author", "first_name": "Kyohhei", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Haruna", "last_name": "Onoyama", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Fujishiro", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fukayama", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Seto", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.bioconjchem.9b00198" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30920803" } }, "mesh": [ { "descriptor": "Dipeptidyl Peptidase 4", "descriptor_ui": "D018819", "major_topic": false }, { "descriptor": "Esophageal Neoplasms", "descriptor_ui": "D004938", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr 17", "date_precision": "day", "issue": "4", "normalized_date": "2019-04-17", "pages": "1055-1060", "proceedings_title": null, "publisher": "", "title": "Bioconjugate chemistry", "volume": "30", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Red Fluorescence Probe Targeted to Dipeptidylpeptidase-IV for Highly Sensitive Detection of Esophageal Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "T cell activation is tightly regulated by both stimulatory and inhibitory co-receptors and has been a focus in the development of interventions for managing cancer or autoimmune diseases. Targeting the inhibitory co-receptors programmed cell death 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) has successfully eradicated tumors but induced immune-related adverse events in humans and mice. The beneficial and adverse effects of targeting these co-receptors highlight their importance in cancer immunity and also autoimmunity. Although the therapeutic potencies of other inhibitory co-receptors are under extensive investigation, their inhibitory mechanisms and their functional differences are not well understood. Here we analyzed the inhibitory mechanisms of lymphocyte activation gene-3 (LAG-3), another inhibitory co-receptor, by using an in vitro T cell activation system and a high-affinity anti-LAG-3 antibody that strongly interferes with the binding of LAG-3 to its ligand. We found that the expression level of LAG-3 strongly correlates with the inhibitory function of LAG-3, suggesting that LAG-3 functions as a rheostat rather than as a breaker of T cell activation. By evaluating the inhibitory capacities of various LAG-3 variants relative to their expression levels, we found that LAG-3 transduces two independent inhibitory signals through an FXXL motif in the membrane-proximal region and the C-terminal EX repeat. These motifs have not been reported previously for inhibitory co-receptors, suggesting that LAG-3 inhibits T cell activation through a nonredundant inhibitory mechanisms along with the other inhibitory co-receptors. Our findings provide a rationale for combinatorial targeting of LAG-3 and the other inhibitory co-receptors to improve cancer immunotherapy.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takeo K.", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Il-Mi", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Okazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.ra119.007455" }, "pmcid": { "normalized": "PMC6463702" }, "pmid": { "normalized": "30760527" } }, "mesh": [ { "descriptor": "Amino Acid Motifs", "descriptor_ui": "D020816", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, CD", "descriptor_ui": "D015703", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": true }, { "descriptor": "Lymphocyte Activation Gene 3 Protein", "descriptor_ui": "D000093322", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Protein Domains", "descriptor_ui": "D000072417", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr 12", "date_precision": "day", "issue": "15", "normalized_date": "2019-04-12", "pages": "6017-6026", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "294", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Atypical motifs in the cytoplasmic region of the inhibitory immune co-receptor LAG-3 inhibit T cell activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Kinetic simulation is a useful approach for elucidating complex cell-signaling systems. The numerical simulations required for kinetic modeling in live cells critically require parameters such as protein concentrations and dissociation constants (Kd ). However, only a limited number of parameters have been measured experimentally in living cells. Here we describe an approach for quantifying the concentration and Kd of endogenous proteins at the single-cell level with CRISPR/Cas9-mediated knock-in and fluorescence cross-correlation spectroscopy. First, the mEGFP gene was knocked in at the end of the mitogen-activated protein kinase 1 (MAPK1) gene, encoding extracellular signal-regulated kinase 2 (ERK2), through homology-directed repair or microhomology-mediated end joining. Next, the HaloTag gene was knocked in at the end of the ribosomal S6 kinase 2 (RSK2) gene. We then used fluorescence correlation spectroscopy to measure the protein concentrations of endogenous ERK2-mEGFP and RSK2-HaloTag fusion constructs in living cells, revealing substantial heterogeneities. Moreover, fluorescence cross-correlation spectroscopy analyses revealed temporal changes in the apparent Kd values of the binding between ERK2-mEGFP and RSK2-HaloTag in response to epidermal growth factor stimulation. Our approach presented here provides a robust and efficient method for quantifying endogenous protein concentrations and dissociation constants in living cells.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akira T.", "last_name": "Komatsubara", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.ra119.007685" }, "pmcid": { "normalized": "PMC6463716" }, "pmid": { "normalized": "30739083" } }, "mesh": [ { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 1", "descriptor_ui": "D019950", "major_topic": false }, { "descriptor": "Ribosomal Protein S6 Kinases, 90-kDa", "descriptor_ui": "D038744", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr 12", "date_precision": "day", "issue": "15", "normalized_date": "2019-04-12", "pages": "6062-6072", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "294", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-cell quantification of the concentrations and dissociation constants of endogenous proteins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Flow control-based paper devices have recently shown great potential for point-of-need analysis, since they allow for the easy operation of multi-step assays by minimizing user operation. In this work, a wax printing method was evaluated as a means to control liquid flow in 3D microfluidic paper-based analytical devices (muPADs). The resulting flow control-based 3D muPADs were applied to determine paraoxon-ethyl as a typical organophosphate pesticide model system. The analytical procedure is as simple as applying a 200-muL sample solution, resulting in reproducible (relative standard deviation of colorimetric signals from 6 independently fabricated devices, 2.63%) colorimetric signals within 1 h of the assay time with the limit of detection (LOD) reaching 25.0 mug/L. Finally, results obtained for pesticide-spiked water samples analyzed by flow control-based 3D muPADs showed good agreement with those from a conventional HPLC analysis with UV detection.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Quoc Trung", "last_name": "Hua", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.2116/analsci.18p435" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30531126" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 Apr 10", "date_precision": "day", "issue": "4", "normalized_date": "2019-04-10", "pages": "393-399", "proceedings_title": null, "publisher": "", "title": "Analytical sciences : the international journal of the Japan Society for Analytical Chemistry", "volume": "35", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Flow Control-based 3D muPADs for Organophosphate Pesticide Detection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer immunotherapies targeting programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 revolutionized cancer treatment and instigated various trials to develop new cancer immunotherapies with higher therapeutic efficacy. Agonistic Abs against tumor necrosis factor receptor super family (TNFRSF) molecules are highly expected due to their high potential to enhance survival, proliferation, and effector function of T cells. To date, agonistic antibodies (Abs) against CD27, GITR, OX40, and 4-1BB have been reported to increase the efficacy of anti-PD-1 therapy in animal models and clinical trials of these combinatorial therapies are underway. However, the mechanisms how agonistic Abs against TNFRSF molecules potentiate anti-PD-1 therapy are not well understood. Here we examined the potency of PD-1 to inhibit the antigen-dependent activation of T cells in the presence of co-stimulation through CD27 and GITR by using in vitro and ex vivo co-culture systems of T cells and antigen presenting cells. The cytokine secretion from T cells upon antigen stimulation was strongly augmented by the engagement of CD27 or GITR with their corresponding ligands. Remarkably, PD-1 efficiently inhibited the activation of T cells even in the presence of co-stimulation through CD27 or GITR. Accordingly, cytokine secretion was synergistically augmented when PD-1 blockade was combined with triggering of CD27 or GITR. These results indicate that the triggering of TNFRSF molecules and PD-1 blockade can act on the same individual cells simultaneously to augment the magnitude of T cell activation, providing the rationale for the combinatorial usage of agonistic Abs against TNFRSF molecules and blocking Abs against PD-1 or PD-L1.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Reina", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Watada", "name": null }, { "creator_type": "author", "first_name": "Il-Mi", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Okazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2019.02.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30771904" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Glucocorticoid-Induced TNFR-Related Protein", "descriptor_ui": "D053450", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": true }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false }, { "descriptor": "Tumor Necrosis Factor Receptor Superfamily, Member 7", "descriptor_ui": "D018127", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr 9", "date_precision": "day", "issue": "3", "normalized_date": "2019-04-09", "pages": "491-497", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "511", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "PD-1 efficiently inhibits T cell activation even in the presence of co-stimulation through CD27 and GITR.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cell manipulation technique using thermoresponsive polymers is currently attracting much attention for applications in the medical field. To achieve arbitrary and accurate cell control, it is necessary to intensely research fibronectin behavior. A smart surface, which has thermoresponsive wettability and which can adsorb or desorb fibronectin repeatedly without the presence of cells, was fabricated by an electrospinning method. The fabricated coating changed its structure as the temperature was changed, and this transformation could substitute for the pulling force generated by the cytoskeletal contraction of cells. Moreover, a coated quartz crystal microbalance was able to detect the fibronectin behavior as frequency shifts, which could be used in the estimation of the mass shift with the aid of suitable equations. This coating and measurement system can contribute greatly not only to the development in the medical field centered on biomaterial manipulation technologies, but also to the improvement of medical instruments.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jiatu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Taisei", "last_name": "Kaku", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Tokura", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Matsukawa", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Homma", "name": null }, { "creator_type": "author", "first_name": "Taihei", "last_name": "Nishimoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Aya Mizutani", "last_name": "Akimoto", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nagase", "name": null }, { "creator_type": "author", "first_name": "Hideko", "last_name": "Kanazawa", "name": null }, { "creator_type": "author", "first_name": "Seimei", "last_name": "Shiratori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.biomac.9b00121" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30785729" } }, "mesh": [ { "descriptor": "Biocompatible Materials", "descriptor_ui": "D001672", "major_topic": false }, { "descriptor": "Fibronectins", "descriptor_ui": "D005353", "major_topic": false }, { "descriptor": "Quartz Crystal Microbalance Techniques", "descriptor_ui": "D058525", "major_topic": false }, { "descriptor": "Surface Properties", "descriptor_ui": "D013499", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr 8", "date_precision": "day", "issue": "4", "normalized_date": "2019-04-08", "pages": "1748-1755", "proceedings_title": null, "publisher": "", "title": "Biomacromolecules", "volume": "20", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Adsorption-Desorption Control of Fibronectin in Real Time at the Liquid/Polymer Interface on a Quartz Crystal Microbalance by Thermoresponsivity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bistable opsins are photopigments expressed in both invertebrates and vertebrates. These light-sensitive G-protein-coupled receptors undergo a reversible reaction upon illumination. A first photon initiates the cis to trans isomerization of the retinal chromophore-attached to the protein through a protonated Schiff base-and a series of transition states that eventually results in the formation of the thermally stable and active Meta state. Excitation by a second photon reverts this process to recover the original ground state. On the other hand, monostable opsins (e.g., bovine rhodopsin) lose their chromophore during the decay of the Meta II state (i.e., they bleach). Spectroscopic studies on the molecular details of the two-photon cycle in bistable opsins are limited. Here, we describe the successful expression and purification of recombinant rhodopsin-1 from the jumping spider Hasarius adansoni (JSR1). In its natural configuration, spectroscopic characterization of JSR1 is hampered by the similar absorption spectra in the visible spectrum of the inactive and active states. We solved this issue by separating their absorption spectra by replacing the endogenous 11-cis retinal chromophore with the blue-shifted 9-cis JSiR1. With this system, we used time-resolved ultraviolet-visible spectroscopy after pulsed laser excitation to obtain kinetic details of the rise and decay of the photocycle intermediates. We also used resonance Raman spectroscopy to elucidate structural changes of the retinal chromophore upon illumination. Our data clearly indicate that the protonated Schiff base is stable throughout the entire photoreaction. We additionally show that the accompanying conformational changes in the protein are different from those of monostable rhodopsin, as recorded by light-induced FTIR difference spectroscopy. Thus, we envisage JSR1 as becoming a model system for future studies on the reaction mechanisms of bistable opsins, e.g., by time-resolved x-ray crystallography.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "David", "last_name": "Ehrenberg", "name": null }, { "creator_type": "author", "first_name": "Niranjan", "last_name": "Varma", "name": null }, { "creator_type": "author", "first_name": "Xavier", "last_name": "Deupi", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null }, { "creator_type": "author", "first_name": "Gebhard F. X.", "last_name": "Schertler", "name": null }, { "creator_type": "author", "first_name": "Joachim", "last_name": "Heberle", "name": null }, { "creator_type": "author", "first_name": "Elena", "last_name": "Lesca", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpj.2019.02.025" }, "pmcid": { "normalized": "PMC6451042" }, "pmid": { "normalized": "30902364" } }, "mesh": [ { "descriptor": "Absorption, Radiation", "descriptor_ui": "D065638", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Insect Proteins", "descriptor_ui": "D019476", "major_topic": false }, { "descriptor": "Photons", "descriptor_ui": "D017785", "major_topic": true }, { "descriptor": "Protein Domains", "descriptor_ui": "D000072417", "major_topic": false }, { "descriptor": "Rhodopsin", "descriptor_ui": "D012243", "major_topic": false }, { "descriptor": "Schiff Bases", "descriptor_ui": "D012545", "major_topic": false }, { "descriptor": "Spiders", "descriptor_ui": "D013112", "major_topic": false }, { "descriptor": "Ultraviolet Rays", "descriptor_ui": "D014466", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr 2", "date_precision": "day", "issue": "7", "normalized_date": "2019-04-02", "pages": "1248-1258", "proceedings_title": null, "publisher": "", "title": "Biophysical journal", "volume": "116", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "The Two-Photon Reversible Reaction of the Bistable Jumping Spider Rhodopsin-1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Liposomes composed of egg phosphatidylcholine and cholesterol were modified with the temperature-responsive polymer poly(N-isopropylacrylamide-co-N, N-dimethylacrylamide) (P(NIPAAm-co-DMAAm)), and exhibited reversible surface properties with temperature. Completely reversible liposome aggregation due to P(NIPAAm-co-DMAAm) hydration/dehydration was demonstrated over four successive cycles of heating and cooling. The P(NIPAAm-co-DMAAm) polymer was hydrated during cooling, which dispersed the liposomes. The rigidity of the liposomal membrane was one of the factors in the reversible aggregation, as was the modification density of the polymer on the liposomes. A low density on relatively rigid liposomes could maintain the polymer property of reversible hydrated layers below critical solution temperature (LCST) boundary. Above the LCST, temperature-responsive polymers could also transport negatively charged liposomes into cells. The reversible behavior of the temperature-responsive polymer-modified liposomes has not been reported previously and could enable new applications for switching deposit forms as alternative drug carriers.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Nemoto", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Fujieda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Mafumi", "last_name": "Hishida", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Ayano", "name": null }, { "creator_type": "author", "first_name": "Yoshie", "last_name": "Maitani", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nagase", "name": null }, { "creator_type": "author", "first_name": "Hideko", "last_name": "Kanazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.colsurfb.2019.01.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30641302" } }, "mesh": [ { "descriptor": "Acrylic Resins", "descriptor_ui": "D000180", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Liposomes", "descriptor_ui": "D008081", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Particle Size", "descriptor_ui": "D010316", "major_topic": false }, { "descriptor": "RAW 264.7 Cells", "descriptor_ui": "D000067996", "major_topic": false }, { "descriptor": "Scattering, Small Angle", "descriptor_ui": "D053838", "major_topic": false }, { "descriptor": "Surface Properties", "descriptor_ui": "D013499", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": true }, { "descriptor": "X-Ray Diffraction", "descriptor_ui": "D014961", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr 1", "date_precision": "day", "issue": "", "normalized_date": "2019-04-01", "pages": "309-316", "proceedings_title": null, "publisher": "", "title": "Colloids and surfaces. B, Biointerfaces", "volume": "176", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Liposomes with temperature-responsive reversible surface properties.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tau is a microtubule‐associated protein (MAP) that is localized to the axon. In Alzheimer's disease (AD), the distribution of tau undergoes a remarkable alteration, leading to the formation of tau inclusions in the somatodendritic compartment. While the abnormal aggregated tau has been extensively studied in human patient tissues and animal models of AD, how normal tau localizes to the axon, which would be the foundation to understand how the mis‐localization occurs, has not been well studied due to the poor detectability of normal unaggregated tau in vivo. Therefore, we developed immunohistochemical techniques that can detect normal mouse and human tau in brain tissues with high sensitivity. Using these techniques, we demonstrate the global distribution of tau in the mouse brain and confirmed that normal tau is exclusively localized to the axonal compartment in vivo. Interestingly, tau antibodies strongly labeled nonmyelinated axons such as hippocampal mossy fibers, while white matters generally exhibited low levels of immunoreactivity. Furthermore, mouse tau is highly expressed not only in neurons but also in oligodendrocytes. With super resolution imaging using the stimulated‐depletion microscopy, axonal tau appeared punctate rather than fibrous, indicating that tau decorates microtubules sparsely. Co‐labeling with presynaptic and postsynaptic markers revealed that normal tau is not localized to synapses but sparsely distributes in the axon. Taken together, this study reports novel antibodies to investigate the localization and mis‐localization of tau in vivo and novel findings of normal tau localization in the mouse brain.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Atsuko", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Misonou", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Matsuyama", "name": null }, { "creator_type": "author", "first_name": "Akane", "last_name": "Nomori", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Wada‐Kakuda", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Miyasaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cne.24577" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30408165" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies", "descriptor_ui": "D000906", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Neuroglia", "descriptor_ui": "D009457", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr 01", "date_precision": "day", "issue": "5", "normalized_date": "2019-04-01", "pages": "985-998", "proceedings_title": null, "publisher": "", "title": "The Journal of Comparative Neurology", "volume": "527", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Distribution of endogenous normal tau in the mouse brain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Calcium ion (Ca2+) is a universal intracellular messenger molecule that drives multiple signaling pathways, leading to diverse biological outputs. The coordination of two Ca2+ signal sources-\"Ca2+ influx\" from outside the cell and \"Ca2+ release\" from the intracellular Ca2+ store endoplasmic reticulum (ER)-is considered to underlie the diverse spatio-temporal patterns of Ca2+ signals that cause multiple biological functions in cells. The purpose of this protocol is to describe a new Ca2+ imaging method that enables monitoring of the very moment of \"Ca2+ influx\" and \"Ca2+ release\". OER-GCaMP6f is a genetically encoded Ca2+ indicator (GECI) comprising GCaMP6f, which is targeted to the ER outer membrane. OER-GCaMP6f can monitor Ca2+ release at a higher temporal resolution than conventional GCaMP6f. Combined with plasma membrane-targeted GECIs, the spatio-temporal Ca2+ signal pattern can be described at a subcellular resolution. The subcellular-targeted Ca2+ indicators described here are, in principle, available for all cell types, even for the in vivo imaging of Caenorhabditis elegans neurons. In this protocol, we introduce Ca2+ imaging in cells from cell lines, neurons, and glial cells in dissociated primary cultures, and describe the preparation of frozen stock of rat cortical neurons.", "classifications": [ { "id": "18H05414", "label": "18H05414", "researcher": "Hiroko Bannai", "type": "grant" }, { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null }, { "creator_type": "author", "first_name": "Matsumi", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Fumihiro", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Mikoshiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.3791/59246" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30958464" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019-03-22", "date_precision": "day", "issue": "145", "normalized_date": "2019-03-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of Visualized Experiments: JoVE", "volume": "", "year": 2019 }, "ssbd": { "database": [ "ssbd-database-000197" ], "repository": [ "ssbd-repos-000197" ] }, "title": "Dissection of Local Ca2+ Signals in Cultured Cells by Membrane-targeted Ca2+ Indicators", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The balance between self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPCs) maintains hematopoietic homeostasis, failure of which can lead to hematopoietic disorder. HSPC fate is controlled by signals from the bone marrow niche resulting in alteration of the stem cell transcription network. Regnase-1, a member of the CCCH zinc finger protein family possessing RNAse activity, mediates post-transcriptional regulatory activity through degradation of target mRNAs. The precise function of Regnase-1 has been explored in inflammation-related cytokine expression but its function in hematopoiesis has not been elucidated. Here, we show that Regnase-1 regulates self-renewal of HSPCs through modulating the stability of Gata2 and Tal1 mRNA. In addition, we found that dysfunction of Regnase-1 leads to the rapid onset of abnormal hematopoiesis. Thus, our data reveal that Regnase-1-mediated post-transcriptional regulation is required for HSPC maintenance and suggest that it represents a leukemia tumor suppressor.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Teppei", "last_name": "Shimamura", "name": null }, { "creator_type": "author", "first_name": "Weizhen", "last_name": "Jia", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Kunisaki", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Osawa", "name": null }, { "creator_type": "author", "first_name": "Shizuo", "last_name": "Akira", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-019-09028-w" }, "pmcid": { "normalized": "PMC6403248" }, "pmid": { "normalized": "30842549" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Marrow", "descriptor_ui": "D001853", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Self Renewal", "descriptor_ui": "D000066673", "major_topic": false }, { "descriptor": "Datasets as Topic", "descriptor_ui": "D066264", "major_topic": false }, { "descriptor": "GATA2 Transcription Factor", "descriptor_ui": "D050989", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cell Transplantation", "descriptor_ui": "D018380", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia, Myeloid, Acute", "descriptor_ui": "D015470", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Ribonucleases", "descriptor_ui": "D012260", "major_topic": false }, { "descriptor": "RNA Processing, Post-Transcriptional", "descriptor_ui": "D012323", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "T-Cell Acute Lymphocytic Leukemia Protein 1", "descriptor_ui": "D000073942", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transplantation Chimera", "descriptor_ui": "D018183", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Mar 6", "date_precision": "day", "issue": "1", "normalized_date": "2019-03-06", "pages": "1072", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Regnase-1-mediated post-transcriptional regulation is essential for hematopoietic stem and progenitor cell homeostasis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Despite their central role in multicellular organization, navigation rules that dictate cell rearrangement remain largely undefined. Contact between neighboring cells and diffusive attractant molecules are two of the major determinants of tissue-level patterning; however, in most cases, molecular and developmental complexity hinders one from decoding the exact governing rules of individual cell movement. A primordial example of tissue patterning by cell rearrangement is found in the social amoeba Dictyostelium discoideum where the organizing center or the \"tip\" self-organizes as a result of sorting of differentiating prestalk and prespore cells. By employing microfluidics and microsphere-based manipulation of navigational cues at the single-cell level, here we uncovered a previously overlooked mode of Dictyostelium cell migration that is strictly directed by cell-cell contact. The cell-cell contact signal is mediated by E-set Ig-like domain-containing heterophilic adhesion molecules TgrB1/TgrC1 that act in trans to induce plasma membrane recruitment of the SCAR complex and formation of dendritic actin networks, and the resulting cell protrusion competes with those induced by chemoattractant cAMP. Furthermore, we demonstrate that both prestalk and prespore cells can protrude toward the contact signal as well as to chemotax toward cAMP; however, when given both signals, prestalk cells orient toward the chemoattractant, whereas prespore cells choose the contact signal. These data suggest a model of cell sorting by competing juxtacrine and diffusive cues, each with potential to drive its own mode of collective cell migration.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Taihei", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1815063116" }, "pmcid": { "normalized": "PMC6410881" }, "pmid": { "normalized": "30782791" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Cell Aggregation", "descriptor_ui": "D002449", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false }, { "descriptor": "Diffusion", "descriptor_ui": "D004058", "major_topic": false }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": false }, { "descriptor": "Microfluidics", "descriptor_ui": "D044085", "major_topic": false }, { "descriptor": "Protozoan Proteins", "descriptor_ui": "D015800", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Mar 5", "date_precision": "day", "issue": "10", "normalized_date": "2019-03-05", "pages": "4291-4296", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "116", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Tissue self-organization based on collective cell migration by contact activation of locomotion and chemotaxis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The original version of this Article contained an error in the author affiliations. Affiliation 5 incorrectly read 'Laboratory for Prediction of Cell Systems Dynamics, RIKEN Center for Biosystems Dynamics Research (BDR), Suite, Hyogo 565-0874, Japan.' This has now been corrected in both the PDF and HTML versions of the Article.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Chizuko", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kojo", "name": null }, { "creator_type": "author", "first_name": "Motoi", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Kazuyo", "last_name": "Moro", "name": null }, { "creator_type": "author", "first_name": "Georges", "last_name": "Lacaud", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Taniuchi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ebihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-019-08932-5" }, "pmcid": { "normalized": "PMC6397247" }, "pmid": { "normalized": "30824704" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 Mar 1", "date_precision": "day", "issue": "1", "normalized_date": "2019-03-01", "pages": "1075", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Author Correction: Runx/Cbfbeta complexes protect group 2 innate lymphoid cells from exhausted-like hyporesponsiveness during allergic airway inflammation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Circadian rhythms are controlled by transcriptional feedback loops of clock genes and proteins. The stability of clock proteins is regulated by post-translational modification, such as phosphorylation by kinases. In particular, casein kinase I (CKI) phosphorylates the PER protein to regulate proteasomal degradation and nuclear localization. Therefore, CKI inhibition can modulate mammalian circadian rhythms. In the present study, we have developed novel CKIalpha and CKIdelta dual inhibitors by extensive structural modification of N9 and C2 position of longdaysin. We identified NCC007 that showed stronger period effects (0.32 muM for 5 h period lengthening) in a cell-based circadian assay. The following in vitro kinase assay showed that NCC007 inhibited CKIalpha and CKIdelta with an IC50 of 1.8 and 3.6 muM. We further demonstrated that NCC007 lengthened the period of mouse behavioral rhythms in vivo. Thus, NCC007 is a valuable tool compound to control circadian rhythms through CKI inhibition.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jae Wook", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Sato", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Keunwan", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Steve A.", "last_name": "Kay", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jmedchem.8b01541" }, "pmcid": { "normalized": "PMC8901179" }, "pmid": { "normalized": "30707835" } }, "mesh": [ { "descriptor": "Adenine", "descriptor_ui": "D000225", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Casein Kinase Ialpha", "descriptor_ui": "D048128", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Drug Design", "descriptor_ui": "D015195", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Molecular Docking Simulation", "descriptor_ui": "D062105", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb 28", "date_precision": "day", "issue": "4", "normalized_date": "2019-02-28", "pages": "1989-1998", "proceedings_title": null, "publisher": "", "title": "Journal of medicinal chemistry", "volume": "62", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Chemical Control of Mammalian Circadian Behavior through Dual Inhibition of Casein Kinase Ialpha and delta.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although the determination of calcium ions (Ca(2+)) is of high importance to monitor water hardness, currently available devices for on-site analysis suffer from a lack of user-friendliness and sensitivity. This work demonstrates fully inkjet-printed and low-cost microfluidic paper-based analytical devices (muPADs) for the simple naked-eye colorimetric determination of calcium ions (Ca(2+)) in drinking and tap water samples. The quantification of Ca(2+) relies on visual readout of the length of a colour-changed detection channel modified with ionophore-doped ion-selective optode nanospheres (nano-optodes), eliminating the requirement of a scanner or a camera. All fabrication steps for deposition of assay reagents have been performed by means of a simple desktop thermal inkjet printer, which is expected to contribute to highly batch-to-batch reproducible device preparation. The detectable Ca(2+) concentrations between 0.05 mmol L(-1) and 5 mmol L(-1) cover the range recommended by the International Organization for Standardization (0.05-2.5 mmol L(-1)) and the World Health Organization (WHO) guideline for Ca(2+) quantification in drinking water (less than 5 mmol L(-1)). The lowest concentration of Ca(2+) detectable by the naked eye was found to be 0.05 mmol L(-1), which is below the value achieved with previously reported paper-based devices. muPAD quantified Ca(2+) concentrations in tap or drinking waters were within 15% error of the results obtained with a classical complexometric titration. Hence, distance-based muPADs relying on nano-optodes are sensitive and reproducible tools for equipment-free on-site assaying of Ca(2+) in real samples.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c8an02146e" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30560965" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 Feb 21", "date_precision": "day", "issue": "4", "normalized_date": "2019-02-21", "pages": "1178-1186", "proceedings_title": null, "publisher": "", "title": "The Analyst", "volume": "144", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Fully inkjet-printed distance-based paper microfluidic devices for colorimetric calcium determination using ion-selective optodes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The activity of biological cells is primarily based on chemical reactions and typically modeled as a reaction-diffusion system. Cells are, however, highly crowded with macromolecules, including a variety of molecular machines such as enzymes. The working cycles of these machines are often coupled with their internal motion (conformational changes). In the crowded environment of a cell, motion interference between neighboring molecules is not negligible, and this interference can affect the reaction dynamics through machine operation. To simulate such a situation, we propose a reaction-diffusion model consisting of particles whose shape depends on an internal state variable, for crowds of nano- to micromachines. The interference between nearby particles is naturally introduced through excluded volume repulsion. In the simulations, we observed segregation and flow-like patterns enhanced by crowding out of relevant molecules, as well as molecular synchronization waves and phase transitions. The presented model is simple and extensible for diverse molecular machinery and may serve as a framework to study the interplay between the mechanical stress/strain network and the chemical reaction network in the cell. Applications to more macroscopic systems, e.g., crowds of cells, are also discussed.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuichi", "last_name": "Togashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jpcb.8b10633" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30681855" } }, "mesh": [ { "descriptor": "Diffusion", "descriptor_ui": "D004058", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": true }, { "descriptor": "Nanotechnology", "descriptor_ui": "D036103", "major_topic": true }, { "descriptor": "Nucleic Acids", "descriptor_ui": "D009696", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb 21", "date_precision": "day", "issue": "7", "normalized_date": "2019-02-21", "pages": "1481-1490", "proceedings_title": null, "publisher": "", "title": "The journal of physical chemistry. B", "volume": "123", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Modeling of Nanomachine/Micromachine Crowds: Interplay between the Internal State and Surroundings.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The undifferentiated state of muscle stem (satellite) cells (MuSCs) is maintained by the canonical Notch pathway. Although three bHLH transcriptional factors, Hey1, HeyL and Hes1, are considered to be potential effectors of the Notch pathway exerting anti-myogenic effects, neither HeyL nor Hes1 inhibits myogenic differentiation of myogenic cell lines. Furthermore, whether these factors work redundantly or cooperatively is unknown. Here, we showed cell-autonomous functions of Hey1 and HeyL in MuSCs using conditional and genetic null mice. Analysis of cultured MuSCs revealed anti-myogenic activity of both HeyL and Hes1. We found that HeyL forms heterodimeric complexes with Hes1 in living cells. Moreover, our ChIP-seq experiments demonstrated that, compared with HeyL alone, the HeyL-Hes1 heterodimer binds with high affinity to specific sites in the chromatin, including the binding sites of Hey1. Finally, analyses of myogenin promoter activity showed that HeyL and Hes1 act synergistically to suppress myogenic differentiation. Collectively, these results suggest that HeyL and Hey1 function redundantly in MuSCs, and that HeyL requires Hes1 for effective DNA binding and biological activity.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yu-Taro", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Nobumasa", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Nogami", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Lidan", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Kazutake", "last_name": "Tsujikawa", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Izawa", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Takefumi", "last_name": "Doi", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kokubo", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Uezumi", "name": null }, { "creator_type": "author", "first_name": "Manfred", "last_name": "Gessler", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "So-Ichiro", "last_name": "Fukada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.163618" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30745427" } }, "mesh": [ { "descriptor": "Alleles", "descriptor_ui": "D000483", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cell Separation", "descriptor_ui": "D002469", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Multimerization", "descriptor_ui": "D055503", "major_topic": false }, { "descriptor": "Protein Structure, Secondary", "descriptor_ui": "D017433", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Satellite Cells, Skeletal Muscle", "descriptor_ui": "D032496", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transcription Factor HES-1", "descriptor_ui": "D000072056", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb 20", "date_precision": "day", "issue": "4", "normalized_date": "2019-02-20", "pages": "dev163618", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "146", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell-autonomous and redundant roles of Hey1 and HeyL in muscle stem cells: HeyL requires Hes1 to bind diverse DNA sites.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Monitoring drug uptake, its metabolism, and response on the single-cell level is invaluable for sustaining drug discovery efforts. In this study, we show the possibility of accessing the information about the aforementioned processes at the single-cell level by monitoring the anticancer drug tamoxifen using live single-cell mass spectrometry (LSC-MS) and Raman spectroscopy. First, we explored whether Raman spectroscopy could be used as a label-free and nondestructive screening technique to identify and predict the drug response at the single-cell level. Then, a subset of the screened cells was isolated and analyzed by LSC-MS to measure tamoxifen and its metabolite, 4-Hydroxytamoxifen (4-OHT) in a highly selective, sensitive, and semiquantitative manner. Our results show the Raman spectral signature changed in response to tamoxifen treatment which allowed us to identify and predict the drug response. Tamoxifen and 4-OHT abundances quantified by LSC-MS suggested some heterogeneity among single-cells. A similar phenomenon was observed in the ratio of metabolized to unmetabolized tamoxifen across single-cells. Moreover, a correlation was found between tamoxifen and its metabolite, suggesting that the drug was up taken and metabolized by the cell. Finally, we found some potential correlations between Raman spectral intensities and tamoxifen abundance, or its metabolism, suggesting a possible relationship between the two signals. This study demonstrates for the first time the potential of using Raman spectroscopy and LSC-MS to investigate pharmacokinetics at the single-cell level.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ahmed", "last_name": "Ali", "name": null }, { "creator_type": "author", "first_name": "Yasmine", "last_name": "Abouleila", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Eiso", "last_name": "Hiyama", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Yanagida", "name": null }, { "creator_type": "author", "first_name": "Arno", "last_name": "Germond", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.8b04393" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30664349" } }, "mesh": [ { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Hep G2 Cells", "descriptor_ui": "D056945", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Multivariate Analysis", "descriptor_ui": "D015999", "major_topic": false }, { "descriptor": "Proof of Concept Study", "descriptor_ui": "D000075082", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "Tamoxifen", "descriptor_ui": "D013629", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb 19", "date_precision": "day", "issue": "4", "normalized_date": "2019-02-19", "pages": "2710-2718", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "91", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-Cell Screening of Tamoxifen Abundance and Effect Using Mass Spectrometry and Raman-Spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "There is large demand for a quantitative method for rapid and ultra-sensitive detection of the influenza virus. Here, we established a digital influenza virus counting (DIViC) method that can detect a single virion without antibody. In the assay, a virion is stochastically entrapped inside a femtoliter reactor array device for the fluorogenic assay of neuraminidase, and incubated for minutes. By analyzing 600,000 reactors, the practical limit of detection reached the order of 10(3) (PFU)/mL, only 10-times less sensitive than RT-PCR and more than 1000-times sensitive than commercial rapid test kits (RIDTs). Interestingly, neuraminidase activity differed among virions. The coefficient of variance was 30-40%, evidently broader than that of alkaline phosphatase measured as a model enzyme for comparison, suggesting the heterogeneity in size and integrity among influenza virus particles. Sensitivity to oseltamivir also differed between virions. We also tested DIViC using clinical gargle samples that imposes less burden for sampling while with less virus titre. The comparison with RIDTs showed that DIViC was largely superior to RIDTs in the sensitivity with the clinical samples although a few false-positive signals were observed in some clinical samples that remains as a technical challenge.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhito V.", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Minagawa", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Moriizumi", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Yamayoshi", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kawaoka", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Noji", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-37994-6" }, "pmcid": { "normalized": "PMC6355933" }, "pmid": { "normalized": "30705374" } }, "mesh": [ { "descriptor": "Influenza A Virus, H1N1 Subtype", "descriptor_ui": "D053118", "major_topic": false }, { "descriptor": "Influenza A Virus, H3N2 Subtype", "descriptor_ui": "D053122", "major_topic": false }, { "descriptor": "Neuraminidase", "descriptor_ui": "D009439", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virion", "descriptor_ui": "D014771", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan 31", "date_precision": "day", "issue": "1", "normalized_date": "2019-01-31", "pages": "1067", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "9", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Antibody-free digital influenza virus counting based on neuraminidase activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "TNF-alpha is a pleiotropic cytokine that has the potential to induce apoptosis under inflammation. How endothelial cells (ECs) are spared from this fate in inflammatory environments where TNF-alpha is present is not known. Here, we show that TGF-beta-activated kinase 1 (TAK1) ensures EC survival and maintains vascular integrity upon TNF-alpha stimulation. Endothelial-specific TAK1 knockout mice exhibit intestinal and liver hemorrhage due to EC apoptosis, leading to vascular destruction and rapid death. This EC apoptosis was induced by TNF-alpha from myeloid cells responding to intestinal microbiota. TNF-alpha secretion associated with inflammation also induced vascular defects in inflamed organs. Additionally, we determined that TAK1 deletion in tumor ECs resulted in blood vessel and hence tumor regression. Our results illuminate mechanisms ensuring survival of intestinal and liver ECs under physiological conditions and ECs of other organs under inflammatory conditions that could be exploited for anti-angiogenic therapy to treat cancer.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Iba", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Ikue", "last_name": "Tai-Nagara", "name": null }, { "creator_type": "author", "first_name": "Jun-Ichi", "last_name": "Suehiro", "name": null }, { "creator_type": "author", "first_name": "Weizhen", "last_name": "Jia", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Eino", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Sakimoto", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Shizuo", "last_name": "Akira", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2018.12.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30639056" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinase 7", "descriptor_ui": "D000099151", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinases", "descriptor_ui": "D020930", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan 28", "date_precision": "day", "issue": "2", "normalized_date": "2019-01-28", "pages": "151-166.e7", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "48", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "TAK1 Prevents Endothelial Apoptosis and Maintains Vascular Integrity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Group 2 innate lymphoid cells (ILC2s) have tissue-resident competence and contribute to the pathogenesis of allergic diseases. However, the mechanisms regulating prolonged ILC2-mediated TH2 cytokine production under chronic inflammatory conditions are unclear. Here we show that, at homeostasis, Runx deficiency induces excessive ILC2 activation due to overly active GATA-3 functions. By contrast, during allergic inflammation, the absence of Runx impairs the ability of ILC2s to proliferate and produce effector TH2 cytokines and chemokines. Instead, functional deletion of Runx induces the expression of exhaustion markers, such as IL-10 and TIGIT, on ILC2s. Finally, these 'exhausted-like' ILC2s are unable to induce type 2 immune responses to repeated allergen exposures. Thus, Runx confers competence for sustained ILC2 activity at the mucosa, and contributes to allergic pathogenesis.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Chizuko", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kojo", "name": null }, { "creator_type": "author", "first_name": "Motoi", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Kazuyo", "last_name": "Moro", "name": null }, { "creator_type": "author", "first_name": "Georges", "last_name": "Lacaud", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Taniuchi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ebihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-019-08365-0" }, "pmcid": { "normalized": "PMC6347616" }, "pmid": { "normalized": "30683858" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Asthma", "descriptor_ui": "D001249", "major_topic": false }, { "descriptor": "Bronchoalveolar Lavage Fluid", "descriptor_ui": "D001992", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Core Binding Factor Alpha 2 Subunit", "descriptor_ui": "D050676", "major_topic": false }, { "descriptor": "Core Binding Factor beta Subunit", "descriptor_ui": "D050658", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "GATA3 Transcription Factor", "descriptor_ui": "D050990", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": true }, { "descriptor": "Interleukin-10", "descriptor_ui": "D016753", "major_topic": false }, { "descriptor": "Intestine, Small", "descriptor_ui": "D007421", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Lymphocytes", "descriptor_ui": "D008214", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Papain", "descriptor_ui": "D010206", "major_topic": false }, { "descriptor": "Receptors, Immunologic", "descriptor_ui": "D011971", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Spleen", "descriptor_ui": "D013154", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan 25", "date_precision": "day", "issue": "1", "normalized_date": "2019-01-25", "pages": "447", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Runx/Cbfbeta complexes protect group 2 innate lymphoid cells from exhausted-like hyporesponsiveness during allergic airway inflammation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Biological systems process information under noisy environment. Sensory adaptation model of E. coli is suitable for investigation because of its simplicity. To understand the adaptation processing quantitatively, stochastic thermodynamic approach has been attempted. Information processing can be assumed as state transition of a system that consists of signal transduction molecules using thermodynamic approach, and efficiency can be measured as thermodynamic cost. Recently, using information geometry and stochastic thermodynamics, a relationship between speed of the transition and the thermodynamic cost has been investigated for a chemical reaction model. Here, we introduce this approach to sensory adaptation model of E. coli, and examined a relationship between adaptation speed and the thermodynamic cost, and efficiency of the adaptation speed. For increasing external noise level in stimulation, the efficiency decreased, but the efficiency was highly robust to external stimulation strength. Moreover, we demonstrated that there is the best noise to achieve the adaptation in the aspect of thermodynamic efficiency. Our quantification method provides a framework to understand the adaptation speed and the thermodynamic cost for various biological systems.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Keita", "last_name": "Ashida", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2018.11.115" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30528391" } }, "mesh": [ { "descriptor": "Adaptation, Physiological", "descriptor_ui": "D000222", "major_topic": true }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Information Theory", "descriptor_ui": "D007257", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Numerical Analysis, Computer-Assisted", "descriptor_ui": "D009716", "major_topic": false }, { "descriptor": "Stochastic Processes", "descriptor_ui": "D013269", "major_topic": false }, { "descriptor": "Thermodynamics", "descriptor_ui": "D013816", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan 15", "date_precision": "day", "issue": "3", "normalized_date": "2019-01-15", "pages": "690-694", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "508", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Stochastic thermodynamic limit on E. coli adaptation by information geometric approach.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Objective: To characterize the distribution of tau pathology in patients with amyotrophic lateral sclerosis/parkinsonism dementia complex on the Kii Peninsula (Kii ALS/PDC) by tau PET using [11C]PBB3 as ligand. Methods: This is a cross-sectional study of 5 patients with ALS/PDC and one asymptomatic participant with a dense family history of ALS/PDC from the Kii Peninsula who took part in this study. All were men, and their age was 76 ± 8 (mean ± SD) years. Thirteen healthy men (69 ± 6 years) participated as healthy controls (HCs). Dynamic PET scans were performed following injection of [11C]PBB3, and parametric PET images were generated by voxel-by-voxel calculation of binding potential (BP*ND) using a multilinear reference tissue model. [11C] Pittsburgh compound B (PiB) PET, MRI, and cognitive tests were also performed. Results: A voxel-based comparison of [11C]PBB3 BP*ND illustrated PET-detectable tau deposition in the cerebral cortex and white matter, and pontine basis including the corticospinal tract in Kii ALS/PDC patients compared with HCs (uncorrected p < 0.05). Group-wise volume of interest analysis of [11C]PBB3 BP*ND images showed increased BP*ND in the hippocampus and in frontal and parietal white matters of Kii ALS/PDC patients relative to HCs (p < 0.05, Holm-Sidak multiple comparisons test). BP*ND in frontal, temporal, and parietal gray matters correlated with Mini-Mental State Examination scores in Kii ALS/PDC patients (p < 0.05). All Kii ALS/PDC patients were negative for [11C]PiB (β-amyloid) except one with marginal positivity. Conclusion: [11C]PBB3 PET visualized the characteristic topography of tau pathology in Kii ALS/PDC, corresponding to clinical phenotypes of this disease.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shinotoh", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Kokubo", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Tagai", "name": null }, { "creator_type": "author", "first_name": "Fumitoshi", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Mimuro", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Ichise", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Ming-Rong", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1212/wnl.0000000000006736" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30530797" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Amyotrophic Lateral Sclerosis", "descriptor_ui": "D000690", "major_topic": false }, { "descriptor": "Benzothiazoles", "descriptor_ui": "D052160", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neuropsychological Tests", "descriptor_ui": "D009483", "major_topic": false }, { "descriptor": "Parkinsonian Disorders", "descriptor_ui": "D020734", "major_topic": false }, { "descriptor": "Positron-Emission Tomography", "descriptor_ui": "D049268", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Tritium", "descriptor_ui": "D014316", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan 08", "date_precision": "day", "issue": "2", "normalized_date": "2019-01-08", "pages": "e136-147", "proceedings_title": null, "publisher": "", "title": "Neurology", "volume": "92", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Tau imaging detects distinctive distribution of tau pathology in ALS/PDC on the Kii Peninsula.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Computational cytometry methods are now frequently used in flow and mass cytometric data analyses. However, systematic bias-free methodologies to assess inter-sample variability have been lacking, thereby hampering efficient data mining from a large set of samples. Here, we devised a computational method termed LAVENDER (latent axes discovery from multiple cytometry samples with nonparametric divergence estimation and multidimensional scaling reconstruction). It measures the Jensen-Shannon distances between samples using the k-nearest neighbor density estimation and reconstructs samples in a new coordinate space, called the LAVENDER space. The axes of this space can then be compared against other omics measurements to obtain biological information. Application of LAVENDER to multidimensional flow cytometry datasets of 301 Japanese individuals immunized with a seasonal influenza vaccine revealed an axis related to baseline immunological characteristics of each individual. This axis correlated with the proportion of plasma cells and the neutrophil-to-lymphocyte ratio, a clinical marker of the systemic inflammatory response. The same method was also applicable to mass cytometry data with more molecular markers. These results demonstrate that LAVENDER is a useful tool for identifying critical heterogeneity among similar, yet different, single-cell datasets.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Daigo", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Setoh", "name": null }, { "creator_type": "author", "first_name": "Takahisa", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Higasa", "name": null }, { "creator_type": "author", "first_name": "Yasuharu", "last_name": "Tabara", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/673434" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2019-01-01", "date_precision": "day", "issue": "", "normalized_date": "2019-01-01", "pages": "673434", "proceedings_title": null, "publisher": "", "title": "bioRxiv", "volume": "", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "LAVENDER: latent axes discovery from multiple cytometry samples with non-parametric divergence estimation and multidimensional scaling reconstruction", "url": "http://biorxiv.org/content/early/2019/06/18/673434.abstract", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "editor", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "editor", "first_name": "Benjamin", "last_name": "Wolozin", "name": null }, { "creator_type": "editor", "first_name": "Luc", "last_name": "Buee", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": null, "normalized_date": "2019", "pages": null, "proceedings_title": null, "publisher": "Springer Singapore", "title": null, "volume": "1184", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Tau Biology", "url": "http://link.springer.com/10.1007/978-981-32-9358-8", "zotero": { "item_type": "book" } }, { "abstract": "Functional neural circuits of mature animals are shaped during postnatal development by eliminating early-formed redundant synapses and strengthening of necessary connections. In the nervous system of newborn animals, redundant synapses are only transient features of the circuit. During subsequent postnatal development, some synapses are strengthened whereas other redundant connections are weakened and eventually eliminated. In this review, we introduce recent studies on the mechanisms of developmental remodeling of climbing fiber–to–Purkinje cell synapses in the cerebellum and synapses from the retina to neurons in the dorsal lateral geniculate nucleus of the visual thalamus (retinogeniculate synapses). These are the two representative models of developmental synapse remodeling in the brain and they share basic principles, including dependency on neural activity. However, recent studies have disclosed that, in several respects, the two models use different molecules and strategies to establish mature synaptic connectivity. We describe similarities and differences between the two models and discuss remaining issues to be tackled in the future in order to understand the general schemes of developmental synapse remodeling.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.12688/f1000research.18903.1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31372212" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": true }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": true }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": true }, { "descriptor": "Thalamus", "descriptor_ui": "D013788", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "", "proceedings_title": null, "publisher": "", "title": "F1000Research", "volume": "8", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Developmental synapse remodeling in the cerebellum and visual thalamus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydrogen sulfide (H(2)S) has been reported to play an important role in biological systems. More recently, sulfane sulfur (sulfur with 0 or -1 charge) molecules have been also reported to be involved in various biological phenomena such as regulation of redox signaling and antioxidant functions. Fluorescent probes are one of the important chemical tools because it is easy to use and enable the real-time detection of the target molecules in living cells and tissues. We have successfully developed a highly selective H(2)S-detecting fluorescent probe, HSip-1. HSip-1 has been designed on the basis of the facts that the macrocyclic polyamine ligands form a stable complex with Cu(2+), and Cu(2+) also reacts with H(2)S and make a stable CuS complex. SSip-1 is a fluorescent probe for detecting sulfane sulfur and this fluorescent probe is designed on the basis of the unique feature of sulfane sulfur to bind reversibly to other sulfur atoms and the intramolecular spirocyclization reaction of xanthene dyes. SSip-1 is a highly selective fluorescent probe and can detect sulfane sulfur reversibly. Both HSip-1 and SSip-1 were able to be used for the live-cell fluorescence imaging. Further, we applied HSip-1 to the high-throughput screening (HTS) for the inhibitors of 3-mercaptopyruvate sulfurtransferase (3MST), one of the reactive sulfur species (RSS)-generating enzymes. We successfully found new 3MST inhibitors by screening of 174,118 compounds. We expect that these fluorescent probes and inhibitors would be useful to elucidate new functions of RSS and RSS-generating enzymes.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Honami", "last_name": "Echizen", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/fpj.154.121" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31527361" } }, "mesh": [ { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "High-Throughput Screening Assays", "descriptor_ui": "D057166", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false }, { "descriptor": "Sulfurtransferases", "descriptor_ui": "D013466", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "3", "normalized_date": "2019", "pages": "121-127", "proceedings_title": null, "publisher": "", "title": "Nihon yakurigaku zasshi. Folia pharmacologica Japonica", "volume": "154", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "[Development of fluorescent probes for detecting reactive sulfur species and their application to development of inhibitors for 3MST].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Due to the growth in aging populations worldwide, prevention and therapy for age-related cognitive decline and dementia are in great demand. We previously demonstrated that long-term intake of iso-α-acids, which are hop-derived bitter compounds found in beer, prevent Alzheimer’s pathology in a rodent model. On the other hand, the effects of iso-α-acids on neural activity in Alzheimer’s disease model mice have not been investigated. Here, we demonstrated that short-term intake of iso-α-acids suppresses inflammation in the hippocampus and improves memory impairment even after disease onset. Importantly, we demonstrated that short-term administration of iso-α-acids attenuated the neural hyperactivation in hippocampus. In 6-month-old 5 × FAD mice exhibiting hippocampus inflammation and memory impairment, oral administration of iso-α-acids for 7 days reduced inflammatory cytokines, including MIP-1α and soluble Aβ and improved object memory in the novel object recognition test. In 12-month-old J20 mice, intake of iso-α-acids for 7 days also suppressed inflammatory cytokines and soluble Aβ in the brain. Manganese-enhanced magnetic resonance imaging (MEMRI) of hippocampi of J20 mice showed increased manganese compared with wild type mice, but iso-α-acids canceled this increased MEMRI signal in J20 mice, particularly in the hippocampus CA1 and CA3 region. Taken together, these findings suggest that short-term intake of iso-α-acids can suppress hippocampus inflammation even after disease onset and improve hyper neural activity in Alzheimer’s disease model mice.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Ano", "name": null }, { "creator_type": "author", "first_name": "Misato", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Takaichi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Michikawa", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fphar.2019.00081" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30804789" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Pharmacology", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Iso-α-Acids, Bitter Components in Beer, Suppress Inflammatory Responses and Attenuate Neural Hyperactivation in the Hippocampus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In mammals, the circadian rhythms are regulated by the central clock located in the hypothalamic suprachiasmatic nucleus (SCN), which is composed of heterogeneous neurons with various neurotransmitters. Among them an inhibitory neurotransmitter, gamma-Amino-Butyric-Acid (GABA), is expressed in almost all SCN neurons, however, its role in the circadian physiology is still unclear. Here, we show that the SCN of fetal mice lacking vesicular GABA transporter (VGAT(-/-)) or GABA synthesizing enzyme, glutamate decarboxylase (GAD65(-/-)/67(-/-)), shows burst firings associated with large Ca(2+) spikes throughout 24 hours, which spread over the entire SCN slice in synchrony. By contrast, circadian PER2 rhythms in VGAT(-/-) and GAD65(-/-)/67(-/-) SCN remain intact. SCN-specific VGAT deletion in adult mice dampens circadian behavior rhythm. These findings indicate that GABA in the fetal SCN is necessary for refinement of the circadian firing rhythm and, possibly, for stabilizing the output signals, but not for circadian integration of multiple cellular oscillations.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Yuchio", "last_name": "Yanagawa", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Sato", "last_name": "Honma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-019-0483-6" }, "pmcid": { "normalized": "PMC6588595" }, "pmid": { "normalized": "31263776" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Glutamate Decarboxylase", "descriptor_ui": "D005968", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Period Circadian Proteins", "descriptor_ui": "D056950", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": false }, { "descriptor": "Vesicular Inhibitory Amino Acid Transport Proteins", "descriptor_ui": "D050495", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "232", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "2", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "GABA in the suprachiasmatic nucleus refines circadian output rhythms in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Current cartilage regenerative therapies are not fully effective in treating osteoarthritis of the knee (OAK). We have developed chondrocyte sheets for autologous transplantation and tested these in in vitro and in vivo preclinical studies, and have reported that the transplantation of chondrocyte sheets promoted hyaline cartilage repair in rat, rabbit, and minipig models. However, autologous transplantation of chondrocyte sheets has yet to be reported in humans. Here, we report our combination therapy in which conventional surgical treatment for OAK, is followed by autologous chondrocyte sheet transplantation for cartilage repair. Eight patients with OAK and cartilage defects categorized arthroscopically as Outerbridge grade III or IV receive the therapy. Patients are thoroughly assessed by preoperative and postoperative X-rays, magnetic resonance imaging (MRI), arthroscopy, Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm Knee Score (LKS), and a laser-induced photoacoustic method to assess cartilage viscoelasticity. Arthroscopic biopsies of all patients are performed 12 months after transplantation for histological evaluation. The properties of the chondrocyte sheets are evaluated using gene expression analysis to investigate the ability to predict the clinical and structural outcomes of the therapy. For this small initial longitudinal series, combination therapy is effective, as assessed by MRI, arthroscopy, viscoelasticity, histology, and the clinical outcomes of KOOS and LKS. Gene marker sets identified in autologous chondrocyte sheets may be predictive of the overall KOOS, LKS, and histological scores after therapy. These predictive gene sets may be potential alternative markers for evaluating OAK treatment.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masato", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yamato", "name": null }, { "creator_type": "author", "first_name": "Genya", "last_name": "Mitani", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Takagaki", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Hamahashi", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Matoba", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Teruo", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Joji", "last_name": "Mochida", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41536-019-0069-4" }, "pmcid": { "normalized": "PMC6384900" }, "pmid": { "normalized": "30820353" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "4", "proceedings_title": null, "publisher": "", "title": "NPJ Regenerative medicine", "volume": "4", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Combined surgery and chondrocyte cell-sheet transplantation improves clinical and structural outcomes in knee osteoarthritis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The accumulation of tau filaments in neurons is a pathological hallmark of various neurodegenerative diseases, including Alzheimer's disease. However, it is not the filamentous aggregates themselves, but non-filamentous tau species, tau oligomer, that is thought to be the culprit in tau-mediated neurodegeneration. The definition of and methodology for isolating tau oligomers vary among researchers. Here we describe how tau oligomers are identified, summarize the differences of tau oligomers among research groups, and discuss their hypothesized functions.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Sumihiro", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-981-32-9358-8_27" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32096050" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neurodegenerative Diseases", "descriptor_ui": "D019636", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "373-380", "proceedings_title": null, "publisher": "", "title": "Advances in experimental medicine and biology", "volume": "1184", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Tau Oligomers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Animals change their behaviors in response to external stimuli, and numerous neurotransmitters are involved in these behavioral changes. In Caenorhabditis elegans, serotonin (5-HT) affects various behaviors such as inhibition of locomotion, stimulation of egg laying, and pharyngeal pumping. Previous research has shown that the neural activity of the RID interneuron increases when the worm moves forward, and the RID is necessary for sustaining forward locomotion. However, the relationship between 5-HT and neural activity of RID, and how it modulates the behavior of the worm has not been investigated. In this article, we reveal the relationship among 5-HT, RID activity, and the behavior of worms using a custom-made tracking and imaging system. We simultaneously measured the neural activity of the RID and behavior in worms with three conditions: mock animals, animals pre-exposed to 5-HT, and 5-HT receptor mod-1 mutants. As shown in previous research, the neural activity of the RID increased during the transition from backward to forward, whereas it decreased during the transition from forward to backward in mock animals. These changes in neural activity were not observed in animals pre-exposed to 5-HT and mod-1 mutants. Moreover, RID activity was correlated with the velocity of the worm in mock animals. However, this correlation was not observed in animals pre-exposed to 5-HT and mod-1 mutants. Our results demonstrate that 5-HT modulates the activity of the RID interneuron, and we infer that the RID plays a role in modulating forward locomotion by changing its activity through 5-HT.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Haruka", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Ashida", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Shidara", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Nikai", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0226044" }, "pmcid": { "normalized": "PMC6892467" }, "pmid": { "normalized": "31800640" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Chloride Channels", "descriptor_ui": "D018118", "major_topic": false }, { "descriptor": "Interneurons", "descriptor_ui": "D007395", "major_topic": false }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": false }, { "descriptor": "Mutagenesis", "descriptor_ui": "D016296", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "12", "normalized_date": "2019", "pages": "e0226044", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "14", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Serotonin modulates behavior-related neural activity of RID interneuron in Caenorhabditis elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Daigo", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1527/tjsai.d-j13" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "5", "normalized_date": "2019", "pages": "D-J13_1", "proceedings_title": null, "publisher": "", "title": "Transactions of the Japanese Society for Artificial Intelligence", "volume": "34", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Extension of Sinkhorn Method: Optimal Movement Estimation of Agents Moving at Constant Velocity", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Absorption spectra of opsin-based pigments are tuned from the UV to the red regions by interactions of the chromophore with surrounding amino acid residues. Both vertebrates and invertebrates possess long-wavelength-sensitive (LWS) opsins, which underlie color vision involving \"red\" sensing. The LWS opsins have independently evolved in each lineage, which suggests the existence of diverse mechanisms in spectral tuning. In vertebrate LWS opsins, the mechanisms underlying spectral tuning have been well characterized by spectroscopic analyses with recombinant pigments of wild type (WT) and mutant opsins. However in invertebrate LWS opsins including insect ones, the mechanisms are largely unknown due to the difficulty in obtaining recombinant pigments. Here we have overcome the problem by analyzing heterologous action spectra based on light-dependent changes in the second messenger in opsin-expressing cultured cells. We found that WTs of two LWS opsins of the butterfly, Papilio xuthus, PxRh3 and PxRh1 have the wavelengths of the absorption maxima at around 570 nm and 540 nm, respectively. Analysis of a series of chimeric mutants showed that helix III is crucial to generating a difference of about 15 nm in the wavelength of absorption maxima of these LWS opsins. Further site-directed mutations in helix III revealed that amino acid residues at position 116 and 120 (bovine rhodopsin numbering system) are involved in the spectral tuning of PxRh1 and PxRh3, suggesting a different spectral tuning mechanism from that of primate LWS opsins.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tomoka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sugihara", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Arikawa", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s40851-019-0150-2" }, "pmcid": { "normalized": "PMC6915953" }, "pmid": { "normalized": "31890273" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "35", "proceedings_title": null, "publisher": "", "title": "Zoological letters", "volume": "5", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Spectral tuning mediated by helix III in butterfly long wavelength-sensitive visual opsins revealed by heterologous action spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Here we investigate the function of Hedgehog (Hh) signaling in thymic gammadelta T-cell maturation and subset differentiation. Analysis of Hh mutants showed that Hh signaling promotes gammadelta T-cell development in the thymus and influences gammadelta T-cell effector subset distribution. Hh-mediated transcription in thymic gammadelta cells increased gammadelta T-cell number, and promoted their maturation and increased the gammadeltaNKT subset, whereas inhibition of Hh-mediated transcription reduced the thymic gammadelta T-cell population and increased expression of many genes that are normally down-regulated during gammadelta T-cell maturation. These changes were also evident in spleen, where increased Hh signaling increased gammadeltaNKT cells, but reduced CD27-CD44+ and Vgamma2+ populations. Systemic in vivo pharmacological Smoothened-inhibition reduced gammadelta T-cell and gammadeltaNKT cells in the thymus, and also reduced splenic gammadelta T-cell and gammadeltaNKT populations, indicating that Hh signaling also influences homeostasis of peripheral gammadelta T-cell populations. Taken together our data indicate that Sonic Hedgehog is an important determinant of gammadelta T-cell effector subset differentiation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Konstantinos", "last_name": "Mengrelis", "name": null }, { "creator_type": "author", "first_name": "Ching-In", "last_name": "Lau", "name": null }, { "creator_type": "author", "first_name": "Jasmine", "last_name": "Rowell", "name": null }, { "creator_type": "author", "first_name": "Anisha", "last_name": "Solanki", "name": null }, { "creator_type": "author", "first_name": "Sonia", "last_name": "Norris", "name": null }, { "creator_type": "author", "first_name": "Susan", "last_name": "Ross", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Susan", "last_name": "Outram", "name": null }, { "creator_type": "author", "first_name": "Tessa", "last_name": "Crompton", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2019.01629" }, "pmcid": { "normalized": "PMC6658896" }, "pmid": { "normalized": "31379834" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Hedgehog Proteins", "descriptor_ui": "D053823", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Smoothened Receptor", "descriptor_ui": "D000072086", "major_topic": false }, { "descriptor": "Spleen", "descriptor_ui": "D013154", "major_topic": false }, { "descriptor": "T-Lymphocyte Subsets", "descriptor_ui": "D016176", "major_topic": false }, { "descriptor": "Thymus Gland", "descriptor_ui": "D013950", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "1629", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Sonic Hedgehog Is a Determinant of gammadelta T-Cell Differentiation in the Thymus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Classical eyeblink conditioning is a representative associative motor learning that requires both the cerebellar cortex and the deep cerebellar nucleus (DCN). Metabotropic glutamate receptor subtype 1 (mGluR1) is richly expressed in Purkinje cells (PCs) of the cerebellar cortex. Global mGluR1 knock-out (KO) mice show a significantly lower percentage of conditioned response (CR%) than wild-type mice in eyeblink conditioning, and the impaired CR% is restored by the introduction of mGluR1 in PCs. However, the specific roles of mGluR1 in major memory processes, including formation, storage and expression have not yet been defined. We thus examined the role of mGluR1 in these processes of eyeblink conditioning, using mGluR1 conditional KO (cKO) mice harboring a selective and reversible expression of mGluR1 in PCs. We have found that eyeblink memory is not latently formed in the absence of mGluR1 in adult mouse PCs. However, once acquired, eyeblink memory is expressed even after the depletion of mGluR1 in PCs. We thus conclude that mGluR1 in PCs is indispensable for the formation of eyeblink memory, while it is not required for the expression of CR.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Harumi", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Miwako", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Kirino", "name": null }, { "creator_type": "author", "first_name": "Atsu", "last_name": "Aiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-019-43744-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31089195" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blinking", "descriptor_ui": "D001767", "major_topic": true }, { "descriptor": "Conditioning, Classical", "descriptor_ui": "D003214", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "9", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "mGluR1 in cerebellar Purkinje cells is essential for the formation but not expression of associative eyeblink memory.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mammalian target of rapamycin (mTOR) is a central regulator of cellular metabolism. The importance of mTORC1 signaling in neuronal development and functions has been highlighted by its strong relationship with many neurological and neuropsychiatric diseases. Previous studies demonstrated that hyperactivation of mTORC1 in forebrain recapitulates tuberous sclerosis and neurodegeneration. In the mouse cerebellum, Purkinje cell-specific knockout of Tsc1/2 has been implicated in autistic-like behaviors. However, since TSC1/2 activity does not always correlate with clinical manifestations as evident in some cases of tuberous sclerosis, the intriguing possibility is raised that phenotypes observed in Tsc1/2 knockout mice cannot be attributable solely to mTORC1 hyperactivation. Here we generated transgenic mice in which mTORC1 signaling is directly hyperactivated in Purkinje cells. The transgenic mice exhibited impaired synapse elimination of climbing fibers and motor discoordination without affecting social behaviors. Furthermore, mTORC1 hyperactivation induced prominent apoptosis of Purkinje cells, accompanied with dysregulated cellular homeostasis including cell enlargement, increased mitochondrial respiratory activity, and activation of pseudohypoxic response. These findings suggest the different contributions between hyperactivated mTORC1 and Tsc1/2 knockout in social behaviors, and reveal the perturbations of cellular homeostasis by hyperactivated mTORC1 as possible underlying mechanisms of neuronal dysfunctions and death in tuberous sclerosis and neurodegenerative diseases.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Kassai", "name": null }, { "creator_type": "author", "first_name": "Hisako", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Fukaya", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Sakagami", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Atsu", "last_name": "Aiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-019-38730-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30808980" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Mechanistic Target of Rapamycin Complex 1", "descriptor_ui": "D000076222", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Sirolimus", "descriptor_ui": "D020123", "major_topic": false }, { "descriptor": "Tuberous Sclerosis Complex 1 Protein", "descriptor_ui": "D000077004", "major_topic": false }, { "descriptor": "Tuberous Sclerosis Complex 2 Protein", "descriptor_ui": "D000077005", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "9", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Hyperactivation of mTORC1 disrupts cellular homeostasis in cerebellar Purkinje cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Rhodamine dyes are among the most widely used fluorescent dyes for bioimaging due to their high fluorescence quantum yield and high photostability. Recently, novel far-red to near-infrared (NIR) fluorescent dyes have been developed: Si-rhodamines (SiRs), in which the O atom of conventional rhodamine dyes at the 10 position of the xanthene moiety is replaced with a Si atom. These SiRs are excellent long-wavelength fluorophores for bioimaging, as they retain the advantageous photophysical properties of conventional rhodamine dyes. Further, we focused on the QSY dark quenchers, which contain the rhodamine scaffold bearing aromatic rings at the N atoms at the 3,6-positions of the xanthene moiety; these show no fluorescence, irrespective of solvent polarity and pH. NIR fluorescent probes based on the Forster resonance energy transfer (FRET) mechanism have various practical advantages, and their molecular design is generally based on the use of NIR dark quenchers as cleavable FRET acceptors. However, few NIR dark quenchers can quench fluorescence in the Cy7 region (over 780 nm). We successfully developed SiR-based NIR dark quenchers (SiNQs) which show broad absorption covering this region. To demonstrate their usefulness, we designed and synthesized a NIR fluorescence probe for matrix metalloproteinase (MMP) activity using SiNQs. The developed probe was able to detect MMP activity in terms of NIR fluorescence, not only in vitro, but also in cultured cells and in a tumor-bearing mouse, in which the tumor was clearly visualized.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1248/yakushi.18-00174-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30713240" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drug Design", "descriptor_ui": "D015195", "major_topic": true }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Matrix Metalloproteinases", "descriptor_ui": "D020782", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": true }, { "descriptor": "Xanthenes", "descriptor_ui": "D014966", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "2", "normalized_date": "2019", "pages": "277-283", "proceedings_title": null, "publisher": "", "title": "Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan", "volume": "139", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "[Development of Novel Dark Quenchers and Their Application to Imaging Probes].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cerebellum has a parasagittal modular architecture characterized by precisely organized climbing fiber (CF) projections that are congruent with alternating aldolase C/zebrin II expression. However, the behavioral relevance of CF inputs into individual modules remains poorly understood. Here, we used two-photon calcium imaging in the cerebellar hemisphere Crus II in mice performing an auditory go/no-go task to investigate the functional differences in CF inputs to modules. CF signals in medial modules show anticipatory decreases, early increases, secondary increases, and reward-related increases or decreases, which represent quick motor initiation, go cues, fast motor behavior, and positive reward outcomes. CF signals in lateral modules show early increases and reward-related decreases, which represent no-go and/or go cues and positive reward outcomes. The boundaries of CF functions broadly correspond to those of aldolase C patterning. These results indicate that spatially segregated CF inputs in different modules play distinct roles in the execution of goal-directed behavior.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Hidaka", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Isomura", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Matsuzaki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.47021" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31596238" } }, "mesh": [ { "descriptor": "Acoustic Stimulation", "descriptor_ui": "D000161", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Fructose-Bisphosphate Aldolase", "descriptor_ui": "D005634", "major_topic": false }, { "descriptor": "Goals", "descriptor_ui": "D006040", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Motion", "descriptor_ui": "D009038", "major_topic": true }, { "descriptor": "Nerve Fibers", "descriptor_ui": "D009412", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Psychomotor Performance", "descriptor_ui": "D011597", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "8", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Modular organization of cerebellar climbing fiber inputs during goal-directed behavior.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Repeated stress is a risk factor for mental disorders and can also lead to sleep disturbances. Although the effects of stress on sleep architecture have been investigated in rodents, the length of the stress exposure period in most studies has been limited to about 10 days, and few studies have analyzed the effects of chronic stress over a longer period. Here we investigated how sleep is affected in a mouse model of depression induced by 3 weeks of daily water immersion and restraint stress (WIRS). Sleep was recorded after 1, 2, and 3 weeks of stress exposure. Some stress-induced changes in several sleep measures were maintained across the 3 weeks, whereas other changes were most prominent during the 1st week. The total amount of non-rapid eye movement sleep (NREMS) was increased and the total amount of time spent awake was decreased across all 3 weeks. On the other hand, the amount of REMS during the dark phase was significantly increased in the 1st week compared with that at baseline or the 2nd and 3rd weeks. Electroencephalogram (EEG) power in the delta range was decreased during NREMS, although the total amount of NREMS was increased. These findings indicate that repeated WIRS, which eventually leads to a depression-like phenotype, differentially affects sleep between the early and subsequent periods. The increase in the amount of REMS during the dark phase in the 1st week significantly correlated with changes in body weight. Our results show how sleep changes throughout a long period of chronic stress in a mouse model of depression.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Yasugaki", "name": null }, { "creator_type": "author", "first_name": "Chih-Yao", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Mitsuaki", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Kanuka", "name": null }, { "creator_type": "author", "first_name": "Takato", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2019.01072" }, "pmcid": { "normalized": "PMC6813282" }, "pmid": { "normalized": "31680813" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "1072", "proceedings_title": null, "publisher": "", "title": "Frontiers in neuroscience", "volume": "13", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Effects of 3 Weeks of Water Immersion and Restraint Stress on Sleep in Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Motile cilia are microtubule-based organelles that play important roles in most eukaryotes. Although axonemal microtubules are sufficiently stable to withstand their beating motion, it remains unknown how they are stabilized while serving as tracks for axonemal dyneins. To address this question, we have identified two uncharacterized proteins, FAP45 and FAP52, as microtubule inner proteins (MIPs) in Chlamydomonas. These proteins are conserved among eukaryotes with motile cilia. Using cryo-electron tomography (cryo-ET) and high-speed atomic force microscopy (HS-AFM), we show that lack of these proteins leads to a loss of inner protrusions in B-tubules and less stable microtubules. These protrusions are located near the inner junctions of doublet microtubules and lack of both FAP52 and a known inner junction protein FAP20 results in detachment of the B-tubule from the A-tubule, as well as flagellar shortening. These results demonstrate that FAP45 and FAP52 bind to the inside of microtubules and stabilize ciliary axonemes.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mikito", "last_name": "Owa", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Uchihashi", "name": null }, { "creator_type": "author", "first_name": "Haru-aki", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yamano", "name": null }, { "creator_type": "author", "first_name": "Hiro", "last_name": "Iguchi", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Fukuzawa", "name": null }, { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Kikkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-019-09051-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30850601" } }, "mesh": [ { "descriptor": "Algal Proteins", "descriptor_ui": "D020418", "major_topic": false }, { "descriptor": "Axonemal Dyneins", "descriptor_ui": "D056444", "major_topic": false }, { "descriptor": "Axoneme", "descriptor_ui": "D054468", "major_topic": false }, { "descriptor": "Chlamydomonas reinhardtii", "descriptor_ui": "D016825", "major_topic": false }, { "descriptor": "Cilia", "descriptor_ui": "D002923", "major_topic": false }, { "descriptor": "Cryoelectron Microscopy", "descriptor_ui": "D020285", "major_topic": false }, { "descriptor": "Electron Microscope Tomography", "descriptor_ui": "D055032", "major_topic": false }, { "descriptor": "Flagella", "descriptor_ui": "D005407", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Microscopy, Atomic Force", "descriptor_ui": "D018625", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Inner lumen proteins stabilize doublet microtubules in cilia and flagella.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nucleosomes are structural units of the chromosome consisting of DNA wrapped around histone proteins, and play important roles in compaction and regulation of the chromatin structure. While the structure and dynamics of canonical nucleosomes have been studied extensively, those of nucleosomes in intermediate states, that occur when their structure or positioning is modulated, have been less understood. In particular, the dynamic features of partially disassembled nucleosomes have not been discussed in previous studies. Using all-atom molecular dynamics simulations, in this study, we investigated the dynamics and stability of nucleosome structures lacking a histone-dimer. DNA in nucleosomes lacking a histone H2A/H2B dimer was drastically deformed due to loss of local interactions between DNA and histones. In contrast, conformation of DNA in nucleosomes lacking H3/H4 was similar to the canonical nucleosome, as the H2A C-terminal domain infiltrated the space originally occupied by the dissociated H3/H4 histones and restricted DNA dynamics in close proximity. Our results suggest that, besides histone chaperones, the intrinsic dynamics of nucleosomes support the exchange of H2A/H2B, which is significantly more frequent than that of H3/H4.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takeru", "last_name": "Kameda", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Awazu", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Togashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fmolb.2019.00133" }, "pmcid": { "normalized": "PMC6896900" }, "pmid": { "normalized": "31850366" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "133", "proceedings_title": null, "publisher": "", "title": "Frontiers in molecular biosciences", "volume": "6", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Histone Tail Dynamics in Partially Disassembled Nucleosomes During Chromatin Remodeling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null } ], "identifiers": { "doi": { "normalized": "10.2222/jsv.69.73" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32938896" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "1", "normalized_date": "2019", "pages": "73-82", "proceedings_title": null, "publisher": "", "title": "Uirusu", "volume": "69", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "[Molecular mechanisms of entry and egress of herpes simplex virus 1].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cryo-electron microscopy and X-ray crystallography have been the major tools of protein structure analysis for decades and will certainly continue to be essential in the future. Moreover, nuclear magnetic resonance or Forster resonance energy transfer can measure structural dynamics. Here, we propose to add optical second-harmonic generation (SHG), which is a nonlinear optical scattering process sensitive to molecular structures in illuminated materials, to the tool-kit of structural analysis methodologies. SHG can be expected to probe the structural changes of proteins in the physiological condition, and thus link protein structure and biological function. We demonstrate that a conformational change as well as its dynamics in protein macromolecular assemblies can be detected by means of SHG polarization measurement. To prove the capability of SHG polarization measurement with regard to protein structure analysis, we developed an SHG polarization microscope to analyze microtubules in solution. The difference in conformation between microtubules with different binding molecules was successfully observed as polarization dependence of SHG intensity. We also succeeded in capturing the temporal variation of structure in a photo-switchable protein crystal in both activation and inactivation processes. These results illustrate the potential of this method for protein structure analysis in physiological solutions at room temperature without any labeling.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Junichi", "last_name": "Kaneshiro", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Tsujii", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Imada", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.16.0_147" }, "pmcid": { "normalized": "PMC6812877" }, "pmid": { "normalized": "31660282" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "147-157", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "16", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Second harmonic generation polarization microscopy as a tool for protein structure analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Bioluminescence imaging (BLI) is one of the most widely used optical platforms in molecular imaging, but it suffers from severe tissue attenuation and autoluminescence in vivo.Methods: Here, we developed a novel BLI platform on the basis of bioluminescence resonance energy transfer (BRET) for achieving a ~300 nm blue-to-near infrared shift of the emission (NIR-BRET) by synthesizing an array of 18 novel coelenterazine (CTZ) derivatives, named “Bottle Blue (BBlue)” and a unique iRFP-linked RLuc8.6-535SG fusion protein as a probe.Results: The best NIR-BRET was achieved by tuning the emission peaks of the CTZ derivatives to a Soret band of the iRFP. In mammalian cells, BBlue2.3, one of the CTZ derivatives, emits light that is ~50-fold brighter than DBlueC when combined with RLuc8.6-535SG, which shows stable BL kinetics. When we used a caged version of BBLue2.3, it showed a BL half decay time of over 60 minutes while maintaining the higher signal sensitivity. This NIR BL is sufficiently brighter to be used for imaging live mammalian cells at single cell level, and also for imaging metastases in deep tissues in live mice without generating considerable autoluminescence. A single-chain probe developed based on this BLI platform allowed us to sensitively image ligand antagonist-specific activation of estrogen receptor in the NIR region.Conclusion: This unique optical platform provides the brightest NIR BLI template that can be used for imaging a diverse group of cellular events in living subjects including protein‒protein interactions and cancer metastasis.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Nishihara", "name": null }, { "creator_type": "author", "first_name": "Ramasamy", "last_name": "Paulmurugan", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Arutselvan", "last_name": "Natarajan", "name": null }, { "creator_type": "author", "first_name": "Rayhaneh", "last_name": "Afjei", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Iwasawa", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Moritoshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Sung Bae", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.7150/thno.32219" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31131059" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Heterografts", "descriptor_ui": "D064593", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Imidazoles", "descriptor_ui": "D007093", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Luminescent Agents", "descriptor_ui": "D049408", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Interaction Domains and Motifs", "descriptor_ui": "D054730", "major_topic": false }, { "descriptor": "Protein Structure, Secondary", "descriptor_ui": "D017433", "major_topic": false }, { "descriptor": "Pyrazines", "descriptor_ui": "D011719", "major_topic": false }, { "descriptor": "Receptors, Estrogen", "descriptor_ui": "D011960", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Red Fluorescent Protein", "descriptor_ui": "D000097573", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "9", "normalized_date": "2019", "pages": "2646-2661", "proceedings_title": null, "publisher": "", "title": "Theranostics", "volume": "9", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Highly bright and stable NIR-BRET with blue-shifted coelenterazine derivatives for deep-tissue imaging of molecular events in vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Animals sense light using photosensitive proteins-rhodopsins-containing a chromophore-retinal-that intrinsically absorbs in the ultraviolet. Visible light-sensitivity depends primarily on protonation of the retinylidene Schiff base (SB), which requires a negatively-charged amino acid residue-counterion-for stabilization. Little is known about how the most common counterion among varied rhodopsins, Glu181, functions. Here, we demonstrate that in a spider visual rhodopsin, orthologue of mammal melanopsins relevant to circadian rhythms, the Glu181 counterion functions likely by forming a hydrogen-bonding network, where Ser186 is a key mediator of the Glu181-SB interaction. We also suggest that upon light activation, the Glu181-SB interaction rearranges while Ser186 changes its contribution. This is in contrast to how the counterion of vertebrate visual rhodopsins, Glu113, functions, which forms a salt bridge with the SB. Our results shed light on the molecular mechanisms of visible light-sensitivity relevant to invertebrate vision and vertebrate non-visual photoreception.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Hisao", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Eshita", "last_name": "Mutt", "name": null }, { "creator_type": "author", "first_name": "Gebhard F. X.", "last_name": "Schertler", "name": null }, { "creator_type": "author", "first_name": "Xavier", "last_name": "Deupi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-019-0409-3" }, "pmcid": { "normalized": "PMC6513861" }, "pmid": { "normalized": "31098413" } }, "mesh": [ { "descriptor": "Amino Acid Substitution", "descriptor_ui": "D019943", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arthropod Proteins", "descriptor_ui": "D060829", "major_topic": false }, { "descriptor": "Hydrogen Bonding", "descriptor_ui": "D006860", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Mutagenesis, Site-Directed", "descriptor_ui": "D016297", "major_topic": false }, { "descriptor": "Photochemical Processes", "descriptor_ui": "D055668", "major_topic": false }, { "descriptor": "Protein Stability", "descriptor_ui": "D055550", "major_topic": false }, { "descriptor": "Rhodopsin", "descriptor_ui": "D012243", "major_topic": false }, { "descriptor": "Schiff Bases", "descriptor_ui": "D012545", "major_topic": false }, { "descriptor": "Spiders", "descriptor_ui": "D013112", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "180", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "2", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "The counterion-retinylidene Schiff base interaction of an invertebrate rhodopsin rearranges upon light activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vaccination strategy that induce efficient antibody responses polytopically in most lymph nodes (LNs) against infections has not been established yet. Because donor-specific blood transfusion induces anti-donor class I MHC antibody production in splenectomized rats, we examined the mechanism and significance of this response. Among the donor blood components, T cells were the most efficient immunogens, inducing recipient T cell and B cell proliferative responses not only in the spleen, but also in the peripheral and gut LNs. Donor T cells soon migrated to the splenic T cell area and the LNs, with a temporary significant increase in recipient NK cells. XCR1(+) resident dendritic cells (DCs), but not XCR1(-) DCs, selectively phagocytosed donor class I MHC(+) fragments after 1 day. After 1.5 days, both DC subsets formed clusters with recipient CD4(+) T cells, which proliferated within these clusters. Inhibition of donor T cell migration or depletion of NK cells by pretreatment with pertussis toxin or anti-asialoGM1 antibody, respectively, significantly suppressed DC phagocytosis and subsequent immune responses. Three allogeneic strains with different NK activities had the same response but with different intensity. Donor T cell proliferation was not required, indicating that the graft vs. host reaction is dispensable. Intravenous transfer of antigen-labeled and mitotic inhibitor-treated allogeneic, but not syngeneic, T cells induced a polytopical antibody response to labeled antigens in the LNs of splenectomized rats. These results demonstrate a novel mechanism of alloresponses polytopically in the secondary lymphoid organs (SLOs) induced by allogeneic T cells. Donor T cells behave as self-migratory antigen ferries to be delivered to resident XCR1(+) DCs with negligible commitment of migratory DCs. Allogeneic T cells may be clinically applicable as vaccine vectors for polytopical prophylactic antibody production even in asplenic or hyposplenic individuals.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kitazawa", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Ueta", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sawanobori", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yoneyama", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ueha", "name": null }, { "creator_type": "author", "first_name": "Kouji", "last_name": "Matsushima", "name": null }, { "creator_type": "author", "first_name": "Nobuko", "last_name": "Tokuda", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Matsuno", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2019.01195" }, "pmcid": { "normalized": "PMC6548820" }, "pmid": { "normalized": "31191552" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Donors", "descriptor_ui": "D001782", "major_topic": false }, { "descriptor": "Blood Transfusion", "descriptor_ui": "D001803", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": false }, { "descriptor": "Epitopes", "descriptor_ui": "D000939", "major_topic": false }, { "descriptor": "G(M1) Ganglioside", "descriptor_ui": "D005677", "major_topic": false }, { "descriptor": "Histocompatibility Antigens Class I", "descriptor_ui": "D015395", "major_topic": false }, { "descriptor": "Isoantibodies", "descriptor_ui": "D007518", "major_topic": false }, { "descriptor": "Killer Cells, Natural", "descriptor_ui": "D007694", "major_topic": false }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Lymphocyte Transfusion", "descriptor_ui": "D017710", "major_topic": false }, { "descriptor": "Pertussis Toxin", "descriptor_ui": "D037342", "major_topic": false }, { "descriptor": "Peyer's Patches", "descriptor_ui": "D010581", "major_topic": false }, { "descriptor": "Phagocytosis", "descriptor_ui": "D010587", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Inbred ACI", "descriptor_ui": "D011912", "major_topic": false }, { "descriptor": "Rats, Inbred Lew", "descriptor_ui": "D011917", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Spleen", "descriptor_ui": "D013154", "major_topic": false }, { "descriptor": "Splenectomy", "descriptor_ui": "D013156", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "1195", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Novel Targeting to XCR1(+) Dendritic Cells Using Allogeneic T Cells for Polytopical Antibody Responses in the Lymph Nodes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Adoptive T cell therapy is an attractive strategy in tumor immunotherapy. The transfer of in vitro expanded tumor-associated antigen (TAA)-specific T cells from patients may effectively destroy the original tumor cells. One of the limitations is a rapid acquisition of tolerant (anergy, deletion, dysfunctional, and/or exhausted) phenotypes. We and others found that stem cell memory T (TSCM) cells are strongly resistant to tolerance, showing strong expansion and persistence in vivo and providing long-lasting antitumor effects. We previously established that phenotypically TSCM cells (iTSCM) can be induced using a simple coculture of activated T cells with OP9 stroma cells expressing a Notch ligand. Here, we describe a defined protocol for generating human iTSCM cells, including reagents, culture setting, and procedure.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Imura", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4939-9728-2_4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31396927" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, Neoplasm", "descriptor_ui": "D000951", "major_topic": false }, { "descriptor": "Calcium-Binding Proteins", "descriptor_ui": "D002135", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Separation", "descriptor_ui": "D002469", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique, Direct", "descriptor_ui": "D019085", "major_topic": false }, { "descriptor": "Healthy Volunteers", "descriptor_ui": "D064368", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunologic Memory", "descriptor_ui": "D007156", "major_topic": false }, { "descriptor": "Immunotherapy, Adoptive", "descriptor_ui": "D016219", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mesenchymal Stem Cells", "descriptor_ui": "D059630", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Primary Cell Culture", "descriptor_ui": "D061251", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Transduction, Genetic", "descriptor_ui": "D014161", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "41-51", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2048", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "In Vitro Conversion of Activated T Cells into Stem Cell Memory-Like T Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alzheimer's disease pathology is characterized by extracellular deposits of amyloid-beta (Abeta) and intracellular inclusions of hyperphosphorylated tau. Although genetic studies of familial Alzheimer's disease suggest a causal link between Abeta and disease symptoms, the failure of various Abeta-targeted strategies to slow or halt disease progression has led to consideration of the idea that inhibition of tau aggregation might be a more promising therapeutic approach. Methylene blue (MB), which inhibits tau aggregation and rescue memory deficits in a mouse model of tauopathy, however, lacked efficacy in a recent Phase III clinical trial. In order to gain insight into this failure, the present study was designed to examine the mechanism through which MB inhibits tau aggregation. We found that MB inhibits heparin-induced tau aggregation in vitro, as measured by thioflavin T fluorescence. Further, MB reduced the amount of tau in precipitants recovered after ultracentrifugation of the aggregation mixture. Atomic force microscopy revealed that MB reduces the number of tau fibrils but increases the number of granular tau oligomers. The latter result was confirmed by sucrose gradient centrifugation: MB treatment was associated with higher levels of granular tau oligomers (fraction 3) and lower levels of tau fibrils (fractions 5 and 6). We previously demonstrated that the formation of granular tau oligomers, rather than tau fibrils, is essential for neuronal death. Thus, the fact that MB actions are limited to inhibition of tau fibril formation provides a mechanistic explanation for the poor performance of MB in the recent Phase III clinical trial.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Soeda", "name": null }, { "creator_type": "author", "first_name": "Marino", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Sumihiro", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Kohki", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.3233/jad-181001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30909223" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Methylene Blue", "descriptor_ui": "D008751", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurofibrillary Tangles", "descriptor_ui": "D016874", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "4", "normalized_date": "2019", "pages": "1677-1686", "proceedings_title": null, "publisher": "", "title": "Journal of Alzheimer's disease : JAD", "volume": "68", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Methylene Blue Inhibits Formation of Tau Fibrils but not of Granular Tau Oligomers: A Plausible Key to Understanding Failure of a Clinical Trial for Alzheimer's Disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "There is conflicting evidence for the association between genetic polymorphisms in the serotonin (5-HT)(2C) receptor (HTR2C) and response to antipsychotic drugs (APD) in schizophrenic patients. We tested the association between the HTR2C polymorphisms, Cys23Ser, -759C/T, and -697G/C, and response to APDs (mainly clozapine) in a 6 month prospective study in 171 patients with schizophrenia. Ser23 was significantly associated with treatment response (positive symptoms, X (2) = 7.540, p = 0.01; negative symptoms, X (2) = 4.796, p = 0.03) in male patients only. A -759C-Ser23 haplotype was similar associated with positive (X (2) = 6.648, p = 0.01) and negative (X (2) = 6.702, p = 0.01) symptom improvement. Logistic regression, after controlling for covariates, also showed significant haplotypic associations. A meta-analysis of six studies for Ser23 and treatment response showed an overall odds ratio of 2.00 (95%CI, 1.38-2.91, p = 0.0003) or 1.94 (95%CI, 1.27-2.99, p = 0.0024) under fixed or random effect models. These results provide additional evidence that HTR2C polymorphisms are associated with treatment response to APD with HTR2C antagonism or inverse agonism, in male schizophrenic patients.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Jiang", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Herbert Y.", "last_name": "Meltzer", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fpsyt.2019.00058" }, "pmcid": { "normalized": "PMC6384235" }, "pmid": { "normalized": "30828307" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "58", "proceedings_title": null, "publisher": "", "title": "Frontiers in psychiatry", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Association of Serotonin(2c) Receptor Polymorphisms With Antipsychotic Drug Response in Schizophrenia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: PACAP and VIP are closely related neuropeptides with wide distribution and potent effect in the vasculature. We previously reported vasomotor activity in peripheral vasculature of male wild type (WT) and PACAP-deficient (KO) mice. However, female vascular responses are still unexplored. We hypothesized that PACAP-like activity is maintained in female PACAP KO mice and the mechanism through which it is regulated differs from that of male PACAP KO animals. METHODS: We investigated the vasomotor effects of VIP and PACAP isoforms and their selective blockers in WT and PACAP KO female mice in carotid and femoral arteries. The expression and level of different PACAP receptors in the vessels were measured by RT-PCR and Western blot. RESULTS: In both carotid and femoral arteries of WT mice, PACAP1-38, PACAP1-27 or VIP induced relaxation, without pronounced differences between them. Reduced relaxation was recorded only in the carotid arteries of KO mice as compared to their WT controls. The specific VPAC1R antagonist completely blocked the PACAP/VIP-induced relaxation in both arteries of all mice, while PAC1R antagonist affected relaxation only in their femoral arteries. CONCLUSION: In female WT mice, VPAC1 receptors appear to play a dominant role in PACAP-induced vasorelaxation both in carotid and in femoral arteries. In the PACAP KO group PAC1R activation exerts vasorelaxation in the femoral arteries but in carotid arteries there is no significant effect of the activation of this receptor. In the background of this regional difference, decreased PAC1R and increased VPAC1R availability in the carotid arteries was found.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ivan", "last_name": "Ivic", "name": null }, { "creator_type": "author", "first_name": "Marta", "last_name": "Balasko", "name": null }, { "creator_type": "author", "first_name": "Balazs D.", "last_name": "Fulop", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Gabor", "last_name": "Toth", "name": null }, { "creator_type": "author", "first_name": "Andrea", "last_name": "Tamas", "name": null }, { "creator_type": "author", "first_name": "Tamas", "last_name": "Juhasz", "name": null }, { "creator_type": "author", "first_name": "Akos", "last_name": "Koller", "name": null }, { "creator_type": "author", "first_name": "Dora", "last_name": "Reglodi", "name": null }, { "creator_type": "author", "first_name": "Margit", "last_name": "Solymar", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0211433" }, "pmcid": { "normalized": "PMC6347420" }, "pmid": { "normalized": "30682157" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carotid Arteries", "descriptor_ui": "D002339", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Femoral Artery", "descriptor_ui": "D005263", "major_topic": false }, { "descriptor": "Insect Proteins", "descriptor_ui": "D019476", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Nitroprusside", "descriptor_ui": "D009599", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Receptors, Vasoactive Intestinal Polypeptide, Type I", "descriptor_ui": "D051238", "major_topic": false }, { "descriptor": "Vasoactive Intestinal Peptide", "descriptor_ui": "D014660", "major_topic": false }, { "descriptor": "Vasodilation", "descriptor_ui": "D014664", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "1", "normalized_date": "2019", "pages": "e0211433", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "14", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "VPAC1 receptors play a dominant role in PACAP-induced vasorelaxation in female mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The neuronal activity forms the basis of functional circuits and brain functions. To understand how the brain operates, recording of neural activity at micro-, meso-, and macro-scales is required. Recently, improved optical microscopic technology helps us to develop a whole-brain imaging system at a single-cell resolution. The combination of a whole-brain imaging system and a reporter system of neuronal activation enables a whole-brain mapping of neuronal activity. In this review, we first describe the high-speed and scalable whole-brain imaging system including our recently developed system, named FAST, and then present the instances of whole-brain mapping of neuronal activity and its analytical methods.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/fpj.153.278" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31178533" } }, "mesh": [ { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Brain Mapping", "descriptor_ui": "D001931", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nervous System Physiological Phenomena", "descriptor_ui": "D009424", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "6", "normalized_date": "2019", "pages": "278-283", "proceedings_title": null, "publisher": "", "title": "Nihon yakurigaku zasshi. Folia pharmacologica Japonica", "volume": "153", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "[Whole-brain activity mapping at single-cell resolution].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Electrophysiological field potential dynamics have been widely used to investigate brain functions and related psychiatric disorders. Considering recent demand for its applicability to freely moving subjects, especially for animals in a group and socially interacting with each other, here we propose a new method based on a bioluminescent voltage indicator LOTUS-V. Using our fiber-free recording method based on the LOTUS-V, we succeeded in capturing dynamic change of brain activity in freely moving mice. Because LOTUS-V is the ratiometric indicator, motion and head-angle artifacts were not significantly detected. Taking advantage of our method as a fiber-free system, we further succeeded in simultaneously recording from multiple independently-locomotive mice that were freely interacting with one another. Importantly, this enabled us to find that the primary visual cortex, a center of visual processing, was activated during the interaction of mice. This methodology may further facilitate a wide range of studies in neurobiology and psychiatry.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shigenori", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Agetsuma", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Ohara", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Iijima", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Tetsuichi", "last_name": "Wazawa", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-019-43897-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31097780" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Environment", "descriptor_ui": "D004777", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Potentials", "descriptor_ui": "D008564", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Movement", "descriptor_ui": "D009068", "major_topic": true }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Phosphoric Monoester Hydrolases", "descriptor_ui": "D010744", "major_topic": false }, { "descriptor": "Visual Cortex", "descriptor_ui": "D014793", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "9", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Imaging local brain activity of multiple freely moving mice sharing the same environment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Exploring for food is important in food-deprived condition. Chemotaxis is one of the important behaviors to search food. Although chemotactic strategies in C. elegans have been well investigated: the pirouette and the weathervane strategies, the change of the chemotactic strategy by food deprivation is largely unclear. Here, we show the change of chemotactic strategy by food deprivation, especially for isoamyl alcohol. To compare chemotaxis under different food-deprivation period, we showed that worms change their chemotactic behaviors by food deprivation. The worms with 1-h food-deprivation change the weathervane strategy. On the other hand, 6-h food deprived animals change the pirouette strategy. These results demonstrate that worms change chemotactic strategy different way depend on period of food deprivation.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kei", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Ashida", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.16.0_167" }, "pmcid": { "normalized": "PMC6975978" }, "pmid": { "normalized": "31984168" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "167-172", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "16", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Food deprivation changes chemotaxis behavior in Caenorhabditis elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase activating polypeptide (PACAP) is a regulatory and cytoprotective neuropeptide, its deficiency implies accelerated aging in mice. It is present in the auditory system having antiapoptotic effects. Expression of Ca2+-binding proteins and its PAC1 receptor differs in the inner ear of PACAP-deficient (KO) and wild-type (WT) mice. Our aim was to elucidate the functional role of PACAP in the auditory system. Auditory brainstem response (ABR) tests found higher hearing thresholds in KO mice at click and low frequency burst stimuli. Hearing impairment at higher frequencies showed as reduced ABR wave amplitudes and latencies in KO animals. Increase in neuronal activity, demonstrated by c-Fos immunolabeling, was lower in KO mice after noise exposure in the ventral and dorsal cochlear nuclei. Noise induced neuronal activation was similar in further relay nuclei of the auditory pathway of WT and KO mice. Based on the similar inflammatory and angiogenic protein profile data from cochlear duct lysates, neither inflammation nor disturbed angiogenesis, as potential pathological components in sensorineural hearing losses, seem to be involved in the pathomechanism of the presented functional and morphological changes in PACAP KO mice. The hearing impairment is probably concomitant with the markedly accelerated aging processes in these animals.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Daniel Balazs", "last_name": "Fulop", "name": null }, { "creator_type": "author", "first_name": "Viktoria", "last_name": "Humli", "name": null }, { "creator_type": "author", "first_name": "Judit", "last_name": "Szepesy", "name": null }, { "creator_type": "author", "first_name": "Virag", "last_name": "Ott", "name": null }, { "creator_type": "author", "first_name": "Dora", "last_name": "Reglodi", "name": null }, { "creator_type": "author", "first_name": "Balazs", "last_name": "Gaszner", "name": null }, { "creator_type": "author", "first_name": "Adrienn", "last_name": "Nemeth", "name": null }, { "creator_type": "author", "first_name": "Agnes", "last_name": "Szirmai", "name": null }, { "creator_type": "author", "first_name": "Laszlo", "last_name": "Tamas", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Tibor", "last_name": "Zelles", "name": null }, { "creator_type": "author", "first_name": "Andrea", "last_name": "Tamas", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-019-50775-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31601840" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cochlea", "descriptor_ui": "D003051", "major_topic": false }, { "descriptor": "Evoked Potentials, Auditory, Brain Stem", "descriptor_ui": "D016057", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Hearing", "descriptor_ui": "D006309", "major_topic": true }, { "descriptor": "Hearing Loss", "descriptor_ui": "D034381", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Models, Animal", "descriptor_ui": "D023421", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Proteome", "descriptor_ui": "D020543", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-fos", "descriptor_ui": "D016760", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "9", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Hearing impairment and associated morphological changes in pituitary adenylate cyclase activating polypeptide (PACAP)-deficient mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Co-receptors cooperatively regulate the function of immune cells to optimize anti-infectious immunity while limiting autoimmunity by providing stimulatory and inhibitory co-signals. Among various co-receptors, those in the CD28/CTLA-4 family play fundamental roles in the regulation of lymphocytes by modulating the strength, quality, and/or duration of the antigen receptor signal. The development of the lethal lymphoproliferative disorder and various tissue-specific autoimmune diseases in mice deficient for CTLA-4 and PD-1, respectively, clearly demonstrates their pivotal roles in the development and the maintenance of immune tolerance. The recent success of immunotherapies targeting CTLA-4 and PD-1 in the treatment of various cancers highlights their critical roles in the regulation of cancer immunity in human. In addition, the development of multifarious autoimmune diseases as immune-related adverse events of anti-CTLA-4 and anti-PD-1/PD-L1 therapies and the successful clinical application of the CD28 blocking therapy using CTLA-4-Ig to the treatment of arthritis assure their crucial roles in the regulation of autoimmunity in human. Accumulating evidences in mice and humans indicate that genetic and environmental factors strikingly modify effects of the targeted inhibition and potentiation of co-signals. In this review, we summarize our current understanding of the roles of CD28, CTLA-4, and PD-1 in autoimmunity. Deeper understandings of the context-dependent and context-independent functions of co-signals are essential for the appropriate usage and the future development of innovative immunomodulatory therapies for a diverse array of diseases.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taku", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Il-Mi", "last_name": "Okazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-981-32-9717-3_8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31758536" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autoimmunity", "descriptor_ui": "D015551", "major_topic": true }, { "descriptor": "CD28 Antigens", "descriptor_ui": "D018106", "major_topic": false }, { "descriptor": "CTLA-4 Antigen", "descriptor_ui": "D060908", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Tolerance", "descriptor_ui": "D007108", "major_topic": false }, { "descriptor": "Immunotherapy", "descriptor_ui": "D007167", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "213-232", "proceedings_title": null, "publisher": "", "title": "Advances in experimental medicine and biology", "volume": "1189", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Stimulatory and Inhibitory Co-signals in Autoimmunity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tau is a microtubule-associated protein, localizing mainly in the axon of mature neurons. Phenotypic analysis of Tau knockout mice has revealed an impairment of synaptic plasticity but without gross changes in brain morphology. Since we previously described the presence of tau mRNA in the somatodendritic compartment, including the postsynapse, and demonstrated that it could be locally translated in response to glutamate, it appears that the regulated translation of synaptic tau can have a direct impact on synaptic function. Using SH-SY5Y cells, we herein confirm that glutamate dose-dependently regulates the translation of tau protein without altering tau mRNA levels. This is supported by the finding that cycloheximide blocks glutamate-stimulated increases in tau protein levels. Our observation that neural excitation can directly upregulate tau mRNA translation helps explain the pathological accumulation of tau in the somatodendrite.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Soeda", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnagi.2019.00322" }, "pmcid": { "normalized": "PMC6879554" }, "pmid": { "normalized": "31824301" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "322", "proceedings_title": null, "publisher": "", "title": "Frontiers in aging neuroscience", "volume": "11", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Enhanced Tau Protein Translation by Hyper-Excitation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mosaic loss of chromosome Y (mLOY) is frequently observed in the leukocytes of ageing men. However, the genetic architecture and biological mechanisms underlying mLOY are not fully understood. In a cohort of 95,380 Japanese men, we identify 50 independent genetic markers in 46 loci associated with mLOY at a genome-wide significant level, 35 of which are unreported. Lead markers overlap enhancer marks in hematopoietic stem cells (HSCs, P ≤ 1.0 × 10−6). mLOY genome-wide association study signals exhibit polygenic architecture and demonstrate strong heritability enrichment in regions surrounding genes specifically expressed in multipotent progenitor (MPP) cells and HSCs (P ≤ 3.5 × 10−6). ChIP-seq data demonstrate that binding sites of FLI1, a fate-determining factor promoting HSC differentiation into platelets rather than red blood cells (RBCs), show a strong heritability enrichment (P = 1.5 × 10−6). Consistent with these findings, platelet and RBC counts are positively and negatively associated with mLOY, respectively. Collectively, our observations improve our understanding of the mechanisms underlying mLOY.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Chikashi", "last_name": "Terao", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Momozawa", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Ishigaki", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Po-Ru", "last_name": "Loh", "name": null }, { "creator_type": "author", "first_name": "Giulio", "last_name": "Genovese", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Sugishita", "name": null }, { "creator_type": "author", "first_name": "Tazro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "John R. B.", "last_name": "Perry", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Kamatani", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-019-12705-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31624269" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": false }, { "descriptor": "Blood Platelets", "descriptor_ui": "D001792", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Chromosome Deletion", "descriptor_ui": "D002872", "major_topic": true }, { "descriptor": "Chromosomes, Human, Y", "descriptor_ui": "D041322", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Erythrocytes", "descriptor_ui": "D004912", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mosaicism", "descriptor_ui": "D009030", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "GWAS of mosaic loss of chromosome Y highlights genetic effects on blood cell differentiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer-immunotherapy targeting programmed cell death 1 (PD-1) activates tumor-specific T cells and provides clinical benefits in various cancers. However, the molecular basis of PD-1 function is still enigmatic. Especially, it is unclear which signaling pathway PD-1 primarily targets. Besides, the capacity of PD-1 to inhibit the T cell receptor (TCR)-dependent activation of T cells in the presence of co-stimulation is also controversial. Here we used co-culture systems of T cells and antigen-presenting cells with targeted deletion and overexpression of co-receptors and ligands and examined the inhibitory potency of PD-1 against T cell activation upon TCR stimulation with CD28 and ICOS co-stimulation. As an unambiguous criterion of T cell activation, we used the acquisition of cytokine production capacity, which represents one of the most important functions of T cells. PD-1 inhibited functional T cell activation upon TCR stimulation in the absence as well as in the presence of CD28 co-stimulation, indicating that PD-1 can directly inhibit TCR signal. Notably, CD28 co-stimulation rather attenuated the efficiency of PD-1 in inhibiting TCR-dependent functional T cell activation. In addition, PD-1 inhibited TCR-dependent functional T cell activation with ICOS co-stimulation as efficiently as that with CD28 co-stimulation. Furthermore, we found that the maintenance of antigen-induced follicular helper T (T(FH)) cells that required ICOS co-stimulation was persistently restrained by PD-1 in vivo. These findings indicate that PD-1 primarily targets TCR signal in the inhibition of functional T cell activation. Thus, PD-1 functions as the rheostat of T cell activation rather than an inhibitor of a specific stimulatory co-receptor.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Reina", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Watada", "name": null }, { "creator_type": "author", "first_name": "Il-Mi", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Okazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2019.00630" }, "pmcid": { "normalized": "PMC6455061" }, "pmid": { "normalized": "31001256" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CD28 Antigens", "descriptor_ui": "D018106", "major_topic": false }, { "descriptor": "Inducible T-Cell Co-Stimulator Protein", "descriptor_ui": "D060889", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "T-Lymphocytes, Helper-Inducer", "descriptor_ui": "D006377", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "630", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "PD-1 Primarily Targets TCR Signal in the Inhibition of Functional T Cell Activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Replicative DNA polymerases are frequently stalled at damaged template strands. Stalled replication forks are restored by the DNA damage tolerance (DDT) pathways, error-prone translesion DNA synthesis (TLS) to cope with excessive DNA damage, and error-free template switching (TS) by homologous DNA recombination. PDIP38 (Pol-delta interacting protein of 38 kDa), also called Pol delta-interacting protein 2 (PolDIP2), physically associates with TLS DNA polymerases, polymerase eta (Poleta), Pollambda, and PrimPol, and activates them in vitro. It remains unclear whether PDIP38 promotes TLS in vivo, since no method allows for measuring individual TLS events in mammalian cells. We disrupted the PDIP38 gene, generating PDIP38-/- cells from the chicken DT40 and human TK6 B cell lines. These PDIP38-/- cells did not show a significant sensitivity to either UV or H2O2, a phenotype not seen in any TLS-polymerase-deficient DT40 or TK6 mutants. DT40 provides a unique opportunity of examining individual TLS and TS events by the nucleotide sequence analysis of the immunoglobulin variable (Ig V) gene as the cells continuously diversify Ig V by TLS (non-templated Ig V hypermutation) and TS (Ig gene conversion) during in vitro culture. PDIP38-/- cells showed a shift in Ig V diversification from TLS to TS. We measured the relative usage of TLS and TS in TK6 cells at a chemically synthesized UV damage (CPD) integrated into genomic DNA. The loss of PDIP38 also caused an increase in the relative usage of TS. The number of UV-induced sister chromatid exchanges, TS events associated with crossover, was increased a few times in PDIP38-/- human and chicken cells. Collectively, the loss of PDIP38 consistently causes a shift in DDT from TLS to TS without enhancing cellular sensitivity to DNA damage. We propose that PDIP38 controls the relative usage of TLS and TS increasing usage of TLS without changing the overall capability of DDT.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masataka", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Saki", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Ooka", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kouji", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Mitsuo", "last_name": "Wakasugi", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Tetsushi", "last_name": "Sakuma", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Sasanuma", "name": null }, { "creator_type": "author", "first_name": "Michelle", "last_name": "Debatisse", "name": null }, { "creator_type": "author", "first_name": "Aidan J.", "last_name": "Doherty", "name": null }, { "creator_type": "author", "first_name": "Robert P.", "last_name": "Fuchs", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Takeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0213383" }, "pmcid": { "normalized": "PMC6402704" }, "pmid": { "normalized": "30840704" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Avian Proteins", "descriptor_ui": "D030161", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chickens", "descriptor_ui": "D002645", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": true }, { "descriptor": "DNA Polymerase beta", "descriptor_ui": "D019951", "major_topic": false }, { "descriptor": "DNA Primase", "descriptor_ui": "D019915", "major_topic": false }, { "descriptor": "DNA Repair", "descriptor_ui": "D004260", "major_topic": false }, { "descriptor": "DNA Replication", "descriptor_ui": "D004261", "major_topic": false }, { "descriptor": "DNA-Directed DNA Polymerase", "descriptor_ui": "D004259", "major_topic": false }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Genes, Immunoglobulin", "descriptor_ui": "D005803", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Multifunctional Enzymes", "descriptor_ui": "D064251", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Templates, Genetic", "descriptor_ui": "D013698", "major_topic": false }, { "descriptor": "Y-Family DNA Polymerases", "descriptor_ui": "D000099270", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "3", "normalized_date": "2019", "pages": "e0213383", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "14", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "PDIP38/PolDIP2 controls the DNA damage tolerance pathways by increasing the relative usage of translesion DNA synthesis over template switching.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "editor", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "editor", "first_name": "Benjamin", "last_name": "Wolozin", "name": null }, { "creator_type": "editor", "first_name": "Luc", "last_name": "Buee", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-981-32-9358-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": null, "normalized_date": "2019", "pages": null, "proceedings_title": null, "publisher": "Springer", "title": null, "volume": "1184", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Tau Biology", "url": "http://link.springer.com/10.1007/978-981-32-9358-8", "zotero": { "item_type": "book" } }, { "abstract": "Thirst has evolved for vertebrate terrestrial adaptation. We previously showed that buccal drying induced a series of drinking behaviours (migration to water–taking water into the mouth–swallowing) in the amphibious mudskipper goby, thereby discovering thirst in ray-finned fish. However, roles of dipsogenic/antidipsogenic hormones, which act on the thirst center in terrestrial tetrapods, have remained unclear in the mudskipper thirst. Here we examined the hormonal effects on the mudskipper drinking behaviours, particularly the antagonistic interaction between angiotensin II (AngII) and atrial natriuretic peptide (ANP) which is important for thirst regulation in mammalian ‘forebrain’. Expectedly, intracerebroventricular injection of ANP in mudskippers reduced AngII-increased drinking rate. ANP also suppressed the neural activity at the ‘hindbrain’ region for the swallowing reflex, and the maintenance of buccopharyngeal water due to the swallowing inhibition may attenuate the motivation to move to water. Thus, the hormonal molecules involved in drinking regulation, as well as the influence of buccopharyngeal water, appear to be conserved in distantly related species to solve osmoregulatory problems, whereas hormonal control of thirst at the forebrain might have been acquired only in tetrapod lineage during evolution.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yukitoshi", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Takei", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-019-52870-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31705012" } }, "mesh": [ { "descriptor": "Angiotensin II", "descriptor_ui": "D000804", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Atrial Natriuretic Factor", "descriptor_ui": "D009320", "major_topic": false }, { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": true }, { "descriptor": "Drinking Behavior", "descriptor_ui": "D004327", "major_topic": false }, { "descriptor": "Ecosystem", "descriptor_ui": "D017753", "major_topic": true }, { "descriptor": "Prosencephalon", "descriptor_ui": "D016548", "major_topic": false }, { "descriptor": "Rhombencephalon", "descriptor_ui": "D012249", "major_topic": false }, { "descriptor": "Skates, Fish", "descriptor_ui": "D012860", "major_topic": false }, { "descriptor": "Thirst", "descriptor_ui": "D013894", "major_topic": false }, { "descriptor": "Vasoconstrictor Agents", "descriptor_ui": "D014662", "major_topic": false }, { "descriptor": "Water-Electrolyte Balance", "descriptor_ui": "D014882", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "9", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Hormonal regulation of thirst in the amphibious ray-finned fish suggests the requirement for terrestrialization during evolution.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The morphogenesis of mammalian embryonic external genitalia (eExG) shows dynamic differences between males and females. In genotypic males, eExG are masculinized in response to androgen signaling. Disruption of this process can give rise to multiple male reproductive organ defects. Currently, mechanisms of androgen-driven sexually dimorphic organogenesis are still unclear. We show here that mesenchymal-derived actomyosin contractility, by MYH10, is essential for the masculinization of mouse eExG. MYH10 is expressed prominently in the bilateral mesenchyme of male eExG. Androgen induces MYH10 protein expression and actomyosin contractility in the bilateral mesenchyme. Inhibition of actomyosin contractility through blebbistatin treatment and mesenchymal genetic deletion induced defective urethral masculinization with reduced mesenchymal condensation. We also suggest that actomyosin contractility regulates androgen-dependent mesenchymal directional cell migration to form the condensation in the bilateral mesenchyme leading to changes in urethral plate shape to accomplish urethral masculinization. Thus, mesenchymal-derived actomyosin contractility is indispensable for androgen-driven urethral masculinization.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Alvin R.", "last_name": "Acebedo", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shinjiro", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Mellissa C.", "last_name": "Alcantara", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Haga", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Mitsuyoshi", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Shimamura", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takeo", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Nakagata", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Miyagawa", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Nishinakamura", "name": null }, { "creator_type": "author", "first_name": "Robert S.", "last_name": "Adelstein", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-019-0336-3" }, "pmcid": { "normalized": "PMC6408527" }, "pmid": { "normalized": "30886905" } }, "mesh": [ { "descriptor": "Actomyosin", "descriptor_ui": "D000205", "major_topic": false }, { "descriptor": "Androgens", "descriptor_ui": "D000728", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Myosin Heavy Chains", "descriptor_ui": "D018995", "major_topic": false }, { "descriptor": "Nonmuscle Myosin Type IIB", "descriptor_ui": "D024501", "major_topic": false }, { "descriptor": "Urethra", "descriptor_ui": "D014521", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "95", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "2", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Mesenchymal actomyosin contractility is required for androgen-driven urethral masculinization in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The golden standard method to obtain accurate blood oxygen saturation is blood gas analysis that needs invasive procedure of blood sampling. Photoacoustic technique enables us to measure real-time blood oxygen saturation without invasive procedure. The aim of this study is to use the photoacoustic technique, an optical method, for accurately determining oxygen saturation in vivo. We measured induced photoacoustic signals of arterial blood in the rabbit model of stable hypoxemia after irradiation at 750 and 800 nm. Oxygen saturation was calculated from the photoacoustic signals using two calibration curves. Calibration curve 1 is a conventional curve derived from the absorbance coefficient of hemoglobin, whereas calibration curve 2 is derived from the photoacoustic signals obtained from the original blood vessel model. Simultaneously, blood-gas analysis was performed to obtain the reference standard of oxygen saturation. Regression analysis and Bland-Altman analysis were performed to assess the accuracy of oxygen saturation obtained using the two methods. The oxygen saturation calculated using calibration curves 1 and 2 showed strong correlations with the reference standard in regression analysis (R = 0.965, 0.964, respectively). The Bland-Altman analysis revealed better agreement and precision with calibration curve 2, whereas there was significant underestimation of values obtained using calibration curve 1. Photoacoustic measurement of oxygen saturation using calibration curve 2 provided an accurate estimate of oxygen saturation, which was similar to that obtained using a portable blood-gas analyzer.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kiguna", "last_name": "Sei", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Okawa", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Sasa", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Furuya", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10877-018-0166-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29876708" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Gas Analysis", "descriptor_ui": "D001784", "major_topic": true }, { "descriptor": "Calibration", "descriptor_ui": "D002138", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hemoglobins", "descriptor_ui": "D006454", "major_topic": false }, { "descriptor": "Hypoxia", "descriptor_ui": "D000860", "major_topic": false }, { "descriptor": "Oximetry", "descriptor_ui": "D010092", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Photoacoustic Techniques", "descriptor_ui": "D061088", "major_topic": true }, { "descriptor": "Pulmonary Gas Exchange", "descriptor_ui": "D011659", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Regression Analysis", "descriptor_ui": "D012044", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "269-279", "proceedings_title": null, "publisher": "", "title": "Journal of clinical monitoring and computing", "volume": "33", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Measurement of blood-oxygen saturation using a photoacoustic technique in the rabbit hypoxemia model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pluripotency of mouse embryonic stem cells is regulated by transcription factor regulatory networks as well as mechanical stimuli sensed by the cells. It has been unclear how the mechanical strain applied to the plasma membrane is transferred to the nucleus in mouse embryonic stem cells (mESCs). We here investigated the machinery of the mechanotransduction based on the finding that spontaneous differentiation of mESCs was inhibited with the downregulation of ROCK2 in cells attached to soft substrates. On examining the effects of actin bindings to both focal adhesions and cell junctions in cells on soft substrates, co-localization of actin filaments and alpha-catenin, which links actin to E-cadherin, decreased after differentiation induction. Also, disrupting actin-nucleus mechanical link through dominant negative assay of Nesprins helps to sustain the pluripotency genes; thus, revealing that mechanical strain relayed by actin-Nesprin connection is required for the initiation of the differentiation process.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Brit Gracy", "last_name": "David", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Kyota", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yulia", "last_name": "Panina", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Ichinose", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.scr.2019.101614" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31715427" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "alpha Catenin", "descriptor_ui": "D051178", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Enzymologic", "descriptor_ui": "D015971", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mouse Embryonic Stem Cells", "descriptor_ui": "D000066450", "major_topic": false }, { "descriptor": "rho-Associated Kinases", "descriptor_ui": "D054460", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Dec", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "101614", "proceedings_title": null, "publisher": "", "title": "Stem cell research", "volume": "41", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Linking substrate and nucleus via actin cytoskeleton in pluripotency maintenance of mouse embryonic stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The human mitochondrion-derived calcium transporter Letm1 was synthesized by reconstituted in vitro transcription-translation (IVTT) in cell-sized liposomes and the dependency of Letm1 on phospholipid composition was investigated. Components for IVTT were encapsulated into cell-sized vesicles together with the DNA encoding Letm1, thereby preparing proteoliposomes. The synthesis of Letm1 and pH-dependent calcium transport activity were confirmed by flow cytometry. Finally, we investigated the effect of phospholipid composition on Letm1 transport activity and found that cardiolipin present in the mitochondrial membrane plays an important role on the transport activity of Letm1.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbiosc.2018.11.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30503650" } }, "mesh": [ { "descriptor": "Calcium-Binding Proteins", "descriptor_ui": "D002135", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liposomes", "descriptor_ui": "D008081", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Phospholipids", "descriptor_ui": "D010743", "major_topic": false }, { "descriptor": "Protein Biosynthesis", "descriptor_ui": "D014176", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "544-548", "proceedings_title": null, "publisher": "", "title": "Journal of bioscience and bioengineering", "volume": "127", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "In vitro synthesis of the human calcium transporter Letm1 within cell-sized liposomes and investigation of its lipid dependency.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A pulsed laser illuminates a target zone that causes rapid thermoelastic expansion, generating broadband high-frequency ultrasonic wave (photoacoustic wave, PA wave). We developed a PA microscopy (PAM) with a confocal area of laser and ultrasonic wave for applications in nondestructive testing (NDT). The synthetic aperture focusing technique (SAFT) is applied in the PAM for the three-dimensional (3D) imaging of interior flaws. Here, we report proof-of-concept experiments for the NDT of a subsurface flaw in a thin laminar material. Graphical abstract (a) shows a specimen of carbon-fiber-reinforced plastic (CFRP) with an artificial delamination. Here, it should be noted that the group velocity varies directionally due to the strong anisotropy of the CFRP specimen (see Graphical abstract (b)). By considering the group velocity distribution in the SAFT, the shape and location of the subsurface delamination were accurately estimated as shown in Graphical abstract (c). Coating the surface of the CFRP specimen with a light-absorbent material improved the amplitude of the PA wave. This finding showed that the signal-to-noise ratio of the waves scattered from the flaws can be improved.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "K.", "last_name": "Nakahata", "name": null }, { "creator_type": "author", "first_name": "K.", "last_name": "Karakawa", "name": null }, { "creator_type": "author", "first_name": "K.", "last_name": "Ogi", "name": null }, { "creator_type": "author", "first_name": "K.", "last_name": "Mizukami", "name": null }, { "creator_type": "author", "first_name": "K.", "last_name": "Ohira", "name": null }, { "creator_type": "author", "first_name": "M.", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "S.", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "T.", "last_name": "Namita", "name": null }, { "creator_type": "author", "first_name": "T.", "last_name": "Shiina", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ultras.2019.05.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31207475" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 Sep", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "82-87", "proceedings_title": null, "publisher": "", "title": "Ultrasonics", "volume": "98", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Three-dimensional SAFT imaging for anisotropic materials using photoacoustic microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recently, we established the GEEP (\"gene editing by electroporation of Cas9 protein\") method, in which the CRISPR/Cas9 system, consisting of a Cas9 protein and single guide RNA (sgRNA), is introduced into pig zygotes by electroporation and thus induces highly efficient targeted gene disruption. In this study, we examined the effects of sgRNA on the blastocyst formation of porcine embryos and evaluated their genome-editing efficiency. To produce an animal model for diabetes, we targeted PDX-1 (pancreas duodenum homeobox 1), a gene that is crucial for pancreas development during the fetal period and whose monoallelic disruption impairs insulin secretion. First, Cas9 protein with different sgRNAs that targeted distinct sites in the PDX-1 exon 1 was introduced into in vitro-fertilized zygotes by the GEEP method. Of the six sgRNAs tested, three sgRNAs (sgRNA1, 2, and 3) successfully modified PDX-1 gene. The blastocyst formation rate of zygotes edited with sgRNA3 was significantly (p < 0.05) lower than that of control zygotes without the electroporation treatment. Our study indicates that the GEEP method can be successfully used to generate PDX-1 mutant blastocysts, but the development and the efficiency of editing the genome of zygotes may be affected by the sgRNA used for CRISPR/Cas9 system.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Fuminori", "last_name": "Tanihara", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Nhien T.", "last_name": "Nguyen", "name": null }, { "creator_type": "author", "first_name": "Quynh A.", "last_name": "Le", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Dai-Ichiro", "last_name": "Fuchimoto", "name": null }, { "creator_type": "author", "first_name": "Takeshige", "last_name": "Otoi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/asj.13129" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30368976" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blastocyst", "descriptor_ui": "D001755", "major_topic": true }, { "descriptor": "Clustered Regularly Interspaced Short Palindromic Repeats", "descriptor_ui": "D064112", "major_topic": false }, { "descriptor": "CRISPR-Associated Protein 9", "descriptor_ui": "D000076987", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Electroporation", "descriptor_ui": "D018274", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fertilization in Vitro", "descriptor_ui": "D005307", "major_topic": false }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "RNA, Guide, CRISPR-Cas Systems", "descriptor_ui": "D000094704", "major_topic": false }, { "descriptor": "Swine", "descriptor_ui": "D013552", "major_topic": false }, { "descriptor": "Trans-Activators", "descriptor_ui": "D015534", "major_topic": false }, { "descriptor": "Zygote", "descriptor_ui": "D015053", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "55-61", "proceedings_title": null, "publisher": "", "title": "Animal science journal = Nihon chikusan Gakkaiho", "volume": "90", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of PDX-1 mutant porcine blastocysts by introducing CRISPR/Cas9-system into porcine zygotes via electroporation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Although recent studies provide insight into the molecular mechanisms of the effects of ketamine, the antidepressant mechanism of ketamine enantiomers and their metabolites is not fully understood. In view of the involvement of mechanisms other than the N-methyl-D-aspartate receptor in ketamine’s action, we investigated the effects of (R)-ketamine, (S)-ketamine, (R)-norketamine [(R)-NK], (S)-NK, (2R,6R)-hydroxynorketamine [(2R,6R)-HNK], and (2S,6S)-HNK on monoaminergic neurotransmission in the prefrontal cortex of mice. Methods: The extracellular monoamine levels in the prefrontal cortex were measured by in vivo microdialysis. Results: (R)-Ketamine and (S)-ketamine acutely increased serotonin release in a dose-dependent manner, and the effect of (R)-ketamine was greater than that of (S)-ketamine. In contrast, (S)-ketamine caused a robust increase in dopamine release compared with (R)-ketamine. Both ketamine enantiomers increased noradrenaline release, but these effects did not differ. (2R,6R)-HNK caused a slight but significant increase in serotonin and noradrenaline but not dopamine release. (S)-NK increased dopamine and noradrenaline but not serotonin release. Differential effects between (R)-ketamine and (S)-ketamine were also observed in a lipopolysaccharide-induced model of depression. An α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist, 2,3-dioxo-6-nitro-1,2,3,4- tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX), attenuated (S)-ketamine-induced, but not (R)-ketamine-induced serotonin release, whereas NBQX blocked dopamine release induced by both enantiomers. Local application of (R)-ketamine into the prefrontal cortex caused a greater increase in prefrontal serotonin release than that of (S)-ketamine. Conclusions: (R)-Ketamine strongly activates the prefrontal serotonergic system through an AMPA receptor-independent mechanism. (S)-Ketamine-induced serotonin and dopamine release was AMPA receptor-dependent. These findings provide a neurochemical basis for the underlying pharmacological differences between ketamine enantiomers and their metabolites.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Momoko", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Shinsaku", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/ijnp/pyz041" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31325908" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Ketamine", "descriptor_ui": "D007649", "major_topic": false }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microdialysis", "descriptor_ui": "D017551", "major_topic": false }, { "descriptor": "Microinjections", "descriptor_ui": "D008845", "major_topic": false }, { "descriptor": "Norepinephrine", "descriptor_ui": "D009638", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Quinoxalines", "descriptor_ui": "D011810", "major_topic": false }, { "descriptor": "Receptors, AMPA", "descriptor_ui": "D018091", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "665-674", "proceedings_title": null, "publisher": "", "title": "International Journal of Neuropsychopharmacology", "volume": "22", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "(R)-Ketamine Induces a Greater Increase in Prefrontal 5-HT Release Than (S)-Ketamine and Ketamine Metabolites via an AMPA Receptor-Independent Mechanism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We previously revealed that the mechanism of demosponge skeleton construction is self-organization by multiple rounds of sequential mechanical reactions of player cells. In these reactions, \"transport cells\" dynamically carry fine skeletal elements (spicules) on epithelia surrounding the inner body space of sponges (basal epithelium (basopinacoderm) and the endodermal epithelium (ENCM)). Once spicules pierce ENCM and apical pinacoderm, subsequently they are cemented to the substratum under the sponge body, or connected to other skeleton-constructing spicules. Thus, the \"pierce\" step is the key to holding up spicules in the temporary periphery of growing sponges' bodies. Since sponges can regress as well as grow, here we asked how skeleton construction occurs during local regression of the body. We found that prior to local basopinacoderm retraction (and thus body regression), the body became thinner. Some spicules that were originally carried outward stagnated for a while, and were then carried inwards either on ENCM or basopinacoderm. Spicules that were carried inwards on ENCM pierced epithelia after a short transport, and thus became held up at relatively inward positions compared to spicules carried on outwardly extending basopinacoderm. The switch of epithelia on which transport cells migrate efficiently occurred in thinner body spaces where basopinacoderm and ENCM became close to each other. Thus, the mechanisms underlying this phenomenon are rather mechanical: the combination of sequential reactions of skeleton construction and the narrowed body space upon local retraction of basopinacoderm cause spicules to be held up at more-inward positions, which might strengthen the basopinacoderm's attachment to substratum.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kouji", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Wakana", "last_name": "Sugano-Yasunaga", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Kiyokazu", "last_name": "Agata", "name": null }, { "creator_type": "author", "first_name": "Shigenori", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Funayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12636" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31820450" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Porifera", "descriptor_ui": "D011161", "major_topic": true }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Dec", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "485-500", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "61", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Skeleton construction upon local regression of the sponge body.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Galectin-3 (Gal-3; gene LGALS3) is a member of the beta-galactose-binding lectin family. Previous studies showed that Gal-3 is expressed in several tissues across species and functions as a regulator of cell proliferation, apoptosis, adhesion, and migration, thus affecting many aspects of events, such as angiogenesis and tumorigenesis. Although several reports have suggested that the level of Gal-3 expression correlates positively with tumor progression, herein we show that highly metastatic mouse melanoma B16/BL6 cells express less Gal-3 than B16 cells with a lower metastatic potential. It was found that overexpression of Gal-3 in melanoma cells in fact suppresses metastasis. In contrast, knocking out Gal-3 expression in cancer cells promoted cell aggregation mediated through interactions with platelets and fibrinogen in vitro and increased the number of metastatic foci in vivo. Thus, reduced Gal-3 expression results in the up-regulation of beta3 integrin expression, and this contributes to metastatic potential. These findings indicate that changes of Gal-3 expression in cancer cells during tumor progression influence the characteristics of metastatic cells.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yumiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Weizhen", "last_name": "Jia", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ajpath.2018.12.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30653955" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Galectin 3", "descriptor_ui": "D037502", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Integrin beta3", "descriptor_ui": "D039661", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Melanoma, Experimental", "descriptor_ui": "D008546", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "900-910", "proceedings_title": null, "publisher": "", "title": "The American journal of pathology", "volume": "189", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Galectin-3 Inhibits Cancer Metastasis by Negatively Regulating Integrin beta3 Expression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The interferon-inducible transmembrane (Ifitm/Fragilis) genes encode homologous proteins that are induced by IFNs. Here, we show that IFITM proteins regulate murine CD4(+) Th cell differentiation. Ifitm2 and Ifitm3 are expressed in wild-type (WT) CD4(+) T cells. On activation, Ifitm3 was downregulated and Ifitm2 was upregulated. Resting Ifitm-family-deficient CD4(+) T cells had higher expression of Th1-associated genes than WT and purified naive Ifitm-family-deficient CD4(+) T cells differentiated more efficiently to Th1, whereas Th2 differentiation was inhibited. Ifitm-family-deficient mice, but not Ifitm3-deficient mice, were less susceptible than WT to induction of allergic airways disease, with a weaker Th2 response and less severe disease and lower Il4 but higher Ifng expression and IL-27 secretion. Thus, the Ifitm family is important in adaptive immunity, influencing Th1/Th2 polarization, and Th2 immunopathology.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Diana C.", "last_name": "Yanez", "name": null }, { "creator_type": "author", "first_name": "Hemant", "last_name": "Sahni", "name": null }, { "creator_type": "author", "first_name": "Susan", "last_name": "Ross", "name": null }, { "creator_type": "author", "first_name": "Anisha", "last_name": "Solanki", "name": null }, { "creator_type": "author", "first_name": "Ching-In", "last_name": "Lau", "name": null }, { "creator_type": "author", "first_name": "Eleftheria", "last_name": "Papaioannou", "name": null }, { "creator_type": "author", "first_name": "Alessandro", "last_name": "Barbarulo", "name": null }, { "creator_type": "author", "first_name": "Rebecca", "last_name": "Powell", "name": null }, { "creator_type": "author", "first_name": "Ulrike C.", "last_name": "Lange", "name": null }, { "creator_type": "author", "first_name": "David J.", "last_name": "Adams", "name": null }, { "creator_type": "author", "first_name": "Martino", "last_name": "Barenco", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Fulvio", "last_name": "D'Acquisto", "name": null }, { "creator_type": "author", "first_name": "Anna L.", "last_name": "Furmanski", "name": null }, { "creator_type": "author", "first_name": "Tessa", "last_name": "Crompton", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/eji.201847692" }, "pmcid": { "normalized": "PMC6396086" }, "pmid": { "normalized": "30365177" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Hypersensitivity", "descriptor_ui": "D006967", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Interferon-gamma", "descriptor_ui": "D007371", "major_topic": false }, { "descriptor": "Interleukin-27", "descriptor_ui": "D064094", "major_topic": false }, { "descriptor": "Interleukin-4", "descriptor_ui": "D015847", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Respiratory System", "descriptor_ui": "D012137", "major_topic": false }, { "descriptor": "Th1 Cells", "descriptor_ui": "D018417", "major_topic": false }, { "descriptor": "Th1-Th2 Balance", "descriptor_ui": "D058408", "major_topic": false }, { "descriptor": "Th2 Cells", "descriptor_ui": "D018418", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "66-78", "proceedings_title": null, "publisher": "", "title": "European journal of immunology", "volume": "49", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This study focuses on the possibility that herbicide-exposed phytoplankton will cause sub-lethal effect on zooplankton. Atrazine, phytoplankton Raphidocelis subcapitata and zooplankton Daphnia magna were chosen as a model chemical and organisms. R. subcapitata was exposed to atrazine at 150mug/L, harvested and fed to D. magna. While the mothers fed with atrazine-exposed phytoplankton did not show any abnormalities, they produced non-viable offspring. Number of non-viable offspring at the first clutch was high but the number was reduced at later stages and viable offspring was produced. This result indicates that phytoplankton exposed to sub-lethal dose of atrazine affects population dynamics of its predator, D. magna.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Pijar", "last_name": "Religia", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Ery Odette", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Muranaka", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.marenvres.2019.02.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30797563" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Atrazine", "descriptor_ui": "D001280", "major_topic": true }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "Food Chain", "descriptor_ui": "D020387", "major_topic": false }, { "descriptor": "Phytoplankton", "descriptor_ui": "D010839", "major_topic": false }, { "descriptor": "Population Dynamics", "descriptor_ui": "D011157", "major_topic": false }, { "descriptor": "Water Pollutants, Chemical", "descriptor_ui": "D014874", "major_topic": true }, { "descriptor": "Zooplankton", "descriptor_ui": "D015048", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Mar", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "177-183", "proceedings_title": null, "publisher": "", "title": "Marine environmental research", "volume": "145", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Atrazine exposed phytoplankton causes the production of non-viable offspring on Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "3q29 microdeletion, a rare recurrent copy number variant (CNV), greatly confers an increased risk of psychiatric disorders, such as schizophrenia and autism spectrum disorder (ASD), as well as intellectual disability. However, disease-relevant cellular phenotypes of 3q29 deletion syndrome remain to be identified. To reveal the molecular and cellular etiology of 3q29 deletion syndrome, we generated a mouse model of human 3q29 deletion syndrome by chromosome engineering, which achieved construct validity. 3q29 deletion (Df/+) mice showed reduced body weight and brain volume and, more importantly, impaired social interaction and prepulse inhibition. Importantly, the schizophrenia-related impaired prepulse inhibition was reversed by administration of antipsychotics. These findings are reminiscent of the growth defects and neuropsychiatric behavioral phenotypes in patients with 3q29 deletion syndrome and exemplify that the mouse model achieves some part of face validity and predictive validity. Unbiased whole-brain imaging revealed that neuronal hyperactivation after a behavioral task was strikingly exaggerated in a restricted region of the cortex of Df/+ mice. We further elucidated the cellular phenotypes of neuronal hyperactivation and the reduction of parvalbumin expression in the cortex of Df/+ mice. Thus, the 3q29 mouse model provides invaluable insight into the disease-causative molecular and cellular pathology of psychiatric disorders.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masayuki", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Kazumasa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Naka", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Momoka", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Misuzu", "last_name": "Hayashida", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41386-019-0441-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31216562" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": false }, { "descriptor": "Chromosome Deletion", "descriptor_ui": "D002872", "major_topic": false }, { "descriptor": "Chromosomes, Human, Pair 3", "descriptor_ui": "D002893", "major_topic": false }, { "descriptor": "Developmental Disabilities", "descriptor_ui": "D002658", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intellectual Disability", "descriptor_ui": "D008607", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Nov", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "2125-2135", "proceedings_title": null, "publisher": "", "title": "Neuropsychopharmacology", "volume": "44", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Psychiatric-disorder-related behavioral phenotypes and cortical hyperactivity in a mouse model of 3q29 deletion syndrome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a transcriptional target of the lineage-survival oncogene NKX2-1/TTF-1 in lung adenocarcinomas. In addition to its kinase-dependent role, ROR1 functions as a scaffold protein to facilitate interaction between caveolin-1 (CAV1) and CAVIN1, and consequently maintains caveolae formation, which in turn sustains pro-survival signaling toward AKT from multiple receptor tyrosine kinases (RTKs), including epidermal growth factor receptor (EGFR), MET (proto-oncogene, receptor tyrosine kinase), and IGF-IR (insulin-like growth factor receptor 1). Therefore, ROR1 is an attractive target for overcoming EGFR-TKI resistance due to various mechanisms such as EGFR T790M double mutation and bypass signaling from other RTKs. Here, we report that ROR1 possesses a novel scaffold function indispensable for efficient caveolae-dependent endocytosis. CAVIN3 was found to bind with ROR1 at a site distinct from sites for CAV1 and CAVIN1, a novel function required for proper CAVIN3 subcellular localization and caveolae-dependent endocytosis, but not caveolae formation itself. Furthermore, evidence of a mechanistic link between ROR1-CAVIN3 interaction and consequential caveolae trafficking, which was found to utilize a binding site distinct from those for ROR1 interactions with CAV1 and CAVIN1, with RTK-mediated pro-survival signaling towards AKT in early endosomes in lung adenocarcinoma cells was also obtained. The present findings warrant future study to enable development of novel therapeutic strategies for inhibiting the multifaceted scaffold functions of ROR1 in order to reduce the intolerable death toll from this devastating cancer.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tomoya", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Miyu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Lisa", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Can", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kajino", "name": null }, { "creator_type": "author", "first_name": "Jinglei", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakatochi", "name": null }, { "creator_type": "author", "first_name": "Hisanori", "last_name": "Isomura", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Motoshi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Toyoshi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41388-019-0785-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30894682" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caveolae", "descriptor_ui": "D021941", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": true }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Proto-Oncogene Mas", "descriptor_ui": "D000090063", "major_topic": false }, { "descriptor": "Receptor Tyrosine Kinase-like Orphan Receptors", "descriptor_ui": "D057050", "major_topic": false }, { "descriptor": "Sf9 Cells", "descriptor_ui": "D061987", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Spodoptera", "descriptor_ui": "D018411", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jun", "date_precision": "unknown", "issue": "26", "normalized_date": null, "pages": "5142-5157", "proceedings_title": null, "publisher": "", "title": "Oncogene", "volume": "38", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "ROR1-CAVIN3 interaction required for caveolae-dependent endocytosis and pro-survival signaling in lung adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: While mechanistic links between tau abnormalities and neurodegeneration have been proven in frontotemporal dementia and parkinsonism linked to chromosome 17 caused by MAPT mutations, variability of the tau pathogenesis and its relation to clinical progressions in the same MAPT mutation carriers are yet to be clarified. Objectives: The present study aimed to analyze clinical profiles, tau accumulations, and their correlations in 3 kindreds with frontotemporal dementia and parkinsonism linked to chromosome 17 attributed to the MAPT N279K mutation. Methods: Four patients with N279K mutant frontotemporal dementia and parkinsonism linked to chromosome 17/MAPT underwent [11C]PBB3‐PET to estimate regional tau loads. Results: Haplotype assays revealed that these kindreds originated from a single founder. Despite homogeneity of the disease‐causing MAPT allele, clinical progression was more rapid in 2 kindreds than in the other. The kindred with slow progression showed mild tau depositions, mostly confined to the midbrain and medial temporal areas. In contrast, kindreds with rapid progression showed profoundly increased [11C]PBB3 binding in widespread regions from an early disease stage. Conclusions: [11C]PBB3‐PET can capture four‐repeat tau pathologies characteristic of N279K mutant frontotemporal dementia and parkinsonism linked to chromosome 17/MAPT. Our findings indicate that, in addition to the mutated MAPT allele, genetic and/or epigenetic modifiers of tau pathologies lead to heterogeneous clinicopathological features. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Aya", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Kenya", "last_name": "Nishioka", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Takanashi", "name": null }, { "creator_type": "author", "first_name": "Arisa", "last_name": "Hayashida", "name": null }, { "creator_type": "author", "first_name": "Yuanzhe", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Hiroyo", "last_name": "Yoshino", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Funayama", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Nobutaka", "last_name": "Hattori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/mds.27623" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30773680" } }, "mesh": [ { "descriptor": "Alleles", "descriptor_ui": "D000483", "major_topic": false }, { "descriptor": "Chromosomes, Human, Pair 17", "descriptor_ui": "D002886", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Frontotemporal Dementia", "descriptor_ui": "D057180", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Neuroimaging", "descriptor_ui": "D059906", "major_topic": false }, { "descriptor": "Parkinsonian Disorders", "descriptor_ui": "D020734", "major_topic": false }, { "descriptor": "Positron-Emission Tomography", "descriptor_ui": "D049268", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "568-574", "proceedings_title": null, "publisher": "", "title": "Movement Disorders", "volume": "34", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical heterogeneity of frontotemporal dementia and Parkinsonism linked to chromosome 17 caused by MAPT N279K mutation in relation to tau positron emission tomography features.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Magnesium (Mg) is the second most abundant cation in mammalian cells, and it is essential for numerous cellular processes including enzymatic reactions, ion channel functions, metabolic cycles, cellular signaling, and DNA/RNA stabilities. Because of the versatile and universal nature of Mg2+, the homeostasis of intracellular Mg2+ is physiologically linked to growth, proliferation, differentiation, energy metabolism, and death of cells. On the cellular and tissue levels, maintaining Mg2+ within optimal levels according to the biological context, such as cell types, developmental stages, extracellular environments, and pathophysiological conditions, is crucial for development, normal functions, and diseases. Hence, Mg2+ is pathologically involved in cancers, diabetes, and neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease, and demyelination. In the research field regarding the roles and mechanisms of Mg2+ regulation, numerous controversies caused by its versatility and complexity still exist. As Mg2+, at least, plays critical roles in neuronal development, healthy normal functions, and diseases, appropriate Mg2+ supplementation exhibits neurotrophic effects in a majority of cases. Hence, the control of Mg2+ homeostasis can be a candidate for therapeutic targets in neuronal diseases. In this review, recent results regarding the roles of intracellular Mg2+ and its regulatory system in determining the cell phenotype, fate, and diseases in the nervous system are summarized, and an overview of the comprehensive roles of Mg2+ is provided.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryu", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms20143439" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31336935" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Disease Susceptibility", "descriptor_ui": "D004198", "major_topic": true }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Genomic Instability", "descriptor_ui": "D042822", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Space", "descriptor_ui": "D042541", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jul", "date_precision": "unknown", "issue": "14", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "International Journal of Molecular Sciences", "volume": "20", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Magnesium Is a Key Player in Neuronal Maturation and Neuropathology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The GINS (Go, Ichi, Nii, and San) complex contains four protein subunits (PSF1, PSF2, PSF3, and SLD5) and has been identified as a factor essential for the initiation and elongation stages of the DNA replication process. A previous study indicated that PSF2 participated in the developing central nervous system (CNS) of Xenopus laevis. However, the expression and function of GINS members in the mammalian developing nervous system remains unclear. Here, we examined the expression of GINS members in mice during nervous system development via immunofluorescence staining. At the beginning of neural development, PSF1 and SLD5 were highly expressed in neuroepithelial stem cells (NSCs) of the inner surface of neural tube (NT) and overlapped with proliferation marker Ki67. After entering the mid- and late-phase of neural development, PSF1 and SLD5 changed their regions of expression. These genes were highly expressed in dorsal root ganglion (DRG) progenitors, but they showed no overlap with Ki67 positive cells. Instead, a reduction of SLD5 expression promoted neuronal differentiation and maturation in the late-phase. PSF2 and PSF3 showed no tissue-specificity. PSF2 was constitutively and highly expressed whereas PSF3 was expressed at very low levels during neural development. In this study, we demonstrated variations in proteins and expression regions of the GINS members during mammalian CNS development and revealed a correlation between GINS expression and cell proliferation. Furthermore, we have suggested a novel function of GINS member SLD5, which regulates the differentiation of neural stem/progenitors.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Weizhen", "last_name": "Jia", "name": null }, { "creator_type": "author", "first_name": "Han-Yun", "last_name": "Hsieh", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuint.2019.104465" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31095979" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "ATP Binding Cassette Transporter, Subfamily B, Member 2", "descriptor_ui": "D000071181", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Ganglia, Spinal", "descriptor_ui": "D005727", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Nervous System", "descriptor_ui": "D009420", "major_topic": false }, { "descriptor": "Protein Subunits", "descriptor_ui": "D021122", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Oct", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "104465", "proceedings_title": null, "publisher": "", "title": "Neurochemistry international", "volume": "129", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Embryonic expression of GINS members in the development of the mammalian nervous system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In addition to maintaining immune tolerance, FOXP3(+) regulatory T (Treg) cells perform specialized functions in tissue homeostasis and remodelling(1,2). However, the characteristics and functions of brain Treg cells are not well understood because there is a low number of Treg cells in the brain under normal conditions. Here we show that there is massive accumulation of Treg cells in the mouse brain after ischaemic stroke, and this potentiates neurological recovery during the chronic phase of ischaemic brain injury. Although brain Treg cells are similar to Treg cells in other tissues such as visceral adipose tissue and muscle(3-5), they are apparently distinct and express unique genes related to the nervous system including Htr7, which encodes the serotonin receptor 5-HT7. The amplification of brain Treg cells is dependent on interleukin (IL)-2, IL-33, serotonin and T cell receptor recognition, and infiltration into the brain is driven by the chemokines CCL1 and CCL20. Brain Treg cells suppress neurotoxic astrogliosis by producing amphiregulin, a low-affinity epidermal growth factor receptor (EGFR) ligand. Stroke is a leading cause of neurological disability, and there are currently few effective recovery methods other than rehabilitation during the chronic phase. Our findings suggest that Treg cells and their products may provide therapeutic opportunities for neuronal protection against stroke and neuroinflammatory diseases.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Komai", "name": null }, { "creator_type": "author", "first_name": "Setsuko", "last_name": "Mise-Omata", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Iizuka-Koga", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Yoshie", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Nakatsukasa", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shichita", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41586-018-0824-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30602786" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Brain Ischemia", "descriptor_ui": "D002545", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Chemokine CCL1", "descriptor_ui": "D054402", "major_topic": false }, { "descriptor": "Chemokine CCL20", "descriptor_ui": "D054418", "major_topic": false }, { "descriptor": "Gliosis", "descriptor_ui": "D005911", "major_topic": false }, { "descriptor": "Interleukin-2", "descriptor_ui": "D007376", "major_topic": false }, { "descriptor": "Interleukin-33", "descriptor_ui": "D000067596", "major_topic": false }, { "descriptor": "Interleukin-6", "descriptor_ui": "D015850", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neuroprotection", "descriptor_ui": "D000066829", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false }, { "descriptor": "Receptors, CCR", "descriptor_ui": "D054388", "major_topic": false }, { "descriptor": "Receptors, Serotonin", "descriptor_ui": "D011985", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "STAT3 Transcription Factor", "descriptor_ui": "D050796", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan", "date_precision": "unknown", "issue": "7738", "normalized_date": null, "pages": "246-250", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "565", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Parasite-mediated selection varying across time and space in metapopulations is expected to result in host local adaptation and the maintenance of genetic diversity in disease-related traits. However, nonadaptive processes like migration and extinction-(re)colonization dynamics might interfere with adaptive evolution. Understanding how adaptive and nonadaptive processes interact to shape genetic variability in life-history and disease-related traits can provide important insights into their evolution in subdivided populations. Here we investigate signatures of spatially fluctuating, parasite-mediated selection in a natural metapopulation of Daphnia magna. Host genotypes from infected and uninfected populations were genotyped at microsatellite markers, and phenotyped for life-history and disease traits in common garden experiments. Combining phenotypic and genotypic data a QST -FST -like analysis was conducted to test for signatures of parasite mediated selection. We observed high variation within and among populations for phenotypic traits, but neither an indication of host local adaptation nor a cost of resistance. Infected populations have a higher gene diversity (Hs) than uninfected populations and Hs is strongly positively correlated with fitness. These results suggest a strong parasite effect on reducing population level inbreeding. We discuss how stochastic processes related to frequent extinction-(re)colonization dynamics as well as host and parasite migration impede the evolution of resistance in the infected populations. We suggest that the genetic and phenotypic patterns of variation are a product of dynamic changes in the host gene pool caused by the interaction of colonization bottlenecks, inbreeding, immigration, hybrid vigor, rare host genotype advantage and parasitism. Our study highlights the effect of the parasite in ameliorating the negative fitness consequences caused by the high drift load in this metapopulation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Andrea P.", "last_name": "Cabalzar", "name": null }, { "creator_type": "author", "first_name": "Peter D.", "last_name": "Fields", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Dieter", "last_name": "Ebert", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/mec.15260" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31591747" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "Genetic Variation", "descriptor_ui": "D014644", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Hybrid Vigor", "descriptor_ui": "D006823", "major_topic": false }, { "descriptor": "Inbreeding", "descriptor_ui": "D007178", "major_topic": false }, { "descriptor": "Microsatellite Repeats", "descriptor_ui": "D018895", "major_topic": false }, { "descriptor": "Parasites", "descriptor_ui": "D010271", "major_topic": false }, { "descriptor": "Population Dynamics", "descriptor_ui": "D011157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Nov", "date_precision": "unknown", "issue": "21", "normalized_date": null, "pages": "4770-4785", "proceedings_title": null, "publisher": "", "title": "Molecular ecology", "volume": "28", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Parasite-mediated selection in a natural metapopulation of Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Major depression and anxiety disorders are a social and economic burden worldwide. Serotonergic signaling has been implicated in the pathophysiology of these disorders and thus has been a crucial target for pharmacotherapy. However, the precise mechanisms underlying these disorders are still unclear. Here, we used species-optimized lentiviral vectors that were capable of efficient and specific transduction of serotonergic neurons in mice and rats for elucidation of serotonergic roles in anxiety-like behaviors and active coping behavior in both species. Immunohistochemical analyses revealed that lentiviral vectors with an upstream sequence of tryptophan hydroxylase 2 gene efficiently transduced serotonergic neurons with a specificity of approximately 95% in both mice and rats. Electrophysiological recordings showed that these lentiviral vectors induced sufficient expression of optogenetic tools for precise control of serotonergic neurons. Using these vectors, we demonstrate that acute activation of serotonergic neurons in the dorsal raphe nucleus increases active coping with inescapable stress in rats and mice in a time-locked manner, and that acute inhibition of these neurons increases anxiety-like behaviors specifically in rats. These findings further our understanding of the pathophysiological role of dorsal raphe serotonergic neurons in different species and the role of these neurons as therapeutic targets in major depression and anxiety disorders.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Naoya", "last_name": "Nishitani", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Asaoka", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Yamashiro", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Andoh", "name": null }, { "creator_type": "author", "first_name": "Yuma", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Norihiro", "last_name": "Shibui", "name": null }, { "creator_type": "author", "first_name": "Beihui", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "James", "last_name": "Hewinson", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Shirakawa", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Sergey", "last_name": "Kasparov", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Kaneko", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41386-018-0254-y" }, "pmcid": { "normalized": "PMC6372597" }, "pmid": { "normalized": "30377380" } }, "mesh": [ { "descriptor": "Adaptation, Psychological", "descriptor_ui": "D000223", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anxiety", "descriptor_ui": "D001007", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Dorsal Raphe Nucleus", "descriptor_ui": "D065847", "major_topic": false }, { "descriptor": "Electrophysiological Phenomena", "descriptor_ui": "D055724", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": false }, { "descriptor": "Lentivirus", "descriptor_ui": "D016086", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Serotonergic Neurons", "descriptor_ui": "D059326", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Mar", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "721-732", "proceedings_title": null, "publisher": "", "title": "Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology", "volume": "44", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Manipulation of dorsal raphe serotonergic neurons modulates active coping to inescapable stress and anxiety-related behaviors in mice and rats.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Anti-PD-1 therapy can induce eradication of tumors and immune-related adverse events (irAEs) in humans and model animals. However, how anti-PD-1 therapy modifies cellular phenotypes of CD8(+) T cells to destroy tumors and damage self-tissues remains to be clarified. Here we performed single cell mRNA expression profiling of autoreactive CD8(+) T cells under or beyond PD-1 suppression in target tissues and reconstructed their activation trajectory. Autoreactive CD8(+) T cells went through four activation phases and PD-1 strongly attenuated the transition from the second- to the third-phase, where effector functions were acquired. Shifts in cluster composition of autoreactive CD8(+) T cells markedly reflected the severity of autoimmunity. In addition, genes up-regulated along the activation-trajectory in autoimmunity were highly expressed in responders of melanoma patients in anti-PD-1 therapy, suggesting that tumor-specific T cells need to be activated in a similar trajectory to destroy tumors in human patients upon PD-1 blockade. These findings reveal that PD-1 blockade facilitates the activation trajectory of CD8(+) T cells to boost their effector functions. Targeted manipulation of the trajectory could lead to new therapeutic opportunities.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hikari", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Il-Mi", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Reina", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Okazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jaut.2019.06.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31277964" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Autoimmunity", "descriptor_ui": "D015551", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Melanoma", "descriptor_ui": "D008545", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Dec", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "102296", "proceedings_title": null, "publisher": "", "title": "Journal of autoimmunity", "volume": "105", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "PD-1 aborts the activation trajectory of autoreactive CD8(+) T cells to prohibit their acquisition of effector functions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Epidermal stem cells (ESCs) are keratinocytes that reside in the basal layer of the epidermis and mediate epidermal homeostasis. Insulin-like growth factor 1 (IGF-1) signaling through its receptor (IGF-1R) has been identified as an important regulator in rodent skin development and differentiation. However, the role of IGF-1/IGF-1R signaling in human keratinocytes is not yet well understood. OBJECTIVE: This study aimed to clarify the role of IGF-1/IGF-1R signaling in human epidermal homeostasis. METHODS: IGF-1R specific knockout (KO) HaCaT keratinocytes were generated by CRISPR-Caspase-9-mediated non-homologous end joining frame-shift mutations. Further, the behavior of these keratinocytes in epidermal homeostasis was investigated using reconstructed epidermis and human skin equivalents. RESULTS: IGF-1R KO HaCaT keratinocytes were successfully established and produced thin epidermis in three-dimensional culture models. Keratin10-positive cells were frequently found in the basal layer of the reconstructed epidermis. CONCLUSIONS: IGF-1/IGF-1R signaling was demonstrated to play a key role in maintaining human epidermal homeostasis. This method provides a new framework to investigate gene function in human epidermal homeostasis.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Taichi", "last_name": "Muraguchi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Nanba", "name": null }, { "creator_type": "author", "first_name": "Emi K.", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Tashiro", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jdermsci.2019.05.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31122679" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Epidermis", "descriptor_ui": "D004817", "major_topic": false }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin-Like Growth Factor I", "descriptor_ui": "D007334", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": false }, { "descriptor": "Receptor, IGF Type 1", "descriptor_ui": "D017526", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "298-305", "proceedings_title": null, "publisher": "", "title": "Journal of dermatological science", "volume": "94", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "IGF-1R deficiency in human keratinocytes disrupts epidermal homeostasis and stem cell maintenance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Image-based cell/colony analyses offer promising solutions to compensate for the lack of quality control (QC) tools for noninvasive monitoring of cultured cells, a regulatory challenge in regenerative medicine. Here, the feasibility of two image analysis algorithms, optical flow and normalised cross-correlation, to noninvasively measure cell/colony motion in human primary oral keratinocytes for screening the proliferative capacity of cells in the early phases of cell culture were examined. We applied our software to movies converted from 96 consecutive time-lapse phase-contrast images of an oral keratinocyte culture. After segmenting the growing colonies, two indices were calculated based on each algorithm. The correlation between each index of the colonies and their proliferative capacity was evaluated. The software was able to assess cell/colony motion noninvasively, and each index reflected the observed cell kinetics. A positive linear correlation was found between cell/colony motion and proliferative capacity, indicating that both algorithms are potential tools for QC.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Emi", "last_name": "Hoshikawa", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Kimori", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Haga", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Tabeta", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Nanba", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Izumi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1177/2041731419881528" }, "pmcid": { "normalized": "PMC6794654" }, "pmid": { "normalized": "31662840" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 Jan-Dec", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "2041731419881528", "proceedings_title": null, "publisher": "", "title": "Journal of tissue engineering", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Noninvasive measurement of cell/colony motion using image analysis methods to evaluate the proliferative capacity of oral keratinocytes as a tool for quality control in regenerative medicine.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: [(11) C]pyridinyl-butadienyl-benzothiazole 3 is a PET imaging agent designed for capturing pathological tau aggregates in diverse neurodegenerative disorders, and would be of clinical utility for neuropathological investigations of PSP. OBJECTIVES: To explore the usefulness of [(11) C]pyridinyl-butadienyl-benzothiazole 3/PET in assessing characteristic distributions of tau pathologies and their association with clinical symptoms in the brains of living PSP patients. METHODS: We assessed 13 PSP patients and 13 age-matched healthy control subjects. Individuals negative for amyloid beta PET with [(11) C]Pittsburgh compound B underwent clinical scoring, MR scans, and [(11) C]pyridinyl-butadienyl-benzothiazole 3/PET. RESULTS: There were significant differences in binding potential for [(11) C]pyridinyl-butadienyl-benzothiazole 3 between PSP patients and healthy control subjects (P = 0.02). PSP patients exhibited greater radioligand retention than healthy control subjects in multiple brain regions, including frontoparietal white matter, parietal gray matter, globus pallidus, STN, red nucleus, and cerebellar dentate nucleus. [(11) C]pyridinyl-butadienyl-benzothiazole 3 deposition in frontoparietal white matter, but not gray matter, was correlated with general severity of parkinsonian and PSP symptoms, whereas both gray matter and white matter [(11) C]pyridinyl-butadienyl-benzothiazole 3 accumulations in the frontoparietal cortices were associated with nonverbal cognitive impairments. Autoradiographic and fluorescence labeling with pyridinyl-butadienyl-benzothiazole 3 was observed in gray matter and white matter of PSP motor cortex tissues. CONCLUSIONS: Our findings support the in vivo detectability of tau fibrils characteristic of PSP by [(11) C]pyridinyl-butadienyl-benzothiazole 3/PET, and imply distinct and synergistic contributions of gray matter and white matte tau pathologies to clinical symptoms. [(11) C]pyridinyl-butadienyl-benzothiazole 3/PET potentially provides a neuroimaging-based index for the evolution of PSP tau pathologies promoting the deterioration of motor and cognitive functions. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hironobu", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Fumitoshi", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Ichise", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shinotoh", "name": null }, { "creator_type": "author", "first_name": "Ming Rong", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Dennis W.", "last_name": "Dickson", "name": null }, { "creator_type": "author", "first_name": "Tatsushi", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/mds.27643" }, "pmcid": { "normalized": "PMC6593859" }, "pmid": { "normalized": "30892739" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Aniline Compounds", "descriptor_ui": "D000814", "major_topic": false }, { "descriptor": "Autoradiography", "descriptor_ui": "D001345", "major_topic": false }, { "descriptor": "Benzothiazoles", "descriptor_ui": "D052160", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Carbon Radioisotopes", "descriptor_ui": "D002250", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Positron-Emission Tomography", "descriptor_ui": "D049268", "major_topic": false }, { "descriptor": "Supranuclear Palsy, Progressive", "descriptor_ui": "D013494", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Thiazoles", "descriptor_ui": "D013844", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "744-754", "proceedings_title": null, "publisher": "", "title": "Movement disorders : official journal of the Movement Disorder Society", "volume": "34", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "In vivo binding of a tau imaging probe, [(11) C]PBB3, in patients with progressive supranuclear palsy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "For early diagnosis of rheumatoid arthritis (RA), it is important to visualize its potential marker, vascularization in the synovial membrane of the finger joints. Photoacoustic (PA) imaging, which can image blood vessels at high contrast and resolution, is expected to be a potential modality for earlier diagnosis of RA. In previous studies of PA finger imaging, different acoustic schemes, such as linear-shaped arrays, have been utilized, but these have limited detection views, rendering inaccurate reconstruction, and most of them require rotational detection. We are developing a PA system for finger vascular imaging using a ring-shaped array ultrasound (US) transducer. By designing the ring-array sensor based on simulations, using phantom experiments, it was demonstrated that we have created a system that can image small objects around 0.1 to 0.5 mm in diameter. The full width at half maximum of the slice direction of the system was within 2 mm and corresponded to that of the simulation. Moreover, we could clearly visualize healthy index finger vasculature and the location of the distal interphalangeal and proximal interphalangeal joints by PA and US echo images. In the future, this system could be used as a method for visualizing the three-dimensional vascularization of RA patients' fingers.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Misaki", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Namita", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null } ], "identifiers": { "doi": { "normalized": "10.1117/1.jbo.24.9.096005" }, "pmcid": { "normalized": "PMC6997662" }, "pmid": { "normalized": "31535539" } }, "mesh": [ { "descriptor": "Arthritis, Rheumatoid", "descriptor_ui": "D001172", "major_topic": false }, { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Fingers", "descriptor_ui": "D005385", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Interpretation, Computer-Assisted", "descriptor_ui": "D007090", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Phantoms, Imaging", "descriptor_ui": "D019047", "major_topic": false }, { "descriptor": "Photoacoustic Techniques", "descriptor_ui": "D061088", "major_topic": false }, { "descriptor": "Transducers", "descriptor_ui": "D014159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "1-12", "proceedings_title": null, "publisher": "", "title": "Journal of biomedical optics", "volume": "24", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Ring-array photoacoustic tomography for imaging human finger vasculature.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An ultrasound (US) examination is a common noninvasive technique widely applied for diagnosis of a variety of diseases. Based on the rapid development of US equipment, many US images have been accumulated and are now available and ready for the preparation of a database for the development of computer-aided US diagnosis with deep learning technology. On the contrary, because of the unique characteristics of the US image, there could be some issues that need to be resolved for the establishment of computer-aided diagnosis (CAD) system in this field. For example, compared to the other modalities, the quality of a US image is, currently, highly operator dependent; the conditions of examination should also directly affect the quality of US images. So far, these factors have hampered the application of deep learning-based technology in the field of US diagnosis. However, the development of CAD and US technologies will contribute to an increase in diagnostic quality, facilitate the development of remote medicine, and reduce the costs in the national health care through the early diagnosis of diseases. From this point of view, it may have a large enough potential to induce a paradigm shift in the field of US imaging and diagnosis of liver diseases.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Naoshi", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Kudo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12072-019-09937-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30790230" } }, "mesh": [ { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": false }, { "descriptor": "Diagnosis, Computer-Assisted", "descriptor_ui": "D003936", "major_topic": false }, { "descriptor": "Forecasting", "descriptor_ui": "D005544", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver Diseases", "descriptor_ui": "D008107", "major_topic": false }, { "descriptor": "Ultrasonography", "descriptor_ui": "D014463", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jul", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "416-421", "proceedings_title": null, "publisher": "", "title": "Hepatology international", "volume": "13", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Current status and perspectives for computer-aided ultrasonic diagnosis of liver lesions using deep learning technology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Since induced pluripotent stem cells (iPSCs) were generated from mice and humans by Professor Shinya Yamanaka et al. in 2006 and 2007, respectively, a variety of human-derived cells have been generated, including myocardial, liver, retinal pigment epithelial, and neuronal cells. These iPSCs are now used not only in clinical research focusing on regeneration and transplantation in diverse medical fields, but also in molecular and cellular pathological studies. Importantly, by using human-derived iPSCs, it has become possible to conduct drug discovery research that more accurately models the pathology of human diseases. In research on psychiatric disorders, iPSC-related technologies, which have enabled the use of neuronal cells that carry the genetic information of the patients, will be important for elucidating not only the molecular and cellular etiology of psychiatric disorders but also the molecular mechanisms of drug action in these disorders. This review outlines the pharmacological research of psychiatric disorders that utilizes iPSC-related technologies.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphs.2019.06.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31257060" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Drug Discovery", "descriptor_ui": "D055808", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Mental Disorders", "descriptor_ui": "D001523", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "321-324", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "140", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Modeling of psychiatric disorders using induced pluripotent stem cell-related technologies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human keratinocyte cultures contain keratinocyte stem cells, and have been involved in significant progress regarding stem cell biology as well as keratinocyte biology. Such cultures have also been applied in cell therapy for extensive severe burns for more than three decades, and in genetic disorders of the skin recently. Human keratinocyte stem cells were firstly characterized as holoclones by ex post clonal analysis, but in situ identification of keratinocyte stem cells is required for clinical applications. Recently, it was demonstrated that human keratinocyte stem cells display a unique rotational motion at early stages of culture, with subsequent dynamic collective motion at later stages. This finding enables image-based identification of keratinocyte stem cells, and noninvasive evaluation of their proliferative capacity, which can be applied for the quality assurance of human keratinocyte cultures. This review summarizes the historical development of human keratinocyte cultures and its applications for cell biology and cell therapy. This article also introduces recent advances in keratinocyte stem cell research with medical relevance and discusses the next-generation of regenerative medicine using human keratinocyte stem cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Nanba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jdermsci.2019.10.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31669183" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autografts", "descriptor_ui": "D064592", "major_topic": false }, { "descriptor": "Burns", "descriptor_ui": "D002056", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell- and Tissue-Based Therapy", "descriptor_ui": "D064987", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Epidermal Cells", "descriptor_ui": "D000078404", "major_topic": false }, { "descriptor": "Epidermolysis Bullosa", "descriptor_ui": "D004820", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": true }, { "descriptor": "Regenerative Medicine", "descriptor_ui": "D044968", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Skin Physiological Phenomena", "descriptor_ui": "D012879", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Nov", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "66-72", "proceedings_title": null, "publisher": "", "title": "Journal of dermatological science", "volume": "96", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Human keratinocyte stem cells: From cell biology to cell therapy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Imbalance of neuronal proteostasis associated with misfolding and aggregation of Tau protein is a common neurodegenerative feature in Alzheimer’s disease (AD) and other Tauopathies. Consistent with suggestions that lifetime stress may be an important AD precipitating factor, we previously reported that environmental stress and high glucocorticoid (GC) levels induce accumulation of aggregated Tau; however, the molecular mechanisms for such process remain unclear. Herein, we monitor a novel interplay between RNA-binding proteins (RBPs) and autophagic machinery in the underlying mechanisms through which chronic stress and high GC levels impact on Tau proteostasis precipitating Tau aggregation. Using molecular, pharmacological and behavioral analysis, we demonstrate that chronic stress and high GC trigger mTOR-dependent inhibition of autophagy, leading to accumulation of Tau aggregates and cell death in P301L-Tau expressing mice and cells. In parallel, we found that environmental stress and GC disturb cellular homeostasis and trigger the insoluble accumulation of different RBPs, such as PABP, G3BP1, TIA-1, and FUS, shown to form stress granules (SGs) and Tau aggregation. Interestingly, an mTOR-driven pharmacological stimulation of autophagy attenuates the GC-driven accumulation of Tau and SG-related proteins as well as the related cell death, suggesting a critical interface between autophagy and the response of the SG-related protein in the neurodegenerative potential of chronic stress and GC. These studies provide novel insights into the RNA–protein intracellular signaling regulating the precipitating role of environmental stress and GC on Tau-driven brain pathology.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Joana Margarida", "last_name": "Silva", "name": null }, { "creator_type": "author", "first_name": "Sara", "last_name": "Rodrigues", "name": null }, { "creator_type": "author", "first_name": "Belém", "last_name": "Sampaio-Marques", "name": null }, { "creator_type": "author", "first_name": "Patrícia", "last_name": "Gomes", "name": null }, { "creator_type": "author", "first_name": "Andreia", "last_name": "Neves-Carvalho", "name": null }, { "creator_type": "author", "first_name": "Chrysoula", "last_name": "Dioli", "name": null }, { "creator_type": "author", "first_name": "Carina", "last_name": "Soares-Cunha", "name": null }, { "creator_type": "author", "first_name": "Brandon F.", "last_name": "Mazuik", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Paula", "last_name": "Ludovico", "name": null }, { "creator_type": "author", "first_name": "Benjamin", "last_name": "Wolozin", "name": null }, { "creator_type": "author", "first_name": "Nuno", "last_name": "Sousa", "name": null }, { "creator_type": "author", "first_name": "Ioannis", "last_name": "Sotiropoulos", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41418-018-0217-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30442948" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": true }, { "descriptor": "Heat-Shock Proteins", "descriptor_ui": "D006360", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "1411-1427", "proceedings_title": null, "publisher": "", "title": "Cell Death and Differentiation", "volume": "26", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Dysregulation of autophagy and stress granule-related proteins in stress-driven Tau pathology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tissue-clearing techniques are powerful tools for biological research and pathological diagnosis. Here, we describe advanced clear, unobstructed brain imaging cocktails and computational analysis (CUBIC) procedures that can be applied to biomedical research. This protocol enables preparation of high-transparency organs that retain fluorescent protein signals within 7-21 d by immersion in CUBIC reagents. A transparent mouse organ can then be imaged by a high-speed imaging system (>0.5 TB/h/color). In addition, to improve the understanding and simplify handling of the data, the positions of all detected cells in an organ (3-12 GB) can be extracted from a large image dataset (2.5-14 TB) within 3-12 h. As an example of how the protocol can be used, we counted the number of cells in an adult whole mouse brain and other distinct anatomical regions and determined the number of cells transduced with mCherry following whole-brain infection with adeno-associated virus (AAV)-PHP.eB. The improved throughput offered by this protocol allows analysis of numerous samples (e.g., >100 mouse brains per study), providing a platform for next-generation biomedical research.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Tomoki T.", "last_name": "Mitani", "name": null }, { "creator_type": "author", "first_name": "Shuhei A.", "last_name": "Horiguchi", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Kaneshiro", "name": null }, { "creator_type": "author", "first_name": "Tatsuya C.", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Fujishima", "name": null }, { "creator_type": "author", "first_name": "Ayumu", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Hiroki R.", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41596-019-0240-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31748753" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Coloring Agents", "descriptor_ui": "D004396", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Indicators and Reagents", "descriptor_ui": "D007202", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neuroimaging", "descriptor_ui": "D059906", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "3506-3537", "proceedings_title": null, "publisher": "", "title": "Nature protocols", "volume": "14", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Advanced CUBIC tissue clearing for whole-organ cell profiling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "mTORC2 plays critical roles in metabolism, cell survival and actin cytoskeletal dynamics through the phosphorylation of AKT. Despite its importance to biology and medicine, it is unclear how mTORC2-mediated AKT phosphorylation is controlled. Here, we identify an unforeseen principle by which a GDP-bound form of the conserved small G protein Rho GTPase directly activates mTORC2 in AKT phosphorylation in social amoebae (Dictyostelium discoideum) cells. Using biochemical reconstitution with purified proteins, we demonstrate that Rho-GDP promotes AKT phosphorylation by assembling a supercomplex with Ras-GTP and mTORC2. This supercomplex formation is controlled by the chemoattractant-induced phosphorylation of Rho-GDP at S192 by GSK-3. Furthermore, Rho-GDP rescues defects in both mTORC2-mediated AKT phosphorylation and directed cell migration in Rho-null cells in a manner dependent on phosphorylation of S192. Thus, in contrast to the prevailing view that the GDP-bound forms of G proteins are inactive, our study reveals that mTORC2-AKT signalling is activated by Rho-GDP.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Senoo", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Kamimura", "name": null }, { "creator_type": "author", "first_name": "Reona", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Sesaki", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Iijima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41556-019-0348-8" }, "pmcid": { "normalized": "PMC6650273" }, "pmid": { "normalized": "31263268" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cytoskeleton", "descriptor_ui": "D003599", "major_topic": false }, { "descriptor": "Dimerization", "descriptor_ui": "D019281", "major_topic": true }, { "descriptor": "Glycogen Synthase Kinase 3", "descriptor_ui": "D038362", "major_topic": false }, { "descriptor": "GTP-Binding Proteins", "descriptor_ui": "D019204", "major_topic": false }, { "descriptor": "Guanosine Diphosphate", "descriptor_ui": "D006153", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mechanistic Target of Rapamycin Complex 2", "descriptor_ui": "D000076225", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "867-878", "proceedings_title": null, "publisher": "", "title": "Nature cell biology", "volume": "21", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Phosphorylated Rho-GDP directly activates mTORC2 kinase towards AKT through dimerization with Ras-GTP to regulate cell migration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Graft-versus host disease (GVHD) is a complication of stem cell transplantation associated with significant morbidity and mortality. Non-specific immune-suppression, the mainstay of treatment, may result in immune-surveillance dysfunction and disease recurrence. Methods: We created humanised mice model for chronic GVHD (cGVHD) by injecting cord blood (CB)-derived human CD34+CD38−CD45RA− haematopoietic stem/progenitor cells (HSPCs) into hIL-6 transgenic NOD/SCID/Il2rgKO (NSG) newborns, and compared GVHD progression with NSG newborns receiving CB CD34− cells mimicking acute GVHD. We characterised human immune cell subsets, target organ infiltration, T-cell repertoire (TCR) and transcriptome in the humanised mice. Findings: In cGVHD humanised mice, we found activation of T cells in the spleen, lung, liver, and skin, activation of macrophages in lung and liver, and loss of appendages in skin, obstruction of bronchioles in lung and portal fibrosis in liver recapitulating cGVHD. Acute GVHD humanised mice showed activation of T cells with skewed TCR repertoire without significant macrophage activation. Interpretation: Using humanised mouse models, we demonstrated distinct immune mechanisms contributing acute and chronic GVHD. In cGVHD model, co-activation of human HSPC-derived macrophages and T cells educated in the recipient thymus contributed to delayed onset, multi-organ disease. In acute GVHD model, mature human T cells contained in the graft resulted in rapid disease progression. These humanised mouse models may facilitate future development of new molecular medicine targeting GVHD.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Rintaro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Tomizawa-Murasawa", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yuho", "last_name": "Najima", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Saera", "last_name": "Fujiki", "name": null }, { "creator_type": "author", "first_name": "Rumi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Hisahiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Yabe", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yoriko", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Leonard D.", "last_name": "Shultz", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Ohara", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Amagai", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Koseki", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Ishikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ebiom.2019.02.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30772305" } }, "mesh": [ { "descriptor": "Acute Disease", "descriptor_ui": "D000208", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Chronic Disease", "descriptor_ui": "D002908", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Graft vs Host Disease", "descriptor_ui": "D006086", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cell Transplantation", "descriptor_ui": "D018380", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interleukin Receptor Common gamma Subunit", "descriptor_ui": "D053631", "major_topic": false }, { "descriptor": "Interleukin-6", "descriptor_ui": "D015850", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Mice, SCID", "descriptor_ui": "D016513", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Survival Rate", "descriptor_ui": "D015996", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Mar", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "584-596", "proceedings_title": null, "publisher": "", "title": "EBioMedicine", "volume": "41", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Co-activation of macrophages and T cells contribute to chronic GVHD in human IL-6 transgenic humanised mouse model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stem cells underlie tissue homeostasis, but their dynamics during ageing-and the relevance of these dynamics to organ ageing-remain unknown. Here we report that the expression of the hemidesmosome component collagen XVII (COL17A1) by epidermal stem cells fluctuates physiologically through genomic/oxidative stress-induced proteolysis, and that the resulting differential expression of COL17A1 in individual stem cells generates a driving force for cell competition. In vivo clonal analysis in mice and in vitro 3D modelling show that clones that express high levels of COL17A1, which divide symmetrically, outcompete and eliminate adjacent stressed clones that express low levels of COL17A1, which divide asymmetrically. Stem cells with higher potential or quality are thus selected for homeostasis, but their eventual loss of COL17A1 limits their competition, thereby causing ageing. The resultant hemidesmosome fragility and stem cell delamination deplete adjacent melanocytes and fibroblasts to promote skin ageing. Conversely, the forced maintenance of COL17A1 rescues skin organ ageing, thereby indicating potential angles for anti-ageing therapeutic intervention.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Nan", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Shizuko", "last_name": "Ichinose", "name": null }, { "creator_type": "author", "first_name": "Aki", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Namiki", "name": null }, { "creator_type": "author", "first_name": "Kyosuke", "last_name": "Asakawa", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Morinaga", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Mohri", "name": null }, { "creator_type": "author", "first_name": "Adele", "last_name": "De Arcangelis", "name": null }, { "creator_type": "author", "first_name": "Elisabeth", "last_name": "Geroges-Labouesse", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Nanba", "name": null }, { "creator_type": "author", "first_name": "Emi K.", "last_name": "Nishimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41586-019-1085-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30944469" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Atrophy", "descriptor_ui": "D001284", "major_topic": false }, { "descriptor": "Autoantigens", "descriptor_ui": "D001324", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Clone Cells", "descriptor_ui": "D002999", "major_topic": false }, { "descriptor": "Collagen Type XVII", "descriptor_ui": "D000097805", "major_topic": false }, { "descriptor": "Epidermal Cells", "descriptor_ui": "D000078404", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "Hemidesmosomes", "descriptor_ui": "D022002", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Models, Animal", "descriptor_ui": "D023421", "major_topic": false }, { "descriptor": "Non-Fibrillar Collagens", "descriptor_ui": "D024041", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Proteolysis", "descriptor_ui": "D059748", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Skin Aging", "descriptor_ui": "D015595", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr", "date_precision": "unknown", "issue": "7752", "normalized_date": null, "pages": "344-350", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "568", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Stem cell competition orchestrates skin homeostasis and ageing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: To investigate whether maternal chewing during prenatal stress alters the responsivity of young offspring to novel stress, we examined the expression of hippocampal glucocorticoid receptors and mineralocorticoid receptors, and the levels of hypothalamic corticotropin-releasing hormone in young adult mouse offspring of dams exposed to restraint stress during pregnancy. DESIGN: To induce stress, the dams were placed in a ventilated restraint tube for 45 min each day from day 12 of pregnancy through parturition. While restrained in the tube, one group of dams was provided a wooden stick for chewing. Hippocampal expression of glucocorticoid receptor and mineralocorticoid receptor messenger ribonucleic acid was assessed in 1-month-old pups. Hypothalamic expression of corticotropin-releasing hormone messenger ribonucleic acid was examined before and after exposing the offspring to a novel stressor. RESULTS: Prenatal stress significantly decreased hippocampal expression of both glucocorticoid receptor and mineralocorticoid receptor messenger ribonucleic acid in the offspring, and increased the expression of corticotropin-releasing hormone messenger ribonucleic acid in the hypothalamic paraventricular nucleus in the offspring after novel stress exposure. Maternal chewing during exposure to prenatal stress attenuated the decreased hippocampal expression of both glucocorticoid receptor and mineralocorticoid receptor messenger ribonucleic acid, and the increased corticotropin-releasing hormone messenger ribonucleic acid expression in the hypothalamic paraventricular nucleus in the offspring. CONCLUSIONS: Downregulation of hippocampal glucocorticoid receptor and mineralocorticoid receptor expression in offspring due to prenatal stress, which may be associated with increased susceptibility to novel stress in adulthood, are attenuated by allowing the dams to chew on a wooden stick.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kin-Ya", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Mitsuo", "last_name": "Iinuma", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Nagashio", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Kagaku", "last_name": "Azuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.archoralbio.2018.10.014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30390464" } }, "mesh": [ { "descriptor": "Adaptation, Psychological", "descriptor_ui": "D000223", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Corticotropin-Releasing Hormone", "descriptor_ui": "D003346", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Mastication", "descriptor_ui": "D008409", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Pregnancy Complications", "descriptor_ui": "D011248", "major_topic": false }, { "descriptor": "Prenatal Exposure Delayed Effects", "descriptor_ui": "D011297", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "Receptors, Glucocorticoid", "descriptor_ui": "D011965", "major_topic": false }, { "descriptor": "Receptors, Mineralocorticoid", "descriptor_ui": "D018161", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Stress, Psychological", "descriptor_ui": "D013315", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "150-155", "proceedings_title": null, "publisher": "", "title": "Archives of oral biology", "volume": "97", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Vulnerability to stress in mouse offspring is ameliorated when pregnant dams are provided a chewing stick during prenatal stress.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chromatin plays a crucial role in gene regulation, and chromatin immunoprecipitation followed by sequencing (ChIP-seq) has been the standard technique for examining protein-DNA interactions across the whole genome. However, it is difficult to obtain epigenomic information from limited numbers of cells by ChIP-seq because of sample loss during chromatin preparation and inefficient immunoprecipitation. In this study, we established an immunoprecipitation-free epigenomic profiling method named chromatin integration labelling (ChIL), which enables the amplification of genomic sequences closely associated with the target molecules before cell lysis. Using ChIL followed by sequencing (ChIL-seq), we reliably detected the distributions of histone modifications and DNA-binding factors in 100-1,000 cells. In addition, ChIL-seq successfully detected genomic regions associated with histone marks at the single-cell level. Thus, ChIL-seq offers an alternative method to ChIP-seq for epigenomic profiling using small numbers of cells, in particular, those attached to culture plates and after immunofluorescence.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Handa", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Arimura", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Nogami", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Hayashi-Takanaka", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Shirahige", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurumizaka", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41556-018-0248-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30532068" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "DNA Probes", "descriptor_ui": "D015342", "major_topic": false }, { "descriptor": "Epigenomics", "descriptor_ui": "D057890", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lysine", "descriptor_ui": "D008239", "major_topic": false }, { "descriptor": "MCF-7 Cells", "descriptor_ui": "D061986", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myoblasts", "descriptor_ui": "D032446", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Sequence Analysis, DNA", "descriptor_ui": "D017422", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "287-296", "proceedings_title": null, "publisher": "", "title": "Nature cell biology", "volume": "21", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "A chromatin integration labelling method enables epigenomic profiling with lower input.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We used single-cell RNA sequencing (seq) on several human induced pluripotent stem (iPS) cell-derived neural stem cell (NSC) lines and one fetal brain-derived NSC line to study inherent cell type heterogeneity at proliferating neural stem cell stage and uncovered predisposed presence of neurogenic and gliogenic progenitors. We observed heterogeneity in neurogenic progenitors that differed between the iPS cell-derived NSC lines and the fetal-derived NSC line, and we also observed differences in spontaneous differentiation potential for inhibitory and excitatory neurons between the iPS cell-derived NSC lines and the fetal-derived NSC line. In addition, using a recently published glia patterning protocol we enriched for gliogenic progenitors and generated glial cells from an iPS cell-derived NSC line.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Matti", "last_name": "Lam", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Sanosaka", "name": null }, { "creator_type": "author", "first_name": "Anders", "last_name": "Lundin", "name": null }, { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Damla", "last_name": "Etal", "name": null }, { "creator_type": "author", "first_name": "Fredrik H.", "last_name": "Karlsson", "name": null }, { "creator_type": "author", "first_name": "Maryam", "last_name": "Clausen", "name": null }, { "creator_type": "author", "first_name": "Jonathan", "last_name": "Cairns", "name": null }, { "creator_type": "author", "first_name": "Ryan", "last_name": "Hicks", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Kohyama", "name": null }, { "creator_type": "author", "first_name": "Malin", "last_name": "Kele", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Falk", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.12731" }, "pmcid": { "normalized": "PMC6916357" }, "pmid": { "normalized": "31651061" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Human Embryonic Stem Cells", "descriptor_ui": "D000066449", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": true }, { "descriptor": "Neuroglia", "descriptor_ui": "D009457", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "836-847", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "24", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-cell study of neural stem cells derived from human iPSCs reveals distinct progenitor populations with neurogenic and gliogenic potential.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nilotinib is widely used for primary treatment of patients with chronic myelogenous leukemia (CML). We previously reported that use of an FRET-based drug sensitivity test at diagnosis efficiently predicts the response to treatment with imatinib or dasatinib. Here, we conducted a phase-II study to evaluate the efficacy and safety of nilotinib treatment and identify useful biomarkers, including results of the FRET-based drug sensitivity test, for predicting treatment response. Data from 42 patients were used in the analysis. Major molecular response (MMR), MR4, and MR4.5 rates at 12 months were 64.3, 42.9, and 28.6%, respectively. Grade 3/4 non-hematologic adverse events occurred in 11 patients (26.2%). The dose intensity of nilotinib (> 76.44%) and halving time (HT, < 13.312 days) were identified as significant factors for MMR at 12 months. However, when we focused on patients whose dose intensity of nilotinib was > 76.44%, the FRET-based drug sensitivity test became a predictive factor of MR4 achievement at 12 months. Our study reconfirmed the efficacy and safety of nilotinib treatment in CML patients. Moreover, our results suggest that the FRET-based drug sensitivity test is an independent predictor for achievement of MR4 in patients treated with a sufficient dose intensity of nilotinib.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Fujisawa", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Takuto", "last_name": "Miyagishima", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Yasutaka", "last_name": "Kakinoki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshihito", "last_name": "Haseyama", "name": null }, { "creator_type": "author", "first_name": "Seisho", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Mitsutoshi", "last_name": "Kurosawa", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Teshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12185-019-02696-w" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31240558" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": true }, { "descriptor": "Drug Screening Assays, Antitumor", "descriptor_ui": "D004354", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia, Myelogenous, Chronic, BCR-ABL Positive", "descriptor_ui": "D015464", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Predictive Value of Tests", "descriptor_ui": "D011237", "major_topic": false }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Oct", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "482-489", "proceedings_title": null, "publisher": "", "title": "International journal of hematology", "volume": "110", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical efficacy and safety of first-line nilotinib therapy and evaluation of the clinical utility of the FRET-based drug sensitivity test.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A 26-year-old woman with a history of feeling nauseated during dental local anesthesia presented to our clinic for tooth extraction under intravenous sedation. Although she had experienced episodes of neurally-mediated syncope, her symptoms were controlled well with drug therapy, stopped 3 years earlier. No syncope episodes developed over the previous 2 years. Tooth extraction was performed under intravenous sedation without incident. When she was returned to a sitting position after being roused, convulsion, loss of consciousness, and cardiac arrest developed. One week later, similar symptoms occurred immediately after suture removal. We suspect that the change in body position triggered these episodes. It is important to avoid abrupt changes in body position and any other triggers and to administer preventive drugs in patients at high risk of syncope.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kaoruko", "last_name": "Hamazaki", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Akari", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Yoneda", "name": null }, { "creator_type": "author", "first_name": "Nahoka", "last_name": "Miyatani", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Momota", "name": null } ], "identifiers": { "doi": { "normalized": "10.2344/anpr-66-01-04" }, "pmcid": { "normalized": "PMC6424170" }, "pmid": { "normalized": "30883228" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Anesthesia, Dental", "descriptor_ui": "D000766", "major_topic": true }, { "descriptor": "Electrocardiography", "descriptor_ui": "D004562", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Heart Arrest", "descriptor_ui": "D006323", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Syncope", "descriptor_ui": "D013575", "major_topic": false }, { "descriptor": "Syncope, Vasovagal", "descriptor_ui": "D019462", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019 Spring", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "33-36", "proceedings_title": null, "publisher": "", "title": "Anesthesia progress", "volume": "66", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "A Case of Cardiac Arrest for 31 Seconds During Recovery After Intravenous Sedation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with neuroprotective and neurotrophic effects. This suggests its influence on the development of teeth, which are, similarly to the nervous system, ectoderm and neural crest derivatives. Our earlier studies have shown morphological differences between wild-type (WT) and PACAP-deficient mice, with upregulated sonic hedgehog (SHH) signaling in the lack of PACAP. Notch signaling is a key element of proper tooth development by regulating apoptosis and cell proliferation. In this study, our main goal was to evaluate the possible effects of PACAP on Notch signaling pathway. Immunohistochemical staining was performed of Notch receptors (Notch1, 2, 3, 4), their ligands [delta-like protein (DLL)1, 3, 4, Jagged1, 2], and intracellular target molecules [CSL (CBF1 humans/Su (H) Drosophila/LAG1 Caenorhabditis elegans transcription factor); TACE (TNF-alpha converting enzyme), NUMB] in molar teeth of 5-day-old WT, and homozygous and heterozygous PACAP-deficient mice. We measured immunopositivity in the enamel-producing ameloblasts and dentin-producing odontoblasts. Notch2 receptor and DLL1 expression were elevated in ameloblasts of PACAP-deficient mice compared to those in WT ones. The expression of CSL showed similar results both in the ameloblasts and odontoblasts. Jagged1 ligand expression was elevated in the odontoblasts of homozygous PACAP-deficient mice compared to WT mice. Other Notch pathway elements did not show significant differences between the genotype groups. The lack of PACAP leads to upregulation of Notch pathway elements in the odontoblast and ameloblast cells. The underlying molecular mechanisms are yet to be elucidated; however, we propose SHH-dependent and independent processes. We hypothesize that this compensatory upregulation of Notch signaling by the lack of PACAP could represent a salvage pathway in PACAP-deficient animals.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "B. D.", "last_name": "Fulop", "name": null }, { "creator_type": "author", "first_name": "B.", "last_name": "Sandor", "name": null }, { "creator_type": "author", "first_name": "E.", "last_name": "Szentleleky", "name": null }, { "creator_type": "author", "first_name": "E.", "last_name": "Karanyicz", "name": null }, { "creator_type": "author", "first_name": "D.", "last_name": "Reglodi", "name": null }, { "creator_type": "author", "first_name": "B.", "last_name": "Gaszner", "name": null }, { "creator_type": "author", "first_name": "R.", "last_name": "Zakany", "name": null }, { "creator_type": "author", "first_name": "H.", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "T.", "last_name": "Juhasz", "name": null }, { "creator_type": "author", "first_name": "A.", "last_name": "Tamas", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12031-018-1146-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30094580" } }, "mesh": [ { "descriptor": "Ameloblasts", "descriptor_ui": "D000565", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium-Binding Proteins", "descriptor_ui": "D002135", "major_topic": false }, { "descriptor": "Jagged-1 Protein", "descriptor_ui": "D000072100", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molar", "descriptor_ui": "D008963", "major_topic": false }, { "descriptor": "Odontoblasts", "descriptor_ui": "D009804", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Receptor, Notch1", "descriptor_ui": "D051881", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jul", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "377-388", "proceedings_title": null, "publisher": "", "title": "Journal of molecular neuroscience : MN", "volume": "68", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Altered Notch Signaling in Developing Molar Teeth of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP)-Deficient Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The proton motive force (PMF) across the chloroplast thylakoid membrane that is generated by electron transport during photosynthesis is the driving force for ATP synthesis in plants. The PMF mainly arises from the oxidation of water in photosystem II and from electron transfer within the cytochrome b(6)f complex. There are two electron transfer pathways related to PMF formation: linear electron flow and cyclic electron flow. Proton gradient regulation 5 (PGR5) is a major component of the cyclic electron flow pathway, and the Arabidopsis pgr5 mutant shows a substantial reduction in the PMF. How the PGR5-dependent cyclic electron flow contributes to ATP synthesis has not, however, been fully delineated. In this study, we monitored in vivo ATP levels in Arabidopsis chloroplasts in real time using a genetically encoded bioluminescence-based ATP indicator, Nano-lantern(ATP1). The increase in ATP in the chloroplast stroma of pgr5 leaves upon illumination with actinic light was significantly slower than in wild type, and the decrease in ATP levels when this illumination stopped was significantly faster in pgr5 leaves than in wild type. These results indicated that PGR5-dependent cyclic electron flow around photosystem I helps to sustain the rate of ATP synthesis, which is important for growth under fluctuating light conditions.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Rinya", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Mai Duy Luu", "last_name": "Trinh", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Masuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s11120-018-0533-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29916043" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Chloroplasts", "descriptor_ui": "D002736", "major_topic": false }, { "descriptor": "Electron Transport", "descriptor_ui": "D004579", "major_topic": false }, { "descriptor": "Photosynthesis", "descriptor_ui": "D010788", "major_topic": false }, { "descriptor": "Photosynthetic Reaction Center Complex Proteins", "descriptor_ui": "D045322", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Mar", "date_precision": "unknown", "issue": "1-3", "normalized_date": null, "pages": "359-365", "proceedings_title": null, "publisher": "", "title": "Photosynthesis research", "volume": "139", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Significance of PGR5-dependent cyclic electron flow for optimizing the rate of ATP synthesis and consumption in Arabidopsis chloroplasts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Change in the intracellular redox state is a consequence of various metabolic reactions, which simultaneously regulates various physiological phenomena in cells. Monitoring the redox state in living cells is thus very important for understanding cellular physiology. Various genetically encoded fluorescent redox sensors have therefore been developed. Recently, we developed oxidation-sensitive fluorescent proteins named Oba-Q (Sugiura, K., et al. (2015) Biochem. Biophys. Res. Commun. 457, 242-248), which exhibit dramatic quenching under oxidizing conditions. To extend the range of uses of redox sensor proteins, we refined these proteins based on the molecular architecture applied to Oba-Q, and successfully produced several redox sensor proteins based on CFP and YFP. Interestingly, some of these sensor proteins showed the reverse changes in emission compared with Oba-Q, implying remarkable fluorescence quenching under reducing conditions. We named this type of sensor protein Re-Q, reduction-sensed quenching protein. The cause of the redox-dependent fluorescence quenching could be clearly explained based on the crystal structure of Re-Q in the reduced and oxidized forms. In addition, by introducing suitable mutations into the sensors, we produced Oba-Q and Re-Q mutants exhibiting various midpoint redox potentials. This series of proteins can cover a wide range of redox potentials in the cell, so they should be applicable to various cells and even intracellular organelles. As an example, we successfully measured the redox responses in different cell compartments of cultured mammalian cells simultaneously against the anticancer reagents Kp372-1.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Genji", "last_name": "Kurisu", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbagen.2019.01.016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30953671" } }, "mesh": [ { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": true }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "1098-1107", "proceedings_title": null, "publisher": "", "title": "Biochimica et biophysica acta. General subjects", "volume": "1863", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Multicolor redox sensor proteins can visualize redox changes in various compartments of the living cell.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Excess energy intake causes obesity, which leads to insulin resistance and various other complications of metabolic syndrome, including diabetes, atherosclerosis, dyslipidemia, and nonalcoholic fatty liver disease. Although recent studies have depicted altered lipid metabolism as an underlying feature, the detailed mechanisms are still unclear. Here we describe a possible role in high-fat diet (HFD)-induced obesity for monoacylglycerol lipase (MGL), an enzyme that is also known to hydrolyze the endocannabinoid 2-arachidonoylglycerol in brain. MGL-deficient [MGL-knockout (KO)] mice fed a HFD gained less body weight than wild-type mice and were protected from insulin resistance and hepatic steatosis. Food intake and energy expenditure were not altered in MGL-KO mice, but blood triglyceride levels after oral olive oil gavage were suppressed, indicating a role for MGL in intestinal fat absorption. Experiments with cannabinoid receptor type 1 (CB(1))/MGL double-KO mice revealed that these phenotypes may include mechanisms that are independent of CB(1)-receptor-mediated endocannabinoid functions. We also noted that MGL-KO mice had less preference for HFD over normal chow diet. Oral but not intraperitoneal lipid administration strongly suppressed the appetites of MGL-KO and CB(1)/MGL double-KO mice, but not of wild-type and CB(1)-KO mice. Appetite suppression was reversed by vagotomy, suggesting involvement of MGL in the gut-brain axis regulation of appetite. Our results provide mechanistic insights of MGL's role in diet-induced obesity, lipid metabolic disorder, and regulation of appetite.-Yoshida, K., Kita, Y., Tokuoka, S. M., Hamano, F., Yamazaki, M., Sakimura, K., Kano, M., Shimizu, T. Monoacylglycerol lipase deficiency affects diet-induced obesity, fat absorption, and feeding behavior in CB(1) cannabinoid receptor-deficient mice.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Suzumi M.", "last_name": "Tokuoka", "name": null }, { "creator_type": "author", "first_name": "Fumie", "last_name": "Hamano", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Shimizu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1096/fj.201801203r" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30265576" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Asialoglycoproteins", "descriptor_ui": "D001212", "major_topic": false }, { "descriptor": "Body Weight", "descriptor_ui": "D001835", "major_topic": false }, { "descriptor": "Diet, High-Fat", "descriptor_ui": "D059305", "major_topic": false }, { "descriptor": "Eating", "descriptor_ui": "D004435", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Fatty Liver", "descriptor_ui": "D005234", "major_topic": false }, { "descriptor": "Feeding Behavior", "descriptor_ui": "D005247", "major_topic": true }, { "descriptor": "Insulin Resistance", "descriptor_ui": "D007333", "major_topic": false }, { "descriptor": "Intestinal Absorption", "descriptor_ui": "D007408", "major_topic": true }, { "descriptor": "Lectins, C-Type", "descriptor_ui": "D037181", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Receptor, Cannabinoid, CB1", "descriptor_ui": "D043884", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "2484-2497", "proceedings_title": null, "publisher": "", "title": "FASEB journal : official publication of the Federation of American Societies for Experimental Biology", "volume": "33", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Monoacylglycerol lipase deficiency affects diet-induced obesity, fat absorption, and feeding behavior in CB(1) cannabinoid receptor-deficient mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Growing evidence suggests pivotal roles for epigenetic mechanisms in both animal models of and individuals with autism spectrum disorders (ASD). Neuron-restrictive silencer factor (NRSF) binds to neuron-restrictive silencing elements in neuronal genes and recruits co-repressors, such as mSin3, to epigenetically inhibit neuronal gene expression. Because dysregulation of NRSF is related to ASD, here we examined the effects of mS-11, a chemically optimized mimetic of the mSin3-binding helix in NRSF, on the behavioral and morphological abnormalities found in a mouse model of valproic acid (VPA)-induced ASD. Chronic treatment with mS-11 improved prenatal VPA-induced deficits in social interaction. Additionally, we found that NRSF mRNA expression was greater in the somatosensory cortex of VPA-exposed mice than of controls. Agreeing with these behavioral findings, mice that were prenatally exposed to VPA showed lower dendritic spine density in the somatosensory cortex, which was reversed by chronic treatment with mS-11. These findings suggest that mS-11 has the potential for improving ASD-related symptoms through inhibition of mSin3-NRSF binding.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Haruki", "last_name": "Kawase", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Momoko", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Mishina", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kouji", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.pbb.2018.11.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30419271" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autistic Disorder", "descriptor_ui": "D001321", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Heterocyclic Compounds, 2-Ring", "descriptor_ui": "D006574", "major_topic": false }, { "descriptor": "Interpersonal Relations", "descriptor_ui": "D007398", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Prenatal Exposure Delayed Effects", "descriptor_ui": "D011297", "major_topic": false }, { "descriptor": "RE1-Silencing Transcription Factor", "descriptor_ui": "D000099229", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Somatosensory Cortex", "descriptor_ui": "D013003", "major_topic": false }, { "descriptor": "Valproic Acid", "descriptor_ui": "D014635", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "1-5", "proceedings_title": null, "publisher": "", "title": "Pharmacology, biochemistry, and behavior", "volume": "176", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "mS-11, a mimetic of the mSin3-binding helix in NRSF, ameliorates social interaction deficits in a prenatal valproic acid-induced autism mouse model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To elucidate the role of Hox genes in limb cartilage development, we identified the target genes of HOXA11 and HOXA13 by ChIP-Seq. The ChIP DNA fragment contained evolutionarily conserved sequences and multiple highly conserved HOX binding sites. A substantial portion of the HOXA11 ChIP fragment overlapped with the HOXA13 ChIP fragment indicating that both factors share common targets. Deletion of the target regions neighboring Bmp2 or Tshz2 reduced their expression in the autopod suggesting that they function as the limb bud-specific enhancers. We identified the Hox downstream genes as exhibiting expression changes in the Hoxa13 knock out (KO) and Hoxd11-13 deletion double mutant (Hox13 dKO) autopod by Genechip analysis. The Hox downstream genes neighboring the ChIP fragment were defined as the direct targets of Hox. We analyzed the spatial expression pattern of the Hox target genes that encode two different categories of transcription factors during autopod development and Hox13dKO limb bud. (a) Bcl11a, encoding a repressor of cartilage differentiation, was expressed in the E11.5 autopod and was substantially reduced in the Hox13dKO. (b) The transcription factors Aff3, Bnc2, Nfib and Runx1t1 were expressed in the zeugopodal cartilage but not in the autopod due to the repressive or relatively weak transcriptional activity of Hox13 at E11.5. Interestingly, the expression of these genes was later observed in the autopodal cartilage at E12.5. These results indicate that Hox13 transiently suspends the cartilage differentiation in the autopodal anlage via multiple pathways until establishing the paddle-shaped structure required to generate five digits.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shiori", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Ohtani", "name": null }, { "creator_type": "author", "first_name": "Erina", "last_name": "Nozaki", "name": null }, { "creator_type": "author", "first_name": "Chunyang", "last_name": "Yin", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Gotoh", "name": null }, { "creator_type": "author", "first_name": "Nayuta", "last_name": "Yakushiji-Kaminatsui", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Yo-Ichi", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kuroiwa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12601" }, "pmcid": { "normalized": "PMC6850407" }, "pmid": { "normalized": "30895612" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Chickens", "descriptor_ui": "D002645", "major_topic": false }, { "descriptor": "Chromatin Immunoprecipitation", "descriptor_ui": "D047369", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "228-251", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "61", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Hoxa13 regulates expression of common Hox target genes involved in cartilage development to coordinate the expansion of the autopodal anlage.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stimuli-responsive smart materials are a key to the realization of next-generation medical technologies. Among them, the temperature-responsive polymer poly(N-isopropylacrylamide) (PNIPAAm) is attracting particular attention because it is easy to use in physiological conditions. PNIPAAm-grafted surfaces can undergo temperature-modulated cell adhesion and detachment without proteolytic enzymes, and can be used as cell-separating materials through selective cell adhesion/detachment. However, cell detachment at reduced temperatures is problematic because it takes several hours. A novel thermoresponsive crosslinked microfiber system that can greatly reduce the cell detachment time is introduced in this study. The crosslinked fibers provide temperature-dependent volume change, and enable cell detachment within 10 min of reducing the temperature, which is one-sixth of the time required in previous studies. The prompt cell detachment is thought to arise from a completely new mechanism derived from fiber swelling. This system will make a significant contribution as a novel cell manipulating system for next-generation medical technology.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tomomi", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Mizutani Akimoto", "name": null }, { "creator_type": "author", "first_name": "Taihei", "last_name": "Nishimoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Tokura", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Tenjimbayashi", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Homma", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Matsukawa", "name": null }, { "creator_type": "author", "first_name": "Taisei", "last_name": "Kaku", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nagase", "name": null }, { "creator_type": "author", "first_name": "Hideko", "last_name": "Kanazawa", "name": null }, { "creator_type": "author", "first_name": "Seimei", "last_name": "Shiratori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/marc.201900464" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31692103" } }, "mesh": [ { "descriptor": "Acrylic Resins", "descriptor_ui": "D000180", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biocompatible Materials", "descriptor_ui": "D001672", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cross-Linking Reagents", "descriptor_ui": "D003432", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "Particle Size", "descriptor_ui": "D010316", "major_topic": false }, { "descriptor": "Surface Properties", "descriptor_ui": "D013499", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Dec", "date_precision": "unknown", "issue": "23", "normalized_date": null, "pages": "e1900464", "proceedings_title": null, "publisher": "", "title": "Macromolecular rapid communications", "volume": "40", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Crosslinked Poly(N-Isopropylacrylamide)-Based Microfibers as Cell Manipulation Materials with Prompt Cell Detachment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "NEW FINDINGS: What is the central question of this study? The effects of Ca(2+) responses on salivary fluid secretion have been studied indirectly by monitoring ion channel activities and other indices. Therefore, Ca(2+) responses during salivary secretion remain poorly understood. What is the main finding and its importance? Herein, we developed a simultaneous monitoring system for Ca(2+) responses and salivary secretion in live animals using a YC-Nano50-expressing submandibular gland and a fibre-optic pressure sensor. This new approach revealed a clear time lag between the onset of Ca(2+) responses and salivary secretion. We also estimated the [Ca(2+) ](i) and provided direct evidence for the regulation of salivary secretion by small increases in [Ca(2+) ](i) in submandibular gland acinar cells. ABSTRACT: We monitored changes in [Ca(2+) ](i) during salivary secretion in the rat submandibular gland in live animals using a combination of intravital Ca(2+) imaging with the ultrasensitive Ca(2+) indicator YC-Nano50 and a fibre-optic pressure sensor. Intravenous infusion of ACh (10-720 nmol min(-1) ) increased [Ca(2+) ](i) and salivary flow rate in a dose-dependent manner. Repetitive stimulation with ACh induced equivalent Ca(2+) responses and salivary secretion in the same individual animals. The accurate ACh stimulation experiments revealed a clear time lag between the onset of the increase in [Ca(2+) ](i) and salivary secretion. The time lag with the lowest dose of ACh (30 nmol min(-1) ) was 106 s, which shortened to 19 s with the dose used for maximal salivary secretion (360 nmol min(-1) ). This time lag might reflect the time required for [Ca(2+) ](i) to reach the level required to activate molecules for fluid secretion. The resting [Ca(2+) ](i) in submandibular gland was 37 nm, and [Ca(2+) ](i) at the onset of salivary secretion was 45-57 nm, irrespective of ACh dose. These results indicate that low [Ca(2+) ](i) is sufficient to trigger fluid secretion in the rat submandibular gland in vivo.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Akihiro", "last_name": "Nezu", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Tanimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1113/ep086868" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30367746" } }, "mesh": [ { "descriptor": "Acinar Cells", "descriptor_ui": "D061354", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Ion Transport", "descriptor_ui": "D017136", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Saliva", "descriptor_ui": "D012463", "major_topic": false }, { "descriptor": "Salivation", "descriptor_ui": "D012472", "major_topic": false }, { "descriptor": "Submandibular Gland", "descriptor_ui": "D013363", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "61-69", "proceedings_title": null, "publisher": "", "title": "Experimental physiology", "volume": "104", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Simultaneous monitoring of Ca(2+) responses and salivary secretion in live animals reveals a threshold intracellular Ca(2+) concentration for salivation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The utility of human pluripotent stem cell-derived kidney organoids relies implicitly on the robustness and transferability of the protocol. Here we analyze the sources of transcriptional variation in a specific kidney organoid protocol. Although individual organoids within a differentiation batch showed strong transcriptional correlation, we noted significant variation between experimental batches, particularly in genes associated with temporal maturation. Single-cell profiling revealed shifts in nephron patterning and proportions of component cells. Distinct induced pluripotent stem cell clones showed congruent transcriptional programs, with interexperimental and interclonal variation also strongly associated with nephron patterning. Epithelial cells isolated from organoids aligned with total organoids at the same day of differentiation, again implicating relative maturation as a confounder. This understanding of experimental variation facilitated an optimized analysis of organoid-based disease modeling, thereby increasing the utility of kidney organoids for personalized medicine and functional genomics.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Belinda", "last_name": "Phipson", "name": null }, { "creator_type": "author", "first_name": "Pei X.", "last_name": "Er", "name": null }, { "creator_type": "author", "first_name": "Alexander N.", "last_name": "Combes", "name": null }, { "creator_type": "author", "first_name": "Thomas A.", "last_name": "Forbes", "name": null }, { "creator_type": "author", "first_name": "Sara E.", "last_name": "Howden", "name": null }, { "creator_type": "author", "first_name": "Luke", "last_name": "Zappia", "name": null }, { "creator_type": "author", "first_name": "Hsan-Jan", "last_name": "Yen", "name": null }, { "creator_type": "author", "first_name": "Kynan T.", "last_name": "Lawlor", "name": null }, { "creator_type": "author", "first_name": "Lorna J.", "last_name": "Hale", "name": null }, { "creator_type": "author", "first_name": "Jane", "last_name": "Sun", "name": null }, { "creator_type": "author", "first_name": "Ernst", "last_name": "Wolvetang", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null }, { "creator_type": "author", "first_name": "Alicia", "last_name": "Oshlack", "name": null }, { "creator_type": "author", "first_name": "Melissa H.", "last_name": "Little", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41592-018-0253-2" }, "pmcid": { "normalized": "PMC6634992" }, "pmid": { "normalized": "30573816" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Clone Cells", "descriptor_ui": "D002999", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Kidney Diseases", "descriptor_ui": "D007674", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "79-87", "proceedings_title": null, "publisher": "", "title": "Nature methods", "volume": "16", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Evaluation of variability in human kidney organoids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Histopathology requires the expertise of specialists to diagnose morphological features of cells and tissues. Raman imaging can provide additional biochemical information to benefit histological disease diagnosis. Using a dietary model of nonalcoholic fatty liver disease in rats, we combine Raman imaging with machine learning and information theory to evaluate cellular-level information in liver tissue samples. After increasing signal-to-noise ratio in the Raman images through superpixel segmentation, we extract biochemically distinct regions within liver tissues, allowing for quantification of characteristic biochemical components such as vitamin A and lipids. Armed with microscopic information about the biochemical composition of the liver tissues, we group tissues having similar composition, providing a descriptor enabling inference of tissue states, contributing valuable information to histological inspection.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Khalifa Mohammad", "last_name": "Helal", "name": null }, { "creator_type": "author", "first_name": "James Nicholas", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Harsono", "last_name": "Cahyadi", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Okajima", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/1873-3468.13520" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31254349" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Non-alcoholic Fatty Liver Disease", "descriptor_ui": "D065626", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Signal-To-Noise Ratio", "descriptor_ui": "D059629", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019 Sep", "date_precision": "unknown", "issue": "18", "normalized_date": null, "pages": "2535-2544", "proceedings_title": null, "publisher": "", "title": "FEBS letters", "volume": "593", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Raman spectroscopic histology using machine learning for nonalcoholic fatty liver disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Circadian rhythms are generated by interlocked transcriptional-translational negative feedback loops (TTFLs), the molecular process implemented within a cell. The contributions, weighting and balancing between the multiple feedback loops remain debated. Dissociated, free-running dynamics in the expression of distinct clock genes has been described in recent experimental studies that applied various perturbations such as slice preparations, light pulses, jet-lag, and culture medium exchange. In this paper, we provide evidence that this \"presumably transient\" dissociation of circadian gene expression oscillations may occur at the single-cell level. Conceptual and detailed mechanistic mathematical modeling suggests that such dissociation is due to a weak interaction between multiple feedback loops present within a single cell. The dissociable loops provide insights into underlying mechanisms and general design principles of the molecular circadian clock.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Christoph", "last_name": "Schmal", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Jihwan", "last_name": "Myung", "name": null }, { "creator_type": "author", "first_name": "J. Patrick", "last_name": "Pett", "name": null }, { "creator_type": "author", "first_name": "Sato", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Hanspeter", "last_name": "Herzel", "name": null }, { "creator_type": "author", "first_name": "Isao T.", "last_name": "Tokuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1007330" }, "pmcid": { "normalized": "PMC6759184" }, "pmid": { "normalized": "31513579" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Circadian Clocks", "descriptor_ui": "D057906", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Feedback", "descriptor_ui": "D005246", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Suprachiasmatic Nucleus Neurons", "descriptor_ui": "D000074523", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "e1007330", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "15", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Weak coupling between intracellular feedback loops explains dissociation of clock gene dynamics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Monoacylglycerol lipase (MAGL) is the main enzyme implicated in the degradation of the most abundant endocannabinoid in the brain, 2-arachidonoylglycerol (2-AG), producing arachidonic acid (AA) and glycerol. MAGL pharmacological inhibition with JZL184 or genetic deletion results in an exacerbated 2-AG signaling and reduced synthesis of prostaglandins (PGs), due to the reduced AA precursor levels. We found that acute JZL184 administration, previously described to exert anti-inflammatory effects, and MAGL knockout (KO) mice display cerebellar, but not hippocampal, microglial reactivity, accompanied with increased expression of the mRNA levels of neuroinflammatory markers, such as cyclooxygenase-2 (COX-2). Notably, this neuroinflammatory phenotype correlated with relevant motor coordination impairment in the beam-walking and the footprint tests. Treatment with the COX-2 inhibitor NS398 during 5 days prevented the deficits in cerebellar function and the cerebellar microglia reactivity in MAGL KO, without affecting hippocampal reactivity. Altogether, this study reveals the brain region-specific response to MAGL inhibition, with an important role of COX-2 in the cerebellar deficits associated, which should be taken into account for the use of MAGL inhibitors as anti-inflammatory drugs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Sara", "last_name": "Martinez-Torres", "name": null }, { "creator_type": "author", "first_name": "Laura", "last_name": "Cutando", "name": null }, { "creator_type": "author", "first_name": "Antoni", "last_name": "Pastor", "name": null }, { "creator_type": "author", "first_name": "Ako", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Rafael", "last_name": "de la Torre", "name": null }, { "creator_type": "author", "first_name": "Emmanuel", "last_name": "Valjent", "name": null }, { "creator_type": "author", "first_name": "Rafael", "last_name": "Maldonado", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Andres", "last_name": "Ozaita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbi.2019.06.036" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31251974" } }, "mesh": [ { "descriptor": "Amidohydrolases", "descriptor_ui": "D000581", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arachidonic Acid", "descriptor_ui": "D016718", "major_topic": false }, { "descriptor": "Arachidonic Acids", "descriptor_ui": "D001095", "major_topic": false }, { "descriptor": "Benzodioxoles", "descriptor_ui": "D052117", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Cyclooxygenase 2", "descriptor_ui": "D051546", "major_topic": false }, { "descriptor": "Cyclooxygenase Inhibitors", "descriptor_ui": "D016861", "major_topic": false }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": false }, { "descriptor": "Glycerides", "descriptor_ui": "D005989", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Monoacylglycerol Lipases", "descriptor_ui": "D008994", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Neuroimmunomodulation", "descriptor_ui": "D015213", "major_topic": false }, { "descriptor": "Nitrobenzenes", "descriptor_ui": "D009578", "major_topic": false }, { "descriptor": "Piperidines", "descriptor_ui": "D010880", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sulfonamides", "descriptor_ui": "D013449", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Oct", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "399-409", "proceedings_title": null, "publisher": "", "title": "Brain, behavior, and immunity", "volume": "81", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Monoacylglycerol lipase blockade impairs fine motor coordination and triggers cerebellar neuroinflammation through cyclooxygenase-2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: We previously demonstrated that step training leads to reorganization of neuronal networks in the lumbar spinal cord of rodents after a hemisection (HX) injury and step training, including increases excitability of spinally evoked potentials in hindlimb motor neurons. METHODS: In this study, we investigated changes in RNA expression and synapse number using RNA-Seq and immunohistochemistry of the lumbar spinal cord 23 days after a mid-thoracic HX in rats with and without post-HX step training. RESULTS: Gene Ontology (GO) term clustering demonstrated that expression levels of 36 synapse-related genes were increased in trained compared with nontrained rats. Many synaptic genes were upregulated in trained rats, but Lrrc4 (coding NGL-2) was the most highly expressed in the lumbar spinal cord caudal to the HX lesion. Trained rats also had a higher number of NGL-2/synaptophysin synaptic puncta in the lumbar ventral horn. CONCLUSIONS: Our findings demonstrate clear activity-dependent regulation of synapse-related gene expression post-HX. This effect is consistent with the concept that activity-dependent phenomena can provide a mechanistic drive for epigenetic neuronal group selection in the shaping of the reorganization of synaptic networks to learn the locomotion task being trained after spinal cord injury.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazu", "last_name": "Kobayakawa", "name": null }, { "creator_type": "author", "first_name": "Kyleigh Alexis", "last_name": "DePetro", "name": null }, { "creator_type": "author", "first_name": "Hui", "last_name": "Zhong", "name": null }, { "creator_type": "author", "first_name": "Bau", "last_name": "Pham", "name": null }, { "creator_type": "author", "first_name": "Masamitsu", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Nogami", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "V. Reggie", "last_name": "Edgerton", "name": null } ], "identifiers": { "doi": { "normalized": "10.1177/1545968319829456" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30782076" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Exercise Test", "descriptor_ui": "D005080", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "GPI-Linked Proteins", "descriptor_ui": "D058851", "major_topic": false }, { "descriptor": "Motor Neurons", "descriptor_ui": "D009046", "major_topic": false }, { "descriptor": "Netrins", "descriptor_ui": "D000075385", "major_topic": false }, { "descriptor": "Physical Conditioning, Animal", "descriptor_ui": "D010805", "major_topic": true }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false }, { "descriptor": "Spinal Cord Injuries", "descriptor_ui": "D013119", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "225-231", "proceedings_title": null, "publisher": "", "title": "Neurorehabilitation and neural repair", "volume": "33", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Locomotor Training Increases Synaptic Structure With High NGL-2 Expression After Spinal Cord Hemisection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Animal morphogenesis can be summarized as a reconfiguration of a mass of cells. Although extracellular matrices that include rigid skeletal elements, such as cartilage/bones and exoskeletons, have important roles in morphogenesis, they are also secreted in situ by accumulated cells or epithelial cells. In contrast, recent studies of the skeleton construction of sponges (Porifera) illuminate a conceptually different mechanism of morphogenesis in which cells manipulate rather fine rigid materials (spicules) to form larger structures. Here, two different types of sponge skeleton formation using calcareous spicules or siliceous spicules are compared with regard to the concept of the production of rigid materials and their use in skeletons. The comparison highlights the advantages of their different strategies of forming sponge skeletons.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Noriko", "last_name": "Funayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.gde.2019.08.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31546193" } }, "mesh": [ { "descriptor": "Animal Shells", "descriptor_ui": "D060105", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cartilage", "descriptor_ui": "D002356", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Porifera", "descriptor_ui": "D011161", "major_topic": false }, { "descriptor": "Skeleton", "descriptor_ui": "D012863", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Aug", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "91-97", "proceedings_title": null, "publisher": "", "title": "Current opinion in genetics & development", "volume": "57", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Produce, carry/position, and connect: morphogenesis using rigid materials.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Prof. Masao Ito contributed greatly to the elucidation of the structure and function of cerebellar neuronal circuits. He formulated a cerebellar motor learning theory and an internal model hypothesis and pursued how complex cerebellar functions resulted from the operation of neural circuits. In this article, we first provide a brief overview of the major cell types and the synaptic organization of cerebellar neural circuits. Then we introduce how mature cerebellar neural circuits are shaped through synapse formation and pruning during postnatal development. We also refer to the maturation of inhibitory neurons and glial cells during postnatal development.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Honoka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.11477/mf.1416201457" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31787626" } }, "mesh": [ { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neuroglia", "descriptor_ui": "D009457", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1373-1383", "proceedings_title": null, "publisher": "", "title": "Brain and nerve = Shinkei kenkyu no shinpo", "volume": "71", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "[Postnatal Development of Cerebellar Neural Circuits].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: To evaluate the preventive effect of an insulin-like growth factor 1 sustained-release collagen urethral catheter on urethral stricture after urethral injury in a rabbit model. METHODS: We made urethral catheters coated either with insulin-like growth factor 1 impregnated collagen or with only collagen, and we divided 19 male Japanese white rabbits into three groups according to the kind of catheter inserted immediately after the rabbit's urethra was injured by electrocoagulation. Group 1 (n = 7) had a catheter coated with insulin-like growth factor 1 impregnated collagen inserted; group 2 (n = 7) had a catheter coated with only collagen inserted; and group 3 (n = 5) had an uncoated catheter inserted. A total of 14 days later, the injured urethras were evaluated by urethrography and urethroscopy, and were also histologically examined. RESULTS: Urethrography showed that the ratio of the urethral lumen diameter in injured urethra to that in normal urethra was the largest in group 1 (P < 0.0001). In addition, five of the seven rabbits in group 1 (71.4%) had a urethral lumen large enough for passage of a urethroscope, a fraction larger than the corresponding fractions in groups 2 (57.1%) and 3 (20%). On histological analysis, the injured area not covered with regenerated urethral epithelium tended to be smaller in group 1 than the other two groups, but the mean difference was not significant (P = 0.19). CONCLUSIONS: An insulin-like growth factor 1 sustained-release collagen urethral catheter significantly improves wound healing and prevents urethral stricture after urethral injury.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shinchi", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Yoshine", "last_name": "Mayumi", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Horiguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/iju.13931" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30806004" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Delayed-Action Preparations", "descriptor_ui": "D003692", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Insulin-Like Growth Factor I", "descriptor_ui": "D007334", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Urethra", "descriptor_ui": "D014521", "major_topic": false }, { "descriptor": "Urethral Stricture", "descriptor_ui": "D014525", "major_topic": false }, { "descriptor": "Urinary Catheters", "descriptor_ui": "D062885", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "572-577", "proceedings_title": null, "publisher": "", "title": "International journal of urology : official journal of the Japanese Urological Association", "volume": "26", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Insulin-like growth factor 1 sustained-release collagen on urethral catheter prevents stricture after urethral injury in a rabbit model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This review highlights recent studies of the functional implications of corticosteroids in some important behaviors of model fish, which are also relevant to human nutrition homeostasis. The primary actions of corticosteroids are mediated by glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), which are transcription factors. Zebrafish and medaka models of GR- and MR-knockout are the first constitutive corticosteroid receptor-knockout animals that are viable in adulthood. Similar receptor knockouts in mice are lethal. In this review, we describe the physiological and behavioral changes following disruption of the corticosteroid receptors in these models. The GR null model has peripheral changes in nutrition metabolism that do not occur in a mutant harboring a point mutation in the GR DNA-binding domain. This suggests that these are not “intrinsic” activities of GR. On the other hand, we propose that integration of visual responses and brain behavior by corticosteroid receptors is a possible “intrinsic”/principal function potentially conserved in vertebrates.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/nu11030611" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30871191" } }, "mesh": [ { "descriptor": "Adrenal Cortex Hormones", "descriptor_ui": "D000305", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": true }, { "descriptor": "Receptors, Steroid", "descriptor_ui": "D011987", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Nutrients", "volume": "11", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "‘Central’ Actions of Corticosteroid Signaling Suggested by Constitutive Knockout of Corticosteroid Receptors in Small Fish.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Studies on regulatory T cells (T(reg) ) have focused on thymic T(reg) as a stable lineage of immunosuppressive T cells, the differentiation of which is controlled by the transcription factor forkhead box protein 3 (Foxp3). This lineage perspective, however, may constrain hypotheses regarding the role of Foxp3 and T(reg) in vivo, particularly in clinical settings and immunotherapy development. In this review, we synthesize a new perspective on the role of Foxp3 as a dynamically expressed gene, and thereby revisit the molecular mechanisms for the transcriptional regulation of Foxp3. In particular, we introduce a recent advancement in the study of Foxp3-mediated T cell regulation through the development of the Timer of cell kinetics and activity (Tocky) system, and show that the investigation of Foxp3 transcriptional dynamics can reveal temporal changes in the differentiation and function of T(reg) in vivo. We highlight the role of Foxp3 as a gene downstream of T cell receptor (TCR) signalling and show that temporally persistent TCR signals initiate Foxp3 transcription in self-reactive thymocytes. In addition, we feature the autoregulatory transcriptional circuit for the Foxp3 gene as a mechanism for consolidating T(reg) differentiation and activating their suppressive functions. Furthermore, we explore the potential mechanisms behind the dynamic regulation of epigenetic modifications and chromatin architecture for Foxp3 transcription. Lastly, we discuss the clinical relevance of temporal changes in the differentiation and activation of T(reg) .", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "D.", "last_name": "Bending", "name": null }, { "creator_type": "author", "first_name": "M.", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cei.13194" }, "pmcid": { "normalized": "PMC6591142" }, "pmid": { "normalized": "30076771" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Immunological", "descriptor_ui": "D018448", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jul", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "14-23", "proceedings_title": null, "publisher": "", "title": "Clinical and experimental immunology", "volume": "197", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "From stability to dynamics: understanding molecular mechanisms of regulatory T cells through Foxp3 transcriptional dynamics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Drosophila provides an inexpensive and quantitative platform for measuring whole animal drug response. A complementary approach is virtual screening, where chemical libraries can be efficiently screened against protein target(s). Here, we present a unique discovery platform integrating structure-based modeling with Drosophila biology and organic synthesis. We demonstrate this platform by developing chemicals targeting a Drosophila model of Medullary Thyroid Cancer (MTC) characterized by a transformation network activated by oncogenic dRetM955T. Structural models for kinases relevant to MTC were generated for virtual screening to identify unique preliminary hits that suppressed dRetM955T-induced transformation. We then combined features from our hits with those of known inhibitors to create a 'hybrid' molecule with improved suppression of dRetM955T transformation. Our platform provides a framework to efficiently explore novel kinase inhibitors outside of explored inhibitor chemical space that are effective in inhibiting cancer networks while minimizing whole body toxicity.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Peter M. U.", "last_name": "Ung", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null }, { "creator_type": "author", "first_name": "Alex P.", "last_name": "Scopton", "name": null }, { "creator_type": "author", "first_name": "Arvin C.", "last_name": "Dar", "name": null }, { "creator_type": "author", "first_name": "Ross L.", "last_name": "Cagan", "name": null }, { "creator_type": "author", "first_name": "Avner", "last_name": "Schlessinger", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1006878" }, "pmcid": { "normalized": "PMC6506148" }, "pmid": { "normalized": "31026276" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Carcinoma, Neuroendocrine", "descriptor_ui": "D018278", "major_topic": true }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Drug Evaluation, Preclinical", "descriptor_ui": "D004353", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Neoplasms, Experimental", "descriptor_ui": "D009374", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Protein Kinases", "descriptor_ui": "D011494", "major_topic": true }, { "descriptor": "Thyroid Neoplasms", "descriptor_ui": "D013964", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "e1006878", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "15", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Integrated computational and Drosophila cancer model platform captures previously unappreciated chemicals perturbing a kinase network.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cells simultaneously utilize different intracellular signaling systems to process environmental information [1-4]. The magnesium ion (Mg(2+)) is recognized as a multitarget analog regulator that performs many roles, such as circadian timekeeping, due to the following properties: (1) it influences wide-ranging biological processes, (2) its concentration is tightly controlled within a narrow sub-millimolar range, and (3) its intracellular dynamics are slow and long lasting [5-11]; its regulatory manner is not all-or-none in contrast to the switch-like signal transduction by the well-established second messenger Ca(2+) [12]. Recent studies, however, have reported another role for Mg(2+) as a second messenger in immune cells-i.e., a switching system for cellular states [13, 14]. These multifaceted characteristics of Mg(2+) raise the question of how Mg(2+) processes information and how common its role is as a signaling molecule. We focused on the trophic effects of gamma-aminobutyric acid (GABA) and its developmental transition, the molecular basis of which also remains poorly understood despite its evolutionarily well-conserved roles [15-19]. Here, we show that in neurons, GABA(A) receptor signaling, whose action is excitatory, triggers Mg(2+) release from mitochondria specifically at early developmental stages, and that released Mg(2+) stimulates the CREB and mTOR signaling pathways, thereby facilitating structural and functional maturation of neural networks. We found that cytosolic Mg(2+) fluctuations within physiological ranges is enough to crucially regulate ERK, CREB, and mTOR activities. Together, intracellular Mg(2+) physiologically integrates and coordinates cellular information, and Mg(2+) is a novel signal transducer for organizing neural networks.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryu", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2018.10.044" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30528584" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Receptors, GABA-A", "descriptor_ui": "D011963", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Dec 17", "date_precision": "day", "issue": "24", "normalized_date": "2018-12-17", "pages": "3984-3991.e5", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "28", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "GABA-Induced Intracellular Mg(2+) Mobilization Integrates and Coordinates Cellular Information Processing for the Maturation of Neural Networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Organized tissue structure in the secondary lymphoid organs (SLOs) tightly depends on the development of fibroblastic stromal cells (FSCs) of mesenchymal origin; however, the mechanisms of this relationship are poorly understood. In this study, we specifically inactivated the canonical NF-kappaB pathway in FSCs in vivo by conditionally inducing IkappaBalpha mutant in a Ccl19-IkappaBSR mouse system in which NF-kappaB activity is likely to be suppressed in fetal FSC progenitors. Given that NF-kappaB activation in fetal FSCs is essential for SLO development, the animals were expected to lack SLOs. However, all SLOs were preserved in Ccl19-IkappaBSR mice. Instead, the T cell area was severely disturbed by the lack of CCL21-expressing FSCs, whereas the follicles and associated FSC networks were formed. Fate mapping revealed that IkappaBSR-expressing cells constituted only a small fraction of stromal compartment outside the follicles. Taken together, our findings indicate an essential role of the canonical NF-kappaB pathway activity in the development of three FSC subsets common to SLOs and suggest transient or stochastic CCL19 expression in FSC progenitors and a compensatory differentiation program of follicular FSCs.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Dana", "last_name": "Bogdanova", "name": null }, { "creator_type": "author", "first_name": "Arata", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Madoka", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "M. Azizur", "last_name": "Rahman", "name": null }, { "creator_type": "author", "first_name": "Burkhard", "last_name": "Ludewig", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Kinashi", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.4049/jimmunol.1800539" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30397032" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chemokine CCL19", "descriptor_ui": "D054415", "major_topic": false }, { "descriptor": "Chemokine CCL21", "descriptor_ui": "D054421", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Lymphoid Tissue", "descriptor_ui": "D008221", "major_topic": false }, { "descriptor": "Mesenchymal Stem Cells", "descriptor_ui": "D059630", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "NF-KappaB Inhibitor alpha", "descriptor_ui": "D000072000", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Dec 15", "date_precision": "day", "issue": "12", "normalized_date": "2018-12-15", "pages": "3580-3586", "proceedings_title": null, "publisher": "", "title": "Journal of immunology (Baltimore, Md. : 1950)", "volume": "201", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Essential Role of Canonical NF-kappaB Activity in the Development of Stromal Cell Subsets in Secondary Lymphoid Organs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "MicroRNAs (miRNAs) modulate the post-transcriptional regulation of target genes and are related to biology of complex human traits, but genetic landscape of miRNAs remains largely unknown. Given the strikingly tissue-specific miRNA expression profiles, we here expand a previous method to quantitatively evaluate enrichment of genome-wide association study (GWAS) signals on miRNA-target gene networks (MIGWAS) to further estimate tissue-specific enrichment. Our approach integrates tissue-specific expression profiles of miRNAs ( approximately 1800 miRNAs in 179 cells) with GWAS to test whether polygenic signals enrich in miRNA-target gene networks and whether they fall within specific tissues. We applied MIGWAS to 49 GWASs (nTotal = 3 520 246), and successfully identified biologically relevant tissues. Further, MIGWAS could point miRNAs as candidate biomarkers of the trait. As an illustrative example, we performed differentially expressed miRNA analysis between rheumatoid arthritis (RA) patients and healthy controls (n = 63). We identified novel biomarker miRNAs (e.g. hsa-miR-762) by integrating differentially expressed miRNAs with MIGWAS results for RA, as well as novel associated loci with significant genetic risk (rs56656810 at MIR762 at 16q11; n = 91 482, P = 3.6 x 10-8). Our result highlighted that miRNA-target gene network contributes to human disease genetics in a cell type-specific manner, which could yield an efficient screening of miRNAs as promising biomarkers.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Saori", "last_name": "Sakaue", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Nii", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kishikawa", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Ishigaki", "name": null }, { "creator_type": "author", "first_name": "Chikashi", "last_name": "Terao", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Naomasa", "last_name": "Suita", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Saeki", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Katsunori", "last_name": "Ikari", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Kawaji", "name": null }, { "creator_type": "author", "first_name": "Timo", "last_name": "Lassmann", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yoshitomi", "name": null }, { "creator_type": "author", "first_name": "Hiromu", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Ohmura", "name": null }, { "creator_type": "author", "first_name": "Alistair R.", "last_name": "R Forrest", "name": null }, { "creator_type": "author", "first_name": "Yoshihide", "last_name": "Hayashizaki", "name": null }, { "creator_type": "author", "first_name": "Piero", "last_name": "Carninci", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kumanogoh", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Kamatani", "name": null }, { "creator_type": "author", "first_name": "Michiel", "last_name": "de Hoon", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yukinori", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nar/gky1066" }, "pmcid": { "normalized": "PMC6294505" }, "pmid": { "normalized": "30407537" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Arthritis, Rheumatoid", "descriptor_ui": "D001172", "major_topic": false }, { "descriptor": "Asthma", "descriptor_ui": "D001249", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Colitis, Ulcerative", "descriptor_ui": "D003093", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": true }, { "descriptor": "Genetic Loci", "descriptor_ui": "D056426", "major_topic": false }, { "descriptor": "Genome, Human", "descriptor_ui": "D015894", "major_topic": true }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": false }, { "descriptor": "Graves Disease", "descriptor_ui": "D006111", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Multifactorial Inheritance", "descriptor_ui": "D020412", "major_topic": false }, { "descriptor": "Organ Specificity", "descriptor_ui": "D009928", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Dec 14", "date_precision": "day", "issue": "22", "normalized_date": "2018-12-14", "pages": "11898-11909", "proceedings_title": null, "publisher": "", "title": "Nucleic acids research", "volume": "46", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Integration of genetics and miRNA-target gene network identified disease biology implicated in tissue specificity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Elastic networks have been used as simple models of proteins to study their slow structural dynamics. They consist of point-like particles connected by linear Hookean springs and hence are convenient for linear normal mode analysis around a given reference structure. Furthermore, dynamic simulations using these models can provide new insights. As the computational cost associated with these models is considerably lower compared to that of all-atom models, they are also convenient for comparative studies between multiple protein structures. In this review, we introduce examples of coarse-grained molecular dynamics studies using elastic network models and their derivatives, focusing on the nonlinear phenomena, and discuss their applicability to large-scale macromolecular assemblies.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuichi", "last_name": "Togashi", "name": null }, { "creator_type": "author", "first_name": "Holger", "last_name": "Flechsig", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms19123899" }, "pmcid": { "normalized": "PMC6320916" }, "pmid": { "normalized": "30563146" } }, "mesh": [ { "descriptor": "Elasticity", "descriptor_ui": "D004548", "major_topic": true }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": true }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Dec 5", "date_precision": "day", "issue": "12", "normalized_date": "2018-12-05", "pages": "E3899", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "19", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Coarse-Grained Protein Dynamics Studies Using Elastic Network Models.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The supramammillary nucleus (SuM) of the hypothalamus projects to the dentate gyrus (DG) and the CA2 region of the hippocampus. Although the SuM-to-hippocampus circuits have been implicated in spatial and emotional memory formation, little is known about precise neural connections between the SuM and hippocampus. Here, we report that axons of SuM neurons make monosynaptic connections to granule cells (GCs) and GABAergic interneurons, but not to hilar mossy cells, in the DG and co-release glutamate and gamma-aminobutyric acid (GABA) at these synapses. Although inputs from the SuM can excite some interneurons, the inputs alone fail to generate spikes in GCs. However, despite the insufficient excitatory drive and GABAergic co-transmission, SuM inputs have net excitatory effects on GCs and can potentiate GC firing when temporally associated with perforant path inputs. Our results indicate that the SuM influences DG information processing by modulating GC outputs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Hashimotodani", "name": null }, { "creator_type": "author", "first_name": "Fuyuki", "last_name": "Karube", "name": null }, { "creator_type": "author", "first_name": "Yuchio", "last_name": "Yanagawa", "name": null }, { "creator_type": "author", "first_name": "Fumino", "last_name": "Fujiyama", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2018.11.016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30517859" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": false }, { "descriptor": "Afferent Pathways", "descriptor_ui": "D000344", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dentate Gyrus", "descriptor_ui": "D018891", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Hypothalamus, Posterior", "descriptor_ui": "D007034", "major_topic": false }, { "descriptor": "Interneurons", "descriptor_ui": "D007395", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mossy Fibers, Hippocampal", "descriptor_ui": "D019599", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Perforant Pathway", "descriptor_ui": "D019580", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Dec 4", "date_precision": "day", "issue": "10", "normalized_date": "2018-12-04", "pages": "2704-2715.e4", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "25", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Supramammillary Nucleus Afferents to the Dentate Gyrus Co-release Glutamate and GABA and Potentiate Granule Cell Output.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Kinesin-1, the founding member of the kinesin superfamily of proteins, is known to use only a subset of microtubules for transport in living cells. This biased use of microtubules is proposed as the guidance cue for polarized transport in neurons, but the underlying mechanisms are still poorly understood. Here, we report that kinesin-1 binding changes the microtubule lattice and promotes further kinesin-1 binding. This high-affinity state requires the binding of kinesin-1 in the nucleotide-free state. Microtubules return to the initial low-affinity state by washing out the binding kinesin-1 or by the binding of non-hydrolyzable ATP analogue AMPPNP to kinesin-1. X-ray fiber diffraction, fluorescence speckle microscopy, and second-harmonic generation microscopy, as well as cryo-EM, collectively demonstrated that the binding of nucleotide-free kinesin-1 to GDP microtubules changes the conformation of the GDP microtubule to a conformation resembling the GTP microtubule.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Manatsu", "last_name": "Morikawa", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Kaneshiro", "name": null }, { "creator_type": "author", "first_name": "Taketoshi", "last_name": "Kambara", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kamimura", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Sotaro", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Shigematsu", "name": null }, { "creator_type": "author", "first_name": "Mikako", "last_name": "Shirouzu", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Nitta", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Nobutaka", "last_name": "Hirokawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1083/jcb.201711178" }, "pmcid": { "normalized": "PMC6279379" }, "pmid": { "normalized": "30297389" } }, "mesh": [ { "descriptor": "Adenylyl Imidodiphosphate", "descriptor_ui": "D000266", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Transport, Active", "descriptor_ui": "D001693", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Guanosine Diphosphate", "descriptor_ui": "D006153", "major_topic": false }, { "descriptor": "Guanosine Triphosphate", "descriptor_ui": "D006160", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kinesins", "descriptor_ui": "D016547", "major_topic": true }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": true }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Dec 3", "date_precision": "day", "issue": "12", "normalized_date": "2018-12-03", "pages": "4164-4183", "proceedings_title": null, "publisher": "", "title": "The Journal of cell biology", "volume": "217", "year": 2018 }, "ssbd": { "database": [ "ssbd-database-000191" ], "repository": [ "ssbd-repos-000191" ] }, "title": "Kinesin-binding-triggered conformation switching of microtubules contributes to polarized transport.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Thioredoxin (Trx) family proteins perform redox regulation in cells, and they are involved in several other biological processes (e.g. oxidative stress tolerance). In the filamentous cyanobacterium Anabaena sp. PCC7120 (A. 7120), eight Trx isoforms have been identified via genomic analysis. Among these Trx isoforms, the absence of Trx-m1 and TrxC appears to result in oxidative stress in A. 7120 together with alterations of the thylakoid membrane structure and phycobiliprotein composition. To analyze the physiological changes in these Trx disruptants thoroughly, quantitative proteomics was applied. Certainly, the mutants exhibited similar alterations in the proteome including decreased relative abundance of phycobiliproteins and an increased level of proteins involved in amino acid and carbohydrate metabolism. Nevertheless, the results also indicated that the mutants exhibited changes in the relative abundance of different sets of proteins participating in reactive oxygen species detoxification, such as Fe-SOD in Deltatrx-m1 and PrxQ in DeltatrxC, suggesting distinct functions of Trx-m1 and TrxC.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Frederic", "last_name": "Deschoenmaeker", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Mihara", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pcp/pcy163" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30101290" } }, "mesh": [ { "descriptor": "Anabaena", "descriptor_ui": "D017033", "major_topic": false }, { "descriptor": "Antioxidants", "descriptor_ui": "D000975", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Catalase", "descriptor_ui": "D002374", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": true }, { "descriptor": "Photosynthesis", "descriptor_ui": "D010788", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Superoxide Dismutase", "descriptor_ui": "D013482", "major_topic": false }, { "descriptor": "Thioredoxins", "descriptor_ui": "D013879", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Dec 1", "date_precision": "day", "issue": "12", "normalized_date": "2018-12-01", "pages": "2432-2441", "proceedings_title": null, "publisher": "", "title": "Plant & cell physiology", "volume": "59", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "The Absence of Thioredoxin m1 and Thioredoxin C in Anabaena sp. PCC 7120 Leads to Oxidative Stress.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": ": The structure and function of tumor blood vessels profoundly affects the tumor microenvironment. Signals mediated through the lysophosphatidic acid receptor 4 (LPA4) promote vascular network formation to restore normal vascular barrier function in subcutaneous tumors and thus improve drug delivery. However, the characteristics of the vasculature vary by organ and tumor types, and how drug delivery and leukocyte trafficking are affected by modification of vascular function by LPA in different cancers is unclear. Here, we show that LPA4 activation promotes the formation of fine vascular structures in brain tumors. RhoA/ROCK signaling contributed to LPA-induced endothelial cell-cell adhesion, and RhoA/ROCK activity following LPA4 stimulation regulated expression of VCAM-1. This resulted in increased lymphocyte infiltration into the tumor. LPA improved delivery of exogenous IgG into brain tumors and enhanced the anticancer effect of anti-programmed cell death-1 antibody therapy. These results indicate the effects of LPA on vascular structure and function apply not only to chemotherapy but also to immunotherapy. SIGNIFICANCE: These findings demonstrate that lysophosphatidic acid, a lipid mediator, promotes development of a fine capillary network in brain tumors by inducing tightening of endothelial cell-to-cell adhesion, facilitating improved drug delivery, and lymphocyte penetration.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Eino", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Yonehiro", "last_name": "Kanemura", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Iba", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kagawa", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takara", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Kishima", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/0008-5472.can-18-0498" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30301839" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents, Immunological", "descriptor_ui": "D000074322", "major_topic": false }, { "descriptor": "Brain Neoplasms", "descriptor_ui": "D001932", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Lymphocytes, Tumor-Infiltrating", "descriptor_ui": "D016246", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false }, { "descriptor": "Receptors, Lysophosphatidic Acid", "descriptor_ui": "D049368", "major_topic": false }, { "descriptor": "Receptors, Purinergic", "descriptor_ui": "D011983", "major_topic": false }, { "descriptor": "rho-Associated Kinases", "descriptor_ui": "D054460", "major_topic": false }, { "descriptor": "rhoA GTP-Binding Protein", "descriptor_ui": "D020742", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false }, { "descriptor": "Vascular Cell Adhesion Molecule-1", "descriptor_ui": "D019010", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Dec 1", "date_precision": "day", "issue": "23", "normalized_date": "2018-12-01", "pages": "6607-6620", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "78", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "LPA4-Mediated Vascular Network Formation Increases the Efficacy of Anti-PD-1 Therapy against Brain Tumors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Escherichia coli lacZ gene encoding beta-galactosidase is a widely used reporter, but few synthetic substrates are available for detecting its activity with single-cell resolution in living samples. Our recently reported fluorogenic substrate SPiDER-betaGal is suitable for this purpose, but its hydrolysis product shows green fluorescence emission, and a red-shifted analogue is therefore required for use in combination with green fluorescent protein (GFP) markers. Herein, we describe the development of a red-shifted fluorogenic substrate for beta-galactosidase, SPiDER-Red-betaGal, based on a silicon rhodol scaffold and a carboxylic group as the intramolecular nucleophile. LacZ-positive cells were successfully labeled with SPiDER-Red-betaGal at single-cell resolution in living samples, which enabled us to visualize different cell types in combination with GFP markers.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Kawamata", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Tsuda-Sakurai", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201808670" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30255610" } }, "mesh": [ { "descriptor": "beta-Galactosidase", "descriptor_ui": "D001616", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Lac Operon", "descriptor_ui": "D007763", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018 Nov 26", "date_precision": "day", "issue": "48", "normalized_date": "2018-11-26", "pages": "15702-15706", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "57", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Red-Shifted Fluorogenic Substrate for Detection of lacZ-Positive Cells in Living Tissue with Single-Cell Resolution.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Ebola virus-encoded major matrix protein VP40 traffics to the plasma membrane, which leads to the formation of filamentous viral particles and subsequent viral egress. However, the cellular machineries underlying this process are not fully understood. In the present study, we have assessed the role of host endocytic recycling in Ebola virus particle formation. We found that a small GTPase Rab11, which regulates recycling of molecules among the trans-Golgi network, recycling endosomes, and the plasma membrane, was incorporated in Ebola virus-like particles. Although Rab11 predominantly localized in the perinuclear region, it distributed diffusely in the cytoplasm and partly localized in the periphery of the cells transiently expressing VP40. In contrast, Rab11 exhibited a perinuclear distribution when 2 VP40 derivatives that lack ability to traffic to the plasma membrane were expressed. Finally, expression of a dominant-negative form of Rab11 or knockdown of Rab11 inhibited both VP40-induced clusters at the plasma membrane and release of viral-like particles. Taken together, our findings demonstrate that Ebola virus exploits host endocytic recycling machinery to facilitate the trafficking of VP40 to the cell surface and the subsequent release of viral-like particles for its establishment of efficient viral egress.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Asuka", "last_name": "Nanbo", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/infdis/jiy460" }, "pmcid": { "normalized": "PMC6249604" }, "pmid": { "normalized": "30476249" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Ebolavirus", "descriptor_ui": "D029043", "major_topic": false }, { "descriptor": "Endosomes", "descriptor_ui": "D011992", "major_topic": false }, { "descriptor": "GTP Phosphohydrolases", "descriptor_ui": "D020558", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Hemorrhagic Fever, Ebola", "descriptor_ui": "D019142", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nucleoproteins", "descriptor_ui": "D009698", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "rab GTP-Binding Proteins", "descriptor_ui": "D020691", "major_topic": false }, { "descriptor": "rab11 GTP-Binding Proteins", "descriptor_ui": "D000099193", "major_topic": false }, { "descriptor": "trans-Golgi Network", "descriptor_ui": "D021601", "major_topic": false }, { "descriptor": "Transport Vesicles", "descriptor_ui": "D022161", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Core Proteins", "descriptor_ui": "D014758", "major_topic": false }, { "descriptor": "Virion", "descriptor_ui": "D014771", "major_topic": false }, { "descriptor": "Virus Release", "descriptor_ui": "D057074", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Nov 22", "date_precision": "day", "issue": "suppl_5", "normalized_date": "2018-11-22", "pages": "S388-S396", "proceedings_title": null, "publisher": "", "title": "The Journal of infectious diseases", "volume": "218", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Budding of Ebola Virus Particles Requires the Rab11-Dependent Endocytic Recycling Pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chondroitin sulfate (CS) proteoglycan is a major component of the extracellular matrix and plays an important part in organogenesis. To elucidate the roles of CS for craniofacial development, we analyzed the craniofacial morphology in CS N-acetylgalactosaminyltransferase-1 (T1) gene knockout (KO) mice. T1KO mice showed the impaired intramembranous ossification in the skull, and the final skull shape of adult mice included a shorter face, higher and broader calvaria. Some of T1KO mice exhibited severe facial developmental defect, such as eye defects and cleft lip and palate, causing embryonic lethality. At the postnatal stages, T1KO mice with severely reduced CS amounts showed malocclusion, general skeletal dysplasia and skin hyperextension, closely resembling Ehlers-Danlos syndrome-like connective tissue disorders. The production of collagen type 1 was significantly downregulated in T1KO mice, and the deposition of CS-binding molecules, Wnt3a, was decreased with CS in extracellular matrices. The collagen fibers were irregular and aggregated, and connective tissues were dysorganized in the skin and calvaria of T1KO mice. These results suggest that CS regulates the shape of the craniofacial skeleton by modulating connective tissue organization and that the remarkable reduction of CS induces hypoplasia of intramembranous ossification and cartilage anomaly, resulting in skeletal dysplasia.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Ida-Yonemochi", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Nobuo", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Morioka", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Hideto", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Ohshima", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-35412-5" }, "pmcid": { "normalized": "PMC6244165" }, "pmid": { "normalized": "30459452" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Cartilage", "descriptor_ui": "D002356", "major_topic": false }, { "descriptor": "Chondroitin Sulfates", "descriptor_ui": "D002809", "major_topic": false }, { "descriptor": "Collagen", "descriptor_ui": "D003094", "major_topic": false }, { "descriptor": "Craniofacial Abnormalities", "descriptor_ui": "D019465", "major_topic": false }, { "descriptor": "Ehlers-Danlos Syndrome", "descriptor_ui": "D004535", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Head", "descriptor_ui": "D006257", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "N-Acetylgalactosaminyltransferases", "descriptor_ui": "D017350", "major_topic": false }, { "descriptor": "Osteochondrodysplasias", "descriptor_ui": "D010009", "major_topic": false }, { "descriptor": "Osteogenesis", "descriptor_ui": "D010012", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Wnt3A Protein", "descriptor_ui": "D060509", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Nov 20", "date_precision": "day", "issue": "1", "normalized_date": "2018-11-20", "pages": "17134", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Craniofacial abnormality with skeletal dysplasia in mice lacking chondroitin sulfate N-acetylgalactosaminyltransferase-1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This work reports on fully integrated “sample‐in‐signal‐out” microfluidic paper‐based analytical devices (μPADs) relying on bioluminescence resonance energy transfer (BRET) switches for analyte recognition and colorimetric signal generation. The devices use BRET‐based antibody sensing proteins integrated into vertically assembled layers of functionalized paper, and their design enables sample volume‐independent and fully reagent‐free operation, including on‐device blood plasma separation. User operation is limited to the application of a single drop (20–30 μL) of sample (serum, whole blood) and the acquisition of a photograph 20 min after sample introduction, with no requirement for precise pipetting, liquid handling, or analytical equipment except for a camera. Simultaneous detection of three different antibodies (anti‐HIV1, anti‐HA, and anti‐DEN1) in whole blood was achieved. Given its simplicity, this type of device is ideally suited for user‐friendly point‐of‐care testing in low‐resource environments.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Tenda", "name": null }, { "creator_type": "author", "first_name": "Benice", "last_name": "van Gerven", "name": null }, { "creator_type": "author", "first_name": "Remco", "last_name": "Arts", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Maarten", "last_name": "Merkx", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201808070" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30168634" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Viral", "descriptor_ui": "D000914", "major_topic": false }, { "descriptor": "Colorimetry", "descriptor_ui": "D003124", "major_topic": false }, { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Microfluidic Analytical Techniques", "descriptor_ui": "D046210", "major_topic": false }, { "descriptor": "Paper", "descriptor_ui": "D010209", "major_topic": true }, { "descriptor": "Point-of-Care Systems", "descriptor_ui": "D019095", "major_topic": false }, { "descriptor": "Swine", "descriptor_ui": "D013552", "major_topic": false }, { "descriptor": "Virus Diseases", "descriptor_ui": "D014777", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Nov 19", "date_precision": "day", "issue": "47", "normalized_date": "2018-11-19", "pages": "15369-15373", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International Ed. in English)", "volume": "57", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Paper‐Based Antibody Detection Devices Using Bioluminescent BRET‐Switching Sensor Proteins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Junichi", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Kinugawa", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Furihata", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Nambu", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Kakutani", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Arata", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hidehisa", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Shigetsugu", "last_name": "Hatakeyama", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Keiichi I.", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Otsuka", "name": null }, { "creator_type": "author", "first_name": "Hisataka", "last_name": "Sabe", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Tsutsui", "name": null }, { "creator_type": "author", "first_name": "Toshihisa", "last_name": "Anzai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1161/circulationaha.118.035212" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30372141" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain-Derived Neurotrophic Factor", "descriptor_ui": "D019208", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": false }, { "descriptor": "Heart Ventricles", "descriptor_ui": "D006352", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Myocardial Infarction", "descriptor_ui": "D009203", "major_topic": false }, { "descriptor": "Physical Conditioning, Animal", "descriptor_ui": "D010805", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Severity of Illness Index", "descriptor_ui": "D012720", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Oct 30", "date_precision": "day", "issue": "18", "normalized_date": "2018-10-30", "pages": "2064-2066", "proceedings_title": null, "publisher": "", "title": "Circulation", "volume": "138", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Brain-Derived Neurotrophic Factor Improves Limited Exercise Capacity in Mice With Heart Failure.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In many animal species, females choose potential mating partners according to their own preferences. Thus, female preference-based mate choice affects intraspecific mating success and prevents interspecific mating. To clarify the neuronal basis of female mate choice, it is essential to identify the important relevant sensory cues. In the fruitfly Drosophila melanogaster, the courtship song of males promotes female sexual receptivity. When wild-type virgin females can freely choose one of two types of courting males (winged or wingless males), they prefer to mate with winged males. Here, we report a crucial sensory cue relevant to this female mate choice. In a female choice test, female receptivity toward winged and wingless males was markedly reduced when females had auditory impairments, although females with visual or olfactory impairments showed normal receptivity similar to wild-type females. However, females with visual impairments did not show clear mate preference toward winged males. Thus, these findings suggest that females utilize visual cues in mate choice between winged and wingless males in Drosophila.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Show", "last_name": "Inami", "name": null }, { "creator_type": "author", "first_name": "Hirono", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1266/ggs.18-00004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29998908" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Courtship", "descriptor_ui": "D003380", "major_topic": false }, { "descriptor": "Cues", "descriptor_ui": "D003463", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mating Preference, Animal", "descriptor_ui": "D052586", "major_topic": false }, { "descriptor": "Sexual Behavior, Animal", "descriptor_ui": "D012726", "major_topic": false }, { "descriptor": "Visual Perception", "descriptor_ui": "D014796", "major_topic": false }, { "descriptor": "Wings, Animal", "descriptor_ui": "D014921", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Oct 30", "date_precision": "day", "issue": "3", "normalized_date": "2018-10-30", "pages": "119-123", "proceedings_title": null, "publisher": "", "title": "Genes & genetic systems", "volume": "93", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Light is required for proper female mate choice between winged and wingless males in Drosophila.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lower vertebrate pineal organs discriminate UV and visible light. Such color discrimination is typically considered to arise from antagonism between two or more spectrally distinct opsins, as, e.g., human cone-based color vision relies on antagonistic relationships between signals produced by red-, green-, and blue-cone opsins. Photosensitive pineal organs contain a bistable opsin (parapinopsin) that forms a signaling-active photoproduct upon UV exposure that may itself be returned to the signaling-inactive \"dark\" state by longer-wavelength light. Here we show the spectrally distinct parapinopsin states (with antagonistic impacts on signaling) allow this opsin alone to provide the color sensitivity of this organ. By using calcium imaging, we show that single zebrafish pineal photoreceptors held under a background light show responses of opposite signs to UV and visible light. Both such responses are deficient in zebrafish lacking parapinopsin. Expressing a UV-sensitive cone opsin in place of parapinopsin recovers UV responses but not color opponency. Changes in the spectral composition of white light toward enhanced UV or visible wavelengths respectively increased vs. decreased calcium signal in parapinopsin-sufficient but not parapinopsin-deficient photoreceptors. These data reveal color opponency from a single kind of bistable opsin establishing an equilibrium-like mixture of the two states with different signaling abilities whose fractional concentrations are defined by the spectral composition of incident light. As vertebrate visual color opsins evolved from a bistable opsin, these findings suggest that color opponency involving a single kind of bistable opsin might have been a prototype of vertebrate color opponency.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Seiji", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Baoguo", "last_name": "Shen", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Kawano-Yamashita", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Hibi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Tamotsu", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1802592115" }, "pmcid": { "normalized": "PMC6217433" }, "pmid": { "normalized": "30322939" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Color", "descriptor_ui": "D003116", "major_topic": false }, { "descriptor": "Color Vision", "descriptor_ui": "D055253", "major_topic": false }, { "descriptor": "Fish Proteins", "descriptor_ui": "D029941", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Pineal Gland", "descriptor_ui": "D010870", "major_topic": false }, { "descriptor": "Retinal Cone Photoreceptor Cells", "descriptor_ui": "D017949", "major_topic": false }, { "descriptor": "Rod Opsins", "descriptor_ui": "D017299", "major_topic": false }, { "descriptor": "Ultraviolet Rays", "descriptor_ui": "D014466", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Oct 30", "date_precision": "day", "issue": "44", "normalized_date": "2018-10-30", "pages": "11310-11315", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "115", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Color opponency with a single kind of bistable opsin in the zebrafish pineal organ.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report the functional synthesis and quantification of membrane proteins-alpha-hemolysin from Staphylococcus aureus and the multidrug transporter EmrE from Escherichia coli-at the stabilized droplet interface bilayer using an in vitro transcription-translation system. The system developed here can expand the list of integral membrane proteins applicable for quantitative functional analysis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Maie A.", "last_name": "Elfaramawy", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Uyeda", "name": null }, { "creator_type": "author", "first_name": "Toshihisa", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c8cc06804f" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30310891" } }, "mesh": [ { "descriptor": "Bacterial Toxins", "descriptor_ui": "D001427", "major_topic": false }, { "descriptor": "Cell-Free System", "descriptor_ui": "D002474", "major_topic": true }, { "descriptor": "Escherichia coli Proteins", "descriptor_ui": "D029968", "major_topic": false }, { "descriptor": "Hemolysin Proteins", "descriptor_ui": "D006460", "major_topic": false }, { "descriptor": "Lipid Bilayers", "descriptor_ui": "D008051", "major_topic": true }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Oct 25", "date_precision": "day", "issue": "86", "normalized_date": "2018-10-25", "pages": "12226-12229", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "54", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative analysis of cell-free synthesized membrane proteins at the stabilized droplet interface bilayer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recently, the design of mechanical networks with protein-inspired responses has become increasingly popular. Here, we review contributions which were motivated by studies of protein dynamics employing coarse-grained elastic network models. First, the concept of evolutionary optimization that we developed to design network structures which execute prescribed tasks is explained. We then review what presumably marks the origin of the idea to design complex functional networks which encode protein-inspired behavior, namely the design of an elastic network structure which emulates the cycles of ATP-powered conformational motion in protein machines. Two recent applications are reviewed. First, the construction of a model molecular motor, whose operation incorporates both the tight coupling power stroke as well as the loose coupling Brownian ratchet mechanism, is discussed. Second, the evolutionary design of network structures which encode optimal long-range communication between remote sites and represent mechanical models of allosteric proteins is presented. We discuss the prospects of designed protein-mimicking elastic networks as model systems to elucidate the design principles and functional signatures underlying the operation of complex protein machinery.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Holger", "last_name": "Flechsig", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Togashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms19103152" }, "pmcid": { "normalized": "PMC6214024" }, "pmid": { "normalized": "30322149" } }, "mesh": [ { "descriptor": "Elasticity", "descriptor_ui": "D004548", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Mechanical Phenomena", "descriptor_ui": "D055595", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Oct 13", "date_precision": "day", "issue": "10", "normalized_date": "2018-10-13", "pages": "E3152", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "19", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Designed Elastic Networks: Models of Complex Protein Machinery.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The in vivo niche and basic cellular properties of nephron progenitors are poorly described. Here we studied the cellular organization and function of the MAPK/ERK pathway in nephron progenitors. Live-imaging of ERK activity by a Forster resonance energy transfer biosensor revealed a dynamic activation pattern in progenitors, whereas differentiating precursors exhibited sustained activity. Genetic experiments demonstrate that MAPK/ERK activity controls the thickness, coherence, and integrity of the nephron progenitor niche. Molecularly, MAPK/ERK activity regulates niche organization and communication with extracellular matrix through PAX2 and ITGA8, and is needed for CITED1 expression denoting undifferentiated status. MAPK/ERK activation in nephron precursors propels differentiation by priming cells for distal and proximal fates induced by the Wnt and Notch pathways. Thus, our results demonstrate a mechanism through which MAPK/ERK activity controls both progenitor maintenance and differentiation by regulating a distinct set of targets, which maintain the biomechanical milieu of tissue-residing progenitors and prime precursors for nephrogenesis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Anneliis", "last_name": "Ihermann-Hella", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null }, { "creator_type": "author", "first_name": "Jussi", "last_name": "Kupari", "name": null }, { "creator_type": "author", "first_name": "Kristen", "last_name": "Kurtzeborn", "name": null }, { "creator_type": "author", "first_name": "Hao", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Hyuk Nam", "last_name": "Kwon", "name": null }, { "creator_type": "author", "first_name": "Cristina", "last_name": "Cebrian", "name": null }, { "creator_type": "author", "first_name": "Abdul", "last_name": "Soofi", "name": null }, { "creator_type": "author", "first_name": "Arvydas", "last_name": "Dapkunas", "name": null }, { "creator_type": "author", "first_name": "Ilkka", "last_name": "Miinalainen", "name": null }, { "creator_type": "author", "first_name": "Gregory R.", "last_name": "Dressler", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Satu", "last_name": "Kuure", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2018.08.012" }, "pmcid": { "normalized": "PMC6178244" }, "pmid": { "normalized": "30220628" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Self Renewal", "descriptor_ui": "D000066673", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Integrin alpha Chains", "descriptor_ui": "D039001", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nephrons", "descriptor_ui": "D009399", "major_topic": false }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": false }, { "descriptor": "PAX2 Transcription Factor", "descriptor_ui": "D051762", "major_topic": false }, { "descriptor": "Stem Cell Niche", "descriptor_ui": "D055153", "major_topic": true }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Oct 9", "date_precision": "day", "issue": "4", "normalized_date": "2018-10-09", "pages": "912-928", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "11", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic MAPK/ERK Activity Sustains Nephron Progenitors through Niche Regulation and Primes Precursors for Differentiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Photoacoustic (PA) imaging (PAI) has been shown to be a promising tool for non-invasive blood vessel imaging. A PAI system comprising a hemispherical detector array (HDA) has been reported previously as a method providing high morphological reproducibility. However, further improvements in diagnostic capability will require improving the image quality of PAI and fusing functional and morphological imaging. Our newly developed PAI system prototype not only enhances the PA image resolution but also acquires ultrasonic (US) B-mode images at continuous positions in the same coordinate axes. In addition, the pulse-to-pulse alternating laser irradiation shortens the measurement time difference between two wavelengths. We scanned extremities and breasts in an imaging region 140 mm in diameter and obtained 3D-PA images of fine blood vessels, including arterioles and venules. We could estimate whether a vessel was an artery or a vein by using the S-factor obtained from the PA images at two wavelengths, which corresponds approximately to the haemoglobin oxygen saturation. Furthermore, we observed tumour-related blood vessels around breast tumours with unprecedented resolution. In the future, clinical studies with our new PAI system will help to elucidate various mechanisms of vascular-associated diseases and events.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Asao", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Sekiguchi", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Nagae", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Tsuge", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kabashima", "name": null }, { "creator_type": "author", "first_name": "Shigehiko", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Togashi", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Toi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-33255-8" }, "pmcid": { "normalized": "PMC6175891" }, "pmid": { "normalized": "30297721" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Arterioles", "descriptor_ui": "D001160", "major_topic": false }, { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Photoacoustic Techniques", "descriptor_ui": "D061088", "major_topic": false }, { "descriptor": "Tomography", "descriptor_ui": "D014054", "major_topic": false }, { "descriptor": "Venules", "descriptor_ui": "D014699", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Oct 8", "date_precision": "day", "issue": "1", "normalized_date": "2018-10-08", "pages": "14930", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualising peripheral arterioles and venules through high-resolution and large-area photoacoustic imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The accumulation of specific phosphorylated protein aggregates in the brain is a hallmark of severe neurodegenerative disorders. Specifically, hyperphosphorylated tau (hp-tau) accumulates in Alzheimer disease, frontotemporal dementia with Parkinsonism linked to chromosome 17, and progressive supranuclear palsy; furthermore, phosphorylated alpha-synuclein (p-alphaSyn) accumulates in Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. Moreover, codeposition of different pathological protein aggregates is common in the brains of individuals with neurodegenerative diseases. In the present report, we describe the detection of p-alphaSyn aggregates in the brain of rTg4510 mice that overexpress human P301L mutant tau. Immunohistochemistry showed that hp-tau and p-alphaSyn aggregates were found within the same neuronal cells in rTg4510 mice and increased with age. Moreover, semiquantitative analysis revealed a significant regional correlation between hp-tau and p-alphaSyn accumulation. These results indicate that endogenous mouse alphaSyn protein is phosphorylated and accumulates with hp-tau aggregation in neurons and suggest that the overexpression of human P301L mutant tau may enhance endogenous alphaSyn phosphorylation and aggregation via a similar hyperphosphorylation mechanism in vivo. This synergic effect between tau and alphaSyn accumulation may exacerbate the pathology of several neurodegenerative disorders that show a cooccurrence of hp-tau and p-alphaSyn aggregation.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Takaichi", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Ano", "name": null }, { "creator_type": "author", "first_name": "James K.", "last_name": "Chambers", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nakayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jnen/nly070" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30107539" } }, "mesh": [ { "descriptor": "alpha-Synuclein", "descriptor_ui": "D051844", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Aggregation, Pathological", "descriptor_ui": "D066263", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Oct 1", "date_precision": "day", "issue": "10", "normalized_date": "2018-10-01", "pages": "920-928", "proceedings_title": null, "publisher": "", "title": "Journal of neuropathology and experimental neurology", "volume": "77", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Deposition of Phosphorylated alpha-Synuclein in the rTg4510 Mouse Model of Tauopathy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chondroitin sulfate proteoglycan (CSPG) is a candidate regulator of embryonic neurogenesis. The aim of this study was to specify the functional significance of CSPG in adult hippocampal neurogenesis using male mice. Here, we showed that neural stem cells and neuronal progenitors in the dentate gyrus were covered in part by CSPG. Pharmacological depletion of CSPG in the dentate gyrus reduced the densities of neuronal progenitors and newborn granule cells. 3D reconstruction of newborn granule cells showed that their maturation was inhibited by CSPG digestion. The novel object recognition test revealed that CSPG digestion caused cognitive memory impairment. Western blot analysis showed that expression of beta-catenin in the dentate gyrus was decreased by CSPG digestion. The amount of CSPG in the dentate gyrus was increased by enriched environment (EE) and was decreased by forced swim stress. In addition, EE accelerated the recovery of CSPG expression in the dentate gyrus from the pharmacological depletion and promoted the restoration of granule cell production. Conversely, the densities of newborn granule cells were also decreased in mice that lacked chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGalNAcT1), a key enzyme for CSPG synthesis (T1KO mice). The capacity of EE to promote granule cell production and improve cognitive memory was impaired in T1KO mice. These findings indicate that CSPG is involved in the regulation of adult hippocampal neurogenesis and suggest that increased synthesis of CSPG by CSGalNacT1 may mediate promotion of granule cell production and improvement of cognitive memory in response to EE.SIGNIFICANCE STATEMENT Chondroitin sulfate proteoglycan (CSPG) is a candidate regulator of embryonic neurogenesis. Here, we specified the role of CSPG in adult neurogenesis in the mouse hippocampus. Digestion of CSPG in the dentate gyrus impaired granule cell production and cognitive memory. Enriched environment (EE) promoted the recovery of CSPG expression and granule cell production from the CSPG digestion. Additionally, adult neurogenesis was impaired in mice that lacked a key enzyme for CSPG synthesis (T1KO mice). The capacity of EE to promote granule cell production and cognitive memory was impaired in T1KO mice. Altogether, these findings indicate that CSPG underlies adult hippocampal neurogenesis and suggest that increased synthesis of CSPG may mediate promotion of granule cell production in response to EE.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Nadanaka", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Shozo", "last_name": "Jinno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.0632-18.2018" }, "pmcid": { "normalized": "PMC6596167" }, "pmid": { "normalized": "30126967" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chondroitin Sulfate Proteoglycans", "descriptor_ui": "D011508", "major_topic": false }, { "descriptor": "Cognition", "descriptor_ui": "D003071", "major_topic": false }, { "descriptor": "Environment", "descriptor_ui": "D004777", "major_topic": true }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "N-Acetylgalactosaminyltransferases", "descriptor_ui": "D017350", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Recognition, Psychology", "descriptor_ui": "D021641", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Sep 26", "date_precision": "day", "issue": "39", "normalized_date": "2018-09-26", "pages": "8496-8513", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "38", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Increased Synthesis of Chondroitin Sulfate Proteoglycan Promotes Adult Hippocampal Neurogenesis in Response to Enriched Environment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Near-haploidy is observed in certain cancer types, but ploidy-dependent alterations in gene regulation in the haploid state remain elusive. Here, by comparative transcriptome analysis between human isogenic haploid and diploid cell lines, we found lowering of cyclin D2 level in haploids. Acute genome duplication in haploids restored cyclin D2 expression to diploid level, indicating that the regulation of cyclin D2 expression is directly linked to ploidy. Downstream pathways of cyclin D2, such as Rb phosphorylation and p27 sequestration remained intact in haploids, suggesting that they adapt to lowered cyclin D level. Interestingly, however, haploid cells were more susceptible to cdk4/6 inhibition compared to diploids. Our finding indicates feasibility of selective growth suppression of haploid cells based on ploidy-linked gene regulation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kan", "last_name": "Yaguchi", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Kiminori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Tokiyoshi", "last_name": "Ayabe", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2018.08.160" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30193733" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cyclin D2", "descriptor_ui": "D056742", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase 4", "descriptor_ui": "D051358", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase 6", "descriptor_ui": "D051361", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Haploidy", "descriptor_ui": "D006238", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Ploidies", "descriptor_ui": "D011003", "major_topic": true }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Sep 26", "date_precision": "day", "issue": "1", "normalized_date": "2018-09-26", "pages": "231-237", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "504", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Ploidy-dependent change in cyclin D2 expression and sensitization to cdk4/6 inhibition in human somatic haploid cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recently, the importance of biopharmaceuticals in medical treatments has been increasing, and effective protein purification methods are strongly required for their production. In the present study, a temperature-responsive solid-phase extraction (SPE) column was developed for the purification of proteins without affecting their bioactivity. A temperature-responsive polymer hydrogel-modified stationary phase was prepared by coating aminopropyl silica beads (average diameter, 40-64 mum) with poly(N-isopropylacrylamide) (PNIPAAm)-based thermoresponsive hydrogels. n-Butyl methacrylate and acrylic acid were copolymerized with PNIPAAm as hydrophobic and anionic monomers, respectively. Using these temperature-responsive SPE columns, targeted proteins were retained on the thermoresponsive hydrogel at 40  degrees C through hydrophobic and electrostatic interactions. After the temperature was reduced from 40  degrees C to 4  degrees C, the retained proteins were successfully eluted from the column. Using the temperature-responsive SPE system, lysozyme was successfully separated from ovalbumin without any loss in bioactivity (99.7 +/- 0.1%). Rituximab, a monoclonal antibody, was also purified from BSA or hybridoma cell culture medium using the prepared SPE column. Denaturation of rituximab was not observed in the rituximab fraction eluted from the SPE column. These results demonstrate that temperature-responsive polymer-based SPE can be applied in biomedical purifications, while maintaining the biological activity of the proteins.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kohei", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Oaku", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nagase", "name": null }, { "creator_type": "author", "first_name": "Hideko", "last_name": "Kanazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chroma.2018.07.027" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30033167" } }, "mesh": [ { "descriptor": "Acrylic Resins", "descriptor_ui": "D000180", "major_topic": false }, { "descriptor": "Chemistry Techniques, Analytical", "descriptor_ui": "D002623", "major_topic": false }, { "descriptor": "Chromatography, Affinity", "descriptor_ui": "D002846", "major_topic": false }, { "descriptor": "Hydrogels", "descriptor_ui": "D020100", "major_topic": false }, { "descriptor": "Hydrophobic and Hydrophilic Interactions", "descriptor_ui": "D057927", "major_topic": false }, { "descriptor": "Muramidase", "descriptor_ui": "D009113", "major_topic": false }, { "descriptor": "Polymerization", "descriptor_ui": "D058105", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Silicon Dioxide", "descriptor_ui": "D012822", "major_topic": false }, { "descriptor": "Solid Phase Extraction", "descriptor_ui": "D052616", "major_topic": true }, { "descriptor": "Static Electricity", "descriptor_ui": "D055672", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018 Sep 21", "date_precision": "day", "issue": "", "normalized_date": "2018-09-21", "pages": "38-48", "proceedings_title": null, "publisher": "", "title": "Journal of chromatography. A", "volume": "1568", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Protein purification using solid-phase extraction on temperature-responsive hydrogel-modified silica beads.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Multiple-system atrophy (MSA) is a neurodegenerative disease characterized by autonomic failure with various combinations of parkinsonism, cerebellar ataxia, and pyramidal dysfunction. We previously reported that functionally impaired variants of COQ2, which encodes an essential enzyme in the biosynthetic pathway of coenzyme Q10, are associated with MSA. Here, we report functional deficiencies in mitochondrial respiration and the antioxidative system in induced pluripotent stem cell (iPSC)-derived neurons from an MSA patient with compound heterozygous COQ2 mutations. The functional deficiencies were rescued by site-specific CRISPR/Cas9-mediated gene corrections. We also report an increase in apoptosis of iPSC-derived neurons from MSA patients. Coenzyme Q10 reduced apoptosis of neurons from the MSA patient with compound heterozygous COQ2 mutations. Our results reveal that cellular dysfunctions attributable to decreased coenzyme Q10 levels are related to neuronal death in MSA, particularly in patients with COQ2 variants, and may contribute to the development of therapy using coenzyme Q10 supplementation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Fumiko Kusunoki", "last_name": "Nakamoto", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Mitsui", "name": null }, { "creator_type": "author", "first_name": "Takefumi", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Yorihiro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Kanegae", "name": null }, { "creator_type": "author", "first_name": "Yuhki", "last_name": "Nakatake", "name": null }, { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Ishiura", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-32573-1" }, "pmcid": { "normalized": "PMC6155102" }, "pmid": { "normalized": "30242188" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Alkyl and Aryl Transferases", "descriptor_ui": "D019883", "major_topic": false }, { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Atrophy", "descriptor_ui": "D001284", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Multiple System Atrophy", "descriptor_ui": "D019578", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Ubiquinone", "descriptor_ui": "D014451", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Sep 21", "date_precision": "day", "issue": "1", "normalized_date": "2018-09-21", "pages": "14215", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "The pathogenesis linked to coenzyme Q10 insufficiency in iPSC-derived neurons from patients with multiple-system atrophy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "G protein-coupled receptors (GPCRs) are major drug targets. Developing a method to measure the activities of GPCRs is essential for pharmacology and drug screening. However, it is difficult to measure the effects of a drug by monitoring the receptor on the cell surface; thus, changes in the concentrations of downstream signaling molecules, which depend on the signaling pathway selectivity of the receptor, are often used as an index of receptor activity. We show that single-molecule imaging analysis provides an alternative method for assessing the effects of ligands on GPCRs. Using total internal reflection fluorescence microscopy (TIRFM), we monitored the dynamics of the diffusion of metabotropic glutamate receptor 3 (mGluR3), a class C GPCR, under various ligand conditions. Our single-molecule tracking analysis demonstrated that increases and decreases in the average diffusion coefficient of mGluR3 quantitatively reflected the ligand-dependent inactivation and activation of receptors, respectively. Through experiments with inhibitors and dual-color single-molecule imaging analysis, we found that the diffusion of receptor molecules was altered by common physiological events associated with GPCRs, including G protein binding, and receptor accumulation in clathrin-coated pits. We also confirmed that agonist also decreased the average diffusion coefficient for class A and B GPCRs, demonstrating that this parameter is a good index for estimating ligand effects on many GPCRs regardless of their phylogenetic groups, the chemical properties of the ligands, or G protein-coupling selectivity.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" }, { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masataka", "last_name": "Yanagawa", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Togashi", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Shichida", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/scisignal.aao1917" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30228224" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "GTP-Binding Proteins", "descriptor_ui": "D019204", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Pertussis Toxin", "descriptor_ui": "D037342", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Radioligand Assay", "descriptor_ui": "D011869", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Xanthenes", "descriptor_ui": "D014966", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Sep 18", "date_precision": "day", "issue": "548", "normalized_date": "2018-09-18", "pages": "eaao1917", "proceedings_title": null, "publisher": "", "title": "Science signaling", "volume": "11", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-molecule diffusion-based estimation of ligand effects on G protein-coupled receptors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ascidians have become a powerful model system in which to uncover basic mechanisms that govern body plan specification and elaboration. In particular, the ascidian notochord is a highly tractable model for tubulogenesis. Here, we use chemical genetics to identify roles for 14-3-3εa, and its binding partner ezrin/radixin/moesin (ERM), in tubulogenesis. Combining genetic and chemical perturbations with live cell imaging, we present evidence that 14-3-3εa–ERM interactions are required for tubulogenesis and that they act by promoting a directed cytoplasmic flow, previously uncharacterized, which carries lumen-associated components from the basal domain to the apical domain to feed lumen growth. Because many core components of this system are highly conserved, these results have broad implications for tubulogenesis in many other contexts.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Mizotani", "name": null }, { "creator_type": "author", "first_name": "Mayu", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kogiku", "last_name": "Shiba", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Etsu", "last_name": "Tashiro", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Imoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1808756115" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30158171" } }, "mesh": [ { "descriptor": "14-3-3 Proteins", "descriptor_ui": "D048948", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzaldehydes", "descriptor_ui": "D001547", "major_topic": false }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Cytoskeletal Proteins", "descriptor_ui": "D003598", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Ezrin", "descriptor_ui": "D000099149", "major_topic": false }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Microfilament Proteins", "descriptor_ui": "D008840", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Morpholinos", "descriptor_ui": "D060172", "major_topic": false }, { "descriptor": "Myosin Type II", "descriptor_ui": "D024462", "major_topic": false }, { "descriptor": "Notochord", "descriptor_ui": "D009672", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Sep 18", "date_precision": "day", "issue": "38", "normalized_date": "2018-09-18", "pages": "E8873-8881", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "115", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "14-3-3εa directs the pulsatile transport of basal factors toward the apical domain for lumen growth in tubulogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herpes simplex virus 1 (HSV-1) UL51 is a phosphoprotein that functions in the final envelopment in the cytoplasm and viral cell-cell spread, leading to efficient viral replication in cell cultures. To clarify the mechanism by which UL51 is regulated in HSV-1-infected cells, we focused on the phosphorylation of UL51. Mass spectrometry analysis of purified UL51 identified five phosphorylation sites in UL51. Alanine replacement of one of the identified phosphorylation sites in UL51, serine 184 (Ser-184), but not the other identified phosphorylation sites, significantly reduced viral replication and cell-cell spread in HaCaT cells. This mutation induced membranous invaginations adjacent to the nuclear membrane, the accumulation of primary enveloped virions in the invaginations and perinuclear space, and mislocalized UL34 and UL31 in punctate structures at the nuclear membrane; however, it had no effect on final envelopment in the cytoplasm of HaCaT cells. Of note, the alanine mutation in UL51 Ser-184 significantly reduced the mortality of mice following ocular infection. Phosphomimetic mutation in UL51 Ser-184 partly restored the wild-type phenotype in cell cultures and in mice. Based on these results, we concluded that some UL51 functions are specifically regulated by phosphorylation at Ser-184 and that this regulation is critical for HSV-1 replication in cell cultures and pathogenicity in vivoIMPORTANCE HSV-1 UL51 is conserved in all members of the Herpesviridae family. This viral protein is phosphorylated and functions in viral cell-cell spread and cytoplasmic virion maturation in HSV-1-infected cells. Although the downstream effects of HSV-1 UL51 have been clarified, there is a lack of information on how this viral protein is regulated as well as the significance of the phosphorylation of this protein in HSV-1-infected cells. In this study, we show that the phosphorylation of UL51 at Ser-184 promotes viral replication, cell-cell spread, and nuclear egress in cell cultures and viral pathogenicity in mice. This is the first report to identify the mechanism by which UL51 is regulated as well as the significance of UL51 phosphorylation in HSV-1 infection. Our study may provide insights into the regulatory mechanisms of other herpesviral UL51 homologs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kozuka-Hata", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01035-18" }, "pmcid": { "normalized": "PMC6146714" }, "pmid": { "normalized": "29976672" } }, "mesh": [ { "descriptor": "Active Transport, Cell Nucleus", "descriptor_ui": "D021581", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "DNA Helicases", "descriptor_ui": "D004265", "major_topic": false }, { "descriptor": "DNA Primase", "descriptor_ui": "D019915", "major_topic": false }, { "descriptor": "Eye", "descriptor_ui": "D005123", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virion", "descriptor_ui": "D014771", "major_topic": false }, { "descriptor": "Virulence", "descriptor_ui": "D014774", "major_topic": false }, { "descriptor": "Virus Assembly", "descriptor_ui": "D019065", "major_topic": false }, { "descriptor": "Virus Release", "descriptor_ui": "D057074", "major_topic": true }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018 Sep 15", "date_precision": "day", "issue": "18", "normalized_date": "2018-09-15", "pages": "e01035-18", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "92", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Roles of the Phosphorylation of Herpes Simplex Virus 1 UL51 at a Specific Site in Viral Replication and Pathogenicity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cellular reducing-oxidizing (redox) potential is mainly determined by the concentration ratio between reduced and oxidized glutathiones. It is normally kept at a moderately reduced state but affected to some extent by metabolic activities such as respiration and/or photosynthesis. Changes in redox potential induce many cellular activities collectively called redox responses. For an understanding of the dynamics of the cellular redox responses, redox potential must be accurately assessed in vivo. In this study, we developed a method to measure the in vivo redox potential in the green alga Chlamydomonas reinhardtii, using Oba-Qc, a recently developed redox-monitoring protein. Taking advantage of the periodic flagellar assembly, we introduced Oba-Qc molecules into the flagella at a constant density. Fluorescence signals from flagella in live cells, calibrated against the fluorescence from the samples in buffers of known redox potentials, determined the redox potential to be approximately -250 mV in the light and approximately -280 mV in the dark. Introduction of a sensor protein fused with a structural protein that assembles at a constant density will be also applicable for measurements of various kinds cellular signals in flagella.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Nishimaki", "name": null }, { "creator_type": "author", "first_name": "Mikito", "last_name": "Owa", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2018.07.163" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30103948" } }, "mesh": [ { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chlamydomonas reinhardtii", "descriptor_ui": "D016825", "major_topic": false }, { "descriptor": "Flagella", "descriptor_ui": "D005407", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Sep 10", "date_precision": "day", "issue": "3", "normalized_date": "2018-09-10", "pages": "2083-2088", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "503", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Assessment of the flagellar redox potential in Chlamydomonas reinhardtii using a redox-sensitive fluorescent protein, Oba-Qc.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The stress-activated protein kinases c-Jun N-terminal kinase (JNK) and p38 are important players in cell-fate decisions in response to environmental stress signals. Crosstalk signaling between JNK and p38 is emerging as an important regulatory mechanism in inflammatory and stress responses. However, it is unknown how this crosstalk affects signaling dynamics, cell-to-cell variation, and cellular responses at the single-cell level. We established a multiplexed live-cell imaging system based on kinase translocation reporters to simultaneously monitor JNK and p38 activities with high specificity and sensitivity at single-cell resolution. Various stresses activated JNK and p38 with various dynamics. In all cases, p38 suppressed JNK activity in a cross-inhibitory manner. We demonstrate that p38 antagonizes JNK through both transcriptional and post-translational mechanisms. This cross-inhibition generates cellular heterogeneity in JNK activity after stress exposure. Our data indicate that this heterogeneity in JNK activity plays a role in fractional killing in response to UV stress.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Haruko", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2018.08.020" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30184500" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Dual Specificity Phosphatase 1", "descriptor_ui": "D054638", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "JNK Mitogen-Activated Protein Kinases", "descriptor_ui": "D048031", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "p38 Mitogen-Activated Protein Kinases", "descriptor_ui": "D048051", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Ultraviolet Rays", "descriptor_ui": "D014466", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Sep 4", "date_precision": "day", "issue": "10", "normalized_date": "2018-09-04", "pages": "2658-2668", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "24", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell-to-Cell Heterogeneity in p38-Mediated Cross-Inhibition of JNK Causes Stochastic Cell Death.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Warburg effect is one of the hallmarks of cancer cells, characterized by enhanced aerobic glycolysis. Despite intense research efforts, its functional relevance or biological significance to facilitate tumor progression is still debatable. Hence the question persists when and how the Warburg effect contributes to carcinogenesis. Especially, the role of metabolic changes at a very early stage of tumorigenesis has received relatively little attention, and how aerobic glycolysis impacts tumor incidence remains largely unknown. Here we discuss a novel paradigm for the effect of the Warburg effect that provides a suppressive role in oncogenesis.Key words: Warburg effect, aerobic glycolysis, cell competition, EDAC.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kojiro", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Riku", "last_name": "Egami", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kon", "name": null } ], "identifiers": { "doi": { "normalized": "10.1247/csf.18018" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30047514" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Sep 1", "date_precision": "day", "issue": "2", "normalized_date": "2018-09-01", "pages": "171-176", "proceedings_title": null, "publisher": "", "title": "Cell structure and function", "volume": "43", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "An Anti-tumorigenic Role of the Warburg Effect at Emergence of Transformed Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "UL13 proteins are serine/threonine protein kinases encoded by herpes simplex virus 1 (HSV-1) and HSV-2. Although the downstream effects of the HSV protein kinases, mostly those of HSV-1 UL13, have been reported, there is a lack of information on how these viral protein kinases are regulated in HSV-infected cells. In this study, we used a large-scale phosphoproteomic analysis of HSV-2-infected cells to identify a physiological phosphorylation site in HSV-2 UL13 (i.e., Ser-18) and investigated the significance of phosphorylation of this site in HSV-2-infected cell cultures and mice. Our results were as follows. (i) An alanine substitution at UL13 Ser-18 (S18A) significantly reduced HSV-2 replication and cell-to-cell spread in U2OS cells to a level similar to those of the UL13-null and kinase-dead mutations. (ii) The UL13 S18A mutation significantly impaired phosphorylation of a cellular substrate of this viral protein kinase in HSV-2-infected U2OS cells. (iii) Following vaginal infection of mice, the UL13 S18A mutation significantly reduced mortality, HSV-2 replication in the vagina, and development of vaginal disease to levels similar to those of the UL13-null and the kinase-dead mutations. (iv) A phosphomimetic substitution at UL13 Ser-18 significantly restored the phenotype observed with the UL13 S18A mutation in U2OS cells and mice. Collectively, our results suggested that phosphorylation of UL13 Ser-18 regulated UL13 function in HSV-2-infected cells and that this regulation was critical for the functional activity of HSV-2 UL13 in vitro and in vivo and also for HSV-2 replication and pathogenesis.IMPORTANCE Based on studies on cellular protein kinases, it is obvious that the regulatory mechanisms of protein kinases are as crucial as their functional consequences. Herpesviruses each encode at least one protein kinase, but the mechanism by which these kinases are regulated in infected cells remains to be elucidated, with a few exceptions, although information on their functional effects has been accumulating. In this study, we have shown that phosphorylation of the HSV-2 UL13 protein kinase at Ser-18 regulated its function in infected cells, and this regulation was critical for HSV-2 replication and pathogenesis in vivo UL13 is conserved in all members of the family Herpesviridae, and this is the first report clarifying the regulatory mechanism of a conserved herpesvirus protein kinase that is involved in viral replication and pathogenesis in vivo Our study may provide insight into the regulatory mechanisms of the other conserved herpesvirus protein kinases.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kozuka-Hata", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00807-18" }, "pmcid": { "normalized": "PMC6096820" }, "pmid": { "normalized": "29899106" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "DNA Mutational Analysis", "descriptor_ui": "D004252", "major_topic": false }, { "descriptor": "Herpes Genitalis", "descriptor_ui": "D006558", "major_topic": false }, { "descriptor": "Herpesvirus 2, Human", "descriptor_ui": "D018258", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Kinases", "descriptor_ui": "D011494", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": true }, { "descriptor": "Virus Internalization", "descriptor_ui": "D053586", "major_topic": false }, { "descriptor": "Virus Release", "descriptor_ui": "D057074", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Sep 1", "date_precision": "day", "issue": "17", "normalized_date": "2018-09-01", "pages": "e00807-18", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "92", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Regulation of Herpes Simplex Virus 2 Protein Kinase UL13 by Phosphorylation and Its Role in Viral Pathogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mammalian sleep comprises REM and NREM stages, but the regulation mechanisms are unclear. In this issue of Cell Reports, Niwa et al. (2018) comprehensively knocked out cholinergic receptors in mice and found that muscarinic signaling is crucial for REM sleep and possibly important for NREM sleep.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuaki", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2018.08.044" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30157417" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Receptors, Muscarinic", "descriptor_ui": "D011976", "major_topic": false }, { "descriptor": "Sleep, REM", "descriptor_ui": "D012895", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Aug 28", "date_precision": "day", "issue": "9", "normalized_date": "2018-08-28", "pages": "2211-2212", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "24", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Life Without Dreams: Muscarinic Receptors Are Required to Regulate REM Sleep in Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vesicle-mediated nucleocytoplasmic transport is a nuclear pore-independent mechanism for the nuclear export of macromolecular complexes, but the molecular basis for this transport remains largely unknown. Here we show that endosomal sorting complex required for transport-III (ESCRT-III) is recruited to the inner nuclear membrane (INM) during the nuclear export of herpes simplex virus 1 (HSV-1). Scission during HSV-1 budding through the INM is prevented by depletion of ESCRT-III proteins. Interestingly, in uninfected human cells, the depletion of ESCRT-III proteins induces aberrant INM proliferation. Our results show that HSV-1 expropriates the ESCRT-III machinery in infected cells for scission of the INM to produce vesicles containing progeny virus nucleocapsids. In uninfected cells, ESCRT-III regulates INM integrity by downregulating excess INM.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Tokai-Nishizumi", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Chihara", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-018-05889-9" }, "pmcid": { "normalized": "PMC6107581" }, "pmid": { "normalized": "30139939" } }, "mesh": [ { "descriptor": "Active Transport, Cell Nucleus", "descriptor_ui": "D021581", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Endosomal Sorting Complexes Required for Transport", "descriptor_ui": "D056827", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "Nuclear Envelope", "descriptor_ui": "D009685", "major_topic": false }, { "descriptor": "Nucleocapsid", "descriptor_ui": "D019251", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Virus Release", "descriptor_ui": "D057074", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018 Aug 23", "date_precision": "day", "issue": "1", "normalized_date": "2018-08-23", "pages": "3379", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "9", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "ESCRT-III mediates budding across the inner nuclear membrane and regulates its integrity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Super-resolution imaging techniques based on single molecule localization microscopy (SMLM) broke the diffraction limit of optical microscopy in living samples with the aid of photoswitchable fluorescent probes and intricate microscopy systems. Here, we developed a fluorescent protein, SPOON, which can be switched off by excitation light illumination and switched on by thermally induced dehydration, resulting in an apparent spontaneous blinking behavior. This unique property of SPOON provides a simple SMLM-based super-resolution imaging platform which requires only a single 488 nm laser.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Takauchi", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Ogami", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acschembio.8b00200" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29963852" } }, "mesh": [ { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Hot Temperature", "descriptor_ui": "D006358", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Mutagenesis", "descriptor_ui": "D016296", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Aug 17", "date_precision": "day", "issue": "8", "normalized_date": "2018-08-17", "pages": "1938-1943", "proceedings_title": null, "publisher": "", "title": "ACS chemical biology", "volume": "13", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Spontaneously Blinking Fluorescent Protein for Simple Single Laser Super-Resolution Live Cell Imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Regulatory T cells (Treg) are negative regulators of the immune response; however, it is poorly understood whether and how Foxp3 transcription is induced and regulated in the periphery during T‐cell responses. Using Foxp3‐Timer of cell kinetics and activity (Tocky) mice, which report real‐time Foxp3 expression, we show that the flux of new Foxp3 expressors and the rate of Foxp3 transcription are increased during inflammation. These persistent dynamics of Foxp3 transcription determine the effector Treg programme and are dependent on a Foxp3 autoregulatory transcriptional circuit. Persistent Foxp3 transcriptional activity controls the expression of coinhibitory molecules, including CTLA‐4 and effector Treg signature genes. Using RNA‐seq, we identify two groups of surface proteins based on their relationship to the temporal dynamics of Foxp3 transcription, and we show proof of principle for the manipulation of Foxp3 dynamics by immunotherapy: new Foxp3 flux is promoted by anti‐TNFRII antibody, and high‐frequency Foxp3 expressors are targeted by anti‐OX40 antibody. Collectively, our study dissects time‐dependent mechanisms behind Foxp3‐driven T‐cell regulation and establishes the Foxp3‐Tocky system as a tool to investigate the mechanisms behind T‐cell immunotherapies.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "David", "last_name": "Bending", "name": null }, { "creator_type": "author", "first_name": "Alina", "last_name": "Paduraru", "name": null }, { "creator_type": "author", "first_name": "Catherine B.", "last_name": "Ducker", "name": null }, { "creator_type": "author", "first_name": "Paz", "last_name": "Prieto Martín", "name": null }, { "creator_type": "author", "first_name": "Tessa", "last_name": "Crompton", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.15252/embj.201899013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29991564" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies", "descriptor_ui": "D000906", "major_topic": false }, { "descriptor": "CTLA-4 Antigen", "descriptor_ui": "D060908", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Receptors, OX40", "descriptor_ui": "D053262", "major_topic": false }, { "descriptor": "Receptors, Tumor Necrosis Factor, Type II", "descriptor_ui": "D047889", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Aug 15", "date_precision": "day", "issue": "16", "normalized_date": "2018-08-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "The EMBO Journal", "volume": "37", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "A temporally dynamic Foxp3 autoregulatory transcriptional circuit controls the effector Treg programme.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bending et al. establish a new tool, Timer of cell kinetics and activity (Tocky), revealing the temporal dynamics of cellular activation and differentiation in vivo. The tool analyzes the temporal sequence of molecular processes during cellular differentiation and can classify cells based on the frequency they receive signaling events in vivo.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "David", "last_name": "Bending", "name": null }, { "creator_type": "author", "first_name": "Paz", "last_name": "Prieto Martín", "name": null }, { "creator_type": "author", "first_name": "Alina", "last_name": "Paduraru", "name": null }, { "creator_type": "author", "first_name": "Catherine", "last_name": "Ducker", "name": null }, { "creator_type": "author", "first_name": "Erik", "last_name": "Marzaganov", "name": null }, { "creator_type": "author", "first_name": "Marie", "last_name": "Laviron", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "Tessa", "last_name": "Crompton", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1083/jcb.201711048" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29941474" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Demethylation", "descriptor_ui": "D000073398", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Aug 06", "date_precision": "day", "issue": "8", "normalized_date": "2018-08-06", "pages": "2931-2950", "proceedings_title": null, "publisher": "", "title": "The Journal of Cell Biology", "volume": "217", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "A timer for analyzing temporally dynamic changes in transcription during differentiation in vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An automated single-molecule imaging system developed for live-cell analyses based on artificial intelligence-assisted microscopy is presented. All significant procedures, i.e., searching for cells suitable for observation, detecting in-focus positions, and performing image acquisition and single-molecule tracking, are fully automated, and numerous highly accurate, efficient, and reproducible single-molecule imaging experiments in living cells can be performed. Here, the apparatus is applied for single-molecule imaging and analysis of epidermal growth factor receptors (EGFRs) in 1600 cells in a 96-well plate within 1 day. Changes in the lateral mobility of EGFRs on the plasma membrane in response to various ligands and drug concentrations are clearly detected in individual cells, and several dynamic and pharmacological parameters are determined, including the diffusion coefficient, oligomer size, and half-maximal effective concentration (EC50). Automated single-molecule imaging for systematic cell signaling analyses is feasible and can be applied to single-molecule screening, thus extensively contributing to biological and pharmacological research.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masato", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Kozuka", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-018-05524-7" }, "pmcid": { "normalized": "PMC6076334" }, "pmid": { "normalized": "30076305" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Tracking", "descriptor_ui": "D058948", "major_topic": false }, { "descriptor": "Cricetulus", "descriptor_ui": "D003412", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Single Molecule Imaging", "descriptor_ui": "D000072760", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Aug 3", "date_precision": "day", "issue": "1", "normalized_date": "2018-08-03", "pages": "3061", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "9", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Automated single-molecule imaging in living cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Allogeneic organ transplants are rejected by the recipient immune system within several days or weeks. However, the rejection process of allogeneic T (allo-T) cells is poorly understood. In this study, using fluorescence-based monitoring and two-photon live imaging in mouse adoptive transfer system, we visualized the fate of allo-T cells in the in vivo environment and showed rapid elimination in secondary lymphoid organs (SLOs). Although i.v. transferred allo-T cells efficiently entered host SLOs, including lymph nodes and the spleen, approximately 70% of the cells had disappeared within 24 h. At early time points, allo-T cells robustly migrated in the T cell area, whereas after 8 h, the numbers of arrested cells and cell fragments were dramatically elevated. Apoptotic breakdown of allo-T cells released a large amount of cell debris, which was efficiently phagocytosed and cleared by CD8(+) dendritic cells. Rapid elimination of allo-T cells was also observed in nu/nu recipients. Depletion of NK cells abrogated allo-T cell reduction only in a specific combination of donor and recipient genetic backgrounds. In addition, F1 hybrid transfer experiments showed that allo-T cell killing was independent of the missing-self signature typically recognized by NK cells. These suggest the presence of a unique and previously uncharacterized modality of allorecognition by the host immune system. Taken together, our findings reveal an extremely efficient and dynamic process of allogeneic lymphocyte elimination in SLOs, which could not be recapitulated in vitro and is distinct from the rejection of solid organ and bone marrow transplants.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Arata", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Madoka", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Kurosawa", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Dana", "last_name": "Bogdanova", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Iioka", "name": null }, { "creator_type": "author", "first_name": "Eisaku", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kitazawa", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Ueta", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Matsuno", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Kinashi", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.4049/jimmunol.1700219" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29925676" } }, "mesh": [ { "descriptor": "Adoptive Transfer", "descriptor_ui": "D019264", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Bone Marrow", "descriptor_ui": "D001853", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Graft Rejection", "descriptor_ui": "D006084", "major_topic": false }, { "descriptor": "Killer Cells, Natural", "descriptor_ui": "D007694", "major_topic": false }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": false }, { "descriptor": "Lymphocytes", "descriptor_ui": "D008214", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Spleen", "descriptor_ui": "D013154", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Aug 1", "date_precision": "day", "issue": "3", "normalized_date": "2018-08-01", "pages": "1062-1072", "proceedings_title": null, "publisher": "", "title": "Journal of immunology (Baltimore, Md. : 1950)", "volume": "201", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualizing the Rapid and Dynamic Elimination of Allogeneic T Cells in Secondary Lymphoid Organs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During development, neurons form synapses with their fate-determined targets. While we begin to elucidate the mechanisms by which extracellular ligand-receptor interactions enhance synapse specificity by inhibiting synaptogenesis, our knowledge about their intracellular mechanisms remains limited. Here we show that Rap2 GTPase (rap-2) and its effector, TNIK (mig-15), act genetically downstream of Plexin (plx-1) to restrict presynaptic assembly and to form tiled synaptic innervation in C. elegans. Both constitutively GTP- and GDP-forms of rap-2 mutants exhibit synaptic tiling defects as plx-1 mutants, suggesting that cycling of the RAP-2 nucleotide state is critical for synapse inhibition. Consistently, PLX-1 suppresses local RAP-2 activity. Excessive ectopic synapse formation in mig-15 mutants causes a severe synaptic tiling defect. Conversely, overexpression of mig-15 strongly inhibited synapse formation, suggesting that mig-15 is a negative regulator of synapse formation. These results reveal that subcellular regulation of small GTPase activity by Plexin shapes proper synapse patterning in vivo.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Xi", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Akihiro Ce", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Ardalan", "last_name": "Hendi", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Kurashina", "name": null }, { "creator_type": "author", "first_name": "Ethan", "last_name": "Fortes", "name": null }, { "creator_type": "author", "first_name": "Nicholas L.", "last_name": "Weilinger", "name": null }, { "creator_type": "author", "first_name": "Brian A.", "last_name": "MacVicar", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Mizumoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.38801" }, "pmcid": { "normalized": "PMC6067881" }, "pmid": { "normalized": "30063210" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": false }, { "descriptor": "Guanosine Diphosphate", "descriptor_ui": "D006153", "major_topic": false }, { "descriptor": "Guanosine Triphosphate", "descriptor_ui": "D006160", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "rap GTP-Binding Proteins", "descriptor_ui": "D020668", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jul 31", "date_precision": "day", "issue": "", "normalized_date": "2018-07-31", "pages": "", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "7", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Rap2 and TNIK control Plexin-dependent tiled synaptic innervation in C. elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "T helper type 1 (Th1) cells form one of the most stable CD4 T-cell subsets, and direct conversion of fully differentiated Th1 to regulatory T (Treg) cells has been poorly investigated. Here, we established a culture method for inducing Foxp3 from Th1 cells of mice and humans. This is achieved simply by resting Th1 cells without T-cell receptor ligation before stimulation in the presence of transforming growth factor-beta (TGF-beta). We named the resulting Th1-derived Foxp3+ cells Th1reg cells. Mouse Th1reg cells showed an inducible Treg-like phenotype and suppressive ability both in vitro and in vivo. Th1reg cells could also be induced from in vivo-developed mouse Th1 cells. Unexpectedly, the resting process enabled Foxp3 expression not through epigenetic changes at the locus, but through metabolic change resulting from reduced mammalian target of rapamycin complex 1 (mTORC1) activity. mTORC1 suppressed TGF-beta-induced phosphorylation of Smad2/3 in Th1 cells, which was restored in rested cells. Our study warrants future research aiming at development of immunotherapy with Th1reg cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Kanamori", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Nakatsukasa", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/intimm/dxy043" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29982622" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false }, { "descriptor": "Th1 Cells", "descriptor_ui": "D018417", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jul 24", "date_precision": "day", "issue": "8", "normalized_date": "2018-07-24", "pages": "357-373", "proceedings_title": null, "publisher": "", "title": "International immunology", "volume": "30", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Reprogramming of Th1 cells into regulatory T cells through rewiring of the metabolic status.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The sarco/endoplasmic reticulum (SR/ER) is the foremost intercellular Ca(2+) store (at submillimolar concentrations), playing a crucial role in controlling intracellular Ca(2+) levels. For the investigation of SR/ER Ca(2+) dynamics in cells, fluorescent protein-based genetically encoded calcium indicators (GECIs) with low Ca(2+) affinity have been used. Recently, bioluminescent protein-based GECIs with high brightness have been reported to counter the constraints of fluorescence imaging, such as phototoxicity. However, their Ca(2+) affinity is high and limited for imaging in the cytosol, nucleus, or mitochondria. In this study, we developed a novel cyan color, low-affinity ( K(d) = 110 muM) intensiometric bioluminescent GECI, which enables monitoring of the Ca(2+) dynamics in the ER of HeLa cells and the SR of C2C12-derived myotubes. To facilitate the broad concentration range of Ca(2+) in cellular organelles, we additionally developed an intermediate affinity ( K(d) = 18 muM), orange color, and bioluminescent GECI, which enables monitoring of Ca(2+) dynamics in the mitochondria of HeLa cells. With these indicators, in conjunction with an existing high-affinity, green, bioluminescent GECI, we succeeded in multicolor bioluminescent Ca(2+) imaging in three distinct organelles (nuclei, mitochondria, and ER) simultaneously. The multicolor, live, bioluminescent Ca(2+) imaging demonstrated here can be used to stably reveal the ER Ca(2+) homeostasis and cooperative Ca(2+) regulation among organelles. This will lead to the further understanding of Ca(2+)-related physiological functions and pathophysiological mechanisms.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Md Nadim", "last_name": "Hossain", "name": null }, { "creator_type": "author", "first_name": "Kazushi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Iwano", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acschembio.7b01014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29494125" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Color", "descriptor_ui": "D003116", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Muscle Fibers, Skeletal", "descriptor_ui": "D018485", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Sarcoplasmic Reticulum", "descriptor_ui": "D012519", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jul 20", "date_precision": "day", "issue": "7", "normalized_date": "2018-07-20", "pages": "1862-1871", "proceedings_title": null, "publisher": "", "title": "ACS chemical biology", "volume": "13", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Bioluminescent Low-Affinity Ca(2+) Indicator for ER with Multicolor Calcium Imaging in Single Living Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Infection of Epstein(-)Barr virus (EBV), a ubiquitous human gamma herpesvirus, is associated with various malignancies in B lymphocytes and epithelial cells. EBV encodes 49 microRNAs in two separated regions, termed the BART and BHRF1 loci. Although accumulating evidence demonstrates that EBV infection regulates the profile of microRNAs in the cells, little is known about the microRNAs in exosomes released from infected cells. Here, we characterized the expression profile of intracellular and exosomal microRNAs in EBV-negative, and two related EBV-infected Burkitt lymphoma cell lines having type I and type III latency by next-generation sequencing. We found that the biogenesis of exosomes is upregulated in type III latently infected cells compared with EBV-negative and type I latently infected cells. We also observed that viral and several specific host microRNAs were predominantly incorporated in the exosomes released from the cells in type III latency. We confirmed that multiple viral microRNAs were transferred to the epithelial cells cocultured with EBV-infected B cells. Our findings indicate that EBV infection, in particular in type III latency, modulates the biogenesis of exosomes and the profile of exosomal microRNAs, potentially contributing to phenotypic changes in cells receiving these exosomes.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Asuka", "last_name": "Nanbo", "name": null }, { "creator_type": "author", "first_name": "Harutaka", "last_name": "Katano", "name": null }, { "creator_type": "author", "first_name": "Michiyo", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Shiho", "last_name": "Hoshina", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Sekizuka", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers10070237" }, "pmcid": { "normalized": "PMC6071279" }, "pmid": { "normalized": "30029522" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018 Jul 19", "date_precision": "day", "issue": "7", "normalized_date": "2018-07-19", "pages": "E237", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "10", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Infection of Epstein(-)Barr Virus in Type III Latency Modulates Biogenesis of Exosomes and the Expression Profile of Exosomal miRNAs in the Burkitt Lymphoma Mutu Cell Lines.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "SNAP-23 is a plasma membrane-localized soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) involved in Fc receptor (FcR)-mediated phagocytosis. However, the regulatory mechanism underlying its function remains elusive. Using phosphorylation-specific antibodies, SNAP-23 was found to be phosphorylated at Ser95 in macrophages. To understand the role of this phosphorylation, we established macrophage lines overexpressing the nonphosphorylatable S95A or the phosphomimicking S95D mutation. The efficiency of phagosome formation and maturation was severely reduced in SNAP-23-S95D-overexpressing cells. To examine whether phosphorylation at Ser95 affected SNAP-23 structure, we constructed intramolecular Förster resonance energy transfer (FRET) probes of SNAP-23 designed to evaluate the approximation of the N termini of the two SNARE motifs. Interestingly, a high FRET efficiency was detected on the membrane when the S95D probe was used, indicating that phosphorylation at Ser95 caused a dynamic structural shift to the closed form. Coexpression of IκB kinase (IKK) 2 enhanced the FRET efficiency of the wild-type probe on the phagosome membrane. Furthermore, the enhanced phagosomal FRET signal in interferon-γ-activated macrophages was largely dependent on IKK2, and this kinase mediated a delay in phagosome-lysosome fusion. These results suggested that SNAP-23 phosphorylation at Ser95 played an important role in the regulation of SNARE-dependent membrane fusion during FcR-mediated phagocytosis.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Chiye", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Itakura", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Seisuke", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Ikuo", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Kiyotaka", "last_name": "Hatsuzawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1091/mbc.e17-08-0523" }, "pmcid": { "normalized": "PMC6080709" }, "pmid": { "normalized": "29771640" } }, "mesh": [ { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interferon-gamma", "descriptor_ui": "D007371", "major_topic": false }, { "descriptor": "Lysosomes", "descriptor_ui": "D008247", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Membrane Fusion", "descriptor_ui": "D008561", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Mutant Proteins", "descriptor_ui": "D050505", "major_topic": false }, { "descriptor": "Phagocytosis", "descriptor_ui": "D010587", "major_topic": false }, { "descriptor": "Phagosomes", "descriptor_ui": "D010588", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Phosphoserine", "descriptor_ui": "D010768", "major_topic": false }, { "descriptor": "Qb-SNARE Proteins", "descriptor_ui": "D050766", "major_topic": false }, { "descriptor": "Qc-SNARE Proteins", "descriptor_ui": "D050767", "major_topic": false }, { "descriptor": "Receptors, Fc", "descriptor_ui": "D011961", "major_topic": false }, { "descriptor": "Structure-Activity Relationship", "descriptor_ui": "D013329", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jul 15", "date_precision": "day", "issue": "13", "normalized_date": "2018-07-15", "pages": "1753-1762", "proceedings_title": null, "publisher": "", "title": "Molecular biology of the cell", "volume": "29", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Phosphorylation of SNAP-23 at Ser95 causes a structural alteration and negatively regulates Fc receptor-mediated phagosome formation and maturation in macrophages.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ovarian cancer is the most aggressive female reproductive tract tumours. Taxane (paclitaxel; TX) is widely used for ovarian cancer treatment. However, ovarian cancers often acquire chemoresistance. MicroRNAs (miR) have been reported to mediate many tumours'chemoresistance. We investigated the role of miR-363 in the chemoresistance of the ovarian cancer cell line, KF, and its TX-resistant derivative (KF-TX) cells. QRT-PCR indicated that miR-363 was upregulated in KF-TX cells, and introduction of miR-363 into sensitive ovarian cancer cells confers TX-resistance and significantly inhibited the expression of the Hippo member, LATS2, as indicated by viability, clonogenic assay and expression analysis. Furthermore, we validated the role of LATS2 in TX-response by sh-based silencing, which also confers TX-resistance to the ovarian cancer cells. On the other hand, specific inhibitor against miR-363 restored the response to TX in the resistant cells. In addition, miR-363 was found to bind to the 3'-UTR of LATS2 mRNA, confirming that miR-363 directly targets LATS2 as indicated by dual luciferase assay. RT-PCR-based evaluation of miR-363 in a panel of human ovarian tumours revealed its upregulation in most of the tumour tissues identified as resistant while it was downregulated in most of the tissues identified as sensitive ones. Moreover, higher levels of miR-363 in human ovarian cancer specimens were significantly correlated with TX chemoresistance. Taken together, our study reveals the involvement of miR-363 in chemoresistance by targeting LATS2 in ovarian cancers, raising the possibility that combination therapy with a miR-363 inhibitor and TX may increase TX efficacy and reduce the chance of TX-resistance.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Zeinab", "last_name": "Mohamed", "name": null }, { "creator_type": "author", "first_name": "Mohamed Kamel", "last_name": "Hassan", "name": null }, { "creator_type": "author", "first_name": "Safwat", "last_name": "Okasha", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Mitamura", "name": null }, { "creator_type": "author", "first_name": "Sarah", "last_name": "Keshk", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Sherif F.", "last_name": "El-Khamisy", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Hidemichi", "last_name": "Watari", "name": null } ], "identifiers": { "doi": { "normalized": "10.18632/oncotarget.25698" }, "pmcid": { "normalized": "PMC6059020" }, "pmid": { "normalized": "30046387" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018 Jul 10", "date_precision": "day", "issue": "53", "normalized_date": "2018-07-10", "pages": "30053-30065", "proceedings_title": null, "publisher": "", "title": "Oncotarget", "volume": "9", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "miR-363 confers taxane resistance in ovarian cancer by targeting the Hippo pathway member, LATS2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Myogenesis-promoting chemicals are an important source of new pharmaceuticals for the treatment of skeletal muscle atrophy that impairs quality of life. This report presents a robust and quantitative bioluminescence-based assay for screening myogenesis-promoting compounds in chemical libraries. The assay system consists of two stable C2C12 myoblast cell lines, each of which expresses either an N-terminal or a C-terminal split luciferase fragment fused to a naturally split DnaE intein as an indicator for cell fusion. Cell fusion during myogenesis induces bioluminescence in the cytosol because of the reconstitution of luciferases. The luminescence intensity quantitatively represents the progress in the cell fusion and therefore indicates the extent of myogenesis. We applied this assay system to a high-throughput screening of myogenesis-promoting compouns in 1191 pharmacologically proven bioactive small molecules, which revealed two chemical compounds as myogenesis-promoting compounds: Imatinib and Doxazosin mesylate. The assay system enabled a robust and quantitative evaluation of the extent of myogenesis through simple luminescence measurements, and is expected to be widely applicable for high-throughput screening of cell fusion-promoting and inhibiting molecules.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Qiaojing", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Komiya", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Tajiri", "name": null }, { "creator_type": "author", "first_name": "Motonari", "last_name": "Uesugi", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c8an00285a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29944152" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Fusion", "descriptor_ui": "D002459", "major_topic": true }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Doxazosin", "descriptor_ui": "D017292", "major_topic": false }, { "descriptor": "Imatinib Mesylate", "descriptor_ui": "D000068877", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle Development", "descriptor_ui": "D024510", "major_topic": true }, { "descriptor": "Myoblasts", "descriptor_ui": "D032446", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jul 9", "date_precision": "day", "issue": "14", "normalized_date": "2018-07-09", "pages": "3472-3480", "proceedings_title": null, "publisher": "", "title": "The Analyst", "volume": "143", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "A robust split-luciferase-based cell fusion screening for discovering myogenesis-promoting molecules.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transforming growth factor-beta (TGF-beta) regulates reciprocal regulatory T cell (T reg) and T helper 17 (Th17) differentiation, the underlying mechanism of which is still not understood. Here, we report that tripartite motif-containing 33 (Trim33), a modulator of TGF-beta signaling that associates with Smad2, regulates the proinflammatory function of Th17 cells. Trim33 deficiency in T cells ameliorated an autoimmune disease in vivo. Trim33 was required for induction in vitro of Th17, but not T reg cells. Moreover, Smad4 and Trim33 play contrasting roles in the regulation of IL-10 expression; loss of Trim33 enhanced IL-10 production. Furthermore, Trim33 was recruited to the Il17a and Il10 gene loci, dependent on Smad2, and mediated their chromatin remodeling during Th17 differentiation. Trim33 thus promotes the proinflammatory function of Th17 cells by inducing IL-17 and suppressing IL-10 expression.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Jiang", "name": null }, { "creator_type": "author", "first_name": "Gustavo J.", "last_name": "Martinez", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Xiaowei", "last_name": "Yan", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kurosaki", "name": null }, { "creator_type": "author", "first_name": "Vesa", "last_name": "Kaartinen", "name": null }, { "creator_type": "author", "first_name": "Xin-Hua", "last_name": "Feng", "name": null }, { "creator_type": "author", "first_name": "Qiang", "last_name": "Tian", "name": null }, { "creator_type": "author", "first_name": "Xiaohu", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Chen", "last_name": "Dong", "name": null } ], "identifiers": { "doi": { "normalized": "10.1084/jem.20170779" }, "pmcid": { "normalized": "PMC6028517" }, "pmid": { "normalized": "29930104" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Genetic Loci", "descriptor_ui": "D056426", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Interleukin-10", "descriptor_ui": "D016753", "major_topic": false }, { "descriptor": "Interleukin-17", "descriptor_ui": "D020381", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Nuclear Receptor Subfamily 1, Group F, Member 3", "descriptor_ui": "D057132", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Smad2 Protein", "descriptor_ui": "D051899", "major_topic": false }, { "descriptor": "Smad4 Protein", "descriptor_ui": "D051901", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false }, { "descriptor": "Th17 Cells", "descriptor_ui": "D058504", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jul 2", "date_precision": "day", "issue": "7", "normalized_date": "2018-07-02", "pages": "1853-1868", "proceedings_title": null, "publisher": "", "title": "The Journal of experimental medicine", "volume": "215", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Trim33 mediates the proinflammatory function of Th17 cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In animals, somatic cells are usually diploid and are unstable when haploid for unknown reasons. In this study, by comparing isogenic human cell lines with different ploidies, we found frequent centrosome loss specifically in the haploid state, which profoundly contributed to haploid instability through subsequent mitotic defects. We also found that the efficiency of centriole licensing and duplication changes proportionally to ploidy level, whereas that of DNA replication stays constant. This caused gradual loss or frequent overduplication of centrioles in haploid and tetraploid cells, respectively. Centriole licensing efficiency seemed to be modulated by astral microtubules, whose development scaled with ploidy level, and artificial enhancement of aster formation in haploid cells restored centriole licensing efficiency to diploid levels. The ploidy-centrosome link was observed in different mammalian cell types. We propose that incompatibility between the centrosome duplication and DNA replication cycles arising from different scaling properties of these bioprocesses upon ploidy changes underlies the instability of non-diploid somatic cells in mammals.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kan", "last_name": "Yaguchi", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Shibanuma", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kamimura", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Koda", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1083/jcb.201701151" }, "pmcid": { "normalized": "PMC6028549" }, "pmid": { "normalized": "29712735" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Centrioles", "descriptor_ui": "D002502", "major_topic": false }, { "descriptor": "Centrosome", "descriptor_ui": "D018385", "major_topic": false }, { "descriptor": "Diploidy", "descriptor_ui": "D004171", "major_topic": false }, { "descriptor": "DNA Replication", "descriptor_ui": "D004261", "major_topic": false }, { "descriptor": "Haploidy", "descriptor_ui": "D006238", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jul 2", "date_precision": "day", "issue": "7", "normalized_date": "2018-07-02", "pages": "2463-2483", "proceedings_title": null, "publisher": "", "title": "The Journal of cell biology", "volume": "217", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Uncoordinated centrosome cycle underlies the instability of non-diploid somatic cells in mammals.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cytokines are key modulators of immunity. Most cytokines use the Janus kinase and signal transducers and activators of transcription (JAK-STAT) pathway to promote gene transcriptional regulation, but their signals must be attenuated by multiple mechanisms. These include the suppressors of cytokine signaling (SOCS) family of proteins, which represent a main negative regulation mechanism for the JAK-STAT pathway. Cytokine-inducible Src homology 2 (SH2)-containing protein (CIS), SOCS1, and SOCS3 proteins regulate cytokine signals that control the polarization of CD4(+) T cells and the maturation of CD8(+) T cells. SOCS proteins also regulate innate immune cells and are involved in tumorigenesis. This review summarizes recent progress on CIS, SOCS1, and SOCS3 in T cells and tumor immunity.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Akanuma", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Nakatsukasa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/cshperspect.a028571" }, "pmcid": { "normalized": "PMC6028070" }, "pmid": { "normalized": "28716890" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jul 2", "date_precision": "day", "issue": "7", "normalized_date": "2018-07-02", "pages": "a028571", "proceedings_title": null, "publisher": "", "title": "Cold Spring Harbor perspectives in biology", "volume": "10", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Negative Regulation of Cytokine Signaling in Immunity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neuronal growth cones are essential for nerve growth and regeneration, as well as for the formation and rearrangement of the neural network. To elucidate phosphorylation-dependent signaling pathways and establish useful molecular markers for axon growth and regeneration, we performed a phosphoproteomics study of mammalian growth cones, which identified >30,000 phosphopeptides of approximately 1,200 proteins. The phosphorylation sites were highly proline directed and primarily MAPK dependent, owing to the activation of JNK, suggesting that proteins that undergo proline-directed phosphorylation mediate nerve growth in the mammalian brain. Bioinformatics analysis revealed that phosphoproteins were enriched in microtubules and the cortical cytoskeleton. The most frequently phosphorylated site was S96 of GAP-43 (growth-associated protein 43-kDa), a vertebrate-specific protein involved in axon growth. This previously uncharacterized phosphorylation site was JNK dependent. S96 phosphorylation was specifically detected in growing and regenerating axons as the most frequent target of JNK signaling; thus it represents a promising new molecular marker for mammalian axonal growth and regeneration.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Asami", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Masayasu", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tamada", "name": null }, { "creator_type": "author", "first_name": "Shujiro", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nozumi", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Tokiwa", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nishina", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Igarashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2018.05.019" }, "pmcid": { "normalized": "PMC6147025" }, "pmid": { "normalized": "30240740" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018 Jun 29", "date_precision": "day", "issue": "", "normalized_date": "2018-06-29", "pages": "190-203", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "4", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Growth Cone Phosphoproteomics Reveals that GAP-43 Phosphorylated by JNK Is a Marker of Axon Growth and Regeneration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "p53 is a tumor suppressor protein, and its missense mutations are frequently found in human cancers. During the multi-step progression of cancer, p53 mutations generally accumulate at the mid or late stage, but not in the early stage, and the underlying mechanism is still unclear. In this study, using mammalian cell culture and mouse ex vivo systems, we demonstrate that when p53R273H- or p53R175H-expressing cells are surrounded by normal epithelial cells, mutant p53 cells undergo necroptosis and are basally extruded from the epithelial monolayer. When mutant p53 cells alone are present, cell death does not occur, indicating that necroptosis results from cell competition with the surrounding normal cells. Furthermore, when p53R273H mutation occurs within RasV12-transformed epithelia, cell death is strongly suppressed and most of the p53R273H-expressing cells remain intact. These results suggest that the order of oncogenic mutations in cancer development could be dictated by cell competition.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kojiro", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Kitamoto", "name": null }, { "creator_type": "author", "first_name": "Nanami", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Hoshiba", "name": null }, { "creator_type": "author", "first_name": "Mugihiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Matsuzawa", "name": null }, { "creator_type": "author", "first_name": "Yasuto", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Morioka", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Imagawa", "name": null }, { "creator_type": "author", "first_name": "Kazuyasu", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Yonezawa", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kon", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2018.05.081" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29949757" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p21", "descriptor_ui": "D050759", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Mutagenesis, Site-Directed", "descriptor_ui": "D016297", "major_topic": false }, { "descriptor": "Receptor-Interacting Protein Serine-Threonine Kinases", "descriptor_ui": "D053422", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jun 26", "date_precision": "day", "issue": "13", "normalized_date": "2018-06-26", "pages": "3721-3729", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "23", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Mutant p53-Expressing Cells Undergo Necroptosis via Cell Competition with the Neighboring Normal Epithelial Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Accumulation of ubiquitinated protein aggregates is a common pathology associated with a number of neurodegenerative diseases and selective autophagy plays a critical role in their elimination. Although aging-related decreases in protein degradation properties may enhance protein aggregation, it remains unclear whether proteasome dysfunction is indispensable for ubiquitinated-protein aggregation in neurodegenerative diseases. Here, we show that N-oleoyl-dopamine and N-arachidonyl-dopamine, which are endogenous brain substances and belong to the N-acyldopamine (AcylDA) family, generate cellular inclusions through aggresome formation without proteasome inhibition. Although AcylDA itself does not inhibit proteasome activity in vitro, it activates the rearrangement of vimentin distribution to form a vimentin cage surrounding aggresomes and sequesters ubiquitinated proteins in aggresomes. The gene transcription of p62/SQSTM1 was significantly increased by AcylDAs, whereas the transcription of other ubiquitin-dependent autophagy receptors was unaffected. Genetic depletion of p62 resulted in the loss of ubiquitinated-protein sequestration in aggresomes, indicating that p62 is a critical component of aggresomes. Furthermore, AcylDAs accelerate the aggregation of mutant huntingtin exon 1 proteins. These results suggest that aggresome formation does not require proteasome dysfunction and AcylDA-induced aggresome formation may participate in forming cytoplasmic protein inclusions.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Gen", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Tomonao", "last_name": "Inobe", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Kiyohito", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Nukina", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-27872-6" }, "pmcid": { "normalized": "PMC6018635" }, "pmid": { "normalized": "29941919" } }, "mesh": [ { "descriptor": "Arachidonic Acids", "descriptor_ui": "D001095", "major_topic": false }, { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Drug Evaluation, Preclinical", "descriptor_ui": "D004353", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Huntingtin Protein", "descriptor_ui": "D000071058", "major_topic": false }, { "descriptor": "Leupeptins", "descriptor_ui": "D007976", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Proteasome Endopeptidase Complex", "descriptor_ui": "D046988", "major_topic": false }, { "descriptor": "Protein Aggregates", "descriptor_ui": "D066329", "major_topic": false }, { "descriptor": "Sequestosome-1 Protein", "descriptor_ui": "D000071456", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jun 25", "date_precision": "day", "issue": "1", "normalized_date": "2018-06-25", "pages": "9585", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "N-Acyldopamine induces aggresome formation without proteasome inhibition and enhances protein aggregation via p62/SQSTM1 expression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Si-Rhodamines are bright fluorophores with red to near-infrared (NIR) emission, and are widely used for fluorescence imaging of biological phenomena. Here, in order to extend the scope of Si-rhodamine fluorophores, we established a versatile synthesis of unsymmetrical Si-rhodamines. To illustrate its value, we used one of these new fluorophores to synthesize a far-red to NIR fluorescence probe for hypoxia, and showed that it can visualize hepatic ischemia in mice in vivo.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Kagami", "name": null }, { "creator_type": "author", "first_name": "Wen", "last_name": "Piao", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Myochin", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Numasawa", "name": null }, { "creator_type": "author", "first_name": "Yugo", "last_name": "Kuriki", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ikeno", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c8cc02451k" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29862387" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018 Jun 19", "date_precision": "day", "issue": "50", "normalized_date": "2018-06-19", "pages": "6939-6942", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "54", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis of unsymmetrical Si-rhodamine fluorophores and application to a far-red to near-infrared fluorescence probe for hypoxia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ghost imaging is a technique used to produce an object's image without using a spatially resolving detector. Here we develop a technique we term \"ghost cytometry,\" an image-free ultrafast fluorescence \"imaging\" cytometry based on a single-pixel detector. Spatial information obtained from the motion of cells relative to a static randomly patterned optical structure is compressively converted into signals that arrive sequentially at a single-pixel detector. Combinatorial use of the temporal waveform with the intensity distribution of the random pattern allows us to computationally reconstruct cell morphology. More importantly, we show that applying machine-learning methods directly on the compressed waveforms without image reconstruction enables efficient image-free morphology-based cytometry. Despite a compact and inexpensive instrumentation, image-free ghost cytometry achieves accurate and high-throughput cell classification and selective sorting on the basis of cell morphology without a specific biomarker, both of which have been challenging to accomplish using conventional flow cytometers.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Horisaki", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Ugawa", "name": null }, { "creator_type": "author", "first_name": "Issei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kamesawa", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Setoyama", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Katsuhito", "last_name": "Fujiu", "name": null }, { "creator_type": "author", "first_name": "Kayo", "last_name": "Waki", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Noji", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.aan0096" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29903975" } }, "mesh": [ { "descriptor": "Cell Separation", "descriptor_ui": "D002469", "major_topic": false }, { "descriptor": "Cells", "descriptor_ui": "D002477", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Cytometry", "descriptor_ui": "D019044", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "MCF-7 Cells", "descriptor_ui": "D061986", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jun 15", "date_precision": "day", "issue": "6394", "normalized_date": "2018-06-15", "pages": "1246-1251", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "360", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Ghost cytometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Influenza A virus (IAV) infection is initiated by the attachment of the viral glycoprotein hemagglutinin (HA) to sialic acid on the host cell surface. However, the sialic acid-containing receptor crucial for IAV infection has remained unidentified. Here, we show that HA binds to the voltage-dependent Ca(2+) channel Cav1.2 to trigger intracellular Ca(2+) oscillations and subsequent IAV entry and replication. IAV entry was inhibited by Ca(2+) channel blockers (CCBs) or by knockdown of Cav1.2. The CCB diltiazem also inhibited virus replication in vivo. Reintroduction of wild-type but not the glycosylation-deficient mutants of Cav1.2 restored Ca(2+) oscillations and virus infection in Cav1.2-depleted cells, demonstrating the significance of Cav1.2 sialylation. Taken together, we identify Cav1.2 as a sialylated host cell surface receptor that binds HA and is critical for IAV entry.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Nishide", "name": null }, { "creator_type": "author", "first_name": "Toyoyuki", "last_name": "Ose", "name": null }, { "creator_type": "author", "first_name": "Tadaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Kosui", "last_name": "Horiuchi", "name": null }, { "creator_type": "author", "first_name": "Aya O.", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Prabha", "last_name": "Nepal", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Jing", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Horiguchi", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Sarad", "last_name": "Paudel", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Nanbo", "name": null }, { "creator_type": "author", "first_name": "Tadaaki", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Maenaka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chom.2018.04.015" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29779930" } }, "mesh": [ { "descriptor": "A549 Cells", "descriptor_ui": "D000072283", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Channels, L-Type", "descriptor_ui": "D020746", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Hemagglutinin Glycoproteins, Influenza Virus", "descriptor_ui": "D019267", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Influenza A virus", "descriptor_ui": "D009980", "major_topic": false }, { "descriptor": "Influenza, Human", "descriptor_ui": "D007251", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Orthomyxoviridae Infections", "descriptor_ui": "D009976", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jun 13", "date_precision": "day", "issue": "6", "normalized_date": "2018-06-13", "pages": "809-818.e5", "proceedings_title": null, "publisher": "", "title": "Cell host & microbe", "volume": "23", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "A Sialylated Voltage-Dependent Ca(2+) Channel Binds Hemagglutinin and Mediates Influenza A Virus Entry into Mammalian Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Box jellyfish and vertebrates are separated by >500 million years of evolution yet have structurally analogous lens eyes that employ rhodopsin photopigments for vision. All opsins possess a negatively charged residue-the counterion-to maintain visible-light sensitivity and facilitate photoisomerization of their retinaldehyde chromophore. In vertebrate rhodopsins, the molecular evolution of the counterion position-from a highly conserved distal location in the second extracellular loop (E181) to a proximal location in the third transmembrane helix (E113)-is established as a key driver of higher fidelity photoreception. Here, we use computational biology and heterologous action spectroscopy to determine whether the appearance of the advanced visual apparatus in box jellyfish was also accompanied by changes in the opsin tertiary structure. We found that the counterion in an opsin from the lens eye of the box jellyfish Carybdea rastonii (JellyOp) has also moved to a unique proximal location within the transmembrane bundle-E94 in TM2. Furthermore, we reveal that this Schiff base/counterion system includes an additional positive charge-R186-that has coevolved with E94 to functionally separate E94 and E181 in the chromophore-binding pocket of JellyOp. By engineering this pocket-neutralizing R186 and E94, or swapping E94 with the vertebrate counterion E113-we can recreate versions of the invertebrate and vertebrate counterion systems, respectively, supporting a relatively similar overall architecture in this region of animal opsins. In summary, our data establish the third only counterion site in animal opsins and reveal convergent evolution of tertiary structure in opsins from distantly related species with advanced visual systems.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Elliot", "last_name": "Gerrard", "name": null }, { "creator_type": "author", "first_name": "Eshita", "last_name": "Mutt", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Tilman", "last_name": "Flock", "name": null }, { "creator_type": "author", "first_name": "Elena", "last_name": "Lesca", "name": null }, { "creator_type": "author", "first_name": "Gebhard F. X.", "last_name": "Schertler", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null }, { "creator_type": "author", "first_name": "Xavier", "last_name": "Deupi", "name": null }, { "creator_type": "author", "first_name": "Robert J.", "last_name": "Lucas", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1721333115" }, "pmcid": { "normalized": "PMC6004467" }, "pmid": { "normalized": "29793939" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cubozoa", "descriptor_ui": "D037462", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": true }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Rhodopsin", "descriptor_ui": "D012243", "major_topic": true }, { "descriptor": "Vision, Ocular", "descriptor_ui": "D014785", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jun 12", "date_precision": "day", "issue": "24", "normalized_date": "2018-06-12", "pages": "6201-6206", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "115", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Convergent evolution of tertiary structure in rhodopsin visual proteins from vertebrates and box jellyfish.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In many species, individual social animals interact with others in their group and change their collective behaviours. For the solitary nematode Caenorhabditis elegans strain N2, previous research suggests that individuals can change the behaviour of other worms via pheromones and mechanosensory interactions. In particular, pheromones affect foraging behaviour, so that the chemotactic behaviours of individuals in a group (population) can be modulated by interactions with other individuals in the population. To investigate this, we directly compared the chemotactic behaviours of isolated (single) worms with those of individual animals within a population. We found that worms approached an odour source in a distinct manner depending on whether they were alone or in a population. Analysis of behaviours of the N2 worm and a pheromone production-defective mutant revealed that the 'pirouette' strategy was modulated by interaction of the worms via pheromones. Thus, pheromones play an important role in the characteristic collective behaviours seen in the population condition.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Toshiki", "last_name": "Yoshimizu", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Shidara", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Ashida", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/jeb.182790" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29691312" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": false }, { "descriptor": "Feeding Behavior", "descriptor_ui": "D005247", "major_topic": false }, { "descriptor": "Pheromones", "descriptor_ui": "D010675", "major_topic": false }, { "descriptor": "Population Density", "descriptor_ui": "D011156", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jun 12", "date_precision": "day", "issue": "Pt 11", "normalized_date": "2018-06-12", "pages": "jeb182790", "proceedings_title": null, "publisher": "", "title": "The Journal of experimental biology", "volume": "221", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Effect of interactions among individuals on the chemotaxis behaviours of Caenorhabditis elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genetically encoded biosensors based on the principle of Forster resonance energy transfer comprise two major classes: biosensors based on fluorescence resonance energy transfer (FRET) and those based on bioluminescence energy transfer (BRET). The FRET biosensors visualize signaling-molecule activity in cells or tissues with high resolution. Meanwhile, due to the low background signal, the BRET biosensors are primarily used in drug screening. Here, we report a protocol to transform intramolecular FRET biosensors to BRET-FRET hybrid biosensors called hyBRET biosensors. The hyBRET biosensors retain all properties of the prototype FRET biosensors and also work as BRET biosensors with dynamic ranges comparable to the prototype FRET biosensors. The hyBRET biosensors are compatible with optogenetics, luminescence microplate reader assays, and non-invasive whole-body imaging of xenograft and transgenic mice. This simple protocol will expand the use of FRET biosensors and enable visualization of the multiscale dynamics of cell signaling in live animals.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Imanishi", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kamioka", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Sumiyama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-27174-x" }, "pmcid": { "normalized": "PMC5997707" }, "pmid": { "normalized": "29895862" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018 Jun 12", "date_precision": "day", "issue": "1", "normalized_date": "2018-06-12", "pages": "8984", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "8", "year": 2018 }, "ssbd": { "database": [ "ssbd-database-000129" ], "repository": [ "ssbd-repos-000129" ] }, "title": "A platform of BRET-FRET hybrid biosensors for optogenetics, chemical screening, and in vivo imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Long noncoding RNAs (lncRNAs) are pervasively transcribed in the eukaryotic genome [1] and are important for the control of master regulatory genes that are involved in cell differentiation and development [2, 3]. Here, we show that a 5' UTR-overlapping lncRNA regulates the male-specific expression of the DM-domain gene doublesex1 (dsx1) in the crustacean Daphnia magna, which produces males in response to environmental stimuli. This lncRNA, named doublesex1 alpha promoter-associated long RNA (DAPALR), is transcribed upstream the transcription start site (TSS) in a sense orientation and subjected to 5' end capping and 3' end processing at a stem-loop structure before the dsx1 coding exon. Similar to dsx1, its expression is only activated in males by the juvenile hormone (JH) and basic-leucine zipper (bZIP) transcription factor Vrille (Vri) and is maintained during embryogenesis. Knockdown of DAPALR in males silenced dsx1 and led to feminization, including egg production, whereas ectopic expression of DAPALR in dsx1-silenced females resulted in the de-repression of dsx1. We further demonstrate that the DAPALR transcript overlaps the dsx1 5'-UTR, and this overlapping region is required for dsx1 activation. Our results suggest that DAPALR can transactivate and possibly maintain dsx1 expression. This might be important for converting transient environmental signals into stable male development, controlled by the continuous expression of dsx1.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Christelle Alexa G.", "last_name": "Perez", "name": null }, { "creator_type": "author", "first_name": "Nur Syafiqah", "last_name": "Mohamad Ishak", "name": null }, { "creator_type": "author", "first_name": "Quang D.", "last_name": "Nong", "name": null }, { "creator_type": "author", "first_name": "Yuumi", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2018.04.029" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29804806" } }, "mesh": [ { "descriptor": "5' Untranslated Regions", "descriptor_ui": "D020121", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arthropod Proteins", "descriptor_ui": "D060829", "major_topic": false }, { "descriptor": "Basic-Leucine Zipper Transcription Factors", "descriptor_ui": "D050976", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Juvenile Hormones", "descriptor_ui": "D007605", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "RNA, Long Noncoding", "descriptor_ui": "D062085", "major_topic": false }, { "descriptor": "Sex Determination Processes", "descriptor_ui": "D019849", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jun 4", "date_precision": "day", "issue": "11", "normalized_date": "2018-06-04", "pages": "1811-1817.e4", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "28", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "A 5' UTR-Overlapping LncRNA Activates the Male-Determining Gene doublesex1 in the Crustacean Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Enhanced infiltration of regulatory T cells (Treg) into tumor tissue is detrimental to patients with cancer and is closely associated with poor prognosis as they create an immunosuppressive state that suppresses antitumor immune responses. Therefore, breaking Treg-mediated immune tolerance is important when considering cancer immunotherapy. Here, we show that the Nr4a nuclear receptors, key transcription factors maintaining Treg genetic programs, contribute to Treg-mediated suppression of antitumor immunity in the tumor microenvironment. Mice lacking Nr4a1 and Nr4a2 genes specifically in Tregs showed resistance to tumor growth in transplantation models without exhibiting any severe systemic autoimmunity. The chemotherapeutic agent camptothecin and a common cyclooxygenase-2 inhibitor were found to inhibit transcriptional activity and induction of Nr4a factors, and they synergistically exerted antitumor effects. Genetic inactivation or pharmacologic inhibition of Nr4a factors unleashed effector activities of CD8(+) cytotoxic T cells and evoked potent antitumor immune responses. These findings demonstrate that inactivation of Nr4a in Tregs breaks immune tolerance toward cancer, and pharmacologic modulation of Nr4a activity may be a novel cancer treatment strategy targeting the immunosuppressive tumor microenvironment.Significance: This study reveals the role of Nr4a transcription factors in Treg-mediated tolerance to antitumor immunity, with possible therapeutic implications for developing effective anticancer therapies. Cancer Res; 78(11); 3027-40. (c)2018 AACR.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sana", "last_name": "Hibino", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Nakatsukasa", "name": null }, { "creator_type": "author", "first_name": "Setsuko", "last_name": "Omata-Mise", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/0008-5472.can-17-3102" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29559474" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autoimmunity", "descriptor_ui": "D015551", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cyclooxygenase 2", "descriptor_ui": "D051546", "major_topic": false }, { "descriptor": "Cyclooxygenase 2 Inhibitors", "descriptor_ui": "D052246", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Tolerance", "descriptor_ui": "D007108", "major_topic": false }, { "descriptor": "Immunotherapy", "descriptor_ui": "D007167", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Receptors, Cytoplasmic and Nuclear", "descriptor_ui": "D018160", "major_topic": false }, { "descriptor": "T-Lymphocytes, Cytotoxic", "descriptor_ui": "D013602", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jun 1", "date_precision": "day", "issue": "11", "normalized_date": "2018-06-01", "pages": "3027-3040", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "78", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Inhibition of Nr4a Receptors Enhances Antitumor Immunity by Breaking Treg-Mediated Immune Tolerance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "T helper 17 (Th17) cell development is programmed by the orphan nuclear receptor RORgammat, but the underlying mechanism is not well understood. Nuclear receptor-mediated transcriptional activation depends on coactivators. Here, we show that steroid receptor coactivator-3 (SRC-3) critically regulates Th17 cell differentiation. Reduced incidence of experimental autoimmune encephalitis (EAE) associated with decreased Th17 cell generation in vivo was observed in mice with SRC-3 deletion specifically in T cells. In vitro, SRC-3 deficiency did not affect TGF-beta/IL-6-induced Th17 cell generation but severely impaired pathogenic Th17 differentiation induced by IL-1/IL-6/IL-23. Microarray analysis revealed that SRC-3 not only regulates IL-17A but also IL-1R1 expression. SRC-3 bound to Il17a and Il1r1 loci in a RORgammat-dependent manner and was required for recruitment of the p300 acetyltransferase. Thus, SRC-3 is critical for RORgammat-dependent gene expression in Th17 cell-driven autoimmune diseases.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kentaro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Gustavo J.", "last_name": "Martinez", "name": null }, { "creator_type": "author", "first_name": "Xiaowei", "last_name": "Yan", "name": null }, { "creator_type": "author", "first_name": "Weiwen", "last_name": "Long", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Ichiyama", "name": null }, { "creator_type": "author", "first_name": "Xinxin", "last_name": "Chi", "name": null }, { "creator_type": "author", "first_name": "Byung-Seok", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Joseph M.", "last_name": "Reynolds", "name": null }, { "creator_type": "author", "first_name": "Yeonseok", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Lan", "last_name": "Liao", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Pan", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Xiaohu", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Qiang", "last_name": "Tian", "name": null }, { "creator_type": "author", "first_name": "Jianming", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Bert W.", "last_name": "O'Malley", "name": null }, { "creator_type": "author", "first_name": "Chen", "last_name": "Dong", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2018.04.088" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29791844" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Encephalomyelitis, Autoimmune, Experimental", "descriptor_ui": "D004681", "major_topic": false }, { "descriptor": "Genetic Loci", "descriptor_ui": "D056426", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interleukins", "descriptor_ui": "D007378", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nuclear Receptor Coactivator 3", "descriptor_ui": "D056921", "major_topic": false }, { "descriptor": "Nuclear Receptor Subfamily 1, Group F, Member 3", "descriptor_ui": "D057132", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Receptors, Interleukin-1", "descriptor_ui": "D017472", "major_topic": false }, { "descriptor": "Th17 Cells", "descriptor_ui": "D058504", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 May 22", "date_precision": "day", "issue": "8", "normalized_date": "2018-05-22", "pages": "2318-2329", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "23", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Regulation of Pathogenic T Helper 17 Cell Differentiation by Steroid Receptor Coactivator-3.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurofibrillary tangles composed of hyperphosphorylated tau protein are primarily neuropathological features of a number of neurodegenerative diseases collectively termed tauopathy. To understand the mechanisms underlying the cause of tauopathy, precise cellular and animal models are required. Recent data suggest that the transient introduction of exogenous tau can accelerate the development of tauopathy in the brains of non-transgenic and transgenic mice expressing wild-type human tau. However, the transmission mechanism leading to tauopathy is not fully understood. In this study, we developed cultured-cell models of tauopathy representing a human tauopathy. Neuro2a (N2a) cells containing propagative tau filaments were generated by introducing purified tau fibrils. These cell lines expressed full-length (2N4R) human tau and the green fluorescent protein (GFP)-fused repeat domain of tau with P301L mutation. Immunocytochemistry and super-resolution microscopic imaging revealed that tau inclusions exhibited filamentous morphology and were composed of both full-length and repeat domain fragment tau. Live-cell imaging analysis revealed that filamentous tau inclusions are transmitted to daughter cells, resulting in yeast-prion-like propagation. By a standard method of tau preparation, both full-length tau and repeat domain fragments were recovered in sarkosyl insoluble fraction. Hyperphosphorylation of full-length tau was confirmed by the immunoreactivity of phospho-Tau antibodies and mobility shifts by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). These properties were similar to the biochemical features of P301L mutated human tau in a mouse model of tauopathy. In addition, filamentous tau aggregates in cells barely co-localized with ubiquitins, suggesting that most tau aggregates were excluded from protein degradation systems, and thus propagated to daughter cells. The present cellular model of tauopathy will provide an advantage for dissecting the mechanisms of tau aggregation and degradation and be a powerful tool for drug screening to prevent tauopathy.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Gen", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms19051497" }, "pmcid": { "normalized": "PMC5983680" }, "pmid": { "normalized": "29772786" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neurofibrillary Tangles", "descriptor_ui": "D016874", "major_topic": false }, { "descriptor": "Protein Aggregates", "descriptor_ui": "D066329", "major_topic": false }, { "descriptor": "Protein Aggregation, Pathological", "descriptor_ui": "D066263", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": false }, { "descriptor": "Ubiquitins", "descriptor_ui": "D014452", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 May 17", "date_precision": "day", "issue": "5", "normalized_date": "2018-05-17", "pages": "E1497", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "19", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Tau Fibril Formation in Cultured Cells Compatible with a Mouse Model of Tauopathy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shiori", "last_name": "Toba", "name": null }, { "creator_type": "author", "first_name": "Mingyue", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Masami", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kanako", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Sakiko", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Takuo", "last_name": "Yasunaga", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Fukunaga", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Miyazawa", "name": null }, { "creator_type": "author", "first_name": "Sakiko", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fushiki", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Wanibuchi", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Hirotsune", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-25979-4" }, "pmcid": { "normalized": "PMC5955941" }, "pmid": { "normalized": "29769584" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018 May 17", "date_precision": "day", "issue": "1", "normalized_date": "2018-05-17", "pages": "8019", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Publisher Correction: Alpha-synuclein facilitates to form short unconventional microtubules that have a unique function in the axonal transport.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Constitutively active mutants (CAMs) of G-protein-coupled receptors (GPCRs) cause various kinds of diseases. Rhodopsin, a light-absorbing GPCR in animal retinas, has retinal as an endogenous ligand; only very low levels of activation of G-protein can be obtained with the ligand-free opsin. However, the CAM of opsin activates G-protein much more efficiently than the wild type, but the mechanism underlying this remains unclear. The present work revisits the constitutive activity of rhodopsin from the standpoint of conformational dynamics. Single-molecule observation of the M257Y mutant of bovine rhodopsin demonstrated that the switch between active and inactive conformations frequently occurred in M257Y opsin, and frequent generation of the active state results in the population shift toward the active state, which accounts for the constitutive activity of M257Y opsin. Our findings demonstrate that the protein function has a direct connection with the structural dynamics.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Akimori", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Shichida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Imamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jpcb.8b02819" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29668280" } }, "mesh": [ { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Rhodopsin", "descriptor_ui": "D012243", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 May 10", "date_precision": "day", "issue": "18", "normalized_date": "2018-05-10", "pages": "4838-4843", "proceedings_title": null, "publisher": "", "title": "The journal of physical chemistry. B", "volume": "122", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Shift in Conformational Equilibrium Induces Constitutive Activity of G-Protein-Coupled Receptor, Rhodopsin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In biological systems, the pH in intracellular organelles or tissues is strictly regulated, and differences of pH are deeply related to key biological events such as protein degradation, intracellular trafficking, renal failure, and cancer. Ratiometric fluorescence imaging is useful for determination of precise pH values, but existing fluorescence probes have substantial limitations, such as inappropriate p K(a) for imaging in the physiological pH range, inadequate photobleaching resistance, and insufficiently long excitation and emission wavelengths. Here we report a versatile scaffold for ratiometric fluorescence pH probes, based on asymmetric rhodamine. To demonstrate its usefulness for biological applications, we employed it to develop two probes. (1) SiRpH5 has suitable p K(a) and water solubility for imaging in acidic intracellular compartments; by using transferrin tagged with SiRpH5, we achieved time-lapse imaging of pH in endocytic compartments during protein trafficking for the first time. (2) Me-pEPPR is a near-infrared (NIR) probe; by using dextrin tagged with Me-pEPPR, we were able to image extracellular pH of renal tubules and tumors in situ. These chemical tools should be useful for studying the influence of intra- and extracellular pH on biological processes, as well as for in vivo imaging.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shodai", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Kagami", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Ikuko", "last_name": "Koyama-Honda", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Mizushima", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.8b00277" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29688713" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": true }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Neoplasms, Experimental", "descriptor_ui": "D009374", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": true }, { "descriptor": "Solubility", "descriptor_ui": "D012995", "major_topic": false }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 May 9", "date_precision": "day", "issue": "18", "normalized_date": "2018-05-09", "pages": "5925-5933", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "140", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a Series of Practical Fluorescent Chemical Tools To Measure pH Values in Living Samples.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the fruitfly Drosophila melanogaster, hunger has a significant impact on its sensory systems and brain functions, and consequently modifies related behaviors. However, it remains unclarified whether hunger affects nociceptive behavioral responses to heat stimuli. In this study, we show that food deprivation reduces responses to noxious heat in wild-type flies. We further identified that the neuropeptide Leucokinin (Lk) and its receptor (Lkr) are essential for the reduction of responses to noxious heat. Temporal silencing of Lk-expressing neurons and a knockout mutation of Lkr generated using the CRISPR/Cas9 system inhibited the reduction of responses to noxious heat. Thus, our results reveal that hunger induces reduction of responses to noxious heat through the Lk/Lkr signaling pathway in Drosophila.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hirono", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2018.03.132" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29559237" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": true }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Electricity", "descriptor_ui": "D004560", "major_topic": false }, { "descriptor": "Food Deprivation", "descriptor_ui": "D005508", "major_topic": false }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Hot Temperature", "descriptor_ui": "D006358", "major_topic": true }, { "descriptor": "Hunger", "descriptor_ui": "D006815", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018 May 5", "date_precision": "day", "issue": "2", "normalized_date": "2018-05-05", "pages": "221-226", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "499", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Leucokinin signaling regulates hunger-driven reduction of behavioral responses to noxious heat in Drosophila.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mathematical modeling and analysis of biochemical reaction networks are key routines in computational systems biology and biophysics; however, it remains difficult to choose the most valid model. Here, we propose a computational framework for data-driven and systematic inference of a nonlinear biochemical network model. The framework is based on the expectation-maximization algorithm combined with particle smoother and sparse regularization techniques. In this method, a \"redundant\" model consisting of an excessive number of nodes and regulatory paths is iteratively updated by eliminating unnecessary paths, resulting in an inference of the most likely model. Using artificial single-cell time-course data showing heterogeneous oscillatory behaviors, we demonstrated that this algorithm successfully inferred the true network without any prior knowledge of network topology or parameter values. Furthermore, we showed that both the regulatory paths among nodes and the optimal number of nodes in the network could be systematically determined. The method presented in this study provides a general framework for inferring a nonlinear biochemical network model from heterogeneous single-cell time-course data.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-25064-w" }, "pmcid": { "normalized": "PMC5931614" }, "pmid": { "normalized": "29717206" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": true }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": false }, { "descriptor": "Nonlinear Dynamics", "descriptor_ui": "D017711", "major_topic": true }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Systems Biology", "descriptor_ui": "D049490", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 May 1", "date_precision": "day", "issue": "1", "normalized_date": "2018-05-01", "pages": "6790", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Inferring a nonlinear biochemical network model from a heterogeneous single-cell time course data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Disturbed balance between immune surveillance and tolerance may lead to poor clinical outcomes in some malignancies. In paired analyses of adenocarcinoma and normal mucosa from 142 patients, we found a significant increase of the CD4/CD8 ratio and accumulation of regulatory T cells (Tregs) within the adenocarcinoma. The increased frequency of Tregs correlated with the local infiltration and extension of the tumor. There was concurrent maturation arrest, upregulation of programmed death-1 expression, and functional impairment in CD8(+) T cells (CTLs) isolated from the adenocarcinoma. Adenocarcinoma-associated Tregs directly inhibit the function of normal human CTLs in vitro. With histopathological analysis, Foxp3(+) Tregs were preferentially located in stroma. Concurrent transcriptome analysis of epithelial cells, stromal cells, and T cell subsets obtained from carcinomatous and normal intestinal samples from patients revealed a distinct gene expression signature in colorectal adenocarcinoma-associated Tregs, with overexpression of CCR1, CCR8, and TNFRSF9, whereas their ligands CCL4 and TNFSF9 were found upregulated in cancerous epithelium. Overexpression of WNT2 and CADM1, associated with carcinogenesis and metastasis, in cancer-associated stromal cells suggests that both cancer cells and stromal cells play important roles in the development and progression of colorectal cancer through the formation of a tumor microenvironment. The identification of CTL anergy by Tregs and the unique gene expression signature of human Tregs and stromal cells in colorectal cancer patients may facilitate the development of new therapeutics against malignancies.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hanae", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Yoriko", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Kenoki", "last_name": "Ohuchida", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Saera", "last_name": "Fujiki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Rintaro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Yuho", "last_name": "Najima", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Lin", "last_name": "Cui", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ueki", "name": null }, { "creator_type": "author", "first_name": "Yoshinao", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Ohara", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Ishikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.4049/jimmunol.1701222" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29581358" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunity, Mucosal", "descriptor_ui": "D018928", "major_topic": false }, { "descriptor": "Immunologic Surveillance", "descriptor_ui": "D007157", "major_topic": false }, { "descriptor": "Intestinal Mucosa", "descriptor_ui": "D007413", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false }, { "descriptor": "Tumor Escape", "descriptor_ui": "D019139", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 May 1", "date_precision": "day", "issue": "9", "normalized_date": "2018-05-01", "pages": "3291-3303", "proceedings_title": null, "publisher": "", "title": "Journal of immunology (Baltimore, Md. : 1950)", "volume": "200", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Deregulated Mucosal Immune Surveillance through Gut-Associated Regulatory T Cells and PD-1(+) T Cells in Human Colorectal Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Photosensitizing fluorescent proteins, which generate reactive oxygen species (ROS) upon light irradiation, are useful for spatiotemporal protein inactivation and cell ablation. They give us clues about protein function, intracellular signaling pathways and intercellular interactions. Since ROS generation of a photosensitizer is specifically controlled by certain excitation wavelengths, utilizing colour variants of photosensitizing protein would allow multi-spatiotemporal control of inactivation. To expand the colour palette of photosensitizing protein, here we developed SuperNova Green from its red predecessor, SuperNova. RESULTS: SuperNova Green is able to produce ROS spatiotemporally upon blue light irradiation. Based on protein characterization, SuperNova Green produces insignificant amounts of singlet oxygen and predominantly produces superoxide and its derivatives. We utilized SuperNova Green to specifically inactivate the pleckstrin homology domain of phospholipase C-delta1 and to ablate cancer cells in vitro. As a proof of concept for multi-spatiotemporal control of inactivation, we demonstrate that SuperNova Green can be used with its red variant, SuperNova, to perform independent protein inactivation or cell ablation studies in a spatiotemporal manner by selective light irradiation. CONCLUSION: Development of SuperNova Green has expanded the photosensitizing protein toolbox to optogenetically control protein inactivation and cell ablation.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yemima Dani", "last_name": "Riani", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Kiwamu", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12915-018-0514-7" }, "pmcid": { "normalized": "PMC5928576" }, "pmid": { "normalized": "29712573" } }, "mesh": [ { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": true }, { "descriptor": "Photosensitizing Agents", "descriptor_ui": "D017319", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Singlet Oxygen", "descriptor_ui": "D026082", "major_topic": false }, { "descriptor": "Superoxides", "descriptor_ui": "D013481", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Apr 30", "date_precision": "day", "issue": "1", "normalized_date": "2018-04-30", "pages": "50", "proceedings_title": null, "publisher": "", "title": "BMC biology", "volume": "16", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Green monomeric photosensitizing fluorescent protein for photo-inducible protein inactivation and cell ablation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell signaling depends on spatiotemporally regulated molecular interactions. Although the movements of signaling proteins have been analyzed with various technologies, how spatial dynamics influence the molecular interactions that transduce signals is unclear. Here, we developed a single-molecule method to analyze the spatiotemporal coupling between motility, clustering, and signaling. The analysis was performed with the epidermal growth factor receptor (EGFR), which triggers signaling through its dimerization and phosphorylation after association with EGF. Our results show that the few EGFRs isolated in membrane subdomains were released by an EGF-dependent increase in their diffusion area, facilitating molecular associations and producing immobile clusters. Using a two-color single-molecule analysis, we found that the EGF-induced state transition alters the properties of the immobile clusters, allowing them to interact for extended periods with the cytoplasmic protein, GRB2. Our study reveals a novel correlation between this molecular interaction and its mesoscale dynamics, providing the initial signaling node.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Chan-Gi", "last_name": "Pack", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Kaizu", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jmb.2018.02.018" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29505756" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CHO Cells", "descriptor_ui": "D016466", "major_topic": false }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "Cricetulus", "descriptor_ui": "D003412", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Epidermal Growth Factor", "descriptor_ui": "D004815", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": false }, { "descriptor": "GRB2 Adaptor Protein", "descriptor_ui": "D051380", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Single Molecule Imaging", "descriptor_ui": "D000072760", "major_topic": false }, { "descriptor": "Spatio-Temporal Analysis", "descriptor_ui": "D062211", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Apr 27", "date_precision": "day", "issue": "9", "normalized_date": "2018-04-27", "pages": "1386-1401", "proceedings_title": null, "publisher": "", "title": "Journal of molecular biology", "volume": "430", "year": 2018 }, "ssbd": { "database": [ "ssbd-database-000211" ], "repository": [ "ssbd-repos-000211" ] }, "title": "Transient Acceleration of Epidermal Growth Factor Receptor Dynamics Produces Higher-Order Signaling Clusters.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent studies have revealed that newly emerging transformed cells are often eliminated from epithelial tissues via cell competition with the surrounding normal epithelial cells. This cancer preventive phenomenon is termed epithelial defense against cancer (EDAC). However, it remains largely unknown whether and how EDAC is diminished during carcinogenesis. In this study, using a cell competition mouse model, we show that high-fat diet (HFD) feeding substantially attenuates the frequency of apical elimination of RasV12-transformed cells from intestinal and pancreatic epithelia. This process involves both lipid metabolism and chronic inflammation. Furthermore, aspirin treatment significantly facilitates eradication of transformed cells from the epithelial tissues in HFD-fed mice. Thus, our work demonstrates that obesity can profoundly influence competitive interaction between normal and transformed cells, providing insights into cell competition and cancer preventive medicine.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ayana", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Nagatake", "name": null }, { "creator_type": "author", "first_name": "Riku", "last_name": "Egami", "name": null }, { "creator_type": "author", "first_name": "Guoqiang", "last_name": "Gu", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Nakatani", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Kunisawa", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2018.03.104" }, "pmcid": { "normalized": "PMC6314181" }, "pmid": { "normalized": "29694905" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "Dietary Fats", "descriptor_ui": "D004041", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": false }, { "descriptor": "Intestinal Mucosa", "descriptor_ui": "D007413", "major_topic": false }, { "descriptor": "Lipid Metabolism", "descriptor_ui": "D050356", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Pancreas", "descriptor_ui": "D010179", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Apr 24", "date_precision": "day", "issue": "4", "normalized_date": "2018-04-24", "pages": "974-982", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "23", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Obesity Suppresses Cell-Competition-Mediated Apical Elimination of RasV12-Transformed Cells from Epithelial Tissues.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cysteine prodrug N-acetyl cysteine (NAC) is widely used as a pharmacological antioxidant and cytoprotectant. It has been reported to lower endogenous oxidant levels and to protect cells against a wide range of pro-oxidative insults. As NAC itself is a poor scavenger of oxidants, the molecular mechanisms behind the antioxidative effects of NAC have remained uncertain. Here we show that NAC-derived cysteine is desulfurated to generate hydrogen sulfide, which in turn is oxidized to sulfane sulfur species predominantly within mitochondria. We provide evidence suggesting the possibility that sulfane sulfur species produced by 3-mercaptopyruvate sulfurtransferase and sulfide:quinone oxidoreductase are the actual mediators of the immediate antioxidative and cytoprotective effects provided by NAC.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Daria", "last_name": "Ezeriņa", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Tobias P.", "last_name": "Dick", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chembiol.2018.01.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29429900" } }, "mesh": [ { "descriptor": "Acetylcysteine", "descriptor_ui": "D000111", "major_topic": false }, { "descriptor": "Antioxidants", "descriptor_ui": "D000975", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false }, { "descriptor": "Sulfurtransferases", "descriptor_ui": "D013466", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Apr 19", "date_precision": "day", "issue": "4", "normalized_date": "2018-04-19", "pages": "447-459.e4", "proceedings_title": null, "publisher": "", "title": "Cell chemical biology", "volume": "25", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "N-acetyl cysteine functions as a fast-acting antioxidant by triggering intracellular H2S and sulfane sulfur production.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Higher- or lower-affinity germinal center (GC) B cells are directed either to plasma cell or GC recycling, respectively; however, how commitment to the plasma cell fate takes place is unclear. We found that a population of light zone (LZ) GC cells, Bcl6(lo)CD69(hi) expressing a transcription factor IRF4 and higher-affinity B cell receptors (BCRs) or Bcl6(hi)CD69(hi) with lower-affinity BCRs, favored the plasma cell or recycling GC cell fate, respectively. Mechanistically, CD40 acted as a dose-dependent regulator for Bcl6(lo)CD69(hi) cell formation. Furthermore, we found that expression of intercellular adhesion molecule 1 (ICAM-1) and signaling lymphocytic activation molecule (SLAM) in Bcl6(lo)CD69(hi) cells was higher than in Bcl6(hi)CD69(hi) cells, thereby affording more stable T follicular helper (Tfh)-GC B cell contacts. These data support a model whereby commitment to the plasma cell begins in the GC and suggest that stability of Tfh-GC B cell contacts is key for plasma cell-prone GC cell formation.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Wataru", "last_name": "Ise", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Kometani", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takaharu", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kurosaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.immuni.2018.03.027" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29669250" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, CD", "descriptor_ui": "D015703", "major_topic": false }, { "descriptor": "Antigens, Differentiation, T-Lymphocyte", "descriptor_ui": "D000945", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "CD40 Antigens", "descriptor_ui": "D019013", "major_topic": false }, { "descriptor": "CD69 Antigens", "descriptor_ui": "D000099192", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Germinal Center", "descriptor_ui": "D018858", "major_topic": false }, { "descriptor": "Intercellular Adhesion Molecule-1", "descriptor_ui": "D018799", "major_topic": false }, { "descriptor": "Lectins, C-Type", "descriptor_ui": "D037181", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Plasma Cells", "descriptor_ui": "D010950", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-bcl-6", "descriptor_ui": "D051560", "major_topic": false }, { "descriptor": "Signaling Lymphocytic Activation Molecule Family", "descriptor_ui": "D000071176", "major_topic": false }, { "descriptor": "T-Lymphocytes, Helper-Inducer", "descriptor_ui": "D006377", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Apr 17", "date_precision": "day", "issue": "4", "normalized_date": "2018-04-17", "pages": "702-715.e4", "proceedings_title": null, "publisher": "", "title": "Immunity", "volume": "48", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "T Follicular Helper Cell-Germinal Center B Cell Interaction Strength Regulates Entry into Plasma Cell or Recycling Germinal Center Cell Fate.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human brain development has generally been studied through the analysis of postmortem tissues because of limited access to fetal brain tissues. This approach, however, only provides information from the perspective of long-term development. To investigate the pathophysiology of neurodevelopmental disorders, it is necessary to understand the detailed mechanisms of human brain development. Recent advances in pluripotent stem cell (PSC) technologies enable us to establish in vitro brain models from human induced PSCs (hiPSCs), which can be used to examine the pathophysiological mechanisms of neurodevelopmental disorders. We previously demonstrated that self-organized cerebral tissues can be generated from human PSCs in a three-dimensional (3D) culture system. Here, we describe the cerebral tissues differentiated from hiPSCs in a further-optimized 3D culture. We found that treatment with FGF2 is helpful to form iPSC aggregates with efficiency. Neuroepithelial structures spontaneously formed with apico-basal polarity in the aggregates expressing forebrain marker FOXG1. The neuroepithelium self-forms a multilayered structure including progenitor zones (ventricular and subventricular zones) and neuronal zone (cortical plate). Furthermore, with the same level of oxygen (O(2)) as in ambient air (20% O(2)), we found that self-formation of cortical structures lasted for 70 days in culture. Thus, our optimized 3D culture for the generation of cortical structure from hiPSCs is a simple yet effective method.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Noriomi", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Sora", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2018.03.049" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29524419" } }, "mesh": [ { "descriptor": "Cell Aggregation", "descriptor_ui": "D002449", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": false }, { "descriptor": "Fibroblast Growth Factor 2", "descriptor_ui": "D016222", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Apr 15", "date_precision": "day", "issue": "4", "normalized_date": "2018-04-15", "pages": "729-735", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "498", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Self-organizing cortex generated from human iPSCs with combination of FGF2 and ambient oxygen.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Regulation of gene expression requires selective incorporation of histone H3 variant H3.3 into chromatin. Histone H3.3 has several subsidiary variants but their functions are unclear. Here we characterize the function of histone H3.3 sub-variant, H3mm7, which is expressed in skeletal muscle satellite cells. H3mm7 knockout mice demonstrate an essential role of H3mm7 in skeletal muscle regeneration. Chromatin analysis reveals that H3mm7 facilitates transcription by forming an open chromatin structure around promoter regions including those of myogenic genes. The crystal structure of the nucleosome containing H3mm7 reveals that, unlike the S57 residue of other H3 proteins, the H3mm7-specific A57 residue cannot form a hydrogen bond with the R40 residue of the cognate H4 molecule. Consequently, the H3mm7 nucleosome is unstable in vitro and exhibited higher mobility in vivo compared with the H3.3 nucleosome. We conclude that the unstable H3mm7 nucleosome may be required for proper skeletal muscle differentiation.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" }, { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Yan", "last_name": "Xie", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Nogami", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Semba", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurumizaka", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-018-03845-1" }, "pmcid": { "normalized": "PMC5895627" }, "pmid": { "normalized": "29643389" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cardiotoxins", "descriptor_ui": "D054715", "major_topic": false }, { "descriptor": "Chromatin Assembly and Disassembly", "descriptor_ui": "D042002", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "MyoD Protein", "descriptor_ui": "D017570", "major_topic": false }, { "descriptor": "Nucleosomes", "descriptor_ui": "D009707", "major_topic": false }, { "descriptor": "PAX7 Transcription Factor", "descriptor_ui": "D051763", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Protein Structure, Secondary", "descriptor_ui": "D017433", "major_topic": false }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": false }, { "descriptor": "Satellite Cells, Skeletal Muscle", "descriptor_ui": "D032496", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Apr 11", "date_precision": "day", "issue": "1", "normalized_date": "2018-04-11", "pages": "1400", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "9", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Histone H3.3 sub-variant H3mm7 is required for normal skeletal muscle regeneration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord controls male sexual function in rats. In contrast, in female rats, GRP neurons could scarcely be detected around puberty when circulating ovarian steroid hormones such as estradiol and progesterone levels are increasing. However, little information is available on feminizing or demasculinizing effects of ovarian steroids on the central nervous system in female puberty and adulthood. In this study, to visualize the spinal GRP neurons in vivo, we generated a GRP-promoter-Venus transgenic (Tg) rat line and studied the effects of the sex steroid hormones on GRP expression in the rat lumbar cord by examining the Venus fluorescence. In these Tg rats, the sexually dimorphic spinal GRP neurons controlling male sexual function were clearly labeled with Venus fluorescence. As expected, Venus fluorescence in the male lumbar cord was markedly decreased after castration and restored by chronic androgen replacement. Furthermore, androgen-induced Venus expression in the spinal cord of adult Tg males was significantly attenuated by chronic treatment with progesterone but not with estradiol. A luciferase assay using a human GRP-promoter construct showed that androgens enhance the spinal GRP system, and more strikingly, that progesterone acts to inhibit the GRP system via an androgen receptor-mediated mechanism. These results demonstrate that circulating androgens may play an important role in the spinal GRP system controlling male sexual function not only in rats but also in humans and that progesterone could be an important feminizing factor in the spinal GRP system in females during pubertal development.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Oti", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Takanami", "name": null }, { "creator_type": "author", "first_name": "Saya", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Ken Ichi", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Jintetsu", "last_name": "Soh", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Ukimura", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1210/en.2018-00043" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29534195" } }, "mesh": [ { "descriptor": "Androgens", "descriptor_ui": "D000728", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gastrin-Releasing Peptide", "descriptor_ui": "D019886", "major_topic": false }, { "descriptor": "Lumbar Vertebrae", "descriptor_ui": "D008159", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Progesterone", "descriptor_ui": "D011374", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Transgenic", "descriptor_ui": "D055647", "major_topic": false }, { "descriptor": "Sexual Behavior, Animal", "descriptor_ui": "D012726", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Apr 1", "date_precision": "day", "issue": "4", "normalized_date": "2018-04-01", "pages": "1886-1896", "proceedings_title": null, "publisher": "", "title": "Endocrinology", "volume": "159", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Effects of Sex Steroids on the Spinal Gastrin-Releasing Peptide System Controlling Male Sexual Function in Rats.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We propose the use of a spectral differential method (SDM) to emphasize the spectral peaks of multispectral photoacoustic images. Because contrast agent signals have spectral peaks at the contrast agent absorption peak, the SDM can selectively emphasize contrast agent signals. Unlike the conventional spectral fitting method (SFM), the SDM does not require reference background spectra and, consequently, does not suffer from separation error caused by the deviation of reference spectra from the measured spectra. We performed multispectral photoacoustic imaging of tissue-mimicking phantoms and subcutaneous tumors of mice injected with small organic molecule-based contrast agents. Contrast agent images obtained by the SDM were clearer than those obtained by SFM.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Ryu J.", "last_name": "Iwatate", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Okawa", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/ao.57.002383" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29714218" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018 Apr 1", "date_precision": "day", "issue": "10", "normalized_date": "2018-04-01", "pages": "2383-2393", "proceedings_title": null, "publisher": "", "title": "Applied optics", "volume": "57", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Spectral-differential-based unmixing for multispectral photoacoustic imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Far-field super-resolution fluorescence microscopy has enabled us to visualize live cells in great detail and with an unprecedented resolution. However, the techniques developed thus far have required high-power illumination (102-106 W/cm2), which leads to considerable phototoxicity to live cells and hampers time-lapse observation of the cells. In this study we show a highly biocompatible super-resolution microscopy technique that requires a very low-power illumination. The present technique combines a fast photoswitchable fluorescent protein, Kohinoor, with SPoD-ExPAN (super-resolution by polarization demodulation/excitation polarization angle narrowing). With this technique, we successfully observed Kohinoor-fusion proteins involving vimentin, paxillin, histone and clathrin expressed in HeLa cells at a spatial resolution of 70-80 nm with illumination power densities as low as ~1 W/cm2 for both excitation and photoswitching. Furthermore, although the previous SPoD-ExPAN technique used L1-regularized maximum-likelihood calculations to reconstruct super-resolved images, we devised an extension to the Lp-regularization to obtain super-resolved images that more accurately describe objects at the specimen plane. Thus, the present technique would significantly extend the applicability of super-resolution fluorescence microscopy for live-cell imaging.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuichi", "last_name": "Wazawa", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Kawahara", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Takauchi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Washio", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jmicro/dfy004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29409007" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Clathrin", "descriptor_ui": "D002966", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Paxillin", "descriptor_ui": "D051419", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Vimentin", "descriptor_ui": "D014746", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Apr 1", "date_precision": "day", "issue": "2", "normalized_date": "2018-04-01", "pages": "89-98", "proceedings_title": null, "publisher": "", "title": "Microscopy (Oxford, England)", "volume": "67", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Highly biocompatible super-resolution fluorescence imaging using the fast photoswitching fluorescent protein Kohinoor and SPoD-ExPAN with Lp-regularized image reconstruction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hierarchical features of the energy landscape of the folding/unfolding behavior of adenylate kinase, including its dependence on denaturant concentration, are elucidated in terms of single-molecule fluorescence resonance energy transfer (smFRET) measurements in which the proteins are encapsulated in a lipid vesicle. The core in constructing the energy landscape from single-molecule time-series across different denaturant concentrations is the application of rate-distortion theory (RDT), which naturally considers the effects of measurement noise and sampling error, in combination with change-point detection and the quantification of the FRET efficiency-dependent photobleaching behavior. Energy landscapes are constructed as a function of observation time scale, revealing multiple partially folded conformations at small time scales that are situated in a superbasin. As the time scale increases, these denatured states merge into a single basin, demonstrating the coarse-graining of the energy landscape as observation time increases. Because the photobleaching time scale is dependent on the conformational state of the protein, possible nonequilibrium features are discussed, and a statistical test for violation of the detailed balance condition is developed based on the state sequences arising from the RDT framework.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "J. Nicholas", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Menahem", "last_name": "Pirchi", "name": null }, { "creator_type": "author", "first_name": "Gilad", "last_name": "Haran", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/1.5016487" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29604865" } }, "mesh": [ { "descriptor": "Adenylate Kinase", "descriptor_ui": "D000263", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Physical Phenomena", "descriptor_ui": "D055585", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Protein Denaturation", "descriptor_ui": "D011489", "major_topic": false }, { "descriptor": "Protein Folding", "descriptor_ui": "D017510", "major_topic": false }, { "descriptor": "Thermodynamics", "descriptor_ui": "D013816", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Mar 28", "date_precision": "day", "issue": "12", "normalized_date": "2018-03-28", "pages": "123325", "proceedings_title": null, "publisher": "", "title": "The Journal of chemical physics", "volume": "148", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Deciphering hierarchical features in the energy landscape of adenylate kinase folding/unfolding.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Glucose 6-phosphate dehydrogenase (G6PDH) catalyzes the first reaction in the oxidative pentose phosphate pathway. In green plant chloroplasts, G6PDH is a unique redox-regulated enzyme, since it is inactivated under the reducing conditions. This regulation is accomplished using a redox-active cysteine pair, which is conserved in plant G6PDH. The inactivation of this enzyme under conditions of light must be beneficial to prevent release of CO(2) from the photosynthetic carbon fixation cycle. In the filamentous, heterocyst-forming, nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120 (Anabaena 7120), G6PDH plays a pivotal role in providing reducing power for nitrogenase, and its activity is also reported to be suppressed by reduction, though Anabaena G6PDH does not conserve the critical cysteines for regulation. Based on the thorough analyses of the redox regulation mechanisms of G6PDH from Anabaena 7120 and its activator protein OpcA, we found that m-type thioredoxin regulates G6PDH activity by changing the redox states of OpcA. Mass spectrometric analysis and mutagenesis studies indicate that Cys(393) and Cys(399) of OpcA are responsible for the redox regulation property of this protein. Moreover, in vivo analyses of the redox states of OpcA showed that more than half of the OpcA is present as an oxidized form, even under conditions of light, when cells are cultured under the nitrogen-fixing conditions. This redox regulation of OpcA might be necessary to provide reducing power for nitrogenase by G6PDH in heterocysts even during the day.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shoko", "last_name": "Mihara", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Wakao", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Higo", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Jiro", "last_name": "Nomata", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1042/bcj20170869" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29440317" } }, "mesh": [ { "descriptor": "Anabaena", "descriptor_ui": "D017033", "major_topic": true }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Bacterial", "descriptor_ui": "D015964", "major_topic": false }, { "descriptor": "Glucosephosphate Dehydrogenase", "descriptor_ui": "D005954", "major_topic": false }, { "descriptor": "Nitrogen Fixation", "descriptor_ui": "D009586", "major_topic": true }, { "descriptor": "Organisms, Genetically Modified", "descriptor_ui": "D030781", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Photosynthesis", "descriptor_ui": "D010788", "major_topic": false }, { "descriptor": "Thioredoxins", "descriptor_ui": "D013879", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Mar 20", "date_precision": "day", "issue": "6", "normalized_date": "2018-03-20", "pages": "1091-1105", "proceedings_title": null, "publisher": "", "title": "The Biochemical journal", "volume": "475", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Thioredoxin regulates G6PDH activity by changing redox states of OpcA in the nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The sensitive detection of thiols including glutathione and cysteine is desirable owing to their roles as indispensable biomolecules in maintaining intracellular biological redox homeostasis. Herein, we report the design and synthesis of SEluc-1 (sulfinate ester luciferin), a chemoselective probe exhibiting a ratiometric and turn-on response towards thiols selectively in fluorescence and bioluminescence, respectively. The probe, which was designed based on the \"caged\" luciferin strategy, displays excellent selectivity, high signal/noise ratio (>240 in the case of bioluminescence), and a biologically relevant limit of detection (LOD, 80 nm for cysteine), which are all desirable traits for a sensitive bioluminescent sensor. SEluc-1 was further applied to fluorescence imaging of thiol activity in living human cervical cancer HeLa cell cultures, and was successfully able to detect fluctuations in thiol concentrations induced by oxidative stress in a bioluminescent assay utilizing African green monkey fibroblast COS-7 cells and human breast adenocarcinoma MCF-7 cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mayu", "last_name": "Hemmi", "name": null }, { "creator_type": "author", "first_name": "Yuma", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Moritoshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/asia.201701774" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29359483" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Firefly Luciferin", "descriptor_ui": "D049454", "major_topic": true }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "MCF-7 Cells", "descriptor_ui": "D061986", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Sulfhydryl Compounds", "descriptor_ui": "D013438", "major_topic": false }, { "descriptor": "Sulfur Compounds", "descriptor_ui": "D013457", "major_topic": true }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Mar 16", "date_precision": "day", "issue": "6", "normalized_date": "2018-03-16", "pages": "648-655", "proceedings_title": null, "publisher": "", "title": "Chemistry, an Asian journal", "volume": "13", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Highly Sensitive Bioluminescent Probe for Thiol Detection in Living Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The fluorescent protein (FP) color palette has greatly contributed to the visualization of molecular and cellular processes. However, most FPs lose fluorescence at a pH lower than their neutral pK(a) ( approximately 6), and this has hampered their application in acidic organelles (pH approximately 4.5-6.0). Currently, several cyan- and red-colored acid-tolerant FPs are available; however, there are few reports of acid-tolerant green FPs (GFPs) that are practically applicable to bioimaging. Here, we developed the acid-tolerant monomeric GFP \"Gamillus\" from the jellyfish Olindias formosa, with excellent brightness, maturation speed, and photostability. Results from X-ray crystallography and point mutagenesis suggest that across a broad pH range the acid tolerance is attributed to stabilization of deprotonation in the chromophore phenyl ring by forming a unique trans configuration. We demonstrate that Gamillus can serve as a molecular tag suitable for imaging in acidic organelles through autophagy-mediated molecular tracking to lysosomes.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hajime", "last_name": "Shinoda", "name": null }, { "creator_type": "author", "first_name": "Yuanqing", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chembiol.2017.12.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29290624" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Crystallography, X-Ray", "descriptor_ui": "D018360", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Hydrozoa", "descriptor_ui": "D037402", "major_topic": false }, { "descriptor": "Lysosomes", "descriptor_ui": "D008247", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Solubility", "descriptor_ui": "D012995", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Mar 15", "date_precision": "day", "issue": "3", "normalized_date": "2018-03-15", "pages": "330-338.e7", "proceedings_title": null, "publisher": "", "title": "Cell chemical biology", "volume": "25", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Acid-Tolerant Monomeric GFP from Olindias formosa.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human pluripotent stem cell (hPSC)-derived kidney organoids may facilitate disease modeling and the generation of tissue for renal replacement. Long-term application, however, will require transferability between hPSC lines and significant improvements in organ maturation. A key question is whether time or a patent vasculature is required for ongoing morphogenesis. Here, we show that hPSC-derived kidney organoids, derived in fully defined medium conditions and in the absence of any exogenous vascular endothelial growth factor, develop host-derived vascularization. In vivo imaging of organoids under the kidney capsule confirms functional glomerular perfusion as well as connection to pre-existing vascular networks in the organoids. Wide-field electron microscopy demonstrates that transplantation results in formation of a glomerular basement membrane, fenestrated endothelial cells, and podocyte foot processes. Furthermore, compared with non-transplanted organoids, polarization and segmental specialization of tubular epithelium are observed. These data demonstrate that functional vascularization is required for progressive morphogenesis of human kidney organoids.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Cathelijne W.", "last_name": "van den Berg", "name": null }, { "creator_type": "author", "first_name": "Laila", "last_name": "Ritsma", "name": null }, { "creator_type": "author", "first_name": "M. Cristina", "last_name": "Avramut", "name": null }, { "creator_type": "author", "first_name": "Loes E.", "last_name": "Wiersma", "name": null }, { "creator_type": "author", "first_name": "Bernard M.", "last_name": "van den Berg", "name": null }, { "creator_type": "author", "first_name": "Danielle G.", "last_name": "Leuning", "name": null }, { "creator_type": "author", "first_name": "Ellen", "last_name": "Lievers", "name": null }, { "creator_type": "author", "first_name": "Marije", "last_name": "Koning", "name": null }, { "creator_type": "author", "first_name": "Jessica M.", "last_name": "Vanslambrouck", "name": null }, { "creator_type": "author", "first_name": "Abraham J.", "last_name": "Koster", "name": null }, { "creator_type": "author", "first_name": "Sara E.", "last_name": "Howden", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null }, { "creator_type": "author", "first_name": "Melissa H.", "last_name": "Little", "name": null }, { "creator_type": "author", "first_name": "Ton J.", "last_name": "Rabelink", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2018.01.041" }, "pmcid": { "normalized": "PMC5918682" }, "pmid": { "normalized": "29503086" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kidney Glomerulus", "descriptor_ui": "D007678", "major_topic": false }, { "descriptor": "Kidney Transplantation", "descriptor_ui": "D016030", "major_topic": false }, { "descriptor": "Kidney Tubules", "descriptor_ui": "D007684", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Podocytes", "descriptor_ui": "D050199", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Mar 13", "date_precision": "day", "issue": "3", "normalized_date": "2018-03-13", "pages": "751-765", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "10", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Abstract\n In T cells, T cell receptor (TCR) signalling initiates downstream transcriptional mechanisms for T cell activation and differentiation. Foxp3-expressing regulatory T cells (Treg) require TCR signals for their suppressive function and maintenance in the periphery. It is, however, unclear how TCR signalling controls the transcriptional programme of Treg. Since most of studies identified the transcriptional features of Treg in comparison to naïve T cells, the relationship between Treg and non-naïve T cells including memory-phenotype T cells (Tmem) and effector T cells (Teff) is not well understood. Here we dissect the transcriptomes of various T cell subsets from independent datasets using the multidimensional analysis method Canonical Correspondence Analysis (CCA). We show that resting Treg share gene modules for activation with Tmem and Teff. Importantly, Tmem activate the distinct transcriptional modules for T cell activation, which are uniquely repressed in Treg. The activation signature of Treg is dependent on TCR signals, and is more actively operating in activated Treg. Furthermore, by analysing single cell RNA-seq data from tumour-infiltrating T cells, we revealed that FOXP3 expression occurs predominantly in activated T cells. Moreover, we identified FOXP3-driven and T follicular helper (Tfh)-like differentiation pathways in tumour microenvironments, and their bifurcation point, which is enriched with recently activated T cells. Collectively, our study reveals the activation mechanisms downstream of TCR signals for the bifurcation of Treg and Teff differentiation and their maturation processes.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Alla", "last_name": "Bradley", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/280818" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2018-03-12", "date_precision": "day", "issue": null, "normalized_date": "2018-03-12", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Elucidating the activation mechanisms for bifurcation of regulatory and effector T cell fates by multidimensional single cell analysis", "url": "http://biorxiv.org/lookup/doi/10.1101/280818", "zotero": { "item_type": "preprint" } }, { "abstract": "The generation of new blood vessels via angiogenesis is critical for meeting tissue oxygen demands. A role for adult stem cells in this process remains unclear. Here, we identified CD157 (bst1, bone marrow stromal antigen 1) as a marker of tissue-resident vascular endothelial stem cells (VESCs) in large arteries and veins of numerous mouse organs. Single CD157(+) VESCs form colonies in vitro and generate donor-derived portal vein, sinusoids, and central vein endothelial cells upon transplantation in the liver. In response to injury, VESCs expand and regenerate entire vasculature structures, supporting the existence of an endothelial hierarchy within blood vessels. Genetic lineage tracing revealed that VESCs maintain large vessels and sinusoids in the normal liver for more than a year, and transplantation of VESCs rescued bleeding phenotypes in a mouse model of hemophilia. Our findings show that tissue-resident VESCs display self-renewal capacity and that vascular regeneration potential exists in peripheral blood vessels.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taku", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Jun-Ichi", "last_name": "Suehiro", "name": null }, { "creator_type": "author", "first_name": "Yang", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Kawaji", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Iba", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Kouno", "name": null }, { "creator_type": "author", "first_name": "Sachi", "last_name": "Ishikawa-Kato", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Furuno", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takara", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Jia", "last_name": "Weizhen", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Yoshihide", "last_name": "Hayashizaki", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Mervin C.", "last_name": "Yoder", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stem.2018.01.010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29429943" } }, "mesh": [ { "descriptor": "ADP-ribosyl Cyclase", "descriptor_ui": "D036541", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, CD", "descriptor_ui": "D015703", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Blood Vessels", "descriptor_ui": "D001808", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Colony-Forming Units Assay", "descriptor_ui": "D003114", "major_topic": false }, { "descriptor": "Endothelial Progenitor Cells", "descriptor_ui": "D066026", "major_topic": false }, { "descriptor": "Factor VIII", "descriptor_ui": "D005169", "major_topic": false }, { "descriptor": "GPI-Linked Proteins", "descriptor_ui": "D058851", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": true }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018 Mar 1", "date_precision": "day", "issue": "3", "normalized_date": "2018-03-01", "pages": "384-397.e6", "proceedings_title": null, "publisher": "", "title": "Cell stem cell", "volume": "22", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "CD157 Marks Tissue-Resident Endothelial Stem Cells with Homeostatic and Regenerative Properties.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Peropsin or retinal pigment epithelium-derived rhodopsin homolog, found in many animals, belongs to the opsin family. Most opsins bind to 11-cis-retinal as a chromophore and act as light-activated G protein-coupled receptors. Some peropsins, however, bind all-trans-retinal and isomerise it into 11-cis form by light, and peropsin has been suggested to supply other visual opsins with 11-cis-retinal. Additionally, peropsin has some amino acid sequence motifs that are highly conserved among G protein-coupled opsins. Here, using chimeric mutant peropsins, we found that peropsin potentially generates an \"active form\" that drives G-protein signalling in the dark by binding to all-trans-retinal and that the active form photo-converts to an inactive form containing 11-cis-retinal. Comparative spectroscopic analysis demonstrated that spider peropsin exhibited catalytic efficiency for retinal photoisomerisation that was much lower than a retinal photoisomerase, squid retinochrome. The chimeric peropsins, constructed by replacing the third intracellular loop region with that of Gs- or Gi-coupled opsin, were active and drove Gs- or Gi-mediated signalling in the dark, respectively, and were inactivated upon illumination in mammalian cultured cells. These results suggest that peropsin acts as a dark-active, light-inactivated G protein-coupled receptor and is useful as a novel optogenetic tool.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Lucas", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-21946-1" }, "pmcid": { "normalized": "PMC5824942" }, "pmid": { "normalized": "29476064" } }, "mesh": [ { "descriptor": "Amino Acid Motifs", "descriptor_ui": "D020816", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cations, Divalent", "descriptor_ui": "D002413", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Decapodiformes", "descriptor_ui": "D049832", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lancelets", "descriptor_ui": "D064175", "major_topic": false }, { "descriptor": "Light Signal Transduction", "descriptor_ui": "D055537", "major_topic": false }, { "descriptor": "Mutant Chimeric Proteins", "descriptor_ui": "D050506", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Photoperiod", "descriptor_ui": "D017440", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Retinal Pigments", "descriptor_ui": "D012168", "major_topic": false }, { "descriptor": "Retinaldehyde", "descriptor_ui": "D012172", "major_topic": false }, { "descriptor": "Rhodopsin", "descriptor_ui": "D012243", "major_topic": false }, { "descriptor": "Spiders", "descriptor_ui": "D013112", "major_topic": false }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Feb 23", "date_precision": "day", "issue": "1", "normalized_date": "2018-02-23", "pages": "3535", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "An all-trans-retinal-binding opsin peropsin as a potential dark-active and light-inactivated G protein-coupled receptor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Elimination of redundant synapses formed early in development and strengthening of necessary connections are crucial for shaping functional neural circuits. Purkinje cells (PCs) in the neonatal cerebellum are innervated by multiple climbing fibers (CFs) with similar strengths. A single CF is strengthened whereas the other CFs are eliminated in each PC during postnatal development. The underlying mechanisms, particularly for the strengthening of single CFs, are poorly understood. Here we report that progranulin, a multi-functional growth factor implicated in the pathogenesis of frontotemporal dementia, strengthens developing CF synaptic inputs and counteracts their elimination from postnatal day 11 to 16. Progranulin derived from PCs acts retrogradely onto its putative receptor Sort1 on CFs. This effect is independent of semaphorin 3A, another retrograde signaling molecule that counteracts CF synapse elimination. We propose that progranulin-Sort1 signaling strengthens and maintains developing CF inputs, and may contribute to selection of single \"winner\" CFs that survive synapse elimination.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Kohtarou", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Sakoori", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tzu-Huei", "last_name": "Kao", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Mikuni", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2018.01.018" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29398357" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Vesicular Transport", "descriptor_ui": "D033942", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Granulins", "descriptor_ui": "D000077155", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": true }, { "descriptor": "Progranulins", "descriptor_ui": "D000077153", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Semaphorin-3A", "descriptor_ui": "D040121", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sortilin", "descriptor_ui": "D000099183", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Feb 21", "date_precision": "day", "issue": "4", "normalized_date": "2018-02-21", "pages": "796-805.e5", "proceedings_title": null, "publisher": "", "title": "Neuron", "volume": "97", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Retrograde Signaling from Progranulin to Sort1 Counteracts Synapse Elimination in the Developing Cerebellum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The AIM2 inflammasome is activated by DNA, leading to caspase-1 activation and release of pro-inflammatory cytokines interleukin 1beta (IL-1beta) and IL-18, which are critical mediators in host innate immune responses against various pathogens. Some viruses employ strategies to counteract inflammasome-mediated induction of pro-inflammatory cytokines, but their in vivo relevance is less well understood. Here we show that the herpes simplex virus 1 (HSV-1) tegument protein VP22 inhibits AIM2-dependent inflammasome activation. VP22 interacts with AIM2 and prevents its oligomerization, an initial step in AIM2 inflammasome activation. A mutant virus lacking VP22 (HSV-1DeltaVP22) activates AIM2 and induces IL-1beta and IL-18 secretion, but these responses are lost in the absence of AIM2. Additionally, HSV-1DeltaVP22 infection results in diminished viral yields in vivo, but HSV-1DeltaVP22 replication is largely restored in AIM2-deficient mice. Collectively, these findings reveal a mechanism of HSV-1 evasion of the host immune response that enables efficient viral replication in vivo.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ichinohe", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Tokuju", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Koshiba", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Shumpei", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chom.2017.12.014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29447697" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "DNA, Viral", "descriptor_ui": "D004279", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": false }, { "descriptor": "Inflammasomes", "descriptor_ui": "D058847", "major_topic": false }, { "descriptor": "Interleukin-18", "descriptor_ui": "D020382", "major_topic": false }, { "descriptor": "Interleukin-1beta", "descriptor_ui": "D053583", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "NLR Family, Pyrin Domain-Containing 3 Protein", "descriptor_ui": "D000071199", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Structural Proteins", "descriptor_ui": "D015678", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Feb 14", "date_precision": "day", "issue": "2", "normalized_date": "2018-02-14", "pages": "254-265.e7", "proceedings_title": null, "publisher": "", "title": "Cell host & microbe", "volume": "23", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Herpes Simplex Virus 1 VP22 Inhibits AIM2-Dependent Inflammasome Activation to Enable Efficient Viral Replication.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Feedback control is a key mechanism in signal transduction, intimately involved in regulating the outcome of the cellular response. Here, we report a novel mechanism by which PHLDA1, Pleckstrin homology-like domain, family A, member 1, negatively regulates ErbB receptor signaling by inhibition of receptor oligomerization. We have found that the ErbB3 ligand, heregulin, induces PHILDA1 expression in MCF-7 cells. Transcriptionally-induced PHLDA1 protein directly binds to ErbB3, whereas knockdown of PHLDA1 increases complex formation between ErbB3 and ErbB2. To provide insight into the mechanism for our time-course and single-cell experimental observations, we performed a systematic computational search of network topologies of the mathematical models based on receptor dimer-tetramer formation in the ErbB activation processes. Our results indicate that only a model in which PHLDA1 inhibits formation of both dimers and tetramer can explain the experimental data. Predictions made from this model were further validated by single-molecule imaging experiments. Our studies suggest a unique regulatory feature of PHLDA1 to inhibit the ErbB receptor oligomerization process and thereby control the activity of receptor signaling network.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Magi", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Yumoto", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Rieko", "last_name": "Ohki", "name": null }, { "creator_type": "author", "first_name": "Amaya", "last_name": "Garcia-Munoz", "name": null }, { "creator_type": "author", "first_name": "Natalia", "last_name": "Volinsky", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Von Kriegsheim", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Boris N.", "last_name": "Kholodenko", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Okada-Hatakeyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m117.778399" }, "pmcid": { "normalized": "PMC5808779" }, "pmid": { "normalized": "29233889" } }, "mesh": [ { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MCF-7 Cells", "descriptor_ui": "D061986", "major_topic": false }, { "descriptor": "Models, Chemical", "descriptor_ui": "D008956", "major_topic": false }, { "descriptor": "Neuregulin-1", "descriptor_ui": "D020890", "major_topic": false }, { "descriptor": "Protein Multimerization", "descriptor_ui": "D055503", "major_topic": false }, { "descriptor": "Receptor, ErbB-3", "descriptor_ui": "D020893", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Single Molecule Imaging", "descriptor_ui": "D000072760", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Feb 9", "date_precision": "day", "issue": "6", "normalized_date": "2018-02-09", "pages": "2206-2218", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "293", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Transcriptionally inducible Pleckstrin homology-like domain, family A, member 1, attenuates ErbB receptor activity by inhibiting receptor oligomerization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Optogenetics has revolutionized the experimental interrogation of neural circuits and holds promise for the treatment of neurological disorders. It is limited, however, because visible light cannot penetrate deep inside brain tissue. Upconversion nanoparticles (UCNPs) absorb tissue-penetrating near-infrared (NIR) light and emit wavelength-specific visible light. Here, we demonstrate that molecularly tailored UCNPs can serve as optogenetic actuators of transcranial NIR light to stimulate deep brain neurons. Transcranial NIR UCNP-mediated optogenetics evoked dopamine release from genetically tagged neurons in the ventral tegmental area, induced brain oscillations through activation of inhibitory neurons in the medial septum, silenced seizure by inhibition of hippocampal excitatory cells, and triggered memory recall. UCNP technology will enable less-invasive optical neuronal activity manipulation with the potential for remote therapy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shuo", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Adam Z.", "last_name": "Weitemier", "name": null }, { "creator_type": "author", "first_name": "Xiao", "last_name": "Zeng", "name": null }, { "creator_type": "author", "first_name": "Linmeng", "last_name": "He", "name": null }, { "creator_type": "author", "first_name": "Xiyu", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Yanqiu", "last_name": "Tao", "name": null }, { "creator_type": "author", "first_name": "Arthur J. Y.", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hashimotodani", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Hirohide", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Laxmi Kumar", "last_name": "Parajuli", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Daniel B. Loong", "last_name": "Teh", "name": null }, { "creator_type": "author", "first_name": "Angelo H.", "last_name": "All", "name": null }, { "creator_type": "author", "first_name": "Iku", "last_name": "Tsutsui-Kimura", "name": null }, { "creator_type": "author", "first_name": "Kenji F.", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Xiaogang", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Thomas J.", "last_name": "McHugh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.aaq1144" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29439241" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Deep Brain Stimulation", "descriptor_ui": "D046690", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Feb 9", "date_precision": "day", "issue": "6376", "normalized_date": "2018-02-09", "pages": "679-684", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "359", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Near-infrared deep brain stimulation via upconversion nanoparticle-mediated optogenetics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Carboxypeptidases (CPs) are a family of hydrolases that cleave one or more amino acids from the C-terminal of peptides or proteins. However, methodology to monitor the activities of CPs is poorly developed. Here, we present the first versatile design strategy to obtain activatable fluorescent probes for CPs by utilizing intramolecular spirocyclization of rhodamine to translate the \"aliphatic carboxamide to aliphatic carboxylate\" structural conversion catalyzed by CPs into dynamic fluorescence activation. Based on this novel strategy, we developed probes for carboxypeptidases A and B. One of these probes was able to detect pancreatic juice leakage in mice ex vivo, suggesting that its suitability for intraoperative diagnosis of pancreatic fistula. This design strategy should be broadly applicable to CPs, as well as other previously untargetable enzymes, enabling development of fluorescent probes to study various pathological and biological processes.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yugo", "last_name": "Kuriki", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Hidemasa", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Kento", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ishizawa", "name": null }, { "creator_type": "author", "first_name": "Norihiro", "last_name": "Kokudo", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.7b11014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29368925" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018 Feb 7", "date_precision": "day", "issue": "5", "normalized_date": "2018-02-07", "pages": "1767-1773", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "140", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Establishment of Molecular Design Strategy To Obtain Activatable Fluorescent Probes for Carboxypeptidases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The heme-based aerotactic transducer (HemAT) is an oxygen-sensor protein consisting of a sensor and a signaling domain in the N- and C-terminal regions, respectively. Time-resolved step-scan FTIR spectroscopy was employed to characterize protein intermediate states obtained by photolysis of the carbon monoxide complexes of sensor-domain, full-length HemAT, and the Y70F (B-helix), L92A (E-helix), T95A (E-helix), and Y133F (G-helix) HemAT mutants. We assign the spectral components to discrete substructures, which originate from a helical structure that is solvated (1638 cm(-1)) and a native helix that is protected from solvation by interhelix tertiary interactions (1654 cm(-1)). The full-length protein is characterized by an additional amide I absorbance at 1661 cm(-1), which is attributed to disordered structure suggesting that further protein conformational changes occur in the presence of the signaling domain in the full-length protein. The kinetics monitored within the amide I absorbance of the polypeptide backbone in the sensor domain exhibit two distinct relaxation phases (t(1) = 24 and t(2) = 694 mus), whereas that of the full-length protein exhibits monophasic behavior for all substructures in a time range of t = 1253-2090 mus. These observations can be instrumental in monitoring helix motion and the role of specific mutants in controlling the dynamics in the communication pathway from the sensor to the signaling domain. The kinetics observed for the amide I relaxation for the full-length protein indicate that the discrete substructures within full-length HemAT, unlike those of the sensor domain, relax independently.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Andrea", "last_name": "Pavlou", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Shigetoshi", "last_name": "Aono", "name": null }, { "creator_type": "author", "first_name": "Eftychia", "last_name": "Pinakoulaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpj.2017.12.012" }, "pmcid": { "normalized": "PMC5985031" }, "pmid": { "normalized": "29414704" } }, "mesh": [ { "descriptor": "Bacillus subtilis", "descriptor_ui": "D001412", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Carbon Monoxide", "descriptor_ui": "D002248", "major_topic": false }, { "descriptor": "Heme-Binding Proteins", "descriptor_ui": "D000081062", "major_topic": false }, { "descriptor": "Hemeproteins", "descriptor_ui": "D006420", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Spectroscopy, Fourier Transform Infrared", "descriptor_ui": "D017550", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Feb 6", "date_precision": "day", "issue": "3", "normalized_date": "2018-02-06", "pages": "584-591", "proceedings_title": null, "publisher": "", "title": "Biophysical journal", "volume": "114", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Protein Dynamics of the Sensor Protein HemAT as Probed by Time-Resolved Step-Scan FTIR Spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Multipotent hematopoietic progenitors must acquire thymus-homing capacity to initiate T lymphocyte development. Despite its importance, the transcriptional program underlying this process remains elusive. Cbfbeta forms transcription factor complexes with Runx proteins, and here we show that Cbfbeta2, encoded by an RNA splice variant of the Cbfb gene, is essential for extrathymic differentiation of T cell progenitors. Furthermore, Cbfbeta2 endows extrathymic progenitors with thymus-homing capacity by inducing expression of the principal thymus-homing receptor, Ccr9. This occurs via direct binding of Cbfbeta2 to cell type-specific enhancers, as is observed in Rorgammat induction during differentiation of lymphoid tissue inducer cells by activation of an intronic enhancer. As in mice, an alternative splicing event in zebrafish generates a Cbfbeta2-specific mRNA, important for ccr9 expression. Thus, despite phylogenetically and ontogenetically variable sites of origin of T cell progenitors, their robust thymus-homing capacity is ensured by an evolutionarily conserved mechanism emerging from functional diversification of Runx transcription factor complexes by acquisition of a novel splice variant.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mari", "last_name": "Tenno", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kojo", "name": null }, { "creator_type": "author", "first_name": "Divine-Fondzenyuy", "last_name": "Lawir", "name": null }, { "creator_type": "author", "first_name": "Isabell", "last_name": "Hess", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ebihara", "name": null }, { "creator_type": "author", "first_name": "Takaho A.", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Sawako", "last_name": "Muroi", "name": null }, { "creator_type": "author", "first_name": "Rumi", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kawamoto", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Boehm", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Taniuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1084/jem.20171221" }, "pmcid": { "normalized": "PMC5789415" }, "pmid": { "normalized": "29343500" } }, "mesh": [ { "descriptor": "Alternative Splicing", "descriptor_ui": "D017398", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Core Binding Factor alpha Subunits", "descriptor_ui": "D050657", "major_topic": false }, { "descriptor": "Core Binding Factor beta Subunit", "descriptor_ui": "D050658", "major_topic": false }, { "descriptor": "Enhancer Elements, Genetic", "descriptor_ui": "D004742", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Mutant Strains", "descriptor_ui": "D008817", "major_topic": false }, { "descriptor": "Nuclear Receptor Subfamily 1, Group F, Member 3", "descriptor_ui": "D057132", "major_topic": false }, { "descriptor": "Precursor Cells, T-Lymphoid", "descriptor_ui": "D054504", "major_topic": false }, { "descriptor": "Receptors, CCR", "descriptor_ui": "D054388", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Species Specificity", "descriptor_ui": "D013045", "major_topic": false }, { "descriptor": "Thymus Gland", "descriptor_ui": "D013950", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false }, { "descriptor": "Zebrafish Proteins", "descriptor_ui": "D029961", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Feb 5", "date_precision": "day", "issue": "2", "normalized_date": "2018-02-05", "pages": "595-610", "proceedings_title": null, "publisher": "", "title": "The Journal of experimental medicine", "volume": "215", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Cbfbeta2 controls differentiation of and confers homing capacity to prethymic progenitors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "For cell division, negatively charged chromatin, in which nucleosome fibers (10 nm fibers) are irregularly folded [1-5], must be condensed into chromosomes and segregated. While condensin and other proteins are critical for organizing chromatin into the appropriate chromosome shape [6-17], free divalent cations such as Mg(2+) and Ca(2+), which condense chromatin or chromosomes in vitro [18-28], have long been considered important, especially for local condensation, because the nucleosome fiber has a net negative charge and is by itself stretched like \"beads on a string\" by electrostatic repulsion. For further folding, other positively charged factors are required to decrease the charge and repulsion [29]. However, technical limitations to measure intracellular free divalent cations, but not total cations [30], especially Mg(2+), have prevented us from elucidating their function. Here, we developed a Forster resonance energy transfer (FRET)-based Mg(2+) indicator that monitors free Mg(2+) dynamics throughout the cell cycle. By combining this indicator with Ca(2+) [31] and adenosine triphosphate (ATP) [32] indicators, we demonstrate that the levels of free Mg(2+), but not Ca(2+), increase during mitosis. The Mg(2+) increase is coupled with a decrease in ATP, which is normally bound to Mg(2+) in the cell [33]. ATP inhibited Mg(2+)-dependent chromatin condensation in vitro. Chelating Mg(2+) induced mitotic cell arrest and chromosome decondensation, while ATP reduction had the opposite effect. Our results suggest that ATP-bound Mg(2+) is released by ATP hydrolysis and contributes to mitotic chromosome condensation with increased rigidity, suggesting a novel regulatory mechanism for higher-order chromatin organization by the intracellular Mg(2+)-ATP balance.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Maeshima", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Syoji", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Noji", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2017.12.035" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29358072" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Chromosome Segregation", "descriptor_ui": "D020090", "major_topic": true }, { "descriptor": "Chromosomes", "descriptor_ui": "D002875", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrolysis", "descriptor_ui": "D006868", "major_topic": false }, { "descriptor": "Ions", "descriptor_ui": "D007477", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Feb 5", "date_precision": "day", "issue": "3", "normalized_date": "2018-02-05", "pages": "444-451.e6", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "28", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "A Transient Rise in Free Mg(2+) Ions Released from ATP-Mg Hydrolysis Contributes to Mitotic Chromosome Condensation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "cAMP is one of the most important second messengers in biological processes. Cellular dynamics of cAMP have been investigated using a series of fluorescent indicators; however, their sensitivity was sub-optimal for detecting cAMP dynamics at a low concentration range, due to a low ligand affinity and/or poor dynamic range. Seeking an indicator with improved detection sensitivity, we performed insertion screening of circularly permuted mApple, a red fluorescent protein, into the cAMP-binding motif of PKA regulatory subunit Ialpha and developed an improved cAMP indicator named R-FlincA (Red Fluorescent indicator for cAMP). Its increased affinity (Kd = 0.3 muM) and expanded dynamic range (860% at pH 7.2) allowed the detection of subtle changes in the cellular cAMP dynamics at sub-muM concentrations, which could not be easily observed with existing indicators. Increased detection sensitivity also strengthened the advantages of using R-FlincA as a red fluorescent indicator, as it permits a series of applications, including multi-channel/function imaging of multiple second messengers and combinatorial imaging with photo-manipulation. These results strongly suggest that R-FlincA is a promising tool that accelerates cAMP research by revealing unobserved cAMP dynamics at a low concentration range.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yusaku", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Furuta", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-20251-1" }, "pmcid": { "normalized": "PMC5789972" }, "pmid": { "normalized": "29382930" } }, "mesh": [ { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin-Secreting Cells", "descriptor_ui": "D050417", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Red Fluorescent Protein", "descriptor_ui": "D000097573", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jan 30", "date_precision": "day", "issue": "1", "normalized_date": "2018-01-30", "pages": "1866", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Red fluorescent cAMP indicator with increased affinity and expanded dynamic range.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The multicellular green alga Volvox rousseletii displays phototaxis by changing its flagellar beating pattern in response to photoreception. However, the molecular mechanism underlying flagellar regulation is unknown. This study describes a method to demembranate whole spheroids using a nonionic detergent, with the addition of ATP reactivating flagellar motility. These reactivated spheroids swam like live spheroids. Flagellar beating direction was altered in a Ca2+-dependent manner, with a greater change in the anterior hemisphere than in the posterior hemisphere. These findings indicate that V. rousseletii has an anterior–posterior gradient of flagellar sensitivity to Ca2+, which likely plays a key role in V. rousseletii phototaxis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Noriko", "last_name": "Ueki", "name": null }, { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Wakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1715489115" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29311312" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Axoneme", "descriptor_ui": "D054468", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Detergents", "descriptor_ui": "D003902", "major_topic": false }, { "descriptor": "Flagella", "descriptor_ui": "D005407", "major_topic": false }, { "descriptor": "Microscopy, Phase-Contrast", "descriptor_ui": "D008858", "major_topic": false }, { "descriptor": "Movement", "descriptor_ui": "D009068", "major_topic": false }, { "descriptor": "Photosynthesis", "descriptor_ui": "D010788", "major_topic": false }, { "descriptor": "Phototaxis", "descriptor_ui": "D000071444", "major_topic": true }, { "descriptor": "Video Recording", "descriptor_ui": "D014741", "major_topic": false }, { "descriptor": "Volvox", "descriptor_ui": "D044446", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jan 30", "date_precision": "day", "issue": "5", "normalized_date": "2018-01-30", "pages": "E1061-1068", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "115", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Detergent-extracted Volvox model exhibits an anterior–posterior gradient in flagellar Ca2+ sensitivity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The chemical receptors present in living organisms are promising tools for developing biomimetic chemical sensors. However, these receptors require lipid membranes for functioning under physiological conditions, which prevents their utilization in the production of cell-free in vitro chemical sensing systems. Here, we report the development of a cell-free biomimetic sensing platform using virus-like particles (VLPs) with intact ligand-gated Ca(2+) channels and genetically encoded Ca(2+) indicator (GECI). We observed that targeting GECI to the plasma membrane was essential for efficient loading GECI in the VLPs. Although the physiological Ca(2+) concentration [Ca(2+)] maintained in the cells was low ( approximately 10 nM), the concentration in the VLPs was high. This prevented the detection of the increase in [Ca(2+)] caused by binding of the ligand to the receptor. To address this problem, we employed Lyn-R-CEPIA1, which had low affinity for Ca(2+), and a membrane targeting sequence. Thus, we succeeded in monitoring the activation of cyclic nucleotide-gated channels (CNG) on the VLPs by measuring the increase in fluorescence of Lyn-R-CEPIA1. Our VLP-based sensing system can act as a fundamental platform for all kinds of ligand-gated channels.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Kushida", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Shimono", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acssensors.7b00537" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29256249" } }, "mesh": [ { "descriptor": "Biomimetics", "descriptor_ui": "D032701", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Channels", "descriptor_ui": "D015220", "major_topic": false }, { "descriptor": "Cyclic Nucleotide-Gated Cation Channels", "descriptor_ui": "D054815", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": true }, { "descriptor": "Ligand-Gated Ion Channels", "descriptor_ui": "D058446", "major_topic": true }, { "descriptor": "Virion", "descriptor_ui": "D014771", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018 Jan 26", "date_precision": "day", "issue": "1", "normalized_date": "2018-01-26", "pages": "87-92", "proceedings_title": null, "publisher": "", "title": "ACS sensors", "volume": "3", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Biomimetic Chemical Sensing by Fluorescence Signals Using a Virus-like Particle-Based Platform.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Diversified species of Drosophila (fruit fly) provide opportunities to study mechanisms of development and genetic changes responsible for evolutionary changes. In particular, the adult stage is a rich source of morphological traits for interspecific comparison, including wing pigmentation comparison. To study developmental differences among species, detailed observation and appropriate staging are required for precise comparison. Here we describe protocols for staging of pupal periods and quantification of wing pigmentation in a polka-dotted fruit fly, Drosophila guttifera. First, we describe the method for detailed morphological observation and definition of pupal stages based on morphologies. This method includes a technique for removing the puparium, which is the outer chitinous case of the pupa, to enable detailed observation of pupal morphologies. Second, we describe the method for measuring the duration of defined pupal stages. Finally, we describe the method for quantification of wing pigmentation based on image analysis using digital images and ImageJ software. With these methods, we can establish a solid basis for comparing developmental processes of adult traits during pupal stages.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "contributor", "first_name": "Yuichi", "last_name": "Fukutomi", "name": null }, { "creator_type": "contributor", "first_name": "Keiji", "last_name": "Matsumoto", "name": null }, { "creator_type": "contributor", "first_name": "Noriko", "last_name": "Funayama", "name": null }, { "creator_type": "contributor", "first_name": "Shigeyuki", "last_name": "Koshikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.3791/56935" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2018 Jan 24", "date_precision": "day", "issue": "", "normalized_date": "2018-01-24", "pages": "", "proceedings_title": null, "publisher": "", "title": "", "volume": "", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Methods for Staging Pupal Periods and Measurement of Wing Pigmentation of Drosophila guttifera.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "F1-ATPase (F1) is an efficient rotary protein motor, whose reactivity is modulated by the rotary angle to utilize thermal fluctuation. In order to elucidate how its kinetics are affected by the change in the fluctuation, we have extended the reaction-diffusion formalism [R. Watanabe et al., Biophys. J., 2013, 105, 2385] applicable to a wider range of temperatures based on experimental data analysis of F1 derived from thermophilic Bacillus under high ATP concentration conditions. Our simulation shows that the rotary angle distribution manifests a stronger non-equilibrium feature as the temperature increases, because ATP hydrolysis and Pi release are more accelerated compared with the timescale of rotary angle relaxation. This effect causes the rate coefficient obtained from dwell time fitting to deviate from the Arrhenius relation in Pi release, which has been assumed in the previous activation thermodynamic quantities estimation using linear Arrhenius fitting. Larger negative correlation is also found between hydrolysis and Pi release waiting time in a catalytic dwell with the increase in temperature. This loss of independence between the two successive reactions at the catalytic dwell sheds doubt on the conventional dwell time fitting to obtain rate coefficients with a double exponential function at temperatures higher than 65 degrees C, which is close to the physiological temperature of the thermophilic Bacillus.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Tamiya", "name": null }, { "creator_type": "author", "first_name": "Rikiya", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Noji", "name": null }, { "creator_type": "author", "first_name": "Chun-Biu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c7cp06256g" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29292807" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Bacillus", "descriptor_ui": "D001407", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Biocatalysis", "descriptor_ui": "D055162", "major_topic": false }, { "descriptor": "Hydrolysis", "descriptor_ui": "D006868", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Proton-Translocating ATPases", "descriptor_ui": "D006180", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false }, { "descriptor": "Thermodynamics", "descriptor_ui": "D013816", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jan 17", "date_precision": "day", "issue": "3", "normalized_date": "2018-01-17", "pages": "1872-1880", "proceedings_title": null, "publisher": "", "title": "Physical chemistry chemical physics : PCCP", "volume": "20", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Effects of non-equilibrium angle fluctuation on F1-ATPase kinetics induced by temperature increase.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recently, dynamic changes in the location of RNA in space and time in living cells have become a target of interest in biology because of their essential roles in controlling physiological phenomena. To visualize RNA, methods for the fluorescent labeling of RNA in living cells have been developed. For RNA labeling, oligonucleotide-based RNA probes have mainly been used because of their high selectivity for target RNAs. By contrast, protein-based RNA probes have not been used widely because of their lack of design flexibility, although they have various potential advantages compared with nucleotide-based probes, such as controllability of intracellular localization, high detectability, and ease of introduction into cells and transgenic organisms in a cell type and tissue specific manner by genetic engineering techniques. This Perspective focuses on a possible approach to the development of protein-based RNA probes using Pumilio homology domain (PUM-HD) mutants. The PUM-HD is a domain of an RNA binding protein that allows custom-made modifications to recognize a given eight-base RNA sequence. PUM-HD-based RNA probes have been applied to visualize various RNAs in living cells. Here, the techniques and RNA imaging results obtained using the PUM-HD are introduced.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.biochem.7b00983" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29164876" } }, "mesh": [ { "descriptor": "3' Untranslated Regions", "descriptor_ui": "D020413", "major_topic": false }, { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Drug Design", "descriptor_ui": "D015195", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Forecasting", "descriptor_ui": "D005544", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intravital Microscopy", "descriptor_ui": "D000069416", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Mutagenesis, Site-Directed", "descriptor_ui": "D016297", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Oligonucleotides", "descriptor_ui": "D009841", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Biosynthesis", "descriptor_ui": "D014176", "major_topic": false }, { "descriptor": "Protein Domains", "descriptor_ui": "D000072417", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jan 16", "date_precision": "day", "issue": "2", "normalized_date": "2018-01-16", "pages": "200-208", "proceedings_title": null, "publisher": "", "title": "Biochemistry", "volume": "57", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Live Cell Imaging of Endogenous RNAs Using Pumilio Homology Domain Mutants: Principles and Applications.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stem cell fate is orchestrated by core transcription factors (TFs) and epigenetic modifications. Although regulatory genes that control cell type specification are identified, the transcriptional circuit and the cross-talk among regulatory factors during cell fate decisions remain poorly understood. To identify the \"time-lapse\" TF networks during B-lineage commitment, we used multipotent progenitors harboring a tamoxifen-inducible form of Id3, an in vitro system in which virtually all cells became B cells within 6 d by simply withdrawing 4-hydroxytamoxifen (4-OHT). Transcriptome and epigenome analysis at multiple time points revealed that approximately 10%-30% of differentially expressed genes were virtually controlled by the core TFs, including E2A, EBF1, and PAX5. Strikingly, we found unexpected transcriptional priming before the onset of the key TF program. Inhibition of the immediate early genes such as Nr4a2, Klf4, and Egr1 severely impaired the generation of B cells. Integration of multiple data sets, including transcriptome, protein interactome, and epigenome profiles, identified three representative transcriptional circuits. Single-cell RNA sequencing (RNA-seq) analysis of lymphoid progenitors in bone marrow strongly supported the three-step TF network model during specification of multipotent progenitors toward B-cell lineage in vivo. Thus, our findings will provide a blueprint for studying the normal and neoplastic development of B lymphocytes.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Miyai", "name": null }, { "creator_type": "author", "first_name": "Junichiro", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Takaho A.", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Yasutoshi", "last_name": "Agata", "name": null }, { "creator_type": "author", "first_name": "Yasutaka", "last_name": "Motomura", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Yukie", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kawamoto", "name": null }, { "creator_type": "author", "first_name": "Tomokatsu", "last_name": "Ikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/gad.309575.117" }, "pmcid": { "normalized": "PMC5830925" }, "pmid": { "normalized": "29440259" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": false }, { "descriptor": "Histone Code", "descriptor_ui": "D042421", "major_topic": false }, { "descriptor": "Kruppel-Like Factor 4", "descriptor_ui": "D000090062", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Congenic", "descriptor_ui": "D020297", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Multipotent Stem Cells", "descriptor_ui": "D039902", "major_topic": false }, { "descriptor": "PAX5 Transcription Factor", "descriptor_ui": "D051757", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Trans-Activators", "descriptor_ui": "D015534", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": true }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jan 15", "date_precision": "day", "issue": "2", "normalized_date": "2018-01-15", "pages": "112-126", "proceedings_title": null, "publisher": "", "title": "Genes & development", "volume": "32", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In order to better understand the roles that melanocortin receptors (cMCRs) and melanocortin-2 receptor accessory proteins (cMRAP1 and cMRAP2) play in the HPA axis and hypothalamus, adrenal gland and hypothalamus mRNA from 1day-old white leghorn chicks (Gallus gallus), were analyzed by real-time PCR. mRNA was also made for kidney, ovary, and liver. Mrap1 mRNA could be detected in adrenal tissue, but not in any of the other tissues, and mrap2 mRNA was also detected in the adrenal gland. Finally, all five melanocortin receptors mRNAs could be detected in the adrenal gland; mc2r and mc5r mRNAs were the most abundant. To evaluate any potential interactions between MRAP1 and the MCRs that may occur in adrenal cells, individual chick mcr cDNA constructs were transiently expressed in CHO cells either in the presence or absence of a chick mrap1 cDNA, and the transfected cells were stimulated with hACTH(1-24) at concentrations ranging from 10(-13)M to 10(-6)M. As expected, MC2R required co-expression with MRAP1 for functional expression; whereas, co-expression of cMC3R with cMRAP1 had no statistically significant effect on sensitivity to hACTH(1-24). However, co-expression of MC4R and MC5R with MRAP1, increased sensitivity for ACTH(1-24) by approximately 35 fold and 365 fold, respectively. However, co-expressing of cMRAP2 with these melanocortin receptors had no effect on sensitivity to hACTH(1-24). Since the real-time PCR analysis detected mrap2 mRNA and mc4r mRNA in the hypothalamus, the interaction between cMC4R and cMRAP2 with respect to sensitivity to ACTH(1-13)NH(2) stimulation was also evaluated. However, no effect, either positive or negative, was observed. Finally, the highest levels of mc5r mRNA were detected in liver cells. This observation raises the possibility that in one-day old chicks, activation of the HPA axis may also involve a physiological response from liver cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Alexa L.", "last_name": "Thomas", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Takaharu", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Perry", "last_name": "Davis", "name": null }, { "creator_type": "author", "first_name": "Robert M.", "last_name": "Dores", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ygcen.2017.09.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28888694" } }, "mesh": [ { "descriptor": "Adrenocorticotropic Hormone", "descriptor_ui": "D000324", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chickens", "descriptor_ui": "D002645", "major_topic": false }, { "descriptor": "CHO Cells", "descriptor_ui": "D016466", "major_topic": false }, { "descriptor": "Cricetinae", "descriptor_ui": "D006224", "major_topic": false }, { "descriptor": "Cricetulus", "descriptor_ui": "D003412", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypothalamo-Hypophyseal System", "descriptor_ui": "D007030", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Pituitary-Adrenal System", "descriptor_ui": "D010913", "major_topic": false }, { "descriptor": "Receptors, Melanocortin", "descriptor_ui": "D044101", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jan 15", "date_precision": "day", "issue": "", "normalized_date": "2018-01-15", "pages": "50-56", "proceedings_title": null, "publisher": "", "title": "General and comparative endocrinology", "volume": "256", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Analyzing the effects of co-expression of chick (Gallus gallus) melanocortin receptors with either chick MRAP1 or MRAP2 in CHO cells on sensitivity to ACTH(1-24) or ACTH(1-13)NH(2): Implications for the avian HPA axis and avian melanocortin circuits in the hypothalamus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular trafficking of G protein-coupled receptors (GPCRs) controls their localization and degradation, which affects a cell's ability to adapt to extracellular stimuli. Although the perturbation of trafficking induces important diseases, these trafficking mechanisms are poorly understood. Herein, we demonstrate an optogenetic method using an optical dimerizer, cryptochrome (CRY) and its partner protein (CIB), to analyze the trafficking mechanisms of GPCRs and their regulatory proteins. Temporally controlling the interaction between beta-arrestin and beta2-adrenergic receptor (ADRB2) reveals that the duration of the beta-arrestin-ADRB2 interaction determines the trafficking pathway of ADRB2. Remarkably, the phosphorylation of ADRB2 by G protein-coupled receptor kinases is unnecessary to trigger clathrin-mediated endocytosis, and beta-arrestin interacting with unphosphorylated ADRB2 fails to activate mitogen-activated protein kinase (MAPK) signaling, in contrast to the ADRB2 agonist isoproterenol. Temporal control of beta-arrestin-GPCR interactions will enable the investigation of the unique roles of beta-arrestin and the mechanism by which it regulates beta-arrestin-specific trafficking pathways of different GPCRs.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Osamu", "last_name": "Takenouchi", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-19130-y" }, "pmcid": { "normalized": "PMC5766490" }, "pmid": { "normalized": "29330504" } }, "mesh": [ { "descriptor": "beta-Arrestins", "descriptor_ui": "D000071557", "major_topic": false }, { "descriptor": "Dimerization", "descriptor_ui": "D019281", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": false }, { "descriptor": "Endosomes", "descriptor_ui": "D011992", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Isoproterenol", "descriptor_ui": "D007545", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": true }, { "descriptor": "Lysosomes", "descriptor_ui": "D008247", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 1", "descriptor_ui": "D019950", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 3", "descriptor_ui": "D048052", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-mdm2", "descriptor_ui": "D051736", "major_topic": false }, { "descriptor": "Receptors, Adrenergic, beta-2", "descriptor_ui": "D018343", "major_topic": false }, { "descriptor": "Ubiquitination", "descriptor_ui": "D054875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jan 12", "date_precision": "day", "issue": "1", "normalized_date": "2018-01-12", "pages": "677", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Unique Roles of beta-Arrestin in GPCR Trafficking Revealed by Photoinducible Dimerizers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We recently showed that a 13-kDa protein (p13), the homolog protein of formation of mitochondrial complex V assembly factor 1 in yeast, acts as a potential protective factor in pancreatic islets under diabetes. Here, we aimed to identify known compounds regulating p13 mRNA expression to obtain therapeutic insight into the cellular stress response. A luciferase reporter system was developed using the putative promoter region of the human p13 gene. Overexpression of peroxisome proliferator-activated receptor gamma coactivator 1alpha, a master player regulating mitochondrial metabolism, increased both reporter activity and p13 expression. Following unbiased screening with 2320 known compounds in HeLa cells, 12 pharmacological agents (including 8 cardiotonics and 2 anthracyclines) that elicited >2-fold changes in p13 mRNA expression were identified. Among them, four cardiac glycosides decreased p13 expression and concomitantly elevated cellular oxidative stress. Additional database analyses showed highest p13 expression in heart, with typically decreased expression in cardiac disease. Accordingly, our results illustrate the usefulness of unbiased compound screening as a method for identifying novel functional roles of unfamiliar genes. Our findings also highlight the importance of p13 in the cellular stress response in heart.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Taisei", "last_name": "Hirouchi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Higashi", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Hiraki", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Nunomura", "name": null }, { "creator_type": "author", "first_name": "Bangzhong", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Omori", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Yoon-Jeong", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Takefumi", "last_name": "Doi", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2017.11.116" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29180011" } }, "mesh": [ { "descriptor": "Cardiac Glycosides", "descriptor_ui": "D002301", "major_topic": false }, { "descriptor": "Drug Evaluation, Preclinical", "descriptor_ui": "D004353", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Glycoproteins", "descriptor_ui": "D006023", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "High-Throughput Screening Assays", "descriptor_ui": "D057166", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Chaperones", "descriptor_ui": "D018832", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Protein Interaction Mapping", "descriptor_ui": "D025941", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jan 8", "date_precision": "day", "issue": "2", "normalized_date": "2018-01-08", "pages": "1992-1997", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "495", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Unbiased compound screening with a reporter gene assay highlights the role of p13 in the cardiac cellular stress response.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tauopathy is characterized by the fibrillar tau accumulation in neurons and glial cells. In order to advance our understanding of the causative mechanisms of tauopathy, neuroinflammation, which has been suggested to play important roles in disease progression, will require particular attention. Neuroinflammation is characterized predominantly by microglial activation. At present, it is still under debate whether microglial activation is a cause or a result of neurodegeneration. To search for a temporal relationship between neurodegeneration and neuroinflammation, our group demonstrated that in vivo imaging (e.g., tau-PET, TSPO-PET, and volumetric MRI) of tauopathy mice strongly supports the evidence of microglial activation along with both pathological tau accumulation and brain atrophy. Both in vivo imaging and histochemical analysis confirmed that microglial TSPO accumulation was the late event during the pathogenesis of tauopathy. On the other hand, it is known that purinergic receptor P2Y12 as a marker of homeostatic microglia cells was reduced at an early stage of disease progression. In this review, we will introduce a phenotypic change of microglia in a mouse model of tauopathy and propose novel approaches to the establishment of imaging biomarkers, thereby targeting the early diagnosis of tauopathy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3233/jad-179933" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29865054" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Early Diagnosis", "descriptor_ui": "D042241", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microglia", "descriptor_ui": "D017628", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "s1", "normalized_date": "2018", "pages": "S353-S359", "proceedings_title": null, "publisher": "", "title": "Journal of Alzheimer's disease : JAD", "volume": "64", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Microglial Activation During Pathogenesis of Tauopathy in rTg4510 Mice: Implications for the Early Diagnosis of Tauopathy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Induced pluripotent stem cell (iPS) reprogramming allows to turn a differentiated somatic cell into a pluripotent cell. This process is accompanied by many changes in fundamental cell properties, such as energy production, cell-to-cell interactions, cytoskeletal organization, and others. Real-time quantitative polymerase chain reaction (RT-qPCR) can be used as a quantitative method of gene expression analysis to investigate iPS reprogramming but it requires a validation of reference genes for the accurate assessment of target genes’ expression. Currently, studies evaluating the performance of reference genes during iPS reprogramming are lacking. In this study we analysed the stability of 12 housekeeping genes during 20 days of iPS reprogramming of murine cells based on statistical analyses of RT-qPCR data using five different statistical algorithms. This study reports strong variations in housekeeping gene stability during the reprogramming process. Most stable genes were Atp5f1, Pgk1 and Gapdh, while the least stable genes were Rps18, Hprt, Tbp and Actb. The results were validated by a proof-of-point qPCR experiment with pluripotent markers Nanog, Rex1 and Oct4 normalized to the best and the worst reference gene identified by the analyses. Overall, this study and its implications are particularly relevant to investigations on the cell-state and pluripotency in iPS reprogramming.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yulia", "last_name": "Panina", "name": null }, { "creator_type": "author", "first_name": "Arno", "last_name": "Germond", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Masui", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-26707-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29880849" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": true }, { "descriptor": "Cellular Reprogramming Techniques", "descriptor_ui": "D000067470", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Genes, Essential", "descriptor_ui": "D020043", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "Reference Standards", "descriptor_ui": "D012015", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Validation of Common Housekeeping Genes as Reference for qPCR Gene Expression Analysis During iPS Reprogramming Process.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Thirst aroused in the forebrain by angiotensin II (AngII) or buccal drying motivates terrestrial vertebrates to search for water, whereas aquatic fish can drink surrounding water only by reflex swallowing generated in the hindbrain. Indeed, AngII induces drinking through the hindbrain even after removal of the whole forebrain in aquatic fish. Here we show that AngII induces thirst also in the amphibious mudskipper goby without direct action on the forebrain, but through buccal drying. Intracerebroventricular injection of AngII motivated mudskippers to move into water and drink as with tetrapods. However, AngII primarily increased immunoreactive c-Fos at the hindbrain swallowing center where AngII receptors were expressed, as in other ray-finned fish, and such direct action on the forebrain was not found. Behavioural analyses showed that loss of buccal water on land by AngII-induced swallowing, by piercing holes in the opercula, or by water-absorptive gel placed in the cavity motivated mudskippers to move to water for refilling. Since sensory detection of water at the bucco-pharyngeal cavity like ‘dry mouth’ has recently been noted to regulate thirst in mammals, similar mechanisms seem to have evolved in distantly related species in order to solve osmoregulatory problems during terrestrialization.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yukitoshi", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Hirotsugu", "last_name": "Tsuchimochi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kaiya", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "James T.", "last_name": "Pearson", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Takei", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-18611-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29330516" } }, "mesh": [ { "descriptor": "Amphibians", "descriptor_ui": "D000663", "major_topic": false }, { "descriptor": "Angiotensin II", "descriptor_ui": "D000804", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": false }, { "descriptor": "Drinking", "descriptor_ui": "D004326", "major_topic": true }, { "descriptor": "Fishes", "descriptor_ui": "D005399", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-fos", "descriptor_ui": "D016760", "major_topic": false }, { "descriptor": "Rhombencephalon", "descriptor_ui": "D012249", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Drinking by amphibious fish: convergent evolution of thirst mechanisms during vertebrate terrestrialization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recently, we observed that tetraploidization of certain types of human cancer cells resulted in upregulation of centrosome duplication cycles and chronic generation of the extra centrosome. Here, we investigated whether tetraploidy-linked upregulation of centrosome duplication also occurs in non-cancer cells using tetraploidized parthenogenetic mouse embryos. Cytokinesis blockage at early embryonic stage before de novo centriole biogenesis provided the unique opportunity in which tetraploidization can be induced without transient doubling of centrosome number. The extra numbers of the centrioles and the centrosomes were observed more frequently in tetraploidized embryos during the blastocyst stage than in their diploid counterparts, demonstrating the generality of the newly found tetraploidy-driven centrosome overduplication in mammalian non-cancer systems.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kan", "last_name": "Yaguchi", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Shibanuma", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kamimura", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Koda", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/19420889.2018.1526605" }, "pmcid": { "normalized": "PMC6284596" }, "pmid": { "normalized": "30534347" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "4", "normalized_date": "2018", "pages": "e1526605", "proceedings_title": null, "publisher": "", "title": "Communicative & integrative biology", "volume": "11", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Tetraploidy-associated centrosome overduplication in mouse early embryos.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The crustacean Daphnia magna is an important model in multi-disciplinary scientific fields such as genetics, evolutionary developmental biology, toxicology, and ecology. Recently, the draft genome sequence and transcriptome data became publicly available for this species. Genetic transformation has also been achieved via the introduction of plasmid DNA into the genome. The identification of a screenable marker gene and generation of mutant strains are essential to further advance D. magna functional genomics. Because crustaceans are closely related to insects, we hypothesized that, similar to Drosophila genetic studies, eye color-related genes can function as marker genes in Daphnia. We searched orthologs of Drosophila eye pigment transporters White, Scarlet, and Brown in the genome of D. magna. Amino acid sequence alignment and phylogenetic analysis suggested that D. magna has six white and one scarlet orthologs, but lacks the brown ortholog. Due to the multiplicity of white orthologs, we analyzed the function of the scarlet ortholog, DapmaSt, using RNA interference. DapmaSt RNAi embryos showed disappearance of black pigments both in the compound eye and in the ocellus, suggesting that DapmaSt is necessary for black pigmentation in Daphnia eyes. To disrupt DapmaSt using the Crispr/Cas9 system, we co-injected DapmaSt-targeting gRNAs with Cas9 mRNAs into eggs and established white-eyed DapmaSt mutant lines that lack eye pigments throughout their lifespan. Our results suggest that DapmaSt can be used as a transformation marker in D. magna and the DapmaSt mutants would be an important resource for genetic transformation of this species in the future.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Nur Izzatur Binti", "last_name": "Ismail", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0205609" }, "pmcid": { "normalized": "PMC6235260" }, "pmid": { "normalized": "30427863" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "ATP-Binding Cassette Transporters", "descriptor_ui": "D018528", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Eye", "descriptor_ui": "D005123", "major_topic": false }, { "descriptor": "Eye Color", "descriptor_ui": "D005127", "major_topic": false }, { "descriptor": "Eye Proteins", "descriptor_ui": "D005136", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": true }, { "descriptor": "Pigmentation", "descriptor_ui": "D010858", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "11", "normalized_date": "2018", "pages": "e0205609", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "13", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of white-eyed Daphnia magna mutants lacking scarlet function.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Glioblastoma is the most aggressive and invasive brain tumor and has a poor prognosis; elucidating the underlying molecular mechanisms is essential to select molecular targeted therapies. Here, we investigated the effect of microRNAs on the marked invasiveness of glioblastoma. U373 glioblastoma cells were infected with 140 different microRNAs from an OncomiR library, and the effects of the invasion-related microRNAs and targeted molecules were investigated after repeated Matrigel invasion assays. Screening of the OncomiR library identified miR-23a as a key regulator of glioblastoma invasion. In six glioblastoma cell lines, a positive correlation was detected between the expression levels of miR-23a and invasiveness. A luciferase reporter assay demonstrated that homeobox D10 (HOXD10) was a miR-23a-target molecule, which was verified by high scores from both the PicTar and miRanda algorithms. Forced expression of miR-23a induced expression of invasion-related molecules, including uPAR, RhoA, and RhoC, and altered expression of glial-mesenchymal transition markers such as Snail, Slug, MMP2, MMP9, MMP14, and E-cadherin; however, these changes in expression levels were reversed by HOXD10 overexpression. Thus, miR-23a significantly promoted invasion of glioblastoma cells with polarized formation of focal adhesions, while exogenous HOXD10 overexpression reversed these phenomena. Here, we identify miR-23a-regulated HOXD10 as a pivotal regulator of invasion in glioblastoma, providing a novel mechanism for the aggressive invasiveness of this tumor and providing insight into potential therapeutic targets.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Yachi", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kohsaka", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Tanikawa", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41392-018-0033-6" }, "pmcid": { "normalized": "PMC6308238" }, "pmid": { "normalized": "30603114" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "33", "proceedings_title": null, "publisher": "", "title": "Signal transduction and targeted therapy", "volume": "3", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "miR-23a promotes invasion of glioblastoma via HOXD10-regulated glial-mesenchymal transition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Objective: Cardiomyocytes derived from human-induced pluripotent stem cells are a powerful platform for high-throughput drug screening in vitro. However, current modalities for drug testing, such as electrophysiology and fluorescence imaging have inherent drawbacks. To circumvent these problems, we report the development of a bioluminescent Ca2+ indicator GmNL(Ca2+), and its application in a customized microscope for high-throughput drug screening. Results: GmNL(Ca2+) gives a 140% signal change with Ca2+, and can image drug-induced changes of Ca2+ dynamics in cultured cells. Since bioluminescence requires application of a chemical substrate, which is consumed over ~ 30 min we made a dedicated microscope with automated drug dispensing inside a light-tight box, to control drug addition. To overcome thermal instability of the luminescent substrate, or small molecule, dual climate control enables distinct temperature settings in the drug reservoir and the biological sample. By combining GmNL(Ca2+) with this adaptation, we could image spontaneous Ca2+ transients in cultured cardiomyocytes and phenotype their response to well-known drugs without accessing the sample directly. In addition, the bioluminescent strategy demonstrates minimal perturbation of contractile parameters and long-term observation attributable to lack of phototoxicity and photobleaching. Overall, bioluminescence may enable more accurate drug screening in a high-throughput manner. Electronic supplementary material: The online version of this article (10.1186/s13104-018-3421-7) contains supplementary material, which is available to authorized users.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazushi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takahito", "last_name": "Onishi", "name": null }, { "creator_type": "author", "first_name": "Chieko", "last_name": "Nakada", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Takei", "name": null }, { "creator_type": "author", "first_name": "Matthew J.", "last_name": "Daniels", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13104-018-3421-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29776438" } }, "mesh": [ { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": true }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Drug Evaluation, Preclinical", "descriptor_ui": "D004353", "major_topic": false }, { "descriptor": "High-Throughput Screening Assays", "descriptor_ui": "D057166", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "BMC Research Notes", "volume": "11", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Uninterrupted monitoring of drug effects in human-induced pluripotent stem cell-derived cardiomyocytes with bioluminescence Ca2+ microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background : A breast-specific photoacoustic imaging (PAI) system prototype equipped with a hemispherical detector array (HDA) has been reported as a promising system configuration for providing high morphological reproducibility for vascular structures in living bodies. Methods : To image the vasculature of human limbs, a newly designed PAI system prototype (PAI-05) with an HDA with a higher density sensor arrangement was developed. The basic device configuration mimicked that of a previously reported breast-specific PAI system. A new imaging table and a holding tray for imaging a subject's limb were adopted. Results : The device's performance was verified using a phantom. Contrast of 8.5 was obtained at a depth of 2 cm, and the viewing angle reached up to 70 degrees, showing sufficient performance for limb imaging. An arbitrary wavelength was set, and a reasonable PA signal intensity dependent on the wavelength was obtained. To prove the concept of imaging human limbs, various parts of the subject were scanned. High-quality still images of a living human with a wider size than that previously reported were obtained by scanning within the horizontal plane and averaging the images. The maximum field of view (FOV) was 270 mm x 180 mm. Even in movie mode, one-shot 3D volumetric data were obtained in an FOV range of 20 mm in diameter, which is larger than values in previous reports. By continuously acquiring these images, we were able to produce motion pictures. Conclusion : We developed a PAI prototype system equipped with an HDA suitable for imaging limbs. As a result, the subject could be scanned over a wide range while in a more comfortable position, and high-quality still images and motion pictures could be obtained.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nagae", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Asao", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Yuusuke", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Ohira", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Otsuka", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Moritoshi", "last_name": "Furu", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Sekiguchi", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Togashi", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kabashima", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Toi", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Yagi", "name": null } ], "identifiers": { "doi": { "normalized": "10.12688/f1000research.16743.2" }, "pmcid": { "normalized": "PMC6396844" }, "pmid": { "normalized": "30854189" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "1813", "proceedings_title": null, "publisher": "", "title": "F1000Research", "volume": "7", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Real-time 3D Photoacoustic Visualization System with a Wide Field of View for Imaging Human Limbs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To be able to predict antibiotic resistance in bacteria from fast label-free microscopic observations would benefit a broad range of applications in the biological and biomedical fields. Here, we demonstrate the utility of label-free Raman spectroscopy in monitoring the type of resistance and the mode of action of acquired resistance in a bacterial population of Escherichia coli, in the absence of antibiotics. Our findings are reproducible. Moreover, we identified spectral regions that best predicted the modes of action and explored whether the Raman signatures could be linked to the genetic basis of acquired resistance. Spectral peak intensities significantly correlated (False Discovery Rate, p < 0.05) with the gene expression of some genes contributing to antibiotic resistance genes. These results suggest that the acquisition of antibiotic resistance leads to broad metabolic effects reflected through Raman spectral signatures and gene expression changes, hinting at a possible relation between these two layers of complementary information.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Arno", "last_name": "Germond", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Chikara", "last_name": "Furusawa", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-018-0093-8" }, "pmcid": { "normalized": "PMC6123714" }, "pmid": { "normalized": "30271966" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "85", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "1", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Raman spectral signature reflects transcriptomic features of antibiotic resistance in Escherichia coli.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Tau imaging using PET is a promising tool for the diagnosis and evaluation of tau-related neurodegenerative disorders, but the relationship among PET-detectable tau, neuroinflammation, and neurodegeneration is not yet fully understood. OBJECTIVE: We aimed to elucidate sequential changes in tau accumulation, neuroinflammation, and brain atrophy by PET and MRI in a tauopathy mouse model. METHODS: rTg4510 transgenic (tg) mice expressing P301L mutated tau and non-tg mice were examined with brain MRI and PET imaging (analyzed numbers: tg = 17, non-tg = 13; age 2.5 approximately 14 months). As PET probes, [11C]PBB3 (Pyridinyl-Butadienyl-Benzothiazole 3) and [11C]AC-5216 were used to visualize tau pathology and 18-kDa translocator protein (TSPO) neuroinflammation. Tau pathology and microglia activation were subsequently analyzed by histochemistry. RESULTS: PET studies revealed age-dependent increases in [11C]PBB3 and [11C]AC-5216 signals, which were correlated with age-dependent volume reduction in the forebrain on MRI. However, the increase in [11C]PBB3 signals reached a plateau at age 7 months, and therefore its significant correlation with [11C]AC-5216 disappeared after age 7 months. In contrast, [11C]AC-5216 showed a strong correlation with both age and volume reduction until age 14 months. Histochemical analyses confirmed the relevance of pathological tau accumulation and elevated TSPO immunoreactivity in putative microglia. CONCLUSION: Our results showed that tau accumulation is associated with neuroinflammation and brain atrophy in a tauopathy mouse model. The time-course of the [11C]PBB3- and TSPO-PET finding suggests that tau deposition triggers progressive neuroinflammation, and the sequential changes can be evaluated in vivo in mouse brains.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ai", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Minamihisamatsu", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Shimojo", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takuwa", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Ruiqing", "last_name": "Ni", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Bin", "last_name": "Ji", "name": null }, { "creator_type": "author", "first_name": "Ming-Rong", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Ichio", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null } ], "identifiers": { "doi": { "normalized": "10.3233/jad-170509" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29332041" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Atrophy", "descriptor_ui": "D001284", "major_topic": false }, { "descriptor": "Benzothiazoles", "descriptor_ui": "D052160", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microglia", "descriptor_ui": "D017628", "major_topic": false }, { "descriptor": "Positron-Emission Tomography", "descriptor_ui": "D049268", "major_topic": false }, { "descriptor": "Receptors, GABA", "descriptor_ui": "D018079", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "3", "normalized_date": "2018", "pages": "1037-1052", "proceedings_title": null, "publisher": "", "title": "Journal of Alzheimer's disease : JAD", "volume": "61", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "In Vivo Visualization of Tau Accumulation, Microglial Activation, and Brain Atrophy in a Mouse Model of Tauopathy rTg4510.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Visualizing RNA in living cells is increasingly important to facilitate accumulation of knowledge about the relation between specific RNA dynamics and physiological events. Single-molecule fluorescence imaging of target RNAs is an excellent approach to analyzing intracellular RNA motion, but it requires special techniques for probe design and microscope setup. Herein, we present a principle and protocol of an RNA visualization probe based on an RNA binding protein of the Pumilio homology domain (PUM-HD). We also describe the setup and operation of a microscope, and introduce an application to visualize telomeric repeats-containing RNA with telomeres and a telomere-related protein: hnRNPA1. This imaging technique is applicable to visualization of different RNAs, especially including repetitive sequences, in living cells.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4939-7213-5_22" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29130208" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Computer Systems", "descriptor_ui": "D003199", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Protein Domains", "descriptor_ui": "D000072417", "major_topic": false }, { "descriptor": "RNA Probes", "descriptor_ui": "D015347", "major_topic": false }, { "descriptor": "RNA, Untranslated", "descriptor_ui": "D022661", "major_topic": false }, { "descriptor": "Single Molecule Imaging", "descriptor_ui": "D000072760", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "337-347", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "1649", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Real-Time Fluorescence Imaging of Single-Molecule Endogenous Noncoding RNA in Living Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herpesvirus subfamilies typically acquire their final envelope in various cytoplasmic compartments such as the trans-Golgi network (TGN), and endosomes prior to their secretion into the extracellular space. However, the sites for the final envelopment of Epstein–Barr virus (EBV), a ubiquitous human gamma herpesvirus, are poorly understood. Here, we characterized the sites for the final envelopment of EBV in Burkitt’s lymphoma cell lines induced into the lytic cycle by crosslinking cell surface IgG. Electron microscopy revealed the various stages of maturation and egress of progeny virions including mature EBV in irregular cytoplasmic vesicles. Immunofluorescence staining showed that gp350/220, the major EBV glycoprotein, and the viral capsid antigen, p18, efficiently colocalized with a cis-Golgi marker, GM130. gp350/220 partly colocalized with the TGN, which was distributed in a fragmented and dispersed pattern in the cells induced into the lytic cycle. In contrast, limited colocalization was observed between gp350/220 and endosomal markers, such as a multi-vesicular bodies marker, CD63, a recycling endosome marker, Rab11, and a regulatory secretion vesicles marker, Rab27a. Finally, we observed that treatment of cells with brefeldin A, an inhibitor of vesicle trafficking between the endoplasmic reticulum and Golgi apparatus, resulted in the perinuclear accumulation of gp350/220 and inhibition of its distribution to the plasma membrane. Brefeldin A also inhibited the release of infectious EBV. Taken together, our findings support a model in which EBV acquires its final envelope in intracellular compartments containing markers of Golgi apparatus, providing new insights into how EBV matures.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Asuka", "last_name": "Nanbo", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fmicb.2018.00454" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29615992" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Microbiology", "volume": "9", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Epstein–Barr Virus Acquires Its Final Envelope on Intracellular Compartments With Golgi Markers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "RATIONALE: Diabetes causes cardiac dysfunction, and understanding of its mechanism is still incomplete. One reason could be limitations in modeling disease conditions by current in vitro cardiomyocyte culture. Emerging evidence suggests that the mechanical properties of the microenvironment affect cardiomyocyte function. Nevertheless, the impact of high glucose on cardiomyocytes cultured on substrates whose stiffness matches that of the heart (approximately 15 kPa) is untested. OBJECTIVE: To test the hypothesis that cardiomyocytes cultured in microenvironments that mimic the mechanical properties of those for cardiomyocytes in vivo may reproduce the pathophysiology characteristics of diabetic cardiomyocytes ex vivo, such as the morphological appearance, ROS accumulation, mitochondrial dysfunction, apoptosis and insulin-stimulated glucose uptake. METHODS AND RESULTS: Isolated neonatal rat cardiomyocytes were seeded on 15 kPa polyacrylamide (PAA) gels, whose stiffness mimics that of heart tissues, or on glass coverslips, which represent conventional culture devices but are unphysiologically stiff. Cells were then cultured at 5 mM glucose, corresponding to the normal blood glucose level, or at high glucose levels (10 to 25 mM). Cytoskeletal disorganization, ROS accumulation, attenuated mitochondrial membrane potential and attenuated ATP level caused by high glucose and their reversal by a ROS scavenger were prominent in cells on gels, but not in cells on coverslips. The lack of response to ROS scavenging could be attributable to enhanced apoptosis in cells on glass, shown by enhanced DNA fragmentation and higher caspase 3/7 activity in cells on glass coverslips. High-glucose treatment also downregulated GLUT4 expression and attenuated insulin-stimulated glucose uptake only in cells on 15 kPa gels. CONCLUSION: Our data suggest that a mechanically compliant microenvironment increases the susceptibility of primary cardiomyocytes to elevated glucose levels, which enables these cells to serve as an innovative model for diabetic heart research.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masaki", "last_name": "Morishima", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Funaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0201891" }, "pmcid": { "normalized": "PMC6107143" }, "pmid": { "normalized": "30138395" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Culture Media", "descriptor_ui": "D003470", "major_topic": true }, { "descriptor": "Cytoskeleton", "descriptor_ui": "D003599", "major_topic": false }, { "descriptor": "Elasticity", "descriptor_ui": "D004548", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Heart Ventricles", "descriptor_ui": "D006352", "major_topic": false }, { "descriptor": "Insulin Resistance", "descriptor_ui": "D007333", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "8", "normalized_date": "2018", "pages": "e0201891", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "13", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Cardiomyocytes cultured on mechanically compliant substrates, but not on conventional culture devices, exhibit prominent mitochondrial dysfunction due to reactive oxygen species and insulin resistance under high glucose.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Live imaging using various microscopic technologies is an indispensable tool for investigating the dynamic nature of immune cells. One of the most powerful techniques is the two-photon laser-scanning microscopy (TP-LSM), which has various advantages in observing deep tissues in vivo. Interstitial T cell migration in the lymph node (LN) is a phenomenon intensively examined using TP-LSM in the field of immunology. Intravital and explant methods have been standards for imaging T cell behaviors in the LN, though there are several limitations. Live imaging of LN slices, an LN explant sliced by a vibratome to expose tissue parenchyma, could provide an alternative approach with technical advantages for an in-depth analysis of interstitial T cell migration in vivo.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4939-7762-8_4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29476486" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Cell Tracking", "descriptor_ui": "D058948", "major_topic": false }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "29-42", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "1763", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Live Imaging of Interstitial T Cell Migration Using Lymph Node Slices.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The successful entry of herpes simplex virus (HSV) into a cell is a complex process requiring the interaction of several surface viral glycoproteins with host cell receptors. These viral glycoproteins are currently thought to work sequentially to trigger fusogenic activity, but the process is complicated by the fact that each glycoprotein is known to interact with a range of target cell surface receptor molecules. The glycoproteins concerned are gB, gD, and gH/gL, with at least four host cell receptor molecules known to bind to gB and gD alone. Redundancy among gD receptors is also evident and binding to both the gB and gD receptors simultaneously is known to be required for successful membrane fusion. Receptor type and tissue distribution are commonly considered to define the extent of viral tropism and thus the magnitude of pathogenesis. Viral entry receptors are therefore attractive pharmaceutical target molecules for the prevention and/or treatment of viral infections. However, the large number of HSV glycoprotein receptors makes a comprehensive understanding of HSV pathogenesis in vivo difficult. Here we summarize our current understanding of the various HSV glycoprotein cell surface receptors, define their redundancy and binding specificity, and discuss the significance of these interactions for viral pathogenesis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-981-10-7230-7_1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29896660" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Glycoproteins", "descriptor_ui": "D006023", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Receptors, Virus", "descriptor_ui": "D011991", "major_topic": false }, { "descriptor": "Simplexvirus", "descriptor_ui": "D018139", "major_topic": false }, { "descriptor": "Viral Envelope Proteins", "descriptor_ui": "D014759", "major_topic": false }, { "descriptor": "Virus Internalization", "descriptor_ui": "D053586", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "3-21", "proceedings_title": null, "publisher": "", "title": "Advances in experimental medicine and biology", "volume": "1045", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "The Role of HSV Glycoproteins in Mediating Cell Entry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Rapid diagnosis of metastatic lymph nodes (mLNs) of colorectal cancer (CRC) is desirable either intraoperatively or in resected fresh specimens. We have developed a series of activatable fluorescence probes for peptidase activities that are specifically upregulated in various tumors. We aimed to discover a target enzyme for detecting mLNs of CRC. Among our probes, we found that gGlu-HMRG, a gamma-glutamyl transpeptidase (GGT)-activatable fluorescence probe, could detect mLNs. This was unexpected, because we have previously reported that gGlu-HMRG could not detect primary CRC. We confirmed that the GGT activity of mLNs was high, whereas that of non-metastatic lymph nodes and CRC cell lines was low. We investigated the reason why GGT activity was upregulated in mLNs, and found that GGT was induced under conditions of hypoxia or low nutritional status. We utilized this feature to achieve rapid detection of mLNs with gGlu-HMRG. GGT appears to be a promising candidate enzyme for fluorescence imaging of mLNs.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hidemasa", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yugo", "last_name": "Kuriki", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Yasutoshi", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Eigo", "last_name": "Otsuji", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-36062-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30542087" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "gamma-Glutamyltransferase", "descriptor_ui": "D005723", "major_topic": false }, { "descriptor": "HCT116 Cells", "descriptor_ui": "D045325", "major_topic": false }, { "descriptor": "HT29 Cells", "descriptor_ui": "D019073", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": false }, { "descriptor": "Lymphatic Metastasis", "descriptor_ui": "D008207", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Rapid detection of metastatic lymph nodes of colorectal cancer with a gamma-glutamyl transpeptidase-activatable fluorescence probe.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sensory processing is regulated by the coordinated excitation and inhibition of neurons in neuronal circuits. The analysis of neuronal activities has greatly benefited from the recent development of genetically encoded Ca2+ indicators (GECIs). These molecules change their fluorescence intensities or colours in response to changing levels of Ca2+ and can, therefore, be used to sensitively monitor intracellular Ca2+ concentration, which enables the detection of neuronal excitation, including action potentials. These GECIs were developed to monitor increases in Ca2+ concentration; therefore, neuronal inhibition cannot be sensitively detected by these GECIs. To overcome this difficulty, we hypothesised that an inverse-type of GECI, whose fluorescence intensity increases as Ca2+ levels decrease, could sensitively monitor reducing intracellular Ca2+ concentrations. We, therefore, developed a Ca2+ indicator named inverse-pericam 2.0 (IP2.0) whose fluorescent intensity decreases 25-fold upon Ca2+ binding in vitro. Using IP2.0, we successfully detected putative neuronal inhibition by monitoring the decrease in intracellular Ca2+ concentration in AWCON and ASEL neurons in Caenorhabditis elegans. Therefore, IP2.0 is a useful tool for studying neuronal inhibition and for the detailed analysis of neuronal activities in vivo.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Sayuri", "last_name": "Hara-Kuge", "name": null }, { "creator_type": "author", "first_name": "Tomonobu", "last_name": "Nishihara", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kitazono", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Teramoto", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0194707" }, "pmcid": { "normalized": "PMC5918796" }, "pmid": { "normalized": "29694380" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "4", "normalized_date": "2018", "pages": "e0194707", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "13", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "An improved inverse-type Ca2+ indicator can detect putative neuronal inhibition in Caenorhabditis elegans by increasing signal intensity upon Ca2+ decrease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Machine learning-based cell classifiers use cell images to automate cell-type discrimination, which is increasingly becoming beneficial in biological studies and biomedical applications. Brightfield or fluorescence images are generally employed as the classifier input variables. We propose to use Raman spectral images and a method to extract features from these spatial patterns and explore the value of this information for cell discrimination. Raman images provide information regarding distribution of chemical compounds of the considered biological entity. Since each spectral wavelength can be used to reconstruct the distribution of a given compound, spectral images provide multiple channels of information, each representing a different pattern, in contrast to brightfield and fluorescence images. Using a dataset of single living cells, we demonstrate that the spatial information can be ranked by a Fisher discriminant score, and that the top-ranked features can accurately classify cell types. This method is compared with the conventional Raman spectral analysis. We also propose to combine the information from whole spectral analyses and selected spatial features and show that this yields higher classification accuracy. This method provides the basis for a novel and systematic analysis of cell-type investigation using Raman spectral imaging, which may benefit several studies and biomedical applications.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Arno", "last_name": "Germond", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Liang-da", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-30276-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30082723" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Principal Component Analysis", "descriptor_ui": "D025341", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell type discrimination based on image features of molecular component distribution.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Infection of Epstein-Barr virus (EBV), a ubiquitous human gamma herpesvirus, is closely linked to various lymphoid and epithelial malignancies. Previous studies demonstrated that the efficiency of EBV infection in epithelial cells is significantly enhanced by coculturing them with latently infected B cells relative to cell-free infection, suggesting that cell-to-cell contact-mediated viral transmission is the dominant mode of infection by EBV in epithelial cells. However, a detailed mechanism underlying this process has not been fully understood. In the present study, we assessed the role of transforming growth factor beta (TGF-beta), which is known to induce EBV's lytic cycle by upregulation of EBV's latent-lytic switch BZLF1 gene. We have found that 5 days of cocultivation facilitated cell-to-cell contact-mediated EBV transmission. Replication of EBV was induced in cocultured B cells both with and without a direct cell contact in a time-dependent manner. Treatment of a blocking antibody for TGF-beta suppressed both induction of the lytic cycle in cocultured B cells and subsequent viral transmission. Cocultivation with epithelial cells facilitated expression of TGF-beta receptors in B cells and increased their susceptibility to TGF-beta. Finally, we confirmed the spontaneous secretion of TGF-beta from epithelial cells, which was not affected by cell-contact. In contrast, the extracellular microvesicles, exosomes derived from cocultured cells partly contributed to cell-to-cell contact-mediated viral transmission. Taken together, our findings support a role for TGF-beta derived from epithelial cells in efficient viral transmission, which fosters induction of the viral lytic cycle in the donor B cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Asuka", "last_name": "Nanbo", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Yoshiyama", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fmicb.2018.00984" }, "pmcid": { "normalized": "PMC5962739" }, "pmid": { "normalized": "29867885" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "984", "proceedings_title": null, "publisher": "", "title": "Frontiers in microbiology", "volume": "9", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "The Role of Transforming Growth Factor beta in Cell-to-Cell Contact-Mediated Epstein-Barr Virus Transmission.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Host-associated microbiota is often acquired by horizontal transmission of microbes present in the environment. It is hypothesized that differences in the environmental pool of colonizers can influence microbiota community assembly on the host and as such affect holobiont composition and host fitness. To investigate this hypothesis, the host-associated microbiota of the invertebrate eco(toxico)logical model Daphnia was experimentally disturbed using different concentrations of the antibiotic oxytetracycline. The community assembly and host-microbiota interactions when Daphnia were colonized by the disturbed microbiota were investigated by inoculating germ-free individuals with the microbiota. Results: Antibiotic-induced disturbance of the microbiota had a strong effect on the subsequent colonization of Daphnia by affecting ecological interactions between members of the microbiota. This resulted in differences in community assembly which, in turn, affected Daphnia growth. Conclusions: These results show that the composition of the pool of colonizing microbiota can be an important structuring factor of the microbiota assembly on Daphnia, affecting holobiont composition and host growth. These findings contribute to a better understanding of how the microbial environment can shape the holobiont composition and affect host-microbiota interactions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Martijn", "last_name": "Callens", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Ellen", "last_name": "Decaestecker", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s40168-018-0444-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29566771" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anti-Bacterial Agents", "descriptor_ui": "D000900", "major_topic": false }, { "descriptor": "Bacterial Load", "descriptor_ui": "D058491", "major_topic": false }, { "descriptor": "Biodiversity", "descriptor_ui": "D044822", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "Host Microbial Interactions", "descriptor_ui": "D000076662", "major_topic": true }, { "descriptor": "Microbiota", "descriptor_ui": "D064307", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "Microbiome", "volume": "6", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Microbiota inoculum composition affects holobiont assembly and host growth in Daphnia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular deposition of microtubule-associated protein tau in the form of filamentous aggregates is a prominent neuropathological feature of neurodegenerative disorders termed tauopathy. Formation of filamentous tau aggregates is presumably initiated by phosphorylation and/or conformational change of protein structure followed by oligomerization and fibril extension. These processes via intermediate oligomers have not yet been entirely resolved. To examine the biochemical properties of tau protein including oligomers, standardized isolation methods will invariably provide molecular mechanisms of tauopathy. In this chapter, we describe the procedures for isolating tau oligomers based on biochemical properties.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Kimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4939-7816-8_26" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29886548" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Electrophoresis, Polyacrylamide Gel", "descriptor_ui": "D004591", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Aggregates", "descriptor_ui": "D066329", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Protein Multimerization", "descriptor_ui": "D055503", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "435-445", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "1779", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Biochemical Properties of Pathology-Related Tau Species in Tauopathy Brains: An Extraction Protocol for Tau Oligomers and Aggregates.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The acquisition of environmental osmolality tolerance traits in individuals and gametes is an important event in the evolution and diversification of organisms. Although teleost fish exhibit considerable intra- and interspecific variation in salinity tolerance, the genetic mechanisms underlying this trait remain unclear. Oryzias celebensis survives in sea and fresh water during both the embryonic and adult stages, whereas its close relative Oryzias woworae cannot survive in sea water at either stage. A linkage analysis using backcross progeny identified a single locus responsible for adult hyperosmotic tolerance on a fused chromosome that corresponds to O. latipes linkage groups (LGs) 6 and 23. Conversely, O. woworae eggs fertilised with O. celebensis sperm died in sea water at the cleavage stages, whereas O. celebensis eggs fertilised with O. woworae sperm developed normally, demonstrating that maternal factor(s) from O. celebensis are responsible for hyperosmotic tolerance during early development. A further linkage analysis using backcrossed females revealed a discrete single locus relating to the maternal hyperosmotic tolerance factor in a fused chromosomal region homologous to O. latipes LGs 17 and 19. These results indicate that a maternal factor governs embryonic hyperosmotic tolerance and maps to a locus distinct from that associated with adult hyperosmotic tolerance.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Taijun", "last_name": "Myosho", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Kento", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Hamaguchi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Sakaizumi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-24621-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29720646" } }, "mesh": [ { "descriptor": "Adaptation, Biological", "descriptor_ui": "D000220", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromosome Mapping", "descriptor_ui": "D002874", "major_topic": false }, { "descriptor": "Chromosomes", "descriptor_ui": "D002875", "major_topic": false }, { "descriptor": "Genetic Association Studies", "descriptor_ui": "D056726", "major_topic": false }, { "descriptor": "Genetic Linkage", "descriptor_ui": "D008040", "major_topic": false }, { "descriptor": "Lod Score", "descriptor_ui": "D008126", "major_topic": false }, { "descriptor": "Oryzias", "descriptor_ui": "D009990", "major_topic": false }, { "descriptor": "Osmotic Pressure", "descriptor_ui": "D009997", "major_topic": true }, { "descriptor": "Quantitative Trait Loci", "descriptor_ui": "D040641", "major_topic": true }, { "descriptor": "Quantitative Trait, Heritable", "descriptor_ui": "D019655", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Hyperosmotic tolerance of adult fish and early embryos are determined by discrete, single loci in the genus Oryzias.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The advent of the genomic era has led to the discovery of linkages of several genes and pathways to schizophrenia and autism spectrum disorder (ASD) that may serve as new biomarkers or therapeutic targets for these diseases. Two large-scale genetic studies published early in 2011 provided evidence that functional microduplications at 7q36.3, containing VIPR2, are a risk factor for schizophrenia. 7q36.3 microduplications were also reported to be significantly increased in ASD. VIPR2 encodes VPAC2, a seven transmembrane heterotrimeric G protein-coupled receptor that binds two homologous neuropeptides with high affinity, PACAP and VIP. These clinical studies demonstrate a VIPR2 genetic linkage to schizophrenia and ASD and should lead to novel insights into the etiology of these mental health disorders. However, the mechanism by which overactive VPAC2 signaling may lead to schizophrenia and ASD is unknown. In the present review, we will describe recent advances in the genetics of schizophrenia and attempt to discuss the pathophysiological role of altered VPAC2 signaling in psychiatric disorders.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/fpj.151.249" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29887574" } }, "mesh": [ { "descriptor": "Autism Spectrum Disorder", "descriptor_ui": "D000067877", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Receptors, Vasoactive Intestinal Peptide, Type II", "descriptor_ui": "D051239", "major_topic": false }, { "descriptor": "Schizophrenia", "descriptor_ui": "D012559", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "6", "normalized_date": "2018", "pages": "249-253", "proceedings_title": null, "publisher": "", "title": "Nihon yakurigaku zasshi. Folia pharmacologica Japonica", "volume": "151", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "[Pathophysiological implication of the VPAC2 receptor in psychiatric disorders].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "TP53 (which encodes p53) is one of the most frequently mutated genes in cancers. In this study, we generated TP53-mutant pigs by gene editing via electroporation of the Cas9 protein (GEEP), a process that involves introducing the Cas9 protein and single-guide RNA (sgRNA) targeting exon 3 and intron 4 of TP53 into in vitro-fertilized zygotes. Zygotes modified by the sgRNAs were transferred to recipients, two of which gave birth to a total of 11 piglets. Of those 11 piglets, 9 survived. Molecular genetic analysis confirmed that 6 of 9 live piglets carried mutations in TP53, including 2 piglets with no wild-type (WT) sequences and 4 genetically mosaic piglets with WT sequences. One mosaic piglet had 142 and 151 bp deletions caused by a combination of the two sgRNAs. These piglets were continually monitored for 16 months and three of the genome-edited pigs (50%) exhibited various tumor phenotypes that we presumed were caused by TP53 mutations. Two mutant pigs with no WT sequences developed mandibular osteosarcoma and nephroblastoma. The mosaic pig with a deletion between targeting sites of two sgRNAs exhibited malignant fibrous histiocytoma. Tumor phenotypes of TP53 mosaic mutant pigs have not been previously reported. Our results indicated that the mutations caused by gene editing successfully induced tumor phenotypes in both TP53 mosaic- and bi-allelic mutant pigs.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Fuminori", "last_name": "Tanihara", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Nhien Thi", "last_name": "Nguyen", "name": null }, { "creator_type": "author", "first_name": "Quynh Anh", "last_name": "Le", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Dai-Ichiro", "last_name": "Fuchimoto", "name": null }, { "creator_type": "author", "first_name": "Takeshige", "last_name": "Otoi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0206360" }, "pmcid": { "normalized": "PMC6198999" }, "pmid": { "normalized": "30352075" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Electroporation", "descriptor_ui": "D018274", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": false }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Histiocytoma, Benign Fibrous", "descriptor_ui": "D018219", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Swine", "descriptor_ui": "D013552", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false }, { "descriptor": "Zygote", "descriptor_ui": "D015053", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "10", "normalized_date": "2018", "pages": "e0206360", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "13", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of a TP53-modified porcine cancer model by CRISPR/Cas9-mediated gene modification in porcine zygotes via electroporation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The optogenetics approach uses a combination of genetic and optical methods to initiate and control functions in specific cells of biological tissues. Since the high-speed control of neuronal activity by irradiating channelrhodopsin-2 with blue light was reported in 2005, tremendous advancement and application of optogenetics in the field of neuroscience, such as in studies that associate neuronal activity with behaviors, have been initiated. Optogenetics is not only used as a research tool, but is also started to apply in the diagnosis of a disease or as therapy in various studies. Here, we summarize reports on therapy using a typical photoreceptor used in optogenetics, channelrhodopsin-2.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.2174/1566523218666180302163814" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29512463" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Channelrhodopsins", "descriptor_ui": "D000075402", "major_topic": false }, { "descriptor": "Genetic Therapy", "descriptor_ui": "D015316", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neurosciences", "descriptor_ui": "D009488", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "1", "normalized_date": "2018", "pages": "40-44", "proceedings_title": null, "publisher": "", "title": "Current gene therapy", "volume": "18", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Application of Optogenetics in Gene Therapy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the past decade, the various types of genetically-encoded optogenetic tools using blue-light sensitive LOV2 domain have been developed and applied in a wide range of areas including neuroscience field. Recently, we succeeded in developing a photoactivatable inhibitory peptide, a genetically-encoded light inducible CaMKⅡ inhibitory peptide. Using this new optogenetic tool, we found that the 1 min of CaMKⅡ activation is sufficient for triggering structural plasticity of synapses(spines)in hippocampal neurons. Furthermore, using passive avoidance test, we found that transient CaMKⅡ activity, but not sustained activity, is only required for fear memory formation/maintenance in amygdala of mice.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29512534" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinase Type 2", "descriptor_ui": "D054732", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": true }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": true }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "3", "normalized_date": "2018", "pages": "414-419", "proceedings_title": null, "publisher": "", "title": "Clinical calcium", "volume": "28", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "[Optogenetics sheds light on memory research.Development and application of photoactivatable CaMKⅡ inhibitory peptide to the study of synaptic plasticity.].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The spatiotemporal regulation of immune responses in the lymph node (LN) depends on its sophisticated tissue architecture, consisting of several subcompartments supported by distinct fibroblastic stromal cells (FSCs). However, the intricate details of stromal structures and associated FSC subsets are not fully understood. Using several gene reporter mice, we sought to discover unrecognized stromal structures and FSCs in the LN. The four previously identified FSC subsets in the cortex are clearly distinguished by the expression pattern of reporters including PDGFRbeta, CCL21-ser, and CXCL12. Herein, we identified a unique FSC subset expressing both CCL21-ser and CXCL12 in the deep cortex periphery (DCP) that is characterized by preferential B cell localization. This subset was clearly different from CXCL12(high)LepR(high) FSCs in the medullary cord, which harbors plasma cells. B cell localization in the DCP was controlled chiefly by CCL21-ser and, to a lesser extent, CXCL12. Moreover, the optimal development of the DCP as well as medulla requires B cells. Together, our findings suggest the presence of a unique microenvironment in the cortex-medulla boundary and offer an advanced view of the multi-layered stromal framework constructed by distinct FSC subsets in the LN.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Arata", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Madoka", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Mina", "last_name": "Kozai", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Ohigashi", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Kurosawa", "name": null }, { "creator_type": "author", "first_name": "Md Azizur", "last_name": "Rahman", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Shichida", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Umemoto", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Miyasaka", "name": null }, { "creator_type": "author", "first_name": "Burkhard", "last_name": "Ludewig", "name": null }, { "creator_type": "author", "first_name": "Yousuke", "last_name": "Takahama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagasawa", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2018.02196" }, "pmcid": { "normalized": "PMC6176096" }, "pmid": { "normalized": "30333825" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Chemokine CCL21", "descriptor_ui": "D054421", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Receptor, Platelet-Derived Growth Factor beta", "descriptor_ui": "D020797", "major_topic": false }, { "descriptor": "Stromal Cells", "descriptor_ui": "D017154", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "2196", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "9", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "A Distinct Subset of Fibroblastic Stromal Cells Constitutes the Cortex-Medulla Boundary Subcompartment of the Lymph Node.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In T cells, T cell receptor (TCR) signaling initiates downstream transcriptional mechanisms for T cell activation and differentiation. Foxp3-expressing regulatory T cells (Treg) require TCR signals for their suppressive function and maintenance in the periphery. It is, however, unclear how TCR signaling controls the transcriptional program of Treg. Since most of studies identified the transcriptional features of Treg in comparison to naïve T cells, the relationship between Treg and non-naïve T cells including memory-phenotype T cells (Tmem) and effector T cells (Teff) is not well understood. Here, we dissect the transcriptomes of various T cell subsets from independent datasets using the multidimensional analysis method canonical correspondence analysis (CCA). We show that at the cell population level, resting Treg share gene modules for activation with Tmem and Teff. Importantly, Tmem activate the distinct transcriptional modules for T cell activation, which are uniquely repressed in Treg. The activation signature of Treg is dependent on TCR signals and is more actively operating in activated Treg. Furthermore, by using a new CCA-based method, single-cell combinatorial CCA, we analyzed unannotated single-cell RNA-seq data from tumor-infiltrating T cells, and revealed that FOXP3 expression occurs predominantly in activated T cells. Moreover, we identified FOXP3-driven and T follicular helper-like differentiation pathways in tumor microenvironments, and their bifurcation point, which is enriched with recently activated T cells. Collectively, our study reveals the activation mechanisms downstream of TCR signals for the bifurcation of Treg and Teff differentiation and their maturation processes.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Alla", "last_name": "Bradley", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2018.01444" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30061879" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Immunology", "volume": "9", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Elucidating T Cell Activation-Dependent Mechanisms for Bifurcation of Regulatory and Effector T Cell Differentiation by Multidimensional and Single-Cell Analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Over the last few decades, Drosophila cancer models have made great contributions to our understanding toward fundamental cancer processes. Particularly, the development of genetic mosaic technique in Drosophila has enabled us to recapitulate basic aspects of human cancers, including clonal evolution, tumor microenvironment, cancer cachexia, and anticancer drug resistance. The mosaic technique has also led to the discovery of important tumor-suppressor pathways such as the Hippo pathway and the elucidation of the mechanisms underlying tumor growth and metastasis via regulation of cell polarity, cell-cell cooperation, and cell competition. Recent approaches toward identification of novel therapeutics using fly cancer models have further proved Drosophila as a robust system with great potentials for cancer research as well as anti-cancer therapy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masato", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Carmen", "last_name": "Siow", "name": null }, { "creator_type": "author", "first_name": "Tatsushi", "last_name": "Igaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-981-13-0529-0_10" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29951820" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "173-194", "proceedings_title": null, "publisher": "", "title": "Advances in experimental medicine and biology", "volume": "1076", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Drosophila As a Cancer Model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tryptophan hydroxylase (TRH) is the rate limiting enzyme in the serotonin synthesis. CRISPR-Cas9 technology was used to generate seven indel TRH mutants in Daphnia magna. Mono-allelic indel TRH−/+ clones showed normal levels of serotonin, measured by both immunohistochemistry and mass spectrometry (LC-MS/MS), whereas bi-allelic indel TRH−/− clones showed no detectable levels of serotonin. Life history and behavioral responses of TRH−/− clones showed the anti-phenotype of those exposed to selective serotonin reuptake inhibitors (SSRI). Mutants lacking serotonin grew less and hence reproduced latter, produced smaller clutches of smaller offspring and responded to a greater extent to light than wild type individuals. Mono-allelic indel TRH−/+ individuals showed the intermediate phenotype. The SSRI fluoxetine enhanced offspring production in all clones and decreased the response to light only in those clones having serotonin, thus indication that behavioral effects of this drug in D. magna are associated to serotonin. Results obtained with the TRH mutants are in line with reported ones in TRH knockouts of Caenorhabditis elegans, Drosophila and mice, indicating that there is one gene encoding TRH, which is the serotonin limiting enzyme in both the central and the periphery nervous system in Daphnia and that deprivation of serotonin increases anxiety-like behavior.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Claudia", "last_name": "Rivetti", "name": null }, { "creator_type": "author", "first_name": "Bruno", "last_name": "Campos", "name": null }, { "creator_type": "author", "first_name": "Benjamín", "last_name": "Piña", "name": null }, { "creator_type": "author", "first_name": "Demetrio", "last_name": "Raldúa", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Carlos", "last_name": "Barata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-19778-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29367674" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": true }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "Heterozygote", "descriptor_ui": "D006579", "major_topic": false }, { "descriptor": "Homozygote", "descriptor_ui": "D006720", "major_topic": false }, { "descriptor": "INDEL Mutation", "descriptor_ui": "D054643", "major_topic": false }, { "descriptor": "Loss of Function Mutation", "descriptor_ui": "D000073658", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Reproduction", "descriptor_ui": "D012098", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false }, { "descriptor": "Tryptophan Hydroxylase", "descriptor_ui": "D014365", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Tryptophan hydroxylase (TRH) loss of function mutations induce growth and behavioral defects in Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A pathological pathway leading from soluble, monomeric to insoluble, filamentous Tau, is believed to underlie human Tauopathies. Cases of frontotemporal dementia are caused by dominantly inherited mutations in MAPT, the Tau gene. They show that dysfunction of Tau protein is sufficient to cause neurodegeneration and dementia. Extrapolation to the more common sporadic Tauopathies leads one to conclude that the pathological pathway is central to the development of all cases of disease, even if there are multiple reasons for Tau assembly. These findings are conceptually similar to those reported for beta-amyloid, alpha-synuclein and prion protein. Here, we provide an overview of Tau filaments and their positron emission tomography ligands.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Michel", "last_name": "Goedert", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Sushil K.", "last_name": "Mishra", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fneur.2018.00070" }, "pmcid": { "normalized": "PMC5818396" }, "pmid": { "normalized": "29497399" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "70", "proceedings_title": null, "publisher": "", "title": "Frontiers in neurology", "volume": "9", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Tau Filaments and the Development of Positron Emission Tomography Tracers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The western blotting technique is widely used to analyze protein expression levels and protein molecular weight. The chemiluminescence method is mainly used for detection due to its high sensitivity and ease of manipulation, but it is unsuitable for detailed analyses because it cannot be used to detect multiple proteins simultaneously. Recently, more attention has been paid to the fluorescence detection method because it is more quantitative and is suitable for the detection of multiple proteins simultaneously. However, fluorescence detection can be limited by poor image resolution and low detection sensitivity. Here, we describe a method to detect fluorescence in western blots using fluorescence microscopy to obtain high-resolution images. In this method, filters and fluorescent dyes are optimized to enhance detection sensitivity to a level similar to that of the chemiluminescence method.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yukari", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Higa", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0191532" }, "pmcid": { "normalized": "PMC5774814" }, "pmid": { "normalized": "29352284" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Glutathione Transferase", "descriptor_ui": "D005982", "major_topic": false }, { "descriptor": "Image Enhancement", "descriptor_ui": "D007089", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "1", "normalized_date": "2018", "pages": "e0191532", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "13", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Sensitive detection of fluorescence in western blotting by merging images.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Biclustering extracts coexpressed genes under certain experimental conditions, providing more precise insight into the genetic behaviors than one-dimensional clustering. For understanding the biological features of genes in a single bicluster, visualizations such as heatmaps or parallel coordinate plots and tools for enrichment analysis are widely used. However, simultaneously handling many biclusters still remains a challenge. Thus, we developed a web service named SiBIC, which, using maximal frequent itemset mining, exhaustively discovers significant biclusters, which turn into networks of overlapping biclusters, where nodes are gene sets and edges show their overlaps in the detected biclusters. SiBIC provides a graphical user interface for manipulating a gene set network, where users can find target gene sets based on the enriched network. This chapter provides a user guide/instruction of SiBIC with background of having developed this software. SiBIC is available at http://utrecht.kuicr.kyoto-u.ac.jp:8080/sibic/faces/index.jsp .", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kei-Ichiro", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "David A.", "last_name": "duVerle", "name": null }, { "creator_type": "author", "first_name": "Sohiya", "last_name": "Yotsukura", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Mamitsuka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4939-8561-6_8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30030806" } }, "mesh": [ { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "Data Mining", "descriptor_ui": "D057225", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": false }, { "descriptor": "Internet", "descriptor_ui": "D020407", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "95-111", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "1807", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "SiBIC: A Tool for Generating a Network of Biclusters Captured by Maximal Frequent Itemset Mining.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The freshwater crustacean Daphnia have a long history in water quality assessments and now lend themselves to detection of targeted chemicals using genetically encoded reporter gene due to recent progress in the development of genome editing tools. By introducing human genes into Daphnia, we may be able to detect chemicals that affect the human system, or even apply it to screening potentially useful chemicals. Here, we aimed to develop a transgenic line of Daphnia magna that contains the human estrogen receptor alpha (hERα) and shows a fluorescence response to exposure of estrogens. We designed plasmids to express hERα in Daphnia (EF1α1:esr1) and to report estrogenic activity via red fluorescence (ERE:mcherry) under the control of estrogen response element (ERE). After confirmation of functionality of the plasmids by microinjection into embryos, the two plasmids were joined, a TALE site was added and integrated into the D. magna genome using TALEN. When the resulting transgenic Daphnia named the ES line was exposed to Diethylstilbestrol (DES) or 17β-Estradiol (E2), the ES line could reliably expressed red fluorescence derived from mCherry in a ligand-dependent manner, indicating that an estrogen-responsive line of D. magna was established. This is the first time a human gene was expressed in Daphnia, showcasing potential for further research.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kerstin", "last_name": "Törner", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0198023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29883470" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "Estrogen Receptor alpha", "descriptor_ui": "D047628", "major_topic": false }, { "descriptor": "Gene Transfer Techniques", "descriptor_ui": "D018014", "major_topic": true }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": true }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "6", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "13", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Genomic integration and ligand-dependent activation of the human estrogen receptor α in the crustacean Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The evolution of multicellular organisms is generally thought (and seems likely) to have been accompanied by the evolution of a stem cell system. Sponges, some of the early-evolved metazoans, have totipotent/pluripotent stem cells. Thus, uncovering the cellular and molecular bases of the sponge stem cells will not only be crucial for understanding the ancestral gene repertoire of animal stem cells, but will also give us clues to understanding the evolution of molecular mechanisms for maintaining multipotency (pluripotency) and differentiation ability during animal evolution. Sponges (Porifera) are a large phylum that includes an enormous number of species, whose cellular compositions and life cycles show striking variations. In the last decade, methodologies for molecular studies and sequencing resources have dramatically advanced and made it possible to clearly define stem cells in sponges in cellular and molecular terms. In this review, together with recent studies of sponges in various classes, the following issues will be discussed: i) recent findings that revealed that the previously proposed model that \"archeocytes and choanocytes are the two types of stem cells\" originally based on work in demosponges can be applied as a unified view of the stem cell system in sponges that have various cellular organizations, ii) the fact that sponge cells are more plastic than previously thought, as shown by recent studies of sponge regeneration both from dissociated cells and upon injury, and iii) the importance of transdifferentiation in sponge stem cell systems and regeneration.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Noriko", "last_name": "Funayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1387/ijdb.180016nf" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29938763" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Plasticity", "descriptor_ui": "D000066670", "major_topic": false }, { "descriptor": "Cell Transdifferentiation", "descriptor_ui": "D054338", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Porifera", "descriptor_ui": "D011161", "major_topic": false }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": false }, { "descriptor": "Reproduction", "descriptor_ui": "D012098", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "6-7-8", "normalized_date": "2018", "pages": "513-525", "proceedings_title": null, "publisher": "", "title": "The International journal of developmental biology", "volume": "62", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "The cellular and molecular bases of the sponge stem cell systems underlying reproduction, homeostasis and regeneration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Momoko", "last_name": "Imakubo", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.2197/ipsjtbio.11.24" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "24-30", "proceedings_title": null, "publisher": "", "title": "IPSJ Transactions on Bioinformatics", "volume": "11", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Improvement and Evaluation of a Mathematical Model for Fertilization Calcium Waves in Caenorhabditis Elegans", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hippocampal hyperactivity, ascribed to amyloid β (Aβ)-induced imbalances in neural excitation and inhibition, is found in patients with mild cognitive impairment, a prodromal stage of Alzheimer's disease (AD). To better understand the relationship between hippocampal hyperactivity and the molecular triggers of behavioral impairments in AD, we used Mn-enhanced MRI (MEMRI) to assess neuronal activity after subjecting mice to a task requiring spatial learning and memory. Depletion of endogenous tau in an amyloid precursor protein (APP) transgenic (J20) mouse line was shown to ameliorate hippocampal hyperactivity in J20 animals, tau depletion failed to reverse memory deficits associated with APP/Aβ overproduction. On the other hand, deletion of tau alleviated the hyperlocomotion displayed by APP transgenics, suggesting that the functional effects of Aβ-tau interactions reflect the temporal appearance of these molecules in individual brain areas.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Misato", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Soeda", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Michikawa", "name": null }, { "creator_type": "author", "first_name": "Osborne F. X.", "last_name": "Almeida", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2018.00124" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29545742" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Neuroscience", "volume": "12", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Tau Depletion in APP Transgenic Mice Attenuates Task-Related Hyperactivation of the Hippocampus and Differentially Influences Locomotor Activity and Spatial Memory.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A pituitary adenylate cyclase-activating polypeptide (PACAP)-specific receptor, PAC1R, is coupled with multiple signal transduction pathways including stimulation of adenylate cyclase, phospholipase C and extracellular-signal regulated kinase (ERK)1/2. PAC1R has been shown to exert its long-lasting and potent signals via beta-arrestin1 and beta-arrestin2. However, the precise roles of the two beta-arrestin isoforms in PACAP-PAC1R signaling remain unclear. Here we examined the interaction between the two beta-arrestin isoforms and PAC1R, beta-arrestin-dependent PAC1R subcellular localization and ERK1/2 activation. Upon PACAP stimulation, although PAC1R similarly interacted with beta-arrestin1 and beta-arrestin2 in HEK293T cells, the complex of PAC1R and beta-arrestin2 was translocated from the cell surface into cytosol, but that of beta-arrestin1 remained in the cell surface regions in HeLa cells and mouse primary cultured neurons. Silencing of beta-arrestin2 blocked PACAP-induced PAC1R internalization and ERK1/2 phosphorylation, but silencing of beta-arrestin1 increased ERK1/2 phosphorylation. These results show that beta-arrestin1 and beta-arrestin2 exert differential actions on PAC1R internalization and PAC1R-dependent ERK1/2 activation, and suggest that the two beta-arrestin isoforms may be involved in fine and precise tuning of the PAC1R signaling pathways.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Moriguchi", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0196946" }, "pmcid": { "normalized": "PMC5937772" }, "pmid": { "normalized": "29734363" } }, "mesh": [ { "descriptor": "Adenylyl Cyclases", "descriptor_ui": "D000262", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "beta-Arrestin 1", "descriptor_ui": "D000071559", "major_topic": false }, { "descriptor": "beta-Arrestin 2", "descriptor_ui": "D000071560", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 3", "descriptor_ui": "D048052", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I", "descriptor_ui": "D051237", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Type C Phospholipases", "descriptor_ui": "D010738", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "5", "normalized_date": "2018", "pages": "e0196946", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "13", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "beta-Arrestin1 and 2 differentially regulate PACAP-induced PAC1 receptor signaling and trafficking.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An increasing age is the greatest risk factor for dementia and related disorders. Therefore, much attention has been focus on researches to understand mechanisms of disease-related brain aging. Neurodegenerative diseases including Alzheimer's disease (AD), dementia with lewy bodies, and frontotemporal lobar degeneration are mostly diagnosed by neuropathological features with protein inclusions such as Abeta, tau, alpha-synuclein, TDP-43, and FUS. These proteins are expected to lose physiological functions and mutual interaction with functional molecule with aging. Consecutively, acquired pathogenicities of aged proteins are accumulated and propagated in neural cells. The research for \"Brain protein aging\" is developed for understanding the mechanisms of initiation and pathogenicity of aging. Tau protein is one of major components of neurofibrillary tangles, which are closely associated with the severity of brain function loss of AD. To investigate tau protein's Brain protein aging, we have currently developed the in vivo multimodal imaging techniques for visualizing the progression of tau pathology. In this review, we will introduce such a novel imaging-based diagnostic procedures on a mouse model of tauopathy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/fpj.152.4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29998952" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "alpha-Synuclein", "descriptor_ui": "D051844", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Multimodal Imaging", "descriptor_ui": "D064847", "major_topic": true }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": true }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "1", "normalized_date": "2018", "pages": "4-9", "proceedings_title": null, "publisher": "", "title": "Nihon yakurigaku zasshi. Folia pharmacologica Japonica", "volume": "152", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "[Development of imaging-based diagnostic procedures for brain protein aging using a mouse model of tauopathy].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Body fluid regulation, or osmoregulation, continues to be a major topic in comparative physiology, and teleost fishes have been the subject of intensive research. Great progress has been made in understanding the osmoregulatory mechanisms including drinking behavior in teleosts and mammals. Mudskipper gobies can bridge the gap from aquatic to terrestrial habitats by their amphibious behavior, but the studies are yet emerging. In this review, we introduce this unique teleost as a model to study osmoregulatory behaviors, particularly amphibious behaviors regulated by the central action of hormones. Regarding drinking behavior of mammals, a thirst sensation is aroused by angiotensin II (Ang II) through direct actions on the forebrain circumventricular structures, which predominantly motivates them to search for water and take it into the mouth for drinking. By contrast, aquatic teleosts can drink water that is constantly present in their mouth only by reflex swallowing, and Ang II induces swallowing by acting on the hindbrain circumventricular organ without inducing thirst. In mudskippers, however, through the loss of buccal water by swallowing, which appears to induce buccal drying on land, Ang II motivates these fishes to move to water for drinking. Thus, mudskippers revealed a unique thirst regulation by sensory detection in the buccal cavity. In addition, the neurohypophysial hormones, isotocin (IT) and vasotocin (VT), promote migration to water via IT receptors in mudskippers. VT is also dipsogenic and the neurons in the forebrain may mediate their thirst. VT regulates social behaviors as well as osmoregulation. The VT-induced migration appears to be a submissive response of subordinate mudskippers to escape from competitive and dehydrating land. Together with implications of VT in aggression, mudskippers may bridge the multiple functions of neurohypophysial hormones. Interestingly, cortisol, an important hormone for seawater adaptation and stress response in teleosts, also stimulates the migration toward water, mediated possibly via the mineralocorticoid receptor. The corticosteroid system that is responsive to external stressors can accelerate emergence of migration to alternative habitats. In this review, we suggest this unique teleost as an important model to deepen insights into the behavioral roles of these hormones in relation to osmoregulation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yukitoshi", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Takanami", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Takei", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fphys.2018.01112" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30154735" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Physiology", "volume": "9", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "The Amphibious Mudskipper: A Unique Model Bridging the Gap of Central Actions of Osmoregulatory Hormones Between Terrestrial and Aquatic Vertebrates.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the stem cell research field, the molecular regulatory network used to define cellular states has been extensively studied, however, the general driving force guiding the collective state dynamics remains to be identified from biophysical aspects. Here we monitored the time-development of the cell-state transition at the single-cell and colony levels, simultaneously, during the early differentiation process in mouse embryonic stem cells. Our quantitative analyses revealed that cellular heterogeneity was a result of spontaneous fluctuation of cellular state and cell-cell cooperativity. We considered that the cell state is like a ball fluctuating on a potential landscape, and found that the cooperativity affects the fluctuation. Importantly, the cooperativity temporarily decreased and increased in the intermediate state of cell differentiation, leading to cell-state transition in unison. This process can be explained using the mathematical equation of flashing-ratchet behaviour, which suggests that a general mechanism is driving the collective decision-making of stem cells.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuko", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Arno", "last_name": "Germond", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Chikara", "last_name": "Furusawa", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-30461-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30097661" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Biophysical Phenomena", "descriptor_ui": "D055592", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Single cell analysis reveals a biophysical aspect of collective cell-state transition in embryonic stem cell differentiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Living tissues undergo deformation during morphogenesis. In this process, cells generate mechanical forces that drive the coordinated cell motion and shape changes. Recent advances in experimental and theoretical techniques have enabled in situ measurement of the mechanical forces, but the characterization of mechanical properties that determine how these forces quantitatively affect tissue deformation remains challenging, and this represents a major obstacle for the complete understanding of morphogenesis. Here, we proposed a non-invasive reverse-engineering approach for the estimation of the mechanical properties, by combining tissue mechanics modeling and statistical machine learning. Our strategy is to model the tissue as a continuum mechanical system and to use passive observations of spontaneous tissue deformation and force fields to statistically estimate the model parameters. This method was applied to the analysis of the collective migration of Madin-Darby canine kidney cells, and the tissue flow and force were simultaneously observed by the phase contrast imaging and traction force microscopy. We found that our monolayer elastic model, whose elastic moduli were reverse-engineered, enabled a long-term forecast of the traction force fields when given the tissue flow fields, indicating that the elasticity contributes to the evolution of the tissue stress. Furthermore, we investigated the tissues in which myosin was inhibited by blebbistatin treatment, and observed a several-fold reduction in the elastic moduli. The obtained results validate our framework, which paves the way to the estimation of mechanical properties of living tissues during morphogenesis.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Ishii", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1006029" }, "pmcid": { "normalized": "PMC5849322" }, "pmid": { "normalized": "29494578" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Elastic Modulus", "descriptor_ui": "D055119", "major_topic": false }, { "descriptor": "Elasticity", "descriptor_ui": "D004548", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "Mechanotransduction, Cellular", "descriptor_ui": "D040542", "major_topic": false }, { "descriptor": "Microscopy, Atomic Force", "descriptor_ui": "D018625", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Stress, Mechanical", "descriptor_ui": "D013314", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "e1006029", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "14", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Inverse tissue mechanics of cell monolayer expansion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mlc1 is a causative gene for megalencephalic leukoencephalopathy with subcortical cysts, and is expressed in astrocytes. Mlc1-over-expressing mice represent an animal model of early-onset leukoencephalopathy, which manifests as astrocytic swelling followed by myelin membrane splitting in the white matter. It has been previously reported that Mlc1 is highly expressed in Bergmann glia, while the cerebellar phenotypes of Mlc1-over-expressing mouse have not been characterized. Here, we examined the cerebellum of Mlc1-over-expressing mouse and found that the distribution of Bergmann glia (BG) was normally compacted along the Purkinje cell (PC) layer until postnatal day 10 (P10), while most BG were dispersed throughout the molecular layer by P28. Ectopic BG were poorly wrapped around somatodendritic elements of PCs and exhibited reduced expression of the glutamate transporter glutamate-aspartate transporter. Extraordinarily slow and small climbing fiber (CF)-mediated excitatory post-synaptic currents, which are known to be elicited under accelerated glutamate spillover, emerged at P20-P28 when BG ectopia was severe, but not at P9-P12 when ectopia was mild. Furthermore, maturation of CF wiring, which translocates the site of innervation from somata to proximal dendrites, was also impaired. Manipulations that restricted the Mlc1-over-expressing period successfully generated mice with and without BG ectopia, depending on the over-expressing period. Together, these findings suggest that there is a critical time window for mechanisms that promote the positioning of BG in the PC layer. Once normal positioning of BG is affected, the differentiation of BG is impaired, leading to insufficient glial wrapping, exacerbated glutamate spillover, and aberrant synaptic wiring in PCs. Open Practices Open Science: This manuscript was awarded with the Open Materials Badge. For more information see: https://cos.io/our-services/open-science-badges/ Cover Image for this issue: doi: 10.1111/jnc.14199.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Saori", "last_name": "Kikuchihara", "name": null }, { "creator_type": "author", "first_name": "Shouta", "last_name": "Sugio", "name": null }, { "creator_type": "author", "first_name": "Kenji F.", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Ikenaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/jnc.14486" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29920672" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nerve Fibers", "descriptor_ui": "D009412", "major_topic": false }, { "descriptor": "Neuroglia", "descriptor_ui": "D009457", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Nov", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "344-360", "proceedings_title": null, "publisher": "", "title": "Journal of neurochemistry", "volume": "147", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Ectopic positioning of Bergmann glia and impaired cerebellar wiring in Mlc1-over-expressing mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fibrillary tau aggregates in Alzheimer disease and allied neurodegenerative disorders have been visualized in vivo by PET, whereas mechanistic links between PET-detectable tau deposits and neurotoxicity remain elusive. Here, we took advantage of transgenic mouse models of tauopathies to evaluate associations between PET and postmortem measures of tau probe binding and their relation to neuronal loss. Methods: PET with a tau probe, (11)C-PBB3 (2-((1E,3E)-4-(6-((11)C-methylamino)pyridine-3-yl)buta-1,3-dienyl)benzo[d]thiazol-6-ol), and volumetric MRI were performed for transgenic rTg4510 mice and nontransgenic mice. Binding of (11)C-PBB3 and its blockade by another tau binding compound, AV-1451 (-(6-fluoropyridine-3-yl)-5H-pyrido[4,3-b]indole), in homogenized brains of tauopathy patients and rTg4510 and PS19 mice were quantified, and (11)C-PBB3-positive and phosphorylated tau lesions in sectioned brains of these mice were assessed. Results: In vivo (11)C-PBB3 binding to the rTg4510 neocortex/hippocampus was increased relative to controls and correlated with local atrophy. In vitro (11)C-PBB3 binding in the neocortex/hippocampus also correlated well with in vivo radioligand binding and regional atrophy in the same individual rTg4510 mice. By contrast, in vitro (11)C-PBB3 binding was elevated in the brain stem but not hippocampus of PS19 mice, despite a pronounced loss of neurons in the hippocampus rather than brain stem. Finally, (11)C-PBB3 and AV-1451 showed similar binding properties between mouse models and tauopathy patients. Conclusion: The present findings support the distinct utilities of (11)C-PBB3 PET and MRI in rTg4510 and PS19 mice for quantitatively pursuing mechanisms connecting PET-detectable and PET-undetectable tau aggregations to neuronal death, which recapitulate 2 different modes of tau-provoked neurotoxicity.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ruiqing", "last_name": "Ni", "name": null }, { "creator_type": "author", "first_name": "Bin", "last_name": "Ji", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Ming-Rong", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Ichio", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Agneta", "last_name": "Nordberg", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.2967/jnumed.117.201632" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29419480" } }, "mesh": [ { "descriptor": "Aminopyridines", "descriptor_ui": "D000631", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Atrophy", "descriptor_ui": "D001284", "major_topic": false }, { "descriptor": "Benzothiazoles", "descriptor_ui": "D052160", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Carbolines", "descriptor_ui": "D002243", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Multimodal Imaging", "descriptor_ui": "D064847", "major_topic": false }, { "descriptor": "Positron-Emission Tomography", "descriptor_ui": "D049268", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "960-966", "proceedings_title": null, "publisher": "", "title": "Journal of nuclear medicine : official publication, Society of Nuclear Medicine", "volume": "59", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparative In Vitro and In Vivo Quantifications of Pathologic Tau Deposits and Their Association with Neurodegeneration in Tauopathy Mouse Models.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The eyestalk hormone, crustacean female sex hormone (CFSH), regulates the development of female secondary sexual characteristics in the blue crab Callinectes sapidus. After its discovery, several CFSH gene orthologs have been identified in some species of the suborder Pleocyemata as well. Similarly, in species of another suborder (Dendrobranchiata), an ortholog (Maj-CFSH) has been characterized as an eyestalk factor expressed in both females and males of the kuruma prawn, Marsupenaeus japonicus. In this study, another novel CFSH isoform was identified in the same species using cDNA cloning, expression analysis, and recombinant protein production. The isoform has \"CFSH-family\" structural characteristics but is dominantly expressed in the ovary, and was therefore designated as Maj-CFSH-ov. Its mRNA and protein levels in vitellogenic ovaries are higher than those in non-vitellogenic ovaries. In the vitellogenic ovary, both mRNA and protein expression of Maj-CFSH-ov are localized to oogonia and previtellogenic oocytes that occupy a small portion of vitellogenic ovaries, but not to the major developing oocytes. A vitellogenesis-inhibiting peptide of M. japonicus (Pej-SGP-I) reduced the expression of vitellogenin in incubated ovarian fragments, but not that of Maj-CFSH-ov. These results indicate that M. japonicus possesses two CFSH isoforms that are derived from distinct tissues, the central X-organ/sinus gland complex and peripheral ovaries. The expression profile of Maj-CFSH-ov suggests its involvement in some reproductive process other than vitellogenesis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naoaki", "last_name": "Tsutsui", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Kotaka", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Ohira", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cbpa.2017.12.009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29277431" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arthropod Proteins", "descriptor_ui": "D060829", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "Crustacea", "descriptor_ui": "D003445", "major_topic": false }, { "descriptor": "DNA, Complementary", "descriptor_ui": "D018076", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Gonadal Steroid Hormones", "descriptor_ui": "D012739", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Ovary", "descriptor_ui": "D010053", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Reproduction", "descriptor_ui": "D012098", "major_topic": false }, { "descriptor": "Sequence Homology, Amino Acid", "descriptor_ui": "D017386", "major_topic": false }, { "descriptor": "Vitellogenins", "descriptor_ui": "D014819", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Mar", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "7-16", "proceedings_title": null, "publisher": "", "title": "Comparative biochemistry and physiology. Part A, Molecular & integrative physiology", "volume": "217", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Characterization of distinct ovarian isoform of crustacean female sex hormone in the kuruma prawn Marsupenaeus japonicus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Jellyfish green fluorescent protein (GFP) and firefly luciferase can serve as versatile tracking markers for identification and quantification of transplanted cancer cells in vivo. However, immune reactions against these markers can hamper the formation of syngraft tumors and metastasis that follows. Here, we report two transgenic (Tg) mouse lines that express nonfunctional mutant marker proteins, namely modified firefly luciferase (Luc2) or enhanced GFP (EGFP). These mice, named as Tg-mLuc2 and Tg-mEGFP, turned out to be immunologically tolerant to the respective tracking markers and thus efficiently accepted syngeneic cancer cells expressing the active forms of the markers. We then injected intrarectally the F(1) hybrid Tg mice (BALB/c x C57BL/6J) with Colon-26 (C26) colon cancer cells that originated from a BALB/c mouse. Even when C26 cells expressed active Luc2 or EGFP, they formed primary tumors in the Tg mice with only 10(4) cells per mouse compared with more than 10(6) cells required in the nontransgenic BALB/c hosts. Furthermore, we detected metastatic foci of C26 cells in the liver and lungs of the Tg mice by tracking the specific reporter activities. These results show the usefulness of the Tg mouse lines as recipients for transplantation experiments with the non-self tracking marker-expressing cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Miyoshi", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Makoto Mark", "last_name": "Taketo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.12592" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29749672" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Isografts", "descriptor_ui": "D064596", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neoplasm Transplantation", "descriptor_ui": "D009368", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "580-589", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "23", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Transgenic mice that accept Luciferase- or GFP-expressing syngeneic tumor cells at high efficiencies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tyrosine kinase inhibitors (TKI) are used for primary therapy in patients with newly diagnosed CML. However, a reliable method for optimal selection of a TKI from the viewpoint of drug sensitivity of CML cells has not been established. We have developed a FRET-based drug sensitivity test in which a CrkL-derived fluorescent biosensor efficiently quantifies the kinase activity of BCR-ABL of living cells and sensitively evaluates the inhibitory activity of a TKI against BCR-ABL. Here, we validated the utility of the FRET-based drug sensitivity test carried out at diagnosis for predicting the molecular efficacy. Sixty-two patients with newly diagnosed chronic phase CML were enrolled in this study and treated with dasatinib. Bone marrow cells at diagnosis were subjected to FRET analysis. The DeltaFRET value was calculated by subtraction of FRET efficiency in the presence of dasatinib from that in the absence of dasatinib. Treatment response was evaluated every 3 months by the BCR-ABL1 International Scale. Based on the DeltaFRET value and molecular response, a threshold of the DeltaFRET value in the top 10% of FRET efficiency was set to 0.31. Patients with DeltaFRET value >/=0.31 had significantly superior molecular responses (MMR at 6 and 9 months and both MR4 and MR4.5 at 6, 9, and 12 months) compared with the responses in patients with DeltaFRET value <0.31. These results suggest that the FRET-based drug sensitivity test at diagnosis can predict early and deep molecular responses. This study is registered with UMIN Clinical Trials Registry (UMIN000006358).", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Takuto", "last_name": "Miyagishima", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Wakasa", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masakatsu", "last_name": "Yonezumi", "name": null }, { "creator_type": "author", "first_name": "Souichi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kazuei", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Chou", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Shuichiro", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Joji", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masatsugu", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Iijima", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Oba", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kishino", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Teshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.13625" }, "pmcid": { "normalized": "PMC6029835" }, "pmid": { "normalized": "29719934" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Dasatinib", "descriptor_ui": "D000069439", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fusion Proteins, bcr-abl", "descriptor_ui": "D016044", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia, Myelogenous, Chronic, BCR-ABL Positive", "descriptor_ui": "D015464", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Patient Selection", "descriptor_ui": "D018579", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "2256-2265", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "109", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Pretreatment evaluation of fluorescence resonance energy transfer-based drug sensitivity test for patients with chronic myelogenous leukemia treated with dasatinib.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Integrating virus-host interactions with host protein-protein interactions, we have created a method using these established network practices to identify host factors (i.e., proteins) that are likely candidates for antiviral drug targeting. We demonstrate that interaction cascades between host proteins that directly interact with viral proteins and host factors that are important to influenza virus replication are enriched for signaling and immune processes. Additionally, we show that host proteins that interact with viral proteins are in network locations of power. Finally, we demonstrate a new network methodology to predict novel host factors and validate predictions with an siRNA screen. Our results show that integrating virus-host proteins interactions is useful in the identification of antiviral drug target candidates.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Emily E.", "last_name": "Ackerman", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Manami", "last_name": "Katoh", "name": null }, { "creator_type": "author", "first_name": "Tokiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuriko", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tiago J.", "last_name": "Lopes", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Jason E.", "last_name": "Shoemaker", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kawaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/mbio.02002-18" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30563907" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Drug Delivery Systems", "descriptor_ui": "D016503", "major_topic": false }, { "descriptor": "Drug Discovery", "descriptor_ui": "D055808", "major_topic": false }, { "descriptor": "Host-Pathogen Interactions", "descriptor_ui": "D054884", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Influenza, Human", "descriptor_ui": "D007251", "major_topic": false }, { "descriptor": "Orthomyxoviridae", "descriptor_ui": "D009975", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Interaction Maps", "descriptor_ui": "D060066", "major_topic": true }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018 Nov-Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "mBio", "volume": "9", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Network-Guided Discovery of Influenza Virus Replication Host Factors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This study was conducted to determine suitable conditions for an experimental method in which the CRISPR/Cas9 system is introduced into in vitro-produced porcine zygotes by electroporation. In the first experiment, when putative zygotes derived from in vitro fertilization (IVF) were electroporated by either unipolar or bipolar pulses, keeping the voltage, pulse duration and pulse number fixed at 30 V/mm, 1 msec and five repeats, respectively, the rate of blastocyst formation from zygotes electroporated by bipolar pulses decreased compared to zygotes electroporated by unipolar pulses. In the second experiment, the putative zygotes were electroporated by electroporation voltages ranging from 20 V/mm-40 V/mm with five 1-msec unipolar pulses. The rate of cleavage and blastocyst formation of zygotes electroporated at 40 V/mm was significantly lower (p < .05) than that of zygotes electroporated at less than 30 V/mm. Moreover, the apoptotic nuclei indices of blastocysts derived from zygotes electroporated by voltages greater than 30 V/mm significantly increased compared with those from zygotes electroporated by voltages less than 25 V/mm (p < .05). When zygotes were electroporated with Cas9 mRNA and single-guide RNA (sgRNA) targeting site in the FGF10 exon 3, the proportions of blastocysts with targeted genomic sequences were 7.7% (2/26) and 3.6% (1/28) in the embryos derived from zygotes electroporated at 25 V/mm and 30 V/mm, respectively. Our results indicate that electroporation at 25 V/mm may be an acceptable condition for introducing Cas9 mRNA and sgRNA into pig IVF zygotes under which the viability of the embryos is not significantly affected.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "K.", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "F.", "last_name": "Tanihara", "name": null }, { "creator_type": "author", "first_name": "T.-V.", "last_name": "Nguyen", "name": null }, { "creator_type": "author", "first_name": "T.", "last_name": "Kunihara", "name": null }, { "creator_type": "author", "first_name": "M.", "last_name": "Nii", "name": null }, { "creator_type": "author", "first_name": "M.", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "T.", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "T.", "last_name": "Otoi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/rda.13106" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29135047" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Clustered Regularly Interspaced Short Palindromic Repeats", "descriptor_ui": "D064112", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Electroporation", "descriptor_ui": "D018274", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fertilization in Vitro", "descriptor_ui": "D005307", "major_topic": false }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": false }, { "descriptor": "RNA, Guide, CRISPR-Cas Systems", "descriptor_ui": "D000094704", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Sus scrofa", "descriptor_ui": "D034421", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "313-318", "proceedings_title": null, "publisher": "", "title": "Reproduction in domestic animals = Zuchthygiene", "volume": "53", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Effects of voltage strength during electroporation on the development and quality of in vitro-produced porcine embryos.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shinya", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Teruki", "last_name": "Yanagi", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inamura-Takashima", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Imafuku", "name": null }, { "creator_type": "author", "first_name": "Hiroo", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Shimizu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jdermsci.2018.01.014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29428816" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dermoscopy", "descriptor_ui": "D046169", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Graft Survival", "descriptor_ui": "D006085", "major_topic": true }, { "descriptor": "Heterografts", "descriptor_ui": "D064593", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Mice, SCID", "descriptor_ui": "D016513", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Predictive Value of Tests", "descriptor_ui": "D011237", "major_topic": false }, { "descriptor": "Prospective Studies", "descriptor_ui": "D011446", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Skin Transplantation", "descriptor_ui": "D016038", "major_topic": true }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 May", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "213-216", "proceedings_title": null, "publisher": "", "title": "Journal of dermatological science", "volume": "90", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Dermoscopic evaluation for skin grafts after surgery; neo-vascularization correlates with survival of skin grafts: A prospective study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Modern cartilaginous fishes are divided into elasmobranchs (sharks, rays and skates) and chimaeras, and the lack of established whole-genome sequences for the former has prevented our understanding of early vertebrate evolution and the unique phenotypes of elasmobranchs. Here we present de novo whole-genome assemblies of brownbanded bamboo shark and cloudy catshark and an improved assembly of the whale shark genome. These relatively large genomes (3.8-6.7 Gbp) contain sparse distributions of coding genes and regulatory elements and exhibit reduced molecular evolutionary rates. Our thorough genome annotation revealed Hox C genes previously hypothesized to have been lost, as well as distinct gene repertories of opsins and olfactory receptors that would be associated with adaptation to unique underwater niches. We also show the early establishment of the genetic machinery governing mammalian homoeostasis and reproduction at the jawed vertebrate ancestor. This study, supported by genomic, transcriptomic and epigenomic resources, provides a foundation for the comprehensive, molecular exploration of phenotypes unique to sharks and insights into the evolutionary origins of vertebrates.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Koh", "last_name": "Onimaru", "name": null }, { "creator_type": "author", "first_name": "Mitsutaka", "last_name": "Kadota", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Sean D.", "last_name": "Keeley", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tatsumi", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Motone", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Nozu", "name": null }, { "creator_type": "author", "first_name": "Noritaka", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Chiharu", "last_name": "Tanegashima", "name": null }, { "creator_type": "author", "first_name": "Itsuki", "last_name": "Kiyatake", "name": null }, { "creator_type": "author", "first_name": "Rui", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Kiyomi", "last_name": "Murakumo", "name": null }, { "creator_type": "author", "first_name": "Kiyonori", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Kuratani", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Hyodo", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Kuraku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41559-018-0673-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30297745" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": true }, { "descriptor": "Elasmobranchii", "descriptor_ui": "D018940", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": true }, { "descriptor": "Sharks", "descriptor_ui": "D012754", "major_topic": false }, { "descriptor": "Vertebrates", "descriptor_ui": "D014714", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "1761-1771", "proceedings_title": null, "publisher": "", "title": "Nature ecology & evolution", "volume": "2", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Shark genomes provide insights into elasmobranch evolution and the origin of vertebrates.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This study aimed to identify the characteristics of the vascular network in the superficial subcutaneous layer of the breast and to analyze differences between breasts with cancer and contralateral unaffected breasts using vessel branching points (VBPs) detected by three-dimensional photoacoustic imaging with a hemispherical detector array. In 22 patients with unilateral breast cancer, the average VBP counts to a depth of 7mm below the skin surface were significantly greater in breasts with cancer than in the contralateral unaffected breasts (p<0.01). The ratio of the VBP count in the breasts with cancer to that in the contralateral breasts was significantly increased in patients with a high histologic grade (p=0.03), those with estrogen receptor-negative disease (p<0.01), and those with highly proliferative disease (p<0.01). These preliminary findings indicate that a higher number of VBPs in the superficial subcutaneous layer of the breast might be a biomarker for primary breast cancer.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Iku", "last_name": "Yamaga", "name": null }, { "creator_type": "author", "first_name": "Nobuko", "last_name": "Kawaguchi-Sakita", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Asao", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Toshifumi", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Elham", "last_name": "Fakhrejahani", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Kanao", "name": null }, { "creator_type": "author", "first_name": "Yoshie", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Tokiwa", "name": null }, { "creator_type": "author", "first_name": "Masae", "last_name": "Torii", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Haga", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Togashi", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Toi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.pacs.2018.06.002" }, "pmcid": { "normalized": "PMC6039965" }, "pmid": { "normalized": "30003041" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018 Sep", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "6-13", "proceedings_title": null, "publisher": "", "title": "Photoacoustics", "volume": "11", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Vascular branching point counts using photoacoustic imaging in the superficial layer of the breast: A potential biomarker for breast cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Single-molecule imaging (SMI) of proteins in operation has a history of intensive investigations over 20 years and is now widely used in various fields of biology and biotechnology. We review the recent advances in SMI of fluorescently-tagged proteins in structural biology, focusing on technical applicability of SMI to the measurements in living cells. Basic technologies and recent applications of SMI in structural biology are introduced. Distinct from other methods in structural biology, SMI directly observes single molecules and single-molecule events one-by-one, thus, explicitly analyzing the distribution of protein structures and the history of protein dynamics. It also allows one to detect single events of protein interaction. One unique feature of SMI is that it is applicable in complicated and heterogeneous environments, including living cells. The numbers, location, movements, interaction, oligomerization, and conformation of single-protein molecules have been determined using SMI in cellular systems.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12551-017-0366-3" }, "pmcid": { "normalized": "PMC5899725" }, "pmid": { "normalized": "29243093" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "317-326", "proceedings_title": null, "publisher": "", "title": "Biophysical reviews", "volume": "10", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-molecule fluorescence-based analysis of protein conformation, interaction, and oligomerization in cellular systems.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Carbon nanotubes (CNTs) interlocked by cyclic compounds through supramolecular interaction are promising rotaxane-like materials applicable as 2D and 3D networks of nanowires and disease-specific theranostic agents having multifunctionalities. Supramolecular complexation of CNTs with cyclic compounds in a \"ring toss'' manner is a straightforward method to prepare interlocked CNTs; however, to date, this has not been reported on. Here, the \"ring toss\" method to prepare interlocked CNTs by using pi-conjugated carbon nanorings: [8]-, [9]-, and [10]cycloparaphenyleneacetylene (CPPA) is reported. CPPAs efficiently interact with CNTs to form CNT@CPPA complexes, while uncomplexed CPPAs can be recovered without decomposition. CNTs, which tightly fit in the cavities of CPPAs through convex-concave interaction, efficiently afford \"tube-in-ring\"-type CNT@CPPA complexes. \"Tube-in-ring\"-type and \"ring-on-tube\"-type complexation modes are successfully distinguished by spectroscopic, thermogravimetric, and microscopic analyses.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Kenzo", "last_name": "Saiki", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Umeyama", "name": null }, { "creator_type": "author", "first_name": "Jinseok", "last_name": "Baek", "name": null }, { "creator_type": "author", "first_name": "Takeru", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Imahori", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kazu", "last_name": "Suenaga", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/smll.201800720" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29782702" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018 Jun", "date_precision": "unknown", "issue": "26", "normalized_date": null, "pages": "e1800720", "proceedings_title": null, "publisher": "", "title": "Small (Weinheim an der Bergstrasse, Germany)", "volume": "14", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Unique Tube-Ring Interactions: Complexation of Single-Walled Carbon Nanotubes with Cycloparaphenyleneacetylenes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Adoptive T-cell therapy is an effective strategy for cancer immunotherapy. However, infused T cells frequently become functionally exhausted, and consequently offer a poor prognosis after transplantation into patients. Adoptive transfer of tumor antigen-specific stem cell memory T (TSCM ) cells is expected to overcome this shortcoming as TSCM cells are close to naive T cells, but are also highly proliferative, long-lived, and produce a large number of effector T cells in response to antigen stimulation. We previously reported that activated effector T cells can be converted into TSCM -like cells (iTSCM ) by coculturing with OP9 cells expressing Notch ligand, Delta-like 1 (OP9-hDLL1). Here we show the methodological parameters of human CD8(+) iTSCM cell generation and their application to adoptive cancer immunotherapy. Regardless of the stimulation by anti-CD3/CD28 antibodies or by antigen-presenting cells, human iTSCM cells were more efficiently induced from central memory type T cells than from effector memory T cells. During the induction phase by coculture with OP9-hDLL1 cells, interleukin (IL)-7 and IL-15 (but not IL-2 or IL-21) could efficiently generate iTSCM cells. Epstein-Barr virus-specific iTSCM cells showed much stronger antitumor potentials than conventionally activated T cells in humanized Epstein-Barr virus transformed-tumor model mice. Thus, adoptive T-cell therapy with iTSCM offers a promising therapeutic strategy for cancer immunotherapy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Imura", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Sana", "last_name": "Hibino", "name": null }, { "creator_type": "author", "first_name": "Setsuko", "last_name": "Omata-Mise", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Akanuma", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Iizuka", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Rimpei", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.13648" }, "pmcid": { "normalized": "PMC6029822" }, "pmid": { "normalized": "29790621" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunologic Memory", "descriptor_ui": "D007156", "major_topic": false }, { "descriptor": "Immunotherapy, Adoptive", "descriptor_ui": "D016219", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "T-Lymphocyte Subsets", "descriptor_ui": "D016176", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "2130-2140", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "109", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation and application of human induced-stem cell memory T cells for adoptive immunotherapy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent advances in the techniques that differentiate induced pluripotent stem cells (iPSCs) into specific types of cells enabled us to establish in vitro cell-based models as a platform for drug discovery. iPSC-derived disease models are advantageous to generation of a large number of cells required for high-throughput screening. Furthermore, disease-relevant cells differentiated from patient-derived iPSCs are expected to recapitulate the disorder-specific pathogenesis and physiology in vitro. Such disease-relevant cells will be useful for developing effective therapies. We demonstrated that cerebellar tissues are generated from human PSCs (hPSCs) in 3D culture systems that recapitulate the in vivo microenvironments associated with the isthmic organizer. Recently, we have succeeded in generation of spinocerebellar ataxia (SCA) patient-derived Purkinje cells by combining the iPSC technology and the self-organizing stem cell 3D culture technology. We demonstrated that SCA6-derived Purkinje cells exhibit vulnerability to triiodothyronine depletion, which is suppressed by treatment with thyrotropin-releasing hormone and Riluzole. We further discuss applications of patient-specific iPSCs to intractable cerebellar disease.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12311-017-0905-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29196977" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Feb", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "37-41", "proceedings_title": null, "publisher": "", "title": "Cerebellum (London, England)", "volume": "17", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Self-Organized Cerebellar Tissue from Human Pluripotent Stem Cells and Disease Modeling with Patient-Derived iPSCs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We found that a female infant presenting with left bundle branch block and left ventricular noncompaction carries uninvestigated gene mutations HCN4(G811E), SCN5A(L1988R), DMD(S2384Y), and EMD(R203H). Here, we explored the possible pathogenicity of HCN4(G811E), which results in a G811E substitution in hyperpolarization-activated cyclic nucleotide-gated channel 4, the main subunit of the cardiac pacemaker channel. Voltage-clamp measurements in a heterologous expression system of HEK293T cells showed that HCN4(G811E) slightly reduced whole-cell HCN4 channel conductance, whereas it did not affect the gating kinetics, unitary conductance, or cAMP-dependent modulation of voltage-dependence. Immunocytochemistry and immunoblot analysis showed that the G811E mutation did not impair the membrane trafficking of the channel subunit in the heterologous expression system. These findings indicate that HCN4(G811E) may not be a monogenic factor to cause the cardiac disorders.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Koshi", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Hirono", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Fukiko", "last_name": "Ichida", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Tabata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00380-018-1116-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29349559" } }, "mesh": [ { "descriptor": "Bradycardia", "descriptor_ui": "D001919", "major_topic": false }, { "descriptor": "Bundle-Branch Block", "descriptor_ui": "D002037", "major_topic": false }, { "descriptor": "DNA Mutational Analysis", "descriptor_ui": "D004252", "major_topic": false }, { "descriptor": "Echocardiography, Doppler, Color", "descriptor_ui": "D018618", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Heart Defects, Congenital", "descriptor_ui": "D006330", "major_topic": false }, { "descriptor": "Heart Ventricles", "descriptor_ui": "D006352", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels", "descriptor_ui": "D064428", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Infant, Newborn", "descriptor_ui": "D007231", "major_topic": false }, { "descriptor": "Muscle Proteins", "descriptor_ui": "D009124", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Potassium Channels", "descriptor_ui": "D015221", "major_topic": false }, { "descriptor": "Sinoatrial Node", "descriptor_ui": "D012849", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "802-819", "proceedings_title": null, "publisher": "", "title": "Heart and vessels", "volume": "33", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "A mutant HCN4 channel in a family with bradycardia, left bundle branch block, and left ventricular noncompaction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "KEY POINTS: Synaptic potentiation in Drosophila is observed at cholinergic synapses between antennal lobe (AL) and mushroom body (MB) neurons in the adult brain; however, depression at the AL-MB synapses has not yet been identified. By ex vivo Ca(2+) imaging in an isolated cultured Drosophila brain, we found novel activity-dependent depression at the AL-MB synapses. The degree of Ca(2+) responses after repetitive AL stimulation is significantly reduced in the dendritic region of MB neurons (calyx) compared with those before AL stimulation, and this reduction of Ca(2+) responses remains for at least 30 min. The expression of rutabaga, which encodes Ca(2+) /calmodulin-dependent adenylyl cyclase, is essential in the MB neurons for the reduction of Ca(2+) responses in the calyx. Our study reveals that elevation of cAMP production in the calyx during repetitive AL stimulation induces the depression at the AL-MB synapses. ABSTRACT: Synaptic plasticity has been studied to reveal the molecular and cellular mechanisms of associative and non-associative learning. The fruit fly Drosophila melanogaster can be used to identify the molecular mechanisms of synaptic plasticity because vast genetic information or tools are available. Here, by ex vivo Ca(2+) imaging of an isolated cultured Drosophila brain, we examined the novel activity-dependent synaptic depression between the projection neurons of the antennal lobe (AL) and mushroom body (MB). Ex vivo Ca(2+) imaging analysis revealed that electrical stimulation of AL elicits Ca(2+) responses in the dendritic (calyx) and axonal (alpha lobe) regions of MB neurons, and the responses are reduced after repetitive AL stimulation. Since the cAMP signalling pathway plays an important role in synaptic plasticity in invertebrates and vertebrates, we examined whether the reduction of Ca(2+) responses is also regulated by the cAMP signalling pathway. The expression of rutabaga (rut), which encodes Ca(2+) /calmodulin-dependent adenylyl cyclase, was essential for the reduction of Ca(2+) responses in the calyx and alpha lobe. Furthermore, imaging analysis using a fluorescence resonance energy transfer-based cAMP indicator revealed that the cAMP level increased in the wild-type calyx during repetitive AL stimulation, whereas it decreased in rut(1) mutant flies with a loss-of-function mutation of rut. Thus, our study suggests that an increase in postsynaptic cAMP level during repetitive AL stimulation contributes to the attenuation of inputs at AL-MB synapses.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shoma", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Saitoe", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1113/jp275799" }, "pmcid": { "normalized": "PMC6002214" }, "pmid": { "normalized": "29659025" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Long-Term Synaptic Depression", "descriptor_ui": "D036881", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mushroom Bodies", "descriptor_ui": "D024521", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jun", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "2447-2461", "proceedings_title": null, "publisher": "", "title": "The Journal of physiology", "volume": "596", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Synaptic depression induced by postsynaptic cAMP production in the Drosophila mushroom body calyx.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare autoimmune diseases in which both genetic and environmental factors play important roles. To identify genetic factors of IIM including polymyositis, dermatomyositis (DM) and clinically amyopathic DM (CADM), we performed the first genome-wide association study for IIM in an Asian population. METHODS: We genotyped and tested 496 819 single nucleotide polymorphism for association using 576 patients with IIM and 6270 control subjects. We also examined the causal mechanism of disease-associated variants by in silico analyses using publicly available data sets as well as by in in vitro analyses using reporter assays and apoptosis assays. RESULTS: We identified a variant in WDFY4 that was significantly associated with CADM (rs7919656; OR=3.87; P=1.5x10(-8)). This variant had a cis-splicing quantitative trait locus (QTL) effect for a truncated WDFY4isoform (tr-WDFY4), with higher expression in the risk allele. Transexpression QTL analysis of this variant showed a positive correlation with the expression of NF-kappaB associated genes. Furthermore, we demonstrated that both WDFY4 and tr-WDFY4 interacted with pattern recognition receptors such as TLR3, TLR4, TLR9 and MDA5 and augmented the NF-kappaB activation by these receptors. WDFY4 isoforms also enhanced MDA5-induced apoptosis to a greater extent in the tr-WDFY4-transfected cells. CONCLUSIONS: As CADM is characterised by the appearance of anti-MDA5 autoantibodies and severe lung inflammation, the WDFY4 variant may play a critical role in the pathogenesis of CADM.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Kochi", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Kamatani", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Akari", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Hiwa", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Momozawa", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Jinnin", "name": null }, { "creator_type": "author", "first_name": "Yoshiya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Robert G.", "last_name": "Cooper", "name": null }, { "creator_type": "author", "first_name": "Hector", "last_name": "Chinoy", "name": null }, { "creator_type": "author", "first_name": "Simon", "last_name": "Rothwell", "name": null }, { "creator_type": "author", "first_name": "Janine A.", "last_name": "Lamb", "name": null }, { "creator_type": "author", "first_name": "Jiri", "last_name": "Vencovsky", "name": null }, { "creator_type": "author", "first_name": "Herman", "last_name": "Mann", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Ohmura", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Myouzen", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Ishigaki", "name": null }, { "creator_type": "author", "first_name": "Ran", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Hidenaga", "last_name": "Kawasumi", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kajiyama", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Horita", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Ogawa-Momohara", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Takamura", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Tsunoda", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Keishi", "last_name": "Fujio", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Mimori", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Hisanori", "last_name": "Umehara", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Yoshinao", "last_name": "Muro", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Atsumi", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Mimura", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Tsuneyo", "last_name": "Mimori", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kohsaka", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Sumida", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1136/annrheumdis-2017-212149" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29331962" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Alleles", "descriptor_ui": "D000483", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": false }, { "descriptor": "Autoantibodies", "descriptor_ui": "D001323", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Dermatomyositis", "descriptor_ui": "D003882", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Genotyping Techniques", "descriptor_ui": "D060005", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interferon-Induced Helicase, IFIH1", "descriptor_ui": "D000072640", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Polymyositis", "descriptor_ui": "D017285", "major_topic": false }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false }, { "descriptor": "Quantitative Trait Loci", "descriptor_ui": "D040641", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false }, { "descriptor": "RNA Splicing", "descriptor_ui": "D012326", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "602-611", "proceedings_title": null, "publisher": "", "title": "Annals of the rheumatic diseases", "volume": "77", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Splicing variant of WDFY4 augments MDA5 signalling and the risk of clinically amyopathic dermatomyositis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Due to the growth in aging populations, prevention for cognitive decline and dementia are in great demand. We previously demonstrated that the consumption of iso-α-acids (IAA), the hop-derived bitter compounds in beer, prevents inflammation and Alzheimer’s disease pathology in model mice. However, the effects of iso-α-acids on inflammation induced by other agents aside from amyloid β have not been investigated. In this study, we demonstrated that the consumption of iso-α-acids suppressed microglial inflammation in the frontal cortex of rTg4510 tauopathy mice. In addition, the levels of inflammatory cytokines and chemokines, including IL-1β and MIP-1β, in the frontal cortex of rTg4510 mice were greater than those of wild-type mice, and were reduced in rTg4510 mice fed with iso-α-acids. Flow cytometry analysis demonstrated that the expression of cells producing CD86, CD68, TSPO, MIP-1α, TNF-α, and IL-1β in microglia was increased in rTg4510 mice compared with wild-type mice. Furthermore, the expression of CD86- and MIP-1α-producing cells was reduced in rTg4510 mice administered with iso-α-acids. Moreover, the consumption of iso-α-acids reduced the levels of phosphorylated tau in the frontal cortex. Collectively, these results suggest that the consumption of iso-α-acids prevents the inflammation induced in tauopathy mice. Thus, iso-α-acids may help in preventing inflammation-related brain disorders.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Ano", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Takaichi", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/molecules23123133" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30501069" } }, "mesh": [ { "descriptor": "Acids", "descriptor_ui": "D000143", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Beer", "descriptor_ui": "D001515", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microglia", "descriptor_ui": "D017628", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Taste", "descriptor_ui": "D013649", "major_topic": true }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Molecules", "volume": "23", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Iso-α-Acids, the Bitter Components of Beer, Suppress Microglial Inflammation in rTg4510 Tauopathy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Organogenesis and metamorphosis require the intricate orchestration of multiple types of cellular interactions and signaling pathways. Glutamate (Glu) is an excitatory extracellular signaling molecule in the nervous system, while Ca(2+) is a major intracellular signaling molecule. The first Glu receptors to be cloned are Ca(2+) -permeable receptors in mammalian brains. Although recent studies have focused on Glu signaling in synaptic mechanisms of the mammalian central nervous system, it is unclear how this signaling functions in development. Our recent article demonstrated that Ca(2+) -permeable AMPA-type Glu receptors (GluAs) are essential for formation of a photosensitive organ, development of some neurons, and metamorphosis, including tail absorption and body axis rotation, in ascidian embryos. Based on findings in these embryos and mammalian brains, we formed several hypotheses regarding the evolution of GluAs, the non-synaptic function of Glu, the origin of GluA-positive neurons, and the neuronal network that controls metamorphosis in ascidians.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinobu", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Okado", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/bies.201800028" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30058076" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Metamorphosis, Biological", "descriptor_ui": "D008675", "major_topic": false }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": false }, { "descriptor": "Receptors, AMPA", "descriptor_ui": "D018091", "major_topic": false }, { "descriptor": "Receptors, Glutamate", "descriptor_ui": "D017470", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "e1800028", "proceedings_title": null, "publisher": "", "title": "BioEssays : news and reviews in molecular, cellular and developmental biology", "volume": "40", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Developmental Roles and Evolutionary Significance of AMPA-Type Glutamate Receptors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The P301 L mutation in tau, a microtubule-associated protein, causes frontotemporal dementia with Parkinsonism linked to chromosome-17 (FTDP-17) that is accompanied by formation of filamentous polymers of tau. The mutation reduces the binding capability of microtubules and enhances tau filament formation. However, it is unclear whether the P301 L mutation increases the formation of the intermediates of tau filaments that are suggested to be a toxic species of tau. To determine the amount and structure of the intermediates harboring with the P301L mutation, we purified recombinant versions of wild-type, P301L, and 4 other mutants (i.e., P301S, P301T, V337M, and R406W) tau proteins and analyzed the heparin-induced aggregation of those tau constructs. We found that all of the FTDP-17 mutants increased levels of the intermediate tau oligomers. The sizes were determined by atomic force microscopy and laser light scattering. The V337M and R406W oligomers were similar in size to the wild-type, but the P301L, P301T, and P301S mutants formed smaller oligomers. In a P301L transgenic mouse model, we found tau aggregates that were similar in size to the recombinant tau oligomer. These results indicate that FTDP-17 mutations contribute to the pathogenesis via the increased formation of tau oligomers.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Sumihiro", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neurobiolaging.2018.04.014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29852407" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromosomes, Human, Pair 17", "descriptor_ui": "D002886", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Frontotemporal Dementia", "descriptor_ui": "D057180", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Parkinsonian Disorders", "descriptor_ui": "D020734", "major_topic": false }, { "descriptor": "Protein Aggregation, Pathological", "descriptor_ui": "D066263", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Sep", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "26-32", "proceedings_title": null, "publisher": "", "title": "Neurobiology of aging", "volume": "69", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Frontotemporal dementia with Parkinsonism linked to chromosome-17 mutations enhance tau oligomer formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ecdysteroid is an important hormone that regulates growth, reproduction, and embryogenesis in arthropods. However, little is known about its role and action mechanism in crustaceans, despite their pivotal role in aquatic ecosystem. Daphnia magna, a freshwater crustacean, is used as a classic model organism in ecology and ecotoxicology. Its ecdysteroid activity has been partially characterized previously. However, the spatio-temporal behavior of ecdysteroid, especially during early embryogenesis, when it is thought to have pivotal roles, is still unclear. Thus, we proposed a genetic modification approach by integrating a reporter gene exhibiting ecdysteroid activity in vivo. We used the clustered regularly interspaced palindromic repeats (CRISPR) genome editing technique, followed by non-homologous end-joining (NHEJ) pathway as the transgenesis method to generate the ecdysteroid reporter transgenic Daphnia. One transgenic Daphnia containing one copy of the ecdysone response element (EcRE)-controlled reporter gene mCherry was successfully obtained and was designated EcRE-mCh. The expression of mCherry was observed during early embryogenesis starting from 12 h after ovulation (hao). The time-lapse imaging during 12-24 hao showed the growing expression of mCherry signal originating from the posterior section of embryo and then migrating toward the anterior section. From 18 hao, the signal was detected around the developing thoracic appendages and localized between the first to third thoracic segments. The establishment of this EcRE-mCh line and its ability to exhibit ecdysteroid activity spatio-temporally might serve as convenient tool to elucidate the roles of ecdysteroid during the early stage of animal development. Moreover, the expression of mCherry in response to the presence of ecdysteroid in water suggests that EcRE-mCh could be used for monitoring ecdysteroid activities in environmental water.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Nikko", "last_name": "Adhitama", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.marenvres.2018.07.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30032995" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "Ecdysteroids", "descriptor_ui": "D026461", "major_topic": false }, { "descriptor": "Environmental Monitoring", "descriptor_ui": "D004784", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Sep", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "375-381", "proceedings_title": null, "publisher": "", "title": "Marine environmental research", "volume": "140", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Monitoring ecdysteroid activities using genetically encoded reporter gene in Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vascular endothelial cells (ECs) isolated from tumors characteristically express certain genes. It has recently been suggested that tumor vessel normalization facilitates effective drug delivery into tumors; however, how tumor vessel normalization can be recognized on the basis of the molecules expressed by tumor ECs is not clearly defined. The degree of cell proliferation is an important indicator to characterize the condition of the ECs. Herein, we generated transgenic mice expressing enhanced green fluorescent protein (EGFP) under the transcriptional control of the DNA replication factor partner of Sld5-1 (PSF1; official name GINS1) promoter to assess whether active ECs can be distinguished from dormant ECs. Predictably, ECs in the adult skin exhibited no EGFP signals. However, after s.c. injection of tumor cells, some ECs shifted to EGFP positivity, enabling distinction of EGFP-positive from EGFP-negative cells. We found that only a fraction of the EGFP-negative ECs strongly expressed the glycosylphosphatidylinositol-anchor protein CD109 associated with the phosphatidylinositol 3-kinase pathway. Taken together, these data indicate that areas of vascular normalization in tumors can be detected by CD109 expression, and this provides a window of opportunity for timing chemotherapy.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Daishi", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Weizhen", "last_name": "Jia", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Hosojima", "name": null }, { "creator_type": "author", "first_name": "Miku", "last_name": "Torigata", "name": null }, { "creator_type": "author", "first_name": "Li", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ajpath.2018.01.015" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29650228" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Neoplasm Transplantation", "descriptor_ui": "D009368", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "1300-1314", "proceedings_title": null, "publisher": "", "title": "The American journal of pathology", "volume": "188", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualization of Proliferative Vascular Endothelial Cells in Tumors in Vivo by Imaging Their Partner of Sld5-1 Promoter Activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During laryngoscopy, the laryngoscope blade sometimes comes in contact with the teeth, fracturing or dislocating them. However, no studies have compared the effects of newly marketed video laryngoscopes and the Macintosh laryngoscope (Mac) on teeth. In this study, we measured and compared the force exerted on the teeth of an intubating manikin by the Mac, the Airway Scope (Pentax), and the McGrath MAC (Covidien). The mean force exerted was 141.1 +/- 15.7 kg by the Mac, 39.2 +/- 10.3 kg by the Airway Scope, and 48.7 +/- 6.7 kg by the McGrath MAC. No significant difference was observed between the Airway Scope and the McGrath MAC. When the Mac is inserted, the glottis has to be visually located from outside the oral cavity. However, a significant force is not necessary when inserting video laryngoscopes because a camera is mounted on the blade tip. In this laboratory model, the lower force exerted by the video laryngoscopes should contribute to a reduction in their impact on fracture or dislocation of teeth.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sakuma", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Momota", "name": null } ], "identifiers": { "doi": { "normalized": "10.2344/anpr-65-03-01" }, "pmcid": { "normalized": "PMC6148694" }, "pmid": { "normalized": "30235428" } }, "mesh": [ { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Incisor", "descriptor_ui": "D007180", "major_topic": false }, { "descriptor": "Intubation, Intratracheal", "descriptor_ui": "D007442", "major_topic": false }, { "descriptor": "Laryngoscopes", "descriptor_ui": "D020704", "major_topic": true }, { "descriptor": "Laryngoscopy", "descriptor_ui": "D007828", "major_topic": false }, { "descriptor": "Manikins", "descriptor_ui": "D008348", "major_topic": false }, { "descriptor": "Risk Assessment", "descriptor_ui": "D018570", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false }, { "descriptor": "Stress, Mechanical", "descriptor_ui": "D013314", "major_topic": false }, { "descriptor": "Tooth Avulsion", "descriptor_ui": "D014084", "major_topic": false }, { "descriptor": "Tooth Fractures", "descriptor_ui": "D014082", "major_topic": false }, { "descriptor": "Video Recording", "descriptor_ui": "D014741", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Fall", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "151-155", "proceedings_title": null, "publisher": "", "title": "Anesthesia progress", "volume": "65", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparison of the Contact Force Exerted on Teeth by Conventional Macintosh Laryngoscope Versus Video Laryngoscopes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Synthetic tailoring of approved drugs for new indications is often difficult, as the most appropriate targets may not be readily apparent, and therefore few roadmaps exist to guide chemistry. Here, we report a multidisciplinary approach for accessing novel target and chemical space starting from an FDA-approved kinase inhibitor. By combining chemical and genetic modifier screening with computational modeling, we identify distinct kinases that strongly enhance ('pro-targets') or limit ('anti-targets') whole-animal activity of the clinical kinase inhibitor sorafenib in a Drosophila medullary thyroid carcinoma (MTC) model. We demonstrate that RAF-the original intended sorafenib target-and MKNK kinases function as pharmacological liabilities because of inhibitor-induced transactivation and negative feedback, respectively. Through progressive synthetic refinement, we report a new class of 'tumor calibrated inhibitors' with unique polypharmacology and strongly improved therapeutic index in fly and human MTC xenograft models. This platform provides a rational approach to creating new high-efficacy and low-toxicity drugs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null }, { "creator_type": "author", "first_name": "Alex P.", "last_name": "Scopton", "name": null }, { "creator_type": "author", "first_name": "Peter M. U.", "last_name": "Ung", "name": null }, { "creator_type": "author", "first_name": "Matthew A.", "last_name": "Murray", "name": null }, { "creator_type": "author", "first_name": "Lisa", "last_name": "Silber", "name": null }, { "creator_type": "author", "first_name": "Andres Y.", "last_name": "Maldonado", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Real", "name": null }, { "creator_type": "author", "first_name": "Avner", "last_name": "Schlessinger", "name": null }, { "creator_type": "author", "first_name": "Ross L.", "last_name": "Cagan", "name": null }, { "creator_type": "author", "first_name": "Arvin C.", "last_name": "Dar", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nchembio.2556" }, "pmcid": { "normalized": "PMC5931369" }, "pmid": { "normalized": "29355849" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Carcinoma", "descriptor_ui": "D002277", "major_topic": false }, { "descriptor": "Carcinoma, Neuroendocrine", "descriptor_ui": "D018278", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Drug Design", "descriptor_ui": "D015195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "HCT116 Cells", "descriptor_ui": "D045325", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Molecular Docking Simulation", "descriptor_ui": "D062105", "major_topic": false }, { "descriptor": "Neoplasm Transplantation", "descriptor_ui": "D009368", "major_topic": false }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-raf", "descriptor_ui": "D019908", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sorafenib", "descriptor_ui": "D000077157", "major_topic": false }, { "descriptor": "Thyroid Neoplasms", "descriptor_ui": "D013964", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "291-298", "proceedings_title": null, "publisher": "", "title": "Nature chemical biology", "volume": "14", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "A whole-animal platform to advance a clinical kinase inhibitor into new disease space.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chondroitin sulfate (CS) is a sulfated glycosaminoglycan composed of a long chain of repeating disaccharide units that are attached to core proteins, resulting in CS proteoglycans (CSPGs). In the mature brain, CS is concentrated in perineuronal nets (PNNs), which are extracellular structures that surround synapses and regulate synaptic plasticity. In addition, CS is rapidly synthesized after CNS injury to create a physical and chemical barrier that inhibits axon growth. Most previous studies used a bacterial CS-degrading enzyme to investigate the physiological roles of CS. Recent studies have shown that CS is synthesized by more than 15 enzymes, all of which have been characterized in vitro. Here we focus on one of those enzymes, CSGalNAcT1 (T1). We produced T1 knockout mice (KO), which show extensive axon regeneration following spinal cord injury, as well as the loss of onset of ocular dominance plasticity. These results from T1KO mice suggest important roles for extracellular CS in the brain regarding neuronal plasticity and axon regeneration.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Michihiro", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Sugiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuint.2017.10.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28987564" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Chondroitin Sulfate Proteoglycans", "descriptor_ui": "D011508", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "N-Acetylgalactosaminyltransferases", "descriptor_ui": "D017350", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Oct", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "77-83", "proceedings_title": null, "publisher": "", "title": "Neurochemistry international", "volume": "119", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Roles of CSGalNAcT1, a key enzyme in regulation of CS synthesis, in neuronal regeneration and plasticity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In mammals, circadian rhythms, such as sleep/wake cycles, are regulated by the central circadian clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN consists of thousands of individual neurons, which exhibit circadian rhythms. They synchronize with each other and produce robust and stable oscillations. Although several neurotransmitters are expressed in the SCN, almost all SCN neurons are gamma-amino butyric acid (GABA)-ergic. Several studies have attempted to understand the roles of GABA in the SCN; however, precise mechanisms of the action of GABA in the SCN are still unclear. GABA exhibits excitatory and/or inhibitory characteristics depending on the circadian phase or region in the SCN. It can both synchronize and destabilize cellular circadian rhythms in individual SCN cells. Differing environmental light conditions, such as a long photoperiod, result in the decoupling of circadian oscillators of the dorsal and ventral SCN. This is due to high intracellular chloride concentrations in the dorsal SCN. Because mice with functional GABA deficiency, such as vesicular GABA transporter- and glutamate decarboxylase-deficient mice, are neonatal lethal, research has been limited to pharmacological approaches. Furthermore, different recording methods have been used to understand the roles of GABA in the SCN. The excitability of GABAergic neurons also changes during the postnatal period. Although there are technical difficulties in understanding the functions of GABA in the SCN, technical developments may help uncover new roles of GABA in circadian physiology and behavior.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Yuchio", "last_name": "Yanagawa", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Sato", "last_name": "Honma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12576-018-0604-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29560549" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Circadian Clocks", "descriptor_ui": "D057906", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Photoperiod", "descriptor_ui": "D017440", "major_topic": false }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jul", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "333-343", "proceedings_title": null, "publisher": "", "title": "The journal of physiological sciences : JPS", "volume": "68", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of GABA in the regulation of the central circadian clock of the suprachiasmatic nucleus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The fluid mosaic model states that molecules in the plasma membrane can freely undergo lateral diffusion; however, in neurons and glia, specific membrane molecules are concentrated in cellular microdomains to overcome the randomizing effects of free diffusion. This specialized distribution of membrane molecules is crucial for various cell functions; one example is the accumulation of neurotransmitter receptors at the postsynaptic neuronal membrane, which enables efficient synaptic transmission. Quantum dot-single particle tracking (QD-SPT) is a super-resolution imaging technique that uses semiconductor nanocrystal quantum dots as fluorescent probes, and is a powerful tool for analyzing protein and lipid behavior in the plasma membrane. In this article, we review studies implementing QD-SPT in neuroscience research and important data gleaned using this technology. Recent QD-SPT experiments have provided critical insights into the mechanism and physiological relevance of membrane self-organization in neurons and astrocytes in the brain. The mobility of some membrane molecules may become abnormal in cellular models of epilepsy and Alzheimer's disease. Based on these findings, we propose that the behavior of membrane molecules reflects the condition of neurons in pathological disease states.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2017.07.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28826905" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Brain Diseases", "descriptor_ui": "D001927", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Diffusion", "descriptor_ui": "D004058", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": false }, { "descriptor": "GABAergic Neurons", "descriptor_ui": "D059330", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neuroglia", "descriptor_ui": "D009457", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Quantum Dots", "descriptor_ui": "D045663", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false }, { "descriptor": "Single Molecule Imaging", "descriptor_ui": "D000072760", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Apr", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "47-56", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "129", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular membrane dynamics: Insights into synaptic function and neuropathological disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Progress in research on endocannabinoid signaling has greatly advanced our understanding of how it controls neural circuit excitability in health and disease. In general, endocannabinoid signaling at excitatory synapses suppresses seizures by inhibiting glutamate release. In contrast, endocannabinoid signaling promotes seizures by inhibiting GABA release at inhibitory synapses. The physiological distribution of endocannabinoid signaling molecules becomes disrupted with the development of epileptic focus in patients with mesial temporal lobe epilepsy and in animal models of experimentally induced epilepsy. Augmentation of endocannabinoid signaling can promote the development of epileptic focus at initial stages. However, at later stages, increased endocannabinoid signaling delays it and suppresses spontaneous seizures. Thus, the regulation of endocannabinoid signaling at specific synapses that cause hyperexcitability during particular stages of disease development may be effective for treating epilepsy and epileptogenesis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugaya", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00018-018-2834-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29737364" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": false }, { "descriptor": "Epilepsy", "descriptor_ui": "D004827", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neural Conduction", "descriptor_ui": "D009431", "major_topic": false }, { "descriptor": "Seizures", "descriptor_ui": "D012640", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Aug", "date_precision": "unknown", "issue": "15", "normalized_date": null, "pages": "2793-2811", "proceedings_title": null, "publisher": "", "title": "Cellular and molecular life sciences : CMLS", "volume": "75", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Control of excessive neural circuit excitability and prevention of epileptic seizures by endocannabinoid signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell surface receptors for phosphatidylserine contribute to the entry of Ebola virus (EBOV) particles, indicating that the presence of phosphatidylserine in the envelope of EBOV is important for the internalization of EBOV particles. Phosphatidylserine is typically distributed in the inner layer of the plasma membrane in normal cells. Progeny virions bud from the plasma membrane of infected cells, suggesting that phosphatidylserine is likely flipped to the outer leaflet of the plasma membrane in infected cells for EBOV virions to acquire it. Currently, the intracellular dynamics of phosphatidylserine during EBOV infection are poorly understood. Here, we explored the role of XK-related protein (Xkr) 8, which is a scramblase responsible for exposure of phosphatidylserine in the plasma membrane of apoptotic cells, to understand its significance in phosphatidylserine-dependent entry of EBOV. We found that Xkr8 and transiently expressed EBOV glycoprotein GP often co-localized in intracellular vesicles and the plasma membrane. We also found that co-expression of GP and viral major matrix protein VP40 promoted incorporation of Xkr8 into ebolavirus-like particles (VLPs) and exposure of phosphatidylserine on their surface, although only a limited amount of phosphatidylserine was exposed on the surface of the cells expressing GP and/or VP40. Downregulating Xkr8 or blocking caspase-mediated Xkr8 activation did not affect VLP production, but they reduced the amount of phosphatidylserine on the VLPs and their uptake in recipient cells. Taken together, our findings indicate that Xkr8 is trafficked to budding sites via GP-containing vesicles, is incorporated into VLPs, and then promote the entry of the released EBOV to cells in a phosphatidylserine-dependent manner.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Asuka", "last_name": "Nanbo", "name": null }, { "creator_type": "author", "first_name": "Junki", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Ujie", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Nishide", "name": null }, { "creator_type": "author", "first_name": "Ayato", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kawaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.ppat.1006848" }, "pmcid": { "normalized": "PMC5786336" }, "pmid": { "normalized": "29338048" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Ebolavirus", "descriptor_ui": "D029043", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Hemorrhagic Fever, Ebola", "descriptor_ui": "D019142", "major_topic": false }, { "descriptor": "Host-Pathogen Interactions", "descriptor_ui": "D054884", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Phosphatidylserines", "descriptor_ui": "D010718", "major_topic": false }, { "descriptor": "Phospholipid Transfer Proteins", "descriptor_ui": "D049294", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Core Proteins", "descriptor_ui": "D014758", "major_topic": false }, { "descriptor": "Virion", "descriptor_ui": "D014771", "major_topic": false }, { "descriptor": "Virus Release", "descriptor_ui": "D057074", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "e1006848", "proceedings_title": null, "publisher": "", "title": "PLoS pathogens", "volume": "14", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Ebola virus requires a host scramblase for externalization of phosphatidylserine on the surface of viral particles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "L-type amino acid transporter 1 (LAT1) is more highly expressed in cancer cells compared with normal cells. LAT1 targeting probes would therefore be a promising tool for cancer cell imaging. In this study, LAT1-targeting thermoresponsive fluorescent polymer probes based on poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (P(NIPAAm-co-DMAAm)) were synthesized and their affinity for LAT1 was evaluated. The synthesized polymer probes interacted with LAT1 on HeLa cells, and inhibition of l-[3H]-leucine, one of the substrates for LAT1 uptake, was investigated. l-Tyrosine-conjugated P(NIPAAm-co-DMAAm) inhibited the uptake of l-[3H]-leucine, while P(NIPAAm-co-DMAAm) and l-phenylalanine-conjugated P(NIPAAm-co-DMAAm) did not. This result indicated that l-tyrosine-conjugated polymer has a high affinity for LAT1. The fluorescent polymer probes were prepared by modification of a terminal polymer group with fluorescein-5-maleimide (FL). Above the polymer transition temperature, cellular uptake of the polymer probes was observed because the polymers became hydrophobic, which enhanced the interaction with the cell membrane. Furthermore, quantitative analysis of the fluorescent probe using flow cytometry indicated that l-tyrosine-conjugated P(NIPAAm-co-DMAAm)-FL shows higher fluorescence intensity earlier than P(NIPAAm-co-DMAAm)-FL. The result suggested that cellular uptake was promoted by the LAT1 affinity site. The developed LAT1-targeting thermoresponsive fluorescent polymer probes are expected to be useful for cancer cell imaging.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Minami", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Ohshima", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nagase", "name": null }, { "creator_type": "author", "first_name": "Hideko", "last_name": "Kanazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms19061646" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29865203" } }, "mesh": [ { "descriptor": "Acrylamides", "descriptor_ui": "D000178", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Hot Temperature", "descriptor_ui": "D006358", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrophobic and Hydrophilic Interactions", "descriptor_ui": "D057927", "major_topic": false }, { "descriptor": "Large Neutral Amino Acid-Transporter 1", "descriptor_ui": "D027283", "major_topic": false }, { "descriptor": "Leucine", "descriptor_ui": "D007930", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "International Journal of Molecular Sciences", "volume": "19", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "LAT1-Targeting Thermoresponsive Fluorescent Polymer Probes for Cancer Cell Imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In multicellular organisms, incidentally emerging suboptimal cells are removed to maintain homeostasis of tissues. The unfavorable cells are excluded by a process termed cell competition whereby the resident normal cells actively eliminate the unfit cells of the identical lineage. Although the phenomenon of cell competition was originally discovered in Drosophila, a number of recent studies have provided implications of cell competition in tissue regeneration, development and oncogenesis in mammals. Here the roles of cell competition in fly to mammals are discussed.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kon", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12415" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29250773" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Physiological Phenomena", "descriptor_ui": "D002468", "major_topic": true }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "14-20", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "60", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Physiological and pathological relevance of cell competition in fly to mammals.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The success of tumor immunotherapy targeting the inhibitory co-receptors PD-1 and CTLA-4 has indicated that many other co-receptors might be potential druggable targets, despite limited information about their functional differences. Here we identified a unique target selectivity for the inhibitory co-receptor LAG-3 that was intrinsic to its immunoregulatory roles. Although LAG-3 has been reported to recognize major histocompatibility complex (MHC) class II, it did not recognize MHC class II universally; instead, we found that it selectively recognized stable complexes of peptide and MHC class II (pMHCII). LAG-3 did not directly interfere with interactions between the co-receptor CD4 and MHC class II or between the T cell antigen receptor and MHC class II. Instead, LAG-3 preferentially suppressed T cells responsive to stable pMHCII by transducing inhibitory signals via its intracellular region. Thus, LAG-3 might function more selectively than previously thought and thereby maintain tolerance to dominant autoantigens.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Il-Mi", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Suzuka", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takeo K.", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Okazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41590-018-0217-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30349037" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, CD", "descriptor_ui": "D015703", "major_topic": false }, { "descriptor": "CD4-Positive T-Lymphocytes", "descriptor_ui": "D015496", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Histocompatibility Antigens Class II", "descriptor_ui": "D000949", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Lymphocyte Activation Gene 3 Protein", "descriptor_ui": "D000093322", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Conformation", "descriptor_ui": "D008968", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1415-1426", "proceedings_title": null, "publisher": "", "title": "Nature immunology", "volume": "19", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "LAG-3 inhibits the activation of CD4(+) T cells that recognize stable pMHCII through its conformation-dependent recognition of pMHCII.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The interior lumen of acidic organelles (e.g., endosomes, secretory granules, lysosomes and plant vacuoles) is an important platform for modification, transport and degradation of biomolecules as well as signal transduction, which remains challenging to investigate using conventional fluorescent proteins (FPs). Due to the highly acidic luminal environment (pH ~ 4.5–6.0), most FPs and related sensors are apt to lose their fluorescence. To address the need to image in acidic environments, several research groups have developed acid-tolerant FPs in a wide color range. Furthermore, the engineering of pH insensitive sensors, and their concomitant use with pH sensitive sensors for the purpose of pH-calibration has enabled characterization of the role of luminal ions. In this short review, we summarize the recent development of acid-tolerant FPs and related functional sensors and discuss the future prospects for this field.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hajime", "last_name": "Shinoda", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Shannon", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms19061548" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29789517" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Endosomes", "descriptor_ui": "D011992", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Protons", "descriptor_ui": "D011522", "major_topic": true }, { "descriptor": "Secretory Vesicles", "descriptor_ui": "D022142", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "International Journal of Molecular Sciences", "volume": "19", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Fluorescent Proteins for Investigating Biological Events in Acidic Environments.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Metabolic syndrome and the presence of metabolic syndrome components are risk factors for cardiovascular disease (CVD). However, the association between personality traits and metabolic syndrome remains controversial, and few studies have been conducted in East Asian populations. METHODS: We measured personality traits using the Japanese version of the Eysenck Personality Questionnaire (Revised Short Form) and five metabolic syndrome components-elevated waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose-in 1322 participants aged 51.1+/-12.7years old from Kakegawa city, Japan. Metabolic syndrome score (MS score) was defined as the number of metabolic syndrome components present, and metabolic syndrome as having the MS score of 3 or higher. We performed multiple logistic regression analyses to examine the relationship between personality traits and metabolic syndrome components and multiple regression analyses to examine the relationship between personality traits and MS scores adjusted for age, sex, education, income, smoking status, alcohol use, and family history of CVD and diabetes mellitus. We also examine the relationship between personality traits and metabolic syndrome presence by multiple logistic regression analyses. RESULTS: \"Extraversion\" scores were higher in those with metabolic syndrome components (elevated waist circumference: P=0.001; elevated triglycerides: P=0.01; elevated blood pressure: P=0.004; elevated fasting glucose: P=0.002). \"Extraversion\" was associated with the MS score (coefficient=0.12, P=0.0003). No personality trait was significantly associated with the presence of metabolic syndrome. CONCLUSIONS: Higher \"extraversion\" scores were related to higher MS scores, but no personality trait was significantly associated with the presence of metabolic syndrome.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hisashi", "last_name": "Ohseto", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Ishikuro", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Kikuya", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Shigihara", "name": null }, { "creator_type": "author", "first_name": "Chizuru", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Miyashita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hirohito", "last_name": "Metoki", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Maeda-Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Kuriyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jpsychores.2018.01.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29502759" } }, "mesh": [ { "descriptor": "Alcohol Drinking", "descriptor_ui": "D000428", "major_topic": false }, { "descriptor": "Cardiovascular Diseases", "descriptor_ui": "D002318", "major_topic": false }, { "descriptor": "Cholesterol, HDL", "descriptor_ui": "D008076", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolic Syndrome", "descriptor_ui": "D024821", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Personality", "descriptor_ui": "D010551", "major_topic": true }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false }, { "descriptor": "Smoking", "descriptor_ui": "D012907", "major_topic": false }, { "descriptor": "Waist Circumference", "descriptor_ui": "D055105", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Apr", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "20-25", "proceedings_title": null, "publisher": "", "title": "Journal of psychosomatic research", "volume": "107", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Relationships among personality traits, metabolic syndrome, and metabolic syndrome scores: The Kakegawa cohort study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Elimination of early-formed redundant synapses during postnatal development is essential for functional neural circuit formation. Purkinje cells (PCs) in the neonatal cerebellum are innervated by multiple climbing fibers (CFs). During postnatal development, a single CF is selectively strengthened in each PC and becomes a \"winner\" CF that is presumed to remain into adulthood, whereas the other \"loser\" CFs are eliminated. These developmental changes are dependent on neural activity and signal cascades in postsynaptic PCs. Several molecules essential for CF synapse elimination have been identified in postsynaptic PCs. Importantly, we have recently uncovered that Semaphorin3A (Sema3A) and Semaphorin7A (Sema7A) derived from postsynaptic PCs act retrogradely onto presynaptic CFs and regulate CF synapse elimination. We demonstrate that Sema3A strengthens and maintains CF synapses from postnatal day 8 (P8) to P18 and opposes the force of CF elimination. In contrast, Sema7A facilitates elimination of weaker CFs from PC somata after P15. In the continuing studies, we searched for molecules that mediate these retrograde semaphorin signals in presynaptic CFs. This short article describes how Sema3A strengthens and maintains, whereas Sema7A promotes elimination of CF synapses through respective receptors and downstream molecules in presynaptic CFs during postnatal cerebellar development.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12311-017-0888-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28965326" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nerve Fibers", "descriptor_ui": "D009412", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Presynaptic Terminals", "descriptor_ui": "D017729", "major_topic": false }, { "descriptor": "Semaphorins", "descriptor_ui": "D039961", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Feb", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "17-22", "proceedings_title": null, "publisher": "", "title": "Cerebellum (London, England)", "volume": "17", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Presynaptic Mechanisms Mediating Retrograde Semaphorin Signals for Climbing Fiber Synapse Elimination During Postnatal Cerebellar Development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurodegenerative diseases such as spinocerebellar ataxias and autoantibody-associated disorders of the central nervous system often affect the cerebellum, resulting in motor deficits. Recent studies have revealed that most of these disorders impair type 1 metabotropic glutamate receptor (mGluR1) and/or the closely associated signaling molecules in cerebellar Purkinje cell. Since the signaling pathway triggered by mGluR1 activation in Purkinje cell plays a pivotal role in coordinated movements and motor learning, pharmacological repair of aberrant mGluR1 signaling in Purkinje cell is critical for mitigation of cerebellar symptoms. Here we review recently identified pathophysiology underlying the neurodegenerative and autoimmune diseases affecting mGluR1 signaling in Purkinje cell and possible therapeutic interventions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.coph.2018.02.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29525719" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebellar Diseases", "descriptor_ui": "D002526", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Feb", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "51-58", "proceedings_title": null, "publisher": "", "title": "Current opinion in pharmacology", "volume": "38", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Type 1 metabotropic glutamate receptor and its signaling molecules as therapeutic targets for the treatment of cerebellar disorders.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Autoimmunity is prevented by the function of the autoimmune regulator [AIRE (Aire in mice)], which promotes the expression of a wide variety of tissue-restricted antigens (TRAs) from medullary thymic epithelial cells (mTECs) and from a subset of peripheral antigen-presenting cells (APCs). We examined the effect of additive expression of human AIRE (huAIRE) in a model of autoimmune diabetes in NOD mice. Unexpectedly, we observed that mice expressing augmented AIRE/Aire developed muscle-specific autoimmunity associated with incomplete maturation of mTECs together with impaired expression of Aire-dependent TRAs. This led to failure of deletion of autoreactive T cells together with dramatically reduced production of regulatory T cells in the thymus. In peripheral APCs, expression of costimulatory molecules was augmented. We suggest that levels of Aire expression need to be tightly controlled for maintenance of immunological tolerance. Our results also highlight the importance of coordinated action between central tolerance and peripheral tolerance under the common control of Aire.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Nishijima", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Mouri", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Nishioka", "name": null }, { "creator_type": "author", "first_name": "Hisanori", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Tsuneyama", "name": null }, { "creator_type": "author", "first_name": "Il-Mi", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Hosomichi", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Shiraki", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Shibutani", "name": null }, { "creator_type": "author", "first_name": "Kunitoshi", "last_name": "Mitsumori", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Matsumoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jaut.2017.09.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28931462" } }, "mesh": [ { "descriptor": "AIRE Protein", "descriptor_ui": "D000096927", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autoantigens", "descriptor_ui": "D001324", "major_topic": false }, { "descriptor": "Autoimmunity", "descriptor_ui": "D015551", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 1", "descriptor_ui": "D003922", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Tolerance", "descriptor_ui": "D007108", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Muscles", "descriptor_ui": "D009132", "major_topic": false }, { "descriptor": "Organ Specificity", "descriptor_ui": "D009928", "major_topic": false }, { "descriptor": "Polymyositis", "descriptor_ui": "D017285", "major_topic": false }, { "descriptor": "Thymus Gland", "descriptor_ui": "D013950", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jan", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "75-92", "proceedings_title": null, "publisher": "", "title": "Journal of autoimmunity", "volume": "86", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Paradoxical development of polymyositis-like autoimmunity through augmented expression of autoimmune regulator (AIRE).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nemerteans (ribbon worms) and phoronids (horseshoe worms) are closely related lophotrochozoans-a group of animals including leeches, snails and other invertebrates. Lophotrochozoans represent a superphylum that is crucial to our understanding of bilaterian evolution. However, given the inconsistency of molecular and morphological data for these groups, their origins have been unclear. Here, we present draft genomes of the nemertean Notospermus geniculatus and the phoronid Phoronis australis, together with transcriptomes along the adult bodies. Our genome-based phylogenetic analyses place Nemertea sister to the group containing Phoronida and Brachiopoda. We show that lophotrochozoans share many gene families with deuterostomes, suggesting that these two groups retain a core bilaterian gene repertoire that ecdysozoans (for example, flies and nematodes) and platyzoans (for example, flatworms and rotifers) do not. Comparative transcriptomics demonstrates that lophophores of phoronids and brachiopods are similar not only morphologically, but also at the molecular level. Despite dissimilar head structures, lophophores express vertebrate head and neuronal marker genes. This finding suggests a common origin of bilaterian head patterning, although different heads evolved independently in each lineage. Furthermore, we observe lineage-specific expansions of innate immunity and toxin-related genes. Together, our study reveals a dual nature of lophotrochozoans, where conserved and lineage-specific features shape their evolution.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yi-Jyun", "last_name": "Luo", "name": null }, { "creator_type": "author", "first_name": "Miyuki", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Kanako", "last_name": "Hisata", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Satoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41559-017-0389-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29203924" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": true }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": true }, { "descriptor": "Head", "descriptor_ui": "D006257", "major_topic": false }, { "descriptor": "Invertebrates", "descriptor_ui": "D007448", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "141-151", "proceedings_title": null, "publisher": "", "title": "Nature ecology & evolution", "volume": "2", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Nemertean and phoronid genomes reveal lophotrochozoan evolution and the origin of bilaterian heads.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To practically apply photoacoustic (PA) imaging technology in medicine, we have developed prototypes of a photoacoustic mammography (PAM) device to acquire images for diagnosing breast cancer in the Kyoto University/Canon joint research project (CK project supported by MEXT, Japan). First, the basic ability of the PAM system to visualize the network of blood vessels and the Hb saturation index was evaluated using a prototype of PAM that has a flat scanning detector and is capable of simultaneously acquiring photoacoustic (PA) and ultrasound images. Next, another prototype of a PAM device with hemispherical sensors was developed to improve the visibility of the 3D structure of vessels by reducing the limited view effect. In clinical examination of breast cancer cases, the PAM system allowed 3D visualization of fine vessel networks with a spatial resolution of a half-millimeter and enabled us to determine the features of tumor-related vascular structures in human breast cancer. In addition, the oxygen saturation status of Hb was visualized using two different wavelengths, enabling more precise characterization of the tumor microenvironment. Results of clinical evaluation using our developed prototype of a PAM device confirmed that PA imaging technology has the potential to promote early detection of breast cancer, and realization of its practical use is expected in the near future.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Toi", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Yagi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s13534-018-0070-7" }, "pmcid": { "normalized": "PMC6208520" }, "pmid": { "normalized": "30603200" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018 May", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "157-165", "proceedings_title": null, "publisher": "", "title": "Biomedical engineering letters", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Development and clinical translation of photoacoustic mammography.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "TLR3 is a sensor of double-stranded RNA that is indispensable for defense against infection with herpes simplex virus type 1 (HSV-1) in the brain. We found here that TLR3 was required for innate immune responses to HSV-1 in neurons and astrocytes. During infection with HSV-1, TLR3 recruited the metabolic checkpoint kinase complex mTORC2, which led to the induction of chemokines and trafficking of TLR3 to the cell periphery. Such trafficking enabled the activation of molecules (including mTORC1) required for the induction of type I interferons. Intracranial infection of mice with HSV-1 was exacerbated by impairment of TLR3 responses with an inhibitor of mTOR and was significantly 'rescued' by potentiation of TLR3 responses with an agonistic antibody to TLR3. These results suggest that the TLR3-mTORC2 axis might be a therapeutic target through which to combat herpes simplex encephalitis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryota", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Chimura", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiroh", "last_name": "Saitoh", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Ryutaro", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Kaiwen", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Yun", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Ge-Hong", "last_name": "Sun-Wada", "name": null }, { "creator_type": "author", "first_name": "Yoh", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Tsuneo", "last_name": "Ikenoue", "name": null }, { "creator_type": "author", "first_name": "Glen N.", "last_name": "Barber", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Manabe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Miyake", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41590-018-0203-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30201994" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Encephalitis, Herpes Simplex", "descriptor_ui": "D020803", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": false }, { "descriptor": "Mechanistic Target of Rapamycin Complex 2", "descriptor_ui": "D000076225", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "Toll-Like Receptor 3", "descriptor_ui": "D051196", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "1071-1082", "proceedings_title": null, "publisher": "", "title": "Nature immunology", "volume": "19", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Combating herpesvirus encephalitis by potentiating a TLR3-mTORC2 axis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dysregulation of neuropeptides may play an important role in aging-induced impairments. Among them, pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent cytoprotective peptide that provides an endogenous control against a variety of tissue-damaging stimuli. We hypothesized that the progressive decline of PACAP throughout life and the well-known general cytoprotective effects of PACAP lead to age-related pathophysiological changes in PACAP deficiency, supported by the increased vulnerability to various stressors of animals partially or totally lacking PACAP. Using young and aging CD1 PACAP knockout (KO) and wild type (WT) mice, we demonstrated pre-senile amyloidosis in young PACAP KO animals and showed that senile amyloidosis appeared accelerated, more generalized, more severe, and affected more individuals. Histopathology showed age-related systemic amyloidosis with mainly kidney, spleen, liver, skin, thyroid, intestinal, tracheal, and esophageal involvement. Mass spectrometry-based proteomic analysis, reconfirmed with immunohistochemistry, revealed that apolipoprotein-AIV was the main amyloid protein in the deposits together with several accompanying proteins. Although the local amyloidogenic protein expression was disturbed in KO animals, no difference was found in laboratory lipid parameters, suggesting a complex pathway leading to increased age-related degeneration with amyloid deposits in the absence of PACAP. In spite of no marked inflammatory histological changes or blood test parameters, we detected a disturbed cytokine profile that possibly creates a pro-inflammatory milieu favoring amyloid deposition. In summary, here we describe accelerated systemic senile amyloidosis in PACAP gene-deficient mice, which might indicate an early aging phenomenon in this mouse strain. Thus, PACAP KO mice could serve as a model of accelerated aging with human relevance. (c) 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Dora", "last_name": "Reglodi", "name": null }, { "creator_type": "author", "first_name": "Adel", "last_name": "Jungling", "name": null }, { "creator_type": "author", "first_name": "Remi", "last_name": "Longuespee", "name": null }, { "creator_type": "author", "first_name": "Joerg", "last_name": "Kriegsmann", "name": null }, { "creator_type": "author", "first_name": "Rita", "last_name": "Casadonte", "name": null }, { "creator_type": "author", "first_name": "Mark", "last_name": "Kriegsmann", "name": null }, { "creator_type": "author", "first_name": "Tamas", "last_name": "Juhasz", "name": null }, { "creator_type": "author", "first_name": "Sebastian", "last_name": "Bardosi", "name": null }, { "creator_type": "author", "first_name": "Andrea", "last_name": "Tamas", "name": null }, { "creator_type": "author", "first_name": "Balazs Daniel", "last_name": "Fulop", "name": null }, { "creator_type": "author", "first_name": "Krisztina", "last_name": "Kovacs", "name": null }, { "creator_type": "author", "first_name": "Zsuzsanna", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Jason", "last_name": "Sparks", "name": null }, { "creator_type": "author", "first_name": "Attila", "last_name": "Miseta", "name": null }, { "creator_type": "author", "first_name": "Gabriel", "last_name": "Mazzucchelli", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Attila", "last_name": "Bardosi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/path.5100" }, "pmcid": { "normalized": "PMC6055756" }, "pmid": { "normalized": "29774542" } }, "mesh": [ { "descriptor": "Age Factors", "descriptor_ui": "D000367", "major_topic": false }, { "descriptor": "Amyloidosis", "descriptor_ui": "D000686", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apolipoproteins A", "descriptor_ui": "D001054", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Inflammation Mediators", "descriptor_ui": "D018836", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Plaque, Amyloid", "descriptor_ui": "D058225", "major_topic": true }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Severity of Illness Index", "descriptor_ui": "D012720", "major_topic": false }, { "descriptor": "Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization", "descriptor_ui": "D019032", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "478-490", "proceedings_title": null, "publisher": "", "title": "The Journal of pathology", "volume": "245", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Accelerated pre-senile systemic amyloidosis in PACAP knockout mice - a protective role of PACAP in age-related degenerative processes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alongside the rapid growth in aging populations, prevention of age-related memory decline and dementia has become a high priority. Several epidemiological and clinical studies have concluded that fermented dairy products can help to prevent cognitive decline; furthermore, intake of Camembert cheese prevents Alzheimer's pathology in model mice. To elucidate molecular mechanisms underlying the preventive effects of fermented dairy products, here we screened peptides from digested fermented dairy products for ability to improve memory function in a scopolamine-induced amnesia mouse model. We found that Trp-Tyr (WY)-containing peptides from whey protein improved memory function in the mice, and the effects were confirmed in aged mice. The WY-containing peptides directly inhibited monoamine oxidase-B activity and increased dopamine levels in brain tissue. Pretreatment with dopamine receptor antagonist abolished the improvement in memory function due to WY-containing peptides. These results suggest that WY-containing peptides in fermented dairy products increase monoamine levels by inhibiting monoamine oxidase-B activity, helping to prevent age-related cognitive decline.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Ano", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Ayabe", "name": null }, { "creator_type": "author", "first_name": "Toshiko", "last_name": "Kutsukake", "name": null }, { "creator_type": "author", "first_name": "Rena", "last_name": "Ohya", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Takaichi", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nakayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neurobiolaging.2018.07.016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30176402" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": true }, { "descriptor": "Amnesia", "descriptor_ui": "D000647", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cognitive Dysfunction", "descriptor_ui": "D060825", "major_topic": false }, { "descriptor": "Cultured Milk Products", "descriptor_ui": "D043302", "major_topic": true }, { "descriptor": "Dipeptides", "descriptor_ui": "D004151", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Dopamine Antagonists", "descriptor_ui": "D018492", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Monoamine Oxidase", "descriptor_ui": "D008995", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Whey Proteins", "descriptor_ui": "D000067816", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018 Dec", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "23-31", "proceedings_title": null, "publisher": "", "title": "Neurobiology of aging", "volume": "72", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Novel lactopeptides in fermented dairy products improve memory function and cognitive decline.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cerebral cortex is subdivided into distinct areas that have particular functions. The rostrocaudal (R-C) gradient of fibroblast growth factor 8 (FGF8) signaling defines this areal identity during neural development. In this study, we recapitulated cortical R-C patterning in human pluripotent stem cell (PSC) cultures. Modulation of FGF8 signaling appropriately regulated the R-C markers, and the patterns of global gene expression resembled those of the corresponding areas of human fetal brains. Furthermore, we demonstrated the utility of this culture system in modeling the area-specific forebrain phenotypes [presumptive upper motor neuron (UMN) phenotypes] of amyotrophic lateral sclerosis (ALS). We anticipate that our culture system will contribute to studies of human neurodevelopment and neurological disease modeling.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Otomo", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Hosoi", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Miyajima", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Warita", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Hadano", "name": null }, { "creator_type": "author", "first_name": "Wado", "last_name": "Akamatsu", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/eneuro.0368-17.2018" }, "pmcid": { "normalized": "PMC5917473" }, "pmid": { "normalized": "29707616" } }, "mesh": [ { "descriptor": "Amyotrophic Lateral Sclerosis", "descriptor_ui": "D000690", "major_topic": true }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": true }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": true }, { "descriptor": "Fibroblast Growth Factor 8", "descriptor_ui": "D051524", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018 Mar-Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "eNeuro", "volume": "5", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Rostrocaudal Areal Patterning of Human PSC-Derived Cortical Neurons by FGF8 Signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Circadian clocks are autonomous oscillators driving daily rhythms in physiology and behavior. In mammals, a network of coupled neurons in the suprachiasmatic nucleus (SCN) is entrained to environmental light-dark cycles and orchestrates the timing of peripheral organs. In each neuron, transcriptional feedbacks generate noisy oscillations. Coupling mediated by neuropeptides such as VIP and AVP lends precision and robustness to circadian rhythms. The detailed coupling mechanisms between SCN neurons are debated. We analyze organotypic SCN slices from neonatal and adult mice in wild-type and multiple knockout conditions. Different degrees of rhythmicity are quantified by pixel-level analysis of bioluminescence data. We use empirical orthogonal functions (EOFs) to characterize spatio-temporal patterns. Simulations of coupled stochastic single cell oscillators can reproduce the diversity of observed patterns. Our combination of data analysis and modeling provides deeper insight into the enormous complexity of the data: (1) Neonatal slices are typically stronger oscillators than adult slices pointing to developmental changes of coupling. (2) Wild-type slices are completely synchronized and exhibit specific spatio-temporal patterns of phases. (3) Some slices of Cry double knockouts obey impaired synchrony that can lead to co-existing rhythms (\"splitting\"). (4) The loss of VIP-coupling leads to desynchronized rhythms with few residual local clusters. Additional information was extracted from co-culturing slices with rhythmic neonatal wild-type SCNs. These co-culturing experiments were simulated using external forcing terms representing VIP and AVP signaling. The rescue of rhythmicity via co-culturing lead to surprising results, since a cocktail of AVP-antagonists improved synchrony. Our modeling suggests that these counter-intuitive observations are pointing to an antagonistic action of VIP and AVP coupling. Our systematic theoretical and experimental study shows that dual coupling mechanisms can explain the astonishing complexity of spatio-temporal patterns in SCN slices.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Isao T.", "last_name": "Tokuda", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Sato", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Hanspeter", "last_name": "Herzel", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1006607" }, "pmcid": { "normalized": "PMC6301697" }, "pmid": { "normalized": "30532130" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arginine Vasopressin", "descriptor_ui": "D001127", "major_topic": false }, { "descriptor": "Circadian Clocks", "descriptor_ui": "D057906", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Period Circadian Proteins", "descriptor_ui": "D056950", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": false }, { "descriptor": "Vasoactive Intestinal Peptide", "descriptor_ui": "D014660", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "e1006607", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "14", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Coherency of circadian rhythms in the SCN is governed by the interplay of two coupling factors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mitochondrial dysfunction in the nigrostriatal dopaminergic system is a critical hallmark of Parkinson's disease (PD). Mitochondrial toxins produce cellular and behavioural dysfunctions resembling those in patients with PD Causative gene products for familial PD play important roles in mitochondrial function. Therefore, targeting proteins that regulate mitochondrial integrity could provide convincing strategies for PD therapeutics. We have recently identified a novel 13-kDa protein (p13) that may be involved in mitochondrial oxidative phosphorylation. In the current study, we examine the mitochondrial function of p13 and its involvement in PD pathogenesis using mitochondrial toxin-induced PD models. We show that p13 overexpression induces mitochondrial dysfunction and apoptosis. p13 knockdown attenuates toxin-induced mitochondrial dysfunction and apoptosis in dopaminergic SH-SY5Y cells via the regulation of complex I. Importantly, we generate p13-deficient mice using the CRISPR/Cas9 system and observe that heterozygous p13 knockout prevents toxin-induced motor deficits and the loss of dopaminergic neurons in the substantia nigra. Taken together, our results suggest that manipulating p13 expression may be a promising avenue for therapeutic intervention in PD.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Sae", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Higashi", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Isotani", "name": null }, { "creator_type": "author", "first_name": "Kousuke", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Harutoshi", "last_name": "Fujimura", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.15252/embr.201744860" }, "pmcid": { "normalized": "PMC5836091" }, "pmid": { "normalized": "29371327" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Dopaminergic Neurons", "descriptor_ui": "D059290", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Mitochondrial Diseases", "descriptor_ui": "D028361", "major_topic": false }, { "descriptor": "Mitochondrial Proteins", "descriptor_ui": "D024101", "major_topic": false }, { "descriptor": "Oxidative Phosphorylation", "descriptor_ui": "D010085", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Parkinson Disease", "descriptor_ui": "D010300", "major_topic": false }, { "descriptor": "Parkinsonian Disorders", "descriptor_ui": "D020734", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "EMBO reports", "volume": "19", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Knockdown of the mitochondria-localized protein p13 protects against experimental parkinsonism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Corticosteroid receptors are critical for homeostasis maintenance, but understanding of the principal roles of the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) throughout vertebrates is limited. Lines of constitutive GR-knockout zebrafish and MR-knockout medaka have recently been generated as the first adult-viable corticosteroid receptor-knockout animals, in contrast to the lethality of these receptor knockouts in mice. Here, we describe behavioral and physiological modifications following disruption of corticosteroid receptor function in these animal models. We suggest these data point toward a potentially conserved function of corticosteroid receptors in integrating brain-behavior and visual responses in vertebrates. Finally, we discuss how future work in cartilaginous fishes (Chondrichthyes) will further advance understanding of the unity and diversity of corticosteroid receptor function, since distinct orthologs of GR and MR derived from an ancestral corticoid receptor appear in these basal jawed vertebrates.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Hyodo", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Takagi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jsbmb.2018.02.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29481854" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Glucocorticoids", "descriptor_ui": "D005938", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mineralocorticoids", "descriptor_ui": "D008901", "major_topic": false }, { "descriptor": "Oryzias", "descriptor_ui": "D009990", "major_topic": false }, { "descriptor": "Receptors, Glucocorticoid", "descriptor_ui": "D011965", "major_topic": false }, { "descriptor": "Receptors, Mineralocorticoid", "descriptor_ui": "D018161", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Nov", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "57-61", "proceedings_title": null, "publisher": "", "title": "The Journal of steroid biochemistry and molecular biology", "volume": "184", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "A possible principal function of corticosteroid signaling that is conserved in vertebrate evolution: Lessons from receptor-knockout small fish.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Functional neural circuits in the mature animals are shaped during postnatal development by elimination of unnecessary synapses and strengthening of necessary ones among redundant synaptic connections formed transiently around birth. In the cerebellum of neonatal rodents, excitatory synapses are formed on the somata of Purkinje cells (PCs) by climbing fibers (CFs) that originate from neurons in the contralateral inferior olive. Each PC receives inputs from multiple (~ five) CFs that have about equal synaptic strengths. Subsequently, a single CF selectively becomes stronger relative to the other CFs during the first postnatal week. Then, from around postnatal day 9 (P9), only the strongest CF (\"winner\" CF) extends its synaptic territory along PC dendrites. In contrast, synapses of the weaker CFs (\"loser\" CFs) remain on the soma and the most proximal portion of the dendrite together with somatic synapses of the \"winner\" CF. These perisomatic CF synapses are eliminated progressively during the second and the third postnatal weeks. From P6 to P11, the elimination proceeds independently of the formation of the synapses on PC dendrites by parallel fibers (PFs). From P12 and thereafter, the elimination requires normal PF-PC synapse formation and is presumably dependent on the PF synaptic inputs. Most PCs become mono-innervated by single strong CFs on their dendrites in the third postnatal week. In this review article, we will describe how adult-type CF mono-innervation of PC is established through these multiple phases of postnatal cerebellar development and make an overview of molecular/cellular mechanisms underlying them.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12311-018-0964-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30009357" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Olivary Nucleus", "descriptor_ui": "D009847", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "722-734", "proceedings_title": null, "publisher": "", "title": "Cerebellum (London, England)", "volume": "17", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Multiple Phases of Climbing Fiber Synapse Elimination in the Developing Cerebellum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lymphadenopathy is a frequently observed symptom in systemic lupus erythematosus, although the immunological role of lymph nodes (LNs) in systemic autoimmunity remains largely unknown. Here, we performed comprehensive and systematic analyses of LNs in lupus-prone NZB x NZW F1 (BWF1) mice, demonstrating extensive tissue re-organization of the systemic LNs with follicular expansion, hyper germinal center (GC) formation, atrophy of the paracortical T-cell area and expansion of the medulla in aged BWF1 mice bearing glomerulonephritis. The proportion of B cells was significantly increased in these reactive LNs but not in the spleen, and lymphocyte subsets involved in antibody production, i.e. GC B cells, follicular helper T cells and plasma cells, were elevated. Draining LNs of the affected organs, such as the renal and cervical nodes, showed enhanced tissue re-organization and accumulation of effector lymphocytes, suggesting the presence of a positive feedback loop of regional responses. LN cells isolated from disease-bearing animals produced anti-DNA antibody, indicating activation of autoreactive lymphocytes in situ. The substantial development of disease and LN alterations in mice that received a splenectomy at a young age points to the importance of other secondary lymphoid organs, most likely LNs, for the progression of autoimmune responses independent of the spleen. Taken together, our findings highlight the value of taking LN alterations and activities into consideration for understanding the pathogenesis of systemic autoimmunity.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoichi", "last_name": "Kurosawa", "name": null }, { "creator_type": "author", "first_name": "Madoka", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Arata", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Ichiei", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/intimm/dxx066" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29202179" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Antinuclear", "descriptor_ui": "D000974", "major_topic": false }, { "descriptor": "Autoimmunity", "descriptor_ui": "D015551", "major_topic": false }, { "descriptor": "Cellular Microenvironment", "descriptor_ui": "D060833", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Disease Susceptibility", "descriptor_ui": "D004198", "major_topic": false }, { "descriptor": "Germinal Center", "descriptor_ui": "D018858", "major_topic": false }, { "descriptor": "Glomerulonephritis", "descriptor_ui": "D005921", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lupus Erythematosus, Systemic", "descriptor_ui": "D008180", "major_topic": false }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred NZB", "descriptor_ui": "D008814", "major_topic": false }, { "descriptor": "Self Tolerance", "descriptor_ui": "D017634", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Dec 31", "date_precision": "day", "issue": "12", "normalized_date": "2017-12-31", "pages": "567-579", "proceedings_title": null, "publisher": "", "title": "International immunology", "volume": "29", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Extensively re-organized systemic lymph nodes provide a feasible environment for self-reactivity in lupus-prone NZB x NZW F1 mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "While both archaeal and eukaryotic transcription initiation systems utilize TBP (TATA box-binding protein) and TFIIB (transcription factor IIB), eukaryotic systems include larger numbers of initiation factors. It remains uncertain how eukaryotic transcription initiation systems have evolved. Here, we investigate the evolutionary development of TBP and TFIIB, each of which has an intramolecular direct repeat, using two evolutionary indicators. Inter-repeat sequence dissimilarity (d(DR), distance between direct repeats) indicates that the asymmetry of two repeats in TBP and TFIIB has gradually increased during evolution. Interspecies sequence diversity (PD, phylogenetic diversity) indicates that the resultant asymmetric structure, which is related to the ability to interact with multiple factors, diverged in archaeal TBP and archaeal/eukaryotic TFIIB during evolution. Our findings suggest that eukaryotic TBP initially acquired multiple Eukarya-specific interactors through asymmetric evolution of the two repeats. After the asymmetric TBP generated the complexity of the eukaryotic transcription initiation systems, its diversification halted and its asymmetric structure spread throughout eukaryotic species.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Senda", "name": null }, { "creator_type": "author", "first_name": "Masami", "last_name": "Horikoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2017.12.034" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29281839" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Conserved Sequence", "descriptor_ui": "D017124", "major_topic": false }, { "descriptor": "Eukaryotic Cells", "descriptor_ui": "D005057", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Methanocaldococcus", "descriptor_ui": "D063747", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "TATA-Box Binding Protein", "descriptor_ui": "D035181", "major_topic": false }, { "descriptor": "Transcription Factor TFIIB", "descriptor_ui": "D035581", "major_topic": false }, { "descriptor": "Transcription Initiation, Genetic", "descriptor_ui": "D061785", "major_topic": true } ], "publication": { "conference_name": null, "date": "2017 Dec 26", "date_precision": "day", "issue": "13", "normalized_date": "2017-12-26", "pages": "3941-3956", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "21", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Leading role of TBP in the Establishment of Complexity in Eukaryotic Transcription Initiation Systems.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In vitro tubulogenesis has been employed as an experimental model system to study tissue morphogenesis of internal organs. It has been previously shown that Madin-Darby canine kidney (MDCK) cells form tubes in the presence of hepatocyte growth factor in 3D cultures. Although these cells are expected to form tube structures in some microenvironments independent of chemical stimulation, little is known about the cellular mechanisms in organizing such an anisotropic multicellular structure. Here, we report 3D culture conditions that induce MDCK tubulogenesis without growth factor stimulation. We found that the cells spontaneously form elongated tube structures through aggregation processes in a specific range of both constituent cell number and scaffold gel concentration, while they form spherical aggregates in other conditions. We then examined cellular activities affecting tubulogenesis and showed that cell proliferation is not required for the tube elongation. Furthermore, we revealed that cells in the tube tips generate traction forces and pull the surrounding scaffold gel to migrate, resulting in the tube elongation. Our results suggest that the constituent cells during the aggregation process interact each other via mechanical forces transmitted in the scaffold gel, leading to the spontaneous tube formation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Hoshuyama", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Adachi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtbi.2017.09.009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28923372" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Cell Aggregation", "descriptor_ui": "D002449", "major_topic": true }, { "descriptor": "Cell Count", "descriptor_ui": "D002452", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Gels", "descriptor_ui": "D005782", "major_topic": false }, { "descriptor": "Kidney Tubules", "descriptor_ui": "D007684", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": true }, { "descriptor": "Spheroids, Cellular", "descriptor_ui": "D018874", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Dec 21", "date_precision": "day", "issue": "", "normalized_date": "2017-12-21", "pages": "110-115", "proceedings_title": null, "publisher": "", "title": "Journal of theoretical biology", "volume": "435", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "In vitro tubulogenesis of Madin-Darby canine kidney (MDCK) spheroids occurs depending on constituent cell number and scaffold gel concentration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Antigen-specific regulatory T cells (Tregs) possess the potential to reduce excess immune responses in autoimmune diseases, allergy, rejection after organ transplantation and graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation. Although in vitro-expanded antigen-specific induced Tregs (iTregs) have been considered to be a promising therapeutic agent against such excessive immune reactions, the instability of iTregs after transfer is a fundamental problem in their clinical application. In this study, we searched for the optimal way to generate stable iTregs for the prevention of the murine GVHD model, in which conventional iTregs are reported to be inefficient. Allo-antigen-specific iTregs were generated by co-culturing naive T cells with allogenic dendritic cells in the presence of TGF-beta and retinoic acid. By examining various agents and genes, we found that vitamin C stabilized Foxp3 expression most effectively in adoptively transferred iTregs under a GVHD environment. Vitamin C treatment caused active DNA demethylation specifically on the conserved non-coding sequence 2 (CNS2) enhancer of the Foxp3 gene locus in allo-antigen-specific iTregs and reduced iTreg conversion into pathogenic exFoxp3 cells. Vitamin C-treated iTregs suppressed GVHD symptoms more efficiently than untreated iTregs. Vitamin C also facilitated induction of a FOXP3high iTreg population from human naive T cells, which was very stable even in the presence of IL-6 in vitro. The treatment of vitamin C for iTreg promises innovative clinical application for adoptive Treg immunotherapy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hidenori", "last_name": "Kasahara", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Nakatsukasa", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Kurebayashi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Taketo", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/intimm/dxx060" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29126272" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ascorbic Acid", "descriptor_ui": "D001205", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "Graft vs Host Disease", "descriptor_ui": "D006086", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunotherapy, Adoptive", "descriptor_ui": "D016219", "major_topic": false }, { "descriptor": "Isoantigens", "descriptor_ui": "D007519", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false }, { "descriptor": "Tretinoin", "descriptor_ui": "D014212", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Dec 18", "date_precision": "day", "issue": "10", "normalized_date": "2017-12-18", "pages": "457-469", "proceedings_title": null, "publisher": "", "title": "International immunology", "volume": "29", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of allo-antigen-specific induced Treg stabilized by vitamin C treatment and its application for prevention of acute graft versus host disease model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genomic variation includes single-nucleotide variants, small insertions or deletions (indels), and copy number variants (CNVs). CNVs affect gene expression by altering the genome structure and transposable elements within a region. CNVs are greater than 1 kb in size; hence, CNVs can produce more variation than can individual single-nucleotide variations that are detected by next-generation sequencing. Multiple system atrophy (MSA) is an alpha-synucleinopathy adult-onset disorder. Pathologically, it is characterized by insoluble aggregation of filamentous alpha-synuclein in brain oligodendrocytes. Generally, MSA is sporadic, although there are rare cases of familial MSA. In addition, the frequencies of the clinical phenotypes differ considerably among countries. Reports indicate that genetic factors play roles in the mechanisms involved in the pathology and onset of MSA. To evaluate the genetic background of this disorder, we attempted to determine whether there are differences in CNVs between patients with MSA and normal control subjects. We found that the number of CNVs on chromosomes 5, 22, and 4 was increased in MSA; 3 CNVs in non-coding regions were considered risk factors for MSA. Our results show that CNVs in non-coding regions influence the expression of genes through transcription-related mechanisms and potentially increase subsequent structural alterations of chromosomes. Therefore, these CNVs likely play roles in the molecular mechanisms underlying MSA.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuka", "last_name": "Hama", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Katsu", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Yabe", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Matsushima", "name": null }, { "creator_type": "author", "first_name": "Ikuko", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Utsumi", "name": null }, { "creator_type": "author", "first_name": "Hidenao", "last_name": "Sasaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13041-017-0335-6" }, "pmcid": { "normalized": "PMC5708077" }, "pmid": { "normalized": "29187220" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Atrophy", "descriptor_ui": "D001284", "major_topic": false }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "DNA Copy Number Variations", "descriptor_ui": "D056915", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Ontology", "descriptor_ui": "D063990", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov 29", "date_precision": "day", "issue": "1", "normalized_date": "2017-11-29", "pages": "54", "proceedings_title": null, "publisher": "", "title": "Molecular brain", "volume": "10", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Genomic copy number variation analysis in multiple system atrophy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although alpha-synuclein (alphaSyn) has been linked to Parkinson's disease (PD), the mechanisms underlying the causative role in PD remain unclear. We previously proposed a model for a transportable microtubule (tMT), in which dynein is anchored to a short tMT by LIS1 followed by the kinesin-dependent anterograde transport; however the mechanisms that produce tMTs have not been determined. Our in vitro investigations of microtubule (MT) dynamics revealed that alphaSyn facilitates the formation of short MTs and preferentially binds to MTs carrying 14 protofilaments (pfs). Live-cell imaging showed that alphaSyn co-transported with dynein and mobile betaIII-tubulin fragments in the anterograde transport. Furthermore, bi-directional axonal transports are severely affected in alphaSyn and gammaSyn depleted dorsal root ganglion neurons. SR-PALM analyses further revealed the fibrous co-localization of alphaSyn, dynein and betaIII-tubulin in axons. More importantly, 14-pfs MTs have been found in rat femoral nerve tissue, and they increased approximately 19 fold the control in quantify upon nerve ligation, indicating the unconventional MTs are mobile. Our findings indicate that alphaSyn facilitates to form short, mobile tMTs that play an important role in the axonal transport. This unexpected and intriguing discovery related to axonal transport provides new insight on the pathogenesis of PD.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shiori", "last_name": "Toba", "name": null }, { "creator_type": "author", "first_name": "Mingyue", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Masami", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kanako", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Sakiko", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Takuo", "last_name": "Yasunaga", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Fukunaga", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Miyazawa", "name": null }, { "creator_type": "author", "first_name": "Sakiko", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fushiki", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Wanibuchi", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Hirotsune", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-15575-3" }, "pmcid": { "normalized": "PMC5703968" }, "pmid": { "normalized": "29180624" } }, "mesh": [ { "descriptor": "alpha-Synuclein", "descriptor_ui": "D051844", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axonal Transport", "descriptor_ui": "D001370", "major_topic": true }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "Femoral Nerve", "descriptor_ui": "D005267", "major_topic": false }, { "descriptor": "Gas Chromatography-Mass Spectrometry", "descriptor_ui": "D008401", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Multimerization", "descriptor_ui": "D055503", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Proteome", "descriptor_ui": "D020543", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Tubulin", "descriptor_ui": "D014404", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov 27", "date_precision": "day", "issue": "1", "normalized_date": "2017-11-27", "pages": "16386", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Alpha-synuclein facilitates to form short unconventional microtubules that have a unique function in the axonal transport.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neural circuits undergo massive refinements during postnatal development. In the developing cerebellum, the climbing fiber (CF) to Purkinje cell (PC) network is drastically reshaped by eliminating early-formed redundant CF to PC synapses. To investigate the impact of CF network refinement on PC population activity during postnatal development, we monitored spontaneous CF responses in neighboring PCs and the activity of populations of nearby CF terminals using in vivo two-photon calcium imaging. Population activity is highly synchronized in newborn mice, and the degree of synchrony gradually declines during the first postnatal week in PCs and, to a lesser extent, in CF terminals. Knockout mice lacking P/Q-type voltage-gated calcium channel or glutamate receptor delta2, in which CF network refinement is severely impaired, exhibit an abnormally high level of synchrony in PC population activity. These results suggest that CF network refinement is a structural basis for developmental desynchronization and maturation of PC population activity.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Jean-Marc", "last_name": "Good", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Mahoney", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Kenji F.", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2017.10.101" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29166599" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Receptors, Glutamate", "descriptor_ui": "D017470", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov 21", "date_precision": "day", "issue": "8", "normalized_date": "2017-11-21", "pages": "2066-2073", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "21", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Maturation of Cerebellar Purkinje Cell Population Activity during Postnatal Refinement of Climbing Fiber Network.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A landmark of developmental biology is the production of reproducible shapes, through stereotyped morphogenetic events. At the cell level, growth is often highly heterogeneous, allowing shape diversity to arise. Yet, how can reproducible shapes emerge from such growth heterogeneity? Is growth heterogeneity filtered out? Here, we focus on rapidly growing trichome cells in the Arabidopsis sepal, a reproducible floral organ. We show via computational modeling that rapidly growing cells may distort organ shape. However, the cortical microtubule alignment along growth-derived maximal tensile stress in adjacent cells would mechanically isolate rapidly growing cells and limit their impact on organ shape. In vivo, we observed such microtubule response to stress and consistently found no significant effect of trichome number on sepal shape in wild-type and lines with trichome number defects. Conversely, modulating the microtubule response to stress in katanin and spiral2 mutant made sepal shape dependent on trichome number, suggesting that, while mechanical signals are propagated around rapidly growing cells, the resistance to stress in adjacent cells mechanically isolates rapidly growing cells, thus contributing to organ shape reproducibility.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Nathan", "last_name": "Hervieux", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsugawa", "name": null }, { "creator_type": "author", "first_name": "Antoine", "last_name": "Fruleux", "name": null }, { "creator_type": "author", "first_name": "Mathilde", "last_name": "Dumond", "name": null }, { "creator_type": "author", "first_name": "Anne-Lise", "last_name": "Routier-Kierzkowska", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null }, { "creator_type": "author", "first_name": "Arezki", "last_name": "Boudaoud", "name": null }, { "creator_type": "author", "first_name": "John C.", "last_name": "Larkin", "name": null }, { "creator_type": "author", "first_name": "Richard S.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Chun-Biu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Olivier", "last_name": "Hamant", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2017.10.033" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29129534" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Flowers", "descriptor_ui": "D035264", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Organ Size", "descriptor_ui": "D009929", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Stress, Physiological", "descriptor_ui": "D013312", "major_topic": false }, { "descriptor": "Trichomes", "descriptor_ui": "D064201", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov 20", "date_precision": "day", "issue": "22", "normalized_date": "2017-11-20", "pages": "3468-3479.e4", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "27", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Mechanical Shielding of Rapidly Growing Cells Buffers Growth Heterogeneity and Contributes to Organ Shape Reproducibility.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The calcium ion (Ca(2+)) is an important second messenger, and a rapid increase in Ca(2+) level (Ca(2+) transient) is involved in various aspects of embryogenesis. Although Ca(2+) transients play an important role in early developmental stages, little is known about their dynamics throughout embryogenesis. Here, Ca(2+) transients were characterized by visualizing Ca(2+) dynamics in developing chordate embryos using a fluorescent protein-based Ca(2+) indicator, GCaMP6s in combination with finely tuned microscopy. Ca(2+) transients were detected in precursors of muscle cells in the late gastrula stage. In the neurula stage, repetitive Ca(2+) transients were observed in left and right neurogenic cells, including visceral ganglion (VG) precursors, and the duration of Ca(2+) transients was 39+/-4s. In the early tailbud stage, Ca(2+) transients were observed in differentiating precursors of nerve cord neurons. A small population of VG precursors showed rhythmical Ca(2+) transients with a duration of 22+/-4s, suggesting a central pattern generator (CPG) origin. At the mid tailbud stage, Ca(2+)transients were observed in a wide area of epidermal cells and named CTECs. The number and frequency of CTECs increased drastically in late tailbud stages, and the timing of the increase coincided with that of the relaxation of the tail bending. The experiment using Ca(2+) chelator showed that the CTECs were largely depending on the extracellular Ca(2+). The waveform analysis of Ca(2+) transients revealed different features according to duration and frequency. The comprehensive characterization of Ca(2+) transients during early ascidian embryogenesis will help our understanding of the role of Ca(2+) signaling in chordate embryogenesis.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Taichi", "last_name": "Akahoshi", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2017.09.019" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28935526" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": true }, { "descriptor": "Gastrula", "descriptor_ui": "D005775", "major_topic": false }, { "descriptor": "Tail", "descriptor_ui": "D013623", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false }, { "descriptor": "Urochordata", "descriptor_ui": "D014561", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov 15", "date_precision": "day", "issue": "2", "normalized_date": "2017-11-15", "pages": "205-214", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "431", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Characterization of calcium transients during early embryogenesis in ascidians Ciona robusta (Ciona intestinalis type A) and Ciona savignyi.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The biophysical framework of collective cell migration has been extensively investigated in recent years; however, it remains elusive how chemical inputs from neighboring cells are integrated to coordinate the collective movement. Here, we provide evidence that propagation waves of extracellular signal-related kinase (ERK) mitogen-activated protein kinase activation determine the direction of the collective cell migration. A wound-healing assay of Mardin-Darby canine kidney (MDCK) epithelial cells revealed two distinct types of ERK activation wave, a \"tidal wave\" from the wound, and a self-organized \"spontaneous wave\" in regions distant from the wound. In both cases, MDCK cells collectively migrated against the direction of the ERK activation wave. The inhibition of ERK activation propagation suppressed collective cell migration. An ERK activation wave spatiotemporally controlled actomyosin contraction and cell density. Furthermore, an optogenetic ERK activation wave reproduced the collective cell migration. These data provide new mechanistic insight into how cells sense the direction of collective cell migration.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Honda", "last_name": "Naoki", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hiratsuka", "name": null }, { "creator_type": "author", "first_name": "Reina E.", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2017.10.016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29112851" } }, "mesh": [ { "descriptor": "Actomyosin", "descriptor_ui": "D000205", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Wound Healing", "descriptor_ui": "D014945", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov 6", "date_precision": "day", "issue": "3", "normalized_date": "2017-11-06", "pages": "305-317.e5", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "43", "year": 2017 }, "ssbd": { "database": [ "ssbd-database-000077" ], "repository": [ "ssbd-repos-000077" ] }, "title": "Propagating Wave of ERK Activation Orients Collective Cell Migration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Accurate quantification of biomolecules in system-wide measurements is in high demand, especially for systems with limited sample amounts such as single cells. Because of this, digital quantification of nucleic acid molecules using molecular barcodes has been developed, making, e.g., transcriptome analysis highly reproducible and quantitative. This counting scheme was shown to work using sequence-restricted barcodes, and non-sequence-restricted (random-base) barcodes that may provide a much higher dynamic range at significantly lower cost have been widely used. However, the efficacy of random-base barcodes is significantly affected by base changes due to amplification and/or sequencing errors and has not been investigated experimentally or quantitatively. Here, we show experimentally that random-base barcodes enable absolute and digital quantification of DNA molecules with high dynamic range (from one to more than 10(4), potentially up to 10(15) molecules) conditional on our barcode design and variety, a certain range of sequencing depths, and computational analyses. Moreover, we quantitatively show further functional advantages of the molecular barcodes: the molecular barcodes enable one to find contaminants and misidentifications of target sequences. Our scheme here may be generally used to confirm that the digital quantification works in each platform.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taisaku", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Kirill", "last_name": "Kryukov", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Imanishi", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-13529-3" }, "pmcid": { "normalized": "PMC5648891" }, "pmid": { "normalized": "29051542" } }, "mesh": [ { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "DNA Barcoding, Taxonomic", "descriptor_ui": "D058893", "major_topic": false }, { "descriptor": "Polymerase Chain Reaction", "descriptor_ui": "D016133", "major_topic": false }, { "descriptor": "Random Allocation", "descriptor_ui": "D011897", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Oct 19", "date_precision": "day", "issue": "1", "normalized_date": "2017-10-19", "pages": "13576", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "The efficacy and further functional advantages of random-base molecular barcodes for absolute and digital quantification of nucleic acid molecules.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "David", "last_name": "Bending", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ni.3852" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29044246" } }, "mesh": [ { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": true }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": true } ], "publication": { "conference_name": null, "date": "2017 Oct 18", "date_precision": "day", "issue": "11", "normalized_date": "2017-10-18", "pages": "1181-1183", "proceedings_title": null, "publisher": "", "title": "Nature immunology", "volume": "18", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "FoxP3 partners up.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "HemAT is a heme-containing oxygen sensor protein that controls aerotaxis. Time-resolved step-scan FTIR studies were performed on the isolated sensor domain and full-length HemAT proteins as well as on the Y70F (B-helix), L92A (E-helix), T95A (E-helix), and Y133F (G-helix) mutants to elucidate the effect of the site-specific mutations on the ligand dynamics subsequent to CO photolysis. The mutations aimed to perturb H-bonding and electrostatic interactions near the heme Fe-bound gaseous ligand (CO) and the heme proximal environment. Rebinding of CO to the heme Fe is biphasic in the sensor domain and full-length HemAT as well as in the mutants, with the exception of the Y133F mutant protein. The monophasic rebinding of CO in Y133F suggests that in the absence of the H-bond between Y133 and the heme proximal H123 residue the ligand rebinding process is significantly affected. The role of the proximal environment is also probed by resonance Raman photodissociation experiments, in which the Fe-His mode of the photoproduct of sensor domain HemAT-CO is detected at a frequency higher than that of the deoxy form in the difference resonance Raman spectra. The role of the conformational changes of Y133 (G-helix) and the role of the distal L92 and T95 residues (E-helix) in regulating ligand dynamics in the heme pocket are discussed.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Andrea", "last_name": "Pavlou", "name": null }, { "creator_type": "author", "first_name": "Andreas", "last_name": "Loullis", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Shigetoshi", "last_name": "Aono", "name": null }, { "creator_type": "author", "first_name": "Eftychia", "last_name": "Pinakoulaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.biochem.7b00558" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28876054" } }, "mesh": [ { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Heme", "descriptor_ui": "D006418", "major_topic": false }, { "descriptor": "Heme-Binding Proteins", "descriptor_ui": "D000081062", "major_topic": false }, { "descriptor": "Hemeproteins", "descriptor_ui": "D006420", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Spectroscopy, Fourier Transform Infrared", "descriptor_ui": "D017550", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Oct 10", "date_precision": "day", "issue": "40", "normalized_date": "2017-10-10", "pages": "5309-5317", "proceedings_title": null, "publisher": "", "title": "Biochemistry", "volume": "56", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Probing the Role of the Heme Distal and Proximal Environment in Ligand Dynamics in the Signal Transducer Protein HemAT by Time-Resolved Step-Scan FTIR and Resonance Raman Spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chondroitin sulfate (CS) is an important glycosaminoglycan and is mainly found in the extracellular matrix as CS proteoglycans. In the brain, CS proteoglycans are highly concentrated in perineuronal nets (PNNs), which surround synapses and modulate their functions. To investigate the importance of CS, we produced and precisely examined mice that were deficient in the CS synthesizing enzyme, CSGalNAcT1 (T1KO). Biochemical analysis of T1KO revealed that loss of this enzyme reduced the amount of CS by approximately 50% in various brain regions. The amount of CS in PNNs was also diminished in T1KO compared to wild-type mice, although the amount of a major CS proteoglycan core protein, aggrecan, was not changed. In T1KO, we observed abnormalities in several behavioral tests, including the open-field test, acoustic startle response, and social preference. These results suggest that T1 is important for plasticity, probably due to regulation of CS-dependent PNNs, and that T1KO is a good model for investigation of PNNs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Nozomu", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tamada", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Asami", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Takao", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Miyakawa", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Igarashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13041-017-0328-5" }, "pmcid": { "normalized": "PMC5629790" }, "pmid": { "normalized": "28982363" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": true }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Chondroitin Sulfates", "descriptor_ui": "D002809", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "N-Acetylgalactosaminyltransferases", "descriptor_ui": "D017350", "major_topic": false }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Oct 5", "date_precision": "day", "issue": "1", "normalized_date": "2017-10-05", "pages": "47", "proceedings_title": null, "publisher": "", "title": "Molecular brain", "volume": "10", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Abnormalities in perineuronal nets and behavior in mice lacking CSGalNAcT1, a key enzyme in chondroitin sulfate synthesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Photodynamic therapy (PDT) utilizes photoirradiation in the presence of photosensitizers to ablate cancer cells via generation of singlet oxygen ((1)O(2)), but it is important to minimize concomitant injury to normal tissues. One approach for achieving this is to use activatable photosensitizers that can generate (1)O(2) only under specific conditions. Here, we report a novel photosensitizer that is selectively activated under hypoxia, a common condition in solid tumors. We found that introducing an azo moiety into the conjugated system of a seleno-rosamine dye effectively hinders the intersystem crossing process that leads to (1)O(2) generation. We show that the azo group is reductively cleaved in cells under hypoxia, enabling production of (1)O(2) to occur. In PDT in vitro, cells under mild hypoxia, within the range typically found in solid tumors (up to about 5% O(2)), were selectively ablated, leaving adjacent normoxic cells intact. This simple and practical azo-based strategy should be widely applicable to design a range of activatable photosensitizers.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Wen", "last_name": "Piao", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tomotsumi", "last_name": "Fujisawa", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tahei", "last_name": "Tahara", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.7b05019" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28872304" } }, "mesh": [ { "descriptor": "Azo Compounds", "descriptor_ui": "D001391", "major_topic": false }, { "descriptor": "Cell Hypoxia", "descriptor_ui": "D015687", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Photochemotherapy", "descriptor_ui": "D010778", "major_topic": true }, { "descriptor": "Photosensitizing Agents", "descriptor_ui": "D017319", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Oct 4", "date_precision": "day", "issue": "39", "normalized_date": "2017-10-04", "pages": "13713-13719", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "139", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of an Azo-Based Photosensitizer Activated under Mild Hypoxia for Photodynamic Therapy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ocular dominance plasticity is easily observed during the critical period in early postnatal life. Chondroitin sulfate (CS) is the most abundant component in extracellular structures called perineuronal nets (PNNs), which surround parvalbumin-expressing interneurons (PV-cells). CS accumulates in PNNs at the critical period, but its function in earlier life is unclear. Here, we show that initiation of ocular dominance plasticity was impaired with reduced CS, using mice lacking a key CS-synthesizing enzyme, CSGalNAcT1. Two-photon in vivo imaging showed a weaker visual response of PV-cells with reduced CS compared to wild-type mice. Plasticity onset was restored by a homeoprotein Otx2, which binds the major CS-proteoglycan aggrecan and promotes its further expression. Continuous CS accumulation together with Otx2 contributed bidirectionally to both onset and offset of plasticity, and was substituted by diazepam, which enhances GABA function. Therefore, CS and Otx2 may act as common inducers of both onset and offset of the critical period by promoting PV-cell function throughout the lifetime.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Xubin", "last_name": "Hou", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Tsukano", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuchio", "last_name": "Yanagawa", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Takao K.", "last_name": "Hensch", "name": null }, { "creator_type": "author", "first_name": "Katsuei", "last_name": "Shibuki", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Sugiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-04007-x" }, "pmcid": { "normalized": "PMC5626782" }, "pmid": { "normalized": "28974755" } }, "mesh": [ { "descriptor": "Aggrecans", "descriptor_ui": "D053674", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chondroitin Sulfates", "descriptor_ui": "D002809", "major_topic": false }, { "descriptor": "Diazepam", "descriptor_ui": "D003975", "major_topic": false }, { "descriptor": "Dominance, Ocular", "descriptor_ui": "D023882", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Interneurons", "descriptor_ui": "D007395", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "N-Acetylgalactosaminyltransferases", "descriptor_ui": "D017350", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Otx Transcription Factors", "descriptor_ui": "D051857", "major_topic": false }, { "descriptor": "Parvalbumins", "descriptor_ui": "D010320", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Visual Cortex", "descriptor_ui": "D014793", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Oct 3", "date_precision": "day", "issue": "1", "normalized_date": "2017-10-03", "pages": "12646", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Chondroitin Sulfate Is Required for Onset and Offset of Critical Period Plasticity in Visual Cortex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herpes simplex virus-1 (HSV-1) is the most common cause of sporadic viral encephalitis, which can be lethal or result in severe neurological defects even with antiviral therapy. While HSV-1 causes encephalitis in spite of HSV-1-specific humoral and cellular immunity, the mechanism by which HSV-1 evades the immune system in the central nervous system (CNS) remains unknown. Here we describe a strategy by which HSV-1 avoids immune targeting in the CNS. The HSV-1 UL13 kinase promotes evasion of HSV-1-specific CD8+ T cell accumulation in infection sites by downregulating expression of the CD8+ T cell attractant chemokine CXCL9 in the CNS of infected mice, leading to increased HSV-1 mortality due to encephalitis. Direct injection of CXCL9 into the CNS infection site enhanced HSV-1-specific CD8+ T cell accumulation, leading to marked improvements in the survival of infected mice. This previously uncharacterized strategy for HSV-1 evasion of CD8+ T cell accumulation in the CNS has important implications for understanding the pathogenesis and clinical treatment of HSV-1 encephalitis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Ayuko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ichinohe", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Takemura", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Kakuta", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Uematsu", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyono", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci92931" }, "pmcid": { "normalized": "PMC5617679" }, "pmid": { "normalized": "28891812" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "Chemokine CXCL9", "descriptor_ui": "D054370", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Encephalitis, Herpes Simplex", "descriptor_ui": "D020803", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Immune Evasion", "descriptor_ui": "D057131", "major_topic": true }, { "descriptor": "Immunity, Cellular", "descriptor_ui": "D007111", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Protein Kinases", "descriptor_ui": "D011494", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Oct 2", "date_precision": "day", "issue": "10", "normalized_date": "2017-10-02", "pages": "3784-3795", "proceedings_title": null, "publisher": "", "title": "The Journal of clinical investigation", "volume": "127", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Herpes simplex virus-1 evasion of CD8+ T cell accumulation contributes to viral encephalitis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mouse Langerhans cell (LC) network is established through the differentiation of embryonic LC precursors. BMP7 and TGFbeta1 initiate cellular signaling that is essential for inducing LC differentiation and preserving LCs in a quiescent state, respectively. Here we show that loss of Cbfbeta2, one of two RNA splice variants of the Cbfb gene, results in long-term persistence of embryonic LC precursors after their developmental arrest at the transition into the EpCAM(+) stage. This phenotype is caused by selective loss of BMP7-mediated signaling essential for LC differentiation, whereas TGFbetaR signaling is intact, maintaining cells in a quiescent state. Transgenic Cbfbeta2 expression at the neonatal stage, but not at the adult stage, restored differentiation from Cbfbeta2-deficient LC precursors. Loss of developmental potential in skin-residential precursor cells was accompanied by diminished BMP7-BMPR1A signaling. Collectively, our results reveal an essential requirement for the Cbfbeta2 variant in LC differentiation and provide novel insight into how the establishment and homeostasis of the LC network is regulated.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mari", "last_name": "Tenno", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null }, { "creator_type": "author", "first_name": "Sawako", "last_name": "Muroi", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Koseki", "name": null }, { "creator_type": "author", "first_name": "Kirill", "last_name": "Kryukov", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Imanishi", "name": null }, { "creator_type": "author", "first_name": "Florent", "last_name": "Ginhoux", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Taniuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1084/jem.20170729" }, "pmcid": { "normalized": "PMC5626404" }, "pmid": { "normalized": "28814567" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Morphogenetic Protein 7", "descriptor_ui": "D055419", "major_topic": false }, { "descriptor": "Bone Morphogenetic Protein Receptors, Type I", "descriptor_ui": "D052005", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Core Binding Factor beta Subunit", "descriptor_ui": "D050658", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Langerhans Cells", "descriptor_ui": "D007801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "Receptors, Transforming Growth Factor beta", "descriptor_ui": "D018125", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Oct 2", "date_precision": "day", "issue": "10", "normalized_date": "2017-10-02", "pages": "2933-2946", "proceedings_title": null, "publisher": "", "title": "The Journal of experimental medicine", "volume": "214", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Cbfbeta2 deficiency preserves Langerhans cell precursors by lack of selective TGFbeta receptor signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Significance: Hydrogen sulfide (H2S) plays roles in many physiological processes, including relaxation of vascular smooth muscles, mediation of neurotransmission, inhibition of insulin signaling, and regulation of inflammation. Also, hydropersulfide (R−S−SH) and polysulfide (−S−Sn−S−) have recently been identified as reactive sulfur species (RSS) that regulate the bioactivities of multiple proteins via S-sulfhydration of cysteine residues (protein Cys−SSH) and show cytoprotection. Chemical tools such as fluorescent probes and selective inhibitors are needed to establish in detail the physiological roles of H2S and polysulfide.Recent Advances: Although many fluorescent probes for H2S are available, fluorescent probes for hydropersulfide and polysulfide have only recently been developed and used to detect these sulfur species in living cells.Critical Issues: In this review, we summarize recent progress in developing chemical tools for the study of H2S, hydropersulfide, and polysulfide, covering fluorescent probes based on various design strategies and selective inhibitors of H2S- and polysulfide-producing enzymes (cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase), and we summarize their applications in biological studies.Future Directions: Despite recent progress, the precise biological functions of H2S, hydropersulfide, and polysulfide remain to be fully established. Fluorescent probes and selective inhibitors are effective chemical tools to study the physiological roles of these sulfur molecules in living cells and tissues. Therefore, further development of a broad range of practical fluorescent probes and selective inhibitors as tools for studies of RSS biology is currently attracting great interest. Antioxid. Redox Signal. 27, 669–683.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoko", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Honami", "last_name": "Echizen", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/ars.2017.7070" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28443673" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cystathionine beta-Synthase", "descriptor_ui": "D003541", "major_topic": false }, { "descriptor": "Cystathionine gamma-Lyase", "descriptor_ui": "D003542", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false }, { "descriptor": "Sulfurtransferases", "descriptor_ui": "D013466", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Oct 01", "date_precision": "day", "issue": "10", "normalized_date": "2017-10-01", "pages": "669-683", "proceedings_title": null, "publisher": "", "title": "Antioxidants & Redox Signaling", "volume": "27", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Fluorescent Probes and Selective Inhibitors for Biological Studies of Hydrogen Sulfide- and Polysulfide-Mediated Signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "VP26 is a herpes simplex virus 1 (HSV-1) small capsomere-interacting protein. In this study, we investigated the function of VP26 in HSV-1-infected cells with the following results. (i) The VP26 null mutation significantly impaired incorporation of minor capsid protein UL25 into nucleocapsids (type C capsids) in the nucleus. (ii) The VP26 mutation caused improper localization of UL25 in discrete punctate domains containing multiple capsid proteins (e.g., the VP5 major capsid protein) in the nucleus; these domains corresponded to capsid aggregates. (iii) The VP26 mutation significantly impaired packaging of replicated viral DNA genomes into capsids but had no effect on viral DNA concatemer cleavage. (iv) The VP26 mutation reduced the frequency of type C capsids, which contain viral DNA but not scaffolding proteins, and produced an accumulation of type A capsids, which lack both viral DNA and scaffold proteins, and had no effect on accumulation of type B capsids, which lack viral DNA but retain cleaved scaffold proteins. Collectively, these results indicated that VP26 was required for efficient viral DNA packaging and proper localization of nuclear capsids. The phenotype of the VP26 null mutation was similar to that reported previously of the UL25 null mutation and of UL25 mutations that preclude UL25 binding to capsids. Thus, VP26 appeared to regulate nucleocapsid maturation by promoting incorporation of UL25 into capsids, which is likely to be required for proper capsid nuclear localization.IMPORTANCE HSV-1 VP26 has been reported to be important for viral replication and virulence in cell cultures and/or mouse models. However, little is known about the function of VP26 during HSV-1 replication, in particular, in viral nucleocapsid maturation although HSV-1 nucleocapsids are estimated to contain 900 copies of VP26. In this study, we present data suggesting that VP26 promoted packaging of HSV-1 DNA genomes into capsids by regulating incorporation of capsid protein UL25 into capsids, which was reported to increase stability of the capsid structure. We also showed that VP26 was required for proper localization of capsids in the infected cell nucleus. This is the first report showing that HSV-1 VP26 is a regulator for nucleocapsid maturation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sagara", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01068-17" }, "pmcid": { "normalized": "PMC5571263" }, "pmid": { "normalized": "28679756" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Capsid Proteins", "descriptor_ui": "D036022", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Nucleocapsid", "descriptor_ui": "D019251", "major_topic": false }, { "descriptor": "Virus Assembly", "descriptor_ui": "D019065", "major_topic": true } ], "publication": { "conference_name": null, "date": "2017 Sep 15", "date_precision": "day", "issue": "18", "normalized_date": "2017-09-15", "pages": "e01068-17", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "91", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Herpes Simplex Virus 1 Small Capsomere-Interacting Protein VP26 Regulates Nucleocapsid Maturation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vertebrates, cephalopods and arthropods are equipped with eyes that have the highest spatiotemporal resolution among the animal phyla. In parallel, only animals in these three phyla have visual arrestin specialized for the termination of visual signaling triggered by opsin, in addition to ubiquitously expressed beta-arrestin that serves in terminating general G protein-coupled receptor signaling. Indeed, visual arrestin in Drosophila and rodents translocates to the opsin-rich subcellular region in response to light to reduce the overall sensitivity of photoreceptors in an illuminated environment (i.e. light adaptation). We thus hypothesized that, during evolution, visual arrestin has taken over the role of beta-arrestin in those animals with eyes of high spatiotemporal resolution. If this is true, it is expected that beta-arrestin plays a role similar to visual arrestin in those animals with low-resolution eyes. In the present study, we focused on the terrestrial mollusk Limax valentianus, a species related to cephalopods but that has only beta-arrestin, and generated antibodies against beta-arrestin. We found that beta-arrestin is highly expressed in photosensory neurons, and translocates into the microvilli of the rhabdomere within 30 min in response to short wavelength light (400 nm), to which the Limax eye exhibits a robust response. These observations suggest that beta-arrestin functions in the visual system of those animals that do not have visual arrestin. We also exploited anti-beta-arrestin antibody to visualize the optic nerve projecting to the brain, and demonstrated its usefulness for tracing a visual ascending pathway.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryota", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Takatori", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Matsuo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/jeb.162701" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28687596" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "beta-Arrestins", "descriptor_ui": "D000071557", "major_topic": false }, { "descriptor": "Gastropoda", "descriptor_ui": "D049851", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": true }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": true }, { "descriptor": "Photoreceptor Cells, Invertebrate", "descriptor_ui": "D017956", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Sep 15", "date_precision": "day", "issue": "Pt 18", "normalized_date": "2017-09-15", "pages": "3301-3314", "proceedings_title": null, "publisher": "", "title": "The Journal of experimental biology", "volume": "220", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Expression and light-dependent translocation of beta-arrestin in the visual system of the terrestrial slug Limax valentianus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Partner of sld five 1 (PSF1) is an evolutionary conserved DNA replication factor involved in DNA replication in lower species, which is strongly expressed in normal stem cell populations and progenitor cell populations. Recently, we have investigated PSF1 functions in cancer cells and found that PSF1 plays a significant role in tumour growth. These findings provide initial evidence for the potential of PSF1 as a therapeutic target. Here, we reveal that PSF1 contains an immunogenic epitope suitable for an antitumour vaccine. We analysed PSF1 peptides eluted from affinity-purified human leukocyte antigen (HLA) by mass spectrometry and identified PSF1(79-87) peptide (YLYDRLLRI) that has the highest prediction score using an in silico algorithm. PSF1(79-87) peptide induced PSF1-specific cytotoxic T lymphocyte responses such as the production of interferon-gamma and cytotoxicity. Because PSF1 is expressed in cancer cell populations and highly expressed in cancer stem cell populations, these data suggest that vaccination with PSF1(79-87) peptide may be a novel therapeutic strategy for cancer treatment.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mari", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yukichi", "last_name": "Ishioka", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Hirohisa", "last_name": "Okuyama", "name": null }, { "creator_type": "author", "first_name": "Motofumi", "last_name": "Iguchi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Nagira", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-11605-2" }, "pmcid": { "normalized": "PMC5593935" }, "pmid": { "normalized": "28894200" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigen Presentation", "descriptor_ui": "D017951", "major_topic": false }, { "descriptor": "ATP Binding Cassette Transporter, Subfamily B, Member 2", "descriptor_ui": "D000071181", "major_topic": false }, { "descriptor": "Cancer Vaccines", "descriptor_ui": "D019496", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "Cytotoxicity, Immunologic", "descriptor_ui": "D003602", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Epitopes, T-Lymphocyte", "descriptor_ui": "D018984", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Histocompatibility Antigens Class I", "descriptor_ui": "D015395", "major_topic": false }, { "descriptor": "HLA Antigens", "descriptor_ui": "D006680", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunogenicity, Vaccine", "descriptor_ui": "D000071497", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "T-Lymphocytes, Cytotoxic", "descriptor_ui": "D013602", "major_topic": false }, { "descriptor": "Tandem Mass Spectrometry", "descriptor_ui": "D053719", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Sep 11", "date_precision": "day", "issue": "1", "normalized_date": "2017-09-11", "pages": "11137", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Soluble HLA-associated peptide from PSF1 has a cancer vaccine potency.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chromatin reorganization is necessary for pluripotent stem cells, including embryonic stem cells (ESCs), to acquire lineage potential. However, it remains unclear how ESCs maintain their characteristic chromatin state for appropriate gene expression upon differentiation. Here, we demonstrate that chromodomain helicase DNA-binding domain 2 (Chd2) is required to maintain the differentiation potential of mouse ESCs. Chd2-depleted ESCs showed suppressed expression of developmentally regulated genes upon differentiation and subsequent differentiation defects without affecting gene expression in the undifferentiated state. Furthermore, chromatin immunoprecipitation followed by sequencing revealed alterations in the nucleosome occupancy of the histone variant H3.3 for developmentally regulated genes in Chd2-depleted ESCs, which in turn led to elevated trimethylation of the histone H3 lysine 27. These results suggest that Chd2 is essential in preventing suppressive chromatin formation for developmentally regulated genes and determines subsequent effects on developmental processes in the undifferentiated state.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Semba", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Chikara", "last_name": "Meno", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Mitsuho", "last_name": "Onimaru", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Nogami", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nar/gkx475" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28549158" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chromatin Assembly and Disassembly", "descriptor_ui": "D042002", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Mice, SCID", "descriptor_ui": "D016513", "major_topic": false }, { "descriptor": "Mouse Embryonic Stem Cells", "descriptor_ui": "D000066450", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Sep 06", "date_precision": "day", "issue": "15", "normalized_date": "2017-09-06", "pages": "8758-8772", "proceedings_title": null, "publisher": "", "title": "Nucleic Acids Research", "volume": "45", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Chd2 regulates chromatin for proper gene expression toward differentiation in mouse embryonic stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Antiviral compounds (eg, the neuraminidase inhibitor oseltamivir) are invaluable for the treatment of individuals infected with influenza A viruses of the H7N9 subtype (A[H7N9]), which have infected and killed hundreds of persons. However, oseltamivir treatment often leads to the emergence of resistant viruses in immunocompromised individuals. To better understand the emergence and properties of oseltamivir-resistant A(H7N9) viruses in immunosuppressed individuals, we infected immunosuppressed cynomolgus macaques with an A(H7N9) virus and treated them with oseltamivir. Disease severity and mortality were higher in immunosuppressed than in immunocompetent animals. Oseltamivir treatment at 2 different doses reduced A(H7N9) viral titers in infected animals, but even high-dose oseltamivir did not block viral replication sufficiently to suppress the emergence of resistant variants. Some resistant variants were not appreciably attenuated in cultured cells, but an oseltamivir-resistant A(H7N9) virus did not transmit among ferrets. These findings are useful for the control of A(H7N9) virus infections in clinical settings.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Maki", "last_name": "Kiso", "name": null }, { "creator_type": "author", "first_name": "Kiyoko", "last_name": "Iwatsuki-Horimoto", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Yamayoshi", "name": null }, { "creator_type": "author", "first_name": "Ryuta", "last_name": "Uraki", "name": null }, { "creator_type": "author", "first_name": "Mutsumi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Yuriko", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fukuyama", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Kazumasa", "last_name": "Ogasawara", "name": null }, { "creator_type": "author", "first_name": "Tiago J. S.", "last_name": "Lopes", "name": null }, { "creator_type": "author", "first_name": "Tokiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Louise H.", "last_name": "Moncla", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Thomas C.", "last_name": "Friedrich", "name": null }, { "creator_type": "author", "first_name": "Gabriele", "last_name": "Neumann", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kawaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/infdis/jix296" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28931216" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antiviral Agents", "descriptor_ui": "D000998", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Drug Resistance, Multiple, Viral", "descriptor_ui": "D024921", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hemagglutinin Glycoproteins, Influenza Virus", "descriptor_ui": "D019267", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Immunocompromised Host", "descriptor_ui": "D016867", "major_topic": true }, { "descriptor": "Influenza A Virus, H7N9 Subtype", "descriptor_ui": "D064766", "major_topic": false }, { "descriptor": "Macaca fascicularis", "descriptor_ui": "D008252", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neuraminidase", "descriptor_ui": "D009439", "major_topic": false }, { "descriptor": "Orthomyxoviridae Infections", "descriptor_ui": "D009976", "major_topic": false }, { "descriptor": "Oseltamivir", "descriptor_ui": "D053139", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Sep 1", "date_precision": "day", "issue": "5", "normalized_date": "2017-09-01", "pages": "582-593", "proceedings_title": null, "publisher": "", "title": "The Journal of infectious diseases", "volume": "216", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Emergence of Oseltamivir-Resistant H7N9 Influenza Viruses in Immunosuppressed Cynomolgus Macaques.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We recently demonstrated that prenatal exposure to valproic acid (VPA) at embryonic day 12.5 causes autism spectrum disorder (ASD)-like phenotypes such as hypolocomotion, anxiety-like behavior, social deficits and cognitive impairment in mice and that it decreases dendritic spine density in the hippocampal CA1 region. Previous studies show that some abnormal behaviors are improved by environmental enrichment in ASD rodent models, but it is not known whether environmental enrichment improves cognitive impairment. In the present study, we examined the effects of early environmental enrichment on behavioral abnormalities and neuromorphological changes in prenatal VPA-treated mice. We also examined the role of dendritic spine formation and synaptic protein expression in the hippocampus. Mice were housed for 4 weeks from 4 weeks of age under either a standard or enriched environment. Enriched housing was found to increase hippocampal brain-derived neurotrophic factor mRNA levels in both control and VPA-exposed mice. Furthermore, in VPA-treated mice, the environmental enrichment improved anxiety-like behavior, social deficits and cognitive impairment, but not hypolocomotion. Prenatal VPA treatment caused loss of dendritic spines in the hippocampal CA1 region and decreases in mRNA levels of postsynaptic density protein-95 and SH3 and multiple ankyrin repeat domains 2 in the hippocampus. These hippocampal changes were improved by the enriched housing. These findings suggest that the environmental enrichment improved most ASD-like behaviors including cognitive impairment in the VPA-treated mice by enhancing dendritic spine function.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Erika", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbr.2017.06.035" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28655565" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anticonvulsants", "descriptor_ui": "D000927", "major_topic": false }, { "descriptor": "Autistic Disorder", "descriptor_ui": "D001321", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Brain-Derived Neurotrophic Factor", "descriptor_ui": "D019208", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Disks Large Homolog 4 Protein", "descriptor_ui": "D000076122", "major_topic": false }, { "descriptor": "Environment", "descriptor_ui": "D004777", "major_topic": true }, { "descriptor": "Exploratory Behavior", "descriptor_ui": "D005106", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Interpersonal Relations", "descriptor_ui": "D007398", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Maze Learning", "descriptor_ui": "D018782", "major_topic": false }, { "descriptor": "Mental Disorders", "descriptor_ui": "D001523", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Prenatal Exposure Delayed Effects", "descriptor_ui": "D011297", "major_topic": false }, { "descriptor": "Valproic Acid", "descriptor_ui": "D014635", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug 30", "date_precision": "day", "issue": "", "normalized_date": "2017-08-30", "pages": "67-73", "proceedings_title": null, "publisher": "", "title": "Behavioural brain research", "volume": "333", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Environmental enrichment attenuates behavioral abnormalities in valproic acid-exposed autism model mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vascular normalization in tumors may improve drug delivery and anti-tumor immunity. Angiogenesis inhibitors induce hypoxia, which may facilitate malignant progression; therefore, we investigated other methods to promote vascular maturation. Here, we show that lysophosphatidic acid (LPA) enhances blood flow by promoting fine vascular networks, thereby improving vascular permeability and suppressing tumor growth when combined with anti-cancer drug treatment. Six different G protein-coupled receptors have been identified as LPA receptors (LPA1-6). In studies using mutant mice, we found that LPA4 is involved in vascular network formation. LPA4 activation induces circumferential actin bundling beneath the cell membrane and enhances linear adherens junction formation by VE-cadherin in endothelial cells. Therefore, we conclude that activation of LPA4 is a promising approach for vascular regulation.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takara", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Eino", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Iba", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Shigetomo", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Kishima", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2017.07.080" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28854359" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, CD", "descriptor_ui": "D015703", "major_topic": false }, { "descriptor": "Cadherin 5", "descriptor_ui": "D000099152", "major_topic": false }, { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Drug Delivery Systems", "descriptor_ui": "D016503", "major_topic": true }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Lysophospholipids", "descriptor_ui": "D008246", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Receptors, Lysophosphatidic Acid", "descriptor_ui": "D049368", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug 29", "date_precision": "day", "issue": "9", "normalized_date": "2017-08-29", "pages": "2072-2086", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "20", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Lysophosphatidic Acid Receptor 4 Activation Augments Drug Delivery in Tumors by Tightening Endothelial Cell-Cell Contact.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Little comparative information is available on the detailed intracellular dynamics (diffusion, active movement, and distribution mechanisms) of nanoparticles (100nm). Here, we quantitatively examined the intracellular movements of different-sized particles and of the endosomal vesicles containing those particles. We showed that silica nanoparticles of various sizes (30 to 100nm) had greater motility than sub-micron particles in A549 cells. Although particles of different sizes localized in the early endosomes, late endosomes, and lysosomes in different proportions, their motilities did not vary, regardless of the vesicles in which they were localized. However, surprisingly, endosomal vesicles containing silica nanoparticles moved faster than those containing sub-micron particles. These results suggest that nanoparticles included within endosomal vesicles do not suppress the motility of the vesicles, whereas sub-micron particles perturb endosomal vesicle transport. Our data support a new hypothesis that differences in particle size influence membrane trafficking of endosomal vesicles.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Michihiko", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Haruna", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Rio", "last_name": "Ishimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Higashisaka", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Tsutsumi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jconrel.2017.06.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28619623" } }, "mesh": [ { "descriptor": "A549 Cells", "descriptor_ui": "D000072283", "major_topic": false }, { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Endosomes", "descriptor_ui": "D011992", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy, Electron, Transmission", "descriptor_ui": "D046529", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": false }, { "descriptor": "Particle Size", "descriptor_ui": "D010316", "major_topic": false }, { "descriptor": "Silicon Dioxide", "descriptor_ui": "D012822", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug 28", "date_precision": "day", "issue": "", "normalized_date": "2017-08-28", "pages": "183-193", "proceedings_title": null, "publisher": "", "title": "Journal of controlled release : official journal of the Controlled Release Society", "volume": "260", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Intracellular trafficking of particles inside endosomal vesicles is regulated by particle size.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We adopted a spirocyclization-based strategy to design gamma-glutamyl hydroxymethyl selenorhodamine green (gGlu-HMSeR) as a photo-inactive compound that would be specifically cleaved by the tumor-associated enzyme gamma-glutamyltranspeptidase (GGT) to generate the potent photosensitizer HMSeR. gGlu-HMSeR has a spirocyclic structure and is colorless and does not show marked phototoxicity toward low-GGT-expressing cells or normal tissues upon irradiation with visible light. In contrast, HMSeR predominantly takes an open structure, is colored, and generates reactive oxygen species upon irradiation. The gamma-glutamyl group thus serves as a tumor-targeting moiety for photodynamic therapy (PDT), switching on tumor-cell-specific phototoxicity. To validate this system, we employed chick chorioallantoic membrane (CAM), a widely used model for preliminary evaluation of drug toxicity. Photoirradiation after gGlu-HMSeR treatment resulted in selective ablation of implanted tumor spheroids without damage to healthy tissue.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mayumi", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Norbert", "last_name": "Lange", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201704793" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28639393" } }, "mesh": [ { "descriptor": "A549 Cells", "descriptor_ui": "D000072283", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Drug Screening Assays, Antitumor", "descriptor_ui": "D004354", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "gamma-Glutamyltransferase", "descriptor_ui": "D005723", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Photochemotherapy", "descriptor_ui": "D010778", "major_topic": false }, { "descriptor": "Photosensitizing Agents", "descriptor_ui": "D017319", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Spiro Compounds", "descriptor_ui": "D013141", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug 21", "date_precision": "day", "issue": "35", "normalized_date": "2017-08-21", "pages": "10418-10422", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "56", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "An Activatable Photosensitizer Targeted to gamma-Glutamyltranspeptidase.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The selective serotonin (5-HT) reuptake inhibitors (SSRIs) are generally used for the treatment of major depressive disorders, and the 5-HT(1A) and sigma(1) receptors are considered to be targets for treatment of psychiatric disorders. Some SSRIs such as fluvoxamine have agonistic activity towards for the sigma(1) receptor, but it is not known whether the effect on the receptor plays a key role in the pharmacological effects. We have recently demonstrated that fluvoxamine shows an anti-anhedonic effect in picrotoxin-induced model of anxiety/depression, while the SSRI paroxetine, which have little affinity for the sigma(1) receptor, does not. We also suggest that the anti-anhedonic effect of fluvoxamine is mediated by combined activation of the 5-HT(1A) and sigma(1) receptors and it is associated with activation of prefrontal dopaminergic system. In these studies, picrotoxin-treated mice and adrenalectomized/castrated mice were used as decreased GABA(A) receptor function and neurosteroid-deficient models, respectively. These findings suggest that the functional interaction between the 5-HT(1A) and sigma(1) receptors activates prefrontal dopaminergic system under the conditions of decreased brain GABA(A) receptor function and the neurochemical effect is linked to the behavioral effect. This review summarizes the pharmacological role of the 5-HT(1A) and sigma(1) receptors, focusing on the functional interaction between these receptors, and the role of prefrontal dopaminergic system in depressive-like behaviors.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Hiramatsu", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ejphar.2017.05.035" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28529139" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mental Disorders", "descriptor_ui": "D001523", "major_topic": false }, { "descriptor": "Psychopharmacology", "descriptor_ui": "D011600", "major_topic": false }, { "descriptor": "Receptor, Serotonin, 5-HT1A", "descriptor_ui": "D044282", "major_topic": false }, { "descriptor": "Receptors, sigma", "descriptor_ui": "D017480", "major_topic": false }, { "descriptor": "Selective Serotonin Reuptake Inhibitors", "descriptor_ui": "D017367", "major_topic": false }, { "descriptor": "Sigma-1 Receptor", "descriptor_ui": "D000097605", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug 15", "date_precision": "day", "issue": "", "normalized_date": "2017-08-15", "pages": "172-177", "proceedings_title": null, "publisher": "", "title": "European journal of pharmacology", "volume": "809", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Psychopharmacology of combined activation of the serotonin(1A) and sigma(1) receptors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alternative splicing (AS) that occurs at the final coding exon (exon 47) of the Cav2.1 voltage-gated calcium channel (VGCC) gene produces two major isoforms in the brain, MPI and MPc. These isoforms differ in their splice acceptor sites; human MPI is translated into a polyglutamine tract associated with spinocerebellar ataxia type 6 (SCA6), whereas MPc splices to an immediate stop codon, resulting in a shorter cytoplasmic tail. To gain insight into the functional role of the AS in vivo and whether modulating the splice patterns at this locus can be a potential therapeutic strategy for SCA6, here we created knockin mice that exclusively express MPc by inserting the splice-site mutation. The resultant Cacna1aCtmKO/CtmKO mice developed non-progressive neurological phenotypes, featuring early-onset ataxia and absence seizure without significant alterations in the basic properties of the channel. Interactions of Cav2.1 with Cavbeta4 and Rimbp2 were significantly reduced while those with GABAB2 were enhanced in the cerebellum of Cacna1aCtmKO/CtmKO mice. Treatment with the GABAB antagonist CGP35348 partially rescued the motor impairments seen in Cacna1aCtmKO/CtmKO mice. These results suggest that the carboxyl-terminal domain of Cav2.1 is not essential for maintaining the basic properties of the channel in the cerebellar Purkinje neurons but is involved in multiple interactions of Cav2.1 with other proteins, and plays an essential role in preventing a complex neurological disease.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tomonori", "last_name": "Aikawa", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Mikuni", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Wakamori", "name": null }, { "creator_type": "author", "first_name": "Miyano", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Aizawa", "name": null }, { "creator_type": "author", "first_name": "Nobutaka", "last_name": "Ishizu", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Hidehiro", "last_name": "Mizusawa", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Watase", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/hmg/ddx193" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28510727" } }, "mesh": [ { "descriptor": "Alternative Splicing", "descriptor_ui": "D017398", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Channels", "descriptor_ui": "D015220", "major_topic": false }, { "descriptor": "Calcium Channels, N-Type", "descriptor_ui": "D020864", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Exons", "descriptor_ui": "D005091", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nervous System Diseases", "descriptor_ui": "D009422", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "RNA Isoforms", "descriptor_ui": "D059368", "major_topic": false }, { "descriptor": "RNA Splice Sites", "descriptor_ui": "D022821", "major_topic": false }, { "descriptor": "Spinocerebellar Ataxias", "descriptor_ui": "D020754", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug 15", "date_precision": "day", "issue": "16", "normalized_date": "2017-08-15", "pages": "3094-3104", "proceedings_title": null, "publisher": "", "title": "Human molecular genetics", "volume": "26", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Alternative splicing in the C-terminal tail of Cav2.1 is essential for preventing a neurological disease in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Foxp3 controls the development and function of regulatory T (Treg) cells, but it remains elusive how Foxp3 functions in vivo. Here, we established mouse models harboring three unique missense Foxp3 mutations that were identified in patients with the autoimmune disease IPEX. The I363V and R397W mutations were loss-of-function mutations, causing multi-organ inflammation by globally compromising Treg cell physiology. By contrast, the A384T mutation induced a distinctive tissue-restricted inflammation by specifically impairing the ability of Treg cells to compete with pathogenic T cells in certain non-lymphoid tissues. Mechanistically, repressed BATF expression contributed to these A384T effects. At the molecular level, the A384T mutation altered Foxp3 interactions with its specific target genes including Batf by broadening its DNA-binding specificity. Our findings identify BATF as a critical regulator of tissue Treg cells and suggest that sequence-specific perturbations of Foxp3-DNA interactions can influence specific facets of Treg cell physiology and the immunopathologies they regulate.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Norihito", "last_name": "Hayatsu", "name": null }, { "creator_type": "author", "first_name": "Takahisa", "last_name": "Miyao", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Takaho A.", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Ruka", "last_name": "Setoguchi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Watarai", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Takuwa", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Hisahiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Hori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.immuni.2017.07.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28778586" } }, "mesh": [ { "descriptor": "Alleles", "descriptor_ui": "D000483", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic-Leucine Zipper Transcription Factors", "descriptor_ui": "D050976", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 1", "descriptor_ui": "D003922", "major_topic": false }, { "descriptor": "Diarrhea", "descriptor_ui": "D003967", "major_topic": false }, { "descriptor": "DNA Mutational Analysis", "descriptor_ui": "D004252", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Genetic Diseases, X-Linked", "descriptor_ui": "D040181", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune System Diseases", "descriptor_ui": "D007154", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mutation, Missense", "descriptor_ui": "D020125", "major_topic": false }, { "descriptor": "Organ Specificity", "descriptor_ui": "D009928", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug 15", "date_precision": "day", "issue": "2", "normalized_date": "2017-08-15", "pages": "268-283.e9", "proceedings_title": null, "publisher": "", "title": "Immunity", "volume": "47", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Analyses of a Mutant Foxp3 Allele Reveal BATF as a Critical Transcription Factor in the Differentiation and Accumulation of Tissue Regulatory T Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Elimination of early-formed redundant synapses during postnatal development is essential for functional neural circuit formation. Purkinje cells (PCs) in the neonatal cerebellum are innervated by multiple climbing fibers (CFs). A single CF is strengthened whereas the other CFs are eliminated in each PC dependent on postsynaptic activity in PC, but the underlying mechanisms are largely unknown. Here, we report that brain-derived neurotrophic factor (BDNF) from PC facilitates CF synapse elimination. By PC-specific deletion of BDNF combined with knockdown of BDNF receptors in CF, we show that BDNF acts retrogradely on TrkB in CFs, and facilitates elimination of CF synapses from PC somata during the third postnatal week. We also show that BDNF shares signaling pathway with metabotropic glutamate receptor 1, a key molecule that triggers a canonical pathway for CF synapse elimination. These results indicate that unlike other synapses, BDNF mediates punishment signal for synapse elimination in the developing cerebellum.During development, synapses are selectively strengthened or eliminated by activity-dependent competition. Here, the authors show that BDNF-TrkB retrograde signaling is a \"punishment\" signal that leads to elimination of climbing fiber-onto-Purkinje cell synapses in the developing cerebellum.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Myeongjeong", "last_name": "Choo", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Meiko", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Jianling", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Asami", "last_name": "Tanimura", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-017-00260-w" }, "pmcid": { "normalized": "PMC5543168" }, "pmid": { "normalized": "28775326" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Brain-Derived Neurotrophic Factor", "descriptor_ui": "D019208", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Receptor, trkB", "descriptor_ui": "D020813", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug 4", "date_precision": "day", "issue": "1", "normalized_date": "2017-08-04", "pages": "195", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Retrograde BDNF to TrkB signaling promotes synapse elimination in the developing cerebellum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Kemp elimination reaction is a well-known chemical reaction that is facilitated on a protein surface microenvironment, and in particular is highly accelerated in a unique binding pocket of serum albumin. We have designed and synthesized a fluorescently activatable coumarin derivative with a benzisoxazole scaffold to enable monitoring of the Kemp elimination reaction in terms of fluorescence change for the first time. We show that this fluorescent sensor can sensitively and selectively quantitate serum albumin in blood samples. It also works in a dry-chemistry format.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shingo", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bmcl.2017.05.076" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28587820" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cattle", "descriptor_ui": "D002417", "major_topic": false }, { "descriptor": "Coumarins", "descriptor_ui": "D003374", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Isoxazoles", "descriptor_ui": "D007555", "major_topic": false }, { "descriptor": "Serum Albumin", "descriptor_ui": "D012709", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug 1", "date_precision": "day", "issue": "15", "normalized_date": "2017-08-01", "pages": "3464-3467", "proceedings_title": null, "publisher": "", "title": "Bioorganic & medicinal chemistry letters", "volume": "27", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Fluorescence detection of serum albumin with a turnover-based sensor utilizing Kemp elimination reaction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reactive oxygen species (ROS), originally characterized based on their harmful effects on cells or organisms, are now recognized as important signal molecules regulating various biological processes. In particular, low levels of ROS released from mitochondria extend lifespan. Here, we identified a novel mechanism of generating appropriate levels of ROS at the plasma membrane through a peroxidase and dual oxidase (DUOX) system, which could extend lifespan in Caenorhabditis elegans A redox co-factor, pyrroloquinoline quinone (PQQ), activates the C. elegans DUOX protein BLI-3 to produce the ROS H2O2 at the plasma membrane, which is subsequently degraded by peroxidase (MLT-7), eventually ensuring adequate levels of ROS. These ROS signals are transduced mainly by the oxidative stress transcriptional factors SKN-1 (Nrf2 or NFE2L2 in mammals) and JUN-1, and partially by DAF-16 (a FOXO protein homolog). Cell biology experiments demonstrated a similarity between the mechanisms of PQQ-induced activation of human DUOX1 and DUOX2 and that of C. elegans BLI-3, suggesting that DUOXs are potential targets of intervention for lifespan extension. We propose that low levels of ROS, fine-tuned by the peroxidase and dual oxidase system at the plasma membrane, act as second messengers to extend lifespan by the effect of hormesis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Sasakura", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Moribe", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Ikemoto", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Ikue", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/jcs.202119" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28676501" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": false }, { "descriptor": "Dual Oxidases", "descriptor_ui": "D000074623", "major_topic": false }, { "descriptor": "Longevity", "descriptor_ui": "D008136", "major_topic": false }, { "descriptor": "Oxidoreductases", "descriptor_ui": "D010088", "major_topic": false }, { "descriptor": "Peroxidase", "descriptor_ui": "D009195", "major_topic": false }, { "descriptor": "PQQ Cofactor", "descriptor_ui": "D045542", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug 1", "date_precision": "day", "issue": "15", "normalized_date": "2017-08-01", "pages": "2631-2643", "proceedings_title": null, "publisher": "", "title": "Journal of cell science", "volume": "130", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Lifespan extension by peroxidase and dual oxidase-mediated ROS signaling through pyrroloquinoline quinone in C. elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Since induced regulatory T cells (iTregs) can be produced in a large quantity in vitro, these cells are expected to be clinically useful to induce immunological tolerance in various immunological diseases. Foxp3 (Forkhead box P3) expression in iTregs is, however, unstable due to the lack of demethylation of the CpG island in the conserved non-coding sequence 2 (CNS2) of the Foxp3 locus. To facilitate the demethylation of CNS2, we over-expressed the catalytic domain (CD) of the ten-eleven translocation (TET) protein, which catalyzes the steps of the iterative demethylation of 5-methylcytosine. TET-CD over-expression in iTregs resulted in partial demethylation of CNS2 and stable Foxp3 expression. We also discovered that TET expression was enhanced under low oxygen (5%) culture conditions, which facilitated CNS2 DNA demethylation and stabilization of Foxp3 expression in a TET2- and TET3-dependent manner. In combination with vitamin C treatment, which has been reported to enhance TET catalytic activity, iTregs generated under low oxygen conditions retained more stable Foxp3 expression in vitro and in vivo and exhibited stronger suppression activity in a colitis model compared with untreated iTregs. Our data indicate that the induction and activation of TET enzymes in iTregs would be an effective method for Treg-mediated adoptive immunotherapy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazue", "last_name": "Someya", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Nakatsukasa", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Kenn-Ichi", "last_name": "Tateda", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Akanuma", "name": null }, { "creator_type": "author", "first_name": "Ikuko", "last_name": "Koya", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Sanosaka", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Kohyama", "name": null }, { "creator_type": "author", "first_name": "Yu-Ichi", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Takeji", "last_name": "Takamura-Enya", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/intimm/dxx049" }, "pmcid": { "normalized": "PMC5890887" }, "pmid": { "normalized": "29048538" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ascorbic Acid", "descriptor_ui": "D001205", "major_topic": false }, { "descriptor": "Colitis", "descriptor_ui": "D003092", "major_topic": false }, { "descriptor": "Conserved Sequence", "descriptor_ui": "D017124", "major_topic": false }, { "descriptor": "CpG Islands", "descriptor_ui": "D018899", "major_topic": false }, { "descriptor": "Demethylation", "descriptor_ui": "D000073398", "major_topic": false }, { "descriptor": "Dioxygenases", "descriptor_ui": "D049308", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Enzyme Induction", "descriptor_ui": "D004790", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypoxia", "descriptor_ui": "D000860", "major_topic": false }, { "descriptor": "Immunotherapy, Adoptive", "descriptor_ui": "D016219", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "T-Lymphocyte Subsets", "descriptor_ui": "D016176", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug 1", "date_precision": "day", "issue": "8", "normalized_date": "2017-08-01", "pages": "365-375", "proceedings_title": null, "publisher": "", "title": "International immunology", "volume": "29", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Improvement of Foxp3 stability through CNS2 demethylation by TET enzyme induction and activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Programmed cell death 1 (PD-1) is highly expressed on exhausted T cells and inhibits T cell activation. Antibodies that block the interaction between PD-1 and its ligand prevent this inhibitory signal and reverse T cell dysfunction, providing beneficial anti-tumor responses in a substantial number of patients. Mechanisms for the induction and maintenance of high PD-1 expression on exhausted T cells have not been fully understood. Utilizing a genome-wide loss-of-function screening method based on the CRISPR-Cas9 system, we identified genes involved in the core fucosylation pathway as positive regulators of cell-surface PD-1 expression. Inhibition of Fut8, a core fucosyltransferase, by genetic ablation or pharmacologic inhibition reduced cell-surface expression of PD-1 and enhanced T cell activation, leading to more efficient tumor eradication. Taken together, our findings suggest that blocking core fucosylation of PD-1 can be a promising strategy for improving anti-tumor immune responses.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Sana", "last_name": "Hibino", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Machiyama", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Yokosuka", "name": null }, { "creator_type": "author", "first_name": "Miyako", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2017.07.027" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28768188" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Fucosyltransferases", "descriptor_ui": "D005647", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": false }, { "descriptor": "Glycosylation", "descriptor_ui": "D006031", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunity, Cellular", "descriptor_ui": "D007111", "major_topic": true }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasm Proteins", "descriptor_ui": "D009363", "major_topic": true }, { "descriptor": "Neoplasms, Experimental", "descriptor_ui": "D009374", "major_topic": true }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": true }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug 1", "date_precision": "day", "issue": "5", "normalized_date": "2017-08-01", "pages": "1017-1028", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "20", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Blockage of Core Fucosylation Reduces Cell-Surface Expression of PD-1 and Promotes Anti-tumor Immune Responses of T Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescence lifetime imaging microscopy (FLIM)-based Forster resonance energy transfer (FRET) measurement (FLIM-FRET) is one of the powerful methods for imaging of intracellular protein activities such as protein-protein interactions and conformational changes. Here, using saturation mutagenesis, we developed a dark yellow fluorescent protein named ShadowY that can serve as an acceptor for FLIM-FRET. ShadowY is spectrally similar to the previously reported dark YFP but has a much smaller quantum yield, greater extinction coefficient, and superior folding property. When ShadowY was paired with mEGFP or a Clover mutant (Clover(T153M/F223R)) and applied to a single-molecule FRET sensor to monitor a light-dependent conformational change of the light-oxygen-voltage domain 2 (LOV2) in HeLa cells, we observed a large FRET signal change with low cell-to-cell variability, allowing for precise measurement of individual cell responses. In addition, an application of ShadowY to a separate-type Ras FRET sensor revealed an EGF-dependent large FRET signal increase. Thus, ShadowY in combination with mEGFP or Clover(T153M/F223R) is a promising FLIM-FRET acceptor.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Akihiro C. E.", "last_name": "Shibata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-07002-4" }, "pmcid": { "normalized": "PMC5533704" }, "pmid": { "normalized": "28754922" } }, "mesh": [ { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Protein Domains", "descriptor_ui": "D000072417", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul 28", "date_precision": "day", "issue": "1", "normalized_date": "2017-07-28", "pages": "6791", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "ShadowY: a dark yellow fluorescent protein for FLIM-based FRET measurement.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The eukaryotic genome is organized within cells as chromatin. For proper information output, higher-order chromatin structures can be regulated dynamically. How such structures form and behave in various cellular processes remains unclear. Here, by combining super-resolution imaging (photoactivated localization microscopy [PALM]) and single-nucleosome tracking, we developed a nuclear imaging system to visualize the higher-order structures along with their dynamics in live mammalian cells. We demonstrated that nucleosomes form compact domains with a peak diameter of approximately 160 nm and move coherently in live cells. The heterochromatin-rich regions showed more domains and less movement. With cell differentiation, the domains became more apparent, with reduced dynamics. Furthermore, various perturbation experiments indicated that they are organized by a combination of factors, including cohesin and nucleosome-nucleosome interactions. Notably, we observed the domains during mitosis, suggesting that they act as building blocks of chromosomes and may serve as information units throughout the cell cycle.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "contributor", "first_name": "Tadasu", "last_name": "Nozaki", "name": null }, { "creator_type": "contributor", "first_name": "Ryosuke", "last_name": "Imai", "name": null }, { "creator_type": "contributor", "first_name": "Mai", "last_name": "Tanbo", "name": null }, { "creator_type": "contributor", "first_name": "Ryosuke", "last_name": "Nagashima", "name": null }, { "creator_type": "contributor", "first_name": "Sachiko", "last_name": "Tamura", "name": null }, { "creator_type": "contributor", "first_name": "Tomomi", "last_name": "Tani", "name": null }, { "creator_type": "contributor", "first_name": "Yasumasa", "last_name": "Joti", "name": null }, { "creator_type": "contributor", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "contributor", "first_name": "Kayo", "last_name": "Hibino", "name": null }, { "creator_type": "contributor", "first_name": "Masato T.", "last_name": "Kanemaki", "name": null }, { "creator_type": "contributor", "first_name": "Kerstin S.", "last_name": "Wendt", "name": null }, { "creator_type": "contributor", "first_name": "Yasushi", "last_name": "Okada", "name": null }, { "creator_type": "contributor", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "contributor", "first_name": "Kazuhiro", "last_name": "Maeshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.molcel.2017.06.018" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Jul 20", "date_precision": "day", "issue": "", "normalized_date": "2017-07-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "", "volume": "67", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic Organization of Chromatin Domains Revealed by Super-Resolution Live-Cell Imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The central channel of the nuclear pore complex (NPC) is occupied by non-structured polypeptides with a high content of Phe-Gly (FG) motifs. This protein-rich environment functions as an entropic barrier that prevents the passage of molecules, as well as the binding sites for karyopherins, to regulate macromolecular traffic between the nucleoplasm and the cytoplasm. In this study, we expressed individual Nups fused with a crowding-sensitive probe (GimRET) to determine the spatial distribution of protein-rich domains within the central channel in vivo, and characterize the properties of the entropic barrier. Analyses of the probe signal revealed that the central channel contains two protein-rich domains at both the nucleoplasmic and cytoplasmic peripheries, and a less-crowded central cavity. Karyopherins and other soluble proteins are not the constituents of the protein-rich domains. The time-lapse observation of the post-mitotic reassembly process also revealed how individual protein-rich domains are constructed by a sequential assembly of nucleoporins.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hide A.", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Asai", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Shige H.", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-05959-w" }, "pmcid": { "normalized": "PMC5515885" }, "pmid": { "normalized": "28720791" } }, "mesh": [ { "descriptor": "Active Transport, Cell Nucleus", "descriptor_ui": "D021581", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Karyopherins", "descriptor_ui": "D028884", "major_topic": false }, { "descriptor": "Macromolecular Substances", "descriptor_ui": "D046911", "major_topic": false }, { "descriptor": "Nuclear Pore", "descriptor_ui": "D022022", "major_topic": false }, { "descriptor": "Nuclear Pore Complex Proteins", "descriptor_ui": "D028861", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul 18", "date_precision": "day", "issue": "1", "normalized_date": "2017-07-18", "pages": "5709", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "In vivo analysis of protein crowding within the nuclear pore complex in interphase and mitosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Astrocytes regulate synaptic transmission through controlling neurotransmitter concentrations around synapses. Little is known, however, about their roles in neural circuit development. Here we report that Bergmann glia (BG), specialized cerebellar astrocytes that thoroughly enwrap Purkinje cells (PCs), are essential for synaptic organization in PCs through the action of the l-glutamate/l-aspartate transporter (GLAST). In GLAST-knockout mice, dendritic innervation by the main ascending climbing fiber (CF) branch was significantly weakened, whereas the transverse branch, which is thin and nonsynaptogenic in control mice, was transformed into thick and synaptogenic branches. Both types of CF branches frequently produced aberrant wiring to proximal and distal dendrites, causing multiple CF-PC innervation. Our electrophysiological analysis revealed that slow and small CF-evoked excitatory postsynaptic currents (EPSCs) were recorded from almost all PCs in GLAST-knockout mice. These atypical CF-EPSCs were far more numerous and had significantly faster 10-90% rise time than those elicited by glutamate spillover under pharmacological blockade of glial glutamate transporters. Innervation by parallel fibers (PFs) was also affected. PF synapses were robustly increased in the entire dendritic trees, leading to impaired segregation of CF and PF territories. Furthermore, lamellate BG processes were retracted from PC dendrites and synapses, leading to the exposure of these neuronal elements to the extracellular milieus. These synaptic and glial phenotypes were reproduced in wild-type mice after functional blockade of glial glutamate transporters. These findings highlight that glutamate transporter function by GLAST on BG plays important roles in development and maintenance of proper synaptic wiring and wrapping in PCs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Miwako", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Kohda", "name": null }, { "creator_type": "author", "first_name": "Michisuke", "last_name": "Yuzaki", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Shimamoto", "name": null }, { "creator_type": "author", "first_name": "Kohichi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1617330114" }, "pmcid": { "normalized": "PMC5514701" }, "pmid": { "normalized": "28655840" } }, "mesh": [ { "descriptor": "Amino Acid Transport System X-AG", "descriptor_ui": "D027322", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Excitatory Amino Acid Transporter 1", "descriptor_ui": "D027341", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neuroglia", "descriptor_ui": "D009457", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul 11", "date_precision": "day", "issue": "28", "normalized_date": "2017-07-11", "pages": "7438-7443", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "114", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Glutamate transporter GLAST controls synaptic wrapping by Bergmann glia and ensures proper wiring of Purkinje cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Indocyanine green (ICG) derivatives having nucleophilic substituents were synthesized as pH-responsive near-infrared dyes. pH-responsive dyes 1-C with closed-ring structures smoothly internalized and converted to emissive open-ring structures 1-O in response to relatively low pHs in acidic intracellular compartments of HeLa cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Oride", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Akiyo", "last_name": "Morinibu", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c7cc03035e" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28650501" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Jul 6", "date_precision": "day", "issue": "55", "normalized_date": "2017-07-06", "pages": "7792-7795", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "53", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "pH-Responsive near-infrared fluorescent cyanine dyes for molecular imaging based on pH sensing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The genome is 3-dimensionally organized in the cell, and the mammalian genome DNA is partitioned into submegabase-sized chromatin domains. Genome functions are regulated within and across the domains according to their organization, whereas the chromatin itself is highly dynamic. However, the details of such dynamic organization of chromatin domains in living cells remain unclear. To unify chromatin dynamics and organization, we recently demonstrated that structural information of chromatin domains in living human cells can be extracted from analyses of the subdiffusive nucleosome movement using mathematical modeling. Our mathematical analysis suggested that as the chromatin domain becomes smaller and more compact, nucleosome movement becomes increasingly restricted. Here, we show the implication of these results for bridging the gap between chromatin dynamics and organization, and provide physical insight into chromatin domains as efficient units to conduct genome functions in the thermal noisy environment of the cell.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Tadasu", "last_name": "Nozaki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Maeshima", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Togashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/19491034.2017.1313937" }, "pmcid": { "normalized": "PMC5597300" }, "pmid": { "normalized": "28406741" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Chromatin Assembly and Disassembly", "descriptor_ui": "D042002", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": true }, { "descriptor": "Diffusion", "descriptor_ui": "D004058", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": true }, { "descriptor": "Nucleosomes", "descriptor_ui": "D009707", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul 4", "date_precision": "day", "issue": "4", "normalized_date": "2017-07-04", "pages": "353-359", "proceedings_title": null, "publisher": "", "title": "Nucleus (Austin, Tex.)", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Bridging the dynamics and organization of chromatin domains by mathematical modeling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Silicon-substituted xanthene dyes, with Si in place of the O atom at the xanthene 10-position, are practically useful as far-red to near-infrared fluorophores. Many fluorescent probes based on them have recently been reported. These fluorophores retain the advantages of typical xanthene dyes and also show unique properties suitable for applications such as multi-color and super-resolution imaging.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ikeno", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/asia.201700385" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28452155" } }, "mesh": [ { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Photochemical Processes", "descriptor_ui": "D055668", "major_topic": false }, { "descriptor": "Silicon", "descriptor_ui": "D012825", "major_topic": false }, { "descriptor": "Xanthenes", "descriptor_ui": "D014966", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul 4", "date_precision": "day", "issue": "13", "normalized_date": "2017-07-04", "pages": "1435-1446", "proceedings_title": null, "publisher": "", "title": "Chemistry, an Asian journal", "volume": "12", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Silicon-substituted Xanthene Dyes and Their Unique Photophysical Properties for Fluorescent Probes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The chemokine receptor CCR7 directs T cell relocation into and within lymphoid organs, including the migration of developing thymocytes into the thymic medulla. However, how three functional CCR7 ligands in mouse, CCL19, CCL21Ser, and CCL21Leu, divide their roles in immune organs is unclear. By producing mice specifically deficient in CCL21Ser, we show that CCL21Ser is essential for the accumulation of positively selected thymocytes in the thymic medulla. CCL21Ser-deficient mice were impaired in the medullary deletion of self-reactive thymocytes and developed autoimmune dacryoadenitis. T cell accumulation in the lymph nodes was also defective. These results indicate a nonredundant role of CCL21Ser in the establishment of self-tolerance in T cells in the thymic medulla, and reveal a functional inequality among CCR7 ligands in vivo.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mina", "last_name": "Kozai", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyonari", "name": null }, { "creator_type": "author", "first_name": "Karin", "last_name": "Schaeuble", "name": null }, { "creator_type": "author", "first_name": "Sanjiv A.", "last_name": "Luther", "name": null }, { "creator_type": "author", "first_name": "Naozumi", "last_name": "Ishimaru", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Ohigashi", "name": null }, { "creator_type": "author", "first_name": "Yousuke", "last_name": "Takahama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1084/jem.20161864" }, "pmcid": { "normalized": "PMC5502431" }, "pmid": { "normalized": "28611158" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autoimmune Diseases", "descriptor_ui": "D001327", "major_topic": false }, { "descriptor": "Central Tolerance", "descriptor_ui": "D061167", "major_topic": false }, { "descriptor": "Chemokine CCL21", "descriptor_ui": "D054421", "major_topic": false }, { "descriptor": "Dacryocystitis", "descriptor_ui": "D003607", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Receptors, CCR7", "descriptor_ui": "D054400", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "Self Tolerance", "descriptor_ui": "D017634", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false }, { "descriptor": "Thymocytes", "descriptor_ui": "D060168", "major_topic": false }, { "descriptor": "Thymus Gland", "descriptor_ui": "D013950", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul 3", "date_precision": "day", "issue": "7", "normalized_date": "2017-07-03", "pages": "1925-1935", "proceedings_title": null, "publisher": "", "title": "The Journal of experimental medicine", "volume": "214", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Essential role of CCL21 in establishment of central self-tolerance in T cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Plakoglobin, also known as gamma-catenin, is a close homolog of beta-catenin and interacts with shared protein partners. Functions of beta-catenin in cell adhesion are well-documented in terms of maintaining endothelial barrier function by interacting with vascular endothelial (VE)-cadherin. Plakoglobin also interacts with VE-cadherin, but its function in cell adhesion is not well understood. Here, we investigated plakoglobin function in vascular endothelial cell (ECs)-cell junction integrity. Knock-down of plakoglobin expression in ECs did not prevent cell proliferation or cell migration, but induced destabilization of the membrane distribution of VE-cadherin and resulted in increased permeability. Plakoglobin contributes to VE-cadherin-dependent adhesion in the steady state, but on stimulation with vascular endothelial growth factor (VEGF), it is essential for inducing sufficient VE-cadherin phosphorylation on VEGF signaling, thereby destabilizing cell-cell junctions. Furthermore, knock-down of plakoglobin expression increased vascular endothelial protein tyrosine phosphatase activity, an endothelial-specific membrane protein associating with VE-cadherin. These results indicate that plakoglobin plays multiple roles in regulation of cell-cell adhesion in a context dependent manner.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Iba", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jb/mvx001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28158602" } }, "mesh": [ { "descriptor": "Antigens, CD", "descriptor_ui": "D015703", "major_topic": false }, { "descriptor": "Cadherin 5", "descriptor_ui": "D000099152", "major_topic": false }, { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "gamma Catenin", "descriptor_ui": "D051185", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Junctions", "descriptor_ui": "D007365", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factors", "descriptor_ui": "D042442", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul 1", "date_precision": "day", "issue": "1", "normalized_date": "2017-07-01", "pages": "55-62", "proceedings_title": null, "publisher": "", "title": "Journal of biochemistry", "volume": "162", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Plakoglobin maintains the integrity of vascular endothelial cell junctions and regulates VEGF-induced phosphorylation of VE-cadherin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Koichi", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Matsuyama", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kainuma", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Mao", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Saeko", "last_name": "Hamaoka", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Itatani", "name": null }, { "creator_type": "author", "first_name": "Teiji", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12872-017-0612-4" }, "pmcid": { "normalized": "PMC5493014" }, "pmid": { "normalized": "28666420" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Jun 30", "date_precision": "day", "issue": "1", "normalized_date": "2017-06-30", "pages": "172", "proceedings_title": null, "publisher": "", "title": "BMC cardiovascular disorders", "volume": "17", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Erratum to: Vector flow mapping analysis of left ventricular energetic performance in healthy adult volunteers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human myosin VIIa (MYO7A) is an actin-linked motor protein associated with human Usher syndrome (USH) type 1B, which causes human congenital hearing and visual loss. Although it has been thought that the role of human myosin VIIa is critical for USH1 protein tethering with actin and transportation along actin bundles in inner-ear hair cells, myosin VIIa's motor function remains unclear. Here, we studied the motor function of the tail-truncated human myosin VIIa dimer (HM7AΔTail/LZ) at the single-molecule level. We found that the HM7AΔTail/LZ moves processively on single actin filaments with a step size of 35 nm. Dwell-time distribution analysis indicated an average waiting time of 3.4 s, yielding ∼0.3 s−1 for the mechanical turnover rate; hence, the velocity of HM7AΔTail/LZ was extremely slow, at 11 nm·s−1. We also examined HM7AΔTail/LZ movement on various actin structures in demembranated cells. HM7AΔTail/LZ showed unidirectional movement on actin structures at cell edges, such as lamellipodia and filopodia. However, HM7AΔTail/LZ frequently missed steps on actin tracks and exhibited bidirectional movement at stress fibers, which was not observed with tail-truncated myosin Va. These results suggest that the movement of the human myosin VIIa motor protein is more efficient on lamellipodial and filopodial actin tracks than on stress fibers, which are composed of actin filaments with different polarity, and that the actin structures influence the characteristics of cargo transportation by human myosin VIIa. In conclusion, myosin VIIa movement appears to be suitable for translocating USH1 proteins on stereocilia actin bundles in inner-ear hair cells.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Osamu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Tsukasaki", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takeomi", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Ikebe", "name": null }, { "creator_type": "author", "first_name": "Mitsuo", "last_name": "Ikebe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m116.765966" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28507101" } }, "mesh": [ { "descriptor": "3T3 Cells", "descriptor_ui": "D016475", "major_topic": false }, { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myosin Heavy Chains", "descriptor_ui": "D018995", "major_topic": false }, { "descriptor": "Myosin Type V", "descriptor_ui": "D024701", "major_topic": false }, { "descriptor": "Myosin VIIa", "descriptor_ui": "D000081412", "major_topic": false }, { "descriptor": "Myosins", "descriptor_ui": "D009218", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Pseudopodia", "descriptor_ui": "D011554", "major_topic": false }, { "descriptor": "Sequence Deletion", "descriptor_ui": "D017384", "major_topic": false }, { "descriptor": "Usher Syndromes", "descriptor_ui": "D052245", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun 30", "date_precision": "day", "issue": "26", "normalized_date": "2017-06-30", "pages": "10950-10960", "proceedings_title": null, "publisher": "", "title": "The Journal of Biological Chemistry", "volume": "292", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Human myosin VIIa is a very slow processive motor protein on various cellular actin structures.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Major depression is a common cause of chronic disability. Despite decades of efforts, no equivocally accepted animal model is available for studying depression. We tested the validity of a new model based on the three-hit concept of vulnerability and resilience. Genetic predisposition (hit 1, mutation of pituitary adenylate cyclase-activating polypeptide, PACAP gene), early-life adversity (hit 2, 180-min maternal deprivation, MD180) and chronic variable mild stress (hit 3, CVMS) were combined. Physical, endocrinological, behavioral and functional morphological tools were used to validate the model. Body- and adrenal weight changes as well as corticosterone titers proved that CVMS was effective. Forced swim test indicated increased depression in CVMS PACAP heterozygous (Hz) mice with MD180 history, accompanied by elevated anxiety level in marble burying test. Corticotropin-releasing factor neurons in the oval division of the bed nucleus of the stria terminalis showed increased FosB expression, which was refractive to CVMS exposure in wild-type and Hz mice. Urocortin1 neurons became over-active in CMVS-exposed PACAP knock out (KO) mice with MD180 history, suggesting the contribution of centrally projecting Edinger-Westphal nucleus to the reduced depression and anxiety level of stressed KO mice. Serotoninergic neurons of the dorsal raphe nucleus lost their adaptation ability to CVMS in MD180 mice. In conclusion, the construct and face validity criteria suggest that MD180 PACAP HZ mice on CD1 background upon CVMS may be used as a reliable model for the three-hit theory.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Jozsef", "last_name": "Farkas", "name": null }, { "creator_type": "author", "first_name": "Laszlo A.", "last_name": "Kovacs", "name": null }, { "creator_type": "author", "first_name": "Laszlo", "last_name": "Gaspar", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Nafz", "name": null }, { "creator_type": "author", "first_name": "Tamas", "last_name": "Gaszner", "name": null }, { "creator_type": "author", "first_name": "Balazs", "last_name": "Ujvari", "name": null }, { "creator_type": "author", "first_name": "Viktoria", "last_name": "Kormos", "name": null }, { "creator_type": "author", "first_name": "Valer", "last_name": "Csernus", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Dora", "last_name": "Reglodi", "name": null }, { "creator_type": "author", "first_name": "Balazs", "last_name": "Gaszner", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuroscience.2017.04.019" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28450265" } }, "mesh": [ { "descriptor": "Adaptation, Ocular", "descriptor_ui": "D000221", "major_topic": false }, { "descriptor": "Adrenal Glands", "descriptor_ui": "D000311", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Body Weight", "descriptor_ui": "D001835", "major_topic": false }, { "descriptor": "Corticotropin-Releasing Hormone", "descriptor_ui": "D003346", "major_topic": false }, { "descriptor": "Depression", "descriptor_ui": "D003863", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "Exploratory Behavior", "descriptor_ui": "D005106", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Maternal Deprivation", "descriptor_ui": "D008426", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Raphe Nuclei", "descriptor_ui": "D011903", "major_topic": false }, { "descriptor": "Septal Nuclei", "descriptor_ui": "D012686", "major_topic": false }, { "descriptor": "Stress, Psychological", "descriptor_ui": "D013315", "major_topic": false }, { "descriptor": "Swimming", "descriptor_ui": "D013550", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun 23", "date_precision": "day", "issue": "", "normalized_date": "2017-06-23", "pages": "11-29", "proceedings_title": null, "publisher": "", "title": "Neuroscience", "volume": "354", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Construct and face validity of a new model for the three-hit theory of depression using PACAP mutant mice on CD1 background.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Subcellular resolution imaging of the whole brain and subsequent image analysis are prerequisites for understanding anatomical and functional brain networks. Here, we have developed a very high-speed serial-sectioning imaging system named FAST (block-face serial microscopy tomography), which acquires high-resolution images of a whole mouse brain in a speed range comparable to that of light-sheet fluorescence microscopy. FAST enables complete visualization of the brain at a resolution sufficient to resolve all cells and their subcellular structures. FAST renders unbiased quantitative group comparisons of normal and disease model brain cells for the whole brain at a high spatial resolution. Furthermore, FAST is highly scalable to non-human primate brains and human postmortem brain tissues, and can visualize neuronal projections in a whole adult marmoset brain. Thus, FAST provides new opportunities for global approaches that will allow for a better understanding of brain systems in multiple animal models and in human diseases.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "contributor", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "contributor", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "contributor", "first_name": "Takeshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "contributor", "first_name": "Wiebke", "last_name": "Schulze", "name": null }, { "creator_type": "contributor", "first_name": "Misaki", "last_name": "Niu", "name": null }, { "creator_type": "contributor", "first_name": "Shun", "last_name": "Yamaguchi", "name": null }, { "creator_type": "contributor", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "contributor", "first_name": "Ken-Ichi", "last_name": "Inoue", "name": null }, { "creator_type": "contributor", "first_name": "Shiori", "last_name": "Uezono", "name": null }, { "creator_type": "contributor", "first_name": "Masahiko", "last_name": "Takada", "name": null }, { "creator_type": "contributor", "first_name": "Yuichiro", "last_name": "Naka", "name": null }, { "creator_type": "contributor", "first_name": "Hisato", "last_name": "Igarashi", "name": null }, { "creator_type": "contributor", "first_name": "Masato", "last_name": "Tanuma", "name": null }, { "creator_type": "contributor", "first_name": "James A.", "last_name": "Waschek", "name": null }, { "creator_type": "contributor", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "contributor", "first_name": "Kenji F.", "last_name": "Tanaka", "name": null }, { "creator_type": "contributor", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "contributor", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "contributor", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "contributor", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "contributor", "first_name": "Yasuto", "last_name": "Kunii", "name": null }, { "creator_type": "contributor", "first_name": "Mizuki", "last_name": "Hino", "name": null }, { "creator_type": "contributor", "first_name": "Junya", "last_name": "Matsumoto", "name": null }, { "creator_type": "contributor", "first_name": "Hirooki", "last_name": "Yabe", "name": null }, { "creator_type": "contributor", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "contributor", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "contributor", "first_name": "Toshio", "last_name": "Matsuda", "name": null }, { "creator_type": "contributor", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "contributor", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "contributor", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2017.05.017" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Jun 21", "date_precision": "day", "issue": "", "normalized_date": "2017-06-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "", "volume": "94", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "High-Speed and Scalable Whole-Brain Imaging in Rodents and Primates.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Phototaxis is a behavior in which organisms move toward or away from the light source (positive or negative phototaxis, respectively). It is crucial for phototrophic microorganisms to inhabit under proper light conditions for phototaxis. The unicellular green alga Chlamydomonas reinhardtii rapidly changes its swimming direction upon light illumination, and thus is a nice model organism for phototaxis research. Here we show two methods to assay Chlamydomonas phototaxis; one is a quick, easy and qualitative analysis, so-called the dish assay; and the other is a quantitative single-cell analysis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Noriko", "last_name": "Ueki", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Wakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.21769/bioprotoc.2356" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34541103" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Jun 20", "date_precision": "day", "issue": "12", "normalized_date": "2017-06-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "Bio-protocol", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Phototaxis Assay for Chlamydomonas reinhardtii.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Recent advances in bioimaging and automated analysis methods have enabled the large-scale systematic analysis of cellular dynamics during the embryonic development of Caenorhabditis elegans. Most of these analyses have focused on cell lineage tracing rather than cell shape dynamics. Cell shape analysis requires cell membrane segmentation, which is challenging because of insufficient resolution and image quality. This problem is currently solved by complicated segmentation methods requiring laborious and time consuming parameter adjustments. RESULTS: Our new framework BCOMS (Biologically Constrained Optimization based cell Membrane Segmentation) automates the extraction of the cell shape of C. elegans embryos. Both the segmentation and evaluation processes are automated. To automate the evaluation, we solve an optimization problem under biological constraints. The performance of BCOMS was validated against a manually created ground truth of the 24-cell stage embryo. The average deviation of 25 cell shape features was 5.6%. The deviation was mainly caused by membranes parallel to the focal planes, which either contact the surfaces of adjacent cells or make no contact with other cells. Because segmentation of these membranes was difficult even by manual inspection, the automated segmentation was sufficiently accurate for cell shape analysis. As the number of manually created ground truths is necessarily limited, we compared the segmentation results between two adjacent time points. Across all cells and all cell cycles, the average deviation of the 25 cell shape features was 4.3%, smaller than that between the automated segmentation result and ground truth. CONCLUSIONS: BCOMS automated the accurate extraction of cell shapes in developing C. elegans embryos. By replacing image processing parameters with easily adjustable biological constraints, BCOMS provides a user-friendly framework. The framework is also applicable to other model organisms. Creating the biological constraints is a critical step requiring collaboration between an experimentalist and a software developer.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12859-017-1717-6" }, "pmcid": { "normalized": "PMC5477254" }, "pmid": { "normalized": "28629355" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Automation", "descriptor_ui": "D001331", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun 19", "date_precision": "day", "issue": "1", "normalized_date": "2017-06-19", "pages": "307", "proceedings_title": null, "publisher": "", "title": "BMC bioinformatics", "volume": "18", "year": 2017 }, "ssbd": { "database": [ "ssbd-database-000020" ], "repository": [ "ssbd-repos-000020" ] }, "title": "Biologically constrained optimization based cell membrane segmentation in C. elegans embryos.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "From March 27-29 2017, the RIKEN Center for Developmental Biology held a symposium entitled 'Towards Understanding Human Development, Heredity, and Evolution' in Kobe, Japan. Recent advances in technologies including stem cell culture, live imaging, single-cell approaches, next-generation sequencing and genome editing have led to an expansion in our knowledge of human development. Organized by Yoshiya Kawaguchi, Mitinori Saitou, Mototsugu Eiraku, Tomoya Kitajima, Fumio Matsuzaki, Takashi Tsuji and Edith Heard, the symposium covered a broad range of topics including human germline development, epigenetics, organogenesis and evolution. This Meeting Review provides a summary of this timely and exciting symposium, which has convinced us that we are moving into the era of science targeted on humans.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Nishinakamura", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.150565" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28634269" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": false }, { "descriptor": "Developmental Biology", "descriptor_ui": "D015509", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Heredity", "descriptor_ui": "D040941", "major_topic": false }, { "descriptor": "Human Development", "descriptor_ui": "D006803", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun 15", "date_precision": "day", "issue": "12", "normalized_date": "2017-06-15", "pages": "2099-2103", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "144", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Human development, heredity and evolution.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Upon herpes simplex virus 1 (HSV-1) infection, the CD98 heavy chain (CD98hc) is redistributed around the nuclear membrane (NM), where it promotes viral de-envelopment during the nuclear egress of nucleocapsids. In this study, we attempted to identify the factor(s) involved in CD98hc accumulation and demonstrated the following: (i) the null mutation of HSV-1 UL34 caused specific dispersion throughout the cytoplasm of CD98hc and the HSV-1 de-envelopment regulators, glycoproteins B and H (gB and gH); (ii) as observed with CD98hc, gB, and gH, wild-type HSV-1 infection caused redistribution of the endoplasmic reticulum (ER) markers calnexin and ERp57 around the NM, whereas the UL34-null mutation caused cytoplasmic dispersion of these markers; (iii) the ER markers colocalized efficiently with CD98hc, gB, and gH in the presence and absence of UL34 in HSV-1-infected cells; (iv) at the ultrastructural level, wild-type HSV-1 infection caused ER compression around the NM, whereas the UL34-null mutation caused cytoplasmic dispersion of the ER; and (v) the UL34-null mutation significantly decreased the colocalization efficiency of lamin protein markers of the NM with CD98hc and gB. Collectively, these results indicate that HSV-1 infection causes redistribution of the ER around the NM, with resulting accumulation of ER-associated CD98hc, gB, and gH around the NM and that UL34 is required for ER redistribution, as well as for efficient recruitment to the NM of the ER-associated de-envelopment factors. Our study suggests that HSV-1 induces remodeling of the global ER architecture for recruitment of regulators mediating viral nuclear egress to the NM.IMPORTANCE The ER is an important cellular organelle that exists as a complex network extending throughout the cytoplasm. Although viruses often remodel the ER to facilitate viral replication, information on the effects of herpesvirus infections on ER morphological integrity is limited. Here, we showed that HSV-1 infection led to compression of the global ER architecture around the NM, resulting in accumulation of ER-associated regulators associated with nuclear egress of HSV-1 nucleocapsids. We also identified HSV-1 UL34 as a viral factor that mediated ER remodeling. Furthermore, we demonstrated that UL34 was required for efficient targeting of these regulators to the NM. To our knowledge, this is the first report showing that a herpesvirus remodels ER global architecture. Our study also provides insight into the mechanism by which the regulators for HSV-1 nuclear egress are recruited to the NM, where this viral event occurs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Fumio", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hirohata", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00271-17" }, "pmcid": { "normalized": "PMC5446647" }, "pmid": { "normalized": "28356536" } }, "mesh": [ { "descriptor": "Active Transport, Cell Nucleus", "descriptor_ui": "D021581", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calnexin", "descriptor_ui": "D037281", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": false }, { "descriptor": "Fusion Regulatory Protein-1", "descriptor_ui": "D027261", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Nuclear Envelope", "descriptor_ui": "D009685", "major_topic": false }, { "descriptor": "Nucleocapsid", "descriptor_ui": "D019251", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virus Assembly", "descriptor_ui": "D019065", "major_topic": false }, { "descriptor": "Virus Release", "descriptor_ui": "D057074", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun 15", "date_precision": "day", "issue": "12", "normalized_date": "2017-06-15", "pages": "e00271-17", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "91", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Herpes Simplex Virus 1 UL34 Protein Regulates the Global Architecture of the Endoplasmic Reticulum in Infected Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: We assessed vortex patterns and energy loss in left ventricular flow in patients who underwent mitral valve repair or replacement with bioprosthetic valves. METHODS: Vector flow mapping was performed before and after the procedure in 15 and 17 patients who underwent repair and replacement, respectively. The preprocedure mitral-septal angle was measured in all patients. Relationships between vortex patterns or energy loss change (ELC) and annuloplasty ring or bioprosthetic valve sizes or the effect of mitral leaflet resection in the repair group were statistically analysed. RESULTS: Normal vortex patterns were observed in 13 and 1 patients who underwent repair and replacement, respectively. Abnormal vortex patterns were observed in 2 and 16 patients who underwent repair and replacement, respectively. ELC was significantly higher in the replacement group (196.6 +/- 180.8) than in the repair group (71.9 +/- 43.9). In the repair group, preoperative mitral-septal angles in patients with normal vortex patterns (79.2 degrees +/- 3.4 degrees ) were significantly larger than those in patients with abnormal vortex patterns (67.5 degrees +/- 3.5 degrees ). No significant differences were observed in the effects of annuloplasty ring and bioprosthetic valve sizes on vortex patterns and ELC, and in the effect of mitral valve resection (80.4 +/- 56.3) and respect (without leaflet resection) (53.8 +/- 28.4) on ELC in the repair group. CONCLUSIONS: Mitral valve replacement alters the intraventricular vortex pattern and increases flow energy loss. A small mitral-septal angle is a risk factor for abnormal vortex patterns after mitral valve repair surgery.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Koichi", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Itatani", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Mao", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Saeko", "last_name": "Hamaoka", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Yasumoto", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Mizobe", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Numata", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Yaku", "name": null }, { "creator_type": "author", "first_name": "Teiji", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/icvts/ivx033" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28329295" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Blood Flow Velocity", "descriptor_ui": "D001783", "major_topic": false }, { "descriptor": "Cardiac Surgical Procedures", "descriptor_ui": "D006348", "major_topic": false }, { "descriptor": "Echocardiography, Doppler, Color", "descriptor_ui": "D018618", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Heart Ventricles", "descriptor_ui": "D006352", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mitral Valve", "descriptor_ui": "D008943", "major_topic": false }, { "descriptor": "Mitral Valve Insufficiency", "descriptor_ui": "D008944", "major_topic": false }, { "descriptor": "Monitoring, Intraoperative", "descriptor_ui": "D016343", "major_topic": false }, { "descriptor": "Prospective Studies", "descriptor_ui": "D011446", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun 1", "date_precision": "day", "issue": "6", "normalized_date": "2017-06-01", "pages": "869-875", "proceedings_title": null, "publisher": "", "title": "Interactive cardiovascular and thoracic surgery", "volume": "24", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Flow-dynamics assessment of mitral-valve surgery by intraoperative vector flow mapping.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell-cell signaling is subject to variability in the extracellular volume, cell number, and dilution that potentially increase uncertainty in the absolute concentrations of the extracellular signaling molecules. To direct cell aggregation, the social amoebae Dictyostelium discoideum collectively give rise to oscillations and waves of cyclic adenosine 3',5'-monophosphate (cAMP) under a wide range of cell density. To date, the systems-level mechanism underlying the robustness is unclear. By using quantitative live-cell imaging, here we show that the magnitude of the cAMP relay response of individual cells is determined by fold change in the extracellular cAMP concentrations. The range of cell density and exogenous cAMP concentrations that support oscillations at the population level agrees well with conditions that support a large fold-change-dependent response at the single-cell level. Mathematical analysis suggests that invariance of the oscillations to density transformation is a natural outcome of combining secrete-and-sense systems with a fold-change detection mechanism.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "contributor", "first_name": "Keita", "last_name": "Kamino", "name": null }, { "creator_type": "contributor", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "contributor", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "contributor", "first_name": "Mai", "last_name": "Honda-Kitahara", "name": null }, { "creator_type": "contributor", "first_name": "Kunihiko", "last_name": "Kaneko", "name": null }, { "creator_type": "contributor", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1702181114" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 May 23", "date_precision": "day", "issue": "", "normalized_date": "2017-05-23", "pages": "", "proceedings_title": null, "publisher": "", "title": "", "volume": "114", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Fold-change detection and scale invariance of cell-cell signaling in social amoeba.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (TSCM) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8(+) TSCM cells can be generated in vitro from naive CD8(+) T cells via Wnt signalling; however, methods do not yet exist for inducing TSCM cells from activated or memory T cells. Here, we show a strategy for generating TSCM-like cells in vitro (iTSCM cells) from activated CD4(+) and CD8(+) T cells in mice and humans by coculturing with stromal cells that express a Notch ligand. iTSCM cells lose PD-1 and CTLA-4 expression, and produce a large number of tumour-specific effector cells after restimulation. This method could therefore be used to generate antigen-specific effector T cells for adoptive immunotherapy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Rimpei", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Yuumi", "last_name": "Okuzono", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Nakatsukasa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shichita", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Kanamori", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kassai", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms15338" }, "pmcid": { "normalized": "PMC5458121" }, "pmid": { "normalized": "28530241" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CD4-Positive T-Lymphocytes", "descriptor_ui": "D015496", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Separation", "descriptor_ui": "D002469", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "CTLA-4 Antigen", "descriptor_ui": "D060908", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunologic Memory", "descriptor_ui": "D007156", "major_topic": false }, { "descriptor": "Immunotherapy, Adoptive", "descriptor_ui": "D016219", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May 22", "date_precision": "day", "issue": "", "normalized_date": "2017-05-22", "pages": "15338", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The inositol 1,4,5-trisphosphate receptors (IP(3)Rs) and intracellular Ca(2+) signaling are critically involved in regulating different steps of autophagy, a lysosomal degradation pathway. The ryanodine receptors (RyR), intracellular Ca(2+)-release channels mainly expressed in excitable cell types including muscle and neurons, have however not yet been extensively studied in relation to autophagy. Yet, aberrant expression and excessive activity of RyRs in these tissues has been implicated in the onset of several diseases including Alzheimer's disease, where impaired autophagy regulation contributes to the pathology. In this study, we determined whether pharmacological RyR inhibition could modulate autophagic flux in ectopic RyR-expressing models, like HEK293 cells and in cell types that endogenously express RyRs, like C2C12 myoblasts and primary hippocampal neurons. Importantly, RyR3 overexpression in HEK293 cells impaired the autophagic flux. Conversely, in all cell models tested, pharmacological inhibition of endogenous or ectopically expressed RyRs, using dantrolene or ryanodine, augmented autophagic flux by increasing lysosomal turn-over (number of autophagosomes and autolysosomes measured as mCherry-LC3 punctae/cell increased from 70.37+/-7.81 in control HEK RyR3 cells to 111.18+/-7.72 and 98.14+/-7.31 after dantrolene and ryanodine treatments, respectively). Moreover, in differentiated C2C12 cells, transmission electron microscopy demonstrated that dantrolene treatment decreased the number of early autophagic vacuoles from 5.9+/-2.97 to 1.8+/-1.03 per cellular cross section. The modulation of the autophagic flux could be linked to the functional inhibition of RyR channels as both RyR inhibitors efficiently diminished the number of cells showing spontaneous RyR3 activity in the HEK293 cell model (from 41.14%+/-2.12 in control cells to 18.70%+/-2.25 and 9.74%+/-2.67 after dantrolene and ryanodine treatments, respectively). In conclusion, basal RyR-mediated Ca(2+)-release events suppress autophagic flux at the level of the lysosomes.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tim", "last_name": "Vervliet", "name": null }, { "creator_type": "author", "first_name": "Isabel", "last_name": "Pintelon", "name": null }, { "creator_type": "author", "first_name": "Kirsten", "last_name": "Welkenhuyzen", "name": null }, { "creator_type": "author", "first_name": "Martin D.", "last_name": "Bootman", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Mikoshiba", "name": null }, { "creator_type": "author", "first_name": "Wim", "last_name": "Martinet", "name": null }, { "creator_type": "author", "first_name": "Nael", "last_name": "Nadif Kasri", "name": null }, { "creator_type": "author", "first_name": "Jan B.", "last_name": "Parys", "name": null }, { "creator_type": "author", "first_name": "Geert", "last_name": "Bultynck", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bcp.2017.03.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28322744" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Dantrolene", "descriptor_ui": "D003620", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Ryanodine Receptor Calcium Release Channel", "descriptor_ui": "D019837", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May 15", "date_precision": "day", "issue": "", "normalized_date": "2017-05-15", "pages": "133-142", "proceedings_title": null, "publisher": "", "title": "Biochemical pharmacology", "volume": "132", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Basal ryanodine receptor activity suppresses autophagic flux.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Astrocytes play key roles in the central nervous system and regulate local blood flow and synaptic transmission via intracellular calcium (Ca(2+)) signaling. Astrocytic Ca(2+) signals are generated by multiple pathways: Ca(2+) release from the endoplasmic reticulum (ER) via the inositol 1, 4, 5-trisphosphate receptor (IP(3)R) and Ca(2+) influx through various Ca(2+) channels on the plasma membrane. However, the Ca(2+) channels involved in astrocytic Ca(2+) homeostasis or signaling have not been fully characterized. Here, we demonstrate that spontaneous astrocytic Ca(2+) transients in cultured hippocampal astrocytes were induced by cooperation between the Ca(2+) release from the ER and the Ca(2+) influx through store-operated calcium channels (SOCCs) on the plasma membrane. Ca(2+) imaging with plasma membrane targeted GCaMP6f revealed that spontaneous astroglial Ca(2+) transients were impaired by pharmacological blockade of not only Ca(2+) release through IP(3)Rs, but also Ca(2+) influx through SOCCs. Loss of SOCC activity resulted in the depletion of ER Ca(2+), suggesting that SOCCs are activated without store depletion in hippocampal astrocytes. Our findings indicate that sustained SOCC activity, together with that of the sarco-endoplasmic reticulum Ca(2+)-ATPase, contribute to the maintenance of astrocytic Ca(2+) store levels, ultimately enabling astrocytic Ca(2+) signaling.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shigeo", "last_name": "Sakuragi", "name": null }, { "creator_type": "author", "first_name": "Fumihiro", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Mikoshiba", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2017.03.096" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28336440" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Channels", "descriptor_ui": "D015220", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Inositol 1,4,5-Trisphosphate Receptors", "descriptor_ui": "D053496", "major_topic": false }, { "descriptor": "Ion Channel Gating", "descriptor_ui": "D015640", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Sarcoplasmic Reticulum", "descriptor_ui": "D012519", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May 13", "date_precision": "day", "issue": "4", "normalized_date": "2017-05-13", "pages": "879-885", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "486", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Astroglial Ca(2+) signaling is generated by the coordination of IP(3)R and store-operated Ca(2+) channels.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The temporal order of physiology and behavior in mammals is primarily regulated by the circadian pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN). Taking advantage of bioluminescence reporters, we monitored the circadian rhythms of the expression of clock genes Per1 and Bmal1 in the SCN of freely moving mice and found that the rate of phase shifts induced by a single light pulse was different in the two rhythms. The Per1-luc rhythm was phase-delayed instantaneously by the light presented at the subjective evening in parallel with the activity onset of behavioral rhythm, whereas the Bmal1-ELuc rhythm was phase-delayed gradually, similar to the activity offset. The dissociation was confirmed in cultured SCN slices of mice carrying both Per1-luc and Bmal1-ELuc reporters. The two rhythms in a single SCN slice showed significantly different periods in a long-term (3 wk) culture and were internally desynchronized. Regional specificity in the SCN was not detected for the period of Per1-luc and Bmal1-ELuc rhythms. Furthermore, neither is synchronized with circadian intracellular Ca(2+) rhythms monitored by a calcium indicator, GCaMP6s, or with firing rhythms monitored on a multielectrode array dish, although the coupling between the circadian firing and Ca(2+) rhythms persisted during culture. These findings indicate that the expressions of two key clock genes, Per1 and Bmal1, in the SCN are regulated in such a way that they may adopt different phases and free-running periods relative to each other and are respectively associated with the expression of activity onset and offset.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Sato", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Enoki", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Honma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1613374114" }, "pmcid": { "normalized": "PMC5422828" }, "pmid": { "normalized": "28416676" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "ARNTL Transcription Factors", "descriptor_ui": "D056930", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": true }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Period Circadian Proteins", "descriptor_ui": "D056950", "major_topic": false }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May 2", "date_precision": "day", "issue": "18", "normalized_date": "2017-05-02", "pages": "E3699-E3708", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "114", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Dissociation of Per1 and Bmal1 circadian rhythms in the suprachiasmatic nucleus in parallel with behavioral outputs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Abnormal epigenetic regulation can cause the nervous system to develop abnormally. Here, we sought to understand the mechanism by which this occurs by investigating the protein complex cohesin, which is considered to regulate gene expression and, when defective, is associated with higher-level brain dysfunction and the developmental disorder Cornelia de Lange syndrome (CdLS). We generated conditional Smc3-knockout mice and observed greater dendritic complexity and larger numbers of immature synapses in the cerebral cortex of Smc3(+/-) mice. Smc3(+/-) mice also exhibited more anxiety-related behavior, which is a symptom of CdLS. Further, a gene ontology analysis after RNA-sequencing suggested the enrichment of immune processes, particularly the response to interferons, in the Smc3(+/-) mice. Indeed, fewer synapses formed in their cortical neurons, and this phenotype was rescued by STAT1 knockdown. Thus, low levels of cohesin expression in the developing brain lead to changes in gene expression that in turn lead to a specific and abnormal neuronal and behavioral phenotype.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Masashige", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Ryuichiro", "last_name": "Nakato", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Katou", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Takao", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Miyakawa", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Shirahige", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Yamashita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1084/jem.20161517" }, "pmcid": { "normalized": "PMC5413336" }, "pmid": { "normalized": "28408410" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anxiety", "descriptor_ui": "D001007", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Brain Chemistry", "descriptor_ui": "D001923", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Chondroitin Sulfate Proteoglycans", "descriptor_ui": "D011508", "major_topic": false }, { "descriptor": "Chromosomal Proteins, Non-Histone", "descriptor_ui": "D002868", "major_topic": false }, { "descriptor": "Cohesins", "descriptor_ui": "D000097722", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May 1", "date_precision": "day", "issue": "5", "normalized_date": "2017-05-01", "pages": "1431-1452", "proceedings_title": null, "publisher": "", "title": "The Journal of experimental medicine", "volume": "214", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Decreased cohesin in the brain leads to defective synapse development and anxiety-related behavior.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Several regions of the brain and spinal cord control male reproductive function. We previously demonstrated that the gastrin-releasing peptide (GRP) system, located in the lumbosacral spinal cord of rats, controls spinal centers to promote penile reflexes during male copulatory behavior. However, little information exists on the male-specific spinal GRP system in animals other than rats. The objective of this study was to examine the functional generality of the spinal GRP system in mammals using the Asian house musk shrew (Suncus murinus; suncus named as the laboratory strain), a specialized placental mammal model. Mice are also used for a representative model of small laboratory animals. We first isolated complementary DNA encoding GRP in suncus. Phylogenetic analysis revealed that suncus preproGRP was clustered to an independent branch. Reverse transcription-PCR showed that GRP and its receptor mRNAs were both expressed in the lumbar spinal cord of suncus and mice. Immunohistochemistry for GRP demonstrated that the sexually dimorphic GRP system and male-specific expression/distribution patterns of GRP in the lumbosacral spinal cord in suncus are similar to those of mice. In suncus, we further found that most GRP-expressing neurons in males also express androgen receptors, suggesting that this male-dominant system in suncus is also androgen-dependent. Taken together, these results indicate that the sexually dimorphic spinal GRP system exists not only in mice but also in suncus, suggesting that this system is a conserved property in mammals. J. Comp. Neurol. 525:1586-1598, 2017. (c) 2016 Wiley Periodicals, Inc.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kei", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Hirooka", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Takanami", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Oti", "name": null }, { "creator_type": "author", "first_name": "Takamichi", "last_name": "Jogahara", "name": null }, { "creator_type": "author", "first_name": "Sen-Ichi", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cne.24138" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27804131" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": false }, { "descriptor": "Gastrin-Releasing Peptide", "descriptor_ui": "D019886", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Lumbosacral Region", "descriptor_ui": "D008161", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Polymerase Chain Reaction", "descriptor_ui": "D016133", "major_topic": false }, { "descriptor": "Reproduction", "descriptor_ui": "D012098", "major_topic": false }, { "descriptor": "Sex Characteristics", "descriptor_ui": "D012727", "major_topic": true }, { "descriptor": "Shrews", "descriptor_ui": "D012788", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May 1", "date_precision": "day", "issue": "7", "normalized_date": "2017-05-01", "pages": "1586-1598", "proceedings_title": null, "publisher": "", "title": "The Journal of comparative neurology", "volume": "525", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of the sexually dimorphic gastrin-releasing peptide system in the lumbosacral spinal cord that controls male reproductive function in the mouse and Asian house musk shrew (Suncus murinus).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Isolation-reared mice show social encounter-induced hyperactivity with activation of prefrontal serotonergic and dopaminergic systems, but it is not known whether this stress response is observed in other pathological conditions. Here we examined whether the social encounter stimulation induces abnormal behavior during withdrawal in chronic methamphetamine-treated mice. METHODS: To induce methamphetamine-induced behavioral sensitization, male mice were injected with methamphetamine (1 mg/kg) once daily for 7 days. RESULTS: The encounter with an intruder elicited hyperactivity 24 h after the last injection of methamphetamine in methamphetamine-sensitized mice. This response was observed even as long as 2 weeks after withdrawal of methamphetamine. The encounter increased c-Fos expression in the prefrontal cortex, dorsal raphe nucleus and ventral tegmental area in methamphetamine-sensitized mice, while it did not in control mice. Furthermore, the encounter increased extracellular serotonin (5-HT) and dopamine, but not noradrenaline, levels in the prefrontal cortex in methamphetamine-sensitized mice. Local injection of 5,7-dihydroxytryptamine and 6-hydroxydopamine into the prefrontal cortex attenuated encounter-induced hyperactivity in methamphetamine-sensitized mice and it markedly decreased prefrontal 5-HT and dopamine levels, respectively. Pharmacological analysis showed that the encounter-induced hyperactivity is mediated by dopamine D1 receptors and 5-HT2A receptors and attenuated by anxiolytics and antidepressants such as diazepam, osemozotan and selective 5-HT reuptake inhibitors. The effect of paroxetine was blocked by the 5-HT3 receptor antagonist azasetron. CONCLUSIONS: The present study shows that psychological stress elicits hyperactivity with activation of prefrontal 5-HT and dopamine systems in methamphetamine-dependent mice and suggests that the abnormal behavior is associated with anxiety and depression.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Umehara", "name": null }, { "creator_type": "author", "first_name": "Emina", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/ijnp/pyw115" }, "pmcid": { "normalized": "PMC5417057" }, "pmid": { "normalized": "28034961" } }, "mesh": [ { "descriptor": "5,7-Dihydroxytryptamine", "descriptor_ui": "D015116", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Central Nervous System Stimulants", "descriptor_ui": "D000697", "major_topic": false }, { "descriptor": "Desipramine", "descriptor_ui": "D003891", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Dopamine Agents", "descriptor_ui": "D015259", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Hyperkinesis", "descriptor_ui": "D006948", "major_topic": false }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Methamphetamine", "descriptor_ui": "D008694", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microdialysis", "descriptor_ui": "D017551", "major_topic": false }, { "descriptor": "Oxidopamine", "descriptor_ui": "D016627", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-fos", "descriptor_ui": "D016760", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false }, { "descriptor": "Serotonin Agents", "descriptor_ui": "D018490", "major_topic": false }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May 1", "date_precision": "day", "issue": "5", "normalized_date": "2017-05-01", "pages": "410-421", "proceedings_title": null, "publisher": "", "title": "The international journal of neuropsychopharmacology", "volume": "20", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of Prefrontal Serotonergic and Dopaminergic Systems in Encounter-Induced Hyperactivity in Methamphetamine-Sensitized Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This study reports the development of temperature-responsive polymer/silica hybrid nanoparticles and their application to temperature-dependent intracellular uptake of hydrophobic encapsulated fluorescence molecules. Amphiphilic diblock copolymer comprising a temperature-responsive segment, poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) [P(NIPAAm-co-DMAAm)] and a trimethyoxysilyl-containing hydrophobic segment was synthesized (PBM-b-ND); this amphiphilic diblock copolymer self-assembled in an aqueous solution, and temperature-responsive polymer/silica hybrid fluorescence nanoparticles were fabricated via a base-catalyzed sol-gel process. The fluorescence probe rhodamine DHPE or boron dipyrromethene derivative was encapsulated into the polymer core with a silica network in a stable manner. Other types of polymer/silica hybrid fluorescence nanoparticles were also developed using either homo-PNIPAAm (PBM-b-N) or homo-PDMAAm (PBM-b-D) segments, instead of P(NIPAAm-co-DMAAm). While PBM-b-D did not exhibit a temperature-dependent phase transition (hydrophilic characteristic), PBM-b-N and PBM-b-ND exhibited temperature-dependent phase transition (hydrophilic/hydrophobic) at 32 degrees C and 38 degrees C, respectively. The cellular uptake of PBM-b-N was clearly observed at both 37 degrees C and 42 degrees C, while the cellular uptake of PBM-b-D was minimal at these temperatures. On the other hand, significant enhancement in the intracellular uptake of PBM-b-ND was observed at 42 degrees C, compared to its uptake at a lower temperature of 37 degrees C. These results indicated that temperature-responsive polymer/silica hybrid nanoparticle, PBM-b-ND demonstrate potential for applications in theranostics with cancer therapy via the combination of local drug delivery and local hyperthermia, as well as for monitoring treatment effectiveness with fluorescence imaging.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Nemoto", "name": null }, { "creator_type": "author", "first_name": "Hideko", "last_name": "Kanazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.colsurfb.2017.01.052" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28192714" } }, "mesh": [ { "descriptor": "Drug Design", "descriptor_ui": "D015195", "major_topic": true }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrophobic and Hydrophilic Interactions", "descriptor_ui": "D057927", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Silicon Dioxide", "descriptor_ui": "D012822", "major_topic": false }, { "descriptor": "Surface-Active Agents", "descriptor_ui": "D013501", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": true }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May 1", "date_precision": "day", "issue": "", "normalized_date": "2017-05-01", "pages": "2-9", "proceedings_title": null, "publisher": "", "title": "Colloids and surfaces. B, Biointerfaces", "volume": "153", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Design and synthesis of temperature-responsive polymer/silica hybrid nanoparticles and application to thermally controlled cellular uptake.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Non-allelic histone variants are considered as epigenetic factors that regulate genomic DNA functions in eukaryotic chromosomes. In this study, we identified three new human histone H3 variants (named H3.6, H3.7, and H3.8), which were previously annotated as pseudogenes. H3.6 and H3.8 conserve the H3.3-specific amino acid residues, but H3.7 shares the specific amino acid residues with H3.1. We successfully reconstituted the nucleosome containing H3.6 in vitro and determined its crystal structure. In the H3.6 nucleosome, the H3.6-specific Val62 residue hydrophobically contacts the cognate H4 molecule, but its contact area is smaller than that of the corresponding H3.3 Ile62 residue. The thermal stability assay revealed that the H3.6 nucleosome is substantially unstable, as compared to the H3.3 nucleosome. Interestingly, mutational analysis demonstrated that the H3.6 Val62 residue is fully responsible for the H3.6 nucleosome instability, probably because of the weakened hydrophobic interaction with H4. We also reconstituted the nucleosome containing H3.8, but its thermal stability was quite low. In contrast, purified H3.7 failed to form nucleosomes in vitro. The identification and characterization of these novel human histone H3 variants provide important new insights into understanding the epigenetic regulation of the human genome.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Yan", "last_name": "Xie", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Horikoshi", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Nogami", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Arimura", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Osakabe", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Kujirai", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Semba", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurumizaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.biochem.6b01098" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28374988" } }, "mesh": [ { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Crystallography, X-Ray", "descriptor_ui": "D018360", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr 25", "date_precision": "day", "issue": "16", "normalized_date": "2017-04-25", "pages": "2184-2196", "proceedings_title": null, "publisher": "", "title": "Biochemistry", "volume": "56", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Crystal Structure and Characterization of Novel Human Histone H3 Variants, H3.6, H3.7, and H3.8.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Angiogenesis is important for normal development as well as for tumour growth. However, the molecular and cellular mechanisms underlying angiogenesis are not fully understood, partly because of the lack of a good animal model for imaging. Here, we report the generation of a novel transgenic (Tg) mouse that expresses a bioluminescent reporter protein, Nano-lantern, under the control of Fetal liver kinase 1 (Flk1). Flk1-Nano-lantern BAC Tg mice recapitulated endogenous Flk1 expression in endothelial cells and lymphatic endothelial cells during development and tumour growth. Importantly, bioluminescence imaging of endothelial cells from the aortic rings of Flk1-Nano-lantern BAC Tg mice enabled us to observe endothelial sprouting for 18 hr without any detectable phototoxicity. Furthermore, Flk1-Nano-lantern BAC Tg mice achieved time-lapse luminescence imaging of tumour angiogenesis in freely moving mice with implanted tumours. Thus, this transgenic mouse line contributes a unique model to study angiogenesis within both physiological and pathological contexts.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Shigenori", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Nishie", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Sakasai", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Chisato", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Miwa", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takara", "name": null }, { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Masatsugu", "last_name": "Ema", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep46597" }, "pmcid": { "normalized": "PMC5397864" }, "pmid": { "normalized": "28425492" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinoma, Lewis Lung", "descriptor_ui": "D018827", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Neovascularization, Physiologic", "descriptor_ui": "D018919", "major_topic": true }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor A", "descriptor_ui": "D042461", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor Receptor-2", "descriptor_ui": "D040301", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr 20", "date_precision": "day", "issue": "", "normalized_date": "2017-04-20", "pages": "46597", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Fluorescence and Bioluminescence Imaging of Angiogenesis in Flk1-Nano-lantern Transgenic Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lipid raft domains, where sphingolipids and cholesterol are enriched, concentrate signaling molecules. To examine how signaling protein complexes are clustered in rafts, we focused on the functions of glycoprotein M6a (GPM6a), which is expressed at a high concentration in developing mouse neurons. Using imaging of lipid rafts, we found that GPM6a congregated in rafts in a GPM6a palmitoylation-dependent manner, thereby contributing to lipid raft clustering. In addition, we found that signaling proteins downstream of GPM6a, such as Rufy3, Rap2, and Tiam2/STEF, accumulated in lipid rafts in a GPM6a-dependent manner and were essential for laminin-dependent polarity during neurite formation in neuronal development. In utero RNAi targeting of GPM6a resulted in abnormally polarized neurons with multiple neurites. These results demonstrate that GPM6a induces the clustering of lipid rafts, which supports the raft aggregation of its associated downstream molecules for acceleration of neuronal polarity determination. Therefore, GPM6a acts as a signal transducer that responds to extracellular signals.SIGNIFICANCE STATEMENT Lipid raft domains, where sphingolipids and cholesterol are enriched, concentrate signaling molecules. We focused on glycoprotein M6a (GPM6a), which is expressed at a high concentration in developing neurons. Using imaging of lipid rafts, we found that GPM6a congregated in rafts in a palmitoylation-dependent manner, thereby contributing to lipid raft clustering. In addition, we found that signaling proteins downstream of GPM6a accumulated in lipid rafts in a GPM6a-dependent manner and were essential for laminin-dependent polarity during neurite formation. In utero RNAi targeting of GPM6a resulted in abnormally polarized neurons with multiple neurites. These results demonstrate that GPM6a induces the clustering of lipid rafts, which supports the raft aggregation of its associated downstream molecules for acceleration of polarity determination. Therefore, GPM6a acts as a signal transducer that responds to extracellular signals.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Atsuko", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Takahashi-Niki", "name": null }, { "creator_type": "author", "first_name": "Natsuki", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nozumi", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Igarashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.3319-16.2017" }, "pmcid": { "normalized": "PMC6596588" }, "pmid": { "normalized": "28275160" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Extracellular Fluid", "descriptor_ui": "D045604", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Glycoproteins", "descriptor_ui": "D008562", "major_topic": false }, { "descriptor": "Membrane Microdomains", "descriptor_ui": "D021962", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr 12", "date_precision": "day", "issue": "15", "normalized_date": "2017-04-12", "pages": "4046-4064", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "37", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Extracellular Signals Induce Glycoprotein M6a Clustering of Lipid Rafts and Associated Signaling Molecules.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In mammals, AMPA-type glutamate receptors (GluAs) are expressed ubiquitously in the central nervous system and play critical roles in synaptic plasticity, learning, and memory. Here we examined GluAs in the ascidian, Ciona intestinalis, and determined that they are expressed in a limited subset of cells during early development. We further find that GluAs are required for development of the ocellus, a photoreceptive organ used during the swimming stage, and for tail resorption and body axis rotation during metamorphosis. These functions require ion influx through GluAs. This is a demonstration of an in vivo requirement for GluAs in organ formation and morphogenesis. GluAs are also expressed during mammalian development, suggesting that developmental roles of GluAs may be functionally conserved.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinobu", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Okado", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1612943114" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28348228" } }, "mesh": [ { "descriptor": "Amino Acid Substitution", "descriptor_ui": "D019943", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Oocytes", "descriptor_ui": "D009865", "major_topic": false }, { "descriptor": "Receptors, Glutamate", "descriptor_ui": "D017470", "major_topic": false }, { "descriptor": "Sense Organs", "descriptor_ui": "D012679", "major_topic": false }, { "descriptor": "Xenopus", "descriptor_ui": "D014981", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr 11", "date_precision": "day", "issue": "15", "normalized_date": "2017-04-11", "pages": "3939-3944", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "114", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "AMPA glutamate receptors are required for sensory-organ formation and morphogenesis in the basal chordate.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Living in a mentally and physically stimulating environment has been suggested to have a beneficial effect on the immune response. This study investigates these effects, utilizing a 2-week program of environmental enrichment (EE) and 2 models of acute inflammation: zymosan-induced peritonitis (ZIP) and the cecal ligation and puncture (CLP) model of sepsis. Our results revealed that following exposure to EE, mice possessed a significantly higher circulating neutrophil to lymphocyte ratio compared with control animals. When subject to ZIP, EE animals exhibit enhanced neutrophil and macrophage influx into their peritoneal cavity. Corresponding results were found in CLP, where we observed an improved capacity for enriched animals to clear systemic microbial infection. Ex vivo investigation of leukocyte activity also revealed that macrophages from EE mice presented an enhanced phagocytic capacity. Supporting these findings, microarray analysis of EE animals revealed the increased expression of immunomodulatory genes associated with a heightened and immunoprotective status. Taken together, these results provide potentially novel mechanisms by which EE influences the development and dynamics of the immune response.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Samuel", "last_name": "Brod", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Gobbetti", "name": null }, { "creator_type": "author", "first_name": "Beatrice", "last_name": "Gittens", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Mauro", "last_name": "Perretti", "name": null }, { "creator_type": "author", "first_name": "Fulvio", "last_name": "D'Acquisto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci.insight.90723" }, "pmcid": { "normalized": "PMC5374068" }, "pmid": { "normalized": "28405616" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cecum", "descriptor_ui": "D002432", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Environment", "descriptor_ui": "D004777", "major_topic": true }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Ligation", "descriptor_ui": "D008026", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microarray Analysis", "descriptor_ui": "D046228", "major_topic": false }, { "descriptor": "Neutrophils", "descriptor_ui": "D009504", "major_topic": false }, { "descriptor": "Peritonitis", "descriptor_ui": "D010538", "major_topic": false }, { "descriptor": "Phagocytosis", "descriptor_ui": "D010587", "major_topic": false }, { "descriptor": "Sepsis", "descriptor_ui": "D018805", "major_topic": false }, { "descriptor": "Zymosan", "descriptor_ui": "D015054", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr 6", "date_precision": "day", "issue": "7", "normalized_date": "2017-04-06", "pages": "e90723", "proceedings_title": null, "publisher": "", "title": "JCI insight", "volume": "2", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "The impact of environmental enrichment on the murine inflammatory immune response.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Elucidating temporal windows of signaling activity required for synaptic and behavioral plasticity is crucial for understanding molecular mechanisms underlying these phenomena. Here, we developed photoactivatable autocamtide inhibitory peptide 2 (paAIP2), a genetically encoded, light-inducible inhibitor of CaMKII activity. The photoactivation of paAIP2 in neurons for 1-2 min during the induction of LTP and structural LTP (sLTP) of dendritic spines inhibited these forms of plasticity in hippocampal slices of rodents. However, photoactivation approximately 1 min after the induction did not affect them, suggesting that the initial 1 min of CaMKII activation is sufficient for inducing LTP and sLTP. Furthermore, the photoactivation of paAIP2 expressed in amygdalar neurons of mice during an inhibitory avoidance task revealed that CaMKII activity during, but not after, training is required for the memory formation. Thus, we demonstrated that paAIP2 is useful to elucidate the temporal window of CaMKII activation required for synaptic plasticity and learning.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Myung Eun", "last_name": "Shin", "name": null }, { "creator_type": "author", "first_name": "Paula", "last_name": "Parra-Bueno", "name": null }, { "creator_type": "author", "first_name": "Erzsebet M.", "last_name": "Szatmari", "name": null }, { "creator_type": "author", "first_name": "Akihiro C. E.", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Yasuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2017.02.036" }, "pmcid": { "normalized": "PMC5425291" }, "pmid": { "normalized": "28318784" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Avoidance Learning", "descriptor_ui": "D001362", "major_topic": false }, { "descriptor": "CA1 Region, Hippocampal", "descriptor_ui": "D056547", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinase Type 2", "descriptor_ui": "D054732", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Electrophoresis, Polyacrylamide Gel", "descriptor_ui": "D004591", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Long-Term Potentiation", "descriptor_ui": "D017774", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Pyramidal Cells", "descriptor_ui": "D017966", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false }, { "descriptor": "Tumor Suppressor Proteins", "descriptor_ui": "D025521", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr 5", "date_precision": "day", "issue": "1", "normalized_date": "2017-04-05", "pages": "37-47.e5", "proceedings_title": null, "publisher": "", "title": "Neuron", "volume": "94", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Kinetics of Endogenous CaMKII Required for Synaptic Plasticity Revealed by Optogenetic Kinase Inhibitor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fertilization calcium waves are a conserved trigger for animal development; however, genetic analysis of these waves has been limited due to the difficulty of imaging in vivo fertilization. Here we describe a protocol to image calcium dynamics during in vivo fertilization in the genetic animal model Caenorhabditis elegans. This protocol consists of germline microinjection of a chemical calcium indicator, worm immobilization, live imaging, and image processing that quantifies the calcium fluorescence in the oocyte region moving in the field-of-view during ovulation. This imaging protocol can also be used to image other cellular processes during in vivo fertilization in C. elegans, such as membrane fusion and cytoskeletal dynamics.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.21769/bioprotoc.2205" }, "pmcid": { "normalized": "PMC8410336" }, "pmid": { "normalized": "34541214" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Apr 5", "date_precision": "day", "issue": "7", "normalized_date": "2017-04-05", "pages": "e2205", "proceedings_title": null, "publisher": "", "title": "Bio-protocol", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "In vivo Live Imaging of Calcium Waves and Other Cellular Processes during Fertilization in Caenorhabditis elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cyclic guanosine monophosphate (cGMP) plays a crucial role as a second messenger in the regulation of sensory signal transduction in many organisms. In AWC olfactory sensory neurons of Caenorhabditis elegans, cGMP also has essential and distinctive functions in olfactory sensation and adaptation. According to molecular genetic studies, when nematodes are exposed to odorants, a decrease in cGMP regulates cGMP-gated channels for olfactory sensation. Conversely, for olfactory adaptation, an increase in cGMP activates protein kinase G to modulate cellular physiological functions. Although these opposing cGMP responses in single neurons may occur at the same time, it is unclear how cGMP actually behaves in AWC sensory neurons. A hypothetical explanation for opposing cGMP responses is region-specific behaviors in AWC: for odor sensation, cGMP levels in cilia could decrease, whereas odor adaptation is mediated by increased cGMP levels in soma. Therefore, we visualized intracellular cGMP in AWC with a genetically encoded cGMP indicator, cGi500, and examined spatiotemporal cGMP responses in AWC neurons. The cGMP imaging showed that, after odor exposure, cGMP levels in AWC cilia decreased transiently, whereas levels in dendrites and soma gradually increased. These region-specific responses indicated that the cGMP responses in AWC neurons are explicitly compartmentalized. In addition, we performed Ca2+ imaging to examine the relationship between cGMP and Ca2+. These results suggested that AWC sensory neurons are in fact analogous to vertebrate photoreceptor neurons.SIGNIFICANCE STATEMENT Cyclic guanosine monophosphate (cGMP) plays crucial roles in the regulation of sensory signal transduction in many animals. In AWC olfactory sensory neurons of Caenorhabditis elegans, cGMP also has essential and distinctive functions involving olfactory sensation and adaptation. Here, we visualized intracellular cGMP in AWC neurons with a genetically encoded cGMP indicator and examined how these different functions could be regulated by the same second messenger in single neurons. cGMP imaging showed that, after odor application, cGMP levels in cilia decreased transiently, whereas levels in dendrites and soma gradually increased. These region-specific responses indicated that the responses in AWC neurons are explicitly compartmentalized. In addition, by combining cGMP and Ca2+ imaging, we observed that AWC neurons are analogous to vertebrate photoreceptor neurons.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hisashi", "last_name": "Shidara", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.2628-16.2017" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28270568" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Odorants", "descriptor_ui": "D009812", "major_topic": false }, { "descriptor": "Olfactory Receptor Neurons", "descriptor_ui": "D018034", "major_topic": false }, { "descriptor": "Sensory Receptor Cells", "descriptor_ui": "D011984", "major_topic": false }, { "descriptor": "Smell", "descriptor_ui": "D012903", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr 5", "date_precision": "day", "issue": "14", "normalized_date": "2017-04-05", "pages": "3753-3763", "proceedings_title": null, "publisher": "", "title": "The Journal of Neuroscience", "volume": "37", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Compartmentalized cGMP Responses of Olfactory Sensory Neurons in Caenorhabditis elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The thalamus is a diencephalic structure that plays crucial roles in relaying and modulating sensory and motor information to the neocortex. The thalamus develops in the dorsal part of the neural tube at the level of the caudal forebrain. However, the molecular mechanisms that are essential for thalamic differentiation are still unknown. Here, we have succeeded in generating thalamic neurons from mouse embryonic stem cells (mESCs) by modifying the default method that induces the most-anterior neural type in self-organizing culture. A low concentration of the caudalizing factor insulin and a MAPK/ERK kinase inhibitor enhanced the expression of the caudal forebrain markers Otx2 and Pax6. BMP7 promoted an increase in thalamic precursors such as Tcf7l2(+)/Gbx2(+) and Tcf7l2(+)/Olig3(+) cells. mESC thalamic precursors began to express the glutamate transporter vGlut2 and the axon-specific marker VGF, similar to mature projection neurons. The mESC thalamic neurons extended their axons to cortical layers in both organotypic culture and subcortical transplantation. Thus, we have identified the minimum elements sufficient for in vitro generation of thalamic neurons. These findings expand our knowledge of thalamic development.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.144071" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28219951" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Morphogenetic Protein 7", "descriptor_ui": "D055419", "major_topic": false }, { "descriptor": "Cell Aggregation", "descriptor_ui": "D002449", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Embryoid Bodies", "descriptor_ui": "D058732", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase Kinases", "descriptor_ui": "D020929", "major_topic": false }, { "descriptor": "Mouse Embryonic Stem Cells", "descriptor_ui": "D000066450", "major_topic": false }, { "descriptor": "Neurites", "descriptor_ui": "D016501", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Organ Culture Techniques", "descriptor_ui": "D009924", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Thalamus", "descriptor_ui": "D013788", "major_topic": false }, { "descriptor": "Transcription Factor 7-Like 2 Protein", "descriptor_ui": "D058118", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr 1", "date_precision": "day", "issue": "7", "normalized_date": "2017-04-01", "pages": "1211-1220", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "144", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of thalamic neurons from mouse embryonic stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Early in the development of the central nervous system, progenitor cells undergo a shape change, called apical constriction, that triggers the neural plate to form a tubular structure. How apical constriction in the neural plate is controlled and how it contributes to tissue morphogenesis are not fully understood. In this study, we show that intracellular calcium ions (Ca(2+)) are required for Xenopus neural tube formation and that there are two types of Ca(2+)-concentration changes, a single-cell and a multicellular wave-like fluctuation, in the developing neural plate. Quantitative imaging analyses revealed that transient increases in Ca(2+) concentration induced cortical F-actin remodeling, apical constriction and accelerations of the closing movement of the neural plate. We also show that extracellular ATP and N-cadherin (cdh2) participate in the Ca(2+)-induced apical constriction. Furthermore, our mathematical model suggests that the effect of Ca(2+) fluctuations on tissue morphogenesis is independent of fluctuation frequency and that fluctuations affecting individual cells are more efficient than those at the multicellular level. We propose that distinct Ca(2+) signaling patterns differentially modulate apical constriction for efficient epithelial folding and that this mechanism has a broad range of physiological outcomes.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masanao", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Yasue", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Robert E.", "last_name": "Campbell", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Ueno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.141952" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28219946" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": true }, { "descriptor": "Extracellular Space", "descriptor_ui": "D005110", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Intracellular Space", "descriptor_ui": "D042541", "major_topic": false }, { "descriptor": "Linear Models", "descriptor_ui": "D016014", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": true }, { "descriptor": "Neural Plate", "descriptor_ui": "D054258", "major_topic": false }, { "descriptor": "Neural Tube", "descriptor_ui": "D054259", "major_topic": false }, { "descriptor": "Xenopus laevis", "descriptor_ui": "D014982", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr 1", "date_precision": "day", "issue": "7", "normalized_date": "2017-04-01", "pages": "1307-1316", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "144", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Distinct intracellular Ca(2+) dynamics regulate apical constriction and differentially contribute to neural tube closure.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Forster resonance energy transfer (FRET) has been widely used to design indicators for biomolecules. Conventional FRET-based indicators enable quantitative measurements of analyzes by calculating the ratio between donor and acceptor fluorophores. However, such 'hetero-FRET'-based indicators, which use multiple differently colored fluorophores, restrict the simultaneous use of other colors of fluorescent molecules. To overcome this problem, we developed a 'homo-FRET'-based Ca2+ indicator, W-Cameleon, composed of two identical yellow fluorescent proteins. The binding of Ca2+ to the indicator induces a change in FRET efficiency, which in turn transforms into changes in fluorescence anisotropy. Given that the fluorescence polarization is depolarized by light passing through a high numerical aperture lens and reflecting on a dichroic mirror, we also developed a microscopy technique that reliably detects fluorescence anisotropy with high precision. Our design is aided by photonic-crystal technology, to compensate for the fluorescence depolarization. We thereby succeeded in the simultaneous visualization of three individual intracellular events by using three different fluorescent indicators. Our system may contribute to an expansion of the number of events that can be observed, which will enable a more quantitative understanding of biological phenomena.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Sang-Yeob", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Tani", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Takatsuka", "name": null }, { "creator_type": "author", "first_name": "Yoshiharu", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Shojiro", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jmicro/dfw110" }, "pmcid": { "normalized": "PMC6402244" }, "pmid": { "normalized": "28043995" } }, "mesh": [ { "descriptor": "Cell Physiological Phenomena", "descriptor_ui": "D002468", "major_topic": true }, { "descriptor": "Cells", "descriptor_ui": "D002477", "major_topic": false }, { "descriptor": "Fluorescence Polarization", "descriptor_ui": "D005454", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Protein Interaction Mapping", "descriptor_ui": "D025941", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr 1", "date_precision": "day", "issue": "2", "normalized_date": "2017-04-01", "pages": "110-119", "proceedings_title": null, "publisher": "", "title": "Microscopy (Oxford, England)", "volume": "66", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Simultaneous imaging of multiple cellular events using high-accuracy fluorescence polarization microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Newly emerging transformed cells are often eliminated from epithelial tissues. Recent studies have revealed that this cancer-preventive process involves the interaction with the surrounding normal epithelial cells; however, the molecular mechanisms underlying this phenomenon remain largely unknown. In this study, using mammalian cell culture and zebrafish embryo systems, we have elucidated the functional involvement of endocytosis in the elimination of RasV12-transformed cells. First, we show that Rab5, a crucial regulator of endocytosis, is accumulated in RasV12-transformed cells that are surrounded by normal epithelial cells, which is accompanied by up-regulation of clathrin-dependent endocytosis. Addition of chlorpromazine or coexpression of a dominant-negative mutant of Rab5 suppresses apical extrusion of RasV12 cells from the epithelium. We also show in zebrafish embryos that Rab5 plays an important role in the elimination of transformed cells from the enveloping layer epithelium. In addition, Rab5-mediated endocytosis of E-cadherin is enhanced at the boundary between normal and RasV12 cells. Rab5 functions upstream of epithelial protein lost in neoplasm (EPLIN), which plays a positive role in apical extrusion of RasV12 cells by regulating protein kinase A. Furthermore, we have revealed that epithelial defense against cancer (EDAC) from normal epithelial cells substantially impacts on Rab5 accumulation in the neighboring transformed cells. This report demonstrates that Rab5-mediated endocytosis is a crucial regulator for the competitive interaction between normal and transformed epithelial cells in mammals.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sayaka", "last_name": "Saitoh", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Yako", "name": null }, { "creator_type": "author", "first_name": "Mihoko", "last_name": "Kajita", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Natsu", "last_name": "Sugama", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kon", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Masazumi", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1602349114" }, "pmcid": { "normalized": "PMC5373379" }, "pmid": { "normalized": "28270608" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": true }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "rab5 GTP-Binding Proteins", "descriptor_ui": "D020696", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transformation, Genetic", "descriptor_ui": "D014170", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false }, { "descriptor": "Zebrafish Proteins", "descriptor_ui": "D029961", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar 21", "date_precision": "day", "issue": "12", "normalized_date": "2017-03-21", "pages": "E2327-E2336", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "114", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Rab5-regulated endocytosis plays a crucial role in apical extrusion of transformed cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The suprachiasmatic nucleus (SCN), the master circadian clock, contains a network composed of multiple types of neurons which are thought to form a hierarchical and multioscillator system. The molecular clock machinery in SCN neurons drives membrane excitability and sends time cue signals to various brain regions and peripheral organs. However, how and at what time of the day these neurons transmit output signals remain largely unknown. Here, we successfully visualized circadian voltage rhythms optically for many days using a genetically encoded voltage sensor, ArcLightD. Unexpectedly, the voltage rhythms are synchronized across the entire SCN network of cultured slices, whereas simultaneously recorded Ca(2+) rhythms are topologically specific to the dorsal and ventral regions. We further found that the temporal order of these two rhythms is cell-type specific: The Ca(2+) rhythms phase-lead the voltage rhythms in AVP neurons but Ca(2+) and voltage rhythms are nearly in phase in VIP neurons. We confirmed that circadian firing rhythms are also synchronous and are coupled with the voltage rhythms. These results indicate that SCN networks with asynchronous Ca(2+) rhythms produce coherent voltage rhythms.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Enoki", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Mieda", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Sato", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Honma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1616815114" }, "pmcid": { "normalized": "PMC5373333" }, "pmid": { "normalized": "28270612" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Potentials", "descriptor_ui": "D008564", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar 21", "date_precision": "day", "issue": "12", "normalized_date": "2017-03-21", "pages": "E2476-E2485", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "114", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Synchronous circadian voltage rhythms with asynchronous calcium rhythms in the suprachiasmatic nucleus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Clozapine is an atypical antipsychotic, that is established as the treatment of choice for treatment-resistant schizophrenia (SCZ). To date, no study investigating comprehensive DNA methylation changes in SCZ patients treated with chronic clozapine has been reported. The purpose of the present study is to reveal the effects of clozapine on DNA methylation in treatment-resistant SCZ. We conducted a genome-wide DNA methylation profiling in peripheral leukocytes (485,764 CpG dinucleotides) from treatment-resistant SCZ patients treated with clozapine (n = 21) in a longitudinal study. Significant changes in DNA methylation were observed at 29,134 sites after one year of treatment with clozapine, and these genes were enriched for \"cell substrate adhesion\" and \"cell matrix adhesion\" gene ontology (GO) terms. Furthermore, DNA methylation changes in the CREBBP (CREB binding protein) gene were significantly correlated with the clinical improvements. Our findings provide insights into the action of clozapine in treatment-resistant SCZ.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Shusuke", "last_name": "Numata", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tajima", "name": null }, { "creator_type": "author", "first_name": "Hidenaga", "last_name": "Yamamori", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hidehiro", "last_name": "Umehara", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Shimodera", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Nakaya", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Issei", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Ohmori", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms18030632" }, "pmcid": { "normalized": "PMC5372645" }, "pmid": { "normalized": "28335437" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Antipsychotic Agents", "descriptor_ui": "D014150", "major_topic": false }, { "descriptor": "Clozapine", "descriptor_ui": "D003024", "major_topic": false }, { "descriptor": "CpG Islands", "descriptor_ui": "D018899", "major_topic": false }, { "descriptor": "CREB-Binding Protein", "descriptor_ui": "D050882", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "Drug Resistance", "descriptor_ui": "D004351", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukocytes", "descriptor_ui": "D007962", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Schizophrenia", "descriptor_ui": "D012559", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar 14", "date_precision": "day", "issue": "3", "normalized_date": "2017-03-14", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "18", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The novel property of reversible regulation of parallel type G-quadruplexes with moderate temperature changes was discovered in thermoresponsive hydrogels using a universal chiroptical spectrophotometer 1 (UCS-1). This study is the first to report the regulation of the ssDNA steric structure by using a poly(N-isopropylacrylamide) (PNIPAAm) gel.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Erika", "last_name": "Hasuike", "name": null }, { "creator_type": "author", "first_name": "Aya Mizutani", "last_name": "Akimoto", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Matsukawa", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Hideko", "last_name": "Kanazawa", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c7cc00279c" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28246660" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Mar 9", "date_precision": "day", "issue": "21", "normalized_date": "2017-03-09", "pages": "3142-3144", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "53", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Reversible conformational changes in the parallel type G-quadruplex structure inside a thermoresponsive hydrogel.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Enzyme/substrate pairs, such as beta-galactosidase with chromogenic x-gal substrate, are widely used as reporters to monitor biological events, but there is still a requirement for new reporter systems, which may be orthogonal to existing systems. Here, we focused on azoreductase (AzoR). We designed and synthesized a library of azo-rhodamine derivatives as candidate fluorogenic substrates. These derivatives were nonfluorescent, probably due to ultrafast conformational change around the N horizontal lineN bond after photoexcitation. We found that AzoR-mediated reduction of the azo bond of derivatives bearing an electron-donating group on the azobenzene moiety was followed by nonenzymatic cleavage to afford highly fluorescent 2-methyl-rhodamine green (2-Me RG), which was well retained in cells. We show that the AzoR/compound 9 reporter system can detect azoreductase-expressing live cells at the single cell level.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Narae", "last_name": "Shin", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Wen", "last_name": "Piao", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Miyakawa", "name": null }, { "creator_type": "author", "first_name": "Tomotsumi", "last_name": "Fujisawa", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Shodai", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tahei", "last_name": "Tahara", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tanokura", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acschembio.6b00852" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28036168" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "NADH, NADPH Oxidoreductases", "descriptor_ui": "D009247", "major_topic": false }, { "descriptor": "Nitroreductases", "descriptor_ui": "D009601", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Feb 17", "date_precision": "day", "issue": "2", "normalized_date": "2017-02-17", "pages": "558-563", "proceedings_title": null, "publisher": "", "title": "ACS chemical biology", "volume": "12", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of an Azoreductase-based Reporter System with Synthetic Fluorogenic Substrates.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herein we examined the extent of replicability of the PDMS microchamber device transferred from the master mold with complex 3D structures fabricated via micro stereolithography. Due to the elastomeric properties of PDMS, the reversely tapered micromold, with the diameter ratio of approximately 5 from the largest to the narrowest part, was precisely transferred without breaking. We obtained the mathematical model to estimate the stress exerted on the mold during the demolding process. Finally, we tested the applicability of this unusual microchamber for single-cell trapping and an enzyme assay.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Mitsuno", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Shiroguchi", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Tsugane", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Tetsuji", "last_name": "Dohi", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Tsuji", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c6lc01313a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28150829" } }, "mesh": [ { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Dimethylpolysiloxanes", "descriptor_ui": "D004129", "major_topic": false }, { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Jurkat Cells", "descriptor_ui": "D019169", "major_topic": false }, { "descriptor": "Microfluidic Analytical Techniques", "descriptor_ui": "D046210", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Feb 14", "date_precision": "day", "issue": "4", "normalized_date": "2017-02-14", "pages": "647-652", "proceedings_title": null, "publisher": "", "title": "Lab on a chip", "volume": "17", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "One-step micromolding of complex 3D microchambers for single-cell analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report development of the first genetically encoded bioluminescent indicator for membrane voltage called LOTUS-V. Since it is bioluminescent, imaging LOTUS-V does not require external light illumination. This allows bidirectional optogenetic control of cellular activity triggered by Channelrhodopsin2 and Halorhodopsin during voltage imaging. The other advantage of LOTUS-V is the robustness of a signal-to-background ratio (SBR) wherever it expressed, even in the specimens where autofluorescence from environment severely interferes fluorescence imaging. Through imaging of moving cardiomyocyte aggregates, we demonstrated the advantages of LOTUS-V in long-term imaging are attributable to the absence of phototoxicity, and photobleaching in bioluminescent imaging, combined with the ratiometric aspect of LOTUS-V design. Collectively LOTUS-V extends the scope of excitable cell control and simultaneous voltage phenotyping, which should enable applications in bioscience, medicine and pharmacology previously not possible.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shigenori", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Tsutsui", "name": null }, { "creator_type": "author", "first_name": "Kazushi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Agetsuma", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Jinno", "name": null }, { "creator_type": "author", "first_name": "Guirong", "last_name": "Bai", "name": null }, { "creator_type": "author", "first_name": "Matthew J.", "last_name": "Daniels", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep42398" }, "pmcid": { "normalized": "PMC5322354" }, "pmid": { "normalized": "28205521" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Electrophysiological Phenomena", "descriptor_ui": "D055724", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": true }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": true }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": true }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": true }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Feb 13", "date_precision": "day", "issue": "", "normalized_date": "2017-02-13", "pages": "42398", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetically encoded bioluminescent voltage indicator for multi-purpose use in wide range of bioimaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The thymus is an organ that produces functionally competent T cells that protect us from pathogens and malignancies. Foxn1 is a transcription factor that is essential for thymus organogenesis; however, the direct target for Foxn1 to actuate thymic T-cell production is unknown. Here we show that a Foxn1-binding cis-regulatory element promotes the transcription of β5t, which has an essential role in cortical thymic epithelial cells to induce positive selection of functionally competent CD8(+) T cells. A point mutation in this genome element results in a defect in β5t expression and CD8(+) T-cell production in mice. The results reveal a Foxn1-β5t transcriptional axis that governs CD8(+) T-cell production in the thymus.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Muhammad Myn", "last_name": "Uddin", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Ohigashi", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Motosugi", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Mie", "last_name": "Sakata", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Hamazaki", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Nishito", "name": null }, { "creator_type": "author", "first_name": "Immanuel", "last_name": "Rode", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Yousuke", "last_name": "Takahama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms14419" }, "pmcid": { "normalized": "PMC5309848" }, "pmid": { "normalized": "28176764" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Mutagenesis, Site-Directed", "descriptor_ui": "D016297", "major_topic": false }, { "descriptor": "Point Mutation", "descriptor_ui": "D017354", "major_topic": false }, { "descriptor": "Proteasome Endopeptidase Complex", "descriptor_ui": "D046988", "major_topic": false }, { "descriptor": "Regulatory Elements, Transcriptional", "descriptor_ui": "D050436", "major_topic": false }, { "descriptor": "Thymus Gland", "descriptor_ui": "D013950", "major_topic": false }, { "descriptor": "Tissue Culture Techniques", "descriptor_ui": "D046509", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Feb 8", "date_precision": "day", "issue": "", "normalized_date": "2017-02-08", "pages": "14419", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Foxn1-β5t transcriptional axis controls CD8(+) T-cell production in the thymus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In mammals, the master circadian clock is located in the suprachiasmatic nucleus (SCN), where most neurons show circadian rhythms of intracellular Ca(2+) levels. However, the origin of these Ca(2+) rhythms remains largely unknown. In this study, we successfully monitored the intracellular circadian Ca(2+) rhythms together with the circadian PER2 and firing rhythms in a single SCN slice ex vivo, which enabled us to explore the origins. The phase relation between the circadian PER2 and Ca(2+) rhythms, but not between the circadian PER2 and firing rhythms, was significantly altered in Cry1/Cry2 double knockout mice, which display a loss of intercellular synchronization in the SCN. In addition, in Cry1/Cry2 double knockout mice, circadian Ca(2+) rhythms were abolished in the dorsolateral SCN, but were maintained in the majority of the ventromedial SCN. These findings indicate that intracellular circadian Ca(2+) rhythms are composed of an exogenous and endogenous component involving PER2 expression.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Enoki", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Sato", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Honma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep41733" }, "pmcid": { "normalized": "PMC5290527" }, "pmid": { "normalized": "28155916" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": true }, { "descriptor": "Cryptochromes", "descriptor_ui": "D056931", "major_topic": false }, { "descriptor": "Intracellular Space", "descriptor_ui": "D042541", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Period Circadian Proteins", "descriptor_ui": "D056950", "major_topic": false }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Feb 3", "date_precision": "day", "issue": "", "normalized_date": "2017-02-03", "pages": "41733", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Dual origins of the intracellular circadian calcium rhythm in the suprachiasmatic nucleus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although the co-development of companion diagnostics with molecular targeted drugs is desirable, truly efficient diagnostics are limited to diseases in which chromosomal translocations or overt mutations are clearly correlated with drug efficacy. Moreover, even for such diseases, few methods are available to predict whether drug administration is effective for each individual patient whose disease is expected to respond to the drug(s). We have previously developed a biosensor based on the principle of Forster resonance energy transfer to measure the activity of the tyrosine kinase BCR-ABL and its response to drug treatment in patient-derived chronic myeloid leukemia cells. The biosensor harbors CrkL, one of the major substrates of BCR-ABL, and is therefore named Pickles after phosphorylation indicator of CrkL en substrate. The efficacy of this technique as a clinical test has been demonstrated, but the number of cells available for analysis is limited in a case-dependent manner, owing to the cleavage of the biosensor in patient-derived leukemia cells. Here, we describe an improved biosensor with an amino acid substitution and a nuclear export signal being introduced. Of the two predicted cleavage positions in CrkL, the mutations inhibited one cleavage completely and the other cleavage partially, thus collectively increasing the number of cells available for drug evaluation. This improved version of the biosensor holds promise in the future development of companion diagnostics to predict responses to tyrosine kinase inhibitors in patients with chronic myeloid leukemia.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mika", "last_name": "Horiguchi", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Xinxin", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Kosui", "last_name": "Horiuchi", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "O Satoh", "name": null }, { "creator_type": "author", "first_name": "Prabha", "last_name": "Nepal", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Nishide", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Nanbo", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Teshima", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1247/csf.16019" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27928132" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Amino Acid Substitution", "descriptor_ui": "D019943", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Biomarkers, Pharmacological", "descriptor_ui": "D054316", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fusion Proteins, bcr-abl", "descriptor_ui": "D016044", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "K562 Cells", "descriptor_ui": "D020014", "major_topic": false }, { "descriptor": "Leukemia, Myelogenous, Chronic, BCR-ABL Positive", "descriptor_ui": "D015464", "major_topic": false }, { "descriptor": "Myeloid Cells", "descriptor_ui": "D022423", "major_topic": false }, { "descriptor": "Nuclear Export Signals", "descriptor_ui": "D049790", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false }, { "descriptor": "Transgenes", "descriptor_ui": "D019076", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Feb 2", "date_precision": "day", "issue": "1", "normalized_date": "2017-02-02", "pages": "15-26", "proceedings_title": null, "publisher": "", "title": "Cell structure and function", "volume": "42", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Improved FRET Biosensor for the Measurement of BCR-ABL Activity in Chronic Myeloid Leukemia Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Damage-associated molecular patterns (DAMPs) have been implicated in sterile inflammation in various tissue injuries. High-mobility group box 1 (HMGB1) is a representative DAMP, and has been shown to transmit signals through receptors for advanced glycation end products (RAGEs) and TLRs, including TLR2 and TLR4. HMGB1 does not, however, bind to TLRs with high affinity; therefore, the mechanism of HMGB1-mediated TLR activation remains unclear. In this study, we found that fluorescently labeled HMGB1 was efficiently internalized into macrophages through class A scavenger receptors. Although both M1- and M2-type macrophages internalized HMGB1, only M1-type macrophages secreted cytokines in response to HMGB1. The pan-class A scavenger receptor competitive inhibitor, maleylated bovine serum albumin (M-BSA), inhibited HMGB1 internalization and reduced cytokine production from macrophages in response to HMGB1 but not to LPS. The C-terminal acidic domain of HMGB1 is responsible for scavenger receptor-mediated internalization and cytokine production. HMGB1 and TLR4 co-localized in macrophages, and this interaction was disrupted by M-BSA, suggesting that class A scavenger receptors function as co-receptors of HMGB1 for TLR activation. M-BSA ameliorated LPS-induced sepsis and dextran sulfate sodium (DSS)-induced colitis models in which HMGB1 has been shown to play progressive roles. These data suggest that scavenger receptors function as co-receptors along with TLRs for HMGB1 in M1-type inflammatory macrophages.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kyoko", "last_name": "Komai", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shichita", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Kanamori", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/intimm/dxx010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28338748" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cattle", "descriptor_ui": "D002417", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Colitis", "descriptor_ui": "D003092", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "HMGB1 Protein", "descriptor_ui": "D024243", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Receptors, Immunologic", "descriptor_ui": "D011971", "major_topic": false }, { "descriptor": "Scavenger Receptors, Class A", "descriptor_ui": "D051117", "major_topic": false }, { "descriptor": "Sepsis", "descriptor_ui": "D018805", "major_topic": false }, { "descriptor": "Serum Albumin, Bovine", "descriptor_ui": "D012710", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Toll-Like Receptor 2", "descriptor_ui": "D051195", "major_topic": false }, { "descriptor": "Toll-Like Receptor 4", "descriptor_ui": "D051197", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Feb 1", "date_precision": "day", "issue": "2", "normalized_date": "2017-02-01", "pages": "59-70", "proceedings_title": null, "publisher": "", "title": "International immunology", "volume": "29", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of scavenger receptors as damage-associated molecular pattern receptors in Toll-like receptor activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fused in sarcoma (FUS) and splicing factor, proline- and glutamine-rich (SFPQ) are RNA binding proteins that regulate RNA metabolism. We found that alternative splicing of the Mapt gene at exon 10, which generates 4-repeat tau (4R-T) and 3-repeat tau (3R-T), is regulated by interactions between FUS and SFPQ in the nuclei of neurons. Hippocampus-specific FUS- or SFPQ-knockdown mice exhibit frontotemporal lobar degeneration (FTLD)-like behaviors, reduced adult neurogenesis, accumulation of phosphorylated tau, and hippocampal atrophy with neuronal loss through an increased 4R-T/3R-T ratio. Normalization of this increased ratio by 4R-T-specific silencing results in recovery of the normal phenotype. These findings suggest a biological link among FUS/SFPQ, tau isoform alteration, and phenotypic expression, which may function in the early pathomechanism of FTLD.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Ishigaki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Riku", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Udagawa", "name": null }, { "creator_type": "author", "first_name": "Daiyu", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yokoi", "name": null }, { "creator_type": "author", "first_name": "Kuniyuki", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Ikenaka", "name": null }, { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Iguchi", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Warita", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Hirohisa", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Okado", "name": null }, { "creator_type": "author", "first_name": "Masahisa", "last_name": "Katsuno", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Sobue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2017.01.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28147269" } }, "mesh": [ { "descriptor": "Alternative Splicing", "descriptor_ui": "D017398", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Exons", "descriptor_ui": "D005091", "major_topic": false }, { "descriptor": "Frontotemporal Lobar Degeneration", "descriptor_ui": "D057174", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false }, { "descriptor": "PTB-Associated Splicing Factor", "descriptor_ui": "D000072670", "major_topic": false }, { "descriptor": "RNA Splicing", "descriptor_ui": "D012326", "major_topic": false }, { "descriptor": "RNA-Binding Protein FUS", "descriptor_ui": "D034702", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan 31", "date_precision": "day", "issue": "5", "normalized_date": "2017-01-31", "pages": "1118-1131", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "18", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Altered Tau Isoform Ratio Caused by Loss of FUS and SFPQ Function Leads to FTLD-like Phenotypes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report a reversible off/on fluorescent probe for monitoring concentration changes of sulfane sulfur by utilizing the unique ability of sulfane sulfur to bind reversibly to other sulfur atoms and the intramolecular spirocyclization reaction of xanthene dyes. It reversibly visualized sulfane sulfur in living A549 cells and primary-cultured hippocampal astrocytes.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoko", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Kazuhito", "last_name": "Shimamoto", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c6cc08372b" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28044156" } }, "mesh": [ { "descriptor": "A549 Cells", "descriptor_ui": "D000072283", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Sulfur Compounds", "descriptor_ui": "D013457", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan 17", "date_precision": "day", "issue": "6", "normalized_date": "2017-01-17", "pages": "1064-1067", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "53", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a reversible fluorescent probe for reactive sulfur species, sulfane sulfur, and its biological application.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cellular differentiation is associated with dynamic chromatin remodeling in establishing a cell-type-specific epigenomic landscape. Here, we find that mouse testis-specific and replication-dependent histone H3 variant H3t is essential for very early stages of spermatogenesis. H3t gene deficiency leads to azoospermia because of the loss of haploid germ cells. When differentiating spermatogonia emerge in normal spermatogenesis, H3t appears and replaces the canonical H3 proteins. Structural and biochemical analyses reveal that H3t-containing nucleosomes are more flexible than the canonical nucleosomes. Thus, by incorporating H3t into the genome during spermatogonial differentiation, male germ cells are able to enter meiosis and beyond.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Urahama", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Machida", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Hada", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Makino", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Nogami", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Horikoshi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Osakabe", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Tachiwana", "name": null }, { "creator_type": "author", "first_name": "Tatsuma", "last_name": "Yao", "name": null }, { "creator_type": "author", "first_name": "Minami", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Isotani", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurumizaka", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Yamagata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2016.12.065" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28099840" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Azoospermia", "descriptor_ui": "D053713", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Haploidy", "descriptor_ui": "D006238", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Meiosis", "descriptor_ui": "D008540", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Nucleosomes", "descriptor_ui": "D009707", "major_topic": false }, { "descriptor": "Spermatogenesis", "descriptor_ui": "D013091", "major_topic": false }, { "descriptor": "Spermatogonia", "descriptor_ui": "D013093", "major_topic": false }, { "descriptor": "Testis", "descriptor_ui": "D013737", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan 17", "date_precision": "day", "issue": "3", "normalized_date": "2017-01-17", "pages": "593-600", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "18", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Testis-Specific Histone Variant H3t Gene Is Essential for Entry into Spermatogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cells may exchange information with other cells and tissues by exerting forces on the extracellular matrix (ECM). Fibronectin (FN) is an important ECM component that forms fibrils through cell contacts and creates directionally biased geometry. Here, we demonstrate that FN is deposited as pillars between widely separated germ layers, namely the somitic mesoderm and the endoderm, in quail embryos. Alongside the FN pillars, long filopodia protrude from the basal surfaces of somite epithelial cells. Loss-of-function of Ena/VASP, alpha5beta1-integrins or talin in the somitic cells abolished the FN pillars, indicating that FN pillar formation is dependent on the basal filopodia through these molecules. The basal filopodia and FN pillars are also necessary for proper somite morphogenesis. We identified a new mechanism contributing to FN pillar formation by focusing on cyclic expansion of adjacent dorsal aorta. Maintenance of the directional alignment of the FN pillars depends on pulsatile blood flow through the dorsal aortae. These results suggest that the FN pillars are specifically established through filopodia-mediated and pulsating force-related mechanisms.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Nagatoshi", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Hamano", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Huss", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Rusty", "last_name": "Lansford", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.141259" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28096216" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Blood Vessels", "descriptor_ui": "D001808", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Endoderm", "descriptor_ui": "D004707", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": false }, { "descriptor": "Fibronectins", "descriptor_ui": "D005353", "major_topic": false }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Pseudopodia", "descriptor_ui": "D011554", "major_topic": false }, { "descriptor": "Quail", "descriptor_ui": "D011784", "major_topic": false }, { "descriptor": "Stress, Mechanical", "descriptor_ui": "D013314", "major_topic": true } ], "publication": { "conference_name": null, "date": "2017 Jan 15", "date_precision": "day", "issue": "2", "normalized_date": "2017-01-15", "pages": "281-291", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "144", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Basal filopodia and vascular mechanical stress organize fibronectin into pillars bridging the mesoderm-endoderm gap.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Vector flow mapping, a novel flow visualization echocardiographic technology, is increasing in popularity. Energy loss reference values for children have been established using vector flow mapping, but those for adults have not yet been provided. We aimed to establish reference values in healthy adults for energy loss, kinetic energy in the left ventricular outflow tract, and the energetic performance index (defined as the ratio of kinetic energy to energy loss over one cardiac cycle). METHODS: Transthoracic echocardiography was performed in fifty healthy volunteers, and the stored images were analyzed to calculate energy loss, kinetic energy, and energetic performance index and obtain ranges of reference values for these. RESULTS: Mean energy loss over one cardiac cycle ranged from 10.1 to 59.1 mW/m (mean +/- SD, 27.53 +/- 13.46 mW/m), with a reference range of 10.32 ~ 58.63 mW/m. Mean systolic energy loss ranged from 8.5 to 80.1 (23.52 +/- 14.53) mW/m, with a reference range of 8.86 ~ 77.30 mW/m. Mean diastolic energy loss ranged from 7.9 to 86 (30.41 +/- 16.93) mW/m, with a reference range of 8.31 ~ 80.36 mW/m. Mean kinetic energy in the left ventricular outflow tract over one cardiac cycle ranged from 200 to 851.6 (449.74 +/- 177.51) mW/m with a reference range of 203.16 ~ 833.15 mW/m. The energetic performance index ranged from 5.3 to 37.6 (18.48 +/- 7.74), with a reference range of 5.80 ~ 36.67. CONCLUSIONS: Energy loss, kinetic energy, and energetic performance index reference values were defined using vector flow mapping. These reference values enable the assessment of various cardiac conditions in any clinical situation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Koichi", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Matsuyama", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kainuma", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Mao", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Saeko", "last_name": "Hamaoka", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Itatani", "name": null }, { "creator_type": "author", "first_name": "Teiji", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12872-016-0444-7" }, "pmcid": { "normalized": "PMC5223342" }, "pmid": { "normalized": "28068909" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Coronary Circulation", "descriptor_ui": "D003326", "major_topic": true }, { "descriptor": "Echocardiography, Doppler, Color", "descriptor_ui": "D018618", "major_topic": false }, { "descriptor": "Energy Transfer", "descriptor_ui": "D004735", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Healthy Volunteers", "descriptor_ui": "D064368", "major_topic": false }, { "descriptor": "Heart Ventricles", "descriptor_ui": "D006352", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Interpretation, Computer-Assisted", "descriptor_ui": "D007090", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Myocardial Contraction", "descriptor_ui": "D009200", "major_topic": true }, { "descriptor": "Myocardial Perfusion Imaging", "descriptor_ui": "D055414", "major_topic": false }, { "descriptor": "Observer Variation", "descriptor_ui": "D015588", "major_topic": false }, { "descriptor": "Predictive Value of Tests", "descriptor_ui": "D011237", "major_topic": false }, { "descriptor": "Reference Values", "descriptor_ui": "D012016", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Ventricular Function, Left", "descriptor_ui": "D016277", "major_topic": true }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan 9", "date_precision": "day", "issue": "1", "normalized_date": "2017-01-09", "pages": "21", "proceedings_title": null, "publisher": "", "title": "BMC cardiovascular disorders", "volume": "17", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Vector flow mapping analysis of left ventricular energetic performance in healthy adult volunteers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sleep-disordered breathing produces cognitive impairments, and is possibly associated with Alzheimer disease (AD). Intermittent hypoxia treatment (IHT), an experimental model for sleep-disordered breathing, results in cognitive impairments in animals via unknown mechanisms. Here, we exposed mice to IHT protocols, and performed biochemical analyses and microarray analyses regarding their hippocampal samples. In particular, we performed gene ontology (GO)-based microarray analysis to elucidate effects of IHT on hippocampal functioning, which were compared with the effects of various previously-reported experimental conditions on that (ref. Gene Expression Omnibus, The National Center for Biotechnology Information). Our microarray analyses revealed that IHT and aging shared alterations in some common GO, which were also observed with kainic acid treatment, Dicer ablation, or moderate glutamate excess. Mapping the altered genes using the Kyoto Encyclopedia of Genes and Genomes PATHWAY database indicated that IHT and aging affected several pathways including \"MAPK signaling pathway\", \"PI3K-Akt signaling pathway\", and \"glutamatergic synapse\". Consistent with the gene analyses, in vivo analyses revealed that IHT increased phosphorylated tau, reflecting an imbalance of kinases and/or phosphatases, and reduced proteins relevant to glutamatergic synapses. In addition, IHT increased phosphorylated p70 S6 kinase, indicating involvement of the mammalian target of rapamycin signaling pathway. Furthermore, IHT mice demonstrated hyperactivity in Y-maze tests, which was also observed in AD models. We obtained important data or something from the massive amount of microarray data, and confirmed the validity by in vivo analyses: the IHT-induced cognitive impairment may be partially explained by the fact that IHT increases phosphorylated tau via biological processes common to aging. Moreover, as aging is a major risk factor for AD, IHT is a novel model for investigating the pathological processes contributing to AD onset.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Sosuke", "last_name": "Yagishita", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Awaji", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13041-016-0282-7" }, "pmcid": { "normalized": "PMC5217192" }, "pmid": { "normalized": "28057021" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Gene Ontology", "descriptor_ui": "D063990", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Hypoxia", "descriptor_ui": "D000860", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Maze Learning", "descriptor_ui": "D018782", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Principal Component Analysis", "descriptor_ui": "D025341", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan 5", "date_precision": "day", "issue": "1", "normalized_date": "2017-01-05", "pages": "2", "proceedings_title": null, "publisher": "", "title": "Molecular brain", "volume": "10", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Treatment of intermittent hypoxia increases phosphorylated tau in the hippocampus via biological processes common to aging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have established a coupled assay system targeting protein l-isoaspartyl methyltransferase (PIMT), a key enzyme in the metabolism of isoaspartyl peptides and proteins. The system utilizes a fluorogenic peptide probe containing an isoaspartyl residue at the P1' position of the caspase-3 recognition sequence. Following PIMT-catalyzed methyl transfer reaction, the methylated probe is specifically cleaved by caspase-3 to give fluorescence activation. High-throughput screening of our chemical library with this assay system identified PIMT inhibitors that may be useful as leads in the design of chemical probes for controlling PIMT activity.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Yanagi", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201608677" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27933714" } }, "mesh": [ { "descriptor": "Caspase 3", "descriptor_ui": "D053148", "major_topic": false }, { "descriptor": "Drug Evaluation, Preclinical", "descriptor_ui": "D004353", "major_topic": false }, { "descriptor": "Enzyme Assays", "descriptor_ui": "D057075", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "High-Throughput Screening Assays", "descriptor_ui": "D057166", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "Protein D-Aspartate-L-Isoaspartate Methyltransferase", "descriptor_ui": "D026601", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan 2", "date_precision": "day", "issue": "1", "normalized_date": "2017-01-02", "pages": "153-157", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "56", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of Chemical Tools to Monitor and Control Isoaspartyl Peptide Methyltransferase Activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An organoid can be defined as a three-dimensional organ-like structure formed from organ-specific progenitor cells. Organ progenitor cells were empirically found to self-organize three-dimensional tissues when they were aggregated and cultivated in vitro. While this nature power of progenitor cells has an amazing potential to recreate artificial organs in vitro, there had been difficulty to apply this technology to human organs due to the inaccessibility to human progenitor cells until human-induced pluripotent stem cell (hiPSC) was invented by Takahashi and Yamanaka in 2007. As embryonic stem cells do, hiPSCs also have pluripotency to give rise to any organs/tissues cell types, including the kidney, via directed differentiation. Here, we provide a detailed protocol for generating kidney organoids using human pluripotent stem cells. The protocol differentiates human pluripotent stem cells into the posterior primitive streak. This is followed by the simultaneous induction of posterior and anterior intermediate mesoderm that are subsequently aggregated and undergo self-organization into the kidney organoid. Such kidney organoids are comprised of all anticipated kidney cell types including nephrons segmented into the glomerulus, proximal tubule, loop of Henle, and distal tubule as well as the collecting duct, endothelial network, and renal interstitium.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null }, { "creator_type": "author", "first_name": "Melissa H.", "last_name": "Little", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4939-6949-4_14" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28361319" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "195-206", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "1597", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Making a Kidney Organoid Using the Directed Differentiation of Human Pluripotent Stem Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pluripotent stem cells (PSCs) possess self-organizing abilities in 3D culture. This property has been demonstrated in recent studies, including the generation of various neuroectodermal and endodermal tissues. For example, PSCs are able to differentiate into specific type of neural tissues, such as the neocortex and the optic cup, in response to local positional information brought about by signals during embryogenesis. In contrast, the generation of cerebellar tissue from PSCs requires a secondary induction by a signaling center, called the isthmic organizer, which first appears in the cell aggregate in 3D culture. Such developmental complexity of cerebellum has hampered establishment of effective differentiation culture system from PSCs, thus far.We recently reported that cerebellar neurons are generated from human PSCs (hPSCs). In this chapter, we describe an efficient protocol for differentiation of 3D cerebellar neuroepithelium from hPSCs. We also describe the protocols for further differentiation into specific neurons in the cerebellar cortex, such as Purkinje cells and the granule cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4939-6949-4_3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28361308" } }, "mesh": [ { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "31-41", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "1597", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "3D Culture for Self-Formation of the Cerebellum from Human Pluripotent Stem Cells Through Induction of the Isthmic Organizer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We propose a novel representation of materials named an 'orbital-field matrix (OFM)', which is based on the distribution of valence shell electrons. We demonstrate that this new representation can be highly useful in mining material data. Experimental investigation shows that the formation energies of crystalline materials, atomization energies of molecular materials, and local magnetic moments of the constituent atoms in bimetal alloys of lanthanide metal and transition-metal can be predicted with high accuracy using the OFM. Knowledge regarding the role of the coordination numbers of the transition-metal and lanthanide elements in determining the local magnetic moments of the transition-metal sites can be acquired directly from decision tree regression analyses using the OFM.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tien", "last_name": "Lam Pham", "name": null }, { "creator_type": "author", "first_name": "Hiori", "last_name": "Kino", "name": null }, { "creator_type": "author", "first_name": "Kiyoyuki", "last_name": "Terakura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null }, { "creator_type": "author", "first_name": "Hieu", "last_name": "Chi Dam", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/14686996.2017.1378060" }, "pmcid": { "normalized": "PMC5678453" }, "pmid": { "normalized": "29152012" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "1", "normalized_date": "2017", "pages": "756-765", "proceedings_title": null, "publisher": "", "title": "Science and technology of advanced materials", "volume": "18", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Machine learning reveals orbital interaction in materials.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: MicroRNAs, small non-coding RNAs, are highly expressed in the mammalian brain, and the dysregulation of microRNA levels may be involved in neurodevelopmental disorders such as autism spectrum disorder (ASD). In the present study, we examined whether prenatal valproic acid (VPA) exposure affects levels of microRNAs, especially the brain specific and enriched microRNAs, in the mouse embryonic brain. RESULTS: Prenatal exposure to VPA at E12.5 immediately increased miR-132 levels, but not miR-9 or miR-124 levels, in the male embryonic brain. Prenatal exposure to VPA at E12.5 also increased miR-132 levels in the female embryonic brain. We further found that the prenatal exposure to VPA at E12.5 increased mRNA levels of Arc, c-Fos and brain-derived neurotrophic factor in both male and female embryonic brains, prior to miR-132 expression. In contrast, prenatal exposure to VPA at E14.5 did not affect miR-132 levels in either male or female embryonic brain. The prenatal VPA exposure at E12.5 also decreased mRNA levels of methyl-CpG-binding protein 2 and Rho GTPase-activating protein p250GAP, both of which are molecular targets of miR-132. Furthermore, RNA sequence analysis revealed that prenatal VPA exposure caused changes in several microRNA levels other than miR-132 in the embryonic whole brain. CONCLUSIONS: These findings suggest that the alterations in neuronal activity-dependent microRNAs levels, including an increased level of miR-132, in the embryonic period, at least in part, underlie the ASD-like behaviors and cortical pathology produced by prenatal VPA exposure.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Erika", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13229-017-0149-5" }, "pmcid": { "normalized": "PMC5490164" }, "pmid": { "normalized": "28670439" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Maternal Exposure", "descriptor_ui": "D018811", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Valproic Acid", "descriptor_ui": "D014635", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "33", "proceedings_title": null, "publisher": "", "title": "Molecular autism", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Prenatal exposure to valproic acid increases miR-132 levels in the mouse embryonic brain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We evaluated usability of a previously developed genetically encoded molecular crowding sensor in various biological phenomena. Molecular crowding refers to intracellular regions that are occupied more by proteins and nucleotides than by water molecules and is thought to have a strong effect on protein function. To evaluate intracellular molecular crowding, usually the diffusion coefficient of a probe is used because it is related to mobility of the surrounding molecular crowding agents. Recently, genetically encoded molecular crowding sensors based on Förster resonance energy transfer were reported. In the present study, to evaluate the usability of a genetically encoded molecular crowding sensor, molecular crowding was monitored during several biological events. Changes in molecular crowding during stem cell differentiation, cell division, and focal adhesion development and difference in molecular crowding in filopodia locations were examined. The results show usefulness of the genetically encoded molecular crowding sensor for understanding the biological phenomena relating to molecular crowding.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Machiyama", "name": null }, { "creator_type": "author", "first_name": "Takamitsu J.", "last_name": "Morikawa", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.14.0_119" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28900589" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "119-125", "proceedings_title": null, "publisher": "", "title": "Biophysics and Physicobiology", "volume": "14", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "The use of a genetically encoded molecular crowding sensor in various biological phenomena.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Association of tau deposition with neurodegeneration in Alzheimer’s disease (AD) and related tau-positive neurological disorders collectively referred to as tauopathies indicates contribution of tau aggregates to neurotoxicity. The discovery of tau gene mutations in FTDP-17-tau kindreds has provided unequivocal evidence that tau abnormalities alone can induce neurodegenerative disorders. Therefore, visualization of tau accumulation would offer a reliable, objective index to aid in the diagnosis of tauopathy and to assess the disease progression. Positron emission tomography (PET) imaging of tau lesions is currently available using several tau PET ligands. Because most tau PET ligands have the property of an extrinsic fluorescent dye, these ligands are considered to be useful for both PET and fluorescence imaging. In addition, small-animal magnetic resonance imaging (MRI) is available for both structural and functional imaging. Using these advanced imaging techniques, in vivo studies on a mouse model of tauopathy will provide significant insight into the translational research of neurodegenerative diseases. In this review, we will discuss the utilities of PET, MRI, and fluorescence imaging for evaluating the disease progression of tauopathy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Shimojo", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takuwa", "name": null }, { "creator_type": "author", "first_name": "Marcelo", "last_name": "Febo", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fneur.2017.00663" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29375461" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Neurology", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "In Vivo Tau Imaging for a Diagnostic Platform of Tauopathy Using the rTg4510 Mouse Line.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Myosin-X, (Myo 10), is an unconventional myosin that transports the specific cargos to filopodial tips, and is associated with the mechanism underlying filopodia formation and extension. To clarify the innate motor characteristic, we studied the single molecule movement of a full-length myosin-X construct with leucine zipper at the C-terminal end of the tail (M10FullLZ) and the tail-truncated myosin-X without artificial dimerization motif (BAP-M101–979HMM). M10FullLZ localizes at the tip of filopodia like myosin-X full-length (M10Full). M10FullLZ moves on actin filaments in the presence of PI(3,4,5)P3, an activator of myosin-X. Single molecule motility analysis revealed that the step sizes of both M10FullLZ and BAP-M101–979HMM are widely distributed on single actin filaments that is consistent with electron microscopy observation. M10FullLZ moves on filopodial actin bundles of cells with a mean step size (~36 nm), similar to the step size on single actin filaments (~38 nm). Cartesian plot analysis revealed that M10FullLZ meandered on filopodial actin bundles to both x- and y- directions. These results suggest that the lever-arm of full-length myosin-X is flexible enough to processively steps on different actin filaments within the actin bundles of filopodia. This characteristic of myosin-X may facilitate actin filament convergence for filopodia production.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Osamu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hyun Suk", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Tsukasaki", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Homma", "name": null }, { "creator_type": "author", "first_name": "Mitsuo", "last_name": "Ikebe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep44237" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28287133" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Amino Acid Motifs", "descriptor_ui": "D020816", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cattle", "descriptor_ui": "D002417", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myosins", "descriptor_ui": "D009218", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Pseudopodia", "descriptor_ui": "D011554", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Activated full-length myosin-X moves processively on filopodia with large steps toward diverse two-dimensional directions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Very recent studies indicate that sulfur atoms with oxidation state 0 or −1, called sulfane sulfurs, are the actual mediators of some physiological processes previously considered to be regulated by hydrogen sulfide (H2S). 3-Mercaptopyruvate sulfurtransferase (3MST), one of three H2S-producing enzymes, was also recently shown to produce sulfane sulfur (H2Sn). Here, we report the discovery of several potent 3MST inhibitors by means of high-throughput screening (HTS) of a large chemical library (174,118 compounds) with our H2S-selective fluorescent probe, HSip-1. Most of the identified inhibitors had similar aromatic ring-carbonyl-S-pyrimidone structures. Among them, compound 3 showed very high selectivity for 3MST over other H2S/sulfane sulfur-producing enzymes and rhodanese. The X-ray crystal structures of 3MST complexes with two of the inhibitors revealed that their target is a persulfurated cysteine residue located in the active site of 3MST. Precise theoretical calculations indicated the presence of a strong long-range electrostatic interaction between the persulfur anion of the persulfurated cysteine residue and the positively charged carbonyl carbon of the pyrimidone moiety of the inhibitor. Our results also provide the experimental support for the idea that the 3MST-catalyzed reaction with 3-mercaptopyruvate proceeds via a ping-pong mechanism.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Sasakura", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Suwanai", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Toma-Fukai", "name": null }, { "creator_type": "author", "first_name": "Kazuhito", "last_name": "Shimamoto", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Norihiro", "last_name": "Shibuya", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ogasawara", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Chao", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep40227" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28079151" } }, "mesh": [ { "descriptor": "Catalytic Domain", "descriptor_ui": "D020134", "major_topic": false }, { "descriptor": "Crystallography, X-Ray", "descriptor_ui": "D018360", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Disulfides", "descriptor_ui": "D004220", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "High-Throughput Screening Assays", "descriptor_ui": "D057166", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Sulfurtransferases", "descriptor_ui": "D013466", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Discovery and Mechanistic Characterization of Selective Inhibitors of H2S-producing Enzyme: 3-Mercaptopyruvate Sulfurtransferase (3MST) Targeting Active-site Cysteine Persulfide.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Temperature is a fundamental physical parameter that plays an important role in biological reactions and events. Although thermometers developed previously have been used to investigate several important phenomena, such as heterogeneous temperature distribution in a single living cell and heat generation in mitochondria, the development of a thermometer with a sensitivity over a wide temperature range and rapid response is still desired to quantify temperature change in not only homeotherms but also poikilotherms from the cellular level to in vivo. To overcome the weaknesses of the conventional thermometers, such as a limitation of applicable species and a low temporal resolution, owing to the narrow temperature range of sensitivity and the thermometry method, respectively, we developed a genetically encoded ratiometric fluorescent temperature indicator, gTEMP, by using two fluorescent proteins with different temperature sensitivities. Our thermometric method enabled a fast tracking of the temperature change with a time resolution of 50 ms. We used this method to observe the spatiotemporal temperature change between the cytoplasm and nucleus in cells, and quantified thermogenesis from the mitochondria matrix in a single living cell after stimulation with carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, which was an uncoupler of oxidative phosphorylation. Moreover, exploiting the wide temperature range of sensitivity from 5 degrees C to 50 degrees C of gTEMP, we monitored the temperature in a living medaka embryo for 15 hours and showed the feasibility of in vivo thermometry in various living species.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Ippei", "last_name": "Kotera", "name": null }, { "creator_type": "author", "first_name": "Kohki", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kamei", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0172344" }, "pmcid": { "normalized": "PMC5315395" }, "pmid": { "normalized": "28212432" } }, "mesh": [ { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Thermometers", "descriptor_ui": "D013821", "major_topic": true }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "2", "normalized_date": "2017", "pages": "e0172344", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "12", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetically encoded ratiometric fluorescent thermometer with wide range and rapid response.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Coarse-grained models of DNA have made important contributions to the determination of the physical properties of genomic DNA, working as a molecular machine for gene regulation. In this study, to analyze the global dynamics of long DNA sequences with consideration of sequence-dependent geometry, we propose elastic network models of DNA where each particle represents k nucleotides (1-particle-per-k-nucleotides, 1PkN). The models were adjusted according to profiles of the anisotropic fluctuations obtained from our previous 1-particle-per-1-nucleotide (1P1N) model, which was proven to reproduce such profiles of all-atom models. We confirmed that the 1P3N and 1P4N models are suitable for the analysis of detailed dynamics such as local twisting motion. The models are intended for the analysis of large structures, e.g., 10-nm fibers in the nucleus, and nucleoids of mitochondrial or phage DNA at low computational costs. As an example, we surveyed the physical characteristics of the whole mitochondrial human and Plasmodium falciparum genomes.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takeru", "last_name": "Kameda", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Isami", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Togashi", "name": null }, { "creator_type": "author", "first_name": "Hiraku", "last_name": "Nishimori", "name": null }, { "creator_type": "author", "first_name": "Naoaki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Awazu", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fphys.2017.00103" }, "pmcid": { "normalized": "PMC5361685" }, "pmid": { "normalized": "28382002" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "103", "proceedings_title": null, "publisher": "", "title": "Frontiers in physiology", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "The 1-Particle-per-k-Nucleotides (1PkN) Elastic Network Model of DNA Dynamics with Sequence-Dependent Geometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To study the critical role of mineralocorticoid signalling, we generated a constitutive mineralocorticoid receptor (MR)-knockout (KO) medaka as the first adult-viable MR-KO animal. This KO medaka displayed abnormal behaviours affected by visual stimuli. In contrast, the loss of MR did not result in overt phenotypic changes in osmoregulation, despite the well-known osmoregulatory functions of MR in mammals. Since glucocorticoid receptor (GR) has been suggested to compensate for loss of MR, we examined expression of duplicated GRs with markedly different ligand sensitivities, in various tissues. qRT-PCR results revealed that the absence of MR induced GR1 in the brain and eyes, but not in osmoregulatory organs. This reinforces the important functions of glucocorticoid signalling, but the minor role of mineralocorticoid signalling, in fish osmoregulation. Because both 11-deoxycorticosterone (DOC) and cortisol are ligands for MR, whereas GRs are specific to cortisol, GR1 signalling may compensate for the absence of cortisol-MR, rather than that of DOC-MR. Thus, this GR expression suggests that our MR-KO model can be used specifically to characterize DOC-MR signalling.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Madoka", "last_name": "Yoshiki", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/sdata.2017.189" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29231924" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Oryzias", "descriptor_ui": "D009990", "major_topic": false }, { "descriptor": "Receptors, Glucocorticoid", "descriptor_ui": "D011965", "major_topic": false }, { "descriptor": "Receptors, Mineralocorticoid", "descriptor_ui": "D018161", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Data", "volume": "4", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "The mineralocorticoid receptor knockout in medaka is further validated by glucocorticoid receptor compensation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sexually dimorphic traits are common and widespread among animals. The expression of the Doublesex-/Mab-3-domain (DM-domain) gene family has been widely studied in model organisms and has been proven to be essential for the development and maintenance of sex-specific traits. However, little is known about the detailed expression patterns in non-model organisms. In the present study, we demonstrated the spatiotemporal expression of the DM-domain gene, doublesex1 (dsx1), in the crustacean Daphnia magna, which parthenogenetically produces males in response to environmental cues. We developed a dsx1 reporter strain to track dsx1 activity in vivo by inserting the mCherry gene into the dsx1 locus using the TALEN-mediated knock-in approach. After confirming dsx1 expression in male-specific traits in juveniles and adults, we performed time-lapse imaging of embryogenesis. Shortly after gastrulation stage, a presumptive primary organiser, named cumulus, first showed male-specific dsx1 expression. This cell mass moved to the posterior growth zone that distributes dsx1-expressing progenitor cells across the body during axial elongation, before embryos start male-specific dsx1 expression in sexually dimorphic structures. The present study demonstrated the sex-specific dsx1 expression in cell populations involved in basal body formation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Quang Dang", "last_name": "Nong", "name": null }, { "creator_type": "author", "first_name": "Nur Syafiqah", "last_name": "Mohamad Ishak", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-13730-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29097757" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arthropod Proteins", "descriptor_ui": "D060829", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Red Fluorescent Protein", "descriptor_ui": "D000097573", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Mapping the expression of the sex determining factor Doublesex1 in Daphnia magna using a knock-in reporter.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydrogen sulfide (H2S) exerts synergistic effects with another gaseous signaling molecule nitric oxide (NO) on ion channels and vasculature. However, the mechanism of the synergy is not well understood. Here, we show that the interaction between H2S and NO generates polysulfides (H2Sn), which activate transient receptor potential ankyrin 1 (TRPA1) channels. High performance liquid chromatography with tandem mass spectrometry analysis, along with the imaging of intracellular Ca2+ and H2Sn, showed that H2Sn and their effects were abolished by cyanolysis and by reducing substances such as dithiothreitol (DTT), cysteine, and glutathione (GSH). However, the effects of nitroxyl or nitrosopersulfide, other potential products of H2S and NO interaction, are not affected by cyanolysis or reducing substances. This study demonstrates that H2Sn are products of synergy between H2S and NO and provides a new insight into the signaling mechanisms.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Norihiro", "last_name": "Shibuya", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ogasawara", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Kimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep45995" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28378773" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": false }, { "descriptor": "Ion Channel Gating", "descriptor_ui": "D015640", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false }, { "descriptor": "Tandem Mass Spectrometry", "descriptor_ui": "D053719", "major_topic": false }, { "descriptor": "TRPA1 Cation Channel", "descriptor_ui": "D000074025", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Polysulfides (H2Sn) produced from the interaction of hydrogen sulfide (H2S) and nitric oxide (NO) activate TRPA1 channels.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The response of peripheral T lymphocytes (T cell) is controlled by multiple checkpoints to avoid unwanted activation against self-tissues. Two opposing costimulatory receptors, CD28 and CTLA-4, on T cells bind to the same ligands (CD80 and CD86) on antigen-presenting cells (APCs), and provide positive and negative feedback for T-cell activation, respectively. Early studies suggested that CTLA-4 is induced on activated T cells and binds to CD80/CD86 with much stronger affinity than CD28, providing a competitive inhibition. Subsequent studies by many researchers revealed the more complex mode of T-cell inhibition by CTLA-4. After T-cell activation, CTLA-4 is stored in the intracellular vesicles, and recruited to the immunological synapse formed between T cells and APCs, and inhibits further activation of T cells by blocking signals initiated by T-cell receptors and CD28. CTLA-4-positive cells can also provide cell-extrinsic regulation on other autoreactive T cells, and are considered to provide an essential regulatory mechanism for FoxP3+ regulatory T cells. Genetic deficiency of CTLA-4 leads to CD28-mediated severe autoimmunity in mice and humans, suggesting its function as a fundamental brake that restrains the expansion and activation of self-reactive T cells. In cancer, therapeutic approaches targeting CTLA-4 by humanized blocking antibodies has been demonstrated to be an effective immunotherapy by reversing T-cell tolerance against tumors. This chapter introduces CTLA-4 biology, including its discovery and mechanism of action, and discusses questions related to CTLA-4.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/82_2017_61" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28900679" } }, "mesh": [ { "descriptor": "Abatacept", "descriptor_ui": "D000069594", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, CD", "descriptor_ui": "D015703", "major_topic": true }, { "descriptor": "CD28 Antigens", "descriptor_ui": "D018106", "major_topic": false }, { "descriptor": "CTLA-4 Antigen", "descriptor_ui": "D060908", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoconjugates", "descriptor_ui": "D018796", "major_topic": true }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "99-126", "proceedings_title": null, "publisher": "", "title": "Current topics in microbiology and immunology", "volume": "410", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "CTLA-4, an Essential Immune-Checkpoint for T-Cell Activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system (Cas) is widely used for mediating the knock-in of foreign DNA into the genomes of various organisms. Here, we report a process of CRISPR/Cas-mediated knock-in via non-homologous end joining by the direct injection of Cas9/gRNA ribonucleoproteins (RNPs) in the crustacean Daphnia magna, which is a model organism for studies on toxicology, ecology, and evolution. First, we confirmed the cleavage activity of Cas9 RNPs comprising purified Cas9 proteins and gRNAs in D. magna. We used a gRNA that targets exon 10 of the eyeless gene. Cas9 proteins were incubated with the gRNAs and the resulting Cas9 RNPs were injected into D. magna eggs, which led to a typical phenotype of the eyeless mutant, i.e., eye deformity. The somatic and heritable mutagenesis efficiencies were up to 96% and 40%, respectively. Second, we tested the CRISPR/Cas-mediated knock-in of a plasmid by the injection of Cas9 RNPs. The donor DNA plasmid harboring the fluorescent reporter gene was designed to contain the gRNA recognition site. The co-injection of Cas9 RNPs together with the donor DNAs resulted in generation of one founder animal that produced fluorescent progenies. This transgenic Daphnia had donor DNA at the targeted genomic site, which suggested the concurrent cleavage of the injected plasmid DNA and genomic DNA. Owing to its simplicity and ease of experimental design, we suggest that the CRISPR/Cas-mediated knock-in method represents a promising tool for studying functional genomics in D. magna.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0186112" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29045453" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "DNA End-Joining Repair", "descriptor_ui": "D059766", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": true }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Genetic Loci", "descriptor_ui": "D056426", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Ribonucleoproteins", "descriptor_ui": "D012261", "major_topic": false }, { "descriptor": "Transgenes", "descriptor_ui": "D019076", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "10", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "12", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "CRISPR/Cas-mediated knock-in via non-homologous end-joining in the crustacean Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cerebellum is a brain structure involved in coordination, control, and learning of movements, as well as certain aspects of cognitive function. Purkinje cells are the sole output neurons from the cerebellar cortex and therefore play crucial roles in the overall function of the cerebellum. The type-1 metabotropic glutamate receptor (mGluR1) is a key \"hub\" molecule that is critically involved in the regulation of synaptic wiring, excitability, synaptic response, and synaptic plasticity of Purkinje cells. In this review, we aim to highlight how mGluR1 controls these events in Purkinje cells. We also describe emerging evidence that altered mGluR1 signaling in Purkinje cells underlies cerebellar dysfunctions in several clinically relevant mouse models of human ataxias.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.12688/f1000research.10485.1" }, "pmcid": { "normalized": "PMC5381626" }, "pmid": { "normalized": "28435670" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "416", "proceedings_title": null, "publisher": "", "title": "F1000Research", "volume": "6", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Type-1 metabotropic glutamate receptor signaling in cerebellar Purkinje cells in health and disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Identification of drug induced electrical instability of the heart curtails development, and introduction, of potentially proarrhythmic drugs. This problem usually requires complimentary contact based approaches such as patch-clamp electrophysiology combined with field stimulation electrodes to observe and control the cell. This produces data with high signal to noise but requires direct physical contact generally preventing high-throughput, or prolonged, phenotyping of single cells or tissues. Combining genetically encoded optogenetic control and spectrally compatible calcium indicator tools into a single adenoviral vector allows the analogous capability for cell control with simultaneous cellular phenotyping without the need for contact. This combination can be applied to single rodent primary adult cardiomyocytes, and human stem cell derived cardiomyocytes, enabling contactless small molecule evaluation for inhibitors of sodium, potassium and calcium channels suggesting it may be useful for early toxicity work. In pancreatic beta-cells it reveals the effects of glucose and the KATP inhibitor gliclazide.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yu-Fen", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Connor N.", "last_name": "Broyles", "name": null }, { "creator_type": "author", "first_name": "Frances A.", "last_name": "Brook", "name": null }, { "creator_type": "author", "first_name": "Mark J.", "last_name": "Davies", "name": null }, { "creator_type": "author", "first_name": "Cameron W.", "last_name": "Turtle", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Matthew J.", "last_name": "Daniels", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0174181" }, "pmcid": { "normalized": "PMC5381843" }, "pmid": { "normalized": "28379974" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Channels", "descriptor_ui": "D015220", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Gliclazide", "descriptor_ui": "D005907", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Guinea Pigs", "descriptor_ui": "D006168", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin-Secreting Cells", "descriptor_ui": "D050417", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Potassium", "descriptor_ui": "D011188", "major_topic": false }, { "descriptor": "Small Molecule Libraries", "descriptor_ui": "D054852", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "4", "normalized_date": "2017", "pages": "e0174181", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "12", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Non-invasive phenotyping and drug testing in single cardiomyocytes or beta-cells by calcium imaging and optogenetics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescent proteins (FPs) displaying distinct spectra have shed their light on a wide range of biological functions. Moreover, sophisticated biosensors engineered to contain single or multiple FPs, including Forster resonance energy transfer (FRET)-based biosensors, spatiotemporally reveal the molecular mechanisms underlying a variety of pathophysiological processes. However, their usefulness for applied life sciences has yet to be fully explored. Recently, our research group has begun to expand the potential of FPs from basic biological research to the clinic. Here, we describe a method to evaluate the responsiveness of leukemia cells from patients to tyrosine kinase inhibitors using a biosensor based on FP technology and the principle of FRET. Upon phosphorylation of the tyrosine residue of the biosensor, binding of the SH2 domain to phosphotyrosine induces conformational change of the biosensor and brings the donor and acceptor FPs into close proximity. Therefore, kinase activity and response to kinase inhibitors can be monitored by an increase and a decrease in FRET efficiency, respectively. As in basic research, this biosensor resolves hitherto arduous tasks and may provide innovative technological advances in clinical laboratory examinations. State-of-the-art detection devices that enable such innovation are also introduced.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mari", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Nakada", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4939-6762-9_30" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28092053" } }, "mesh": [ { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Bone Marrow Cells", "descriptor_ui": "D001854", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fusion Proteins, bcr-abl", "descriptor_ui": "D016044", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Leukemic", "descriptor_ui": "D015973", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Leukemia, Myelogenous, Chronic, BCR-ABL Positive", "descriptor_ui": "D015464", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Interaction Domains and Motifs", "descriptor_ui": "D054730", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false }, { "descriptor": "src Homology Domains", "descriptor_ui": "D018909", "major_topic": true }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "513-534", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "1555", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "SH2 Domain-Based FRET Biosensor for Measuring BCR-ABL Activity in Living CML Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Dahee", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Yu J.", "last_name": "Hwang", "name": null }, { "creator_type": "author", "first_name": "Hoon", "last_name": "Ryu", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Jeiwon", "last_name": "Cho", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnbeh.2017.00242" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29242712" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Behavioral Neuroscience", "volume": "11", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Corrigendum: Conditional Knockout of Cav2.1 Disrupts the Accuracy of Spatial Recognition of CA1 Place Cells and Spatial/Contextual Recognition Behavior.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Aberrant crypt foci (ACF), the earliest precursor lesion of colorectal cancers (CRCs), are a good surrogate marker for CRC risk stratification and chemoprevention. However, the conventional ACF detection method with dye-spraying by magnifying colonoscopy is labor- and skill-intensive. We sought to identify rat and human ACF using a fluorescent imaging technique that targets a molecule specific for ACF. We found that glutathione S-transferase (GST) P1-1 was overexpressed in ACF tissues in a screening experiment. We then synthesized the fluorogenic probe, DNAT-Me, which is fluorescently quenched but is activated by GSTP1-1. A CRC cell line incubated with DNAT-Me showed strong fluorescence in the cytosol. Fluorescence intensities correlated significantly with GST activities in cancer cell lines. When we sprayed DNAT-Me onto colorectal mucosa excised from azoxymethane-treated rats and surgically resected from CRC patients, ACF with strong fluorescent signals were clearly observed. The ACF number determined by postoperative DNAT-Me imaging was almost identical to that determined by preoperative methylene blue staining. The signal-to-noise ratio for ACF in DNAT-Me images was significantly higher than that in methylene blue staining. Thus, we sensitively visualized ACF on rat and human colorectal mucosa by using a GST-activated fluorogenic probe without dye-spraying and magnifying colonoscopy.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Tadahiko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Katsutaka", "last_name": "Sannomiya", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Mitsui", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Higashijima", "name": null }, { "creator_type": "author", "first_name": "Mitsuo", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Horino", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Shibutani", "name": null }, { "creator_type": "author", "first_name": "Tetsuji", "last_name": "Takayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-06857-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28747791" } }, "mesh": [ { "descriptor": "Aberrant Crypt Foci", "descriptor_ui": "D058739", "major_topic": false }, { "descriptor": "Colon", "descriptor_ui": "D003106", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Glutathione Transferase", "descriptor_ui": "D005982", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular imaging of aberrant crypt foci in the human colon targeting glutathione S-transferase P1-1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Filopodia protrude from the leading edge of cells and play important roles in cell motility. Here we report the mechanism of myosin X (encoded by Myo10)-induced multi-cycle filopodia extension. We found that actin, Arp2/3, vinculin and integrin-β first accumulated at the cell’s leading edge. Myosin X was then gathered at these sites, gradually clustered by lateral movement, and subsequently initiated filopodia formation. During filopodia extension, we found the translocation of Arp2/3 and integrin-β along filopodia. Arp2/3 and integrin-β then became localized at the tip of filopodia, from where myosin X initiated the second extension of filopodia with a change in extension direction, thus producing long filopodia. Elimination of integrin-β, Arp2/3 and vinculin by siRNA significantly attenuated the myosin-X-induced long filopodia formation. We propose the following mechanism. Myosin X accumulates at nascent focal adhesions at the cell’s leading edge, where myosin X promotes actin convergence to create the base of filopodia. Then myosin X moves to the filopodia tip and attracts integrin-β and Arp2/3 for further actin nucleation. The tip-located myosin X then initiates the second cycle of filopodia elongation to produce the long filopodia.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kangmin", "last_name": "He", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Tsukasaki", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Mitsuo", "last_name": "Ikebe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-06147-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29057977" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cattle", "descriptor_ui": "D002417", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Focal Adhesions", "descriptor_ui": "D022001", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Integrin beta Chains", "descriptor_ui": "D039641", "major_topic": false }, { "descriptor": "Myosins", "descriptor_ui": "D009218", "major_topic": false }, { "descriptor": "Pseudopodia", "descriptor_ui": "D011554", "major_topic": false }, { "descriptor": "Vinculin", "descriptor_ui": "D016596", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Myosin X is recruited to nascent focal adhesions at the leading edge and induces multi-cycle filopodial elongation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid neuropeptide which has been shown to exert various neuroprotective actions in vitro and in vivo; however, the ability of endogenous PACAP to prevent cell death in vivo remains to be elucidated. To explore the capacity of endogenous PACAP to prevent ethanol toxicity, adolescent and adult PACAP knockout (KO) mice were injected with ethanol in a binge drinking-like manner. Biochemical analyses revealed that ethanol administration induced an increase in the production of reactive oxygen species and the activity of caspase-3 in PACAP KO mice in an age-independent manner. In order to characterize the mechanisms underlying the sensitivity of PACAP KO mice, a whole-genome microarray analysis was performed to compare gene regulations induced by ethanol in adolescent and adult wild-type and PACAP KO mice. Gene expression substantially differed between adolescent and adult wild-type mice, suggesting distinct effects of ethanol according to the state of brain maturation. Interestingly, in adolescent and adult PACAP KO mice, the set of genes regulated were also markedly different but seemed to inhibit some similar regulatory network processes associated in particular with DNA repair and cell cycle. These data imply that ethanol induces serious DNA damages and cell cycle alteration in PACAP KO mice. This hypothesis, based on the transcriptomic data, could be confirmed by functional studies which showed that cell proliferation decreased in adolescent and adult PACAP KO mice treated with ethanol but recovered after a 30-day withdrawal period. These data, obtained with PACAP KO animals, demonstrate that endogenous PACAP protects the brain of adolescent and adult mice from alcohol toxicity and modulates distinct sets of genes according to the maturation status of the brain.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Helene", "last_name": "Lacaille", "name": null }, { "creator_type": "author", "first_name": "Dominique", "last_name": "Duterte-Boucher", "name": null }, { "creator_type": "author", "first_name": "Hubert", "last_name": "Vaudry", "name": null }, { "creator_type": "author", "first_name": "Yasmine", "last_name": "Zerdoumi", "name": null }, { "creator_type": "author", "first_name": "Jean-Michel", "last_name": "Flaman", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Vaudry", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12035-016-0204-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27826748" } }, "mesh": [ { "descriptor": "Age Factors", "descriptor_ui": "D000367", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Ethanol", "descriptor_ui": "D000431", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "7534-7548", "proceedings_title": null, "publisher": "", "title": "Molecular neurobiology", "volume": "54", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "PACAP Protects the Adolescent and Adult Mice Brain from Ethanol Toxicity and Modulates Distinct Sets of Genes Regulating Similar Networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide. In addition to its diverse physiological roles, PACAP has important functions in the embryonic development of various tissues, and it is also considered as a trophic factor during development and in the case of neuronal injuries. Data suggest that the development of the nervous system is severely affected by the lack of endogenous PACAP. Short-term neurofunctional outcome correlates with long-term functional deficits; however, the early neurobehavioral development of PACAP-deficient mice has not yet been evaluated. Therefore, the aim of the present study was to describe the postnatal development of physical signs and neurological reflexes in mice partially or completely lacking PACAP. We examined developmental hallmarks during the first 3 weeks of the postnatal period, during which period most neurological reflexes and motor coordination show most intensive development, and we describe the neurobehavioral development using a complex battery of tests. In the present study, we found that PACAP-deficient mice had slower weight gain throughout the observation period. Interestingly, mice partially lacking PACAP weighed significantly less than homozygous mice. There was no difference between male and female mice during the first 3 weeks. Some other signs were also more severely affected in the heterozygous mice than in the homozygous mice, such as air righting, grasp, and gait initiation reflexes. Interestingly, incisor teeth erupted earlier in mice lacking PACAP. Motor coordination, shown by the number of foot-faults on an elevated grid, was also less developed in PACAP-deficient mice. In summary, our results show that mice lacking endogenous PACAP have slower weight gain during the first weeks of development and slower neurobehavioral development regarding a few developmental hallmarks.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Jozsef", "last_name": "Farkas", "name": null }, { "creator_type": "author", "first_name": "Balazs", "last_name": "Sandor", "name": null }, { "creator_type": "author", "first_name": "Andrea", "last_name": "Tamas", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Kiss", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Andras D.", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Balazs D.", "last_name": "Fulop", "name": null }, { "creator_type": "author", "first_name": "Tamas", "last_name": "Juhasz", "name": null }, { "creator_type": "author", "first_name": "Sridharan", "last_name": "Manavalan", "name": null }, { "creator_type": "author", "first_name": "Dora", "last_name": "Reglodi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12031-017-0887-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28168413" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Weight", "descriptor_ui": "D001835", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Heterozygote", "descriptor_ui": "D006579", "major_topic": false }, { "descriptor": "Homozygote", "descriptor_ui": "D006720", "major_topic": false }, { "descriptor": "Incisor", "descriptor_ui": "D007180", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": true }, { "descriptor": "Nervous System", "descriptor_ui": "D009420", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Reflex", "descriptor_ui": "D012018", "major_topic": true } ], "publication": { "conference_name": null, "date": "2017 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "468-478", "proceedings_title": null, "publisher": "", "title": "Journal of molecular neuroscience : MN", "volume": "61", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Early Neurobehavioral Development of Mice Lacking Endogenous PACAP.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A major cause of cancer death is its metastasis to the vital organs. Few effective therapies are available for metastatic castration-resistant prostate cancer (PCa), and progressive metastatic lesions such as lymph nodes and bones cause mortality. We recently identified AES as a metastasis suppressor for colon cancer. Here, we have studied the roles of AES in PCa progression. We analyzed the relationship between AES expression and PCa stages of progression by immunohistochemistry of human needle biopsy samples. We then performed overexpression and knockdown of AES in human PCa cell lines LNCaP, DU145 and PC3, and determined the effects on proliferation, invasion and metastasis in culture and in a xenograft model. We also compared the PCa phenotypes of Aes/Pten compound knockout mice with those of Pten simple knockout mice. Expression levels of AES were inversely correlated with clinical stages of human PCa. Exogenous expression of AES suppressed the growth of LNCaP cells, whereas the AES knockdown promoted it. We also found that AES suppressed transcriptional activities of androgen receptor and Notch signaling. Notably, AES overexpression in AR-defective DU145 and PC3 cells reduced invasion and metastasis to lymph nodes and bones without affecting proliferation in culture. Consistently, prostate epithelium-specific inactivation of Aes in Pten(flox/flox) mice increased expression of Snail and MMP9, and accelerated growth, invasion and lymph node metastasis of the mouse prostate tumor. These results suggest that AES plays an important role in controlling tumor growth and metastasis of PCa by regulating both AR and Notch signaling pathways.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Kakizaki", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Yoshiro", "last_name": "Itatani", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Uegaki", "name": null }, { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Kamba", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "M. Mark", "last_name": "Taketo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.13187" }, "pmcid": { "normalized": "PMC5406606" }, "pmid": { "normalized": "28178391" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Co-Repressor Proteins", "descriptor_ui": "D056970", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Mice, SCID", "descriptor_ui": "D016513", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false }, { "descriptor": "Prostatic Neoplasms", "descriptor_ui": "D011471", "major_topic": false }, { "descriptor": "PTEN Phosphohydrolase", "descriptor_ui": "D051059", "major_topic": false }, { "descriptor": "Receptors, Androgen", "descriptor_ui": "D011944", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transplantation, Heterologous", "descriptor_ui": "D014183", "major_topic": false }, { "descriptor": "Tumor Suppressor Proteins", "descriptor_ui": "D025521", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "744-752", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "108", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Amino-terminal enhancer of split gene AES encodes a tumor and metastasis suppressor of prostate cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Inhibitory synapses are established during development but continue to be generated and modulated in strength in the mature nervous system. In the spinal cord and brainstem, presynaptically released inhibitory neurotransmitter dominantly switches from GABA to glycine during normal development in vivo. While presynaptic mechanisms of the shift of inhibitory neurotransmission are well investigated, the contribution of postsynaptic neurotransmitter receptors to this shift is not fully elucidated. Synaptic clustering of glycine receptors (GlyRs) is regulated by activation-dependent depolarization in early development. However, GlyR activation induces hyperpolarization after the first postnatal week, and little is known whether and how presynaptically released glycine regulates postsynaptic receptors in a depolarization-independent manner in mature developmental stage. Here we developed spinal cord neuronal culture of rodents using chronic strychnine application to investigate whether initial activation of GlyRs in mature stage could change postsynaptic localization of GlyRs. Immunocytochemical analyses demonstrate that chronic blockade of GlyR activation until mature developmental stage resulted in smaller clusters of postsynaptic GlyRs that could be enlarged upon receptor activation for 1 h in the mature stage. Furthermore, live cell-imaging techniques show that GlyR activation decreases its lateral diffusion at synapses, and this phenomenon is dependent on PKC, but neither Ca(2+) nor CaMKII activity. These results suggest that the GlyR activation can regulate receptor diffusion and cluster size at inhibitory synapses in mature stage, providing not only new insights into the postsynaptic mechanism of shifting inhibitory neurotransmission but also the inhibitory synaptic plasticity in mature nervous system.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Nakahata", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Eto", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Kuriu", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Andrew J.", "last_name": "Moorhouse", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Nabekura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/eneuro.0194-16.2017" }, "pmcid": { "normalized": "PMC5292596" }, "pmid": { "normalized": "28197549" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Excitatory Amino Acid Antagonists", "descriptor_ui": "D018691", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glycine Agents", "descriptor_ui": "D018684", "major_topic": false }, { "descriptor": "Inhibitory Postsynaptic Potentials", "descriptor_ui": "D053444", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Photobleaching", "descriptor_ui": "D038761", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Receptors, Glycine", "descriptor_ui": "D018009", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false }, { "descriptor": "Strychnine", "descriptor_ui": "D013331", "major_topic": false }, { "descriptor": "Vesicular Inhibitory Amino Acid Transport Proteins", "descriptor_ui": "D050495", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan-Feb", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "ENEURO.0194-16.2017", "proceedings_title": null, "publisher": "", "title": "eNeuro", "volume": "4", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Activation-Dependent Rapid Postsynaptic Clustering of Glycine Receptors in Mature Spinal Cord Neurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Inhibition of immune checkpoint molecules, PD-1 and CTLA4, has been shown to be a promising cancer treatment. PD-1 and CTLA4 inhibit TCR and co-stimulatory signals. The third T cell activation signal represents the signals from the cytokine receptors. The cytokine interferon-gamma (IFNgamma) plays an important role in anti-tumor immunity by activating cytotoxic T cells (CTLs). Most cytokines use the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, and the suppressors of cytokine signaling (SOCS) family of proteins are major negative regulators of the JAK/STAT pathway. Among SOCS proteins, CIS, SOCS1, and SOCS3 proteins can be considered the third immunocheckpoint molecules since they regulate cytokine signals that control the polarization of CD4(+) T cells and the maturation of CD8(+) T cells. This review summarizes recent progress on CIS, SOCS1, and SOCS3 in terms of their anti-tumor immunity and potential applications.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Kanamori", "name": null }, { "creator_type": "author", "first_name": "Setsuko", "last_name": "Mise-Omata", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.13194" }, "pmcid": { "normalized": "PMC5406529" }, "pmid": { "normalized": "28188673" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunotherapy", "descriptor_ui": "D007167", "major_topic": false }, { "descriptor": "Models, Immunological", "descriptor_ui": "D018448", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Suppressor of Cytokine Signaling 1 Protein", "descriptor_ui": "D000071222", "major_topic": false }, { "descriptor": "Suppressor of Cytokine Signaling 3 Protein", "descriptor_ui": "D000071223", "major_topic": false }, { "descriptor": "Suppressor of Cytokine Signaling Proteins", "descriptor_ui": "D050826", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "574-580", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "108", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Suppressors of cytokine signaling: Potential immune checkpoint molecules for cancer immunotherapy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fusion tyrosine kinases play a crucial role in the development of hematological malignancies. FIP1L1-PDGFRA is a leukemogenic fusion kinase that causes chronic eosinophilic leukemia. As a constitutively active kinase, FIP1L1-PDGFRA stimulates downstream signaling molecules, leading to cellular proliferation and the generation of an anti-apoptotic state. Contribution of the N-terminal FIP1L1 portion is necessary for FIP1L1-PDGFRA to exert its full transforming activity, but the underlying mechanisms have not been fully characterized. We identified PIAS1 as a FIP1L1-PDGFRA association molecule by yeast two-hybrid screening. Our analyses indicate that the FIP1L1 portion of FIP1L1-PDGFRA is required for efficient association with PIAS1. As a consequence of the association, FIP1L1-PDGFRA phosphorylates PIAS1. Moreover, the kinase activity of FIP1L1-PDGFRA stabilizes PIAS1. Therefore, PIAS1 is one of the downstream targets of FIP1L1-PDGFRA. Moreover, we found that PIAS1, as a SUMO E3 ligase, sumoylates and stabilizes FIP1L1-PDGFRA. In addition, suppression of PIAS1 activity by a knockdown experiment resulted in destabilization of FIP1L1-PDGFRA. Therefore, FIP1L1-PDGFRA and PIAS1 form a positive cross-talk through their enzymatic activities. Suppression of sumoylation by ginkgolic acid, a small molecule compound inhibiting a SUMO E1-activating enzyme, also destabilizes FIP1L1-PDGFRA, and while the tyrosine kinase inhibitor imatinib suppresses FIP1L1-PDGFRA-dependent cell growth, ginkgolic acid or siRNA of PIAS1 has a synergistic effect with imatinib. In conclusion, our results suggest that sumoylation by PIAS1 is a potential target in the treatment of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Ibata", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Stephanie", "last_name": "Darmanin", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Onozawa", "name": null }, { "creator_type": "author", "first_name": "Daigo", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Shigetsugu", "last_name": "Hatakeyama", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Teshima", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kondo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.13129" }, "pmcid": { "normalized": "PMC5367148" }, "pmid": { "normalized": "27960034" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypereosinophilic Syndrome", "descriptor_ui": "D017681", "major_topic": false }, { "descriptor": "Imatinib Mesylate", "descriptor_ui": "D000068877", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Immunoprecipitation", "descriptor_ui": "D047468", "major_topic": false }, { "descriptor": "mRNA Cleavage and Polyadenylation Factors", "descriptor_ui": "D039221", "major_topic": false }, { "descriptor": "Oncogene Proteins, Fusion", "descriptor_ui": "D015514", "major_topic": false }, { "descriptor": "Protein Inhibitors of Activated STAT", "descriptor_ui": "D050828", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Protein-Tyrosine Kinases", "descriptor_ui": "D011505", "major_topic": false }, { "descriptor": "Receptor, Platelet-Derived Growth Factor alpha", "descriptor_ui": "D020796", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "STAT1 Transcription Factor", "descriptor_ui": "D050794", "major_topic": false }, { "descriptor": "Sumoylation", "descriptor_ui": "D058207", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "200-207", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "108", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Leukemogenic kinase FIP1L1-PDGFRA and a small ubiquitin-like modifier E3 ligase, PIAS1, form a positive cross-talk through their enzymatic activities.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The synaptic delivery of neurotransmitter receptors, such as GluA1 AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors, mediates important processes in cognitive function, including memory acquisition and retention. Understanding the roles of these receptors has been hampered by the lack of a method to inactivate them in vivo with high spatiotemporal precision. We developed a technique to inactivate synaptic GluA1 AMPA receptors in vivo using chromophore-assisted light inactivation (CALI). We raised a monoclonal antibody specific for the extracellular domain of GluA1 that induced effective CALI when conjugated with a photosensitizer (eosin). Mice that had been injected in the CA1 hippocampal region with the antibody conjugate underwent a fear memory task. Exposing the hippocampus to green light using an implanted cannula erased acquired fear memory in the animals by inactivation of synaptic GluA1. Our optical technique for inactivating synaptic proteins will enable elucidation of their physiological roles in cognition.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kiwamu", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Iwanari", "name": null }, { "creator_type": "author", "first_name": "Hirobumi", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Suyama", "name": null }, { "creator_type": "author", "first_name": "Akane", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Hamakubo", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nbt.3710" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27918547" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Extinction, Psychological", "descriptor_ui": "D005108", "major_topic": false }, { "descriptor": "Fear", "descriptor_ui": "D005239", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Neural Inhibition", "descriptor_ui": "D009433", "major_topic": false }, { "descriptor": "Photic Stimulation", "descriptor_ui": "D010775", "major_topic": false }, { "descriptor": "Receptors, AMPA", "descriptor_ui": "D018091", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "38-47", "proceedings_title": null, "publisher": "", "title": "Nature biotechnology", "volume": "35", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Optical inactivation of synaptic AMPA receptors erases fear memory.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Various organisms have color patterns on their body surfaces, and these color patterns are thought to contribute to physiological regulation, communication with conspecifics, and signaling with the environment. An adult fly of Drosophila guttifera (Insecta: Diptera: Drosophilidae) has melanin pigmentation patterns on its body and wings. Though D. guttifera has been used for research into color pattern formation, how its pupal development proceeds and when the pigmentation starts have not been well studied. In this study, we defined the pupal stages of D. guttifera and measured the pigment content of wing spots from the pupal period to the period after eclosion. Using a transgenic line which carries eGFP connected with an enhancer of yellow, a gene necessary for melanin synthesis, we analyzed the timing at which the yellow enhancer starts to drive eGFP. We also analyzed the distribution of Yellow-producing cells, as indicated by the expression of eGFP during pupal and young adult periods. The results suggested that Yellow-producing cells were removed from wings within 3 h after eclosion, and wing pigmentation continued without epithelial cells. Furthermore, the results of vein cutting experiments showed that the transport of melanin precursors through veins was necessary for wing pigmentation. These results showed the importance of melanin precursors transported through veins and of extracellular factors which were secreted from epithelial cells and left in the cuticle.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuichi", "last_name": "Fukutomi", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Kiyokazu", "last_name": "Agata", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Funayama", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Koshikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00427-017-0578-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28280924" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Pigmentation", "descriptor_ui": "D010858", "major_topic": false }, { "descriptor": "Pupa", "descriptor_ui": "D011679", "major_topic": false }, { "descriptor": "Wings, Animal", "descriptor_ui": "D014921", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "171-180", "proceedings_title": null, "publisher": "", "title": "Development genes and evolution", "volume": "227", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Pupal development and pigmentation process of a polka-dotted fruit fly, Drosophila guttifera (Insecta, Diptera).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: To investigate a link between the appearance of photoacoustic imaging (PAI) and microvasculature in prostate cancer and to assess the feasibility of PAI for angiogenesis imaging in prostate cancer. METHODS: We have developed a PAI system equipped with a transrectal ultrasound (TRUS)-type probe. Three patients who underwent PAI just before prostate biopsy and subsequently underwent radical prostatectomy were included. The PAI appearance was retrospectively reviewed, and in each patient, 4 representative areas were selected: 1 with high PAI signal intensity, 1 with low PAI signal intensity, 1 peripheral to the index tumor, and 1 inside the index tumor. The correlation of PAI intensity with 3 microvascular parameters-microvascular density, total vascular area (TVA), and total vascular length (TVL)-assessed by CD34-immunostaining in resected specimens was analyzed. RESULTS: In all 3 patients the PAI intensity, TVA, and TVL in areas with high-intensity PAI signals were significantly higher than those in areas with low-intensity PAI signals, suggesting that PAI appearance describes the distribution of microvasculature in prostatic tissue correctly. All index tumors showed a ring-like PAI appearance consisting of a peripheral area of high signal intensity completely or partially surrounding an area with low signal intensity. The PAI intensity, TVA, and TVL in the periphery of the index tumors were significantly higher than those inside of the index tumors. CONCLUSION: The intensity of PAI signals might reflect the microvascularity in normal prostatic tissues and index tumors. PAI could be a novel modality for imaging prostate cancer angiogenesis.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akio", "last_name": "Horiguchi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shinchi", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Takatsugu", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Shinmoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.urology.2017.07.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28735020" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microvessels", "descriptor_ui": "D055806", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Photoacoustic Techniques", "descriptor_ui": "D061088", "major_topic": false }, { "descriptor": "Pilot Projects", "descriptor_ui": "D010865", "major_topic": false }, { "descriptor": "Prostate", "descriptor_ui": "D011467", "major_topic": false }, { "descriptor": "Prostatectomy", "descriptor_ui": "D011468", "major_topic": false }, { "descriptor": "Prostatic Neoplasms", "descriptor_ui": "D011471", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Ultrasonography", "descriptor_ui": "D014463", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Oct", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "212-219", "proceedings_title": null, "publisher": "", "title": "Urology", "volume": "108", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Pilot Study of Prostate Cancer Angiogenesis Imaging Using a Photoacoustic Imaging System.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Damage-associated molecular patterns (DAMPs) trigger sterile inflammation after tissue injury, but the mechanisms underlying the resolution of inflammation remain unclear. In this study, we demonstrate that common DAMPs, such as high-mobility-group box 1 (HMGB1), peroxiredoxins (PRXs), and S100A8 and S100A9, were internalized through the class A scavenger receptors MSR1 and MARCO in vitro. In ischemic murine brain, DAMP internalization was largely mediated by MSR1. An elevation of MSR1 levels in infiltrating myeloid cells observed 3 d after experimental stroke was dependent on the transcription factor Mafb. Combined deficiency for Msr1 and Marco, or for Mafb alone, in infiltrating myeloid cells caused impaired clearance of DAMPs, more severe inflammation, and exacerbated neuronal injury in a murine model of ischemic stroke. The retinoic acid receptor (RAR) agonist Am80 increased the expression of Mafb, thereby enhancing MSR1 expression. Am80 exhibited therapeutic efficacy when administered, even at 24 h after the onset of experimental stroke. Our findings uncover cellular mechanisms contributing to DAMP clearance in resolution of the sterile inflammation triggered by tissue injury.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Shichita", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Rimpei", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Komai", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Ooboshi", "name": null }, { "creator_type": "author", "first_name": "Ryusuke", "last_name": "Koshida", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Kodama", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nm.4312" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28394332" } }, "mesh": [ { "descriptor": "Alarmins", "descriptor_ui": "D000067531", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzoates", "descriptor_ui": "D001565", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Brain Ischemia", "descriptor_ui": "D002545", "major_topic": false }, { "descriptor": "Calgranulin A", "descriptor_ui": "D040501", "major_topic": false }, { "descriptor": "Calgranulin B", "descriptor_ui": "D040502", "major_topic": false }, { "descriptor": "Chromatin Immunoprecipitation", "descriptor_ui": "D047369", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "HMGB1 Protein", "descriptor_ui": "D024243", "major_topic": false }, { "descriptor": "Infarction, Middle Cerebral Artery", "descriptor_ui": "D020244", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "MafB Transcription Factor", "descriptor_ui": "D051258", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myeloid Cells", "descriptor_ui": "D022423", "major_topic": false }, { "descriptor": "Peroxiredoxins", "descriptor_ui": "D054464", "major_topic": false }, { "descriptor": "Receptors, Immunologic", "descriptor_ui": "D011971", "major_topic": false }, { "descriptor": "Receptors, Retinoic Acid", "descriptor_ui": "D018168", "major_topic": false }, { "descriptor": "Scavenger Receptors, Class A", "descriptor_ui": "D051117", "major_topic": false }, { "descriptor": "Stroke", "descriptor_ui": "D020521", "major_topic": false }, { "descriptor": "Tetrahydronaphthalenes", "descriptor_ui": "D013764", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "723-732", "proceedings_title": null, "publisher": "", "title": "Nature medicine", "volume": "23", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "MAFB prevents excess inflammation after ischemic stroke by accelerating clearance of damage signals through MSR1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nowadays, the application of chemiluminescence imaging is no longer limited to the monitoring of slow biological phenomena such as circadian rhythms and in vivo tracking of cells. The expanded color palette of bright chemiluminescent protein and near-infrared-emitting luciferins have greatly improved the sensitivity of in vivo tracking of cells as well as enabling real-time cellular chemiluminescence imaging with high spatial resolution. Furthermore, functional chemiluminescent indicators based on the novel concept have been developed, providing more information related to physiological and pathological processes in living organisms. In this short review, we summarized the recent protein- and substrate-based approaches for tuning the emission wavelength, as well as for development of the functional indicators.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazushi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.copbio.2017.04.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28482221" } }, "mesh": [ { "descriptor": "Cell Tracking", "descriptor_ui": "D058948", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescence", "descriptor_ui": "D049449", "major_topic": true }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Dec", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "135-141", "proceedings_title": null, "publisher": "", "title": "Current opinion in biotechnology", "volume": "48", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Recent progress in expanding the chemiluminescent toolbox for bioimaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nonribosomal peptide synthetases (NRPSs) are multidomain enzyme templates for the synthesis of bioactive peptides. Large-scale conformational changes during peptide assembly are obvious from crystal structures, yet their dynamics and coupling to catalysis are poorly understood. We have designed an NRPS FRET sensor to monitor, in solution and in real time, the adoption of the productive transfer conformation between phenylalanine-binding adenylation (A) and peptidyl-carrier-protein domains of gramicidin synthetase I from Aneurinibacillus migulanus. The presence of ligands, substrates or intermediates induced a distinct fluorescence resonance energy transfer (FRET) readout, which was pinpointed to the population of specific conformations or, in two cases, mixtures of conformations. A pyrophosphate switch and lysine charge sensors control the domain alternation of the A domain. The phenylalanine-thioester and phenylalanine-AMP products constitute a mechanism of product inhibition and release that is involved in ordered assembly-line peptide biosynthesis. Our results represent insights from solution measurements into the conformational dynamics of the catalytic cycle of NRPSs.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Jonas", "last_name": "Alfermann", "name": null }, { "creator_type": "author", "first_name": "Xun", "last_name": "Sun", "name": null }, { "creator_type": "author", "first_name": "Florian", "last_name": "Mayerthaler", "name": null }, { "creator_type": "author", "first_name": "Thomas E.", "last_name": "Morrell", "name": null }, { "creator_type": "author", "first_name": "Eva", "last_name": "Dehling", "name": null }, { "creator_type": "author", "first_name": "Gerrit", "last_name": "Volkmann", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null }, { "creator_type": "author", "first_name": "Haw", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Henning D.", "last_name": "Mootz", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nchembio.2435" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28759017" } }, "mesh": [ { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": true }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Peptide Synthases", "descriptor_ui": "D010453", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "1009-1015", "proceedings_title": null, "publisher": "", "title": "Nature chemical biology", "volume": "13", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "FRET monitoring of a nonribosomal peptide synthetase.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "RATIONALE: Rodents exposed prenatally to valproic acid (VPA) exhibit autism spectrum disorder (ASD)-like behavioral abnormalities. We recently found that prenatal VPA exposure causes hypofunction of the prefrontal dopaminergic system in mice. This suggests that the dopaminergic system may be a potential pharmacological target for treatment of behavioral abnormalities in ASD patients. OBJECTIVES: In the present study, we examined the effects of antipsychotic drugs, which affect the dopaminergic system, on the social interaction deficits, recognition memory impairment, and reduction in dendritic spine density in the VPA mouse model of ASD. RESULTS: Both acute and chronic administrations of the atypical antipsychotic drugs risperidone and aripiprazole increased prefrontal dopamine (DA) release, while the typical antipsychotic drug haloperidol did not. Chronic risperidone and aripiprazole, but not haloperidol, increased the expression of c-Fos in the prefrontal cortex, although they all increased c-Fos expression in the striatum. Chronic, but not acute, administrations of risperidone and aripiprazole improved the VPA-induced social interaction deficits and recognition memory impairment, as well as the reduction in dendritic spine density in the prefrontal cortex and hippocampus. In contrast, chronic administration of haloperidol did not ameliorate VPA-induced abnormalities in behaviors and dendritic spine density. CONCLUSIONS: These findings indicate that chronic risperidone and aripiprazole treatments improve VPA-induced abnormalities in behaviors and prefrontal dendritic spine density, which may be mediated by repeated elevation of extracellular DA in the prefrontal cortex. Our results also imply that loss of prefrontal dendritic spines may be involved in the abnormal behaviors in the VPA mouse model of ASD.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Atsuki", "last_name": "Taruta", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Haruki", "last_name": "Kawase", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00213-017-4703-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28798977" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aripiprazole", "descriptor_ui": "D000068180", "major_topic": false }, { "descriptor": "Autism Spectrum Disorder", "descriptor_ui": "D000067877", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Dopamine Antagonists", "descriptor_ui": "D018492", "major_topic": false }, { "descriptor": "Dopaminergic Neurons", "descriptor_ui": "D059290", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Haloperidol", "descriptor_ui": "D006220", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Prenatal Exposure Delayed Effects", "descriptor_ui": "D011297", "major_topic": true }, { "descriptor": "Risperidone", "descriptor_ui": "D018967", "major_topic": false }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": false }, { "descriptor": "Valproic Acid", "descriptor_ui": "D014635", "major_topic": true } ], "publication": { "conference_name": null, "date": "2017 Nov", "date_precision": "unknown", "issue": "21", "normalized_date": null, "pages": "3217-3228", "proceedings_title": null, "publisher": "", "title": "Psychopharmacology", "volume": "234", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Risperidone and aripiprazole alleviate prenatal valproic acid-induced abnormalities in behaviors and dendritic spine density in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Divergence of upstream regulatory pathways of the transcription factor Doublesex (Dsx) serves as a basis for evolution of sex-determining mechanisms in animals. However, little is known about the regulation of Dsx in environmental sex determination. In the crustacean Daphnia magna, environmental sex determination is implemented by male-specific expression of the Dsx ortholog, Dsx1. Transcriptional regulation of Dsx1 comprises at least three phases during embryogenesis: non-sex-specific initiation, male-specific up-regulation, and its maintenance. Herein, we demonstrate that the male-specific up-regulation is controlled by the bZIP transcription factor, Vrille (Vri), an ortholog of the circadian clock genes—Drosophila Vri and mammalian E4BP4/NFIL3. Sequence analysis of the Dsx1 promoter/enhancer revealed a conserved element among two Daphnia species (D. magna and D. pulex), which contains a potential enhancer harboring a consensus Vri binding site overlapped with a consensus Dsx binding site. Besides non-sex-specific expression of Vri in late embryos, we found male-specific expression in early gastrula before the Dsx1 up-regulation phase begins. Knockdown of Vri in male embryos showed reduction of Dsx1 expression. In addition, transient overexpression of Vri in early female embryos up-regulated the expression of Dsx1 and induced male-specific trait. Targeted mutagenesis using CRISPR/Cas9 disrupted the enhancer on genome in males, which led to the reduction of Dsx1 expression. These results indicate that Vri was co-opted as a transcriptional activator of Dsx1 in environmental sex determination of D. magna. The data suggests the remarkably plastic nature of gene regulatory network in sex determination.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Nur Syafiqah", "last_name": "Mohamad Ishak", "name": null }, { "creator_type": "author", "first_name": "Quang Dang", "last_name": "Nong", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pgen.1006953" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29095827" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic-Leucine Zipper Transcription Factors", "descriptor_ui": "D050976", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Enhancer Elements, Genetic", "descriptor_ui": "D004742", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": false }, { "descriptor": "Genetic Loci", "descriptor_ui": "D056426", "major_topic": false }, { "descriptor": "Genotyping Techniques", "descriptor_ui": "D060005", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Sequence Analysis, DNA", "descriptor_ui": "D017422", "major_topic": false }, { "descriptor": "Sex Determination Processes", "descriptor_ui": "D019849", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS Genetics", "volume": "13", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Co-option of the bZIP transcription factor Vrille as the activator of Doublesex1 in environmental sex determination of the crustacean Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In gene function analysis, it is arduous to identify gene function individually, and the way to screen out all involved genes according to a particular phenotype or disease usually shows us little information for a specific problem. We present a data-driven analysis system based on wild type (WT) embryos to study the concrete function of each gene associated with certain category of abnormal phenotypes. It can be applied to genes with very few RNAi embryos. Instead of presupposing the particular function of a gene, its function is confirmed by the statistical testing of built models. The scheme includes the following five: first, verify the to be detected genes and determine related recognized features according to the given category; second, compute the value of each feature based on WT embryos and merge them by principal component analysis (PCA); third, for each of the selected components of PCA, build a normal distribution and verify its normality; fourth, project the RNAi embryos to each component and probe them; and finally, analyze the more detailed functions of each gene based on the physical or biological meaning of each component. Choosing the first-round asymmetric division process of Caenorhabditis elegans as the phenotype, experimental results show that on the different aspects of the asymmetric division process, par-2, par-3, and let-754 are related to scalar differences; dcn-1 and mcm-5 are associated with the divergences of scalar variation, which may reflect the disaccord in development; and dcn-1, par-2, and par-3 are involved with morphological discrepancies.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Sihai", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Xianhua", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Tohsato", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Ikuko", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Yenwei", "last_name": "Chen", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/cmb.2016.0210" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28177654" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Asymmetric Cell Division", "descriptor_ui": "D060049", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Gene Silencing", "descriptor_ui": "D020868", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Principal Component Analysis", "descriptor_ui": "D025341", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "436-446", "proceedings_title": null, "publisher": "", "title": "Journal of computational biology : a journal of computational molecular cell biology", "volume": "24", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Phenotype Analysis Method for Identification of Gene Functions Involved in Asymmetric Division of Caenorhabditis elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The molecular mechanism that governs cytoskeleton-membrane interaction during animal cytokinesis remains elusive. Here, we investigated the dynamics and functions of ERM (Ezrin/Radixin/Moesin) proteins during cytokinesis in human cultured cells. We found that ezrin is recruited to the cleavage furrow through its membrane-associated domain in a cholesterol-dependent but largely Rho-independent manner. While ERMs are dispensable for furrow ingression, they play a pivotal role in contractile activity of the polar cortex. Notably, when anillin and supervillin are codepleted, ERMs increasingly accumulate at the cleavage furrow and substantially contribute to the furrow ingression. These results reveal a supportive role of ERMs in cortical activities during cytokinesis, and also provide insight into the selective mechanism that preferentially associates cytokinesis-relevant proteins with the division site.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shota", "last_name": "Hiruma", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Kamasaki", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Otomo", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Nemoto", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/1873-3468.12844" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28889652" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Cell Line, Transformed", "descriptor_ui": "D002461", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cytokinesis", "descriptor_ui": "D048749", "major_topic": false }, { "descriptor": "Cytoskeletal Proteins", "descriptor_ui": "D003598", "major_topic": false }, { "descriptor": "Ezrin", "descriptor_ui": "D000099149", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Microfilament Proteins", "descriptor_ui": "D008840", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": false }, { "descriptor": "rhoA GTP-Binding Protein", "descriptor_ui": "D020742", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Oct", "date_precision": "unknown", "issue": "20", "normalized_date": null, "pages": "3296-3309", "proceedings_title": null, "publisher": "", "title": "FEBS letters", "volume": "591", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamics and function of ERM proteins during cytokinesis in human cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The tau PET ligand 2-((1E,3E)-4-(6-([(11) C]methylamino)pyridin-3-yl)buta-1,3-dienyl)benzo[d]thiazol-6-ol ([(11) C]PBB3) binds to a wide range of tau pathology; however, binding property of PBB3 to non-tau inclusions remains unknown. To clarify whether [(11) C]PBB3 binds to alpha-synuclein pathology, reactivity of PBB3 was assessed by in vitro fluorescence and autoradiographic labeling of brain sections from alpha-synucleinopathies patients. METHOD: Of 10 pure Lewy body disease and 120 multiple system atrophy (MSA) cases in the Mayo Clinic brain bank, we selected 3 Lewy body disease and 4 MSA cases with a range of alpha-synuclein severity based on the quantitative analysis of alpha-synuclein burden. PBB3 fluorescence labeling, double or single immunostaining for alpha-synuclein and phospho-tau, Prussian blue staining, and in vitro autoradiography with [(11) C]PBB3 were performed for these selected samples. RESULTS: PBB3 fluorescence labeled various alpha-synuclein lesions including Lewy bodies, Lewy neurites, spheroids, glial cytoplasmic inclusions, and neuronal cytoplasmic inclusions. Meanwhile, autoradiographic labeling with [(11) C]PBB3 at 10 nM demonstrated no significant binding in Lewy body disease cases. In contrast, significant autoradiographic binding of [(11) C]PBB3 to the striatopallidal fibers was found in 2 MSA cases, which had high densities of glial cytoplasmic inclusions without tau or iron deposits in this region. CONCLUSIONS: Given that the maximum concentration of [(11) C]PBB3 in human PET scans is approximately 10 nM, the present data imply that alpha-synuclein pathology in Lewy body disease is undetectable by [(11) C]PBB3-PET, whereas those in a subset of MSA cases with high densities of glial cytoplasmic inclusions could be captured by this radioligand. (c) 2017 International Parkinson and Movement Disorder Society.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Dennis W.", "last_name": "Dickson", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/mds.27013" }, "pmcid": { "normalized": "PMC5577807" }, "pmid": { "normalized": "28440890" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "alpha-Synuclein", "descriptor_ui": "D051844", "major_topic": false }, { "descriptor": "Amygdala", "descriptor_ui": "D000679", "major_topic": false }, { "descriptor": "Autoradiography", "descriptor_ui": "D001345", "major_topic": false }, { "descriptor": "Basal Ganglia", "descriptor_ui": "D001479", "major_topic": false }, { "descriptor": "Benzothiazoles", "descriptor_ui": "D052160", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lewy Body Disease", "descriptor_ui": "D020961", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Multiple System Atrophy", "descriptor_ui": "D019578", "major_topic": false }, { "descriptor": "Positron-Emission Tomography", "descriptor_ui": "D049268", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Tissue Banks", "descriptor_ui": "D014015", "major_topic": true } ], "publication": { "conference_name": null, "date": "2017 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "884-892", "proceedings_title": null, "publisher": "", "title": "Movement disorders : official journal of the Movement Disorder Society", "volume": "32", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Fluorescence and autoradiographic evaluation of tau PET ligand PBB3 to alpha-synuclein pathology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tau proteins form diverse conformers known as strains in Alzheimer's disease and allied disorders. Ono et al. report differential selectivity of two tau PET radioligands, [11C]PBB3 and [18F]AV-1451, for these fibril subspecies, supporting the utility of these imaging agents for pursuing roles of tau strains in the pathogenesis of tauopathies.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Maiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Katsushi", "last_name": "Kumata", "name": null }, { "creator_type": "author", "first_name": "Bin", "last_name": "Ji", "name": null }, { "creator_type": "author", "first_name": "Ruiqing", "last_name": "Ni", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Dennis W.", "last_name": "Dickson", "name": null }, { "creator_type": "author", "first_name": "John Q.", "last_name": "Trojanowski", "name": null }, { "creator_type": "author", "first_name": "Virginia M.-Y.", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Hozumi", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Yoshiyama", "name": null }, { "creator_type": "author", "first_name": "John C.", "last_name": "van Swieten", "name": null }, { "creator_type": "author", "first_name": "Agneta", "last_name": "Nordberg", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Ming-Rong", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/brain/aww339" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28087578" } }, "mesh": [ { "descriptor": "Autoradiography", "descriptor_ui": "D001345", "major_topic": false }, { "descriptor": "Benzothiazoles", "descriptor_ui": "D052160", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "Butadienes", "descriptor_ui": "D002070", "major_topic": false }, { "descriptor": "Carbolines", "descriptor_ui": "D002243", "major_topic": false }, { "descriptor": "Diagnosis", "descriptor_ui": "D003933", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neurofibrillary Tangles", "descriptor_ui": "D016874", "major_topic": false }, { "descriptor": "Phenazopyridine", "descriptor_ui": "D010621", "major_topic": false }, { "descriptor": "Positron-Emission Tomography", "descriptor_ui": "D049268", "major_topic": true }, { "descriptor": "Radioligand Assay", "descriptor_ui": "D011869", "major_topic": false }, { "descriptor": "Radiopharmaceuticals", "descriptor_ui": "D019275", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": true }, { "descriptor": "Thiadiazoles", "descriptor_ui": "D013830", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "764-780", "proceedings_title": null, "publisher": "", "title": "Brain", "volume": "140", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Distinct binding of PET ligands PBB3 and AV-1451 to tau fibril strains in neurodegenerative tauopathies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: Sleep bruxism (SB) is classified as a sleep-related movement disorder characterized by grinding and clenching of the teeth during sleep, which is responsible for a variety of clinical problems such as abnormal tooth attrition and fracture of teeth or roots. Little is known about the etiology of SB. Our previous study identified a genomic association of the serotonin 2A receptor (5-HT2A) single nucleotide polymorphism (SNP), rs6313 C>T, with SB, where the C allele carrier is associated with a 4.25-fold increased risk of SB. Based on this finding, the aim of this study was to generate of neural cells using SB patient-specific induced pluripotent stem cells (iPSCs). METHODS: Two SB patients with C/C genotype of rs6313 and two controls with T/T genotype were screened by laboratory-based polysomnographic recordings and the TaqMan genotyping assay. Four lines of iPSCs, two from SB patients and two from controls, were established from peripheral blood mononuclear cells by introduction of reprogramming factors. We performed quality control assays on iPSCs using expression of markers for undifferentiated pluripotent cells, immunostaining for pluripotency markers, a three-germ layer assay, and karyotype analysis. The established iPSCs were differentiated into neurons using the neurosphere culture system. 5-HT2A gene expression in these neurons was evaluated by quantitative real-time PCR. RESULTS: Patient-specific iPSCs were successfully differentiated into neurons expressing 5-HT2A. CONCLUSIONS: This report is the first successful generation of neural cells using iPSCs from sleep bruxism patients with 5-HT2A polymorphism, which has the potential to elucidate the etiology and underlying mechanism of SB.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yurie", "last_name": "Hoashi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Mishima", "name": null }, { "creator_type": "author", "first_name": "Wado", "last_name": "Akamatsu", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jpor.2016.11.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27916472" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Alleles", "descriptor_ui": "D000483", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": true }, { "descriptor": "Genetic Association Studies", "descriptor_ui": "D056726", "major_topic": true }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": true }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "Receptor, Serotonin, 5-HT2A", "descriptor_ui": "D044402", "major_topic": false }, { "descriptor": "Risk", "descriptor_ui": "D012306", "major_topic": false }, { "descriptor": "Sleep Bruxism", "descriptor_ui": "D020186", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "242-250", "proceedings_title": null, "publisher": "", "title": "Journal of prosthodontic research", "volume": "61", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of neural cells using iPSCs from sleep bruxism patients with 5-HT2A polymorphism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The present study was conducted to clarify whether the meiotic stage of porcine oocytes has the highest sensitivity to hyperthermia during in vitro maturation by evaluating meiotic competence and DNA damage. Oocytes were exposed to 41 degrees C for 12 h at various intervals during 48 h of maturation culture. When the oocytes were exposed to 41 degrees C from 12 to 24 h of the maturation culture, the proportion of oocytes reaching metaphase II (MII) decreased as compared to the control oocytes cultured at 38.5 degrees C (P < 0.05). Moreover, the proportions of DNA fragmentation in all oocytes exposed to 41 degrees C in each culture period after 12 h from the start of maturation culture were significantly higher (P < 0.05) than for the control oocytes. When the meiotic stage of oocytes cultured at 38.5 degrees C between 12 and 24 h was examined, the majority of oocytes remained at the germinal vesicle (GV) stage at 12 h and approximately half of the oocytes reached metaphase I (MI) at 24 h. These results indicate that the meiotic stage of porcine oocytes having the highest sensitivity to hyperthermia during in vitro maturation is a transition period from the GV stage to the MI stage.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Katsutoshi", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Mado", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Masayasu", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Besshi", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Kunihara", "name": null }, { "creator_type": "author", "first_name": "Fuminori", "last_name": "Tanihara", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Takeshige", "last_name": "Otoi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1556/004.2017.012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28244334" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": false }, { "descriptor": "Hot Temperature", "descriptor_ui": "D006358", "major_topic": true }, { "descriptor": "In Vitro Oocyte Maturation Techniques", "descriptor_ui": "D059471", "major_topic": false }, { "descriptor": "Meiosis", "descriptor_ui": "D008540", "major_topic": false }, { "descriptor": "Oocytes", "descriptor_ui": "D009865", "major_topic": false }, { "descriptor": "Swine", "descriptor_ui": "D013552", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "115-123", "proceedings_title": null, "publisher": "", "title": "Acta veterinaria Hungarica", "volume": "65", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Sensitivity of the meiotic stage to hyperthermia during in vitro maturation of porcine oocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Shigeyoshi", "last_name": "Itohara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2017.04.014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28622895" } }, "mesh": [ { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": false }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "1-2", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "118", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Cutting-edge approaches to unwrapping the mysteries of sleep.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The structurally related neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) have been implicated in stress regulation and learning and memory. Several bodies of research have shown the impact of the PACAP specific receptor PAC1 on fear memory, but the roles of other PACAP receptors in regulating fear stress responses remain to be elucidated. Here we aimed to investigate the effects of genetic deletion of VIPR2 encoding the VPAC2 receptor, which binds both VIP and PACAP, on fear-related memory and on dendritic morphology in the brain regions of the fear circuitry. Male VPAC2 receptor knockout (VPAC2-KO) and littermate wild-type control mice were subjected to Pavlovian fear conditioning paradigm. VPAC2-KO mice displayed normal acquisition of fear conditioning, contextual and cued fear memory, but impaired extinction of cued fear memory. Morphological analyses revealed reductions in cell body size and total branch number and length of apical and basal dendrites of prelimbic cortex neurons in VPAC2-KO mice. In addition, Sholl analysis indicated that the amount of dendritic material distal to the soma was decreased, while proximal dendritic material was increased. In the infralimbic cortex, the amount of apical dendritic material proximal to the soma was increased in VPAC2-KO mice, while other indices of morphology did not differ. Finally, there were no differences in dendritic morphology in basolateral amygdala neurons between genotypes. These findings suggest that the VPAC2 receptor plays an important role in the fear extinction processes and the regulation of the dendritic morphology in the prelimbic and infralimbic cortices.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Kawanai", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Shuto", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Jesse D.", "last_name": "Cushman", "name": null }, { "creator_type": "author", "first_name": "Abha K.", "last_name": "Rajbhandari", "name": null }, { "creator_type": "author", "first_name": "Michael S.", "last_name": "Fanselow", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "James A.", "last_name": "Waschek", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.nlm.2017.10.010" }, "pmcid": { "normalized": "PMC5698124" }, "pmid": { "normalized": "29030297" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Conditioning, Classical", "descriptor_ui": "D003214", "major_topic": false }, { "descriptor": "Cues", "descriptor_ui": "D003463", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": true }, { "descriptor": "Extinction, Psychological", "descriptor_ui": "D005108", "major_topic": false }, { "descriptor": "Fear", "descriptor_ui": "D005239", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Receptors, Vasoactive Intestinal Peptide, Type II", "descriptor_ui": "D051239", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "222-231", "proceedings_title": null, "publisher": "", "title": "Neurobiology of learning and memory", "volume": "145", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Impaired extinction of cued fear memory and abnormal dendritic morphology in the prelimbic and infralimbic cortices in VPAC2 receptor (VIPR2)-deficient mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The crustacean zooplankton Daphnia magna has been widely used for chemical toxicity tests. Although abiotic factors have been well documented in ecotoxicological test protocols, biotic factors that may affect the sensitivity to chemical compounds remain limited. Recently, we identified symbiotic bacteria that are critical for the growth and reproduction of D. magna. The presence of symbiotic bacteria on Daphnia raised the question as to whether these bacteria have a positive or negative effect on toxicity tests. In order to evaluate the effects of symbiotic bacteria on toxicity tests, bacteria-free Daphnia were prepared, and their chemical sensitivities were compared with that of Daphnia with symbiotic bacteria based on an acute immobilization test. The Daphnia with symbiotic bacteria showed higher chemical resistance to nonylphenol, fenoxycarb, and pentachlorophenol than bacteria-free Daphnia. These results suggested potential roles of symbiotic bacteria in the chemical resistance of its host Daphnia.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Patcharaporn", "last_name": "Manakul", "name": null }, { "creator_type": "author", "first_name": "Saranya", "last_name": "Peerakietkhajorn", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.marenvres.2017.03.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28292585" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "Ecotoxicology", "descriptor_ui": "D054750", "major_topic": false }, { "descriptor": "Symbiosis", "descriptor_ui": "D013559", "major_topic": true }, { "descriptor": "Toxicity Tests", "descriptor_ui": "D018675", "major_topic": false }, { "descriptor": "Water Pollutants, Chemical", "descriptor_ui": "D014874", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "70-75", "proceedings_title": null, "publisher": "", "title": "Marine environmental research", "volume": "128", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Effects of symbiotic bacteria on chemical sensitivity of Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Myogenic progenitor/stem cells retain their skeletal muscle differentiation potential by maintaining myogenic transcription factors such as MyoD. However, the mechanism of how MyoD expression is maintained in proliferative progenitor cells has not been elucidated. Here, we found that MyoD expression was reduced at the mRNA level by cell cycle arrest in S and G2 phases, which in turn led to the absence of skeletal muscle differentiation. The reduction of MyoD mRNA was correlated with the reduced expression of factors regulating RNA metabolism, including methyltransferase like 3 (Mettl3), which induces N6-methyladenosine (m6A) modifications of RNA. Knockdown of Mettl3 revealed that MyoD RNA was specifically downregulated and that this was caused by a decrease in processed, but not unprocessed, mRNA. Potential m6A modification sites were profiled by m6A sequencing and identified within the 5′ untranslated region (UTR) of MyoD mRNA. Deletion of the 5′ UTR revealed that it has a role in MyoD mRNA processing. These data showed that Mettl3 is required for MyoD mRNA expression in proliferative myoblasts.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kensuke", "last_name": "Kudou", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Nogami", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Saeki", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1098/rsob.170119" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28878038" } }, "mesh": [ { "descriptor": "5' Untranslated Regions", "descriptor_ui": "D020121", "major_topic": true }, { "descriptor": "Adenosine", "descriptor_ui": "D000241", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "ELAV-Like Protein 1", "descriptor_ui": "D000067780", "major_topic": false }, { "descriptor": "G2 Phase", "descriptor_ui": "D016195", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Methyltransferases", "descriptor_ui": "D008780", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle Development", "descriptor_ui": "D024510", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Myoblasts", "descriptor_ui": "D032446", "major_topic": false }, { "descriptor": "MyoD Protein", "descriptor_ui": "D017570", "major_topic": false }, { "descriptor": "Quinolines", "descriptor_ui": "D011804", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "S Phase", "descriptor_ui": "D016196", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Thiazoles", "descriptor_ui": "D013844", "major_topic": false }, { "descriptor": "Thymidine", "descriptor_ui": "D013936", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Open Biology", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "The requirement of Mettl3-promoted MyoD mRNA maintenance in proliferative myoblasts for skeletal muscle differentiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE The aim of this study was to evaluate whether combined gene therapy with vascular endothelial growth factor (VEGF) plus apelin during indirect vasoreconstructive surgery enhances brain angiogenesis in a chronic cerebral hypoperfusion model in rats. METHODS A chronic cerebral hypoperfusion model induced by the permanent ligation of bilateral common carotid arteries (CCAs; a procedure herein referred to as \"CCA occlusion\" [CCAO]) in rats was employed in this study. Seven days after the CCAO procedure, the authors performed encephalo-myo-synangiosis (EMS) and injected plasmid(s) into each rat's temporal muscle. Rats were divided into 4 groups based on which plasmid was received (i.e., LacZ group, VEGF group, apelin group, and VEGF+apelin group). Protein levels in the cortex and attached muscle were assessed with enzyme-linked immunosorbent assay (ELISA) on Day 7 after EMS, while immunofluorescent analysis of cortical vessels was performed on Day 14 after EMS. RESULTS The total number of blood vessels in the cortex on Day 14 after EMS was significantly larger in the VEGF group and the VEGF+apelin group than in the LacZ group (p < 0.05, respectively). Larger vessels appeared in the VEGF+apelin group than in the other groups (p < 0.05, respectively). Apelin protein on Day 7 after EMS was not detected in the cortex for any of the groups. In the attached muscle, apelin protein was detected only in the apelin group and the VEGF+apelin group. Immunofluorescent analysis revealed that apelin and its receptor, APJ, were expressed on endothelial cells (ECs) 7 days after the CCAO. CONCLUSIONS Combined gene therapy (VEGF plus apelin) during EMS in a chronic cerebral hypoperfusion model can enhance angiogenesis in rats. This treatment has the potential to be a feasible option in a clinical setting for patients with moyamoya disease.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masafumi", "last_name": "Hiramatsu", "name": null }, { "creator_type": "author", "first_name": "Tomohito", "last_name": "Hishikawa", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Nishihiro", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Haruma", "name": null }, { "creator_type": "author", "first_name": "Tomohisa", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Takasugi", "name": null }, { "creator_type": "author", "first_name": "Yukei", "last_name": "Shinji", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sugiu", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Date", "name": null } ], "identifiers": { "doi": { "normalized": "10.3171/2016.8.jns16366" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28009234" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apelin", "descriptor_ui": "D000073861", "major_topic": false }, { "descriptor": "Brain Ischemia", "descriptor_ui": "D002545", "major_topic": false }, { "descriptor": "Chronic Disease", "descriptor_ui": "D002908", "major_topic": false }, { "descriptor": "Combined Modality Therapy", "descriptor_ui": "D003131", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Genetic Therapy", "descriptor_ui": "D015316", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Moyamoya Disease", "descriptor_ui": "D009072", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor A", "descriptor_ui": "D042461", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Sep", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "679-686", "proceedings_title": null, "publisher": "", "title": "Journal of neurosurgery", "volume": "127", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Combined gene therapy with vascular endothelial growth factor plus apelin in a chronic cerebral hypoperfusion model in rats.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Many mammalian species, including humans, spend a substantial fraction of their life sleeping. Sleep deprivation in rats ultimately leads to death, indicating the essential role of sleep. Exactly why sleep is so essential, however, remains largely unknown. From an evolutionary point of view, almost all animal species that have been investigated exhibit sleep or sleep-like states, suggesting that sleep may benefit survival. In certain mammalian and avian species, sleep can be further divided into at least two stages, rapid eye movement (REM) sleep and non-REM sleep. In addition to a widely conserved role for sleep, these individual sleep stages may have roles unique to these animals. The recent use of state-of-the-art techniques, including optogenetics and chemogenetics, has greatly broadened our understanding of the neural mechanisms of sleep regulation, allowing us to address the function of sleep. Studies focusing on non-mammalian animals species have also provided novel insights into the evolution of sleep. This review provides a comprehensive overview regarding the current knowledge of the function and evolution of sleep.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinichi", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Chih-Yao", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2017.04.017" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28501499" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Invertebrates", "descriptor_ui": "D007448", "major_topic": false }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": false }, { "descriptor": "Vertebrates", "descriptor_ui": "D014714", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "3-12", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "118", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Sleep in vertebrate and invertebrate animals, and insights into the function and evolution of sleep.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent studies have revealed that newly emerging transformed cells are often apically extruded from epithelial tissues. During this process, normal epithelial cells can recognize and actively eliminate transformed cells, a process called epithelial defence against cancer (EDAC). Here, we show that mitochondrial membrane potential is diminished in RasV12-transformed cells when they are surrounded by normal cells. In addition, glucose uptake is elevated, leading to higher lactate production. The mitochondrial dysfunction is driven by upregulation of pyruvate dehydrogenase kinase 4 (PDK4), which positively regulates elimination of RasV12-transformed cells. Furthermore, EDAC from the surrounding normal cells, involving filamin, drives the Warburg-effect-like metabolic alteration. Moreover, using a cell-competition mouse model, we demonstrate that PDK-mediated metabolic changes promote the elimination of RasV12-transformed cells from intestinal epithelia. These data indicate that non-cell-autonomous metabolic modulation is a crucial regulator for cell competition, shedding light on the unexplored events at the initial stage of carcinogenesis.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "contributor", "first_name": "Shunsuke", "last_name": "Kon", "name": null }, { "creator_type": "contributor", "first_name": "Kojiro", "last_name": "Ishibashi", "name": null }, { "creator_type": "contributor", "first_name": "Hiroto", "last_name": "Katoh", "name": null }, { "creator_type": "contributor", "first_name": "Sho", "last_name": "Kitamoto", "name": null }, { "creator_type": "contributor", "first_name": "Takanobu", "last_name": "Shirai", "name": null }, { "creator_type": "contributor", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "contributor", "first_name": "Mihoko", "last_name": "Kajita", "name": null }, { "creator_type": "contributor", "first_name": "Susumu", "last_name": "Ishikawa", "name": null }, { "creator_type": "contributor", "first_name": "Hajime", "last_name": "Yamauchi", "name": null }, { "creator_type": "contributor", "first_name": "Yuta", "last_name": "Yako", "name": null }, { "creator_type": "contributor", "first_name": "Tomoko", "last_name": "Kamasaki", "name": null }, { "creator_type": "contributor", "first_name": "Tomohiro", "last_name": "Matsumoto", "name": null }, { "creator_type": "contributor", "first_name": "Hirotaka", "last_name": "Watanabe", "name": null }, { "creator_type": "contributor", "first_name": "Riku", "last_name": "Egami", "name": null }, { "creator_type": "contributor", "first_name": "Ayana", "last_name": "Sasaki", "name": null }, { "creator_type": "contributor", "first_name": "Atsuko", "last_name": "Nishikawa", "name": null }, { "creator_type": "contributor", "first_name": "Ikumi", "last_name": "Kameda", "name": null }, { "creator_type": "contributor", "first_name": "Takeshi", "last_name": "Maruyama", "name": null }, { "creator_type": "contributor", "first_name": "Rika", "last_name": "Narumi", "name": null }, { "creator_type": "contributor", "first_name": "Tomoko", "last_name": "Morita", "name": null }, { "creator_type": "contributor", "first_name": "Yoshiteru", "last_name": "Sasaki", "name": null }, { "creator_type": "contributor", "first_name": "Ryosuke", "last_name": "Enoki", "name": null }, { "creator_type": "contributor", "first_name": "Sato", "last_name": "Honma", "name": null }, { "creator_type": "contributor", "first_name": "Hiromi", "last_name": "Imamura", "name": null }, { "creator_type": "contributor", "first_name": "Masanobu", "last_name": "Oshima", "name": null }, { "creator_type": "contributor", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "contributor", "first_name": "Jun-Ichi", "last_name": "Miyazaki", "name": null }, { "creator_type": "contributor", "first_name": "Michael R.", "last_name": "Duchen", "name": null }, { "creator_type": "contributor", "first_name": "Jin-Min", "last_name": "Nam", "name": null }, { "creator_type": "contributor", "first_name": "Yasuhito", "last_name": "Onodera", "name": null }, { "creator_type": "contributor", "first_name": "Shingo", "last_name": "Yoshioka", "name": null }, { "creator_type": "contributor", "first_name": "Junichi", "last_name": "Kikuta", "name": null }, { "creator_type": "contributor", "first_name": "Masaru", "last_name": "Ishii", "name": null }, { "creator_type": "contributor", "first_name": "Masamichi", "last_name": "Imajo", "name": null }, { "creator_type": "contributor", "first_name": "Eisuke", "last_name": "Nishida", "name": null }, { "creator_type": "contributor", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "contributor", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "contributor", "first_name": "Toshiro", "last_name": "Sato", "name": null }, { "creator_type": "contributor", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncb3509" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 May", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "", "volume": "19", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell competition with normal epithelial cells promotes apical extrusion of transformed cells through metabolic changes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Peripheral blood mononuclear cells (PBMCs) were collected from a clinically diagnosed 20-year-old dystonia patient with a GCH1 mutation (DYT5). Episomal vectors were used to introduce reprogramming factors (OCT3/4, SOX2, KLF4, L-MYC, LIN28, and p53 carboxy-terminal dominant-negative fragment) to the PBMCs. The generated iPSCs expressed pluripotency markers, and were capable of differentiating into derivates of all three germ layers in vitro. The iPSC line also showed a normal karyotype and preserved the GCH1 mutation. This cellular model can provide opportunities to perform pathophysiological studies for aberrant dopamine metabolism-related disorders.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Nagahisa", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Taizo", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Tsukita", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Enami", "name": null }, { "creator_type": "author", "first_name": "Misato", "last_name": "Funayama", "name": null }, { "creator_type": "author", "first_name": "Ran", "last_name": "Shibukawa", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yuishin", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Obata", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Kaji", "name": null }, { "creator_type": "author", "first_name": "Haruhisa", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.scr.2017.07.029" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29034893" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Kruppel-Like Factor 4", "descriptor_ui": "D000090062", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Oct", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "36-39", "proceedings_title": null, "publisher": "", "title": "Stem cell research", "volume": "24", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Establishment of DYT5 patient-specific induced pluripotent stem cells with a GCH1 mutation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Acute myeloid leukaemia (AML) is distinguished by the generation of dysfunctional leukaemic blasts, and patients characteristically suffer from fatal infections and anaemia due to insufficient normal myelo-erythropoiesis. Direct physical crowding of bone marrow (BM) by accumulating leukaemic cells does not fully account for this haematopoietic failure. Here, analyses from AML patients were applied to both in vitro co-culture platforms and in vivo xenograft modelling, revealing that human AML disease specifically disrupts the adipocytic niche in BM. Leukaemic suppression of BM adipocytes led to imbalanced regulation of endogenous haematopoietic stem and progenitor cells, resulting in impaired myelo-erythroid maturation. In vivo administration of PPARgamma agonists induced BM adipogenesis, which rescued healthy haematopoietic maturation while repressing leukaemic growth. Our study identifies a previously unappreciated axis between BM adipogenesis and normal myelo-erythroid maturation that is therapeutically accessible to improve symptoms of BM failure in AML via non-cell autonomous targeting of the niche.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Allison L.", "last_name": "Boyd", "name": null }, { "creator_type": "author", "first_name": "Jennifer C.", "last_name": "Reid", "name": null }, { "creator_type": "author", "first_name": "Kyle R.", "last_name": "Salci", "name": null }, { "creator_type": "author", "first_name": "Lili", "last_name": "Aslostovar", "name": null }, { "creator_type": "author", "first_name": "Yannick D.", "last_name": "Benoit", "name": null }, { "creator_type": "author", "first_name": "Zoya", "last_name": "Shapovalova", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Deanna P.", "last_name": "Porras", "name": null }, { "creator_type": "author", "first_name": "Mohammed", "last_name": "Almakadi", "name": null }, { "creator_type": "author", "first_name": "Clinton J. V.", "last_name": "Campbell", "name": null }, { "creator_type": "author", "first_name": "Michael F.", "last_name": "Jackson", "name": null }, { "creator_type": "author", "first_name": "Catherine A.", "last_name": "Ross", "name": null }, { "creator_type": "author", "first_name": "Ronan", "last_name": "Foley", "name": null }, { "creator_type": "author", "first_name": "Brian", "last_name": "Leber", "name": null }, { "creator_type": "author", "first_name": "David S.", "last_name": "Allan", "name": null }, { "creator_type": "author", "first_name": "Mitchell", "last_name": "Sabloff", "name": null }, { "creator_type": "author", "first_name": "Anargyros", "last_name": "Xenocostas", "name": null }, { "creator_type": "author", "first_name": "Tony J.", "last_name": "Collins", "name": null }, { "creator_type": "author", "first_name": "Mickie", "last_name": "Bhatia", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncb3625" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29035359" } }, "mesh": [ { "descriptor": "Adipocytes", "descriptor_ui": "D017667", "major_topic": false }, { "descriptor": "Adipogenesis", "descriptor_ui": "D050156", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Marrow", "descriptor_ui": "D001853", "major_topic": false }, { "descriptor": "Bone Marrow Cells", "descriptor_ui": "D001854", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Erythropoiesis", "descriptor_ui": "D004920", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia, Myeloid, Acute", "descriptor_ui": "D015470", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "PPAR gamma", "descriptor_ui": "D047495", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "1336-1347", "proceedings_title": null, "publisher": "", "title": "Nature cell biology", "volume": "19", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Acute myeloid leukaemia disrupts endogenous myelo-erythropoiesis by compromising the adipocyte bone marrow niche.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Schizophrenia is a chronic psychiatric disorder with complex genetic and environmental origins. While many antipsychotics have been demonstrated as effective in the treatment of schizophrenia, a substantial number of schizophrenia patients are partially or fully unresponsive to the treatment. Clozapine is the most effective antipsychotic drug for treatment-resistant schizophrenia; however, clozapine has rare but serious side-effects. Furthermore, there is inter-individual variability in the drug response to clozapine treatment. Therefore, the identification of the molecular mechanisms underlying the action of clozapine and drug response predictors is imperative. In the present study, we focused on a pair of monozygotic twin cases with treatment-resistant schizophrenia, in which one twin responded well to clozapine treatment and the other twin did not. Using induced pluripotent stem (iPS) cell-based technology, we generated neurons from iPS cells derived from these patients and subsequently performed RNA-sequencing to compare the transcriptome profiles of the mock or clozapine-treated neurons. Although, these iPS cells similarly differentiated into neurons, several genes encoding homophilic cell adhesion molecules, such as protocadherin genes, showed differential expression patterns between these two patients. These results, which contribute to the current understanding of the molecular mechanisms of clozapine action, establish a new strategy for the use of monozygotic twin studies in schizophrenia research.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Hidenaga", "last_name": "Yamamori", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Mikiya", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Shusuke", "last_name": "Numata", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Wado", "last_name": "Akamatsu", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Nakaya", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.schres.2016.10.012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28277309" } }, "mesh": [ { "descriptor": "Antipsychotic Agents", "descriptor_ui": "D014150", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Biological Variation, Population", "descriptor_ui": "D000073537", "major_topic": false }, { "descriptor": "Clozapine", "descriptor_ui": "D003024", "major_topic": false }, { "descriptor": "Diseases in Twins", "descriptor_ui": "D004200", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Schizophrenia", "descriptor_ui": "D012559", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false }, { "descriptor": "Twins, Monozygotic", "descriptor_ui": "D014430", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "75-82", "proceedings_title": null, "publisher": "", "title": "Schizophrenia research", "volume": "181", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Differential gene expression profiles in neurons generated from lymphoblastoid B-cell line-derived iPS cells from monozygotic twin cases with treatment-resistant schizophrenia and discordant responses to clozapine.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Transdermal delivery of hydrophilic peptides remains a challenge due to their poor cellular uptake and transdermal penetration. We hypothesize that combination of a CO(2) fractional laser to enhance percutaneous absorption and liposomes as transdermal carriers would improve skin penetration of hydrophilic drugs. STUDY DESIGN: NA. METHODS: Liposomes were prepared using membrane fusion lipid dioleoylphosphatidylethanolamine, and used to deliver 5-carboxyfluorescein (CF) and fluorescein isothiocyanate-conjugated ovalbumin (OVA-FITC) as model hydrophilic peptide drugs. Liposome size was estimated by dynamic light scattering. Liposome uptake into murine macrophage cells and penetration or permeation into Yucatan micropig skin after irradiation by CO(2) fractional laser at varying energy levels (laser power and exposure duration) were investigated using Franz cell and fluorescence microscopy. Oxidative damage to the irradiated mouse skin was assessed by electron spin resonance. RESULTS: Size of CF and OVA-FITC encapsulated liposomes was 324 +/- 75 nm. Cellular uptake of OVA-FITC delivered by liposomes was 10-fold higher (1,370 relative fluorescence units, RFU) than delivered in solution form (130 RFU). Fractional laser irradiation increased skin permeation rate of CF liposomes (0-10%) and OVA-FITC liposomes (4-40%) in a dose-dependent manner. Although peeling off the stratum corneum facilitated CF liposome penetration at low energy levels (2.69-3.29 J/cm(2) ; 10-20 W for 500 mus), drug permeation was similar (7-8%) in peeled or untreated skin at higher laser energy levels (6.06 J/cm(2) ; 20 W for 1,500 mus). FITC penetrated deeper in the skin after laser irradiation. However, OH, O2-, and VC reactive oxygen species were generated upon irradiation of the skin with a fractional CO(2) laser. CONCLUSIONS: Increasing laser power and irradiation, time increased liposome uptake by cells and penetration of peptide drugs across the skin in a dose-dependent manner. High-energy CO(2) fractional laser overcomes the rate-limiting barrier function of the stratum corneum. Further investigations are required to establish the safety and efficacy of fractional laser-irradiation assisted delivery of liposome-encapsulated drugs as a transcutaneous drug delivery system. Lasers Surg. Med. 49:525-532, 2017. (c) 2016 Wiley Periodicals, Inc.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takahiro", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Jian", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Shinobu", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hideko", "last_name": "Kanazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/lsm.22616" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27990655" } }, "mesh": [ { "descriptor": "Administration, Cutaneous", "descriptor_ui": "D000279", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drug Delivery Systems", "descriptor_ui": "D016503", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluoresceins", "descriptor_ui": "D005452", "major_topic": false }, { "descriptor": "Lasers, Gas", "descriptor_ui": "D054020", "major_topic": false }, { "descriptor": "Liposomes", "descriptor_ui": "D008081", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Skin Absorption", "descriptor_ui": "D012869", "major_topic": false }, { "descriptor": "Swine", "descriptor_ui": "D013552", "major_topic": false }, { "descriptor": "Tissue Culture Techniques", "descriptor_ui": "D046509", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "525-532", "proceedings_title": null, "publisher": "", "title": "Lasers in surgery and medicine", "volume": "49", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Transcutaneous drug delivery by liposomes using fractional laser technology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tau is a major component of the neurofibrillary tangles (NFT) that represent a pathological hallmark of Alzheimer's disease (AD). Although generally considered an axonal protein, Tau is found in the somato-dendritic compartment of degenerating neurons and this redistribution is thought to be a trigger of neurodegeneration in AD. Here, we show the presence of tau mRNA in a dendritic ribonucleoprotein (RNP) complex that includes Ca2+-calmodulin dependent protein kinase (CaMK)IIα mRNA and that is translated locally in response to glutamate stimulation. Further, we show that Tau mRNA is a component of mRNP granules that contain RNA-binding proteins, and that it interacts with Myosin Va, a postsynaptic motor protein; these findings suggest that tau mRNA is transported into dendritic spines. We also report that tau mRNA localized in the somato-dendritic component of primary hippocampal cells and that a sub-toxic concentration of glutamate enhances local translation and hyperphosphorylation of tau, effects that are blocked by the gluatamatergic antagonists MK801 and NBQX. These data thus demonstrate that alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-d-aspartate (NMDA) stimulation redistributes tau to the somato-dendritic region of neurons where it may trigger neurodegeneration.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Soeda", "name": null }, { "creator_type": "author", "first_name": "Osborne F. X.", "last_name": "Almeida", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ebiom.2017.05.012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28566250" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Biosynthesis", "descriptor_ui": "D014176", "major_topic": true }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Receptors, AMPA", "descriptor_ui": "D018091", "major_topic": false }, { "descriptor": "Receptors, N-Methyl-D-Aspartate", "descriptor_ui": "D016194", "major_topic": false }, { "descriptor": "Ribonucleoproteins", "descriptor_ui": "D012261", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "120-126", "proceedings_title": null, "publisher": "", "title": "EBioMedicine", "volume": "20", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Local Somatodendritic Translation and Hyperphosphorylation of Tau Protein Triggered by AMPA and NMDA Receptor Stimulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Serotonin enhancement during developmental stages restores autism symptoms in a mouse model of human 15q11-13 duplication.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Fumihito", "last_name": "Saitow", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Kawamoto", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Tamada", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Mizuma", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Onoe", "name": null }, { "creator_type": "author", "first_name": "Yasuyoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hiromu", "last_name": "Monai", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Hirase", "name": null }, { "creator_type": "author", "first_name": "Jin", "last_name": "Nakatani", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takumi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.1603001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28691086" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autism Spectrum Disorder", "descriptor_ui": "D000067877", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Chromosomes", "descriptor_ui": "D002875", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "DNA Copy Number Variations", "descriptor_ui": "D056915", "major_topic": true }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Pyramidal Cells", "descriptor_ui": "D017966", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": false }, { "descriptor": "Somatosensory Cortex", "descriptor_ui": "D013003", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Science Advances", "volume": "3", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Serotonin rebalances cortical tuning and behavior linked to autism symptoms in 15q11-13 CNV mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: The aim of this study was to examine the effect of basic fibroblast growth factor (FGF-2) on osseointegration of dental implants with low primary stability in a beagle dog model. MATERIALS AND METHODS: Customized titanium implants that were designed to have low contact with the existing bone were installed into the edentulous mandible of beagle dogs. To degrade the primary stability of the implants, the diameters of the bone sockets exceeded the implant diameters. FGF-2 (0.3%) plus vehicle (hydroxypropyl cellulose) or vehicle alone was topically applied to the sockets in the FGF-2 and control groups, respectively. In Study 1, the new bone area and length of new bone-to-implant contact (BIC) were evaluated at 4, 8, and 12 weeks after installation using histomorphometry and scanning electron microscopy. In Study 2, the implant stability quotient (ISQ) values were sequentially measured for 16 weeks using an Osstell system. RESULTS: The histomorphometric analysis revealed that the new bone area and length of BIC in the FGF-2 group were significantly larger than those in the control group at 4 weeks. Electron microscopic observation showed intimate contact between the mature lamellar bone and the implant surfaces, osseointegration, in both groups. The ISQ values in the FGF-2 group were significantly increased from 6 to 16 weeks compared with those in the control group. CONCLUSIONS: Taken together, our study demonstrates that FGF-2 promoted new bone formation around the dental implants and subsequent osseointegration, resulting in promotion of stability of implants with low primary stability.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Toshie", "last_name": "Nagayasu-Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takenori", "last_name": "Nozaki", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Sawada", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Murakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/clr.12797" }, "pmcid": { "normalized": "PMC5347960" }, "pmid": { "normalized": "26919334" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Dental Implantation, Endosseous", "descriptor_ui": "D003758", "major_topic": false }, { "descriptor": "Dental Implants", "descriptor_ui": "D015921", "major_topic": true }, { "descriptor": "Dental Prosthesis Design", "descriptor_ui": "D017267", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fibroblast Growth Factor 2", "descriptor_ui": "D016222", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mandible", "descriptor_ui": "D008334", "major_topic": false }, { "descriptor": "Osseointegration", "descriptor_ui": "D016348", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "291-297", "proceedings_title": null, "publisher": "", "title": "Clinical oral implants research", "volume": "28", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "FGF-2 promotes initial osseointegration and enhances stability of implants with low primary stability.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The viral 2A peptides have recently been used for bicistronic expression in various organisms. In this system, a single mRNA that codes for two proteins flanking the 2A peptide can be translated simultaneously into each protein by ribosomal skipping at this peptide sequence. Here, we tested the function of the Thosea asigna insect virus 2A (T2A) peptide in the branchiopod crustacean Daphnia magna-an emerging model of evolutionary developmental biology. First, we used transgenic Daphnia that expresses a potential bicistronic RNA containing mCherry and histone H2B- green fluorescent protein (GFP) open reading frames upstream and downstream of the T2A sequence, respectively. Microscopic observation revealed difference of localization of the two proteins in the cell, homogenous distribution of mCherry and nuclear localization of H2B-GFP. Second, we changed localization of mCherry from cytoplasm to plasma membrane by attachment of a consensus myristoylation motif in the bicistronic reporter. RNA that codes for this new bicistronic reporter was injected into eggs. At gastrulation stage, we found spectrally distinct fluorescence with enough intensity and resolution to detect membrane localized mCherry and nuclear GFP. These results indicate that the T2A peptide functions in D. magna and T2A-mediated bicistronic expression would be a promising tool for evo-devo studies of this species.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/dvg.23083" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29086479" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Genes", "descriptor_ui": "D005796", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Ovum", "descriptor_ui": "D010063", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "Ribosomes", "descriptor_ui": "D012270", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Genesis (New York, N.Y. : 2000)", "volume": "55", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a bicistronic expression system in the branchiopod crustacean Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In this data article, we described the detailed synthetic procedure and the experimental data for the synthesis of a red-fluorescent probe for calcium ions (Ca2+) with improved water solubility. This Ca2+ red-fluorescent probe CaTM-3 AM could be applied to fluorescence imaging of physiological Ca2+ concentration changes in not only live cells, but also brain slices, with high cell-membrane permeability leading to bright fluorescence in biosamples. The data provided herein are in association with the research article “The Development of Practical Red Fluorescent Probe for Cytoplasmic Calcium Ions with Greatly Improved Cell-membrane Permeability” in Cell Calcium (Hirabayashi et al., 2016) [1].", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Hirabayashi", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Egawa", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Shodai", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Ikegaya", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.dib.2017.04.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28491938" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Jun", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "351-357", "proceedings_title": null, "publisher": "", "title": "Data in Brief", "volume": "12", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis of practical red fluorescent probe for cytoplasmic calcium ions with greatly improved cell-membrane permeability.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The commitment to and execution of differentiation programs involves a significant change in gene expression in the precursor cell to facilitate development of the mature cell type. In addition to being regulated by lineage-determining and auxiliary transcription factors that drive these changes, the structural status of the chromatin has a considerable impact on the transcriptional competence of differentiation-specific genes, which is clearly demonstrated by the large number of cofactors and the extraordinary complex mechanisms by which these genes become activated. The terminal differentiation of myoblasts to myotubes and mature skeletal muscle is an excellent system to illustrate these points. The MyoD family of closely related, lineage-determining transcription factors directs, largely through targeting to chromatin, a cascade of cooperating transcription factors and enzymes that incorporate or remove variant histones, post-translationally modify histones, and alter nucleosome structure and positioning via energy released by ATP hydrolysis. The coordinated action of these transcription factors and enzymes prevents expression of differentiation-specific genes in myoblasts and facilitates the transition of these genes from transcriptionally repressed to activated during the differentiation process. Regulation is achieved in both a temporal as well as spatial manner, as at least some of these factors and enzymes affect local chromatin structure at myogenic gene regulatory sequences as well as higher-order genome organization. Here we discuss the transition of genes that promote myoblast differentiation from the silenced to the activated state with an emphasis on the changes that occur to individual histones and the chromatin structure present at these loci.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Anthony N.", "last_name": "Imbalzano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.semcdb.2017.10.022" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29079444" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Chromatin Assembly and Disassembly", "descriptor_ui": "D042002", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Muscle Development", "descriptor_ui": "D024510", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Myoblasts", "descriptor_ui": "D032446", "major_topic": false }, { "descriptor": "MyoD Protein", "descriptor_ui": "D017570", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Dec", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "77-86", "proceedings_title": null, "publisher": "", "title": "Seminars in cell & developmental biology", "volume": "72", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Temporal Regulation of Chromatin During Myoblast Differentiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cells, irrespective of whether they are from multicellular or single-celled organisms, must communicate with the external environment through dynamic regulation of their internal metabolism, which are critical for their survival. Fluorescent and bioluminescent proteins, and related genetic engineering technologies, have provided new opportunities to investigate the molecular dynamics of cells and their internal compartments, with high spatio-temporal resolution. In this review article, since there is a sufficient number of previous reviews summarizing the history of their development and the techniques behind them, here we will focus on molecular features or technologies that have the potential to further open novel investigations of cellular and subcellular dynamics.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masakazu", "last_name": "Agetsuma", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ceca.2016.12.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27989646" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Compartmentation", "descriptor_ui": "D002451", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Subcellular Fractions", "descriptor_ui": "D013347", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "12-19", "proceedings_title": null, "publisher": "", "title": "Cell calcium", "volume": "64", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Methods for monitoring signaling molecules in cellular compartments.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mathematical modeling is an essential approach for the understanding of complex multicellular behaviors in tissue morphogenesis. Here, we review the cellular Potts model (CPM; also known as the Glazier-Graner-Hogeweg model), an effective computational modeling framework. We discuss its usability for modeling complex developmental phenomena by examining four fundamental examples of tissue morphogenesis: (i) cell sorting, (ii) cyst formation, (iii) tube morphogenesis in kidney development, and (iv) blood vessel formation. The review provides an introduction for biologists for starting simulation analysis using the CPM framework.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null }, { "creator_type": "author", "first_name": "Elisabeth G.", "last_name": "Rens", "name": null }, { "creator_type": "author", "first_name": "Roeland M. H.", "last_name": "Merks", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12358" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28593653" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Vessels", "descriptor_ui": "D001808", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "329-339", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "59", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Cellular Potts modeling of complex multicellular behaviors in tissue morphogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Photoacoustic imaging is a unique imaging method that involves extracting information from points at different depths, an advantage of ultrasound imaging, while maintaining functional information, a key feature of conventional photo imaging. This makes it easy to add functional images to ultrasound images by adding a laser pulse source to the conventional ultrasound imaging device and detecting a photo-ultrasound signal via a conventional ultrasound probe. One challenge when using normal one-dimensional (1D) probes and generating photoacoustic images is the limited-view problem, in which artefacts are observed due to the positions of the ultrasound transducers. In this study, we used a photoacoustic transmission matrix (PA-TM) for simulation and performed a verification test using a 1D probe and a phantom. The results confirmed that the eigenvalues of the PA-TM visualized the light absorber itself in the limited-view measurement system, which eliminates reconstruction artefacts and further scattering artefacts, and that visualization is possible by signal intensity amplification through further phase modulation.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.pacs.2017.06.003" }, "pmcid": { "normalized": "PMC5510525" }, "pmid": { "normalized": "28736704" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Dec", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "1-7", "proceedings_title": null, "publisher": "", "title": "Photoacoustics", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualization of photoacoustic images in a limited-View measuring system using eigenvalues of a photoacoustic transmission matrix.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sleep is one of the most important physiological functions in mammals. It is regulated by not only homeostatic regulation but also circadian clock. Several neuropeptide-producing neurons located in the hypothalamus are implicated in the regulation of sleep/wakefulness. Among them, orexin/hypocretin-producing neurons (orexin neurons) are a crucial component for maintenance of wakefulness, because lack of orexin function results in narcolepsy, which is a sleep disorder. Recent findings have identified substances that excite or inhibit neural activity of orexin neurons. Furthermore neural projections of the neurons which release these substances have been revealed. In addition to orexin, melanin concentrating hormone (MCH)-producing neurons in the lateral hypothalamic area (LHA) are also implicated in the regulation of sleep/wakefulness. MCH neurons are active during sleep but become silent during wakefulness. Recently developed innovative methods including optogenetics and pharmacogenetics have provided substantial insights into the regulation of sleep/wakefulness. In vivo optical recordings and retrograde and anterograde tracing methods will allow us to understand additional details regarding important interactions between these two types of neurons in the LHA and other neurons in the brain. Finally we discuss the circadian clock and sleep/wake cycle. Understanding of the neural networks and its circadian modulation of sleep/wake cycles remain to be investigated.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2017.03.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28526553" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypothalamic Hormones", "descriptor_ui": "D007028", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Melanins", "descriptor_ui": "D008543", "major_topic": false }, { "descriptor": "Orexins", "descriptor_ui": "D000068797", "major_topic": false }, { "descriptor": "Pituitary Hormones", "descriptor_ui": "D010907", "major_topic": false }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": false }, { "descriptor": "Wakefulness", "descriptor_ui": "D014851", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "74-81", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "118", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Hypothalamic regulation of the sleep/wake cycle.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A novel pretreatment method, which was performed using a two-dimensional high-performance liquid chromatography (2D-HPLC) system, was proposed for the direct analysis of drugs in human serum. A temperature-responsive column was used as a pretreatment column. The stationary phase of the temperature-responsive column exhibits temperature-regulated hydrophilic/hydrophobic characteristics. Controlling the ionic strength of the eluent enables human serum albumin (HSA) to pass through the column without retention. When serum samples containing barbiturates or benzodiazepines were injected into the temperature-responsive column using 10 mM of ammonium acetate (pH 6.5) as the mobile phase and in the temperature range of 10-40 degrees C, HSA was eluted from the column near the dead time, followed by the individual drugs. When the column temperature was changed, the retention times of the drugs were altered owing to surface property changes within the pretreatment column. These closely eluted compounds were subsequently introduced into the analytical column using a column-switching valve, with a minimal gap time to avoid foreign substance contamination. This new 2D-HPLC method afforded high-quality chromatograms of multiple drugs without unwanted peaks from foreign substances. The present technique could be an attractive choice in selecting the analytical method for drug analysis.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Toshiyasu", "last_name": "Mikuma", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Kajiya", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Hideko", "last_name": "Kanazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00216-016-0024-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27796461" } }, "mesh": [ { "descriptor": "Chromatography, High Pressure Liquid", "descriptor_ui": "D002851", "major_topic": false }, { "descriptor": "Hydrophobic and Hydrophilic Interactions", "descriptor_ui": "D057927", "major_topic": false }, { "descriptor": "Osmolar Concentration", "descriptor_ui": "D009994", "major_topic": false }, { "descriptor": "Pharmaceutical Preparations", "descriptor_ui": "D004364", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": true } ], "publication": { "conference_name": null, "date": "2017 Feb", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "1059-1065", "proceedings_title": null, "publisher": "", "title": "Analytical and bioanalytical chemistry", "volume": "409", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "The use of a temperature-responsive column for the direct analysis of drugs in serum by two-dimensional heart-cutting liquid chromatography.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Scar formation is a prominent pathological feature of traumatic central nervous system (CNS) injury, which has long been implicated as a major impediment to the CNS regeneration. However, the factors affecting such scar formation remain to be elucidated. We herein demonstrate that the extracellular matrix protein periostin (POSTN) is a key player in scar formation after traumatic spinal cord injury (SCI). Using high-throughput RNA sequencing data sets, we found that the genes involved in the extracellular region, such as POSTN, were significantly expressed in the injured spinal cord. The expression of POSTN peaked at 7 days after SCI, predominantly in the scar-forming pericytes. Notably, we found that genetic deletion of POSTN in mice reduced scar formation at the lesion site by suppressing the proliferation of the pericytes. Conversely, we found that recombinant POSTN promoted the migration capacity of the monocytes/macrophages and increased the expression of tumor necrosis factor-alpha from the monocytes/macrophages in vitro, which facilitated the proliferation of pericytes. Furthermore, we revealed that the pharmacological blockade of POSTN suppressed scar formation and improved the long-term functional outcome after SCI. Our findings suggest a potential mechanism whereby POSTN regulates the scar formation after SCI and provide significant evidence that POSTN is a promising therapeutic target for CNS injury.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuya", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Kazu", "last_name": "Kobayakawa", "name": null }, { "creator_type": "author", "first_name": "Takeyuki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Masamitsu", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Kijima", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kudo", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ajpath.2016.11.010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28082119" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Neutralizing", "descriptor_ui": "D057134", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Cell Adhesion Molecules", "descriptor_ui": "D015815", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cicatrix", "descriptor_ui": "D002921", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Monocytes", "descriptor_ui": "D009000", "major_topic": false }, { "descriptor": "Nerve Regeneration", "descriptor_ui": "D009416", "major_topic": false }, { "descriptor": "Pericytes", "descriptor_ui": "D020286", "major_topic": false }, { "descriptor": "Recovery of Function", "descriptor_ui": "D020127", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Spinal Cord Injuries", "descriptor_ui": "D013119", "major_topic": false }, { "descriptor": "Tumor Necrosis Factor-alpha", "descriptor_ui": "D014409", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "639-653", "proceedings_title": null, "publisher": "", "title": "The American journal of pathology", "volume": "187", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Periostin Promotes Scar Formation through the Interaction between Pericytes and Infiltrating Monocytes/Macrophages after Spinal Cord Injury.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Astrocytes regulate hippocampal synaptic plasticity by the Ca(2+) dependent release of the N-methyl d-aspartate receptor (NMDAR) co-agonist d-serine. Previous evidence indicated that d-serine release would be regulated by the intracellular Ca(2+) release channel IP(3) receptor (IP(3) R), however, genetic deletion of IP(3) R2, the putative astrocytic IP(3) R subtype, had no impact on synaptic plasticity or transmission. Although IP(3) R2 is widely believed to be the only functional IP(3) R in astrocytes, three IP(3) R subtypes (1, 2, and 3) have been identified in vertebrates. Therefore, to better understand gliotransmission, we investigated the functionality of IP(3) R and the contribution of the three IP(3) R subtypes to Ca(2+) signalling. As a proxy for gliotransmission, we found that long-term potentiation (LTP) was impaired by dialyzing astrocytes with the broad IP(3) R blocker heparin, and rescued by exogenous d-serine, indicating that astrocytic IP(3) Rs regulate d-serine release. To explore which IP(3) R subtypes are functional in astrocytes, we used pharmacology and two-photon Ca(2+) imaging of hippocampal slices from transgenic mice (IP(3) R2(-/-) and IP(3) R2(-/-) ;3(-/-) ). This approach revealed that underneath IP(3) R2-mediated global Ca(2+) events are an overlooked class of IP(3) R-mediated local events, occurring in astroglial processes. Notably, multiple IP(3) Rs were recruited by high frequency stimulation of the Schaffer collaterals, a classical LTP induction protocol. Together, these findings show the dependence of LTP and gliotransmission on Ca(2+) release by astrocytic IP(3) Rs. GLIA 2017;65:502-513.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mark William", "last_name": "Sherwood", "name": null }, { "creator_type": "author", "first_name": "Misa", "last_name": "Arizono", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Hisatsune", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Ebisui", "name": null }, { "creator_type": "author", "first_name": "John Lawrence", "last_name": "Sherwood", "name": null }, { "creator_type": "author", "first_name": "Aude", "last_name": "Panatier", "name": null }, { "creator_type": "author", "first_name": "Stephane Henri Richard", "last_name": "Oliet", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Mikoshiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/glia.23107" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28063222" } }, "mesh": [ { "descriptor": "Age Factors", "descriptor_ui": "D000367", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Calcium-Binding Proteins", "descriptor_ui": "D002135", "major_topic": false }, { "descriptor": "Electric Stimulation", "descriptor_ui": "D004558", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Inositol 1,4,5-Trisphosphate Receptors", "descriptor_ui": "D053496", "major_topic": false }, { "descriptor": "Long-Term Potentiation", "descriptor_ui": "D017774", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Methoxyhydroxyphenylglycol", "descriptor_ui": "D008734", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Organ Culture Techniques", "descriptor_ui": "D009924", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "502-513", "proceedings_title": null, "publisher": "", "title": "Glia", "volume": "65", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Astrocytic IP(3) Rs: Contribution to Ca(2+) signalling and hippocampal LTP.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Scientists are always on the lookout for new modalities of information which could reveal new biological features that are useful for deciphering the complexity of biological systems. Here, we introduce Raman spectroscopy as a prime candidate for ecology and evolution. To encourage the integration of this microscopy technique in the field of ecology and evolution, it is crucial to discuss first how Raman spectroscopy fits within the conceptual, technical and pragmatic considerations of ecology and evolution. In this paper, we show that the spectral information holds reliable indicators of intra- and interspecies variations, which can be related to the environment, selective pressures and fitness. Moreover, we show how the technical and pragmatic aspects of this modality (non-destructive, non-labelling, speed, relative low cost, etc.) enable it to be combined with more conventional methodologies. With this paper, we hope to open new avenues of research and extend the scope of available methodologies used in ecology and evolution.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Arno", "last_name": "Germond", "name": null }, { "creator_type": "author", "first_name": "Vipin", "last_name": "Kumar", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Jerome", "last_name": "Moreau", "name": null }, { "creator_type": "author", "first_name": "Chikara", "last_name": "Furusawa", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1098/rsif.2017.0174" }, "pmcid": { "normalized": "PMC5493802" }, "pmid": { "normalized": "28592661" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": true }, { "descriptor": "Ecology", "descriptor_ui": "D004463", "major_topic": false }, { "descriptor": "Ecosystem", "descriptor_ui": "D017753", "major_topic": false }, { "descriptor": "Species Specificity", "descriptor_ui": "D013045", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun", "date_precision": "unknown", "issue": "131", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of the Royal Society, Interface", "volume": "14", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Raman spectroscopy as a tool for ecology and evolution.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Micro-/nanosphere-mediated femtosecond laser cell perforation is one of the high throughput technologies used for macro-molecule-delivery into multiple cells. We have demonstrated the delivery of plasmid-DNA/liposome complexes into cells using biodegradable polymer microspheres and a femtosecond laser and investigated the intracellular localization of the complexes by delivering fluorescence-labeled plasmid-DNA/liposome complexes into cells. The utilization of liposomes increases the number of complexes delivered into the cytoplasm by laser illumination, which contributed to the increased transfection rate. In the experiment involving polystyrene (PS) microspheres of different diameters, the fluorescence of the complexes was detected in the nucleus as well as cytoplasm after laser illumination for PS microspheres of 3.0 mum diameter. The direct delivery of complexes into the nucleus is probably attributed to the enhancement of the nuclear membrane permeability by the enhanced optical field obtained close to the nucleus. These revelations on the intracellular localization of foreign DNA would provide effective laser-based transfection. Picture: Intranuclear delivery of plasmid-DNA/liposome complexes by utilizing dielectric microspheres and a femtosecond laser.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Atsuhiro", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Dag", "last_name": "Heinemann", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Heisterkamp", "name": null }, { "creator_type": "author", "first_name": "Hideko", "last_name": "Kanazawa", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Terakawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/jbio.201600323" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28464530" } }, "mesh": [ { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Drug Carriers", "descriptor_ui": "D004337", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Space", "descriptor_ui": "D042541", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": true }, { "descriptor": "Liposomes", "descriptor_ui": "D008081", "major_topic": false }, { "descriptor": "Microspheres", "descriptor_ui": "D008863", "major_topic": true }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1723-1731", "proceedings_title": null, "publisher": "", "title": "Journal of biophotonics", "volume": "10", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Intracellular localization and delivery of plasmid DNA by biodegradable microsphere-mediated femtosecond laser optoporation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent studies have reported that oxytocin ameliorates behavioral abnormalities in both animal models and individuals with autism spectrum disorders (ASD). However, the mechanisms underlying the ameliorating effects of oxytocin remain unclear. In this study, we examined the effects of intranasal oxytocin on impairments in social interaction and recognition memory in an ASD mouse model in which animals are prenatally exposed to valproic acid (VPA). We found that a single intranasal administration of oxytocin restored social interaction deficits for up to 2h in mice prenatally exposed to VPA, but there was no effect on recognition memory impairments. Additionally, administration of oxytocin across 2weeks improved prenatal VPA-induced social interaction deficits for at least 24h. In contrast, there were no effects on the time spent sniffing in control mice. Immunohistochemical analysis revealed that intranasal administration of oxytocin increased c-Fos expression in the paraventricular nuclei (PVN), prefrontal cortex, and somatosensory cortex, but not the hippocampal CA1 and CA3 regions of VPA-exposed mice, suggesting the former regions may underlie the effects of oxytocin. These findings suggest that oxytocin attenuates social interaction deficits through the activation of higher cortical areas and the PVN in an ASD mouse model.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Momoko", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.yhbeh.2017.09.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28942000" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autistic Disorder", "descriptor_ui": "D001321", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Interpersonal Relations", "descriptor_ui": "D007398", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Oxytocin", "descriptor_ui": "D010121", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Prenatal Exposure Delayed Effects", "descriptor_ui": "D011297", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-fos", "descriptor_ui": "D016760", "major_topic": false }, { "descriptor": "Recognition, Psychology", "descriptor_ui": "D021641", "major_topic": false }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": false }, { "descriptor": "Social Learning", "descriptor_ui": "D000067570", "major_topic": false }, { "descriptor": "Valproic Acid", "descriptor_ui": "D014635", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "130-136", "proceedings_title": null, "publisher": "", "title": "Hormones and behavior", "volume": "96", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Oxytocin attenuates deficits in social interaction but not recognition memory in a prenatal valproic acid-induced mouse model of autism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "David", "last_name": "Bending", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jaci.2017.03.015" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28392329" } }, "mesh": [ { "descriptor": "Dermatitis, Atopic", "descriptor_ui": "D003876", "major_topic": false }, { "descriptor": "Eczema", "descriptor_ui": "D004485", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "1790-1792", "proceedings_title": null, "publisher": "", "title": "The Journal of allergy and clinical immunology", "volume": "139", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Interplay between the skin barrier and immune cells in patients with atopic dermatitis unraveled by means of mathematical modeling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The role of myristoylation in the localization and catalytic activity of Src at focal adhesions was investigated by live-cell imaging and site-directed mutagenesis. Although the majority of activated Src molecules are localized at focal adhesions, it is unclear how activated Src molecules are recruited to focal adhesions. Because Src is activated at the cell membrane, translocation of Src to cell membranes is considered to be essential for its recruitment to focal adhesions. Membrane-targeting-deficient Src mutant SrcG2A localizes at focal adhesions, indicating direct recruitment of Src from cytosol to focal adhesions. Furthermore, directly recruited Src molecules are shown to enhance paxillin dynamics at focal adhesions. These results reveal that the regulation of Src activation and translocation is more complex than previously suggested.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Machiyama", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/1873-3468.12696" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28543306" } }, "mesh": [ { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "CSK Tyrosine-Protein Kinase", "descriptor_ui": "D000081247", "major_topic": false }, { "descriptor": "Cytosol", "descriptor_ui": "D003600", "major_topic": false }, { "descriptor": "Focal Adhesion Kinase 1", "descriptor_ui": "D051417", "major_topic": false }, { "descriptor": "Focal Adhesions", "descriptor_ui": "D022001", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mechanotransduction, Cellular", "descriptor_ui": "D040542", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Myristic Acid", "descriptor_ui": "D019814", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "src-Family Kinases", "descriptor_ui": "D019061", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul", "date_precision": "unknown", "issue": "13", "normalized_date": null, "pages": "1940-1946", "proceedings_title": null, "publisher": "", "title": "FEBS letters", "volume": "591", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "A novel c-Src recruitment pathway from the cytosol to focal adhesions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sepsis is a systemic inflammatory response to infection, accounting for the most common cause of death in intensive care units. Here, we report that peripheral administration of the hypothalamic neuropeptide orexin improves the survival of mice with lipopolysaccharide (LPS) induced endotoxin shock, a well-studied septic shock model. The effect is accompanied by a suppression of excessive cytokine production and an increase of catecholamines and corticosterone. We found that peripherally administered orexin penetrates the blood-brain barrier under endotoxin shock, and that central administration of orexin also suppresses the cytokine production and improves the survival, indicating orexin's direct action in the central nervous system (CNS). Orexin helps restore body temperature and potentiates cardiovascular function in LPS-injected mice. Pleiotropic modulation of inflammatory response by orexin through the CNS may constitute a novel therapeutic approach for septic shock.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Irukayama-Tomobe", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Kiyama", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Hosokawa", "name": null }, { "creator_type": "author", "first_name": "Hiromu", "last_name": "Tominaga", "name": null }, { "creator_type": "author", "first_name": "Shuntaro", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Saki", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Kanuka", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Michito", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.21055" }, "pmcid": { "normalized": "PMC5245965" }, "pmid": { "normalized": "28035899" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood-Brain Barrier", "descriptor_ui": "D001812", "major_topic": false }, { "descriptor": "Body Temperature Regulation", "descriptor_ui": "D001833", "major_topic": false }, { "descriptor": "Bradycardia", "descriptor_ui": "D001919", "major_topic": false }, { "descriptor": "Chemokine CCL3", "descriptor_ui": "D054405", "major_topic": false }, { "descriptor": "Chemokine CCL4", "descriptor_ui": "D054407", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Injections, Subcutaneous", "descriptor_ui": "D007279", "major_topic": false }, { "descriptor": "Interferon-gamma", "descriptor_ui": "D007371", "major_topic": false }, { "descriptor": "Interleukin-17", "descriptor_ui": "D020381", "major_topic": false }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Orexins", "descriptor_ui": "D000068797", "major_topic": false }, { "descriptor": "Shock, Septic", "descriptor_ui": "D012772", "major_topic": false }, { "descriptor": "Survival Analysis", "descriptor_ui": "D016019", "major_topic": false }, { "descriptor": "Tumor Necrosis Factor-alpha", "descriptor_ui": "D014409", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec 30", "date_precision": "day", "issue": "", "normalized_date": "2016-12-30", "pages": "e21055", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "5", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Peripherally administered orexin improves survival of mice with endotoxin shock.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Gastrin-releasing peptide (GRP) has recently been identified as an itch-signaling molecule in the primary afferents and spinal cord of rodents. However, little information exists on the expression and localization of GRP in the trigeminal somatosensory system other than in rats. We examined the generality of the trigeminal GRP system in mammals using two distinct species, suncus as a model of specialized placental mammals known to have a well-developed trigeminal sensory system and mice as a representative small laboratory animal. We first analyzed the gross morphology of the trigeminal somatosensory system in suncus to provide a brainstem atlas on which to map GRP distribution. Immunohistochemical analyses showed that 8% of trigeminal ganglion neurons in suncus and 6% in mice expressed GRP. Expression was restricted to cells with smaller somata. The GRP-containing fibers were densely distributed in the superficial layers of the caudal part of the trigeminal spinal nucleus (Vc) but rare in the rostral parts, both in suncus and mice. Expression of GRP receptor mRNA and protein was also detected in the Vc of suncus. Taken together, these results suggest that the trigeminal GRP system mediating itch sensation is conserved in mammals.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Takanami", "name": null }, { "creator_type": "author", "first_name": "Kaihei", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Mukai", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Takamichi", "last_name": "Jogahara", "name": null }, { "creator_type": "author", "first_name": "Sen-ichi", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1267/ahc.16030" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28127106" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Dec 28", "date_precision": "day", "issue": "6", "normalized_date": "2016-12-28", "pages": "181-190", "proceedings_title": null, "publisher": "", "title": "Acta Histochemica et Cytochemica", "volume": "49", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparative Anatomy of Gastrin-releasing Peptide Pathways in the Trigeminal Sensory System of Mouse and the Asian House Musk Shrew Suncus murinus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular signal transduction involves a number of biochemical reactions, which largely consist of protein-protein interactions and protein conformational changes. Monitoring Forster resonance energy transfer (FRET) by fluorescence lifetime imaging microscopy (FLIM), called FLIM-FRET, is one of the best ways to visualize such protein dynamics. Here, we attempted to apply dark red fluorescent proteins with significantly smaller quantum yields. Application of the dark mCherry mutants to single-molecule FRET sensors revealed that these dark mCherry mutants are a good acceptor in a pair with mRuby2. Because the FRET measurement between mRuby2 and dark mCherry requires only the red region of wavelengths, it facilitates dual observation with other signaling sensors such as genetically encoded Ca(2+) sensors. Taking advantage of this approach, we attempted dual observation of Ca(2+) and Rho GTPase (RhoA and Cdc42) activities in astrocytes and found that ATP triggers both RhoA and Cdc42 activation. In early phase, while Cdc42 activity is independent of Ca(2+) transient evoked by ATP, RhoA activity is Ca(2+) dependent. Moreover, the transient Ca(2+) upregulation triggers long-lasting Cdc42 and RhoA activities, thereby converting short-term Ca(2+) signaling to long-term signaling. Thus, the new FRET pair should be useful for dual observation of intracellular biochemical reactions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Nakahata", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Nabekura", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep39564" }, "pmcid": { "normalized": "PMC5177924" }, "pmid": { "normalized": "28004840" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "cdc42 GTP-Binding Protein", "descriptor_ui": "D020764", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "GTP Phosphohydrolase Activators", "descriptor_ui": "D020549", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Red Fluorescent Protein", "descriptor_ui": "D000097573", "major_topic": false }, { "descriptor": "rhoA GTP-Binding Protein", "descriptor_ui": "D020742", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec 22", "date_precision": "day", "issue": "", "normalized_date": "2016-12-22", "pages": "39564", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Dual observation of the ATP-evoked small GTPase activation and Ca(2+) transient in astrocytes using a dark red fluorescent protein.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Liposome display is a method that enables the directed evolution of membrane proteins in vitro. The method is based on the syntheses of membrane proteins using an in vitro transcription-translation system (IVTT) inside cell-sized phospholipid vesicles from a single copy of template DNA. So far, a large number of membrane proteins have been synthesized by IVTT; however, none of these proteins, except for alpha-hemolysin, has been tested for use in gene screening with liposome display. Here, using EmrE, a multidrug transporter from Escherichia coli,, as a model protein, we developed an in vitro screening system of the transporter gene based on its function, which was made possible by using liposome display. The screening was performed based on two functions of EmrE: substrate transport activity and membrane integration activity. Starting from a mock gene library prepared by mixing an active and an inactive gene, 10- to 35-fold enrichment of the active genes was obtained, which was in the same range as theoretically calculated values. In addition, starting from a random mutagenized gene library of wild-type EmrE, a gene pool exhibiting ethidium bromide (EtBr) transport activity higher than that of the wild-type was obtained, indicating the validity of the established screening system.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Atsuko", "last_name": "Uyeda", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.6b02308" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28193053" } }, "mesh": [ { "descriptor": "Antiporters", "descriptor_ui": "D017920", "major_topic": false }, { "descriptor": "Cell-Free System", "descriptor_ui": "D002474", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Escherichia coli Proteins", "descriptor_ui": "D029968", "major_topic": false }, { "descriptor": "Ethidium", "descriptor_ui": "D004996", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Gene Library", "descriptor_ui": "D015723", "major_topic": false }, { "descriptor": "Liposomes", "descriptor_ui": "D008081", "major_topic": false }, { "descriptor": "Protein Biosynthesis", "descriptor_ui": "D014176", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec 20", "date_precision": "day", "issue": "24", "normalized_date": "2016-12-20", "pages": "12028-12035", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "88", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Construction of an in Vitro Gene Screening System of the E. coli EmrE Transporter Using Liposome Display.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The abrupt and irreversible transition from interphase to M phase is essential to separate DNA replication from chromosome segregation. This transition requires the switch-like phosphorylation of hundreds of proteins by the cyclin-dependent kinase 1 (Cdk1):cyclin B (CycB) complex. Previous studies have ascribed these switch-like phosphorylations to the auto-activation of Cdk1:CycB through the removal of inhibitory phosphorylations on Cdk1-Tyr15 [1, 2]. The positive feedback in Cdk1 activation creates a bistable switch that makes mitotic commitment irreversible [2-4]. Here, we surprisingly find that Cdk1 auto-activation is dispensable for irreversible, switch-like mitotic entry due to a second mechanism, whereby Cdk1:CycB inhibits its counteracting phosphatase (PP2A:B55). We show that the PP2A:B55-inhibiting Greatwall (Gwl)-endosulfine (ENSA) pathway is both necessary and sufficient for switch-like phosphorylations of mitotic substrates. Using purified components of the Gwl-ENSA pathway in a reconstituted system, we found a sharp Cdk1 threshold for phosphorylation of a luminescent mitotic substrate. The Cdk1 threshold to induce mitotic phosphorylation is distinctly higher than the Cdk1 threshold required to maintain these phosphorylations-evidence for bistability. A combination of mathematical modeling and biochemical reconstitution show that the bistable behavior of the Gwl-ENSA pathway emerges from its mutual antagonism with PP2A:B55. Our results demonstrate that two interlinked bistable mechanisms provide a robust solution for irreversible and switch-like mitotic entry.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Mochida", "name": null }, { "creator_type": "author", "first_name": "Scott", "last_name": "Rata", "name": null }, { "creator_type": "author", "first_name": "Hirotsugu", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Bela", "last_name": "Novak", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2016.10.022" }, "pmcid": { "normalized": "PMC5196020" }, "pmid": { "normalized": "27889260" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CDC2 Protein Kinase", "descriptor_ui": "D016203", "major_topic": false }, { "descriptor": "Cell Cycle Checkpoints", "descriptor_ui": "D059447", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Enzymologic", "descriptor_ui": "D015971", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Phosphatase 2", "descriptor_ui": "D054648", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec 19", "date_precision": "day", "issue": "24", "normalized_date": "2016-12-19", "pages": "3361-3367", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "26", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Two Bistable Switches Govern M Phase Entry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Directed differentiation of human pluripotent stem cells (hPSCs) can provide us any required tissue/cell types by recapitulating the development in vitro. The kidney is one of the most challenging organs to generate from hPSCs as the kidney progenitors are composed of at least 4 different cell types, including nephron, collecting duct, endothelial and interstitium progenitors, that are developmentally distinguished populations. Although the actual developmental process of the kidney during human embryogenesis has not been clarified yet, studies using model animals accumulated knowledge about the origins of kidney progenitors. The implications of these findings for the directed differentiation of hPSCs into the kidney include the mechanism of the intermediate mesoderm specification and its patterning along with anteroposterior axis. Using this knowledge, we previously reported successful generation of hPSCs-derived kidney organoids that contained all renal components and modelled human kidney development in vitro. In this review, we explain the developmental basis of the strategy behind this differentiation protocol and compare strategies of studies that also recently reported the induction of kidney cells from hPSCs. We also discuss the characterization of such kidney organoids and limitations and future applications of this technology.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null }, { "creator_type": "author", "first_name": "Melissa H.", "last_name": "Little", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2016.08.024" }, "pmcid": { "normalized": "PMC6186756" }, "pmid": { "normalized": "27565022" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Organ Culture Techniques", "descriptor_ui": "D009924", "major_topic": false }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Primitive Streak", "descriptor_ui": "D054240", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec 15", "date_precision": "day", "issue": "2", "normalized_date": "2016-12-15", "pages": "210-220", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "420", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "A strategy for generating kidney organoids: Recapitulating the development in human pluripotent stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Luminescence imaging has gained attention as a promising bio-imaging modality in situations where fluorescence imaging cannot be applied. However, wider application to multicolour and dynamic imaging is limited by the lack of bright luminescent proteins with emissions across the visible spectrum. Here we report five new spectral variants of the bright luminescent protein, enhanced Nano-lantern (eNL), made by concatenation of the brightest luciferase, NanoLuc, with various colour hues of fluorescent proteins. eNLs allow five-colour live-cell imaging, as well as detection of single protein complexes and even single molecules. We also develop an eNL-based Ca(2+) indicator with a 500% signal change, which can image spontaneous Ca(2+) dynamics in cardiomyocyte and neural cell models. These eNL probes facilitate not only multicolour imaging in living cells but also sensitive imaging of a wide repertoire of proteins, even at very low expression levels.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazushi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Taichi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Shinoda", "name": null }, { "creator_type": "author", "first_name": "Guirong", "last_name": "Bai", "name": null }, { "creator_type": "author", "first_name": "Matthew J.", "last_name": "Daniels", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms13718" }, "pmcid": { "normalized": "PMC5171807" }, "pmid": { "normalized": "27966527" } }, "mesh": [ { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Color", "descriptor_ui": "D003116", "major_topic": true }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec 14", "date_precision": "day", "issue": "", "normalized_date": "2016-12-14", "pages": "13718", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Five colour variants of bright luminescent protein for real-time multicolour bioimaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Telomeric repeat-containing RNA (TERRA) controls the structure and length of telomeres through interactions with numerous telomere-binding proteins. However, little is known about the mechanism by which TERRA regulates the accessibility of the proteins to telomeres, mainly because of the lack of spatiotemporal information of TERRA and its-interacting proteins. We developed a fluorescent probe to visualize endogenous TERRA to investigate its dynamics in living cells. Single-particle fluorescence imaging revealed that TERRA accumulated in a telomere-neighboring region and trapped diffusive heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), thereby inhibiting hnRNPA1 localization to the telomere. These results suggest that TERRA regulates binding of hnRNPA1 to the telomere in a region surrounding the telomere, leading to a deeper understanding of the mechanism of TERRA function.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Toshimichi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Rintaro", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Takahiro K.", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Kusumi", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep38910" }, "pmcid": { "normalized": "PMC5153658" }, "pmid": { "normalized": "27958374" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Heterogeneous Nuclear Ribonucleoprotein A1", "descriptor_ui": "D000076245", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "RNA Probes", "descriptor_ui": "D015347", "major_topic": true }, { "descriptor": "RNA, Long Noncoding", "descriptor_ui": "D062085", "major_topic": false }, { "descriptor": "Spatio-Temporal Analysis", "descriptor_ui": "D062211", "major_topic": false }, { "descriptor": "Telomere", "descriptor_ui": "D016615", "major_topic": false }, { "descriptor": "Telomere-Binding Proteins", "descriptor_ui": "D034501", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec 13", "date_precision": "day", "issue": "", "normalized_date": "2016-12-13", "pages": "38910", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatiotemporal analysis with a genetically encoded fluorescent RNA probe reveals TERRA function around telomeres.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chromosome condensation is essential for the faithful transmission of genetic information to daughter cells during cell division. The depletion of chromosome scaffold proteins does not prevent chromosome condensation despite structural defects. This suggests that other factors contribute to condensation. Here we investigated the contribution of divalent cations, particularly Ca(2+), to chromosome condensation in vitro and in vivo. Ca(2+) depletion caused defects in proper mitotic progression, particularly in chromosome condensation after the breakdown of the nuclear envelope. Fluorescence lifetime imaging microscopy-Forster resonance energy transfer and electron microscopy demonstrated that chromosome condensation is influenced by Ca(2+). Chromosomes had compact globular structures when exposed to Ca(2+) and expanded fibrous structures without Ca(2+). Therefore, we have clearly demonstrated a role for Ca(2+) in the compaction of chromatin fibres.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Rinyaporn", "last_name": "Phengchat", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Morii", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Inada", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Kiichi", "last_name": "Fukui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep38281" }, "pmcid": { "normalized": "PMC5133622" }, "pmid": { "normalized": "27910894" } }, "mesh": [ { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Chelating Agents", "descriptor_ui": "D065096", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Chromatin Assembly and Disassembly", "descriptor_ui": "D042002", "major_topic": false }, { "descriptor": "DNA Packaging", "descriptor_ui": "D042003", "major_topic": false }, { "descriptor": "Egtazic Acid", "descriptor_ui": "D004533", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Fura-2", "descriptor_ui": "D016257", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Metaphase", "descriptor_ui": "D008677", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Nuclear Envelope", "descriptor_ui": "D009685", "major_topic": false }, { "descriptor": "Red Fluorescent Protein", "descriptor_ui": "D000097573", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec 2", "date_precision": "day", "issue": "", "normalized_date": "2016-12-02", "pages": "38281", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Calcium ions function as a booster of chromosome condensation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "As in osmoregulation, mineralocorticoid signaling is implicated in the control of brain-behavior actions. Nevertheless, the understanding of this role is limited, partly due to the mortality of mineralocorticoid receptor (MR)-knockout (KO) mice due to impaired Na(+) reabsorption. In teleost fish, a distinct mineralocorticoid system has only been identified recently. Here, we generated a constitutive MR-KO medaka as the first adult-viable MR-KO animal, since MR expression is modest in osmoregulatory organs but high in the brain of adult medaka as for most teleosts. Hyper- and hypo-osmoregulation were normal in MR-KO medaka. When we studied the behavioral phenotypes based on the central MR localization, however, MR-KO medaka failed to track moving dots despite having an increase in acceleration of swimming. These findings reinforce previous results showing a minor role for mineralocorticoid signaling in fish osmoregulation, and provide the first convincing evidence that MR is required for normal locomotor activity in response to visual motion stimuli, but not for the recognition of these stimuli per se. We suggest that MR potentially integrates brain-behavioral and visual responses, which might be a conserved function of mineralocorticoid signaling through vertebrates. Importantly, this fish model allows for the possible identification of novel aspects of mineralocorticoid signaling.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Madoka", "last_name": "Yoshiki", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Ogino", "name": null }, { "creator_type": "author", "first_name": "Toshitaka", "last_name": "Ikeuchi", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Nakamachi", "name": null }, { "creator_type": "author", "first_name": "Norifumi", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Kouhei", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep37991" }, "pmcid": { "normalized": "PMC5126551" }, "pmid": { "normalized": "27897263" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Eye", "descriptor_ui": "D005123", "major_topic": false }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": false }, { "descriptor": "Mineralocorticoids", "descriptor_ui": "D008901", "major_topic": false }, { "descriptor": "Oryzias", "descriptor_ui": "D009990", "major_topic": false }, { "descriptor": "Osmoregulation", "descriptor_ui": "D064587", "major_topic": false }, { "descriptor": "Receptors, Mineralocorticoid", "descriptor_ui": "D018161", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Visual Perception", "descriptor_ui": "D014796", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov 29", "date_precision": "day", "issue": "", "normalized_date": "2016-11-29", "pages": "37991", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Principal function of mineralocorticoid signaling suggested by constitutive knockout of the mineralocorticoid receptor in medaka fish.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Glutamatergic N-methyl-d-aspartate (NMDA) receptors play critical roles in several neurological and psychiatric diseases. Blockade by noncompetitive NMDA receptor antagonist leads to psychotomimetic effects; however, the brain regions responsible for the effects are not well understood. Here, we determined the specific brain regions responsive to MK-801, a noncompetitive NMDA receptor antagonist, by mapping Arc expression as an indicator of neuronal activity using Arc::dVenus reporter mice. MK-801 increased dVenus expression predominantly in the orbitofrontal cortex (OFC) and, as expected, induced a marked hyperlocomotion. Local OFC lesions selectively attenuated the early phase (0-30 min) of MK-801-induced hyperlocomotion. Further, clozapine, an atypical antipsychotic, effectively attenuated both the MK-801-induced dVenus expression in the OFC and hyperlocomotion. These results suggest that the OFC may be critically involved in NMDA receptor-mediated psychotic-like behavioral abnormalities.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuwaki", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2016.10.089" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27793672" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dizocilpine Maleate", "descriptor_ui": "D016291", "major_topic": false }, { "descriptor": "Frontal Lobe", "descriptor_ui": "D005625", "major_topic": false }, { "descriptor": "Hyperkinesis", "descriptor_ui": "D006948", "major_topic": false }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Psychoses, Substance-Induced", "descriptor_ui": "D011605", "major_topic": false }, { "descriptor": "Receptors, N-Methyl-D-Aspartate", "descriptor_ui": "D016194", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov 25", "date_precision": "day", "issue": "4", "normalized_date": "2016-11-25", "pages": "558-563", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "480", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Critical involvement of the orbitofrontal cortex in hyperlocomotion induced by NMDA receptor blockade in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transcription activator-like effector (TALE) nuclease (TALEN) is widely used as a tool in genome editing. The DNA binding part of TALEN consists of a tandem array of TAL-repeats that form a right-handed superhelix. Each TAL-repeat recognises a specific base by the repeat variable diresidue (RVD) at positions 12 and 13. TALEN comprising the TAL-repeats with periodic mutations to residues at positions 4 and 32 (non-RVD sites) in each repeat (VT-TALE) exhibits increased efficacy in genome editing compared with a counterpart without the mutations (CT-TALE). The molecular basis for the elevated efficacy is unknown. In this report, comparison of the physicochemical properties between CT- and VT-TALEs revealed that VT-TALE has a larger amplitude motion along the superhelical axis (superhelical motion) compared with CT-TALE. The greater superhelical motion in VT-TALE enabled more TAL-repeats to engage in the target sequence recognition compared with CT-TALE. The extended sequence recognition by the TAL-repeats improves site specificity with limiting the spatial distribution of FokI domains to facilitate their dimerization at the desired site. Molecular dynamics simulations revealed that the non-RVD mutations alter inter-repeat hydrogen bonding to amplify the superhelical motion of VT-TALE. The TALEN activity is associated with the inter-repeat hydrogen bonding among the TAL repeats.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Naoya", "last_name": "Tochio", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Umehara", "name": null }, { "creator_type": "author", "first_name": "Jun-Ichi", "last_name": "Uewaki", "name": null }, { "creator_type": "author", "first_name": "Holger", "last_name": "Flechsig", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Takehisa", "last_name": "Dewa", "name": null }, { "creator_type": "author", "first_name": "Tetsushi", "last_name": "Sakuma", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Saitoh", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Togashi", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Tate", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep37887" }, "pmcid": { "normalized": "PMC5121632" }, "pmid": { "normalized": "27883072" } }, "mesh": [ { "descriptor": "Chromatography, Gel", "descriptor_ui": "D002850", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Dynamic Light Scattering", "descriptor_ui": "D000067493", "major_topic": false }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": true }, { "descriptor": "Hydrogen Bonding", "descriptor_ui": "D006860", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Repetitive Sequences, Amino Acid", "descriptor_ui": "D020449", "major_topic": false }, { "descriptor": "Thermodynamics", "descriptor_ui": "D013816", "major_topic": false }, { "descriptor": "Transcription Activator-Like Effector Nucleases", "descriptor_ui": "D000069896", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov 24", "date_precision": "day", "issue": "", "normalized_date": "2016-11-24", "pages": "37887", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Non-RVD mutations that enhance the dynamics of the TAL repeat array along the superhelical axis improve TALEN genome editing efficacy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Multicellular spheroids have been studied in the fields of oncology, stem cell biology, and tissue engineering. In this study, we found a new polymer material for thermo-controlled spheroid/monolayer cell culture switching. The polymers that have pendant ureido groups (ureido polymers) exhibited upper critical solution temperature-type phase separation behavior. Cells in monolayer culture were converted to spheroids by the addition of ureido polymers below phase separation temperature (T(p)). Time-lapse observations indicated that cells began to migrate and aggregate to form the spheroids to avoid contact with phase-separated polymer (coacervates) on the surface of the culture dish. We supposed that the coacervates seemingly suppressed interaction between cell and the dish surface or extracellular matrices. By increasing culture temperature above T(p), the spheroids began to collapse into a monolayer of cells due to dissolution of the coacervates. These results indicated that cell morphology could be repeatedly switched by changing the culture temperature in the presence of ureido polymers.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Naohiko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Shukuri", "name": null }, { "creator_type": "author", "first_name": "Sotaro", "last_name": "Kuroyanagi", "name": null }, { "creator_type": "author", "first_name": "Thasaneeya", "last_name": "Kuboki", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Kidoaki", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Maruyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsami.6b07614" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27802011" } }, "mesh": [ { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": true }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Spheroids, Cellular", "descriptor_ui": "D018874", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false }, { "descriptor": "Tissue Engineering", "descriptor_ui": "D023822", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov 23", "date_precision": "day", "issue": "46", "normalized_date": "2016-11-23", "pages": "31524-31529", "proceedings_title": null, "publisher": "", "title": "ACS applied materials & interfaces", "volume": "8", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Reversible Monolayer/Spheroid Cell Culture Switching by UCST-Type Thermoresponsive Ureido Polymers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The acquired immune system, mainly composed of T and B lymphocytes, plays a key role in protecting the host from infection. It is important and technically challenging to identify cell types and their activation status in living and intact immune cells, without staining or killing the cells. Using Raman spectroscopy, we succeeded in discriminating between living T cells and B cells, and visualized the activation status of living T cells without labeling. Although the Raman spectra of T cells and B cells were similar, they could be distinguished by discriminant analysis of the principal components. Raman spectra of activated T cells with anti-CD3 and anti-CD28 antibodies largely differed compared to that of naive T cells, enabling the prediction of T cell activation status at a single cell level. Our analysis revealed that the spectra of individual T cells gradually change from the pattern of naive T cells to that of activated T cells during the first 24 h of activation, indicating that changes in Raman spectra reflect slow changes rather than rapid changes in cell state during activation. Our results indicate that the Raman spectrum enables the detection of dynamic changes in individual cell state scattered in a heterogeneous population.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Liang-da", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Machiyama", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep37562" }, "pmcid": { "normalized": "PMC5120326" }, "pmid": { "normalized": "27876845" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov 23", "date_precision": "day", "issue": "", "normalized_date": "2016-11-23", "pages": "37562", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [ "ssbd-database-000053" ], "repository": [ "ssbd-repos-000053" ] }, "title": "Non-label immune cell state prediction using Raman spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sleep is conserved from invertebrates to vertebrates, and is tightly regulated in a homeostatic manner. The molecular and cellular mechanisms that determine the amount of rapid eye movement sleep (REMS) and non-REMS (NREMS) remain unknown. Here we identify two dominant mutations that affect sleep and wakefulness by using an electroencephalogram/electromyogram-based screen of randomly mutagenized mice. A splicing mutation in the Sik3 protein kinase gene causes a profound decrease in total wake time, owing to an increase in inherent sleep need. Sleep deprivation affects phosphorylation of regulatory sites on the kinase, suggesting a role for SIK3 in the homeostatic regulation of sleep amount. Sik3 orthologues also regulate sleep in fruitflies and roundworms. A missense, gain-of-function mutation in the sodium leak channel NALCN reduces the total amount and episode duration of REMS, apparently by increasing the excitability of REMS-inhibiting neurons. Our results substantiate the use of a forward-genetics approach for studying sleep behaviours in mice, and demonstrate the role of SIK3 and NALCN in regulating the amount of NREMS and REMS, respectively.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Funato", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Miyoshi", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Fujiyama", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Makito", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Zhiqiang", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Jing", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Nakane", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Ikkyu", "name": null }, { "creator_type": "author", "first_name": "Miyo", "last_name": "Kakizaki", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Hotta-Hirashima", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Kanno", "name": null }, { "creator_type": "author", "first_name": "Haruna", "last_name": "Komiya", "name": null }, { "creator_type": "author", "first_name": "Fuyuki", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Takato", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Staci J.", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Kanako", "last_name": "Harano", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Muramoto", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Yonezawa", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Linzi", "last_name": "Connor", "name": null }, { "creator_type": "author", "first_name": "Vivek", "last_name": "Kumar", "name": null }, { "creator_type": "author", "first_name": "Ikuo", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Fumihiro", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Qinghua", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Kume", "name": null }, { "creator_type": "author", "first_name": "Shigeharu", "last_name": "Wakana", "name": null }, { "creator_type": "author", "first_name": "Joseph S.", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nature20142" }, "pmcid": { "normalized": "PMC6076225" }, "pmid": { "normalized": "27806374" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": false }, { "descriptor": "Conserved Sequence", "descriptor_ui": "D017124", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Electroencephalography", "descriptor_ui": "D004569", "major_topic": false }, { "descriptor": "Electromyography", "descriptor_ui": "D004576", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Ion Channels", "descriptor_ui": "D007473", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutagenesis", "descriptor_ui": "D016296", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Random Allocation", "descriptor_ui": "D011897", "major_topic": false }, { "descriptor": "RNA Splicing", "descriptor_ui": "D012326", "major_topic": false }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": false }, { "descriptor": "Sleep Deprivation", "descriptor_ui": "D012892", "major_topic": false }, { "descriptor": "Sleep, REM", "descriptor_ui": "D012895", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Wakefulness", "descriptor_ui": "D014851", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov 17", "date_precision": "day", "issue": "7629", "normalized_date": "2016-11-17", "pages": "378-383", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "539", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Forward-genetics analysis of sleep in randomly mutagenized mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Apterous (Ap), the best studied LIM-homeodomain transcription factor in Drosophila, cooperates with the cofactor Chip (Chi) to regulate transcription of specific target genes. Although Ap regulates various developmental processes, its function in the adult brain remains unclear. Here, we report that Ap and Chi in the neurons expressing PDF, a neuropeptide, play important roles in proper sleep/wake regulation in adult flies. PDF-expressing neurons consist of two neuronal clusters: small ventral-lateral neurons (s-LNvs) acting as the circadian pacemaker and large ventral-lateral neurons (l-LNvs) regulating light-driven arousal. We identified that Ap localizes to the nuclei of s-LNvs and l-LNvs. In light-dark (LD) cycles, RNAi knockdown or the targeted expression of dominant-negative forms of Ap or Chi in PDF-expressing neurons or l-LNvs promoted arousal. In contrast, in constant darkness, knockdown of Ap in PDF-expressing neurons did not promote arousal, indicating that a reduced Ap function in PDF-expressing neurons promotes light-driven arousal. Furthermore, Ap expression in l-LNvs showed daily rhythms (peaking at midnight), which are generated by a direct light-dependent mechanism rather than by the endogenous clock. These results raise the possibility that the daily oscillation of Ap expression in l-LNvs may contribute to the buffering of light-driven arousal in wild-type flies.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naoto", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Show", "last_name": "Inami", "name": null }, { "creator_type": "author", "first_name": "Shoma", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kitamoto", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep37255" }, "pmcid": { "normalized": "PMC5112534" }, "pmid": { "normalized": "27853240" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arousal", "descriptor_ui": "D001143", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": true }, { "descriptor": "LIM-Homeodomain Proteins", "descriptor_ui": "D060850", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov 17", "date_precision": "day", "issue": "", "normalized_date": "2016-11-17", "pages": "37255", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Modulation of light-driven arousal by LIM-homeodomain transcription factor Apterous in large PDF-positive lateral neurons of the Drosophila brain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herpes simplex virus 1 (HSV-1) envelope glycoprotein D (gD) plays an essential role in viral entry. The functional regions of gD responsible for viral entry have been mapped to its extracellular domain, whereas the gD cytoplasmic domain plays no obvious role in viral entry. Thus far, the role(s) of the gD cytoplasmic domain in HSV-1 replication has remained to be elucidated. In this study, we show that ectopic expression of gD induces microvillus-like tubular structures at the plasma membrane which resemble the reported projection structures of the plasma membrane induced in HSV-1-infected cells. Mutations in the arginine cluster (residues 365 to 367) in the gD cytoplasmic domain greatly reduced gD-induced plasma membrane remodeling. In agreement with this, the mutations in the arginine cluster in the gD cytoplasmic domain reduced the number of microvillus-like tubular structures at the plasma membrane in HSV-1-infected cells. In addition, the mutations produced an accumulation of unenveloped nucleocapsids in the cytoplasm and reduced viral replication and cell-cell spread. These results suggest that the arginine cluster in the gD cytoplasmic domain is required for the efficient induction of plasma membrane projections and viral final envelopment, and these functions of the gD domain may lead to efficient viral replication and cell-cell spread. IMPORTANCE: The cytoplasmic domain of HSV-1 gD, an envelope glycoprotein essential for viral entry, was reported to promote viral replication and cell-cell spread, but the role(s) of the domain during HSV-1 infection has remained unknown. In this study, we clarify two functions of the arginine cluster in the HSV-1 gD cytoplasmic domain, both of which require host cell membrane remodeling, i.e., the formation of microvillus-like projections at the plasma membrane and viral final envelopment in HSV-1-infected cells. We also show that the gD arginine cluster is required for efficient HSV-1 replication and cell-cell spread. This is the first report clarifying not only the functions of the gD cytoplasmic domain but also identifying the gD arginine cluster to be the HSV-1 factor responsible for the induction of plasma membrane projections in HSV-1-infected cells. Our results elucidate some of the functions of this multifunctional envelope glycoprotein during HSV-1 infection.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01396-16" }, "pmcid": { "normalized": "PMC5105654" }, "pmid": { "normalized": "27581980" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nucleocapsid", "descriptor_ui": "D019251", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Envelope Proteins", "descriptor_ui": "D014759", "major_topic": false }, { "descriptor": "Virus Internalization", "descriptor_ui": "D053586", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov 15", "date_precision": "day", "issue": "22", "normalized_date": "2016-11-15", "pages": "10170-10181", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "90", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Multiple Roles of the Cytoplasmic Domain of Herpes Simplex Virus 1 Envelope Glycoprotein D in Infected Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "MOTIVATION: Rapid advances in live-cell imaging analysis and mathematical modeling have produced a large amount of quantitative data on spatiotemporal dynamics of biological objects ranging from molecules to organisms. There is now a crucial need to bring these large amounts of quantitative biological dynamics data together centrally in a coherent and systematic manner. This will facilitate the reuse of this data for further analysis. RESULTS: We have developed the Systems Science of Biological Dynamics database (SSBD) to store and share quantitative biological dynamics data. SSBD currently provides 311 sets of quantitative data for single molecules, nuclei and whole organisms in a wide variety of model organisms from Escherichia coli to Mus musculus The data are provided in Biological Dynamics Markup Language format and also through a REST API. In addition, SSBD provides 188 sets of time-lapse microscopy images from which the quantitative data were obtained and software tools for data visualization and analysis. AVAILABILITY AND IMPLEMENTATION: SSBD is accessible at http://ssbd.qbic.riken.jp CONTACT: sonami@riken.jp.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukako", "last_name": "Tohsato", "name": null }, { "creator_type": "author", "first_name": "Kenneth H. L.", "last_name": "Ho", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/bioinformatics/btw417" }, "pmcid": { "normalized": "PMC5181557" }, "pmid": { "normalized": "27412095" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Phenomena", "descriptor_ui": "D001686", "major_topic": true }, { "descriptor": "Databases, Factual", "descriptor_ui": "D016208", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov 15", "date_precision": "day", "issue": "22", "normalized_date": "2016-11-15", "pages": "3471-3479", "proceedings_title": null, "publisher": "", "title": "Bioinformatics (Oxford, England)", "volume": "32", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "SSBD: a database of quantitative data of spatiotemporal dynamics of biological phenomena.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2), which is a second receptor for prostaglandin (PG) D2, is involved in inflammatory responses in peripheral tissue; however, its role in cognitive function remains unclear. Here, we demonstrate that CRTH2 is involved in cognitive function using a well-established animal model of cognitive dysfunction induced by MK-801, an N-methyl-d-aspartate receptor antagonist. Genetic deletion and pharmacological inhibition of CRTH2 suppressed MK-801-induced cognitive dysfunction. Pharmacological inhibition of cyclooxygenase-1, a rate-limiting enzyme in PG synthesis, also suppressed MK-801-induced cognitive dysfunction. Moreover, an MK-801-induced increase in c-Fos expression in the paraventricular nucleus (PVN) was abolished in the CRTH2-deficient mice. Together, these results suggest that PGD2-CRTH2 signaling is involved in both MK-801-induced cognitive dysfunction and neuronal activity regulation in the PVN. Furthermore, genetic association studies suggest that CRTH2 is weakly associated with cognitive function in humans. Our study provides evidence that PGD2-CRTH2 signaling is involved in cognitive function and may represent a potential therapeutic target for cognitive dysfunction in patients with psychiatric disorders.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Onaka", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Kanoh", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Ohi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Kin-Ya", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Asao", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbr.2016.07.050" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27481693" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cognitive Dysfunction", "descriptor_ui": "D060825", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Dizocilpine Maleate", "descriptor_ui": "D016291", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Prostaglandin D2", "descriptor_ui": "D015230", "major_topic": false }, { "descriptor": "Receptors, Immunologic", "descriptor_ui": "D011971", "major_topic": false }, { "descriptor": "Receptors, N-Methyl-D-Aspartate", "descriptor_ui": "D016194", "major_topic": false }, { "descriptor": "Receptors, Prostaglandin", "descriptor_ui": "D011982", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov 1", "date_precision": "day", "issue": "", "normalized_date": "2016-11-01", "pages": "77-86", "proceedings_title": null, "publisher": "", "title": "Behavioural brain research", "volume": "314", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Prostaglandin D2 signaling mediated by the CRTH2 receptor is involved in MK-801-induced cognitive dysfunction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have constructed a prototype photoacoustic mammography system (PAM-02) capable of simultaneously acquiring photoacoustic (PA) and ultrasound (US) images. Each PA, US, and fused PA/US image can be acquired over a wide area of the breast using the scanning module of a US transducer, a PA detector, and optical prisms. The resolution of the PA images exhibits improvement from 2 to 1 mm compared to images acquired using our previous prototype. The maximum scan area of PAM-02 is 90 mm along the horizontal axis and 150 mm along the vertical axis. In a phantom experiment, the available depth was at least 45 mm. A representative example of the application of the PAM-02 prototype in clinical research at Kyoto University is presented and shows S-factor images, which are considered an approximation parameter related to hemoglobin saturation of tumor-related blood vessels. We confirmed the applicability of the system for anatomical and biological research.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Asao", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Suita", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Nagae", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Fukutani", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Toshikazu", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Tokiwa", "name": null }, { "creator_type": "author", "first_name": "Iku", "last_name": "Yamaga", "name": null }, { "creator_type": "author", "first_name": "Elham", "last_name": "Fakhrejahani", "name": null }, { "creator_type": "author", "first_name": "Masae", "last_name": "Torii", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Kanao", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Toi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1117/1.jbo.21.11.116009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27893089" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Breast", "descriptor_ui": "D001940", "major_topic": false }, { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Mammography", "descriptor_ui": "D008327", "major_topic": false }, { "descriptor": "Phantoms, Imaging", "descriptor_ui": "D019047", "major_topic": false }, { "descriptor": "Photoacoustic Techniques", "descriptor_ui": "D061088", "major_topic": false }, { "descriptor": "Ultrasonography", "descriptor_ui": "D014463", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov 1", "date_precision": "day", "issue": "11", "normalized_date": "2016-11-01", "pages": "116009", "proceedings_title": null, "publisher": "", "title": "Journal of biomedical optics", "volume": "21", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Photoacoustic mammography capable of simultaneously acquiring photoacoustic and ultrasound images.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Spinocerebellar ataxia type 6 (SCA6) is a dominantly inherited neurodegenerative disease characterized by loss of Purkinje cells in the cerebellum. SCA6 is caused by CAG trinucleotide repeat expansion in CACNA1A, which encodes Cav2.1, alpha1A subunit of P/Q-type calcium channel. However, the pathogenic mechanism and effective therapeutic treatments are still unknown. Here, we have succeeded in generating differentiated Purkinje cells that carry patient genes by combining disease-specific iPSCs and self-organizing culture technologies. Patient-derived Purkinje cells exhibit increased levels of full-length Cav2.1 protein but decreased levels of its C-terminal fragment and downregulation of the transcriptional targets TAF1 and BTG1. We further demonstrate that SCA6 Purkinje cells exhibit thyroid hormone depletion-dependent degeneration, which can be suppressed by two compounds, thyroid releasing hormone and Riluzole. Thus, we have constructed an in vitro disease model recapitulating both ontogenesis and pathogenesis. This model may be useful for pathogenic investigation and drug screening.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihito", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null }, { "creator_type": "author", "first_name": "Haruhisa", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2016.10.026" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27806289" } }, "mesh": [ { "descriptor": "Calcium Channels, N-Type", "descriptor_ui": "D020864", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Protein Domains", "descriptor_ui": "D000072417", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Riluzole", "descriptor_ui": "D019782", "major_topic": false }, { "descriptor": "Spinocerebellar Ataxias", "descriptor_ui": "D020754", "major_topic": false }, { "descriptor": "Thyrotropin", "descriptor_ui": "D013972", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov 1", "date_precision": "day", "issue": "6", "normalized_date": "2016-11-01", "pages": "1482-1490", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "17", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Vulnerability of Purkinje Cells Generated from Spinocerebellar Ataxia Type 6 Patient-Derived iPSCs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurofibrillar tangles caused by intracellular hyperphosphorylated tau inclusion and extracellular amyloid beta peptide deposition are hallmarks of Alzheimer's disease. Tau contains one or two cysteine residues in three or four repeats of the microtubule binding region following alternative splicing of exon 10, and formation of intermolecular cysteine disulfide bonds accelerates tau aggregation. 8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) acts as a novel second messenger of nitric oxide (NO) by covalently binding cGMP to cysteine residues by electrophilic properties, a process termed protein S-guanylation. Here we studied S-guanylation of tau and its effects on tau aggregation. 8-Nitro-cGMP exposure induced S-guanylation of tau both in vitro and in tau-overexpressed HEK293T cells. S-guanylated tau inhibited heparin-induced tau aggregation in a thioflavin T assay. Atomic force microscopy observations indicated that S-guanylated tau could not form tau granules and fibrils. Further biochemical analyses showed that S-guanylated tau was inhibited at the step of tau oligomer formation. In P301L tau-expressing Neuro2A cells, 8-nitro-cGMP treatment significantly reduced the amount of sarcosyl-insoluble tau. NO-linked chemical modification on cysteine residues of tau could block tau aggregation, and therefore, increasing 8-nitro-cGMP levels in the brain could become a potential therapeutic strategy for Alzheimer's disease.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Yoshitake", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Soeda", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Sumioka", "name": null }, { "creator_type": "author", "first_name": "Misato", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m116.734350" }, "pmcid": { "normalized": "PMC5077206" }, "pmid": { "normalized": "27601475" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Protein Aggregates", "descriptor_ui": "D066329", "major_topic": true }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": true }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct 21", "date_precision": "day", "issue": "43", "normalized_date": "2016-10-21", "pages": "22714-22720", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "291", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Modification of Tau by 8-Nitroguanosine 3',5'-Cyclic Monophosphate (8-Nitro-cGMP): EFFECTS OF NITRIC OXIDE-LINKED CHEMICAL MODIFICATION ON TAU AGGREGATION.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tissue pattern formation during development is a reproducible morphogenetic process organized by a series of kinetic cellular activities, leading to the building of functional and stable organs. Recent studies focusing on mechanical aspects have revealed physical mechanisms on how the cellular activities contribute to the formation of reproducible tissue patterns; however, the understanding for what factors achieve the reproducibility of such patterning and how it occurs is far from complete. Here, I focus on a tube pattern formation during murine epididymal development, and show that two factors influencing physical design for the patterning, the proliferative zone within the tubule and the viscosity of tissues surrounding to the tubule, control the reproducibility of epididymal tubule pattern, using a mathematical model based on experimental data. Extensive numerical simulation of the simple mathematical model revealed that a spatially localized proliferative zone within the tubule, observed in experiments, results in more reproducible tubule pattern. Moreover, I found that the viscosity of tissues surrounding to the tubule imposes a trade-off regarding pattern reproducibility and spatial accuracy relating to the region where the tubule pattern is formed. This indicates an existence of optimality in material properties of tissues for the robust patterning of epididymal tubule. The results obtained by numerical analysis based on experimental observations provide a general insight on how physical design realizes robust tissue pattern formation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtbi.2016.07.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27396360" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Epididymis", "descriptor_ui": "D004822", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Numerical Analysis, Computer-Assisted", "descriptor_ui": "D009716", "major_topic": false }, { "descriptor": "Viscosity", "descriptor_ui": "D014783", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct 21", "date_precision": "day", "issue": "", "normalized_date": "2016-10-21", "pages": "71-80", "proceedings_title": null, "publisher": "", "title": "Journal of theoretical biology", "volume": "407", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Mathematical study on robust tissue pattern formation in growing epididymal tubule.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In fundamental biological processes, cells often move in groups, a process termed collective cell migration. Collectively migrating cells are much better organized than a random assemblage of individual cells. Many molecules have been identified as factors involved in collective cell migration, and no one molecule is adequate to explain the whole picture. Here we show that JRAB/MICAL-L2, an effector protein of Rab13 GTPase, provides the \"law and order\" allowing myriad cells to behave as a single unit just by changing its conformation. First, we generated a structural model of JRAB/MICAL-L2 by a combination of bioinformatic and biochemical analyses and showed how JRAB/MICAL-L2 interacts with Rab13 and how its conformational change occurs. We combined cell biology, live imaging, computational biology, and biomechanics to show that impairment of conformational plasticity in JRAB/MICAL-L2 causes excessive rigidity and loss of directionality, leading to imbalance in cell group behavior. This multidisciplinary approach supports the concept that the conformational plasticity of a single molecule provides \"law and order\" in collective cell migration.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ayuko", "last_name": "Sakane", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Masaomi", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Natsuki", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Issei", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Chiharu", "last_name": "Mizuguchi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takato", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Sachi", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Haga", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Deguchi", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Mizuguchi", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Sasaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1091/mbc.e16-05-0332" }, "pmcid": { "normalized": "PMC5063617" }, "pmid": { "normalized": "27582384" } }, "mesh": [ { "descriptor": "Actinin", "descriptor_ui": "D000185", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Focal Adhesions", "descriptor_ui": "D022001", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "Microfilament Proteins", "descriptor_ui": "D008840", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "rab GTP-Binding Proteins", "descriptor_ui": "D020691", "major_topic": false }, { "descriptor": "Tight Junctions", "descriptor_ui": "D019108", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct 15", "date_precision": "day", "issue": "20", "normalized_date": "2016-10-15", "pages": "3095-3108", "proceedings_title": null, "publisher": "", "title": "Molecular biology of the cell", "volume": "27", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Conformational plasticity of JRAB/MICAL-L2 provides \"law and order\" in collective cell migration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mutations in the gene MAPT encoding tau, a microtubules-associated protein, cause a subtype of familial neurodegenerative disorder, known as frontotemporal lobar degeneration tauopathy (FTLD-Tau), which presents with dementia and is characterized by atrophy in the frontal and temporal lobes of the brain. Although induced pluripotent stem cell (iPSC) technology has facilitated the investigation of phenotypes of FTLD-Tau patient neuronal cells in vitro, it remains unclear how FTLD-Tau patient neurons degenerate. Here, we established neuronal models of FTLD-Tau by Neurogenin2-induced direct neuronal differentiation from FTLD-Tau patient iPSCs. We found that FTLD-Tau neurons, either with an intronic MAPT mutation or with an exonic mutation, developed accumulation and extracellular release of misfolded tau followed by neuronal death, which we confirmed by correction of the intronic mutation with CRISPR/Cas9. FTLD-Tau neurons showed dysregulation of the augmentation of Ca(2+) transients evoked by electrical stimulation. Chemogenetic or pharmacological control of neuronal activity-relevant Ca(2+) influx by the introduction of designer receptors exclusively activated by designer drugs (DREADDs) or by the treatment with glutamate receptor blockers attenuated misfolded tau accumulation and neuronal death. These data suggest that neuronal activity may regulate neurodegeneration in tauopathy. This FTLD-Tau model provides mechanistic insights into tauopathy pathogenesis and potential avenues for treatments.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Nicholas M.", "last_name": "Kanaan", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Tsukita", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Kutoku", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Ohsawa", "name": null }, { "creator_type": "author", "first_name": "Yoshihide", "last_name": "Sunada", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Akitsu", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yawata", "name": null }, { "creator_type": "author", "first_name": "Dai", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "John Q.", "last_name": "Trojanowski", "name": null }, { "creator_type": "author", "first_name": "Virginia M.-Y.", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Haruhisa", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep34904" }, "pmcid": { "normalized": "PMC5056519" }, "pmid": { "normalized": "27721502" } }, "mesh": [ { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Frontotemporal Lobar Degeneration", "descriptor_ui": "D057174", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Protein Folding", "descriptor_ui": "D017510", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct 10", "date_precision": "day", "issue": "", "normalized_date": "2016-10-10", "pages": "34904", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Calcium dysregulation contributes to neurodegeneration in FTLD patient iPSC-derived neurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Calcium (Ca(2+)) is a versatile intracellular second messenger that operates in various signaling pathways leading to multiple biological outputs. The diversity of spatiotemporal patterns of Ca(2+) signals, generated by the coordination of Ca(2+) influx from the extracellular space and Ca(2+) release from the intracellular Ca(2+) store the endoplasmic reticulum (ER), is considered to underlie the diversity of biological outputs caused by a single signaling molecule. However, such Ca(2+) signaling diversity has not been well described because of technical limitations. Here, we describe a new method to report Ca(2+) signals at subcellular resolution. We report that OER-GCaMP6f, a genetically encoded Ca(2+) indicator (GECI) targeted to the outer ER membrane, can monitor Ca(2+) release from the ER at higher spatiotemporal resolution than conventional GCaMP6f. OER-GCaMP6f was used for in vivo Ca(2+) imaging of C. elegans. We also found that the spontaneous Ca(2+) elevation in cultured astrocytes reported by OER-GCaMP6f showed a distinct spatiotemporal pattern from that monitored by plasma membrane-targeted GCaMP6f (Lck-GCaMP6f); less frequent Ca(2+) signal was detected by OER-GCaMP6f, in spite of the fact that Ca(2+) release from the ER plays important roles in astrocytes. These findings suggest that targeting of GECIs to the ER outer membrane enables sensitive detection of Ca(2+) release from the ER at subcellular resolution, avoiding the diffusion of GECI and Ca(2+). Our results indicate that Ca(2+) imaging with OER-GCaMP6f in combination with Lck-GCaMP6f can contribute to describing the diversity of Ca(2+) signals, by enabling dissection of Ca(2+) signals at subcellular resolution.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Fumihiro", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Sakuragi", "name": null }, { "creator_type": "author", "first_name": "Ayana", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Mikoshiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2016.09.034" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27616195" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Cytosol", "descriptor_ui": "D003600", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct 7", "date_precision": "day", "issue": "1", "normalized_date": "2016-10-07", "pages": "67-73", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "479", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Dissection of local Ca(2+) signals inside cytosol by ER-targeted Ca(2+) indicator.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Rho GTPase proteins Rac1, RhoA and Cdc42 have a central role in regulating the actin cytoskeleton in dendritic spines, thereby exerting control over the structural and functional plasticity of spines and, ultimately, learning and memory. Although previous work has shown that precise spatiotemporal coordination of these GTPases is crucial for some forms of cell morphogenesis, the nature of such coordination during structural spine plasticity is unclear. Here we describe a three-molecule model of structural long-term potentiation (sLTP) of murine dendritic spines, implicating the localized, coincident activation of Rac1, RhoA and Cdc42 as a causal signal of sLTP. This model posits that complete tripartite signal overlap in spines confers sLTP, but that partial overlap primes spines for structural plasticity. By monitoring the spatiotemporal activation patterns of these GTPases during sLTP, we find that such spatiotemporal signal complementation simultaneously explains three integral features of plasticity: the facilitation of plasticity by brain-derived neurotrophic factor (BDNF), the postsynaptic source of which activates Cdc42 and Rac1, but not RhoA; heterosynaptic facilitation of sLTP, which is conveyed by diffusive Rac1 and RhoA activity; and input specificity, which is afforded by spine-restricted Cdc42 activity. Thus, we present a form of biochemical computation in dendrites involving the controlled complementation of three molecules that simultaneously ensures signal specificity and primes the system for plasticity.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Nathan G.", "last_name": "Hedrick", "name": null }, { "creator_type": "author", "first_name": "Stephen C.", "last_name": "Harward", "name": null }, { "creator_type": "author", "first_name": "Charles E.", "last_name": "Hall", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "James O.", "last_name": "McNamara", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Yasuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nature19784" }, "pmcid": { "normalized": "PMC5361895" }, "pmid": { "normalized": "27680697" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain-Derived Neurotrophic Factor", "descriptor_ui": "D019208", "major_topic": false }, { "descriptor": "cdc42 GTP-Binding Protein", "descriptor_ui": "D020764", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Long-Term Potentiation", "descriptor_ui": "D017774", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neural Inhibition", "descriptor_ui": "D009433", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Post-Synaptic Density", "descriptor_ui": "D057907", "major_topic": false }, { "descriptor": "rac1 GTP-Binding Protein", "descriptor_ui": "D020830", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "rho GTP-Binding Proteins", "descriptor_ui": "D020741", "major_topic": false }, { "descriptor": "rhoA GTP-Binding Protein", "descriptor_ui": "D020742", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Spatio-Temporal Analysis", "descriptor_ui": "D062211", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct 6", "date_precision": "day", "issue": "7623", "normalized_date": "2016-10-06", "pages": "104-108", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "538", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Rho GTPase complementation underlies BDNF-dependent homo- and heterosynaptic plasticity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To investigate the molecular mechanism(s) by which herpes simplex virus 1 (HSV-1) tegument protein UL51 promotes viral replication, we screened for viral proteins that interact with UL51 in infected cells. Affinity purification of tagged UL51 in HSV-1-infected Vero cells was coupled with immunoblotting of the purified UL51 complexes with various antibodies to HSV-1 virion proteins. Subsequent analyses revealed that UL51 interacted with another tegument protein, UL14, in infected cells. Mutational analyses of UL51 showed that UL51 amino acid residues Leu-111, Ile-119, and Tyr-123 were required for interaction with UL14 in HSV-1-infected cells. Alanine substitutions of these UL51 amino acid residues reduced viral replication and produced an accumulation of unenveloped and partially enveloped nucleocapsids in the cytoplasm at levels comparable to those of UL51-null, UL14-null, and UL51/UL14 double-null mutations. In addition, although UL51 and UL14 colocalized at juxtanuclear domains in HSV-1-infected cells, the amino acid substitutions in UL51 produced aberrant localization of UL51 and UL14. The effects of these substitutions on localization of UL51 and UL14 were similar to those of the UL51-null and UL14-null mutations on localization of UL14 and UL51, respectively. These results suggested that the interaction between UL51 and UL14 was required for proper localization of these viral proteins in infected cells and that the UL51-UL14 complex regulated final viral envelopment for efficient viral replication. IMPORTANCE: Herpesviruses contain a unique virion structure designated the tegument, which is a protein layer between the nucleocapsid and the envelope. HSV-1 has dozens of viral proteins in the tegument, which are thought to facilitate viral envelopment by interacting with other virion components. However, although numerous interactions among virion proteins have been reported, data on how these interactions facilitate viral envelopment is limited. In this study, we have presented data showing that the interaction of HSV-1 tegument proteins UL51 and UL14 promoted viral final envelopment for efficient viral replication. In particular, prevention of this interaction induced aberrant accumulation of partially enveloped capsids in the cytoplasm, suggesting that the UL51-UL14 complex acted in the envelopment process but not in an upstream event, such as transport of capsids to the site for envelopment. This is the first report showing that an interaction between HSV-1 tegument proteins directly regulated final virion envelopment.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shinya", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01258-16" }, "pmcid": { "normalized": "PMC5021402" }, "pmid": { "normalized": "27440890" } }, "mesh": [ { "descriptor": "Amino Acid Substitution", "descriptor_ui": "D019943", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "DNA Mutational Analysis", "descriptor_ui": "D004252", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Phosphoproteins", "descriptor_ui": "D010750", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Interaction Mapping", "descriptor_ui": "D025941", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virion", "descriptor_ui": "D014771", "major_topic": false }, { "descriptor": "Virus Assembly", "descriptor_ui": "D019065", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016 Oct 1", "date_precision": "day", "issue": "19", "normalized_date": "2016-10-01", "pages": "8754-8767", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "90", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "The Interaction between Herpes Simplex Virus 1 Tegument Proteins UL51 and UL14 and Its Role in Virion Morphogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The CRISPR/Cas9 system is a powerful tool for elucidating the roles of genes in a wide variety of organisms including mice. To obtain genetically modified embryos or mice by this method, Cas9 mRNA and sgRNA are usually introduced into zygotes by microinjection or electroporation. However, most mutants generated with this method are genetically mosaic, composed of several types of cells carrying different mutations, which complicates phenotype analysis in founder embryos or mice. To simplify the analysis and to elucidate the roles of genes involved in developmental processes, a method for producing non-mosaic mutants is needed. Here, we established a method for generating non-mosaic mouse mutant embryos. We introduced Cas9 protein and sgRNA into in vitro fertilized (IVF) zygotes by electroporation, which enabled the genome editing to occur before the first replication of the mouse genome. As a result, all of the cells in the mutant carried the same set of mutations. This method solves the problem of mosaicism/allele complexity in founder mutant embryos or mice generated by the CRIPSR/Cas9 system.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masakazu", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2016.07.017" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27474397" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Clustered Regularly Interspaced Short Palindromic Repeats", "descriptor_ui": "D064112", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Electroporation", "descriptor_ui": "D018274", "major_topic": false }, { "descriptor": "Endonucleases", "descriptor_ui": "D004720", "major_topic": false }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred DBA", "descriptor_ui": "D008811", "major_topic": false }, { "descriptor": "Mosaicism", "descriptor_ui": "D009030", "major_topic": false }, { "descriptor": "RNA, Guide, CRISPR-Cas Systems", "descriptor_ui": "D000094704", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Zygote", "descriptor_ui": "D015053", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct 1", "date_precision": "day", "issue": "1", "normalized_date": "2016-10-01", "pages": "1-9", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "418", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Electroporation of Cas9 protein/sgRNA into early pronuclear zygotes generates non-mosaic mutants in the mouse.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In long-term depression (LTD) at synapses in the adult brain, synaptic strength is reduced in an experience-dependent manner. LTD thus provides a cellular mechanism for information storage in some forms of learning. A similar activity-dependent reduction in synaptic strength also occurs in the developing brain and there provides an essential step in synaptic pruning and the postnatal development of neural circuits. Here we review evidence suggesting that LTD and synaptic pruning share components of their underlying molecular machinery and may thus represent two developmental stages of the same type of synaptic modulation that serve different, but related, functions in neural circuit plasticity. We also assess the relationship between LTD and synaptic pruning in the context of recent findings of LTD dysregulation in several mouse models of autism spectrum disorder (ASD) and discuss whether LTD deficits can indicate impaired pruning processes that are required for proper brain development.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Claire", "last_name": "Piochon", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Hansel", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nn.4389" }, "pmcid": { "normalized": "PMC5070480" }, "pmid": { "normalized": "27669991" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autism Spectrum Disorder", "descriptor_ui": "D000067877", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Long-Term Synaptic Depression", "descriptor_ui": "D036881", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Sep 27", "date_precision": "day", "issue": "10", "normalized_date": "2016-09-27", "pages": "1299-1310", "proceedings_title": null, "publisher": "", "title": "Nature neuroscience", "volume": "19", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "LTD-like molecular pathways in developmental synaptic pruning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Photoacoustic imaging, which enables high-resolution imaging in deep tissues, has lately attracted considerable attention. For tumor imaging, photoacoustic probes have been proposed to enhance the photoacoustic effect to improve detection sensitivity. Here, we evaluated the feasibility of using a biocompatible hydrophilic polymer, polyoxazoline, conjugated with indocyanine green (ICG) as a tumor-targeted photoacoustic probe via enhanced permeability and retention effect. ICG molecules were multivalently conjugated to partially hydrolyzed polyoxazoline, thereby serving as highly sensitive photoacoustic probes. Interestingly, loading multiple ICG molecules to polyoxazoline significantly enhanced photoacoustic signal intensity under the same ICG concentration. In vivo biodistribution studies using tumor bearing mice demonstrated that 5% hydrolyzed polyoxazoline (50 kDa) conjugated with ICG (ICG/polyoxazoline = 7.8), P14-ICG7.8, showed relatively high tumor accumulation (9.4%ID/g), resulting in delivery of the highest dose of ICG among the probes tested. P14-ICG7.8 enabled clear visualization of the tumor regions by photoacoustic imaging 24 h after administration; the photoacoustic signal increased in proportion with the injected dose. In addition, the signal intensity in blood vessels in the photoacoustic images did not show much change, which was attributed to the high tumor-to-blood ratios of P14-ICG7.8. These results suggest that polyoxazoline-ICG would serve as a robust probe for sensitive photoacoustic tumor imaging.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kengo", "last_name": "Kanazaki", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Makino", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Homma", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Saji", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep33798" }, "pmcid": { "normalized": "PMC5036052" }, "pmid": { "normalized": "27667374" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Sep 26", "date_precision": "day", "issue": "", "normalized_date": "2016-09-26", "pages": "33798", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Polyoxazoline multivalently conjugated with indocyanine green for sensitive in vivo photoacoustic imaging of tumors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurodegenerative lesions induce sprouting of new collaterals from surviving axons, but the extent to which this form of axonal remodelling alters brain functional structure remains unclear. To understand how collateral sprouting proceeds in the adult brain, we imaged post-lesion sprouting of cerebellar climbing fibres (CFs) in mice using in vivo time-lapse microscopy. Here we show that newly sprouted CF collaterals innervate multiple Purkinje cells (PCs) over several months, with most innervations emerging at 3-4 weeks post lesion. Simultaneous imaging of cerebellar functional structure reveals that surviving CFs similarly innervate functionally relevant and non-relevant PCs, but have more synaptic area on PCs near the collateral origin than on distant PCs. These results suggest that newly sprouted axon collaterals do not preferentially innervate functionally relevant postsynaptic targets. Nonetheless, the spatial gradient of collateral innervation might help to loosely maintain functional synaptic circuits if functionally relevant neurons are clustered in the lesioned area.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Matasha", "last_name": "Dhar", "name": null }, { "creator_type": "author", "first_name": "Joshua M.", "last_name": "Brenner", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nishiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms12938" }, "pmcid": { "normalized": "PMC5036008" }, "pmid": { "normalized": "27651000" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nerve Fibers", "descriptor_ui": "D009412", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Olivary Nucleus", "descriptor_ui": "D009847", "major_topic": false }, { "descriptor": "Spatio-Temporal Analysis", "descriptor_ui": "D062211", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016 Sep 21", "date_precision": "day", "issue": "", "normalized_date": "2016-09-21", "pages": "12938", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatiotemporal dynamics of lesion-induced axonal sprouting and its relation to functional architecture of the cerebellum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stroke is a highly debilitating, often fatal disorder for which current therapies are suitable for only a minor fraction of patients. Discovery of novel, effective therapies is hampered by the fact that advanced age, primary age-related tauopathy or comorbidities typical to several types of dementing diseases are usually not taken into account in preclinical studies, which predominantly use young, healthy rodents. Here we investigated for the first time the neuroprotective potential of bexarotene, an FDA-approved agent, in a co-morbidity model of stroke that combines high age and tauopathy with thromboembolic cerebral ischemia. Following thromboembolic stroke bexarotene enhanced autophagy in the ischemic brain concomitantly with a reduction in lesion volume and amelioration of behavioral deficits in aged transgenic mice expressing the human P301L-Tau mutation. In in vitro studies bexarotene increased the expression of autophagy markers and reduced autophagic flux in neuronal cells expressing P301L-Tau. Bexarotene also restored mitochondrial respiration deficits in P301L-Tau neurons. These newly described actions of bexarotene add to the growing amount of compelling data showing that bexarotene is a potent neuroprotective agent, and identify a novel autophagy-modulating effect of bexarotene.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mikko T.", "last_name": "Huuskonen", "name": null }, { "creator_type": "author", "first_name": "Sanna", "last_name": "Loppi", "name": null }, { "creator_type": "author", "first_name": "Hiramani", "last_name": "Dhungana", "name": null }, { "creator_type": "author", "first_name": "Velta", "last_name": "Keksa-Goldsteine", "name": null }, { "creator_type": "author", "first_name": "Sighild", "last_name": "Lemarchant", "name": null }, { "creator_type": "author", "first_name": "Paula", "last_name": "Korhonen", "name": null }, { "creator_type": "author", "first_name": "Sara", "last_name": "Wojciechowski", "name": null }, { "creator_type": "author", "first_name": "Eveliina", "last_name": "Pollari", "name": null }, { "creator_type": "author", "first_name": "Piia", "last_name": "Valonen", "name": null }, { "creator_type": "author", "first_name": "Juho", "last_name": "Koponen", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Gary", "last_name": "Landreth", "name": null }, { "creator_type": "author", "first_name": "Gundars", "last_name": "Goldsteins", "name": null }, { "creator_type": "author", "first_name": "Tarja", "last_name": "Malm", "name": null }, { "creator_type": "author", "first_name": "Jari", "last_name": "Koistinaho", "name": null }, { "creator_type": "author", "first_name": "Katja M.", "last_name": "Kanninen", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep33176" }, "pmcid": { "normalized": "PMC5021977" }, "pmid": { "normalized": "27624652" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": false }, { "descriptor": "Bexarotene", "descriptor_ui": "D000077610", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neuroprotective Agents", "descriptor_ui": "D018696", "major_topic": false }, { "descriptor": "Stroke", "descriptor_ui": "D020521", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": false }, { "descriptor": "Tetrahydronaphthalenes", "descriptor_ui": "D013764", "major_topic": false }, { "descriptor": "Thromboembolism", "descriptor_ui": "D013923", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Sep 14", "date_precision": "day", "issue": "", "normalized_date": "2016-09-14", "pages": "33176", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Bexarotene targets autophagy and is protective against thromboembolic stroke in aged mice with tauopathy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neural circuits formed during postnatal development have to be maintained stably thereafter, but their mechanisms remain largely unknown. Here we report that the metabotropic glutamate receptor subtype 1 (mGluR1) is essential for the maintenance of mature synaptic connectivity in the dorsal lateral geniculate nucleus (dLGN). In mGluR1 knockout (mGluR1-KO) mice, strengthening and elimination at retinogeniculate synapses occurred normally until around postnatal day 20 (P20). However, during the subsequent visual-experience-dependent maintenance phase, weak retinogeniculate synapses were newly recruited. These changes were similar to those of wild-type (WT) mice that underwent visual deprivation or inactivation of mGluR1 in the dLGN from P21. Importantly, visual deprivation was ineffective in mGluR1-KO mice, and the changes induced by visual deprivation in WT mice were rescued by pharmacological activation of mGluR1 in the dLGN. These results demonstrate that mGluR1 is crucial for the visual-experience-dependent maintenance of mature synaptic connectivity in the dLGN.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Madoka", "last_name": "Narushima", "name": null }, { "creator_type": "author", "first_name": "Motokazu", "last_name": "Uchigashima", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yagasaki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Nagumo", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Atsu", "last_name": "Aiba", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2016.07.035" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27545713" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carbamates", "descriptor_ui": "D002219", "major_topic": false }, { "descriptor": "Geniculate Bodies", "descriptor_ui": "D005829", "major_topic": false }, { "descriptor": "Glycine", "descriptor_ui": "D005998", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false }, { "descriptor": "Resorcinols", "descriptor_ui": "D012118", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Sensory Deprivation", "descriptor_ui": "D012683", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Thalamus", "descriptor_ui": "D013788", "major_topic": false }, { "descriptor": "Visual Pathways", "descriptor_ui": "D014795", "major_topic": false }, { "descriptor": "Xanthenes", "descriptor_ui": "D014966", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Sep 7", "date_precision": "day", "issue": "5", "normalized_date": "2016-09-07", "pages": "1097-1109", "proceedings_title": null, "publisher": "", "title": "Neuron", "volume": "91", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "The Metabotropic Glutamate Receptor Subtype 1 Mediates Experience-Dependent Maintenance of Mature Synaptic Connectivity in the Visual Thalamus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) has been implicated in stress adaptation with potential relevance in mood disorder management. PACAP deficient (KO) mice on CD1 background were shown to have depression-like phenotype. Here we aimed at investigating effects of chronic variable mild stress (CVMS) in non-injected, vehicle and imipramine-treated KO mice vs. wildtype (WT) counterparts. We hypothesized reduced FosB neuronal activity in stress-related centers, altered activity and peptide/neurotransmitter content of corticotropin-releasing factor (CRF) cells of the oval (ovBST) bed nucleus of stria terminalis (BST), urocortin 1 (Ucn1) neurons of centrally projecting Edinger-Westphal nucleus (cpEW) and serotonin (5HT) cells of dorsal raphe (DR) in PACAP deficiency. CVMS caused decreased body weight and increased adrenal size, corticosterone (CORT) titers and depression-like behavior in WT mice, in contrast to KO animals. CVMS increased FosB in the central (CeA) and medial amygdala, dorsomedial (dmBST), ventral (vBST), ovBST, CA1 area, dentate gyrus (DG), ventral lateral septum, parvo- (pPVN) and magnocellular paraventricular nucleus, lateral periaqueductal gray, cpEW and DR. Lack of PACAP blunted the CVMS-induced FosB rise in the CeA, ovBST, dmBST, vBST, CA1 area, pPVN and DR. The CVMS-induced FosB expression in ovBST-CRF and cpEW-Ucn1 neurons was abolished in KO mice. Although CVMS did not induce FosB in 5HT-DR neurons, PACAP KO mice had increased 5HT cell counts and 5HT content. We conclude that PACAP deficiency affects neuronal reactivity in a brain area-specific manner in stress centers, as well as in ovBST-CRF, cpEW-Ucn1 and 5HT-DR neurons leading to reduced CVMS response and altered depression level.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Viktoria", "last_name": "Kormos", "name": null }, { "creator_type": "author", "first_name": "Laszlo", "last_name": "Gaspar", "name": null }, { "creator_type": "author", "first_name": "Laszlo A.", "last_name": "Kovacs", "name": null }, { "creator_type": "author", "first_name": "Jozsef", "last_name": "Farkas", "name": null }, { "creator_type": "author", "first_name": "Tamas", "last_name": "Gaszner", "name": null }, { "creator_type": "author", "first_name": "Valer", "last_name": "Csernus", "name": null }, { "creator_type": "author", "first_name": "Andras", "last_name": "Balogh", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Dora", "last_name": "Reglodi", "name": null }, { "creator_type": "author", "first_name": "Zsuzsanna", "last_name": "Helyes", "name": null }, { "creator_type": "author", "first_name": "Balazs", "last_name": "Gaszner", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuroscience.2016.06.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27282087" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antidepressive Agents, Tricyclic", "descriptor_ui": "D000929", "major_topic": false }, { "descriptor": "Brain Stem", "descriptor_ui": "D001933", "major_topic": false }, { "descriptor": "Chronic Disease", "descriptor_ui": "D002908", "major_topic": false }, { "descriptor": "Depressive Disorder", "descriptor_ui": "D003866", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Imipramine", "descriptor_ui": "D007099", "major_topic": false }, { "descriptor": "Limbic System", "descriptor_ui": "D008032", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Prosencephalon", "descriptor_ui": "D016548", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-fos", "descriptor_ui": "D016760", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false }, { "descriptor": "Stress, Psychological", "descriptor_ui": "D013315", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Aug 25", "date_precision": "day", "issue": "", "normalized_date": "2016-08-25", "pages": "335-358", "proceedings_title": null, "publisher": "", "title": "Neuroscience", "volume": "330", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Reduced response to chronic mild stress in PACAP mutant mice is associated with blunted FosB expression in limbic forebrain and brainstem centers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Microglia are the immune cells of the central nervous system that play important roles in brain pathologies. Microglia also help shape neuronal circuits during development, via phagocytosing weak synapses and regulating neurogenesis. Using in vivo multiphoton imaging of layer 2/3 pyramidal neurons in the developing somatosensory cortex, we demonstrate here that microglial contact with dendrites directly induces filopodia formation. This filopodia formation occurs only around postnatal day 8-10, a period of intense synaptogenesis and when microglia have an activated phenotype. Filopodia formation is preceded by contact-induced Ca(2+) transients and actin accumulation. Inhibition of microglia by genetic ablation decreases subsequent spine density, functional excitatory synapses and reduces the relative connectivity from layer 4 neurons. Our data provide the direct demonstration of microglial-induced spine formation and provide further insights into immune system regulation of neuronal circuit development, with potential implications for developmental disorders of immune and brain dysfunction.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akiko", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Wake", "name": null }, { "creator_type": "author", "first_name": "Ayako Wendy", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Eto", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Schuichi", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Andrew J.", "last_name": "Moorhouse", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Nabekura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms12540" }, "pmcid": { "normalized": "PMC5007295" }, "pmid": { "normalized": "27558646" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Immune System", "descriptor_ui": "D007107", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microglia", "descriptor_ui": "D017628", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence, Multiphoton", "descriptor_ui": "D036641", "major_topic": false }, { "descriptor": "Models, Animal", "descriptor_ui": "D023421", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Pseudopodia", "descriptor_ui": "D011554", "major_topic": false }, { "descriptor": "Pyramidal Cells", "descriptor_ui": "D017966", "major_topic": false }, { "descriptor": "Somatosensory Cortex", "descriptor_ui": "D013003", "major_topic": false }, { "descriptor": "Spine", "descriptor_ui": "D013131", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Aug 25", "date_precision": "day", "issue": "", "normalized_date": "2016-08-25", "pages": "12540", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Microglia contact induces synapse formation in developing somatosensory cortex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell polarity arises through the spatial segregation of polarity regulators. PAR proteins are polarity regulators that localize asymmetrically to two opposing cortical domains. However, it is unclear how the spatially segregated PAR proteins interact to maintain their mutually exclusive partitioning. Here, single-molecule detection analysis in Caenorhabditis elegans embryos reveals that cortical PAR-2 diffuses only short distances, and, as a result, most PAR-2 molecules associate and dissociate from the cortex without crossing into the opposing domain. Our results show that cortical PAR-2 asymmetry is maintained by the local exchange reactions that occur at the cortical-cytoplasmic boundary. Additionally, we demonstrate that local exchange reactions are sufficient to maintain cortical asymmetry in a parameter-free mathematical model. These findings suggest that anterior and posterior PAR proteins primarily interact through the cytoplasmic pool and not via cortical diffusion.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukinobu", "last_name": "Arata", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Chan-Gi", "last_name": "Pack", "name": null }, { "creator_type": "author", "first_name": "Ravikrishna", "last_name": "Ramanujam", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Motegi", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nakazato", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Paul W.", "last_name": "Wiseman", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hugo B.", "last_name": "Brandao", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2016.07.047" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27524610" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": false }, { "descriptor": "Cell Compartmentation", "descriptor_ui": "D002451", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Models, Statistical", "descriptor_ui": "D015233", "major_topic": true }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Single Molecule Imaging", "descriptor_ui": "D000072760", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Aug 23", "date_precision": "day", "issue": "8", "normalized_date": "2016-08-23", "pages": "2156-2168", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "16", "year": 2016 }, "ssbd": { "database": [ "ssbd-database-000037" ], "repository": [ "ssbd-repos-000037" ] }, "title": "Cortical Polarity of the RING Protein PAR-2 Is Maintained by Exchange Rate Kinetics at the Cortical-Cytoplasmic Boundary.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydrogen sulfide (H2S) and hydrogen polysulfides (H2Sn, n > 1) are endogenous regulators of many physiological processes. In order to better understand the symbiotic relationship and cellular cross-talk between H2S and H2Sn, it is highly desirable to develop single fluorescent probes which enable dual-channel discrimination between H2S and H2Sn. Herein we report the rational design, synthesis, and evaluation of the first dual-detection fluorescent probe DDP-1 that can visualize H2S and H2Sn with different fluorescence signals. The probe showed high selectivity and sensitivity to H2S and H2Sn in aqueous media and in cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Wei", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Armando", "last_name": "Pacheco", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Jacob J.", "last_name": "Day", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Xian", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201604892" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27410794" } }, "mesh": [ { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": true }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Aug 16", "date_precision": "day", "issue": "34", "normalized_date": "2016-08-16", "pages": "9993-9996", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "55", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "A Single Fluorescent Probe to Visualize Hydrogen Sulfide and Hydrogen Polysulfides with Different Fluorescence Signals.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dictyostelium morphogenesis requires the tip, which acts as an organizer and conducts orchestrated cell movement and cell differentiation. At the slug stage the tip region contains prestalk A (pstA) cells, which are usually recognized by their expression of reporter constructs that utilize a fragment of the promoter of the ecmA gene. Here, using the promoter region of the o-methyl transferase 12 gene (omt12) to drive reporter expression, we demonstrate the presence, also within the pstA region, of a novel prestalk cell subtype: the pstV(A) cells. Surprisingly, a sub-population of the vegetative cells express a pstV(A): GFP marker and, sort out to the tip, both when developing alone and when co-developed with an excess of unmarked cells. The development of such a purified GFP-marked population is greatly accelerated: by precocious cell aggregation and tip formation with accompanying precocious elevation of developmental gene transcription. We therefore suggest that the tip contains at least two prestalk cell subtypes: the developmentally-specified pstA cells and the lineage-primed pstV(A) cells. It is presumably the pstV(A) cells that play the dominant role in morphogenesis during the earlier stages of development. The basis for the lineage priming is, however, unclear because we can find no correlation between pstV(A) differentiation and nutrient status during growth or cell cycle position at the time of starvation, the two known determinants of probable cell fate.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "contributor", "first_name": "Satoshi", "last_name": "Kuwana", "name": null }, { "creator_type": "contributor", "first_name": "Hiroshi", "last_name": "Senoo", "name": null }, { "creator_type": "contributor", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "contributor", "first_name": "Masashi", "last_name": "Fukuzawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2016.06.032" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Aug 15", "date_precision": "day", "issue": "", "normalized_date": "2016-08-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "", "volume": "416", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "A novel, lineage-primed prestalk cell subtype involved in the morphogenesis of D. discoideum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "SLD5 is a member of the GINS complex, essential for DNA replication in eukaryotes. It has been reported that SLD5 is involved in early embryogenesis in the mouse, and cell cycle progression and genome integrity in Drosophila. SLD5 may be involved in malignant tumor progression, but its relevance in human cancer has not been determined. Here, we found strong SLD5 expression in both human bladder cancer tissues from patients and cell lines. Knockdown of SLD5 using small interfering RNA resulted in reduction of cell growth both in vitro and an in vivo xenograft model. Moreover, we found that high levels of SLD5 in bladder cancer cells result from downregulation of microRNA (miR)-370 that otherwise suppresses its expression. High level expression of DNA-methyltransferase (DNMT) 1 and IL-6 were also observed in bladder cancer cells. Knockdown of IL-6 led to downregulation of DNMT1 and SLD5 expression, suggesting that IL-6-induced overexpression of DNMT1 suppresses miR-370, resulting in high SLD5 expression. Our findings could contribute to understanding tumorigenic processes and progression of human bladder cancer, whereby inhibition of SLD5 could represent a novel strategy to prevent tumor growth.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Keitaro", "last_name": "Yamane", "name": null }, { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Iba", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep30941" }, "pmcid": { "normalized": "PMC4976388" }, "pmid": { "normalized": "27499248" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Chromosomal Proteins, Non-Histone", "descriptor_ui": "D002868", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Heterografts", "descriptor_ui": "D064593", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Neoplasm Transplantation", "descriptor_ui": "D009368", "major_topic": false }, { "descriptor": "Urinary Bladder Neoplasms", "descriptor_ui": "D001749", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Aug 8", "date_precision": "day", "issue": "", "normalized_date": "2016-08-08", "pages": "30941", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Regulation of SLD5 gene expression by miR-370 during acute growth of cancer cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Endocannabinoid signaling is considered to suppress excessive excitability of neural circuits and to protect the brain from seizures. However, the precise mechanisms of this effect are poorly understood. Here, we report that 2-arachidonoylglycerol (2-AG), one of the two major endocannabinoids, is crucial for suppressing seizures. We found that kainate-induced seizures in mice lacking the 2-AG synthesizing enzyme, diacylglycerol lipase alpha, were much more severe compared with those in cannabinoid CB1 receptor knockout mice and were comparable to those in mice lacking both CB1- and CB2-receptor-mediated signaling. In the dentate gyrus, 2-AG suppressed excitatory input around the inner and middle molecular layers through CB1 and presumably CB2 receptors, respectively. This 2-AG-mediated suppression contributed to decreased granule cell excitability and the dampening of seizures. Furthermore, lack of 2-AG signaling enhanced kindling epileptogenesis and spontaneous seizures after kainate-induced status epilepticus. These results highlight critical roles of 2-AG signaling in the suppression of epileptic seizures.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugaya", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Motokazu", "last_name": "Uchigashima", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2016.06.083" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27452464" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arachidonic Acids", "descriptor_ui": "D001095", "major_topic": false }, { "descriptor": "Dentate Gyrus", "descriptor_ui": "D018891", "major_topic": false }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glycerides", "descriptor_ui": "D005989", "major_topic": false }, { "descriptor": "Lipoprotein Lipase", "descriptor_ui": "D008071", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Receptor, Cannabinoid, CB1", "descriptor_ui": "D043884", "major_topic": false }, { "descriptor": "Receptor, Cannabinoid, CB2", "descriptor_ui": "D043885", "major_topic": false }, { "descriptor": "Seizures", "descriptor_ui": "D012640", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Aug 2", "date_precision": "day", "issue": "5", "normalized_date": "2016-08-02", "pages": "1405-1415", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "16", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Crucial Roles of the Endocannabinoid 2-Arachidonoylglycerol in the Suppression of Epileptic Seizures.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "UNLABELLED: p53 is a critical host cell factor in the cellular response to a broad range of stress factors. We recently reported that p53 is required for efficient herpes simplex virus 1 (HSV-1) replication in cell culture. However, a defined role for p53 in HSV-1 replication and pathogenesis in vivo remains elusive. In this study, we examined the effects of p53 on HSV-1 infection in vivo using p53-deficient mice. Following intracranial inoculation, p53 knockout reduced viral replication in the brains of mice and led to significantly reduced rates of mortality due to herpes simplex encephalitis. These results suggest that p53 is an important host cell regulator of HSV-1 replication and pathogenesis in the central nervous system (CNS). IMPORTANCE: HSV-1 causes sporadic cases of encephalitis, which, even with antiviral therapy, can result in severe neurological defects and even death. Many host cell factors involved in the regulation of CNS HSV-1 infection have been investigated using genetically modified mice. However, most of these factors are immunological regulators and act via immunological pathways in order to restrict CNS HSV-1 infection. They therefore provide limited information on intrinsic host cell regulators that may be involved in the facilitation of CNS HSV-1 infection. Here we demonstrate that a host cell protein, p53, which has generally been considered a host cell restriction factor for various viral infections, is required for efficient HSV-1 replication and pathogenesis in the CNS of mice. This is the first report showing that p53 positively regulates viral replication and pathogenesis in vivo and provides insights into its molecular mechanism, which may suggest novel clinical treatment options for herpes simplex encephalitis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Takemura", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Uematsu", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00846-16" }, "pmcid": { "normalized": "PMC4944289" }, "pmid": { "normalized": "27170756" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Encephalitis, Herpes Simplex", "descriptor_ui": "D020803", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Simplexvirus", "descriptor_ui": "D018139", "major_topic": false }, { "descriptor": "Survival Rate", "descriptor_ui": "D015996", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016 Aug 1", "date_precision": "day", "issue": "15", "normalized_date": "2016-08-01", "pages": "6738-6745", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "90", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "p53 Is a Host Cell Regulator during Herpes Simplex Encephalitis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PD-1 (programmed-death 1), an immune-inhibitory receptor required for immune self-tolerance whose deficiency causes autoimmunity with variable severity and tissue specificity depending on other genetic factors, is expressed on activated T cells, including the transcription factor FoxP3(+) Treg cells known to play critical roles in maintaining immune tolerance. However, whether PD-1 expression by the Treg cells is required for their immune regulatory function, especially in autoimmune settings, is still unclear. We found that mice with partial FoxP3 insufficiency developed early-onset lympho-proliferation and lethal autoimmune pancreatitis only when PD-1 is absent. The autoimmune phenotype was rescued by the transfer of FoxP3-sufficient T cells, regardless of whether they were derived from WT or PD-1-deficient mice, indicating that Treg cells dominantly protect against development of spontaneous autoimmunity without intrinsic expression of PD-1. The absence of PD-1 combined with partial FoxP3 insufficiency, however, led to generation of ex-FoxP3 T cells with proinflammatory properties and expansion of effector/memory T cells that contributed to the autoimmune destruction of target tissues. Altogether, the results suggest that PD-1 and FoxP3 work collaboratively in maintaining immune tolerance mostly through nonoverlapping pathways. Thus, PD-1 is modulating the activation threshold and maintaining the balance between regulatory and effector T cells, whereas FoxP3 is sufficient for dominant regulation through maintaining the integrity of the Treg function. We suggest that genetic or environmental factors that even moderately affect the expression of both PD-1 and FoxP3 can cause life-threatening autoimmune diseases by disrupting the T-cell homeostasis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Baihao", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Sidonia", "last_name": "Fagarasan", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Honjo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1608873113" }, "pmcid": { "normalized": "PMC4968716" }, "pmid": { "normalized": "27410049" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autoimmune Diseases", "descriptor_ui": "D001327", "major_topic": false }, { "descriptor": "Autoimmunity", "descriptor_ui": "D015551", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Tolerance", "descriptor_ui": "D007108", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Pancreatitis", "descriptor_ui": "D010195", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jul 26", "date_precision": "day", "issue": "30", "normalized_date": "2016-07-26", "pages": "8490-8495", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "113", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Nonoverlapping roles of PD-1 and FoxP3 in maintaining immune tolerance in a novel autoimmune pancreatitis mouse model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Some neurons have the ability to enhance output voltage to input current with a preferred frequency, which is called resonance. Resonance is thought to be a basis for membrane potential oscillation. Although ion channels responsible for resonance have been reported, the precise mechanisms by which these channels work remain poorly understood. We have found that resonance is reduced but clearly present in the inferior olivary neurons of Cav3.1 T-type voltage-dependent Ca(2+) channel knockout (KO) mice. The activation of Cav3.1 channels is strongly membrane potential dependent, but less frequency dependent. Residual resonance in Cav3.1 KO mice is abolished by a hyper-polarization-activated cyclic nucleotide-gated (HCN) channel blocker, ZD7288, and is partially suppressed by voltage-dependent K(+) channel blockers. Resonance is inhibited by ZD7288 in wild-type mice and impaired in HCN1 KO mice, suggesting that the HCN1 channel is essential for resonance. The ZD7288-sensitive current is nearly sinusoidal and strongly frequency dependent. These results suggest that Cav3.1 and HCN1 channels act as amplifying and resonating conductances, respectively.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Matsumoto-Makidono", "name": null }, { "creator_type": "author", "first_name": "Hisako", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Miwako", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2016.06.053" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27425615" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Channels, T-Type", "descriptor_ui": "D020747", "major_topic": false }, { "descriptor": "Cerebellar Cortex", "descriptor_ui": "D002525", "major_topic": false }, { "descriptor": "Cyclic Nucleotide-Gated Cation Channels", "descriptor_ui": "D054815", "major_topic": false }, { "descriptor": "Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels", "descriptor_ui": "D064428", "major_topic": false }, { "descriptor": "Membrane Potentials", "descriptor_ui": "D008564", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Potassium Channels", "descriptor_ui": "D015221", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jul 26", "date_precision": "day", "issue": "4", "normalized_date": "2016-07-26", "pages": "994-1004", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "16", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Ionic Basis for Membrane Potential Resonance in Neurons of the Inferior Olive.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "scl is a spontaneous medaka mutant deficient in P450c17I, which is required for production of sex steroids, but not of cortisol, the major role of which is osmoregulation in teleost fish. The scl mutant provides a new model to study the functions of these hormones. We first found that fish homozygous for this mutation have plasma cortisol constitutively at a high physiological level (1000 nM). Since we previously showed that this level reversed the seawater-type differentiation of the medaka gastrointestinal tract, hypoosmoregulation of the scl mutant was analyzed. Muscle water contents in freshwater were normal in scl homozygotes, but the contents were lower than those of the wild type (WT) after seawater transfer. There were no differences in gill mRNA levels of corticosteroid receptors or ion transporters between scl homozygotes and WT. In the intestine, expression of glucocorticoid receptors and Na(+)/K(+)/2Cl(-) cotransporter were induced in WT during seawater acclimation, but not in scl homozygotes. The high plasma cortisol may prevent hypoosmoregulation by inhibition of increased intestinal water absorption, essentially by the Na(+)/K(+)/2Cl(-) cotransporter, in seawater.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hideya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Toshitaka", "last_name": "Ikeuchi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Sakaizumi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.mce.2016.04.009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27107936" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Enzymologic", "descriptor_ui": "D015971", "major_topic": false }, { "descriptor": "Hydrocortisone", "descriptor_ui": "D006854", "major_topic": false }, { "descriptor": "Intestinal Mucosa", "descriptor_ui": "D007413", "major_topic": false }, { "descriptor": "Ion Transport", "descriptor_ui": "D017136", "major_topic": false }, { "descriptor": "Muscles", "descriptor_ui": "D009132", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Oryzias", "descriptor_ui": "D009990", "major_topic": false }, { "descriptor": "Osmoregulation", "descriptor_ui": "D064587", "major_topic": true }, { "descriptor": "Receptors, Glucocorticoid", "descriptor_ui": "D011965", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Sodium-Potassium-Chloride Symporters", "descriptor_ui": "D028021", "major_topic": false }, { "descriptor": "Sodium-Potassium-Exchanging ATPase", "descriptor_ui": "D000254", "major_topic": false }, { "descriptor": "Steroid 17-alpha-Hydroxylase", "descriptor_ui": "D013254", "major_topic": false }, { "descriptor": "Steroids", "descriptor_ui": "D013256", "major_topic": false }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jul 15", "date_precision": "day", "issue": "", "normalized_date": "2016-07-15", "pages": "25-32", "proceedings_title": null, "publisher": "", "title": "Molecular and cellular endocrinology", "volume": "430", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "High levels of plasma cortisol and impaired hypoosmoregulation in a mutant medaka deficient in P450c17I.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genetically encoded indicators driven by the Forster resonance energy transfer (FRET) mechanism are reliable tools for live imaging. While the properties of FRET-based indicators have been improved over the years, they often suffer from a poor dynamic range due to the lack of comprehensive understanding about how to apply an appropriate strategy to optimize the FRET parameters. One of the most successful optimizations is the incorporation of circularly permuted fluorescent proteins (cpFPs). To better understand the effects of this strategy, we systematically investigated the properties of the indicators by utilizing a set of FRET backbones consisting of native or one of the most effective cp variants (cp173FPs) with considerations of their order. As a result, the ordering of donor and acceptor FPs, which has been ignored in previous studies, was found to significantly affect the dynamic range of indicators. By utilizing these backbones, we succeeded in improving a cGMP indicator with 3.6-fold increased dynamic range and in generating an ultrasensitive cAMP indicator capable of environmental imaging, demonstrating the practical importance of the ordering of donors and acceptors in the engineering of FRET-based indicators.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yusaku", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Kamagata", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Mukai", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acschembio.6b00221" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27232891" } }, "mesh": [ { "descriptor": "Color", "descriptor_ui": "D003116", "major_topic": true }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jul 15", "date_precision": "day", "issue": "7", "normalized_date": "2016-07-15", "pages": "1816-1822", "proceedings_title": null, "publisher": "", "title": "ACS chemical biology", "volume": "11", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Nontrivial Effect of the Color-Exchange of a Donor/Acceptor Pair in the Engineering of Forster Resonance Energy Transfer (FRET)-Based Indicators.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Organ sizes and shapes are strikingly reproducible, despite the variable growth and division of individual cells within them. To reveal which mechanisms enable this precision, we designed a screen for disrupted sepal size and shape uniformity in Arabidopsis and identified mutations in the mitochondrial i-AAA protease FtsH4. Counterintuitively, through live imaging we observed that variability of neighboring cell growth was reduced in ftsh4 sepals. We found that regular organ shape results from spatiotemporal averaging of the cellular variability in wild-type sepals, which is disrupted in the less-variable cells of ftsh4 mutants. We also found that abnormal, increased accumulation of reactive oxygen species (ROS) in ftsh4 mutants disrupts organ size consistency. In wild-type sepals, ROS accumulate in maturing cells and limit organ growth, suggesting that ROS are endogenous signals promoting termination of growth. Our results demonstrate that spatiotemporal averaging of cellular variability is required for precision in organ size.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Lilan", "last_name": "Hong", "name": null }, { "creator_type": "author", "first_name": "Mathilde", "last_name": "Dumond", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsugawa", "name": null }, { "creator_type": "author", "first_name": "Aleksandra", "last_name": "Sapala", "name": null }, { "creator_type": "author", "first_name": "Anne-Lise", "last_name": "Routier-Kierzkowska", "name": null }, { "creator_type": "author", "first_name": "Yong", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Catherine", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Annamaria", "last_name": "Kiss", "name": null }, { "creator_type": "author", "first_name": "Mingyuan", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Olivier", "last_name": "Hamant", "name": null }, { "creator_type": "author", "first_name": "Richard S.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null }, { "creator_type": "author", "first_name": "Chun-Biu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Arezki", "last_name": "Boudaoud", "name": null }, { "creator_type": "author", "first_name": "Adrienne H. K.", "last_name": "Roeder", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2016.06.016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27404356" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Flowers", "descriptor_ui": "D035264", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Organ Specificity", "descriptor_ui": "D009928", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jul 11", "date_precision": "day", "issue": "1", "normalized_date": "2016-07-11", "pages": "15-32", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "38", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Variable Cell Growth Yields Reproducible OrganDevelopment through Spatiotemporal Averaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Low-temperature processable polymers have attracted increasing interest as ecological materials because of their reduced energy consumption during processing and suitability for making composites with heat-sensitive biomolecules at ambient temperature. In the current study, low-temperature processable biodegradable block copolymers were synthesized by ring-opening polymerization of l-lactide (LLA) using polyphosphoester as a macroinitiator. The polymer films could be processed under a hydraulic pressure of 35 MPa. The block copolymer films swelled in water because the polyphosphoester block was partially hydrated. Interestingly, the swelling ratio of the films changed with temperature. The pressure-induced order-to-disorder transition of the block copolymers was characterized by small-angle X-ray scattering; a crystallinity reduction in the block copolymers was observed after application of pressure. The crystallinity of the block copolymers was recovered after removing the applied pressure. The Young's modulus of the block copolymer films increased as the LLA unit content increased. Moreover, the modulus did not change after multiple processing cycles and the recyclability of the block copolymers was also confirmed. Finally, polymer films with embedded proteinase K as a model protein were prepared. The activity of catalase loaded into the polymer films was evaluated after processing at different temperatures. The activity of catalase was preserved when the polymer films were processed at room temperature but was significantly reduced after high-temperature processing. The suitability of low-temperature processable biodegradable polymers for making biofunctional composites without reducing protein activity was clarified. These materials will be useful for biomedical and therapeutic applications.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Kyohei", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ikuo", "last_name": "Taniguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.biomac.6b00641" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27280847" } }, "mesh": [ { "descriptor": "Biocompatible Materials", "descriptor_ui": "D001672", "major_topic": false }, { "descriptor": "Cold Temperature", "descriptor_ui": "D003080", "major_topic": false }, { "descriptor": "Elastic Modulus", "descriptor_ui": "D055119", "major_topic": false }, { "descriptor": "Endopeptidase K", "descriptor_ui": "D019286", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Preservation, Biological", "descriptor_ui": "D011309", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016 Jul 11", "date_precision": "day", "issue": "7", "normalized_date": "2016-07-11", "pages": "2466-2471", "proceedings_title": null, "publisher": "", "title": "Biomacromolecules", "volume": "17", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Low-Temperature Processable Block Copolymers That Preserve the Function of Blended Proteins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Investigation of the unexpected photo-instability of 2,6-sulfonamide-substituted derivatives of the boron dipyrromethene (BODIPY) fluorophore led to the discovery of a photoreaction accompanied by multiple bond scissions. We characterized the photoproducts and utilized the photoreaction to design a caged gamma-aminobutyric acid (GABA) derivative that can release GABA upon irradiation in the visible range (>450 nm). This allowed us to stimulate neural cells in mouse brain slices.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Aoi", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Masamitsu", "last_name": "Naka", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Matsuki", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Ikegaya", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cbic.201600097" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27038199" } }, "mesh": [ { "descriptor": "Acetaldehyde", "descriptor_ui": "D000079", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Baclofen", "descriptor_ui": "D001418", "major_topic": false }, { "descriptor": "Basolateral Nuclear Complex", "descriptor_ui": "D066272", "major_topic": false }, { "descriptor": "Boron Compounds", "descriptor_ui": "D001896", "major_topic": false }, { "descriptor": "Formaldehyde", "descriptor_ui": "D005557", "major_topic": false }, { "descriptor": "GABA Antagonists", "descriptor_ui": "D018756", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Methylamines", "descriptor_ui": "D008744", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Picrotoxin", "descriptor_ui": "D010852", "major_topic": false }, { "descriptor": "Sulfonamides", "descriptor_ui": "D013449", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jul 1", "date_precision": "day", "issue": "13", "normalized_date": "2016-07-01", "pages": "1233-1240", "proceedings_title": null, "publisher": "", "title": "Chembiochem : a European journal of chemical biology", "volume": "17", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Unexpected Photo-instability of 2,6-Sulfonamide-Substituted BODIPYs and Its Application to Caged GABA.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Simultaneous nanometric tracking of multiple motor proteins was achieved by combining multicolor fluorescent labeling of target proteins and imaging spectroscopy, revealing dynamic behaviors of multiple motor proteins at the sub-diffraction-limit scale. Using quantum dot probes of distinct colors, we experimentally verified the localization precision to be a few nanometers at temporal resolution of 30 ms or faster. One-dimensional processive movement of two heads of a single myosin molecule and multiple myosin molecules was successfully traced. Furthermore, the system was modified for two-dimensional measurement and applied to tracking of multiple myosin molecules. Our approach is useful for investigating cooperative movement of proteins in supramolecular nanomachinery.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taishi", "last_name": "Kakizuka", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Ikezaki", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Kaneshiro", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/boe.7.002475" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27446684" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Jul 01", "date_precision": "day", "issue": "7", "normalized_date": "2016-07-01", "pages": "2475-2493", "proceedings_title": null, "publisher": "", "title": "Biomedical Optics Express", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Simultaneous nano-tracking of multiple motor proteins via spectral discrimination of quantum dots.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dry eye syndrome is caused by a reduction in the volume or quality of tears. Here, we show that pituitary adenylate cyclase-activating polypeptide (PACAP)-null mice develop dry eye-like symptoms such as corneal keratinization and tear reduction. PACAP immunoreactivity is co-localized with a neuronal marker, and PACAP receptor (PAC1-R) immunoreactivity is observed in mouse infraorbital lacrimal gland acinar cells. PACAP eye drops stimulate tear secretion and increase cAMP and phosphorylated (p)-protein kinase A levels in the infraorbital lacrimal glands that could be inhibited by pre-treatment with a PAC1-R antagonist or an adenylate cyclase inhibitor. Moreover, these eye drops suppress corneal keratinization in PACAP-null mice. PACAP eye drops increase aquaporin 5 (AQP5) levels in the membrane and pAQP5 levels in the infraorbital lacrimal glands. AQP5 siRNA treatment of the infraorbital lacrimal gland attenuates PACAP-induced tear secretion. Based on these results, PACAP might be clinically useful to treat dry eye disorder.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoya", "last_name": "Nakamachi", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Ohtaki", "name": null }, { "creator_type": "author", "first_name": "Tamotsu", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Yofu", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Kagami", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Laszlo", "last_name": "Mark", "name": null }, { "creator_type": "author", "first_name": "Ingela", "last_name": "Lanekoff", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Kiss", "name": null }, { "creator_type": "author", "first_name": "Jozsef", "last_name": "Farkas", "name": null }, { "creator_type": "author", "first_name": "Dora", "last_name": "Reglodi", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Shioda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms12034" }, "pmcid": { "normalized": "PMC4931240" }, "pmid": { "normalized": "27345595" } }, "mesh": [ { "descriptor": "Administration, Ophthalmic", "descriptor_ui": "D060433", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dry Eye Syndromes", "descriptor_ui": "D015352", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Ophthalmic Solutions", "descriptor_ui": "D009883", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jun 27", "date_precision": "day", "issue": "", "normalized_date": "2016-06-27", "pages": "12034", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "PACAP suppresses dry eye signs by stimulating tear secretion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Predicting responsible transcription regulators on the basis of transcriptome data is one of the most promising computational approaches to understanding cellular processes and characteristics. Here, we present a novel method employing vast amounts of chromatin immunoprecipitation (ChIP) experimental data to address this issue. Global high-throughput ChIP data was collected to construct a comprehensive database, containing 8 578 738 binding interactions of 454 transcription regulators. To incorporate information about heterogeneous frequencies of transcription factor (TF)-binding events, we developed a flexible framework for gene set analysis employing the weighted t-test procedure, namely weighted parametric gene set analysis (wPGSA). Using transcriptome data as an input, wPGSA predicts the activities of transcription regulators responsible for observed gene expression. Validation of wPGSA with published transcriptome data, including that from over-expressed TFs, showed that the method can predict activities of various TFs, regardless of cell type and conditions, with results totally consistent with biological observations. We also applied wPGSA to other published transcriptome data and identified potential key regulators of cell reprogramming and influenza virus pathogenesis, generating compelling hypotheses regarding underlying regulatory mechanisms. This flexible framework will contribute to uncovering the dynamic and robust architectures of biological regulation, by incorporating high-throughput experimental data in the form of weights.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Nakaoka", "name": null }, { "creator_type": "author", "first_name": "Tazro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kitano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nar/gkw355" }, "pmcid": { "normalized": "PMC4914117" }, "pmid": { "normalized": "27131787" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": true }, { "descriptor": "Chromatin Immunoprecipitation", "descriptor_ui": "D047369", "major_topic": true }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Databases, Genetic", "descriptor_ui": "D030541", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016 Jun 20", "date_precision": "day", "issue": "11", "normalized_date": "2016-06-20", "pages": "5010-5021", "proceedings_title": null, "publisher": "", "title": "Nucleic acids research", "volume": "44", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Weighted enrichment method for prediction of transcription regulators from transcriptome and global chromatin immunoprecipitation data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The herpes simplex virus 1 (HSV-1) Us8A gene overlaps the gene that encodes glycoprotein E (gE). Previous studies have investigated the roles of Us8A in HSV-1 infection using null mutations in Us8A and gE; therefore, the role of Us8A remains to be elucidated. In this study, we investigated the function of Us8A and its phosphorylation at serine 61 (Ser-61), which we recently identified as a phosphorylation site by mass spectrometry-based phosphoproteomic analysis of HSV-1-infected cells, in HSV-1 pathogenesis. We observed that (i) the phosphorylation of Us8A Ser-61 in infected cells was dependent on the activity of the virus-encoded Us3 protein kinase; (ii) the Us8A null mutant virus exhibited a 10-fold increase in the 50% lethal dose for virulence in the central nervous system (CNS) of mice following intracranial infection compared with a repaired virus; (iii) replacement of Ser-61 with alanine (S61A) in Us8A had little effect on virulence in the CNS of mice following intracranial infection, whereas it significantly reduced the mortality of mice following ocular infection to levels similar to the Us8A null mutant virus; (iv) the Us8A S61A mutation also significantly reduced viral yields in mice following ocular infection, mainly in the trigeminal ganglia and brains; and (v) a phosphomimetic mutation at Us8A Ser-61 restored wild-type viral yields and virulence. Collectively, these results indicate that Us8A is a novel HSV-1 virulence factor and suggest that the Us3-mediated phosphorylation of Us8A Ser-61 regulates Us8A function for viral invasion into the CNS from peripheral sites. IMPORTANCE: The DNA genomes of viruses within the subfamily Alphaherpesvirinae are divided into unique long (UL) and unique short (Us) regions. Us regions contain alphaherpesvirus-specific genes. Recently, high-throughput sequencing of ocular isolates of HSV-1 showed that Us8A was the most highly conserved of 13 herpes simplex virus 1 (HSV-1) genes mapped to the Us region, suggesting Us8A may have an important role in the HSV-1 life cycle. However, the specific role of Us8A in HSV-1 infection remains to be elucidated. Here, we show that Us8A is a virulence factor for HSV-1 infection in mice, and the function of Us8A for viral invasion into the central nervous system from peripheral sites is regulated by Us3-mediated phosphorylation of the protein at Ser-61. This is the first study to report the significance of Us8A and its regulation in HSV-1 infection.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00446-16" }, "pmcid": { "normalized": "PMC4886770" }, "pmid": { "normalized": "27030266" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Keratitis, Herpetic", "descriptor_ui": "D016849", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Trigeminal Ganglion", "descriptor_ui": "D012668", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virulence Factors", "descriptor_ui": "D037521", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jun 15", "date_precision": "day", "issue": "12", "normalized_date": "2016-06-15", "pages": "5622-5635", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "90", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Roles of Us8A and Its Phosphorylation Mediated by Us3 in Herpes Simplex Virus 1 Pathogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Angiogenesis plays a crucial role in tumor growth, with an undisputed contribution of resident endothelial cells (EC) to new blood vessels in the tumor. Here, we report the definition of a small population of vascular-resident stem/progenitor-like EC that contributes predominantly to new blood vessel formation in the tumor. Although the surface markers of this population are similar to other ECs, those from the lung vasculature possess colony-forming ability in vitro and contribute to angiogenesis in vivo These specific ECs actively proliferate in lung tumors, and the percentage of this population significantly increases in the tumor vasculature relative to normal lung tissue. Using genetic recombination and bone marrow transplant models, we show that these cells are phenotypically true ECs and do not originate from hematopoietic cells. After treatment of tumors with antiangiogenic drugs, these specific ECs selectively survived and remained in the tumor. Together, our results established that ECs in the peripheral vasculature are heterogeneous and that stem/progenitor-like ECs play an indispensable role in tumor angiogenesis as EC-supplying cells. The lack of susceptibility of these ECs to antiangiogenic drugs may account for resistance of the tumor to this drug type. Thus, inhibiting these ECs might provide a promising strategy to overcome antiangiogenic drug resistance. Cancer Res; 76(11); 3200-10. (c)2016 AACR.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takara", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Eino", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Yamane", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Iba", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/0008-5472.can-15-2998" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27197162" } }, "mesh": [ { "descriptor": "Angiogenesis Inhibitors", "descriptor_ui": "D020533", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Carcinoma, Lewis Lung", "descriptor_ui": "D018827", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": true }, { "descriptor": "Endothelium, Vascular", "descriptor_ui": "D004730", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": false }, { "descriptor": "Immunoenzyme Techniques", "descriptor_ui": "D007124", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Side-Population Cells", "descriptor_ui": "D058985", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jun 1", "date_precision": "day", "issue": "11", "normalized_date": "2016-06-01", "pages": "3200-3210", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "76", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Endothelial Side Population Cells Contribute to Tumor Angiogenesis and Antiangiogenic Drug Resistance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Melanocortin (MC) systems are composed of MC peptides such as adrenocorticotropic hormone (ACTH), several molecular forms of melanocyte-stimulating hormones (MSHs) and MC receptors (MCRs). Here we demonstrated that the cartilaginous fish, Dasyatis akajei (stingray) expresses five subtypes of MCR genes-mc1r to mc5r-as in the case of teleost and tetrapod species. This is the first evidence showing the presence of the full repertoire of melanocortin receptors in a single of cartilaginous fish. Expression of respective stingray mcr cDNAs in Chinese hamster ovary cells revealed that Des-acetyl-alpha-MSH exhibited cAMP-producing activity indistinguishable to ACTH(1-24) on MC1R and MC2R, while the activity of Des-acetyl-alpha-MSH on MC3R, MC4R, and MC5R were similar to or slightly greater than that of ACTH(1-24). Notably, in contrast to the other vertebrates, MC2R did not require coexpression with a melanocortin receptor-2 accessory protein 1 (mrap1) cDNA for functional expression. One of the roles of MC system resides in regulation of the pituitary-interrenal (PI) axis-a homologue of tetrapod pituitary-adrenal axis. In stingray, interrenal tissues were shown to express mc2r and mc5r as major MCR genes. These results established the presence of functional PI axis in stingray at the level of receptor molecule. While MC2R participates in adrenal functions together with MRAP1 in tetrapod species, the fact that sensitivity of MC5R to Des-acetyl-alpha-MSH and ACTH(1-24) were two order of magnitude higher than MC2R without coexpression with MRAP1 suggested that MC5R could play a more important role than MC2R to transmit signals conveyed by ACTH and MSHs if MRAP1 is really absent in the stingray.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Perry", "last_name": "Davis", "name": null }, { "creator_type": "author", "first_name": "Christina", "last_name": "Reinick", "name": null }, { "creator_type": "author", "first_name": "Kanta", "last_name": "Mizusawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Robert M.", "last_name": "Dores", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ygcen.2016.03.030" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27021018" } }, "mesh": [ { "descriptor": "Adrenocorticotropic Hormone", "descriptor_ui": "D000324", "major_topic": false }, { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "CHO Cells", "descriptor_ui": "D016466", "major_topic": false }, { "descriptor": "Cricetinae", "descriptor_ui": "D006224", "major_topic": false }, { "descriptor": "Cricetulus", "descriptor_ui": "D003412", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fishes", "descriptor_ui": "D005399", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Melanocyte-Stimulating Hormones", "descriptor_ui": "D009074", "major_topic": false }, { "descriptor": "Pituitary-Adrenal System", "descriptor_ui": "D010913", "major_topic": false }, { "descriptor": "Receptors, Melanocortin", "descriptor_ui": "D044101", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jun 1", "date_precision": "day", "issue": "", "normalized_date": "2016-06-01", "pages": "115-124", "proceedings_title": null, "publisher": "", "title": "General and comparative endocrinology", "volume": "232", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Characterization of melanocortin receptors from stingray Dasyatis akajei, a cartilaginous fish.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Postsynaptic kainate-type glutamate receptors (KARs) regulate synaptic network activity through their slow channel kinetics, most prominently at mossy fiber (MF)-CA3 synapses in the hippocampus. Nevertheless, how KARs cluster and function at these synapses has been unclear. Here, we show that C1q-like proteins C1ql2 and C1ql3, produced by MFs, serve as extracellular organizers to recruit functional postsynaptic KAR complexes to the CA3 pyramidal neurons. C1ql2 and C1ql3 specifically bound the amino-terminal domains of postsynaptic GluK2 and GluK4 KAR subunits and the presynaptic neurexin 3 containing a specific sequence in vitro. In C1ql2/3 double-null mice, CA3 synaptic responses lost the slow, KAR-mediated components. Furthermore, despite induction of MF sprouting in a temporal lobe epilepsy model, KARs were not recruited to postsynaptic sites in C1ql2/3 double-null mice, leading to reduced recurrent circuit activities. C1q family proteins, broadly expressed, are likely to modulate KAR function throughout the brain and represent promising antiepileptic targets.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Timotheus", "last_name": "Budisantoso", "name": null }, { "creator_type": "author", "first_name": "Nikolaos", "last_name": "Mitakidis", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugaya", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Kakegawa", "name": null }, { "creator_type": "author", "first_name": "Miwako", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Kohtarou", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Motokazu", "last_name": "Uchigashima", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "A. Radu", "last_name": "Aricescu", "name": null }, { "creator_type": "author", "first_name": "Michisuke", "last_name": "Yuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2016.04.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27133466" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Kainic Acid Receptors", "descriptor_ui": "D018092", "major_topic": false }, { "descriptor": "Membrane Glycoproteins", "descriptor_ui": "D008562", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mossy Fibers, Hippocampal", "descriptor_ui": "D019599", "major_topic": false }, { "descriptor": "Pyramidal Cells", "descriptor_ui": "D017966", "major_topic": false }, { "descriptor": "Receptors, Complement", "descriptor_ui": "D011951", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 May 18", "date_precision": "day", "issue": "4", "normalized_date": "2016-05-18", "pages": "752-767", "proceedings_title": null, "publisher": "", "title": "Neuron", "volume": "90", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Transsynaptic Modulation of Kainate Receptor Functions by C1q-like Proteins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The phototactic behavior of the unicellular green alga Chlamydomonas reinhardtii is thought to rely on photoreception by the eyespot apparatus. Here, we isolated an eyespot-less mutant that clearly exhibits phototaxis. Intriguingly, the phototactic sign (the direction of cell migration) in this mutant is opposite to that of the wild type after treatment with reagents that enhance the sign, a property that we also detected in previously reported eyespot-less mutants. The reversed phototactic-sign phenotype was attributed to the fact that the photoreceptors were exposed to condensed light from their rear side. This report demonstrates the importance of the eyespot, in which carotenoid layers shield the photoreceptors from light condensed by the cell body, which functions as a convex lens.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Noriko", "last_name": "Ueki", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Mochiji", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Ryutaro", "last_name": "Tokutsu", "name": null }, { "creator_type": "author", "first_name": "Norikazu", "last_name": "Ohnishi", "name": null }, { "creator_type": "author", "first_name": "Katsushi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Shigenobu", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Minagawa", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Hirono", "name": null }, { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Wakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1525538113" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27122315" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carotenoids", "descriptor_ui": "D002338", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Chlamydomonas reinhardtii", "descriptor_ui": "D016825", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Photoreceptor Cells, Invertebrate", "descriptor_ui": "D017956", "major_topic": false }, { "descriptor": "Phototaxis", "descriptor_ui": "D000071444", "major_topic": false }, { "descriptor": "Pigmentation", "descriptor_ui": "D010858", "major_topic": false }, { "descriptor": "Radiation Dosage", "descriptor_ui": "D011829", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 May 10", "date_precision": "day", "issue": "19", "normalized_date": "2016-05-10", "pages": "5299-5304", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "113", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Eyespot-dependent determination of the phototactic sign in Chlamydomonas reinhardtii.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "NAD(P)H-dependent oxidoreductases play important roles in biology. Recently, we reported that the luminescence lifetime of some Tb(3+) complexes is sensitive to NAD(P)H, and we used this phenomenon to detect activities of these enzymes. However, conventional time-resolved luminescence assays are susceptible to static quenchers such as ATP. Herein we describe a detection methodology that overcomes this issue: the intensity of the sample is measured twice with different delay times and the intensity ratio value is used as an index of NAD(P)H concentration. The method is more robust than single-point measurement, and is compatible with high-throughput assays using conventional microplate readers.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bmcl.2016.03.038" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27013390" } }, "mesh": [ { "descriptor": "Luminescence", "descriptor_ui": "D049449", "major_topic": false }, { "descriptor": "NADP", "descriptor_ui": "D009249", "major_topic": false }, { "descriptor": "Terbium", "descriptor_ui": "D013725", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 May 1", "date_precision": "day", "issue": "9", "normalized_date": "2016-05-01", "pages": "2314-2317", "proceedings_title": null, "publisher": "", "title": "Bioorganic & medicinal chemistry letters", "volume": "26", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Detection of NAD(P)H-dependent enzyme activity by time-domain ratiometry of terbium luminescence.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The order and orientation of cortical microtubule (CMT) arrays and their dynamics play an essential role in plant morphogenesis. To extract detailed CMT alignment structures in an objective, local, and accurate way, we propose an error-based extraction method that applies to general fluorescence intensity data on three-dimensional cell surfaces. Building on previous techniques to quantify alignments, our method can determine the statistical error for specific local regions, or the minimal scales of local regions for a desired accuracy goal. After validating our method with synthetic images with known alignments, we demonstrate the ability of our method to quantify subcellular CMT alignments on images with microtubules marked with green fluorescent protein in various cell types. Our method could also be applied to detect alignment structures in other fibrillar elements, such as actin filaments, cellulose, and collagen.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsugawa", "name": null }, { "creator_type": "author", "first_name": "Nathan", "last_name": "Hervieux", "name": null }, { "creator_type": "author", "first_name": "Oliver", "last_name": "Hamant", "name": null }, { "creator_type": "author", "first_name": "Arezki", "last_name": "Boudaoud", "name": null }, { "creator_type": "author", "first_name": "Richard S.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Chun-Biu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpj.2016.03.011" }, "pmcid": { "normalized": "PMC4850328" }, "pmid": { "normalized": "27119643" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Apr 26", "date_precision": "day", "issue": "8", "normalized_date": "2016-04-26", "pages": "1836-1844", "proceedings_title": null, "publisher": "", "title": "Biophysical journal", "volume": "110", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Extracting Subcellular Fibrillar Alignment with Error Estimation: Application to Microtubules.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sperm induce Ca(2+) waves in the fertilized egg by introducing soluble factors or by surface interactions, which activate egg Ca(2+) channels. Involvement of sperm Ca(2+) channels is predicted by the conduit model; however, this model has not been validated. In Caenorhabditis elegans, the sperm-specific TRP family Ca(2+) channel TRP-3 mediates sperm-oocyte fusion. Here, using high-speed in vivo imaging and image analyses, we show that sperm induce an immediate local Ca(2+) rise followed by a Ca(2+) wave in fertilized C. elegans oocytes. Oocytes fertilized by rare trp-3 escaper sperm showed a lack of local rise and a delay in onset of the Ca(2+) wave. Sperm Ca(2+) imaging suggests that the local rise is not due to the bolus introduction of stored Ca(2+). These results suggest that, along with its primary function in sperm-oocyte fusion, TRP-3 induces Ca(2+) waves in fertilized oocytes, consistent with the conduit model.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2016.03.040" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27068469" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": false }, { "descriptor": "Calcium Channels", "descriptor_ui": "D015220", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Fertilization", "descriptor_ui": "D005306", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Genetic Loci", "descriptor_ui": "D056426", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Fusion", "descriptor_ui": "D008561", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Oocytes", "descriptor_ui": "D009865", "major_topic": false }, { "descriptor": "Spermatozoa", "descriptor_ui": "D013094", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Transgenes", "descriptor_ui": "D019076", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Apr 19", "date_precision": "day", "issue": "3", "normalized_date": "2016-04-19", "pages": "625-637", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "15", "year": 2016 }, "ssbd": { "database": [ "ssbd-database-000012" ], "repository": [ "ssbd-repos-000012" ] }, "title": "The Sperm TRP-3 Channel Mediates the Onset of a Ca(2+) Wave in the Fertilized C. elegans Oocyte.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Social amoeba, Dictyostelium discoideum, is a well-established model organism for studying cellular physiology and developmental pattern formation. Its haploid genome facilitates functional analysis of genes by a single round of mutagenesis including targeted disruption. Although the efficient generation of knockout strains based on an intrinsically high homologous recombination rate has been demonstrated, successful reports for knockin strains have been limited. As social amoeba has an exceptionally high adenine and thymine (A/T)-content, conventional plasmid-based vector construction has been constrained due to deleterious deletion in E. coli. RESULTS: We describe here a simple and efficient strategy to construct GFP-knockin cassettes by using a linear DNA cloning vector derived from N15 bacteriophage. This allows reliable handling of DNA fragments whose A/T-content may be as high as 85 %, and which cannot be cloned into a circular plasmid. By optimizing the length of recombination arms, we successfully generate GFP-knockin strains for five genes involved in cAMP signalling, including a triple-colour knockin strain. CONCLUSIONS: This robust strategy would be useful in handling DNA fragments with biased A/T-contents such as the genome of lower organisms and the promoter/terminator regions of higher organisms.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Asuka", "last_name": "Mukai", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Ichiraku", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12896-016-0267-8" }, "pmcid": { "normalized": "PMC4831088" }, "pmid": { "normalized": "27075750" } }, "mesh": [ { "descriptor": "Adenine", "descriptor_ui": "D000225", "major_topic": false }, { "descriptor": "AT Rich Sequence", "descriptor_ui": "D020856", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false }, { "descriptor": "DNA, Protozoan", "descriptor_ui": "D016054", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "Thymine", "descriptor_ui": "D013941", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Apr 14", "date_precision": "day", "issue": "", "normalized_date": "2016-04-14", "pages": "37", "proceedings_title": null, "publisher": "", "title": "BMC biotechnology", "volume": "16", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Reliable handling of highly A/T-rich genomic DNA for efficient generation of knockin strains of Dictyostelium discoideum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Colonic epithelial cells are covered by thick inner and outer mucus layers. The inner mucus layer is free of commensal microbiota, which contributes to the maintenance of gut homeostasis. In the small intestine, molecules critical for prevention of bacterial invasion into epithelia such as Paneth-cell-derived anti-microbial peptides and regenerating islet-derived 3 (RegIII) family proteins have been identified. Although there are mucus layers providing physical barriers against the large number of microbiota present in the large intestine, the mechanisms that separate bacteria and colonic epithelia are not fully elucidated. Here we show that Ly6/PLAUR domain containing 8 (Lypd8) protein prevents flagellated microbiota invading the colonic epithelia in mice. Lypd8, selectively expressed in epithelial cells at the uppermost layer of the large intestinal gland, was secreted into the lumen and bound flagellated bacteria including Proteus mirabilis. In the absence of Lypd8, bacteria were present in the inner mucus layer and many flagellated bacteria invaded epithelia. Lypd8(-/-) mice were highly sensitive to intestinal inflammation induced by dextran sulfate sodium (DSS). Antibiotic elimination of Gram-negative flagellated bacteria restored the bacterial-free state of the inner mucus layer and ameliorated DSS-induced intestinal inflammation in Lypd8(-/-) mice. Lypd8 bound to flagella and suppressed motility of flagellated bacteria. Thus, Lypd8 mediates segregation of intestinal bacteria and epithelial cells in the colon to preserve intestinal homeostasis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryu", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kurakawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Hisako", "last_name": "Kayama", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Motooka", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Gotoh", "name": null }, { "creator_type": "author", "first_name": "Taishi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Naganori", "last_name": "Kamiyama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kusu", "name": null }, { "creator_type": "author", "first_name": "Yoshiyasu", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Hong", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Iijima", "name": null }, { "creator_type": "author", "first_name": "Soumik", "last_name": "Barman", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Osawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Matsuno", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Umemoto", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Takeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nature17406" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27027293" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacterial Adhesion", "descriptor_ui": "D001422", "major_topic": false }, { "descriptor": "Caco-2 Cells", "descriptor_ui": "D018938", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Colitis", "descriptor_ui": "D003092", "major_topic": false }, { "descriptor": "Colon", "descriptor_ui": "D003106", "major_topic": false }, { "descriptor": "Dextran Sulfate", "descriptor_ui": "D016264", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Flagella", "descriptor_ui": "D005407", "major_topic": true }, { "descriptor": "GPI-Linked Proteins", "descriptor_ui": "D058851", "major_topic": false }, { "descriptor": "Gram-Negative Bacteria", "descriptor_ui": "D006090", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Intestinal Mucosa", "descriptor_ui": "D007413", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Proteus mirabilis", "descriptor_ui": "D011513", "major_topic": false }, { "descriptor": "Symbiosis", "descriptor_ui": "D013559", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Apr 7", "date_precision": "day", "issue": "7597", "normalized_date": "2016-04-07", "pages": "117-121", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "532", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mechanisms by which the diffusion rate in the plasma membrane (PM) is regulated remain unresolved, despite their importance in spatially regulating the reaction rates in the PM. Proposed models include entrapment in nanoscale noncontiguous domains found in PtK2 cells, slow diffusion due to crowding, and actin-induced compartmentalization. Here, by applying single-particle tracking at high time resolutions, mainly to the PtK2-cell PM, we found confined diffusion plus hop movements (termed \"hop diffusion\") for both a nonraft phospholipid and a transmembrane protein, transferrin receptor, and equal compartment sizes for these two molecules in all five of the cell lines used here (actual sizes were cell dependent), even after treatment with actin-modulating drugs. The cross-section size and the cytoplasmic domain size both affected the hop frequency. Electron tomography identified the actin-based membrane skeleton (MSK) located within 8.8 nm from the PM cytoplasmic surface of PtK2 cells and demonstrated that the MSK mesh size was the same as the compartment size for PM molecular diffusion. The extracellular matrix and extracellular domains of membrane proteins were not involved in hop diffusion. These results support a model of anchored TM-protein pickets lining actin-based MSK as a major mechanism for regulating diffusion.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takahiro K.", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Kokoro", "last_name": "Iwasawa", "name": null }, { "creator_type": "author", "first_name": "Ziya", "last_name": "Kalay", "name": null }, { "creator_type": "author", "first_name": "Taka A.", "last_name": "Tsunoyama", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro M.", "last_name": "Umemura", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Kenichi G. N.", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yuri L.", "last_name": "Nemoto", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Morone", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Kusumi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1091/mbc.e15-04-0186" }, "pmcid": { "normalized": "PMC4814218" }, "pmid": { "normalized": "26864625" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Diffusion", "descriptor_ui": "D004058", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Phospholipids", "descriptor_ui": "D010743", "major_topic": false }, { "descriptor": "Potoroidae", "descriptor_ui": "D048328", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Receptors, Transferrin", "descriptor_ui": "D011990", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Apr 1", "date_precision": "day", "issue": "7", "normalized_date": "2016-04-01", "pages": "1101-1119", "proceedings_title": null, "publisher": "", "title": "Molecular biology of the cell", "volume": "27", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Confined diffusion of transmembrane proteins and lipids induced by the same actin meshwork lining the plasma membrane.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cellular interactions with the extracellular matrix play critical roles in tumor progression. We previously reported that receptor activator of NF-kappaB ligand (RANKL) specifically facilitates head and neck squamous cell carcinoma (HNSCC) progression in vivo. Here, we report a novel role for RANKL in the regulation of cell adhesion. Among the major type I collagen receptors, integrin alpha2 was significantly upregulated in RANKL-expressing cells, and its knockdown suppressed cell adhesion. The mRNA abundance of integrin alpha2 positively correlated with that of RANKL in human HNSCC tissues. We also revealed that RANK-NF-kappaB signaling mediated integrin alpha2 expression in an autocrine/paracrine manner. Interestingly, the amount of active integrin beta1 on the cell surface was increased in RANKL-expressing cells through the upregulation of integrin alpha2 and endocytosis. Moreover, the RANK-integrin alpha2 pathway contributed to RANKL-dependent enhanced survival in a collagen gel and inhibited apoptosis in a xenograft model, demonstrating an important role for RANKL-mediated cell adhesion in three-dimensional environments.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tamaki", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Wagatsuma", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Aya O.", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Kosui", "last_name": "Horiuchi", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Nishide", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Nanbo", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Totsuka", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Haga", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Shindoh", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep23545" }, "pmcid": { "normalized": "PMC4806381" }, "pmid": { "normalized": "27009236" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Head and Neck Neoplasms", "descriptor_ui": "D006258", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Integrin alpha2", "descriptor_ui": "D039421", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasm Transplantation", "descriptor_ui": "D009368", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "RANK Ligand", "descriptor_ui": "D053245", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Mar 24", "date_precision": "day", "issue": "", "normalized_date": "2016-03-24", "pages": "23545", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Receptor activator of NF-kappaB ligand induces cell adhesion and integrin alpha2 expression via NF-kappaB in head and neck cancers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Calcium (Ca(2+))-mediated signaling is a conserved mechanism in eukaryotes, including the human malaria parasite, Plasmodium falciparum. Due to its small size (<10 mum) measurement of intracellular Ca(2+) in Plasmodium is technically challenging, and thus Ca(2+) regulation in this human pathogen is not well understood. Here we analyze Ca(2+) homeostasis via a new approach using transgenic P. falciparum expressing the Ca(2+) sensor yellow cameleon (YC)-Nano. We found that cytosolic Ca(2+) concentration is maintained at low levels only during the intraerythrocytic trophozoite stage (30 nM), and is increased in the other blood stages (>300 nM). We determined that the mammalian SERCA inhibitor thapsigargin and antimalarial dihydroartemisinin did not perturb SERCA activity. The change of the cytosolic Ca(2+) level in P. falciparum was additionally detectable by flow cytometry. Thus, we propose that the developed YC-Nano-based system is useful to study Ca(2+) signaling in P. falciparum and is applicable for drug screening.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kishor", "last_name": "Pandey", "name": null }, { "creator_type": "author", "first_name": "Pedro E.", "last_name": "Ferreira", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kazuhide", "last_name": "Yahata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep23454" }, "pmcid": { "normalized": "PMC4804237" }, "pmid": { "normalized": "27006284" } }, "mesh": [ { "descriptor": "Artemisinins", "descriptor_ui": "D037621", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Calcium-Binding Proteins", "descriptor_ui": "D002135", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cytosol", "descriptor_ui": "D003600", "major_topic": false }, { "descriptor": "Erythrocytes", "descriptor_ui": "D004912", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Organisms, Genetically Modified", "descriptor_ui": "D030781", "major_topic": false }, { "descriptor": "Plasmodium falciparum", "descriptor_ui": "D010963", "major_topic": false }, { "descriptor": "Sarcoplasmic Reticulum Calcium-Transporting ATPases", "descriptor_ui": "D053498", "major_topic": false }, { "descriptor": "Thapsigargin", "descriptor_ui": "D019284", "major_topic": false }, { "descriptor": "Trophozoites", "descriptor_ui": "D053058", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Mar 23", "date_precision": "day", "issue": "", "normalized_date": "2016-03-23", "pages": "23454", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Ca(2+) monitoring in Plasmodium falciparum using the yellow cameleon-Nano biosensor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We employed a fluorescent substrate-based target discovery approach to screen the enzymome for metabolic activity towards pyruvyl-amidated peptides, and identified an acylamino acid-releasing enzyme (APEH). Cells overexpressing APEH exhibited higher metabolic activity towards the probe, N-pyruvyl-leucyl-7-amido-4-methylcoumarin (Pyr-Leu-AMC), while the selective APEH inhibitor AA74-1 blocked the reaction. Metabolism of various pyruvylated peptides in liver lysate was almost completely blocked by AA74-1. Pyruvyl peptides are synthesized in response to oxidative stress, but their biological role is poorly understood; identification of a key contributor to their metabolism should stimulate research on pathways leading from oxidative stress to protein modification and biological output.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kentaro", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c6cc00829a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26925595" } }, "mesh": [ { "descriptor": "Enzymes", "descriptor_ui": "D004798", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Pyruvates", "descriptor_ui": "D011773", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Mar 21", "date_precision": "day", "issue": "23", "normalized_date": "2016-03-21", "pages": "4377-4380", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "52", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Discovery of a pyruvylated peptide-metabolizing enzyme using a fluorescent substrate-based protein discovery technique.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To investigate comprehensive synaptic connectivity, we examined Ca(2+) responses with quantitative electric current stimulation by indium-tin-oxide (ITO) glass electrode with transparent and high electro-conductivity. The number of neurons with Ca(2+) responses was low during the application of stepwise increase of electric current in short-term cultured neurons (less than 17 days in-vitro (DIV)). The neurons cultured over 17 DIV showed two-type responses: S-shaped (sigmoid) and monotonous saturated responses, and Scatchard plots well illustrated the difference of these two responses. Furthermore, sigmoid like neural network responses over 17 DIV were altered to the monotonous saturated ones by the application of the mixture of AP5 and CNQX, specific blockers of NMDA and AMPA receptors, respectively. This alternation was also characterized by the change of Hill coefficients. These findings indicate that the neural network with sigmoid-like responses has strong synergetic or cooperative synaptic connectivity via excitatory glutamate synapses.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Tanamoto", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Niwano", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Norihisa", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2016.02.048" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26896767" } }, "mesh": [ { "descriptor": "6-Cyano-7-nitroquinoxaline-2,3-dione", "descriptor_ui": "D018750", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Chemistry Techniques, Analytical", "descriptor_ui": "D002623", "major_topic": false }, { "descriptor": "Electric Stimulation", "descriptor_ui": "D004558", "major_topic": false }, { "descriptor": "Electrodes", "descriptor_ui": "D004566", "major_topic": false }, { "descriptor": "Excitatory Amino Acid Antagonists", "descriptor_ui": "D018691", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Receptors, AMPA", "descriptor_ui": "D018091", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Tin Compounds", "descriptor_ui": "D017971", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Mar 18", "date_precision": "day", "issue": "4", "normalized_date": "2016-03-18", "pages": "486-491", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "471", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Qualitative and quantitative estimation of comprehensive synaptic connectivity in short- and long-term cultured rat hippocampal neurons with new analytical methods inspired by Scatchard and Hill plots.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "LRRK2 is the causal molecule of autosomal dominant familial Parkinson's disease. B2 cells express a much higher LRRK2 mRNA level than B1 cells. To reveal the function of LRRK2 in B cells, we analyzed B cell functions in LRRK2-knockout (LRRK2(-/-)) mice. LRRK2(-/-) mice had significantly higher counts of peritoneal B1 cells than wild-type mice. After BCR stimulation, phosphor-Erk1/2 of splenic B2 cells was enhanced to a higher degree in LRRK2(-/-) mice. LRRK2(-/-) mice had a significantly higher serum IgA level, and TNP-Ficoll immunization increased the titer of serum anti-TNP IgM antibody. LRRK2 may play important roles in B cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Isobe", "name": null }, { "creator_type": "author", "first_name": "Mitsue", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Eshima", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Iwabuchi", "name": null }, { "creator_type": "author", "first_name": "Toshikuni", "last_name": "Sasaoka", "name": null }, { "creator_type": "author", "first_name": "Sadahiro", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Heather L.", "last_name": "Melrose", "name": null }, { "creator_type": "author", "first_name": "Matthew J.", "last_name": "Farrer", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Obata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jneuroim.2016.01.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26943952" } }, "mesh": [ { "descriptor": "Age Factors", "descriptor_ui": "D000367", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, CD", "descriptor_ui": "D015703", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Enzyme-Linked Immunosorbent Assay", "descriptor_ui": "D004797", "major_topic": false }, { "descriptor": "Ficoll", "descriptor_ui": "D005362", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Immunoglobulin A", "descriptor_ui": "D007070", "major_topic": false }, { "descriptor": "Leucine-Rich Repeat Serine-Threonine Protein Kinase-2", "descriptor_ui": "D000071158", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Peritoneal Cavity", "descriptor_ui": "D010529", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Spleen", "descriptor_ui": "D013154", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta1", "descriptor_ui": "D053773", "major_topic": false }, { "descriptor": "Trinitrobenzenes", "descriptor_ui": "D014301", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Mar 15", "date_precision": "day", "issue": "", "normalized_date": "2016-03-15", "pages": "1-8", "proceedings_title": null, "publisher": "", "title": "Journal of neuroimmunology", "volume": "292", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Leucine-rich repeat kinase 2 is a regulator of B cell function, affecting homeostasis, BCR signaling, IgA production, and TI antigen responses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "CD4+ T cells that express the transcription factor FOXP3 (FOXP3+ T cells) are commonly regarded as immunosuppressive regulatory T cells (Tregs). FOXP3+ T cells are reported to be increased in tumor-bearing patients or animals and are considered to suppress antitumor immunity, but the evidence is often contradictory. In addition, accumulating evidence indicates that FOXP3 is induced by antigenic stimulation and that some non-Treg FOXP3+ T cells, especially memory-phenotype FOXP3low cells, produce proinflammatory cytokines. Accordingly, the subclassification of FOXP3+ T cells is fundamental for revealing the significance of FOXP3+ T cells in tumor immunity, but the arbitrariness and complexity of manual gating have complicated the issue. In this article, we report a computational method to automatically identify and classify FOXP3+ T cells into subsets using clustering algorithms. By analyzing flow cytometric data of melanoma patients, the proposed method showed that the FOXP3+ subpopulation that had relatively high FOXP3, CD45RO, and CD25 expressions was increased in melanoma patients, whereas manual gating did not produce significant results on the FOXP3+ subpopulations. Interestingly, the computationally identified FOXP3+ subpopulation included not only classical FOXP3high Tregs, but also memory-phenotype FOXP3low cells by manual gating. Furthermore, the proposed method successfully analyzed an independent data set, showing that the same FOXP3+ subpopulation was increased in melanoma patients, validating the method. Collectively, the proposed method successfully captured an important feature of melanoma without relying on the existing criteria of FOXP3+ T cells, revealing a hidden association between the T cell profile and melanoma, and providing new insights into FOXP3+ T cells and Tregs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Julie", "last_name": "Josse", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Tanioka", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "François", "last_name": "Husson", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.4049/jimmunol.1402695" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26864030" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Automation, Laboratory", "descriptor_ui": "D057205", "major_topic": false }, { "descriptor": "Cell Separation", "descriptor_ui": "D002469", "major_topic": false }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunologic Memory", "descriptor_ui": "D007156", "major_topic": false }, { "descriptor": "Interleukin-2 Receptor alpha Subunit", "descriptor_ui": "D053645", "major_topic": false }, { "descriptor": "Leukocyte Common Antigens", "descriptor_ui": "D017493", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Melanoma", "descriptor_ui": "D008545", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Skin Neoplasms", "descriptor_ui": "D012878", "major_topic": false }, { "descriptor": "T-Lymphocyte Subsets", "descriptor_ui": "D016176", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Mar 15", "date_precision": "day", "issue": "6", "normalized_date": "2016-03-15", "pages": "2885-2892", "proceedings_title": null, "publisher": "", "title": "The Journal of Immunology Author Choice", "volume": "196", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Regulatory T Cells in Melanoma Revisited by a Computational Clustering of FOXP3+ T Cell Subpopulations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescent proteins have been widely used in biology because of their compatibility and varied applications in living specimens. Fluorescent proteins are often undesirably sensitive to intracellular conditions such as pH and ion concentration, generating considerable issues at times. However, harnessing these intrinsic sensitivities can help develop functional probes. In this study, we found that the fluorescence of yellow fluorescent protein (YFP) depends on the protein concentration in the solution and that this dependence can be enhanced by adding a glycine residue in to the YFP; we applied this finding to construct an intracellular protein-crowding sensor. A Forster resonance energy transfer (FRET) pair, involving a cyan fluorescent protein (CFP) insensitive to protein concentration and a glycine-inserted YFP, works as a genetically encoded probe to evaluate intracellular crowding. By measuring the fluorescence of the present FRET probe, we were able to detect dynamic changes in protein crowding in living cells.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takamitsu J.", "last_name": "Morikawa", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Horio", "name": null }, { "creator_type": "author", "first_name": "Johtaro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Kinjo", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Machiyama", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Imada", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep22342" }, "pmcid": { "normalized": "PMC4783657" }, "pmid": { "normalized": "26956628" } }, "mesh": [ { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Glycine", "descriptor_ui": "D005998", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Solutions", "descriptor_ui": "D012996", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Mar 9", "date_precision": "day", "issue": "", "normalized_date": "2016-03-09", "pages": "22342", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Dependence of fluorescent protein brightness on protein concentration in solution and enhancement of it.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Modeling of neurological diseases using induced pluripotent stem cells (iPSCs) derived from the somatic cells of patients has provided a means of elucidating pathogenic mechanisms and performing drug screening. T cells are an ideal source of patient-specific iPSCs because they can be easily obtained from samples. Recent studies indicated that iPSCs retain an epigenetic memory relating to their cell of origin that restricts their differentiation potential. The classical method of differentiation via embryoid body formation was not suitable for T cell-derived iPSCs (TiPSCs). We developed a neurosphere-based robust differentiation protocol, which enabled TiPSCs to differentiate into functional neurons, despite differences in global gene expression between TiPSCs and adult human dermal fibroblast-derived iPSCs. Furthermore, neurons derived from TiPSCs generated from a juvenile patient with Parkinson's disease exhibited several Parkinson's disease phenotypes. Therefore, we conclude that TiPSCs are a useful tool for modeling neurological diseases.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takuya", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Andoh-Noda", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Kuzumaki", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Toyoshima", "name": null }, { "creator_type": "author", "first_name": "Hirobumi", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Isoda", "name": null }, { "creator_type": "author", "first_name": "Zhi", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Shigeto", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Manami", "last_name": "Ohtaka", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kurosawa", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Mahito", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Ohyama", "name": null }, { "creator_type": "author", "first_name": "Nobutaka", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Wado", "last_name": "Akamatsu", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2016.01.010" }, "pmcid": { "normalized": "PMC4788773" }, "pmid": { "normalized": "26905201" } }, "mesh": [ { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Primary Cell Culture", "descriptor_ui": "D061251", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Mar 8", "date_precision": "day", "issue": "3", "normalized_date": "2016-03-08", "pages": "422-435", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Functional Neurons Generated from T Cell-Derived Induced Pluripotent Stem Cells for Neurological Disease Modeling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Markovian dynamics on complex reaction networks are one of the most intriguing subjects in a wide range of research fields including chemical reactions, biological physics, and ecology. To represent the global kinetics from one node (corresponding to a basin on an energy landscape) to another requires information on multiple pathways that directly or indirectly connect these two nodes through the entire network. In this paper we present a scheme to extract a hierarchical set of global transition states (TSs) over a discrete-time Markov chain derived from first-order rate equations. The TSs can naturally take into account the multiple pathways connecting any pair of nodes. We also propose a new type of disconnectivity graph (DG) to capture the hierarchical organization of different time scales of reactions that can capture changes in the network due to changes in the time scale of observation. The crux is the introduction of the minimum conductance cut (MCC) in graph clustering, corresponding to the dividing surface across the network having the \"smallest\" transition probability between two disjoint subnetworks (superbasins on the energy landscape) in the network. We present a new combinatorial search algorithm for finding this MCC. We apply our method to a reaction network of Claisen rearrangement of allyl vinyl ether that consists of 23 nodes and 66 links (saddles on the energy landscape) connecting them. We compare the kinetic properties of our DG to those of the transition matrix of the rate equations and show that our graph can properly reveal the hierarchical organization of time scales in a network.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yutaka", "last_name": "Nagahata", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Teramoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Horiyama", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Taketsugu", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jpcb.5b09941" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26641663" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Mar 3", "date_precision": "day", "issue": "8", "normalized_date": "2016-03-03", "pages": "1961-1971", "proceedings_title": null, "publisher": "", "title": "The journal of physical chemistry. B", "volume": "120", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Deciphering Time Scale Hierarchy in Reaction Networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The impact of microRNA (miRNA) on the genetics of human complex traits, especially in the context of miRNA-target gene networks, has not been fully assessed. Here, we developed a novel analytical method, MIGWAS, to comprehensively evaluate enrichment of genome-wide association study (GWAS) signals in miRNA-target gene networks. We applied the method to the GWAS results of the 18 human complex traits from >1.75 million subjects, and identified significant enrichment in rheumatoid arthritis (RA), kidney function, and adult height (P < 0.05/18 = 0.0028, most significant enrichment in RA with P = 1.7 x 10(-4)). Interestingly, these results were consistent with current literature-based knowledge of the traits on miRNA obtained through the NCBI PubMed database search (adjusted P = 0.024). Our method provided a list of miRNA and target gene pairs with excess genetic association signals, part of which included drug target genes. We identified a miRNA (miR-4728-5p) that downregulates PADI2, a novel RA risk gene considered as a promising therapeutic target (rs761426, adjusted P = 2.3 x 10(-9)). Our study indicated the significant impact of miRNA-target gene networks on the genetics of human complex traits, and provided resources which should contribute to drug discovery and nucleic acid medicine.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukinori", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Naomasa", "last_name": "Suita", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Valentina", "last_name": "Iotchkova", "name": null }, { "creator_type": "author", "first_name": "Nicole", "last_name": "Soranzo", "name": null }, { "creator_type": "author", "first_name": "Johji", "last_name": "Inazawa", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep22223" }, "pmcid": { "normalized": "PMC4772006" }, "pmid": { "normalized": "26927695" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Arthritis, Rheumatoid", "descriptor_ui": "D001172", "major_topic": false }, { "descriptor": "Body Height", "descriptor_ui": "D001827", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrolases", "descriptor_ui": "D006867", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Molecular Targeted Therapy", "descriptor_ui": "D058990", "major_topic": false }, { "descriptor": "Multifactorial Inheritance", "descriptor_ui": "D020412", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Protein-Arginine Deiminase Type 2", "descriptor_ui": "D000080064", "major_topic": false }, { "descriptor": "Protein-Arginine Deiminases", "descriptor_ui": "D000076342", "major_topic": false }, { "descriptor": "Risk", "descriptor_ui": "D012306", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Mar 1", "date_precision": "day", "issue": "", "normalized_date": "2016-03-01", "pages": "22223", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Significant impact of miRNA-target gene networks on genetics of human complex traits.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "For a better understanding of the mechanisms behind cellular functions, quantification of the heterogeneity in an organism or cells is essential. Recently, the importance of quantifying temperature has been highlighted, as it correlates with biochemical reaction rates. Several methods for detecting intracellular temperature have recently been established. Here we develop a novel method for sensing temperature in living cells based on the imaging technique of fluorescence of quantum dots. We apply the method to quantify the temperature difference in a human derived neuronal cell line, SH-SY5Y. Our results show that temperatures in the cell body and neurites are different and thus suggest that inhomogeneous heat production and dissipation happen in a cell. We estimate that heterogeneous heat dissipation results from the characteristic shape of neuronal cells, which consist of several compartments formed with different surface-volume ratios. Inhomogeneous heat production is attributable to the localization of specific organelles as the heat source.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Tanimoto", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Hiraiwa", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Hiroi", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Funahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep22071" }, "pmcid": { "normalized": "PMC4772094" }, "pmid": { "normalized": "26925874" } }, "mesh": [ { "descriptor": "Cell Compartmentation", "descriptor_ui": "D002451", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Hot Temperature", "descriptor_ui": "D006358", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Organelles", "descriptor_ui": "D015388", "major_topic": false }, { "descriptor": "Quantum Dots", "descriptor_ui": "D045663", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false }, { "descriptor": "Thermogenesis", "descriptor_ui": "D022722", "major_topic": false }, { "descriptor": "Thermometry", "descriptor_ui": "D062125", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Mar 1", "date_precision": "day", "issue": "", "normalized_date": "2016-03-01", "pages": "22071", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Detection of Temperature Difference in Neuronal Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During anaphase, distinct populations of microtubules (MTs) form by either centrosome-dependent or augmin-dependent nucleation. It remains largely unknown whether these different MT populations contribute distinct functions to cytokinesis. Here we show that augmin-dependent MTs are required for the progression of both furrow ingression and abscission. Augmin depletion reduced the accumulation of anillin, a contractile ring regulator at the cell equator, yet centrosomal MTs were sufficient to mediate RhoA activation at the furrow. This defect in contractile ring organization, combined with incomplete spindle pole separation during anaphase, led to impaired furrow ingression. During the late stages of cytokinesis, astral MTs formed bundles in the intercellular bridge, but these failed to assemble a focused midbody structure and did not establish tight linkage to the plasma membrane, resulting in furrow regression. Thus augmin-dependent acentrosomal MTs and centrosomal MTs contribute to nonredundant targeting mechanisms of different cytokinesis factors, which are required for the formation of a functional contractile ring and midbody.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Kamasaki", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Hiruma", "name": null }, { "creator_type": "author", "first_name": "Ina", "last_name": "Poser", "name": null }, { "creator_type": "author", "first_name": "Kinya", "last_name": "Yoda", "name": null }, { "creator_type": "author", "first_name": "Junichiro", "last_name": "Yajima", "name": null }, { "creator_type": "author", "first_name": "Daniel W.", "last_name": "Gerlich", "name": null }, { "creator_type": "author", "first_name": "Gohta", "last_name": "Goshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1091/mbc.e15-02-0101" }, "pmcid": { "normalized": "PMC4803307" }, "pmid": { "normalized": "26764096" } }, "mesh": [ { "descriptor": "Anaphase", "descriptor_ui": "D000705", "major_topic": false }, { "descriptor": "Aniline Compounds", "descriptor_ui": "D000814", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Chromosome Segregation", "descriptor_ui": "D020090", "major_topic": false }, { "descriptor": "Cytokinesis", "descriptor_ui": "D048749", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microtubule-Associated Proteins", "descriptor_ui": "D008869", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "rhoA GTP-Binding Protein", "descriptor_ui": "D020742", "major_topic": false }, { "descriptor": "Spindle Apparatus", "descriptor_ui": "D008941", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Mar 1", "date_precision": "day", "issue": "5", "normalized_date": "2016-03-01", "pages": "812-827", "proceedings_title": null, "publisher": "", "title": "Molecular biology of the cell", "volume": "27", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Augmin shapes the anaphase spindle for efficient cytokinetic furrow ingression and abscission.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP, encoded by adcyap1) plays an important role in ectodermal development. However, the involvement of PACAP in the development of other germ layers is still unclear. This study assessed the expression of a PACAP-specific receptor (PAC1) gene and protein in mouse bone marrow (BM). Cells strongly expressing PAC1(+) were large in size, had oval nuclei, and merged with CD34(+) cells, suggesting that the former were hematopoietic progenitor cells (HPCs). Compared with wild-type mice, adcyap1(-/-) mice exhibited lower multiple potential progenitor cell populations and cell frequency in the S-phase of the cell cycle. Exogenous PACAP38 significantly increased the numbers of colony forming unit-granulocyte/macrophage progenitor cells (CFU-GM) with two peaks in semi-solid culture. PACAP also increased the expression of cyclinD1 and Ki67 mRNAs. These increases were completely and partially inhibited by the PACAP receptor antagonists, PACAP6-38 and VIP6-28, respectively. Little or no adcyap1 was expressed in BM and the number of CFU-GM colonies was similar in adcyap1(-/-) and wild-type mice. However, PACAP mRNA and protein were expressed in paravertebral sympathetic ganglia, which innervate tibial BM, and in the sympathetic fibers of BM cavity. These results suggested that sympathetic nerve innervation may be responsible for PACAP-regulated hematopoiesis in BM, mainly via PAC1.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Zhifang", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Ohtaki", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Norimitsu", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Hiraizumi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Numazawa", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Shioda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep22373" }, "pmcid": { "normalized": "PMC4772629" }, "pmid": { "normalized": "26925806" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, CD34", "descriptor_ui": "D018952", "major_topic": false }, { "descriptor": "Bone Marrow", "descriptor_ui": "D001853", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cyclin D1", "descriptor_ui": "D019938", "major_topic": false }, { "descriptor": "Granulocytes", "descriptor_ui": "D006098", "major_topic": false }, { "descriptor": "Hematopoiesis", "descriptor_ui": "D006410", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "Ki-67 Antigen", "descriptor_ui": "D019394", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I", "descriptor_ui": "D051237", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Sympathetic Nervous System", "descriptor_ui": "D013564", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Feb 29", "date_precision": "day", "issue": "", "normalized_date": "2016-02-29", "pages": "22373", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Pituitary adenylate cyclase-activating polypeptide (PACAP) contributes to the proliferation of hematopoietic progenitor cells in murine bone marrow via PACAP-specific receptor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In Purkinje cells (PCs) of the cerebellum, a single \"winner\" climbing fiber (CF) monopolizes proximal dendrites, whereas hundreds of thousands of parallel fibers (PFs) innervate distal dendrites, and both CF and PF inputs innervate a narrow intermediate domain. It is unclear how this segregated CF and PF innervation is established on PC dendrites. Through reconstruction of dendritic innervation by serial electron microscopy, we show that from postnatal day 9-15 in mice, both CF and PF innervation territories vigorously expand because of an enlargement of the region of overlapping innervation. From postnatal day 15 onwards, segregation of these territories occurs with robust shortening of the overlapping proximal region. Thus, innervation territories by the heterologous inputs are refined during the early postnatal period. Intriguingly, this transition is arrested in mutant mice lacking the type 1 metabotropic glutamate receptor (mGluR1) or protein kinase Cgamma (PKCgamma), resulting in the persistence of an abnormally expanded overlapping region. This arrested territory refinement is rescued by lentivirus-mediated expression of mGluR1alpha into mGluR1-deficient PCs. At the proximal dendrite of rescued PCs, PF synapses are eliminated and free spines emerge instead, whereas the number and density of CF synapses are unchanged. Because the mGluR1-PKCgamma signaling pathway is also essential for the late-phase of CF synapse elimination, this signaling pathway promotes the two key features of excitatory synaptic wiring in PCs, namely CF monoinnervation by eliminating redundant CF synapses from the soma, and segregated territories of CF and PF innervation by eliminating competing PF synapses from proximal dendrites.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Motokazu", "last_name": "Uchigashima", "name": null }, { "creator_type": "author", "first_name": "Miwako", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Atsu", "last_name": "Aiba", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1511513113" }, "pmcid": { "normalized": "PMC4776453" }, "pmid": { "normalized": "26858447" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, 129 Strain", "descriptor_ui": "D057507", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Microscopy, Electron", "descriptor_ui": "D008854", "major_topic": false }, { "descriptor": "Models, Neurological", "descriptor_ui": "D008959", "major_topic": false }, { "descriptor": "Protein Kinase C", "descriptor_ui": "D011493", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Feb 23", "date_precision": "day", "issue": "8", "normalized_date": "2016-02-23", "pages": "2282-2287", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "113", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Territories of heterologous inputs onto Purkinje cell dendrites are segregated by mGluR1-dependent parallel fiber synapse elimination.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "KEY POINTS: At the parallel fibre-Purkinje cell glutamatergic synapse, little or no Ca(2+) entry takes place through postsynaptic neurotransmitter receptors, although postsynaptic calcium increases are clearly involved in the synaptic plasticity. Postsynaptic voltage-gated Ca(2+) channels therefore constitute the sole rapid postsynaptic Ca(2+) signalling mechanism, making it essential to understand how they contribute to the synaptic signalling. Using a selective T-type calcium channel antagonist, we describe a T-type component of the EPSC that is activated by the AMPA receptor-mediated depolarization of the spine and thus will contribute to the local calcium dynamics. This component can amount up to 20% of the EPSC, and this fraction is maintained even at the high frequencies sometimes encountered in sensory processing. Modelling based on our biophysical characterization of T-type calcium channels in Purkinje cells suggests that the brief spine EPSCs cause the activated T-type channels to deactivate rather than inactivate, enabling repetitive activation. ABSTRACT: In the cerebellum, sensory information is conveyed to Purkinje cells (PC) via the granule cell/parallel fibre (PF) pathway. Plasticity at the PF-PC synapse is considered to be a mechanism of information storage in motor learning. The induction of synaptic plasticity in the cerebellum and elsewhere usually involves intracellular Ca(2+) signals. Unusually, postsynaptic Ca(2+) signalling in PF-PC spines does not involve ionotropic glutamatergic receptors because postsynaptic NMDA receptors are absent and the AMPA receptors are Ca(2+) -impermeable; postsynaptic voltage-gated Ca(2+) channels therefore constitute the sole rapid Ca(2+) signalling mechanism. Low-threshold activated T-type calcium channels are present at the synapse, although their contribution to PF-PC synaptic responses is unknown. Taking advantage of 3,5-dichloro-N-[1-(2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-4-fluoro-piperidin-4-ylmethyl]-benzamide, a selective T-type channel antagonist, we show in the mouse that inhibition of these channels reduces PF-PC excitatory postsynaptic currents and excitatory postsynaptic potentials by 15-20%. This contribution was preserved during sparse input and repetitive activity. We characterized the biophysical properties of native T-type channels in young animals and modelled their activation during simulated dendritic excitatory postsynaptic potential waveforms. The comparison of modelled and observed synaptic responses suggests that T-type channels only activate in spines that are strongly depolarized by their synaptic input, a process requiring a high spine neck resistance. This brief and local activation ensures that T-type channels rapidly deactivate, thereby limiting inactivation during repetitive synaptic activity. T-type channels are therefore ideally situated to provide synaptic Ca(2+) entry at PF-PC spines.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Romain", "last_name": "Ly", "name": null }, { "creator_type": "author", "first_name": "Guy", "last_name": "Bouvier", "name": null }, { "creator_type": "author", "first_name": "German", "last_name": "Szapiro", "name": null }, { "creator_type": "author", "first_name": "Haydn M.", "last_name": "Prosser", "name": null }, { "creator_type": "author", "first_name": "Andrew D.", "last_name": "Randall", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Philippe", "last_name": "Isope", "name": null }, { "creator_type": "author", "first_name": "Boris", "last_name": "Barbour", "name": null }, { "creator_type": "author", "first_name": "Anne", "last_name": "Feltz", "name": null } ], "identifiers": { "doi": { "normalized": "10.1113/jp271623" }, "pmcid": { "normalized": "PMC4753263" }, "pmid": { "normalized": "26627919" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Channel Blockers", "descriptor_ui": "D002121", "major_topic": false }, { "descriptor": "Calcium Channels, T-Type", "descriptor_ui": "D020747", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Feb 15", "date_precision": "day", "issue": "4", "normalized_date": "2016-02-15", "pages": "915-936", "proceedings_title": null, "publisher": "", "title": "The Journal of physiology", "volume": "594", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Contribution of postsynaptic T-type calcium channels to parallel fibre-Purkinje cell synaptic responses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Photoacoustic imaging, a noninvasive imaging based on optical excitation and ultrasonic detection, enables one to visualize the distribution of hemoglobin and acquire a map of microvessels without using contrast agents. We examined whether it helps visualize periprostatic microvessels and improves visualization of the neurovascular bundle. METHODS: We developed a photoacoustic imaging (PAI) system with a hand-held probe combining optical illumination and a conventional linear array ultrasound probe. In experiments with a phantom model, it was able to visualize vessels with diameters as small as 300 mum within a depth of 10 mm. We also developed a TRUS type probe for our photoacoustic imaging system and used it to intraoperatively monitor periprostatic tissues in seven patients with clinically organ-confined prostate cancer who were undergoing non-nerve-sparing retropubic radical prostatectomy. Images of periprostatic tissues from resected prostatectomy specimens were also obtained using the linear photoacoustic probe, and the consistency of the microvessel distribution and co-existence of nerve fibers was examined by double immunostaining of paraffin-embedded sections with anti-CD31 and anti-S-100 antibodies. RESULTS: Intraoperative monitoring of periprostatic tissues with the TRUS photoacoustic probe showed substantial signals on the posterolateral surface of the prostate and clearly demonstrated the location and extent of the neurovascular bundle better than does TRUS alone. Photoacoustic images of the periprostatic tissues in resected specimens also showed substantial signals that were especially strong on the posterolateral surface of the prostate. Nerve fibers were closely co-localized with periprostatic microvessels and the pattern of their distribution was consistent with that of PAI signals. CONCLUSIONS: The intraoperative photoacoustic imaging located the microvascular complex in the neurovascular bundle. Moreover, the neurovascular bundle was easier to identify by PAI than by TRUS alone, suggesting that PAI could be helpful in nerve-sparing radical prostatectomy.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akio", "last_name": "Horiguchi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Tsujita", "name": null }, { "creator_type": "author", "first_name": "Kaku", "last_name": "Irisawa", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shinchi", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Shinmoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/pros.23122" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26493623" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Computer Systems", "descriptor_ui": "D003199", "major_topic": true }, { "descriptor": "Diagnostic Imaging", "descriptor_ui": "D003952", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intraoperative Neurophysiological Monitoring", "descriptor_ui": "D064795", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Photoacoustic Techniques", "descriptor_ui": "D061088", "major_topic": false }, { "descriptor": "Pilot Projects", "descriptor_ui": "D010865", "major_topic": false }, { "descriptor": "Prostatectomy", "descriptor_ui": "D011468", "major_topic": false }, { "descriptor": "Prostatic Neoplasms", "descriptor_ui": "D011471", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Feb 15", "date_precision": "day", "issue": "3", "normalized_date": "2016-02-15", "pages": "307-315", "proceedings_title": null, "publisher": "", "title": "The Prostate", "volume": "76", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "A pilot study of photoacoustic imaging system for improved real-time visualization of neurovascular bundle during radical prostatectomy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Angiotensin II (AII) type 2 receptor (AT2R) negatively regulates type 1 receptor (AT1R) signaling. However, the precise molecular mechanism of AT2R-mediated AT1R inhibition remains poorly understood. Here, we characterized the local and functional interaction of AT2R with AT1R. AT2R colocalized and formed a complex with AT1R at the plasma membrane, even in the absence of AII. Upon AII stimulation, the spatial arrangement of the complex was modulated, as confirmed by Forster resonance energy transfer (FRET) analysis, followed by AT2R internalization along with AT1R. AT2R internalization was specifically observed only in the presence of AT1R; AT2R alone could not be internalized. The AT1R-specific inhibitor losartan completely inhibited both the conformational change and the internalization of AT2R with AT1R, whereas the AT2R-specific inhibitor PD123319 partially hindered these phenomena, demonstrating that the activation of both receptors was indispensable for these effects. In addition, treatment with the protein kinase C (PKC) inhibitors inhibited the ligand-dependent accumulation of AT2R but not that of AT1R in the endosomes. A mutation in the putative phosphorylation sites of AT2R also abrogated the co-internalization of ATR2 with AT1R and the inhibitory effect of ATR2 on AT1R. These data suggest that AT2R inhibits ligand-induced AT1R signaling through the PKC-dependent pathway.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takayuki", "last_name": "Inuzuka", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Aya O.", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Kosui", "last_name": "Horiuchi", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Nishide", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Nanbo", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep21613" }, "pmcid": { "normalized": "PMC4746669" }, "pmid": { "normalized": "26857745" } }, "mesh": [ { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Endosomes", "descriptor_ui": "D011992", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Protein Kinase C", "descriptor_ui": "D011493", "major_topic": false }, { "descriptor": "Receptor, Angiotensin, Type 1", "descriptor_ui": "D044140", "major_topic": false }, { "descriptor": "Receptor, Angiotensin, Type 2", "descriptor_ui": "D044139", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Feb 9", "date_precision": "day", "issue": "", "normalized_date": "2016-02-09", "pages": "21613", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Attenuation of ligand-induced activation of angiotensin II type 1 receptor signaling by the type 2 receptor via protein kinase C.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Temperature-responsive polymers incorporating molecular-recognition sites were developed as stationary phases for high-performance liquid chromatography (HPLC). The grafted stationary phases consisted of functional copolymers composed of N-isopropylacrylamide (NIPAAm) and N-acryloyl aromatic amino acid methyl esters, i.e., phenylalanine and tryptophan methyl esters (Phe-OMe and Trp-OMe). Three novel temperature-responsive polymers, P(NIPAAm-co-Phe-OMe5), P(NIPAAm-co-Phe-OMe10), and P(NIPAAm-co-Trp-OMe5), were synthesized. These copolymers exhibited a reversible hydrophilic/hydrophobic phase transition at their lower critical solution temperatures (LCSTs). The polymers were grafted onto aminopropyl silica using an activated ester-amine coupling method, and were packed into a stainless steel column, which was connected to an HPLC system. Temperature-responsive chromatography was conducted using water as the sole mobile phase. More hydrophobic analytes were retained longer, and the retention times of aromatic steroids and aromatic amino acids were dramatically increased. This indicated that pi-pi interactions occurred between the phenyl or indole moieties of phenylalanine or tryptophan, respectively, and the aromatic compounds. Furthermore, the retention times of compounds with hydrogen bond acceptors were higher with P(NIPAAm-co-Trp-OMe5), which contained indole as a hydrogen bond donor, than with P(NIPAAm-co-Phe-OMe5). This indicated that hydrogen bonding occurred between the stationary phase and the analytes. These results indicate that hydrophobic, pi-pi, and hydrogen bonding interactions all affected the separation mode of the temperature-responsive chromatography, and led to selective separation with molecular recognition. Both temperature-response and molecular recognition characteristics are present in the proposed separation system that utilizes a temperature-responsive polymer bearing aromatic amino acid derivatives.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kanazashi", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Ayano", "name": null }, { "creator_type": "author", "first_name": "Teruo", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Hideko", "last_name": "Kanazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c5an01996f" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26646169" } }, "mesh": [ { "descriptor": "Acrylic Resins", "descriptor_ui": "D000180", "major_topic": false }, { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Chromatography, High Pressure Liquid", "descriptor_ui": "D002851", "major_topic": false }, { "descriptor": "Estradiol", "descriptor_ui": "D004958", "major_topic": false }, { "descriptor": "Estriol", "descriptor_ui": "D004964", "major_topic": false }, { "descriptor": "Fluocinonide", "descriptor_ui": "D005447", "major_topic": false }, { "descriptor": "Hydrogen Bonding", "descriptor_ui": "D006860", "major_topic": false }, { "descriptor": "Hydrophobic and Hydrophilic Interactions", "descriptor_ui": "D057927", "major_topic": false }, { "descriptor": "Naphthalenes", "descriptor_ui": "D009281", "major_topic": false }, { "descriptor": "Nitro Compounds", "descriptor_ui": "D009574", "major_topic": false }, { "descriptor": "Phase Transition", "descriptor_ui": "D044367", "major_topic": false }, { "descriptor": "Phenylalanine", "descriptor_ui": "D010649", "major_topic": false }, { "descriptor": "Silicon Dioxide", "descriptor_ui": "D012822", "major_topic": false }, { "descriptor": "Testosterone", "descriptor_ui": "D013739", "major_topic": false }, { "descriptor": "Tryptophan", "descriptor_ui": "D014364", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Feb 7", "date_precision": "day", "issue": "3", "normalized_date": "2016-02-07", "pages": "910-917", "proceedings_title": null, "publisher": "", "title": "The Analyst", "volume": "141", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Temperature-responsive molecular recognition chromatography using phenylalanine and tryptophan derived polymer modified silica beads.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular trafficking of receptor proteins is essential for neurons to detect various extracellular factors during the formation and refinement of neural circuits. However, the precise mechanisms underlying the trafficking of neurotrophin receptors to synapses remain elusive. Here, we demonstrate that a brain-enriched sorting nexin, ARHGAP33, is a new type of regulator for the intracellular trafficking of TrkB, a high-affinity receptor for brain-derived neurotrophic factor. ARHGAP33 knockout (KO) mice exhibit reduced expression of synaptic TrkB, impaired spine development and neuropsychiatric disorder-related behavioural abnormalities. These deficits are rescued by specific pharmacological enhancement of TrkB signalling in ARHGAP33 KO mice. Mechanistically, ARHGAP33 interacts with SORT1 to cooperatively regulate TrkB trafficking. Human ARHGAP33 is associated with brain phenotypes and reduced SORT1 expression is found in patients with schizophrenia. We propose that ARHGAP33/SORT1-mediated TrkB trafficking is essential for synapse development and that the dysfunction of this mechanism may be a new molecular pathology of neuropsychiatric disorders.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Sakoori", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugaya", "name": null }, { "creator_type": "author", "first_name": "Asami", "last_name": "Tanimura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hashimotodani", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Ohi", "name": null }, { "creator_type": "author", "first_name": "Hidenaga", "last_name": "Yamamori", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Umeda-Yano", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kiyama", "name": null }, { "creator_type": "author", "first_name": "Kohtarou", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Kazumasa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Shusuke", "last_name": "Numata", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Ohnuma", "name": null }, { "creator_type": "author", "first_name": "Nakao", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Manabe", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms10594" }, "pmcid": { "normalized": "PMC4742909" }, "pmid": { "normalized": "26839058" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Vesicular Transport", "descriptor_ui": "D033942", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": true }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "GTPase-Activating Proteins", "descriptor_ui": "D020690", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "Receptor, trkB", "descriptor_ui": "D020813", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Schizophrenia", "descriptor_ui": "D012559", "major_topic": false }, { "descriptor": "Sortilin", "descriptor_ui": "D000099183", "major_topic": false }, { "descriptor": "Sorting Nexins", "descriptor_ui": "D058305", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Feb 3", "date_precision": "day", "issue": "", "normalized_date": "2016-02-03", "pages": "10594", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Emerging roles of ARHGAP33 in intracellular trafficking of TrkB and pathophysiology of neuropsychiatric disorders.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epithelial cell plasticity is controlled by extracellular cues, but the underlying mechanisms remain to be fully understood. Epidermal growth factor (EGF) and amphiregulin (AREG) are high- and low-affinity ligands for EGF receptor (EGFR), respectively. EGFR signaling is known to promote epithelial-mesenchymal transition (EMT) by the activation of ERK and the induction of an EMT transcription factor, ZEB1. Here, we demonstrate that ligand-switching between EGF and AREG at equivalent molarity reversibly interconverts epithelial and mesenchymal-like states of EGFR signal-dependent mammary epithelial cells. The EGF- and AREG-cultured cells also differ in their epithelial characteristics, including the expression of cell surface markers, the mode of migration and the ability for acinus-formation. The ligand-switching between EGF and AREG temporally alters strength of the shared EGFR-ERK signaling. This alteration inverts relative expression levels of ZEB1 and its antagonizing microRNAs, miR-205 and miR-200c, those are critical determinants of the epithelial phenotype. Further, AREG-induced EGFR accumulation on the plasma membrane compensates for the weak association between AREG and EGFR. The EGFR dynamics enables AREG to support proliferation as efficiently as EGF at equivalent molarity and to maintain epithelial characteristics. Our findings reveal a role of EGFR ligands-generated signal strength in the regulation of mammary epithelial cell plasticity.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Hisayo", "last_name": "Nishida-Fukuda", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Nanba", "name": null }, { "creator_type": "author", "first_name": "Koh-ichi", "last_name": "Nakashiro", "name": null }, { "creator_type": "author", "first_name": "Hironao", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Higashiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep20209" }, "pmcid": { "normalized": "PMC4735799" }, "pmid": { "normalized": "26831618" } }, "mesh": [ { "descriptor": "Amphiregulin", "descriptor_ui": "D066258", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Epidermal Growth Factor", "descriptor_ui": "D004815", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Epithelial-Mesenchymal Transition", "descriptor_ui": "D058750", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": true }, { "descriptor": "Mammary Glands, Human", "descriptor_ui": "D042361", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Feb 2", "date_precision": "day", "issue": "", "normalized_date": "2016-02-02", "pages": "20209", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Reversible interconversion and maintenance of mammary epithelial cell characteristics by the ligand-regulated EGFR system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Normal epithelial cells have an ability to sense and actively eliminate neighboring transformed cells, a process called epithelial defense against cancer (EDAC). Exogenous S1P plays a crucial role in EDAC; the S1P–S1PR2 pathway regulates Rho–Rho kinase–filamin in the surrounding normal cells, promoting apical extrusion of RasV12-transformed cells from epithelia.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sayaka", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Yako", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Mihoko", "last_name": "Kajita", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kameyama", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kon", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Kihara", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1091/mbc.e15-03-0161" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26631556" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Filamins", "descriptor_ui": "D064448", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lysophospholipids", "descriptor_ui": "D008246", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "Mutation, Missense", "descriptor_ui": "D020125", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": false }, { "descriptor": "Pyrazoles", "descriptor_ui": "D011720", "major_topic": false }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false }, { "descriptor": "Receptors, Lysosphingolipid", "descriptor_ui": "D049349", "major_topic": false }, { "descriptor": "rho-Associated Kinases", "descriptor_ui": "D054460", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sphingosine", "descriptor_ui": "D013110", "major_topic": false }, { "descriptor": "Sphingosine-1-Phosphate Receptors", "descriptor_ui": "D000081025", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Feb 01", "date_precision": "day", "issue": "3", "normalized_date": "2016-02-01", "pages": "491-499", "proceedings_title": null, "publisher": "", "title": "Molecular Biology of the Cell", "volume": "27", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "A role of the sphingosine-1-phosphate (S1P)–S1P receptor 2 pathway in epithelial defense against cancer (EDAC).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Naive T cells differentiate into various effector T cells, including CD4(+) helper T cell subsets and CD8(+) cytotoxic T cells (CTL). Although cytotoxic CD4(+) T cells (CD4 +: CTL) also develop from naive T cells, the mechanism of development is elusive. We found that a small fraction of CD4(+) T cells that express class I-restricted T cell-associated molecule (CRTAM) upon activation possesses the characteristics of both CD4(+) and CD8(+) T cells. CRTAM(+) CD4(+) T cells secrete IFN-gamma, express CTL-related genes, such as eomesodermin (Eomes), Granzyme B, and perforin, after cultivation, and exhibit cytotoxic function, suggesting that CRTAM(+) T cells are the precursor of CD4(+)CTL. Indeed, ectopic expression of CRTAM in T cells induced the production of IFN-gamma, expression of CTL-related genes, and cytotoxic activity. The induction of CD4(+)CTL and IFN-gamma production requires CRTAM-mediated intracellular signaling. CRTAM(+) T cells traffic to mucosal tissues and inflammatory sites and developed into CD4(+)CTL, which are involved in mediating protection against infection as well as inducing inflammatory response, depending on the circumstances, through IFN-gamma secretion and cytotoxic activity. These results reveal that CRTAM is critical to instruct the differentiation of CD4(+)CTL through the induction of Eomes and CTL-related gene.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Arata", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Mohamed El Sherif Gadelhaq", "last_name": "Badr", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Miyauchi", "name": null }, { "creator_type": "author", "first_name": "Chitose", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Onishi", "name": null }, { "creator_type": "author", "first_name": "Zijin", "last_name": "Guo", "name": null }, { "creator_type": "author", "first_name": "Yoshiteru", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ike", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Takumi", "name": null }, { "creator_type": "author", "first_name": "Noriko M.", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1084/jem.20150519" }, "pmcid": { "normalized": "PMC4710199" }, "pmid": { "normalized": "26694968" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CD4-Positive T-Lymphocytes", "descriptor_ui": "D015496", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Colitis", "descriptor_ui": "D003092", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoglobulins", "descriptor_ui": "D007136", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Interferon-gamma", "descriptor_ui": "D007371", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Mucous Membrane", "descriptor_ui": "D009092", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "T-Box Domain Proteins", "descriptor_ui": "D020825", "major_topic": false }, { "descriptor": "T-Lymphocyte Subsets", "descriptor_ui": "D016176", "major_topic": false }, { "descriptor": "T-Lymphocytes, Cytotoxic", "descriptor_ui": "D013602", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jan 11", "date_precision": "day", "issue": "1", "normalized_date": "2016-01-11", "pages": "123-138", "proceedings_title": null, "publisher": "", "title": "The Journal of experimental medicine", "volume": "213", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "CRTAM determines the CD4+ cytotoxic T lymphocyte lineage.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "UNLABELLED: To investigate the molecular mechanism(s) by which herpes simplex virus 1 (HSV-1) regulatory protein ICP0 promotes viral gene expression and replication, we screened cells overexpressing ICP0 for ICP0-binding host cell proteins. Tandem affinity purification of transiently expressed ICP0 coupled with mass spectrometry-based proteomics technology and subsequent analyses showed that ICP0 interacted with cell protein RanBP10, a known transcriptional coactivator, in HSV-1-infected cells. Knockdown of RanBP10 in infected HEp-2 cells resulted in a phenotype similar to that observed with the ICP0-null mutation, including reduction in viral replication and in the accumulation of viral immediate early (ICP27), early (ICP8), and late (VP16) mRNAs and proteins. In addition, RanBP10 knockdown or the ICP0-null mutation increased the level of histone H3 association with the promoters of these viral genes, which is known to repress transcription. These effects observed in wild-type HSV-1-infected HEp-2 RanBP10 knockdown cells or those observed in ICP0-null mutant virus-infected control HEp-2 cells were remarkably increased in ICP0-null mutant virus-infected HEp-2 RanBP10 knockdown cells. Our results suggested that ICP0 and RanBP10 redundantly and synergistically promoted viral gene expression by regulating chromatin remodeling of the HSV-1 genome for efficient viral replication. IMPORTANCE: Upon entry of herpesviruses into a cell, viral gene expression is restricted by heterochromatinization of the viral genome. Therefore, HSV-1 has evolved multiple mechanisms to counteract this epigenetic silencing for efficient viral gene expression and replication. HSV-1 ICP0 is one of the viral proteins involved in counteracting epigenetic silencing. Here, we identified RanBP10 as a novel cellular ICP0-binding protein and showed that RanBP10 and ICP0 appeared to act synergistically to promote viral gene expression and replication by modulating viral chromatin remodeling. Our results provide insight into the mechanisms by which HSV-1 regulates viral chromatin remodeling for efficient viral gene expression and replication.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuka", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kozuka-Hata", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.03043-15" }, "pmcid": { "normalized": "PMC4810668" }, "pmid": { "normalized": "26739050" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Viral", "descriptor_ui": "D015967", "major_topic": true }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Guanine Nucleotide Exchange Factors", "descriptor_ui": "D020662", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Host-Pathogen Interactions", "descriptor_ui": "D054884", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immediate-Early Proteins", "descriptor_ui": "D017874", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Microtubule-Associated Proteins", "descriptor_ui": "D008869", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Interaction Mapping", "descriptor_ui": "D025941", "major_topic": false }, { "descriptor": "Proteome", "descriptor_ui": "D020543", "major_topic": false }, { "descriptor": "Ubiquitin-Protein Ligases", "descriptor_ui": "D044767", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016 Jan 6", "date_precision": "day", "issue": "6", "normalized_date": "2016-01-06", "pages": "3173-3186", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "90", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Cellular Transcriptional Coactivator RanBP10 and Herpes Simplex Virus 1 ICP0 Interact and Synergistically Promote Viral Gene Expression and Replication.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Apoptosis plays a pivotal role in development and tissue homeostasis in multicellular organisms. Dysfunction of apoptosis is involved in many fatal diseases such as cancer. Visualization of apoptosis in living animals is necessary to understand the mechanism of apoptosis-related diseases. Here, we describe a genetically encoded fluorescent probe for imaging apoptosis in living multicellular organisms, based on spontaneous complementation of two fragments of a green fluorescent protein (GFP) variant (GFP OPT). The probe is designed for detection of mitochondria-mediated apoptosis during which a mitochondrial protein of Smac is released into cytosol. The Smac is connected with a carboxy-terminal fragment of GFP OPT (GFP11), whereas the remainder of GFP OPT (GFP(1-10)) is located in the cytosol. Under an apoptotic condition, the Smac is released from mitochondria into cytosol, allowing complementation of the GFP-OPT fragments and the emission of fluorescence. Live-cell imaging demonstrates that the probe enables detection of apoptosis in living cells with a high signal-to-background ratio. We applied the probe to living zebrafish, in which apoptotic cells were visualized with fluorescence. The technique provides a useful tool for the study of apoptosis in living animals, facilitating elucidation of the mechanisms of apoptosis-related diseases.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nasu", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Asaoka", "name": null }, { "creator_type": "author", "first_name": "Misako", "last_name": "Namae", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nishina", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.5b03367" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26597767" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Genetic Complementation Test", "descriptor_ui": "D005816", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Mitochondrial Proteins", "descriptor_ui": "D024101", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jan 5", "date_precision": "day", "issue": "1", "normalized_date": "2016-01-05", "pages": "838-844", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "88", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetically Encoded Fluorescent Probe for Imaging Apoptosis in Vivo with Spontaneous GFP Complementation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Claudin protein family members, of which there are at least 27 in humans and mice, polymerize to form tight junctions (TJs) between epithelial cells, in a tissue- and developmental stage-specific manner. Claudins have a paracellular barrier function. In addition, certain claudins function as paracellular channels for small ions and/or solutes by forming selective pores at the TJs, although the specific claudins involved and their functional mechanisms are still in question. Here we show for the first time that claudin-21, which is more highly expressed in the embryonic than the postnatal stages, acts as a paracellular channel for small cations, such as Na(+), similar to the typical channel-type claudins claudin-2 and -15. Claudin-21 also allows the paracellular passage of larger solutes. Our findings suggest that claudin-21-based TJs allow the passage of small and larger solutes by both paracellular channel-based and some additional mechanisms.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroka", "last_name": "Kashihara", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Kazutoshi", "last_name": "Tani", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Fujiyoshi", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Mineta", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Tsukita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/mcb.00758-15" }, "pmcid": { "normalized": "PMC4810463" }, "pmid": { "normalized": "26729464" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cations, Monovalent", "descriptor_ui": "D002414", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Claudins", "descriptor_ui": "D057167", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Sequence Alignment", "descriptor_ui": "D016415", "major_topic": false }, { "descriptor": "Sodium", "descriptor_ui": "D012964", "major_topic": false }, { "descriptor": "Tight Junctions", "descriptor_ui": "D019108", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jan 4", "date_precision": "day", "issue": "6", "normalized_date": "2016-01-04", "pages": "954-964", "proceedings_title": null, "publisher": "", "title": "Molecular and cellular biology", "volume": "36", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Claudin-21 Has a Paracellular Channel Role at Tight Junctions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Us3 protein kinases encoded by herpes simplex virus 1 (HSV-1) and 2 (HSV-2) play important roles in viral replication and pathogenicity. To investigate type-specific differences between HSV-1 Us3 and HSV-2 Us3 in cells infected by viruses with all the same viral gene products except for their Us3 kinases, we constructed and characterized a recombinant HSV-1 in which its Us3 gene was replaced with the HSV-2 Us3 gene. Replacement of HSV-1 Us3 with HSV-2 Us3 had no apparent effect on viral growth in cell cultures or on the range of proteins phosphorylated by Us3. HSV-2 Us3 efficiently compensated for HSV-1 Us3 functions, including blocking apoptosis, controlling infected cell morphology, and downregulating cell surface expression of viral envelope glycoprotein B. In contrast, replacement of HSV-1 Us3 by HSV-2 Us3 changed the phosphorylation status of UL31 and UL34, which are critical viral regulators of nuclear egress. It also caused aberrant localization of these viral proteins and aberrant accumulation of primary enveloped virions in membranous vesicle structures adjacent to the nuclear membrane, and it reduced viral cell-cell spread in cell cultures and pathogenesis in mice. These results clearly demonstrated biological differences between HSV-1 Us3 and HSV-2 Us3, especially in regulation of viral nuclear egress and phosphorylation of viral regulators critical for this process. Our study also suggested that the regulatory role(s) of HSV-1 Us3, which was not carried out by HSV-2 Us3, was important for HSV-1 cell-cell spread and pathogenesis in vivo. IMPORTANCE: A previous study comparing the phenotypes of HSV-1 and HSV-2 suggested that the HSV-2 Us3 kinase lacked some of the functions of HSV-1 Us3 kinase. The difference between HSV-1 and HSV-2 Us3 kinases appeared to be due to the fact that some Us3 phosphorylation sites in HSV-1 proteins are not conserved in the corresponding HSV-2 proteins. Therefore, we generated recombinant HSV-1 strains YK781 (Us3-chimera) with HSV-2 Us3 and its repaired virus YK783 (Us3-repair) with HSV-1 Us3, to compare the activities of HSV-1 Us3 and HSV-2 Us3 in cells infected by viruses with the same HSV-1 gene products except for their Us3 kinases. We report here that some processes in viral nuclear egress and pathogenesis in vivo that have been attributed to HSV-1 Us3 could not be carried out by HSV-2 Us3. Therefore, our study clarified the biological differences between HSV-1 Us3 and HSV-2 Us3, which may be relevant to viral pathogenesis in vivo.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sagara", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.02376-15" }, "pmcid": { "normalized": "PMC4702531" }, "pmid": { "normalized": "26491159" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Genetic Complementation Test", "descriptor_ui": "D005816", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Host-Pathogen Interactions", "descriptor_ui": "D054884", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Recombination, Genetic", "descriptor_ui": "D011995", "major_topic": true }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virus Release", "descriptor_ui": "D057074", "major_topic": true }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016 Jan 1", "date_precision": "day", "issue": "1", "normalized_date": "2016-01-01", "pages": "457-473", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "90", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Characterization of a Herpes Simplex Virus 1 (HSV-1) Chimera in Which the Us3 Protein Kinase Gene Is Replaced with the HSV-2 Us3 Gene.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A sexually dimorphic spinal gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord, which projects to the lower spinal centers, controls erection and ejaculation in rats. However, little is known about the postnatal development of this system. In this study, we therefore examined the postnatal development of the male-dominant spinal GRP system and its sexual differentiation in rats using immunohistochemistry. Our results show that male-dominant expression of GRP is prominent from the onset of puberty and that sexually dimorphism persists into adulthood. These results suggest that androgen surge during male puberty plays an important role in the development and maintenance of the male-specific GRP function in the rat spinal cord.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Nao", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Oti", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Takanami", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.2183/pjab.92.69" }, "pmcid": { "normalized": "PMC4906813" }, "pmid": { "normalized": "26860455" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ejaculation", "descriptor_ui": "D004542", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gastrin-Releasing Peptide", "descriptor_ui": "D019886", "major_topic": false }, { "descriptor": "Lumbosacral Region", "descriptor_ui": "D008161", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Penile Erection", "descriptor_ui": "D010410", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "2", "normalized_date": "2016", "pages": "69-75", "proceedings_title": null, "publisher": "", "title": "Proceedings of the Japan Academy. Series B, Physical and biological sciences", "volume": "92", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Postnatal development of the gastrin-releasing peptide system in the lumbosacral spinal cord controlling male reproductive function in rats.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Identification of immunoglobulin genes in hybridomas is essential for producing antibodies for research and clinical applications. A couple of methods such as RACE and degenerative PCR have been developed for determination of the Igh and Igl/Igk coding sequences (CDSs) but it has been difficult to process a number of hybridomas both with accuracy and rapidness. Here, we propose a new strategy for antibody sequence determination by mRNA-seq of hybridomas. We demonstrated that hybridomas highly expressed the Igh and Igl/Igk genes and that de novo transcriptome assembly using mRNA-seq data enabled identification of the CDS of both Igh and Igl/Igk accurately. Furthermore, we estimated that only 30,000 sequenced reads are required to identify immunoglobulin sequences from four different hybridoma clones. Thus, our approach would facilitate determining variable CDSs drastically.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Kuniyoshi", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Masayasu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Semba", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0165473" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27788226" } }, "mesh": [ { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Genes, Immunoglobulin", "descriptor_ui": "D005803", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hybridomas", "descriptor_ui": "D006825", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "10", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "11", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of Immunoglobulin Gene Sequences from a Small Read Number of mRNA-Seq Using Hybridomas.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Most animals possess multiple opsins which sense light for visual and non-visual functions. Here, we show spectral characteristics of non-visual opsins, vertebrate Opn3s, which are widely distributed among vertebrates. We successfully expressed zebrafish Opn3 in mammalian cultured cells and measured its absorption spectrum spectroscopically. When incubated with 11-cis retinal, zebrafish Opn3 formed a blue-sensitive photopigment with an absorption maximum around 465 nm. The Opn3 converts to an all-trans retinal-bearing photoproduct with an absorption spectrum similar to the dark state following brief blue-light irradiation. The photoproduct experienced a remarkable blue-shift, with changes in position of the isosbestic point, during further irradiation. We then used a cAMP-dependent luciferase reporter assay to investigate light-dependent cAMP responses in cultured cells expressing zebrafish, pufferfish, anole and chicken Opn3. The wild type opsins did not produce responses, but cells expressing chimera mutants (WT Opn3s in which the third intracellular loops were replaced with the third intracellular loop of a Gs-coupled jellyfish opsin) displayed light-dependent changes in cAMP. The results suggest that Opn3 is capable of activating G protein(s) in a light-dependent manner. Finally, we used this assay to measure the relative wavelength-dependent response of cells expressing Opn3 chimeras to multiple quantally-matched stimuli. The inferred spectral sensitivity curve of zebrafish Opn3 accurately matched the measured absorption spectrum. We were unable to estimate the spectral sensitivity curve of mouse or anole Opn3, but, like zebrafish Opn3, the chicken and pufferfish Opn3-JiL3 chimeras also formed blue-sensitive pigments. These findings suggest that vertebrate Opn3s may form blue-sensitive G protein-coupled pigments. Further, we suggest that the method described here, combining a cAMP-dependent luciferase reporter assay with chimeric opsins possessing the third intracellular loop of jellyfish opsin, is a versatile approach for estimating absorption spectra of opsins with unknown signaling cascades or for which absorption spectra are difficult to obtain.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sugihara", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Benjamin", "last_name": "Mason", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0161215" }, "pmcid": { "normalized": "PMC4988782" }, "pmid": { "normalized": "27532629" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chickens", "descriptor_ui": "D002645", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Fish Proteins", "descriptor_ui": "D029941", "major_topic": false }, { "descriptor": "GTP-Binding Proteins", "descriptor_ui": "D019204", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Retinaldehyde", "descriptor_ui": "D012172", "major_topic": false }, { "descriptor": "Rod Opsins", "descriptor_ui": "D017299", "major_topic": false }, { "descriptor": "Scyphozoa", "descriptor_ui": "D037401", "major_topic": false }, { "descriptor": "Spectrophotometry", "descriptor_ui": "D013053", "major_topic": false }, { "descriptor": "Tetraodontiformes", "descriptor_ui": "D023721", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false }, { "descriptor": "Zebrafish Proteins", "descriptor_ui": "D029961", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "8", "normalized_date": "2016", "pages": "e0161215", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "11", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Absorption Characteristics of Vertebrate Non-Visual Opsin, Opn3.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Structured illumination microscopy (SIM) is a wide-field technique in fluorescence microscopy that provides fast data acquisition and two-fold resolution improvement beyond the Abbe limit. We observed a further resolution improvement using the nonlinear emission response of a fluorescent protein. We demonstrated a two-beam nonlinear structured illumination microscope by introducing only a minor change into the system used for linear SIM (LSIM). To achieve the required nonlinear dependence in nonlinear SIM (NL-SIM) we exploited the photoswitching of the recently introduced fluorophore Kohinoor. It is particularly suitable due to its positive contrast photoswitching characteristics. Contrary to other reversibly photoswitchable fluorescent proteins which only have high photostability in living cells, Kohinoor additionally showed little degradation in fixed cells over many switching cycles.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hui-Wen", "last_name": "Lu-Walther", "name": null }, { "creator_type": "author", "first_name": "Wenya", "last_name": "Hou", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Kielhorn", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Michael M.", "last_name": "Kessels", "name": null }, { "creator_type": "author", "first_name": "Britta", "last_name": "Qualmann", "name": null }, { "creator_type": "author", "first_name": "Rainer", "last_name": "Heintzmann", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0165148" }, "pmcid": { "normalized": "PMC5082623" }, "pmid": { "normalized": "27783656" } }, "mesh": [ { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": true }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Nonlinear Dynamics", "descriptor_ui": "D017711", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "10", "normalized_date": "2016", "pages": "e0165148", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "11", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Nonlinear Structured Illumination Using a Fluorescent Protein Activating at the Readout Wavelength.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Disease-associated alterations of enzymatic functions are potentially useful as disease biomarkers, and here we show that an enzymomics (omics of active enzymes) approach, in which enzymatic activities are screened with panels of substrates, can be an effective way to identify such alterations. In the present study, we used a panel of fluorogenic substrates to search for altered enzyme activities in bronchoalveolar lavage fluid (BALF) from a mouse model of lung inflammation. We found that acylamino acid releasing enzyme (APEH) activity was highly elevated, apparently reflecting the increased population of immune cells in the inflamed lung.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1248/cpb.c16-00540" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27803464" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bronchoalveolar Lavage Fluid", "descriptor_ui": "D001992", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Fluorometry", "descriptor_ui": "D005470", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Peptide Hydrolases", "descriptor_ui": "D010447", "major_topic": false }, { "descriptor": "Pneumonia", "descriptor_ui": "D011014", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "11", "normalized_date": "2016", "pages": "1533-1538", "proceedings_title": null, "publisher": "", "title": "Chemical & pharmaceutical bulletin", "volume": "64", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of Lung Inflammation-Related Elevation of Acylamino Acid Releasing Enzyme (APEH) Activity Using an Enzymomics Approach.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cellular stress responses require exquisite coordination between intracellular signaling molecules to integrate multiple stimuli and actuate specific cellular behaviors. Deciphering the web of complex interactions underlying stress responses is a key challenge in understanding robust biological systems and has the potential to lead to the discovery of targeted therapeutics for diseases triggered by dysregulation of stress response pathways. We constructed large-scale molecular interaction maps of six major stress response pathways in Saccharomyces cerevisiae (baker's or budding yeast). Biological findings from over 900 publications were converted into standardized graphical formats and integrated into a common framework. The maps are posted at http://www.yeast-maps.org/yeast-stress-response/ for browse and curation by the research community. On the basis of these maps, we undertook systematic analyses to unravel the underlying architecture of the networks. A series of network analyses revealed that yeast stress response pathways are organized in bow-tie structures, which have been proposed as universal sub-systems for robust biological regulation. Furthermore, we demonstrated a potential role for complexes in stabilizing the conserved core molecules of bow-tie structures. Specifically, complex-mediated reversible reactions, identified by network motif analyses, appeared to have an important role in buffering the concentration and activity of these core molecules. We propose complex-mediated reactions as a key mechanism mediating robust regulation of the yeast stress response. Thus, our comprehensive molecular interaction maps provide not only an integrated knowledge base, but also a platform for systematic network analyses to elucidate the underlying architecture in complex biological systems.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Vivek K.", "last_name": "Singh", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Hase", "name": null }, { "creator_type": "author", "first_name": "Priya", "last_name": "Kulkarni", "name": null }, { "creator_type": "author", "first_name": "Kenaz", "last_name": "Siddiqui", "name": null }, { "creator_type": "author", "first_name": "Janhavi", "last_name": "Kodilkar", "name": null }, { "creator_type": "author", "first_name": "Nitisha", "last_name": "Danve", "name": null }, { "creator_type": "author", "first_name": "Indhupriya", "last_name": "Subramanian", "name": null }, { "creator_type": "author", "first_name": "Manami", "last_name": "Katoh", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shimizu-Yoshida", "name": null }, { "creator_type": "author", "first_name": "Samik", "last_name": "Ghosh", "name": null }, { "creator_type": "author", "first_name": "Abhay", "last_name": "Jere", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kitano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/npjsba.2015.18" }, "pmcid": { "normalized": "PMC5516916" }, "pmid": { "normalized": "28725465" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "15018", "proceedings_title": null, "publisher": "", "title": "NPJ systems biology and applications", "volume": "2", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Network analyses based on comprehensive molecular interaction maps reveal robust control structures in yeast stress response pathways.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: In rats, a sexually dimorphic spinal gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord projects to spinal centers that control erection and ejaculation. This system controls the sexual function of adult males in an androgen-dependent manner. In the present study, we assessed the influence of androgen exposure on the spinal GRP system during a critical period of the development of sexual dimorphism. METHODS: Immunohistochemistry was used to determine if the development of the spinal GRP system is regulated by the perinatal androgen surge. We first analyzed the responses of neonates administered with anti-androgen flutamide. To remove endogenous androgens, rats were castrated at birth. Further, neonatal females were administered androgens during a critical period to evaluate the development of the male-specific spinal GRP system. RESULTS: Treatment of neonates with flutamide on postnatal days 0 and 1 attenuated the spinal GRP system during adulthood. Castrating male rats at birth resulted in a decrease in the number of GRP neurons and the intensity of neuronal GRP in the spinal cord during adulthood despite testosterone supplementation during puberty. This effect was prevented if the rats were treated with testosterone propionate immediately after castration. Moreover, treating female rats with androgens on the day of birth and the next day, masculinized the spinal GRP system during adulthood, which resembled the masculinized phenotype of adult males and induced a hypermasculine appearance. CONCLUSIONS: The perinatal androgen surge plays a key role in masculinization of the spinal GRP system that controls male sexual behavior. Further, the present study provides potentially new approaches to treat sexual disorders of males.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Oti", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Takanami", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Tomoca", "last_name": "Edey", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13293-016-0058-x" }, "pmcid": { "normalized": "PMC4710030" }, "pmid": { "normalized": "26759714" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "4", "proceedings_title": null, "publisher": "", "title": "Biology of sex differences", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Perinatal testosterone exposure is critical for the development of the male-specific sexually dimorphic gastrin-releasing peptide system in the lumbosacral spinal cord that mediates erection and ejaculation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "MicroRNAs (miRNAs) participate in a variety of functions in the brain. Understanding the in vivo localization of miRNAs is an important step for uncovering their roles in brain function. However, the in situ detection of low-abundance miRNAs in brain tissues remains difficult and requires extensive optimization of in situ hybridization (ISH) protocols in individual laboratories. Thus, detailed information regarding experimental conditions would serve as a useful reference for researchers in this field. Here, we investigated and summarized the effects of adjusting a series of critical steps, including tissue fixation, probe accessibility and hybridization stringency, to standardize the currently used miRNA ISH procedures. As a result, we successfully detected several low-abundance miRNAs by ISH using the following experimental conditions: (1) use of fresh brain tissues, (2) digestion of brain samples with proteinase K, (3) LNA-probe hybridization at a temperature 37 degrees C below the melting temperature of the RNA, (4) performance of high-stringency wash steps using 50% formamide in 1 x standard saline citrate (SSC) buffer. RT-PCR of the punched-out tissues using TaqMan(TM) primers confirmed the ISH results. Finally, double-fluorescence ISH successfully demonstrated the colocalization of miRNAs and mRNAs. Thus, the detailed information regarding the miRNA ISH procedures used in this study may help to resolve the technical hurdles observed in the in vivo localization of miRNAs, and the elucidation of the specific roles of miRNAs.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Sora", "last_name": "Kakihara", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Hazama", "name": null }, { "creator_type": "author", "first_name": "Misaki", "last_name": "Niu", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnmol.2016.00126" }, "pmcid": { "normalized": "PMC5118840" }, "pmid": { "normalized": "27920667" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "126", "proceedings_title": null, "publisher": "", "title": "Frontiers in molecular neuroscience", "volume": "9", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Double In situ Hybridization for MicroRNAs and mRNAs in Brain Tissues.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "T cells are known to be plastic and to change their phenotype according to the cellular and biochemical milieu they are embedded in. In this study, we transposed this concept at a macroscopic level assessing whether changes in the environmental housing conditions of C57/BL6 mice would influence the phenotype and function of T cells. Our study shows that exposure to 2 weeks in an enriched environment (EE) does not impact the T cell repertoire in vivo and causes no changes in the early TCR-driven activation events of these cells. Surprisingly, however, T cells from enriched mice showed a unique T helper effector cell phenotype upon differentiation in vitro. This was featured by a significant reduction in their ability to produce IFN-γ and by an increased release of IL-10 and IL-17. Microarray analysis of these cells also revealed a unique gene fingerprint with key signaling pathways involved in autoimmunity being modulated. Together, our results provide first evidence for a specific effect of EE on T cell differentiation and its associated changes in gene expression profile. In addition, our study sheds new light on the possible mechanisms by which changes in environmental factors can significantly influence the immune response of the host and favor the resolution of the inflammatory response.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Lorenza", "last_name": "Rattazzi", "name": null }, { "creator_type": "author", "first_name": "Giuseppa", "last_name": "Piras", "name": null }, { "creator_type": "author", "first_name": "Samuel", "last_name": "Brod", "name": null }, { "creator_type": "author", "first_name": "Koval", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Fulvio", "last_name": "D'Acquisto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2016.00381" }, "pmcid": { "normalized": "PMC5042968" }, "pmid": { "normalized": "27746779" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "381", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Impact of Enriched Environment on Murine T Cell Differentiation and Gene Expression Profile.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) acts on multiple processes of glucose and energy metabolism. PACAP potentiates insulin action in adipocytes and insulin release from pancreatic beta-cells, thereby enhancing glucose tolerance. Contrary to these effects at organ levels, PACAP null mice exhibit hypersensitivity to insulin. However, this apparent discrepancy remains to be solved. We aimed to clarify the mechanism underlying the antidiabetic phenotype of PACAP null mice. Feeding with high-fat diet (HFD) impaired insulin sensitivity and glucose tolerance in wild type mice, whereas these changes were prevented in PACAP null mice. HFD also impaired insulin-induced Akt phosphorylation in the liver in wild type mice, but not in PACAP null mice. Using GeneFishing method, HFD increased the leukocyte common antigen-related (LAR) protein tyrosine phosphatase in the liver in wild type mice. Silencing of LAR restored the insulin signaling in the liver of HFD mice. Moreover, the increased LAR expression by HFD was prevented in PACAP null mice. HFD increased the expression of VPAC1 receptor (VPAC1-R), one of three PACAP receptors, in the liver of wild type mice. These data indicate that PACAP-VPAC1-R signaling induces LAR expression and insulin resistance in the liver of HFD mice. Antagonism of VPAC1-R may prevent progression of HFD-induced insulin resistance in the liver, providing a novel antidiabetic strategy.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masanori", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Boyang", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Yifei", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Yada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1155/2016/9321395" }, "pmcid": { "normalized": "PMC5156820" }, "pmid": { "normalized": "28044141" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Diet, High-Fat", "descriptor_ui": "D059305", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Hypoglycemic Agents", "descriptor_ui": "D007004", "major_topic": false }, { "descriptor": "Insulin Resistance", "descriptor_ui": "D007333", "major_topic": true }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Receptor-Like Protein Tyrosine Phosphatases, Class 2", "descriptor_ui": "D054623", "major_topic": false }, { "descriptor": "Receptors, Vasoactive Intestinal Polypeptide, Type I", "descriptor_ui": "D051238", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "9321395", "proceedings_title": null, "publisher": "", "title": "Journal of diabetes research", "volume": "2016", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "High-Fat Diet Augments VPAC1 Receptor-Mediated PACAP Action on the Liver, Inducing LAR Expression and Insulin Resistance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tumour blood vessels are gateways for distant metastasis. Recent studies have revealed that tumour endothelial cells (TECs) demonstrate distinct phenotypes from their normal counterparts. We have demonstrated that features of TECs are different depending on tumour malignancy, suggesting that TECs communicate with surrounding tumour cells. However, the contribution of TECs to metastasis has not been elucidated. Here, we show that TECs actively promote tumour metastasis through a bidirectional interaction between tumour cells and TECs. Co-implantation of TECs isolated from highly metastatic tumours accelerated lung metastases of low metastatic tumours. Biglycan, a small leucine-rich repeat proteoglycan secreted from TECs, activated tumour cell migration via nuclear factor-κB and extracellular signal–regulated kinase 1/2. Biglycan expression was upregulated by DNA demethylation in TECs. Collectively, our results demonstrate that TECs are altered in their microenvironment and, in turn, instigate tumour cells to metastasize, which is a novel mechanism for tumour metastasis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Nako", "last_name": "Maishi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Noritaka", "last_name": "Ohga", "name": null }, { "creator_type": "author", "first_name": "Jun-ichi", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Nagao-Kitamoto", "name": null }, { "creator_type": "author", "first_name": "Mohammad Towfik", "last_name": "Alam", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kawamoto", "name": null }, { "creator_type": "author", "first_name": "Nobuo", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Akinobu", "last_name": "Taketomi", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Shindoh", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Hida", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Hida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep28039" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27295191" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biglycan", "descriptor_ui": "D058578", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": true }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Melanoma", "descriptor_ui": "D008545", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false }, { "descriptor": "Neoplasm Transplantation", "descriptor_ui": "D009368", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "RAW 264.7 Cells", "descriptor_ui": "D000067996", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cellular energy production processes are composed of many Mg2+ dependent enzymatic reactions. In fact, dysregulation of Mg2+ homeostasis is involved in various cellular malfunctions and diseases. Recently, mitochondria, energy-producing organelles, have been known as major intracellular Mg2+ stores. Several biological stimuli alter mitochondrial Mg2+ concentration by intracellular redistribution. However, in living cells, whether mitochondrial Mg2+ alteration affect cellular energy metabolism remains unclear. Mg2+ transporter of mitochondrial inner membrane MRS2 is an essential component of mitochondrial Mg2+ uptake system. Here, we comprehensively analyzed intracellular Mg2+ levels and energy metabolism in Mrs2 knockdown (KD) cells using fluorescence imaging and metabolome analysis. Dysregulation of mitochondrial Mg2+ homeostasis disrupted ATP production via shift of mitochondrial energy metabolism and morphology. Moreover, Mrs2 KD sensitized cellular tolerance against cellular stress. These results indicate regulation of mitochondrial Mg2+via MRS2 critically decides cellular energy status and cell vulnerability via regulation of mitochondrial Mg2+ level in response to physiological stimuli.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryu", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep30027" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27458051" } }, "mesh": [ { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Cation Transport Proteins", "descriptor_ui": "D027682", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Physiological Phenomena", "descriptor_ui": "D002468", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Membrane Potential, Mitochondrial", "descriptor_ui": "D053078", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Mitochondrial Proteins", "descriptor_ui": "D024101", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Stress, Physiological", "descriptor_ui": "D013312", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Mitochondrial Mg2+ homeostasis decides cellular energy metabolism and vulnerability to stress.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The microvillus is a versatile organelle that serves important functions in disparate animal cell types. However, from a molecular perspective, the microvillus has been well studied in only a few, predominantly vertebrate, contexts. Little is known about how differences in microvillar structure contribute to differences in function, and how these differences evolved. We sequenced the transcriptome of the freshwater sponge, Ephydatia muelleri, and examined the expression of vertebrate microvillar gene homologs in choanocytes-the only microvilli-bearing cell type present in sponges. Sponges offer a distant phylogenetic comparison with vertebrates, and choanocytes are central to discussions about early animal evolution due to their similarity with choanoflagellates, the single-celled sister lineage of modern animals. RESULTS: We found that, from a genomic perspective, sponges have conserved homologs of most vertebrate microvillar genes, most of which are expressed in choanocytes, and many of which exhibit choanocyte-specific or choanocyte-enriched expression. Possible exceptions include the cadherins that form intermicrovillar links in the enterocyte brush border and hair cell stereocilia of vertebrates and cnidarians. No obvious orthologs of these proteins were detected in sponges, but at least four candidate cadherins were identified as choanocyte-enriched and might serve this function. In contrast to the evidence for conserved microvillar structure in sponges and vertebrates, we found that choanoflagellates and ctenophores lack homologs of many fundamental microvillar genes, suggesting that microvillar structure may diverge significantly in these lineages, warranting further study. CONCLUSIONS: The available evidence suggests that microvilli evolved early in the prehistory of modern animals and have been repurposed to serve myriad functions in different cellular contexts. Detailed understanding of the sequence by which different microvilli-bearing cell/tissue types diversified will require further study of microvillar composition and development in disparate cell types and lineages. Of particular interest are the microvilli of choanoflagellates, ctenophores, and sponges, which collectively bracket the earliest events in animal evolution.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Jesus F.", "last_name": "Pena", "name": null }, { "creator_type": "author", "first_name": "Alexandre", "last_name": "Alie", "name": null }, { "creator_type": "author", "first_name": "Daniel J.", "last_name": "Richter", "name": null }, { "creator_type": "author", "first_name": "Lingyu", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Funayama", "name": null }, { "creator_type": "author", "first_name": "Scott A.", "last_name": "Nichols", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13227-016-0050-x" }, "pmcid": { "normalized": "PMC4942974" }, "pmid": { "normalized": "27413529" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "13", "proceedings_title": null, "publisher": "", "title": "EvoDevo", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Conserved expression of vertebrate microvillar gene homologs in choanocytes of freshwater sponges.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Histone acetylation is generally associated with gene activation and chromatin decondensation. Recent mass spectrometry analysis has revealed that histone H4 lysine 20, a major methylation site, can also be acetylated. To understand the function of H4 lysine 20 acetylation (H4K20ac), we have developed a specific monoclonal antibody and performed ChIP-seq analysis using HeLa-S3 cells. H4K20ac was enriched around the transcription start sites (TSSs) of minimally expressed genes and in the gene body of expressed genes, in contrast to most histone acetylation being enriched around the TSSs of expressed genes. The distribution of H4K20ac showed little correlation with known histone modifications, including histone H3 methylations. A motif search in H4K20ac-enriched sequences, together with transcription factor binding profiles based on ENCODE ChIP-seq data, revealed that most transcription activators are excluded from H4K20ac-enriched genes and a transcription repressor NRSF/REST co-localized with H4K20ac. These results suggest that H4K20ac is a unique acetylation mark associated with gene repression.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jun-Ya", "last_name": "Kaimori", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Hayashi-Takanaka", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Naotsugu", "last_name": "Ichimaru", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Umehara", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Ikura", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Chikashi", "last_name": "Obuse", "name": null }, { "creator_type": "author", "first_name": "Naohito", "last_name": "Nozaki", "name": null }, { "creator_type": "author", "first_name": "Shiro", "last_name": "Takahara", "name": null }, { "creator_type": "author", "first_name": "Toshifumi", "last_name": "Takao", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Isaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep24318" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27064113" } }, "mesh": [ { "descriptor": "Acetylation", "descriptor_ui": "D000107", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Chromatin Immunoprecipitation", "descriptor_ui": "D047369", "major_topic": false }, { "descriptor": "Chromatography, High Pressure Liquid", "descriptor_ui": "D002851", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lysine", "descriptor_ui": "D008239", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization", "descriptor_ui": "D019032", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcription Initiation Site", "descriptor_ui": "D024363", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Histone H4 lysine 20 acetylation is associated with gene repression in human cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: A spontaneous de novo mutation is a new mutation appeared in a child that neither the parent carries. Recent studies suggest that recurrent de novo loss-of-function mutations identified in patients with sporadic autism spectrum disorder (ASD) play a key role in the etiology of the disorder. POGZ is one of the most recurrently mutated genes in ASD patients. Our laboratory and other groups have recently found that POGZ has at least 18 independent de novo possible loss-of-function mutations. Despite the apparent importance, these mutations have never previously been assessed via functional analysis. METHODS: Using wild-type, the Q1042R-mutated, and R1008X-mutated POGZ, we performed DNA-binding experiments for proteins that used the CENP-B box sequence in vitro. Data were statistically analyzed by one-way ANOVA followed by Tukey-Kramer post hoc tests. RESULTS: This study reveals that ASD-associated de novo mutations (Q1042R and R1008X) in the POGZ disrupt its DNA-binding activity. CONCLUSIONS: Here, we report the first functional characterization of de novo POGZ mutations identified in sporadic ASD cases. These findings provide important insights into the cellular basis of ASD.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kensuke", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Nanaka", "last_name": "Gotoda-Nishimura", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Hidenaga", "last_name": "Yamamori", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s40303-016-0016-x" }, "pmcid": { "normalized": "PMC4839133" }, "pmid": { "normalized": "27103995" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "1", "proceedings_title": null, "publisher": "", "title": "Journal of molecular psychiatry", "volume": "4", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "De novo POGZ mutations in sporadic autism disrupt the DNA-binding activity of POGZ.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Human histone H3.5 is a non-allelic H3 variant evolutionally derived from H3.3. The H3.5 mRNA is highly expressed in human testis. However, the function of H3.5 has remained poorly understood. Results: We found that the H3.5 nucleosome is less stable than the H3.3 nucleosome. The crystal structure of the H3.5 nucleosome showed that the H3.5-specific Leu103 residue, which corresponds to the H3.3 Phe104 residue, reduces the hydrophobic interaction with histone H4. Mutational analyses revealed that the H3.5-specific Leu103 residue is responsible for the instability of the H3.5 nucleosome, both in vitro and in living cells. The H3.5 protein was present in human seminiferous tubules, but little to none was found in mature sperm. A chromatin immunoprecipitation coupled with sequencing analysis revealed that H3.5 accumulated around transcription start sites (TSSs) in testicular cells. Conclusions: We performed comprehensive studies of H3.5, and found the instability of the H3.5 nucleosome and the accumulation of H3.5 protein around TSSs in human testis. The unstable H3.5 nucleosome may function in the chromatin dynamics around the TSSs, during spermatogenesis.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Urahama", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Horikoshi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Norihiro", "last_name": "Sugino", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Osakabe", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Tachiwana", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Kagawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurumizaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13072-016-0051-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26779285" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "Epigenetics & Chromatin", "volume": "9", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Histone H3.5 forms an unstable nucleosome and accumulates around transcription start sites in human testis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hippocampal pyramidal neurons play an essential role in processing spatial information as implicated with its place-dependent firing. Although, previous slice physiology studies have reported that voltage gated calcium channels contribute to spike shapes and corresponding firing rate in the hippocampus, the roles of P/Q type calcium channels (Cav2.1) underlying neural activity in behaving mice have not been well-investigated. To determine physiological and behavioral roles of Cav2.1, we conducted place cell recordings in CA1 and hippocampus dependent learning/memory tasks using mice lacking Cav2.1 in hippocampal pyramidal neurons under CamK2alpha-Cre recombinase expression. Results suggested that impairments shown in behavioral tasks requiring spatial and contextual information processing were statistically significant while general neurological behaviors did not differ between groups. In particular, deficits were more profound in recognition than in acquisition. Furthermore, place cell recordings also revealed that the ability to recollect spatial representation on re-visit in the conditional knockout was also altered in terms of the cue recognition while the capability of a place cell to encode a place was intact compared to the control group. Interestingly, CA1 pyramidal neurons of conditional knockout mice showed reduced burst frequency as well as abnormal temporal patterns of burst spiking. These results provide potential evidence that Cav2.1 in hippocampal pyramidal cells modulates temporal integration of bursts, which, in turn, might influence the recognition of place field and consequently disrupt spatial recognition ability.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Dahee", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Yu J.", "last_name": "Hwang", "name": null }, { "creator_type": "author", "first_name": "Hoon", "last_name": "Ryu", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Jeiwon", "last_name": "Cho", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnbeh.2016.00214" }, "pmcid": { "normalized": "PMC5093114" }, "pmid": { "normalized": "27857685" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "214", "proceedings_title": null, "publisher": "", "title": "Frontiers in behavioral neuroscience", "volume": "10", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Conditional Knockout of Cav2.1 Disrupts the Accuracy of Spatial Recognition of CA1 Place Cells and Spatial/Contextual Recognition Behavior.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Protein synthesis using an in vitro transcription-translation system (IVTT) inside cell-sized liposomes has become a valuable tool to study the properties of biological systems under cell-mimicking conditions. However, previous liposome systems lacked the machinery for membrane protein translocation. Here, we reconstituted the translocon consisting of SecYEG from Escherichia coli inside cell-sized liposomes. The cell-sized liposomes also carry the reconstituted IVTT, thereby providing a cell-mimicking environment for membrane protein synthesis. By using EmrE, a multidrug transporter from E. coli, as a model membrane protein, we found that both the amount and activity of EmrE synthesized inside the liposome is increased approximately three-fold by incorporating the Sec translocon. The topological change of EmrE induced by the translocon was also identified. The membrane integration of 6 out of 9 E. coli inner membrane proteins that was tested was increased by incorporation of the translocon. By introducing the Sec translocon, the membrane integration efficiency of the membrane protein of interest was increased, and enabled the integration of membrane proteins that otherwise cannot be inserted. In addition, this work represents an essential step toward the construction of an artificial cell through a bottom-up approach.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hirotada", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep36466" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27808179" } }, "mesh": [ { "descriptor": "Antiporters", "descriptor_ui": "D017920", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Escherichia coli Proteins", "descriptor_ui": "D029968", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Liposomes", "descriptor_ui": "D008081", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Phycoerythrin", "descriptor_ui": "D010799", "major_topic": false }, { "descriptor": "SEC Translocation Channels", "descriptor_ui": "D000069816", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "In vitro membrane protein synthesis inside Sec translocon-reconstituted cell-sized liposomes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transcription activator-like effector nucleases (TALENs) are versatile tools that enable the insertion of DNA into different organisms. Here, we confirmed TALEN-mediated knock-in via non-homologous end joining in the crustacean Daphnia magna, a model organism for ecological and toxicological genomics. We tested two different TALENs, ey1 TALEN and ey2 TALEN, both of which target the eyeless locus. The donor DNA plasmid, harbouring the H2B-GFP reporter gene, was designed to contain both TALEN target sites and was co-injected with each TALEN mRNA into eggs. The ey1 TALEN and ey2 TALEN constructs both resulted in H2B-GFP expression in Daphnia with a germline transmission efficiency of 3%. Of the three transgenic animals generated, two had donor DNA at the targeted genomic site, which suggested concurrent cleavage of the injected plasmid DNA and genome DNA. The availability of such tools that are capable of targeted knock-in of foreign genes will be extremely useful for advancing the knowledge of gene function and contribute to an increased understanding of functional genomics in Daphnia.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep36252" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27819301" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "DNA End-Joining Repair", "descriptor_ui": "D059766", "major_topic": true }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Transcription Activator-Like Effector Nucleases", "descriptor_ui": "D000069896", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "TALEN-mediated knock-in via non-homologous end joining in the crustacean Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Eukaryotic cells respond to a chemoattractant gradient by forming intracellular gradients of signaling molecules that reflect the extracellular chemical gradient-an ability called directional sensing. Quantitative experiments have revealed two characteristic input-output relations of the system: First, in a static chemoattractant gradient, the shapes of the intracellular gradients of the signaling molecules are determined by the relative steepness, rather than the absolute concentration, of the chemoattractant gradient along the cell body. Second, upon a spatially homogeneous temporal increase in the input stimulus, the intracellular signaling molecules are transiently activated such that the response magnitudes are dependent on fold changes of the stimulus, not on absolute levels. However, the underlying mechanism that endows the system with these response properties remains elusive. Here, by adopting a widely used modeling framework of directional sensing, local excitation and global inhibition (LEGI), we propose a hypothesis that the two rescaling behaviors stem from a single design principle, namely, invariance of the governing equations to a scale transformation of the input level. Analyses of the LEGI-based model reveal that the invariance can be divided into two parts, each of which is responsible for the respective response properties. Our hypothesis leads to an experimentally testable prediction that a system with the invariance detects relative steepness even in dynamic gradient stimuli as well as in static gradients. Furthermore, we show that the relation between the response properties and the scale invariance is general in that it can be implemented by models with different network topologies.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Keita", "last_name": "Kamino", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0164674" }, "pmcid": { "normalized": "PMC5085096" }, "pmid": { "normalized": "27792738" } }, "mesh": [ { "descriptor": "Chemotactic Factors", "descriptor_ui": "D002630", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": false }, { "descriptor": "Eukaryotic Cells", "descriptor_ui": "D005057", "major_topic": false }, { "descriptor": "Feedback", "descriptor_ui": "D005246", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Receptors, Formyl Peptide", "descriptor_ui": "D044042", "major_topic": false }, { "descriptor": "Spatio-Temporal Analysis", "descriptor_ui": "D062211", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "10", "normalized_date": "2016", "pages": "e0164674", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "11", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Rescaling of Spatio-Temporal Sensing in Eukaryotic Chemotaxis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Volvox sect. Volvox is characterized by having unique morphological characteristics, such as thick cytoplasmic bridges between adult somatic cells in the spheroids and spiny zygote walls. Species of this section are found from various freshwater habitats. Recently, three species of Volvox sect. Volvox originating from rice paddies and a marsh were studied taxonomically based on molecular and morphological data of cultured materials. However, taxonomic studies have not been performed on cultured materials of this section originating from large lake water bodies. We studied a new morphological type of Volvox sect. Volvox (“Volvox sp. Sagami”), using cultured materials originating from two large lakes and a pond in Japan. Volvox sp. Sagami produced monoecious sexual spheroids and may represent a new morphological species; it could be clearly distinguished from all previously described monoecious species of Volvox sect. Volvox by its small number of eggs or zygotes (5–25) in sexual spheroids, with short acute spines (up to 3 μm long) on the zygote walls and elongated anterior somatic cells in asexual spheroids. Based on sequences of internal transcribed spacer (ITS) regions of nuclear ribosomal DNA (rDNA; ITS-1, 5.8S rDNA and ITS-2) and plastid genes, however, the Volvox sp. Sagami lineage and its sister lineage (the monoecious species V. ferrisii) showed very small genetic differences, which correspond to the variation within a single biological species in other volvocalean algae. Since V. ferrisii was different from Volvox sp. Sagami, by having approximately 100–200 zygotes in the sexual spheroids and long spines (6–8.5 μm long) on the zygote walls, as well as growing in Japanese rice paddies, these two morphologically distinct lineages might have diverged rapidly in the two different freshwater habitats. In addition, the swimming velocity during phototaxis of Volvox sp. Sagami spheroids originating from large lakes was significantly higher than that of V. ferrisii originating from rice paddies, suggesting adaptation of Volvox sp. Sagami to large water bodies.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hisayoshi", "last_name": "Nozaki", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Ueki", "name": null }, { "creator_type": "author", "first_name": "Nanako", "last_name": "Isaka", "name": null }, { "creator_type": "author", "first_name": "Tokiko", "last_name": "Saigo", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Matsuzaki", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kawachi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0167148" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27880842" } }, "mesh": [ { "descriptor": "DNA, Plant", "descriptor_ui": "D018744", "major_topic": false }, { "descriptor": "DNA, Ribosomal Spacer", "descriptor_ui": "D021903", "major_topic": false }, { "descriptor": "Ecosystem", "descriptor_ui": "D017753", "major_topic": true }, { "descriptor": "Genome, Plastid", "descriptor_ui": "D054627", "major_topic": true }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Lakes", "descriptor_ui": "D060106", "major_topic": true }, { "descriptor": "Seeds", "descriptor_ui": "D012639", "major_topic": true }, { "descriptor": "Volvox", "descriptor_ui": "D044446", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "11", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "11", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "A New Morphological Type of Volvox from Japanese Large Lakes and Recent Divergence of this Type and V. ferrisii in Two Different Freshwater Habitats.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "External cues that dictate the direction of cell migration are likely dynamic during many biological processes such as embryonic development and wound healing. Until recently, how cells integrate spatial and temporal information to determine the direction of migration has remained elusive. In Dictyostelium discoideum, the chemoattractant cAMP that directs cell aggregation propagates as periodic waves. In light of the fact that any temporally evolving complex signals, in principle, can be expressed as a sum of sinusoidal functions with various frequencies, the Dictyostelium system serves as a minimal example, where the dynamic signal is in the simplest form of near sinusoidal wave with one dominant frequency. Here, we describe a method to emulate the traveling waves in a fluidics device. The text provides step-by-step instructions on the device setup and describes ways to analyze the acquired data. These include quantification of membrane translocation of fluorescently labeled proteins in individual Dictyostelium cells and estimation of exogenous cAMP profiles. The described approach has already helped decipher spatial and temporal aspects of chemotactic sensing in Dictyostelium. More specifically, it allowed one to discriminate the temporal and the spatial sensing aspects of directional sensing. With some modifications, one should be able to implement similar analysis in other cell types.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4939-3480-5_8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27271897" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": true }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "107-122", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "1407", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Dissecting Spatial and Temporal Sensing in Dictyostelium Chemotaxis Using a Wave Gradient Generator.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "T cells are highly concentrated in the lymph node (LN) paracortex, which serves an important role in triggering adoptive immune responses. Live imaging using two-photon laser scanning microscopy revealed vigorous and non-directional T cell migration within this area at average velocity of more than 10 mum/min. Active interstitial T cell movement is considered to be crucial for scanning large numbers of dendritic cells (DCs) to find rare cognate antigens. However, the mechanism by which T cells achieve such high-speed movement in a densely packed, dynamic tissue environment is not fully understood. Several new findings suggest that fibroblastic reticular cells (FRCs) and DCs control T cell movement in a multilateral manner. Chemokines and lysophosphatidic acid produced by FRCs cooperatively promote the migration, while DCs facilitate LFA-1-dependent motility via expression of ICAM-1. Furthermore, the highly dense and confined microenvironment likely plays a key role in anchorage-independent motility. We propose that T cells dynamically switch between two motility modes; anchorage-dependent and -independent manners. Unique tissue microenvironment and characteristic migration modality of T cells cooperatively generate high-speed interstitial movement in the LN.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Kinashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2016.00194" }, "pmcid": { "normalized": "PMC4865483" }, "pmid": { "normalized": "27242799" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "194", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Microenvironmental Control of High-Speed Interstitial T Cell Migration in the Lymph Node.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Identifying the genes required for environmental sex determination is important for understanding the evolution of diverse sex determination mechanisms in animals. Orthologs of Drosophila orphan receptor Fushi tarazu factor-1 (Ftz-F1) are known to function in genetic sex determination. In contrast, their roles in environmental sex determination remain unknown. In this study, we have cloned and characterized the Ftz-F1 ortholog in the branchiopod crustacean Daphnia magna, which produces males in response to environmental stimuli. Similar to that observed in Drosophila, D. magna Ftz-F1 (DapmaFtz-F1) produces two splicing variants, αFtz-F1 and βFtz-F1, which encode 699 and 777 amino acids, respectively. Both isoforms share a DNA-binding domain, a ligand-binding domain, and an AF-2 activation domain and differ only at the A/B domain. The phylogenetic position and genomic structure of DapmaFtz-F1 suggested that this gene has diverged from an ancestral gene common to branchiopod crustacean and insect Ftz-F1 genes. qRT-PCR showed that at the one cell and gastrulation stages, both DapmaFtz-F1 isoforms are two-fold more abundant in males than in females. In addition, in later stages, their sexual dimorphic expressions were maintained in spite of reduced expression. Time-lapse imaging of DapmaFtz-F1 RNAi embryos was performed in H2B-GFP expressing transgenic Daphnia, demonstrating that development of the RNAi embryos slowed down after the gastrulation stage and stopped at 30–48 h after ovulation. DapmaFtz-F1 shows high homology to insect Ftz-F1 orthologs based on its amino acid sequence and exon-intron organization. The sexually dimorphic expression of DapmaFtz-F1 suggests that it plays a role in environmental sex determination of D. magna.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Nur Syafiqah", "last_name": "Mohamad Ishak", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0154636" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27138373" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Conserved Sequence", "descriptor_ui": "D017124", "major_topic": true }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "DNA, Complementary", "descriptor_ui": "D018076", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Sex Characteristics", "descriptor_ui": "D012727", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "5", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "11", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Sequence Conservation and Sexually Dimorphic Expression of the Ftz-F1 Gene in the Crustacean Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND OBJECTIVE: Existing ophthalmoscopy methods are unable to obtain clear fundus autofluorescence (FAF) images in gas-filled eyes. The purpose of this study was to evaluate the capability of wide-field laser ophthalmoscopy (Optos) in obtaining FAF images in gas-filled eyes for the assessment of macular hole (MH) closure after surgery. METHODS: This was an interventional case series. Eighteen consecutive patients with unilateral MH underwent vitrectomy with internal limiting membrane peeling and 20% sulfur hexafluoride gas tamponade. FAF images using Optos were recorded preoperatively and postoperatively (days 1, 2, and 7). RESULTS: On postoperative days 1, 2, and 7, FAF images were obtained from 11/18 (61.1%), 9/18 (50.0%), and 17/18 eyes (94.4%), respectively, using Optos. The quality of FAF images using Optos was sufficient to determine MH closure in 9/18 (50.0%) of gas-filled eyes postoperatively. Quantitative analysis of FAF images was helpful in determining complete or partial closure of the MH. CONCLUSION: FAF imaging using Optos might be a useful adjunct to optical coherence tomography as a supportive method to guide the release from facedown posturing in some cases of MH.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shintaro", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Enaida", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Hani", "last_name": "Salehi-Had", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Koh-Hei", "last_name": "Sonoda", "name": null } ], "identifiers": { "doi": { "normalized": "10.2147/opth.s109900" }, "pmcid": { "normalized": "PMC5003554" }, "pmid": { "normalized": "27601877" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "1623-1630", "proceedings_title": null, "publisher": "", "title": "Clinical ophthalmology (Auckland, N.Z.)", "volume": "10", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Wide-field laser ophthalmoscopy for imaging of gas-filled eyes after macular hole surgery.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell activities primarily depend on chemical reactions, especially those mediated by enzymes, and this has led to these activities being modeled as catalytic reaction networks. Although deterministic ordinary differential equations of concentrations (rate equations) have been widely used for modeling purposes in the field of systems biology, it has been pointed out that these catalytic reaction networks may behave in a way that is qualitatively different from such deterministic representation when the number of molecules for certain chemical species in the system is small. Apart from this, representing these phenomena by simple binary (on/off) systems that omit the quantities would also not be feasible. As recent experiments have revealed the existence of rare chemical species in cells, the importance of being able to model potential small-number phenomena is being recognized. However, most preceding studies were based on numerical simulations, and theoretical frameworks to analyze these phenomena have not been sufficiently developed. Motivated by the small-number issue, this work aimed to develop an analytical framework for the chemical master equation describing the distributional behavior of catalytic reaction networks. For simplicity, we considered networks consisting of two-body catalytic reactions. We used the probability generating function method to obtain the steady-state solutions of the chemical master equation without specifying the parameters. We obtained the time evolution equations of the first- and second-order moments of concentrations, and the steady-state analytical solution of the chemical master equation under certain conditions. These results led to the rank conservation law, the connecting state to the winner-takes-all state, and analysis of 2-molecules M-species systems. A possible interpretation of the theoretical conclusion for actual biochemical pathways is also discussed.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masaki", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Togashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fphys.2016.00089" }, "pmcid": { "normalized": "PMC4805594" }, "pmid": { "normalized": "27047384" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "89", "proceedings_title": null, "publisher": "", "title": "Frontiers in physiology", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "An Analytical Framework for Studying Small-Number Effects in Catalytic Reaction Networks: A Probability Generating Function Approach to Chemical Master Equations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Luminescence exerts an ideal optical readout for imaging living subjects including no external light source, whereas the dim luminescence and poor color pallet should be addressed for the better utilities. To address the demerits and to prevail the advantages, we developed a bright luminescent protein, named yellow Nano-lantern, exhibiting about 10-20 times brighter than wild-type RLuc. In this chapter, we demonstrate two luminescence-based protocols in detail: i.e., (a) multicolor visualization of Ca(2+) dynamics in different cellular compartments in a single cell using Ca(2+) indicators based on cyan- and orange-Nano-lanterns and (b) video-rate tumor detection in a freely moving mouse using yellow Nano-lantern.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kenta", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4939-3813-1_24" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27424914" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Heterografts", "descriptor_ui": "D064593", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Space", "descriptor_ui": "D042541", "major_topic": false }, { "descriptor": "Luciferases, Renilla", "descriptor_ui": "D049410", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "289-297", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "1461", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Luminescence Imaging: (a) Multicolor Visualization of Ca(2+) Dynamics in Different Cellular Compartments and (b) Video-Rate Tumor Detection in a Freely Moving Mouse.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Acetylation, which modulates protein function, is an important process in intracellular signalling. In mitochondria, protein acetylation regulates a number of enzymatic activities and, therefore, modulates mitochondrial functions. Our previous report showed that tributylphosphine (PBu3), an artificial reaction promoter that promotes acetylransfer reactions in vitro, also promotes the reaction between acetyl-CoA and an exogenously introduced fluorescent probe in mitochondria. In this study, we demonstrate that PBu3 induces the acetylation of mitochondrial proteins and a decrease in acetyl-CoA concentration in PBu3-treated HeLa cells. This indicates that PBu3 can promote the acetyltransfer reaction between acetyl-CoA and mitochondrial proteins in living cells. PBu3-induced acetylation gradually reduced mitochondrial ATP concentrations in HeLa cells without changing the cytoplasmic ATP concentration, suggesting that PBu3 mainly affects mitochondrial functions. In addition, pyruvate, which is converted into acetyl-CoA in mitochondria and transiently increases ATP concentrations in the absence of PBu3, elicited a further decrease in mitochondrial ATP concentrations in the presence of PBu3. Moreover, the application and removal of PBu3 reversibly alternated mitochondrial fragmentation and elongation. These results indicate that PBu3 enhances acetyltransfer reactions in mitochondria and modulates mitochondrial functions in living cells.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ariga", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep29224" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27374857" } }, "mesh": [ { "descriptor": "Acetyl Coenzyme A", "descriptor_ui": "D000105", "major_topic": false }, { "descriptor": "Acetylation", "descriptor_ui": "D000107", "major_topic": false }, { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "DNA Fragmentation", "descriptor_ui": "D053938", "major_topic": false }, { "descriptor": "DNA, Mitochondrial", "descriptor_ui": "D004272", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Mitochondrial Proteins", "descriptor_ui": "D024101", "major_topic": false }, { "descriptor": "Phosphines", "descriptor_ui": "D010720", "major_topic": false }, { "descriptor": "Pyruvic Acid", "descriptor_ui": "D019289", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "An Artificial Reaction Promoter Modulates Mitochondrial Functions via Chemically Promoting Protein Acetylation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the fruitfly Drosophila melanogaster, females take the initiative to mate successfully because they decide whether to mate or not. However, little is known about the molecular and neuronal mechanisms regulating sexual receptivity in virgin females. Genetic tools available in Drosophila are useful for identifying molecules and neural circuits involved in the regulation of sexual receptivity. We previously demonstrated that insulin-producing cells (IPCs) in the female brain are critical to the regulation of female sexual receptivity. Ablation and inactivation of IPCs enhance female sexual receptivity, suggesting that neurosecretion from IPCs inhibits female sexual receptivity. IPCs produce and release insulin-like peptides (Ilps) that modulate various biological processes such as metabolism, growth, lifespan and behaviors. Here, we report a novel role of the Ilps in sexual behavior in Drosophila virgin females. Compared with wild-type females, females with knockout mutations of Ilps showed a high mating success rate toward wild-type males, whereas wild-type males courted wild-type and Ilp-knockout females to the same extent. Wild-type receptive females retard their movement during male courtship and this reduced female mobility allows males to copulate. Thus, it was anticipated that knockout mutations of Ilps would reduce general locomotion. However, the locomotor activity in Ilp-knockout females was significantly higher than that in wild-type females. Thus, our findings indicate that the high mating success rate in Ilp-knockout females is caused by their enhanced sexual receptivity, but not by improvement of their sex appeal or by general sluggishness.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1266/ggs.15-00025" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26617266" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Insulin Secretion", "descriptor_ui": "D000078790", "major_topic": false }, { "descriptor": "Insulins", "descriptor_ui": "D061385", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Sexual Behavior, Animal", "descriptor_ui": "D012726", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "4", "normalized_date": "2016", "pages": "237-241", "proceedings_title": null, "publisher": "", "title": "Genes & genetic systems", "volume": "90", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Knockout mutations of insulin-like peptide genes enhance sexual receptivity in Drosophila virgin females.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We previously identified receptor tyrosine kinase-like orphan receptor 1 (ROR1) as a transcriptional target of the NKX2-1/TTF-1 lineage-survival oncogene in lung adenocarcinoma. ROR1 consequently sustains a favorable balance between pro-survival phosphatidylinositol 3-kinase-protein kinase B and pro-apoptotic apoptosis signal-regulating kinase 1 (ASK1)-p38MAPK signaling. In contrast to recent advances in understanding how ROR1 sustains pro-survival signaling, the mechanism of ROR1 repression of pro-apoptotic signaling remains rather elusive. In the present study, we investigated the underlying mechanism of ROR1-mediated inhibition of the ASK1-p38MAPK signaling pathway. Growth inhibition mediated by siROR1 was partially but significantly alleviated by ASK1 co-knockdown in lung adenocarcinoma cell lines. Also, ASK1 phosphorylation at Thr845, which reflects its activated state, was clearly inhibited by ROR1 overexpression in both steady state and oxidative stress-elicited conditions in MSTO-211H cells. In addition, we found that ROR1 was physically associated with ASK1 at the C-terminal serine threonine-rich domain of ROR1. Furthermore, ROR1 kinase activity was shown to be required to repress the ASK1-p38 axis and oxidative stress-induced cell death. The present findings thus support our notion that ROR1 sustains lung adenocarcinoma survival, at least in part, through direct physical interaction with ASK1 and consequential repression of the pro-apoptotic ASK1-p38 axis in a ROR1 kinase activity-dependent manner.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Lisa", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kajino", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Motoshi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.12858" }, "pmcid": { "normalized": "PMC4768386" }, "pmid": { "normalized": "26661061" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoprecipitation", "descriptor_ui": "D047468", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinase 5", "descriptor_ui": "D048848", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Oncogenes", "descriptor_ui": "D009857", "major_topic": false }, { "descriptor": "Receptor Tyrosine Kinase-like Orphan Receptors", "descriptor_ui": "D057050", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Thyroid Nuclear Factor 1", "descriptor_ui": "D000074482", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "155-161", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "107", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Receptor tyrosine kinase-like orphan receptor 1, a target of NKX2-1/TTF-1 lineage-survival oncogene, inhibits apoptosis signal-regulating kinase 1-mediated pro-apoptotic signaling in lung adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Non-clinical studies are necessary at each stage of the development of oncology drugs. Many experimental cancer models have been developed to investigate carcinogenesis, cancer progression, metastasis, and other aspects in cancer biology and these models turned out to be useful in the efficacy evaluation and the safety prediction of oncology drugs. While the diversity and the degree of engagement in genetic changes in the initiation of cancer cell growth and progression are widely accepted, it has become increasingly clear that the roles of host cells, tissue microenvironment, and the immune system also play important roles in cancer. Therefore, the methods used to develop oncology drugs should continuously be revised based on the advances in our understanding of cancer. In this review, we extensively summarize the effective use of those models, their advantages and disadvantages, ranges to be evaluated and limitations of the models currently used for the development and for the evaluation of oncology drugs.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Hiroyoshi", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Ochiya", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Saya", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Seimiya", "name": null }, { "creator_type": "author", "first_name": "Ryoji", "last_name": "Yao", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Chieko", "last_name": "Kai", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Naoe", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Ohtsu", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Saji", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Sata", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Sugimura", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Toi", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Irimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.12857" }, "pmcid": { "normalized": "PMC4768389" }, "pmid": { "normalized": "26919617" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "Drug Discovery", "descriptor_ui": "D055808", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Medical Oncology", "descriptor_ui": "D008495", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "189-202", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "107", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Report on the use of non-clinical studies in the regulatory evaluation of oncology drugs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The suprachiasmatic nucleus (SCN) is the site of the master circadian clock in mammals. The SCN neural network plays a critical role in expressing the tissue-level circadian rhythm. Previously, we demonstrated postnatal changes in the SCN network in mice, in which the clock gene products CRYPTOCHROMES (CRYs) are involved. Here, we show that vasoactive intestinal polypeptide (VIP) signaling is essential for the tissue-level circadian PER2::LUC rhythm in the neonatal SCN of CRY double-deficient mice (Cry1,2 (-/-) ). VIP and arginine vasopressin (AVP) signaling showed redundancy in expressing the tissue-level circadian rhythm in the SCN. AVP synthesis was significantly attenuated in the Cry1,2 (-/-) SCN, which contributes to aperiodicity in the adult mice together with an attenuation of VIP signaling as a natural process of ontogeny. The SCN network consists of multiple clusters of cellular circadian rhythms that are differentially integrated by AVP and VIP signaling, depending on the postnatal period.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Sato", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Honma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.1600960" }, "pmcid": { "normalized": "PMC5017821" }, "pmid": { "normalized": "27626074" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arginine Vasopressin", "descriptor_ui": "D001127", "major_topic": false }, { "descriptor": "Circadian Clocks", "descriptor_ui": "D057906", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Cryptochromes", "descriptor_ui": "D056931", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Period Circadian Proteins", "descriptor_ui": "D056950", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": false }, { "descriptor": "Vasoactive Intestinal Peptide", "descriptor_ui": "D014660", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "e1600960", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "2", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Differential roles of AVP and VIP signaling in the postnatal changes of neural networks for coherent circadian rhythms in the SCN.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Autism spectrum disorder (ASD) is a complex group of clinically heterogeneous neurodevelopmental disorders with unclear etiology and pathogenesis. Genetic studies have identified numerous candidate genetic variants, including de novo mutated ASD-associated genes; however, the function of these de novo mutated genes remains unclear despite extensive bioinformatics resources. Accordingly, it is not easy to assign priorities to numerous candidate ASD-associated genes for further biological analysis. Here we developed a convenient system for identifying an experimental evidence-based annotation of candidate ASD-associated genes. We performed trio-based whole-exome sequencing in 30 sporadic cases of ASD and identified 37 genes with de novo single-nucleotide variations (SNVs). Among them, 5 of those 37 genes, POGZ, PLEKHA4, PCNX, PRKD2 and HERC1, have been previously reported as genes with de novo SNVs in ASD; and consultation with in silico databases showed that only HERC1 might be involved in neural function. To examine whether the identified gene products are involved in neural functions, we performed small hairpin RNA-based assays using neuroblastoma cell lines to assess neurite development. Knockdown of 8 out of the 14 examined genes significantly decreased neurite development (P<0.05, one-way analysis of variance), which was significantly higher than the number expected from gene ontology databases (P=0.010, Fisher's exact test). Our screening system may be valuable for identifying the neural functions of candidate ASD-associated genes for further analysis and a substantial portion of these genes with de novo SNVs might have roles in neuronal systems, although further detailed analysis might eliminate false positive genes from identified candidate ASD genes.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Tsurusaki", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Hidenaga", "last_name": "Yamamori", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Ohi", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Umeda-Yano", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Fukunaga", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Fujino", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Naomichi", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/jhg.2015.141" }, "pmcid": { "normalized": "PMC4819764" }, "pmid": { "normalized": "26582266" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autism Spectrum Disorder", "descriptor_ui": "D000067877", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Exome", "descriptor_ui": "D059472", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neurites", "descriptor_ui": "D016501", "major_topic": true }, { "descriptor": "Sequence Analysis", "descriptor_ui": "D017421", "major_topic": true }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "199-206", "proceedings_title": null, "publisher": "", "title": "Journal of human genetics", "volume": "61", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Whole-exome sequencing and neurite outgrowth analysis in autism spectrum disorder.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jshs.2016.08.009" }, "pmcid": { "normalized": "PMC6188920" }, "pmid": { "normalized": "30356578" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Dec", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "391-392", "proceedings_title": null, "publisher": "", "title": "Journal of sport and health science", "volume": "5", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Mechanism of neurodegeneration through tau and therapy for Alzheimer's disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mark D. A.", "last_name": "van Logtestijn", "name": null }, { "creator_type": "author", "first_name": "Peter J.", "last_name": "Caspers", "name": null }, { "creator_type": "author", "first_name": "Sanja", "last_name": "Kezic", "name": null }, { "creator_type": "author", "first_name": "Douglas R.", "last_name": "Hoffman", "name": null }, { "creator_type": "author", "first_name": "David W.", "last_name": "Koenig", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Georgios N.", "last_name": "Stamatas", "name": null }, { "creator_type": "author", "first_name": "Reiko J.", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jdermsci.2015.10.017" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26616204" } }, "mesh": [ { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Dermatitis, Atopic", "descriptor_ui": "D003876", "major_topic": false }, { "descriptor": "Diffusion", "descriptor_ui": "D004058", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Permeability", "descriptor_ui": "D010539", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Sodium Dodecyl Sulfate", "descriptor_ui": "D012967", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "Surface-Active Agents", "descriptor_ui": "D013501", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": false }, { "descriptor": "Water Loss, Insensible", "descriptor_ui": "D014870", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "126-128", "proceedings_title": null, "publisher": "", "title": "Journal of dermatological science", "volume": "81", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Water resistance profile as a marker of skin barrier damage in atopic dermatitis patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herpes simplex virus 1 (HSV-1) expresses infected cell protein 0 (ICP0), a multi-functional protein with E3 ubiquitin ligase activity and a critical regulator of the viral life cycle. To obtain novel insights into the molecular mechanism by which ICP0 regulates HSV-1 replication, we analyzed HEp-2 cells infected with HSV-1 by tandem affinity purification and mass spectrometry-based proteomics. This screen identified 50 host-cell proteins that potentially interact with ICP0, including ubiquitin-specific protease 9X (USP9X). The interaction between ICP0 and USP9X was confirmed by co-immunoprecipitation. Notably, USP9X depletion increased the ICP0 abundance and promoted viral replication. These results suggest that USP9X-dependent regulation of ICP0 expression is part of a complex feedback mechanism that facilitates optimal HSV-1 replication.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuka", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kozuka-Hata", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1292/jvms.15-0598" }, "pmcid": { "normalized": "PMC4829507" }, "pmid": { "normalized": "26596467" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immediate-Early Proteins", "descriptor_ui": "D017874", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Ubiquitin Thiolesterase", "descriptor_ui": "D043222", "major_topic": false }, { "descriptor": "Ubiquitin-Protein Ligases", "descriptor_ui": "D044767", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "405-410", "proceedings_title": null, "publisher": "", "title": "The Journal of veterinary medical science", "volume": "78", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Ubiquitin-specific protease 9X in host cells interacts with herpes simplex virus 1 ICP0.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Cryopreservation of semen is one of the most important methods for the preservation of endangered tigers. OBJECTIVE: This study evaluated the effects of sugar supplementation on the cryosurvival of spermatozoa from Sumatran tigers (Panthera tigris sumatrae). MATERIALS AND METHODS: The post-thaw characteristics and fertility of spermatozoa cryopreserved with different sugars (glucose, lactose, and trehalose) were evaluated using heterologous in-vitro fertilisation with cat oocytes. RESULTS: All parameters of post-thaw spermatozoa significantly decreased as compared with those of fresh spermatozoa. The index of sperm motility for semen cryopreserved with lactose was significantly higher than that for semen cryopreserved with trehalose. The percentage of total fertilisation for tiger spermatozoa cryopreserved with trehalose was significantly lower than that for control cat spermatozoa. CONCLUSION: Our findings indicated that supplementation with lactose or glycerol as the main sugar in the egg yolk extender resulted in a better motility and fertility potential for post-thawed spermatozoa.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ni", "last_name": "Wayan Kurniani Karja", "name": null }, { "creator_type": "author", "first_name": "Mokhamad", "last_name": "Fahrudin", "name": null }, { "creator_type": "author", "first_name": "Mohamad Agus", "last_name": "Setiadi", "name": null }, { "creator_type": "author", "first_name": "Ligaya Ita", "last_name": "Tumbelaka", "name": null }, { "creator_type": "author", "first_name": "Retno", "last_name": "Sudarwati", "name": null }, { "creator_type": "author", "first_name": "Yohana Tri", "last_name": "Hastuti", "name": null }, { "creator_type": "author", "first_name": "Bongot Huas", "last_name": "Mulia", "name": null }, { "creator_type": "author", "first_name": "Ardyta", "last_name": "Widianti", "name": null }, { "creator_type": "author", "first_name": "Keni", "last_name": "Sultan", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Terazono", "name": null }, { "creator_type": "author", "first_name": "Zhao", "last_name": "Namula", "name": null }, { "creator_type": "author", "first_name": "Masayasu", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Fuminori", "last_name": "Tanihara", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takeshige", "last_name": "Otoi", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27925009" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cryopreservation", "descriptor_ui": "D015925", "major_topic": false }, { "descriptor": "Cryoprotective Agents", "descriptor_ui": "D003451", "major_topic": false }, { "descriptor": "Fertility", "descriptor_ui": "D005298", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Lactose", "descriptor_ui": "D007785", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Semen Preservation", "descriptor_ui": "D012662", "major_topic": false }, { "descriptor": "Spermatozoa", "descriptor_ui": "D013094", "major_topic": false }, { "descriptor": "Tigers", "descriptor_ui": "D046010", "major_topic": true }, { "descriptor": "Trehalose", "descriptor_ui": "D014199", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jul/Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "264-271", "proceedings_title": null, "publisher": "", "title": "Cryo letters", "volume": "37", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "CHARACTERISTICS AND FERTILITY OF SUMATRAN TIGER SPERMATOZOA CRYOPRESERVED WITH DIFFERENT SUGARS.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "RATIONALE: We previously reported that the fluvoxamine-induced increase in prefrontal dopamine levels is enhanced by adrenalectomy/castration (which results in circulating neurosteroid deficiency), via combined activation of serotonin1A (5-HT1A) and sigma1 receptors. However, the mechanistic details of the interaction between 5-HT1A and sigma1 receptors are unknown. OBJECTIVES: Because most neurosteroids have affinity for gamma-aminobutyric acid (GABA)A receptors, in the present study, we examined the involvement of GABAA receptors in this process. RESULTS: Adrenalectomy/castration decreased pentobarbital-induced sleeping time in mice, suggesting that it reduced GABAA receptor function. The GABAA receptor antagonist picrotoxin (1 mg/kg) enhanced the fluvoxamine-induced increase in prefrontal dopamine, but not noradrenaline or serotonin, levels in mice, suggesting that picrotoxin mimicked the effect of adrenalectomy/castration. Picrotoxin also potentiated the increase in prefrontal dopamine levels mediated by co-administration of the 5-HT1A receptor agonist osemozotan and the sigma1 receptor agonist (+)-SKF-10,047, while it did not affect the co-administration-induced changes in noradrenaline and serotonin levels. Conversely, the GABAA receptor agonist diazepam (1 mg/kg) blocked the effect of adrenalectomy/castration on the fluvoxamine-induced increase in prefrontal dopamine levels. Co-administration of osemozotan and (+)-SKF-10,047 did not affect the expression of the neuronal activity marker c-Fos in the prefrontal cortex, ventral tegmental area, and nucleus accumbens in control mice, while it increased the c-Fos expression only in the prefrontal cortex and ventral tegmental area in picrotoxin-treated mice. CONCLUSIONS: These results suggest that the GABAA receptor plays a key role in mediating the synergistic effects of 5-HT1A and sigma1 receptor activation on prefrontal dopamine neurotransmission.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Hiramatsu", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Watabe", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Onaka", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00213-016-4353-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27339616" } }, "mesh": [ { "descriptor": "Adrenalectomy", "descriptor_ui": "D000315", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antipsychotic Agents", "descriptor_ui": "D014150", "major_topic": false }, { "descriptor": "Castration", "descriptor_ui": "D002369", "major_topic": false }, { "descriptor": "Diazepam", "descriptor_ui": "D003975", "major_topic": false }, { "descriptor": "Dioxanes", "descriptor_ui": "D004146", "major_topic": false }, { "descriptor": "Dioxoles", "descriptor_ui": "D004149", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Fluvoxamine", "descriptor_ui": "D016666", "major_topic": false }, { "descriptor": "GABA Antagonists", "descriptor_ui": "D018756", "major_topic": false }, { "descriptor": "GABA Modulators", "descriptor_ui": "D018757", "major_topic": false }, { "descriptor": "GABA-A Receptor Antagonists", "descriptor_ui": "D058787", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Norepinephrine", "descriptor_ui": "D009638", "major_topic": false }, { "descriptor": "Nucleus Accumbens", "descriptor_ui": "D009714", "major_topic": false }, { "descriptor": "Orchiectomy", "descriptor_ui": "D009919", "major_topic": false }, { "descriptor": "Phenazocine", "descriptor_ui": "D010620", "major_topic": false }, { "descriptor": "Picrotoxin", "descriptor_ui": "D010852", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-fos", "descriptor_ui": "D016760", "major_topic": false }, { "descriptor": "Receptor, Serotonin, 5-HT1A", "descriptor_ui": "D044282", "major_topic": false }, { "descriptor": "Receptors, GABA", "descriptor_ui": "D018079", "major_topic": false }, { "descriptor": "Receptors, GABA-A", "descriptor_ui": "D011963", "major_topic": false }, { "descriptor": "Receptors, sigma", "descriptor_ui": "D017480", "major_topic": false }, { "descriptor": "Selective Serotonin Reuptake Inhibitors", "descriptor_ui": "D017367", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false }, { "descriptor": "Serotonin 5-HT1 Receptor Agonists", "descriptor_ui": "D058825", "major_topic": false }, { "descriptor": "Sigma-1 Receptor", "descriptor_ui": "D000097605", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false }, { "descriptor": "Ventral Tegmental Area", "descriptor_ui": "D017557", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Sep", "date_precision": "unknown", "issue": "17", "normalized_date": null, "pages": "3125-3134", "proceedings_title": null, "publisher": "", "title": "Psychopharmacology", "volume": "233", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Involvement of GABAA receptors in 5-HT1A and sigma1 receptor synergism on prefrontal dopaminergic transmission under circulating neurosteroid deficiency.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The transcription factor gene Sox2, centrally involved in neural primordial regulation, is activated by many enhancers. During the early stages of embryonic development, Sox2 is regulated by the enhancers N2 and N1 in the anterior neural plate (ANP) and posterior neural plate (PNP), respectively. This differential use of the enhancers reflects distinct regulatory mechanisms underlying the genesis of ANP and PNP. The ANP develops directly from the epiblast, triggered by nodal signal inhibition, and via the combined action of TFs SOX2, OTX2, POU3F1, and ZIC2, which promotes the the ANP development and inhibits other cell lineages. In contrast, the PNP is derived from neuromesodermal bipotential axial stem cells that develop into the neural plate when Sox2 is activated by the N1 enhancer, whereas they develop into the paraxial mesoderm when the N1 enhancer is repressed by the action of TBX6. The axial stem cells are maintained by the activity of WNT3a and T (Brachyury). However, at axial levels more anterior to the 8th somites (cervical levels), the development of both the neural plate and somite proceeds in the absence of WNT3a, T, or TBX6. These observations indicate that distinct molecular and cellular mechanisms determine neural plate genesis based on the axial level, and contradict the classical concept of the term \"neural induction,\" which assumes a pan-neural plate mechanism.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hisato", "last_name": "Kondoh", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12295" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27279156" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Enhancer Elements, Genetic", "descriptor_ui": "D004742", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neural Plate", "descriptor_ui": "D054258", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jun", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "427-436", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "58", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Axial level-dependent molecular and cellular mechanisms underlying the genesis of the embryonic neural plate.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The unicellular green alga Chlamydomonas reinhardtii is a model organism for various studies in biology. CC-124 is a laboratory strain widely used as a wild type. However, this strain is known to carry agg1 mutation, which causes cells to swim away from the light source (negative phototaxis), in contrast to the cells of other wild-type strains, which swim toward the light source (positive phototaxis). Here we identified the causative gene of agg1 (AGG1) using AFLP-based gene mapping and whole genome next-generation sequencing. This gene encodes a 36-kDa protein containing a Fibronectin type III domain and a CHORD-Sgt1 (CS) domain. The gene product is localized to the cell body and not to flagella or basal body.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takahiro", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Mochiji", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Ueki", "name": null }, { "creator_type": "author", "first_name": "Katsushi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Shigenobu", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Hirono", "name": null }, { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Wakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrep.2016.07.016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28955929" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Sep", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "379-385", "proceedings_title": null, "publisher": "", "title": "Biochemistry and Biophysics Reports", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of the agg1 mutation responsible for negative phototaxis in a “wild-type” strain of Chlamydomonas reinhardtii.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Successful cancer treatment requires understanding host immune response against tumor cells. PD-1 belongs to the CD28 superfamily of receptors that work as \"checkpoints\" of immune activation. PD-1 maintains immune self-tolerance to prevent autoimmunity and controls T-cell reaction during infection to prevent excessive tissue damage. Tumor cells that arise from normal tissue acquire mutations that can be targeted by lymphocytes. Accumulating lines of evidence suggest that tumor cells evade host immune attack by expressing physiological PD-1 ligands and stimulating PD-1 on the lymphocytes. Based on this idea, researchers have successfully demonstrated that systemic administration of monoclonal antibodies that inhibit the binding of PD-1 to the ligands reactivated T cells and augmented the anti-cancer immune response. In this review, I summarize the basics of T-cell biology and its regulation by PD-1 and discuss the current understanding and questions about this multifaceted molecule.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10147-016-0958-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26864303" } }, "mesh": [ { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "CTLA-4 Antigen", "descriptor_ui": "D060908", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infections", "descriptor_ui": "D007239", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false }, { "descriptor": "Self Tolerance", "descriptor_ui": "D017634", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false }, { "descriptor": "Tumor Escape", "descriptor_ui": "D019139", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jun", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "448-455", "proceedings_title": null, "publisher": "", "title": "International journal of clinical oncology", "volume": "21", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Basics of PD-1 in self-tolerance, infection, and cancer immunity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The development of the mammalian cerebellum is orchestrated by both cell-autonomous programs and inductive environmental influences. Here, we describe the main processes of cerebellar ontogenesis, highlighting the neurogenic strategies used by developing progenitors, the genetic programs involved in cell fate specification, the progressive changes of structural organization, and some of the better-known abnormalities associated with developmental disorders of the cerebellum.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ketty", "last_name": "Leto", "name": null }, { "creator_type": "author", "first_name": "Marife", "last_name": "Arancillo", "name": null }, { "creator_type": "author", "first_name": "Esther B. E.", "last_name": "Becker", "name": null }, { "creator_type": "author", "first_name": "Annalisa", "last_name": "Buffo", "name": null }, { "creator_type": "author", "first_name": "Chin", "last_name": "Chiang", "name": null }, { "creator_type": "author", "first_name": "Baojin", "last_name": "Ding", "name": null }, { "creator_type": "author", "first_name": "William B.", "last_name": "Dobyns", "name": null }, { "creator_type": "author", "first_name": "Isabelle", "last_name": "Dusart", "name": null }, { "creator_type": "author", "first_name": "Parthiv", "last_name": "Haldipur", "name": null }, { "creator_type": "author", "first_name": "Mary E.", "last_name": "Hatten", "name": null }, { "creator_type": "author", "first_name": "Mikio", "last_name": "Hoshino", "name": null }, { "creator_type": "author", "first_name": "Alexandra L.", "last_name": "Joyner", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Daniel L.", "last_name": "Kilpatrick", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Koibuchi", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Marino", "name": null }, { "creator_type": "author", "first_name": "Salvador", "last_name": "Martinez", "name": null }, { "creator_type": "author", "first_name": "Kathleen J.", "last_name": "Millen", "name": null }, { "creator_type": "author", "first_name": "Thomas O.", "last_name": "Millner", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Elena", "last_name": "Parmigiani", "name": null }, { "creator_type": "author", "first_name": "Karl", "last_name": "Schilling", "name": null }, { "creator_type": "author", "first_name": "Gabriella", "last_name": "Sekerkova", "name": null }, { "creator_type": "author", "first_name": "Roy V.", "last_name": "Sillitoe", "name": null }, { "creator_type": "author", "first_name": "Constantino", "last_name": "Sotelo", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Annika", "last_name": "Wefers", "name": null }, { "creator_type": "author", "first_name": "Richard J. T.", "last_name": "Wingate", "name": null }, { "creator_type": "author", "first_name": "Richard", "last_name": "Hawkes", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12311-015-0724-2" }, "pmcid": { "normalized": "PMC4846577" }, "pmid": { "normalized": "26439486" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "789-828", "proceedings_title": null, "publisher": "", "title": "Cerebellum (London, England)", "volume": "15", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Consensus Paper: Cerebellar Development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Valproic acid (VPA) is a multi-target drug and an inhibitor of histone deacetylase (HDAC). We have previously demonstrated that prenatal exposure to VPA at embryonic day 12.5 (E12.5), but not at E14.5, causes autism-like behavioral abnormalities in male mouse offspring. We have also found that prenatal VPA exposure causes transient histone hyperacetylation in the embryonic brain, followed by decreased neuronal cell numbers in the prefrontal and somatosensory cortices after birth. In the present study, we examined whether prenatal HDAC inhibition affects neuronal maturation in primary mouse cortical neurons. Pregnant mice were injected intraperitoneally with VPA (500 mg/kg) and the more selective HDAC inhibitor trichostatin A (TSA; 500 microg/kg) at E12.5 or E14.5, and primary neuronal cultures were prepared from the cerebral cortices of their embryos. Prenatal exposure to VPA at E12.5, but not at E14.5, decreased total number, total length, and complexity of neuronal dendrites at 14 days in vitro (DIV). The effects of VPA weakened at 21 DIV. Exposure to TSA at E12.5, but not at E14.5, also delayed maturation of cortical neurons. In addition, real-time quantitative PCR revealed that the prenatal exposure to TSA decreased neuroligin-1 (Nlgn1), Shank2, and Shank3 mRNA levels and increased contactin-associated protein-like 2 mRNA level. The delay in neuronal maturation was also observed in Nlgn1-knockdown cells, which were transfected with Nlgn1 siRNA. These findings suggest that prenatal HDAC inhibition causes changes in gene expression of autism-related molecules linked to a delay of neuronal maturation.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takuya", "last_name": "Kawanai", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Atsuki", "last_name": "Taruta", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Onaka", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s11064-016-1969-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27300699" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autistic Disorder", "descriptor_ui": "D001321", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Histone Deacetylase Inhibitors", "descriptor_ui": "D056572", "major_topic": false }, { "descriptor": "Histone Deacetylases", "descriptor_ui": "D006655", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Prenatal Exposure Delayed Effects", "descriptor_ui": "D011297", "major_topic": false }, { "descriptor": "Valproic Acid", "descriptor_ui": "D014635", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "2574-2584", "proceedings_title": null, "publisher": "", "title": "Neurochemical research", "volume": "41", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Prenatal Exposure to Histone Deacetylase Inhibitors Affects Gene Expression of Autism-Related Molecules and Delays Neuronal Maturation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Rodents exposed prenatally to valproic acid (VPA) show autism-related behavioral abnormalities. We recently found that prenatal VPA exposure causes a reduction of dopaminergic activity in the prefrontal cortex of male, but not female, mice. This suggests that reduced prefrontal dopaminergic activity is associated with behavioral abnormalities in VPA-treated mice. In the present study, we examined whether the attention deficit/hyperactivity disorder drugs methylphenidate and atomoxetine (which increase dopamine release in the prefrontal cortex, but not striatum, in mice) could alleviate the behavioral abnormalities and changes in dendritic spine morphology induced by prenatal VPA exposure. We found that methylphenidate and atomoxetine increased prefrontal dopamine and noradrenaline release in VPA-treated mice. Acute treatment with methylphenidate or atomoxetine did not alleviate the social interaction deficits or recognition memory impairment in VPA-treated mice, while chronic treatment for 2 weeks did. Methylphenidate or atomoxetine for 2 weeks also improved the prenatal VPA-induced decrease in dendritic spine density in the prefrontal cortex. The effects of these drugs on behaviors and dendritic spine morphology were antagonized by concomitant treatment with the dopamine-D1 receptor antagonist SCH39166 or the dopamine-D2 receptor antagonist raclopride, but not by the alpha2 -adrenoceptor antagonist idazoxan. These findings suggest that chronic treatment with methylphenidate or atomoxetine improves abnormal behaviors and diminishes the reduction in spine density in VPA-treated mice via a prefrontal dopaminergic system-dependent mechanism. Autism Res 2016, 9: 926-939. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Atsuki", "last_name": "Taruta", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Katashiba", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Erika", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Onaka", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/aur.1596" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26714434" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Atomoxetine Hydrochloride", "descriptor_ui": "D000069445", "major_topic": false }, { "descriptor": "Autistic Disorder", "descriptor_ui": "D001321", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interpersonal Relations", "descriptor_ui": "D007398", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Methylphenidate", "descriptor_ui": "D008774", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Norepinephrine", "descriptor_ui": "D009638", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Receptors, Dopamine D1", "descriptor_ui": "D017447", "major_topic": false }, { "descriptor": "Recognition, Psychology", "descriptor_ui": "D021641", "major_topic": false }, { "descriptor": "Valproic Acid", "descriptor_ui": "D014635", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "926-939", "proceedings_title": null, "publisher": "", "title": "Autism research : official journal of the International Society for Autism Research", "volume": "9", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Improvement by methylphenidate and atomoxetine of social interaction deficits and recognition memory impairment in a mouse model of valproic acid-induced autism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the social amoeba Dictyostelium discoideum, travelling waves of extracellular cyclic adenosine monophosphate (cAMP) self-organize in cell populations and direct aggregation of individual cells to form multicellular fruiting bodies. In contrast to the large body of studies that addressed how movement of cells is determined by spatial and temporal cues encoded in the dynamic cAMP gradients, how cell mechanics affect the formation of a self-generated chemoattractant field has received less attention. Here, we show, by live cell imaging analysis, that the periodicity of the synchronized cAMP waves increases in cells treated with the actin inhibitor latrunculin. Detail analysis of the extracellular cAMP-induced transients of cytosolic cAMP (cAMP relay response) in well-isolated cells demonstrated that their amplitude and duration were markedly reduced in latrunculin-treated cells. Similarly, in cells strongly adhered to a poly-l-lysine-coated surface, the response was suppressed, and the periodicity of the population-level oscillations was markedly lengthened. Our results suggest that cortical F-actin is dispensable for the basic low amplitude relay response but essential for its full amplification and that this enhanced response is necessary to establish high-frequency signalling centres. The observed F-actin dependence may prevent aggregation centres from establishing in microenvironments that are incompatible with cell migration.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Fumihito", "last_name": "Fukujin", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1098/rsif.2016.0233" }, "pmcid": { "normalized": "PMC4938087" }, "pmid": { "normalized": "27358278" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Chemotactic Factors", "descriptor_ui": "D002630", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jun", "date_precision": "unknown", "issue": "119", "normalized_date": null, "pages": "20160233", "proceedings_title": null, "publisher": "", "title": "Journal of the Royal Society, Interface", "volume": "13", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Self-organization of chemoattractant waves in Dictyostelium depends on F-actin and cell-substrate adhesion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Alexandre", "last_name": "Alie", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Manuel", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Funayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1051/medsci/20163208002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27615163" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": true }, { "descriptor": "Genes, Developmental", "descriptor_ui": "D050437", "major_topic": true }, { "descriptor": "Genetic Speciation", "descriptor_ui": "D049810", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Porifera", "descriptor_ui": "D011161", "major_topic": true }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 8-9", "date_precision": "unknown", "issue": "8-9", "normalized_date": null, "pages": "665-668", "proceedings_title": null, "publisher": "", "title": "Medecine sciences : M/S", "volume": "32", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "[The ancestral gene repertoire of animal stem cells].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We recently found that the product of the AES gene functions as a metastasis suppressor of colorectal cancer (CRC) in both humans and mice. Expression of amino-terminal enhancer of split (AES) protein is significantly decreased in liver metastatic lesions compared with primary colon tumors. To investigate its downregulation mechanism in metastases, we searched for transcriptional regulators of AES in human CRC and found that its expression is reduced mainly by transcriptional dysregulation and, in some cases, by additional haploidization of its coding gene. The AES promoter-enhancer is in a typical CpG island, and contains a Yin-Yang transcription factor recognition sequence (YY element). In human epithelial cells of normal colon and primary tumors, transcription factor YY2, a member of the YY family, binds directly to the YY element, and stimulates expression of AES. In a transplantation mouse model of liver metastases, however, expression of Yy2 (and therefore of Aes) is downregulated. In human CRC metastases to the liver, the levels of AES protein are correlated with those of YY2. In addition, we noticed copy-number reduction for the AES coding gene in chromosome 19p13.3 in 12% (5/42) of human CRC cell lines. We excluded other mechanisms such as point or indel mutations in the coding or regulatory regions of the AES gene, CpG methylation in the AES promoter enhancer, expression of microRNAs, and chromatin histone modifications. These results indicate that Aes may belong to a novel family of metastasis suppressors with a CpG-island promoter enhancer, and it is regulated transcriptionally.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Kakizaki", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Miyoshi", "name": null }, { "creator_type": "author", "first_name": "Yoshiro", "last_name": "Itatani", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Yoshiharu", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "M. Mark", "last_name": "Taketo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.13063" }, "pmcid": { "normalized": "PMC5132282" }, "pmid": { "normalized": "27561171" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Co-Repressor Proteins", "descriptor_ui": "D056970", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "CpG Islands", "descriptor_ui": "D018899", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Genes, Tumor Suppressor", "descriptor_ui": "D016147", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Response Elements", "descriptor_ui": "D020218", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false }, { "descriptor": "YY1 Transcription Factor", "descriptor_ui": "D050986", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "1622-1631", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "107", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Expression of metastasis suppressor gene AES driven by a Yin Yang (YY) element in a CpG island promoter and transcription factor YY2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydrogen sulfide (H2S) functions in many physiological processes, including relaxation of vascular smooth muscles, mediation of neurotransmission, inhibition of insulin signaling, and regulation of inflammation. On the other hand, sulfane sulfur, which is a sulfur atom with six valence electrons but no charge, has the unique ability to bind reversibly to other sulfur atoms to form hydropersulfides (R-S-SH) and polysulfides (-S-Sn-S-). H2S and sulfane sulfur always coexist, and recent work suggests that sulfane sulfur species may be the actual signaling molecules in at least some biological phenomena. For example, one of the mechanisms of activity regulation of proteins by H2S is the S-sulfhydration of cysteine residues (protein Cys-SSH). In this review, we summarize recent progress on chemical tools for the study of H2S and sulfane sulfur, covering fluorescence probes utilizing various design strategies, H2S caged compounds, inhibitors of physiological H2S-producing enzymes (cystathionine γ-lyase, cystathionine β-synthase and 3-mercaptopyruvate sulfurtransferase), and labeling reagents. Fluorescence probes offer particular advantages as chemical tools to study physiological functions of biomolecules, including ease of use and real-time, nondestructive visualization of biological processes in live cells and tissues.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoko", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Kazuhito", "last_name": "Shimamoto", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.3164/jcbn.15-91" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26798192" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "7-15", "proceedings_title": null, "publisher": "", "title": "Journal of Clinical Biochemistry and Nutrition", "volume": "58", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Chemical tools for the study of hydrogen sulfide (H2S) and sulfane sulfur and their applications to biological studies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "LPS-induced acute lung injury requires IL-23 and proceeds via IL-22 from memory Th17 cells", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryota", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Chikuma", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shichita", "name": null }, { "creator_type": "author", "first_name": "Rimpei", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Wenjun", "last_name": "Ouyang", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Morisaki", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/intimm/dxv070" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26647405" } }, "mesh": [ { "descriptor": "Acute Lung Injury", "descriptor_ui": "D055371", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bronchoalveolar Lavage", "descriptor_ui": "D018893", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Th17 Cells", "descriptor_ui": "D058504", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "233-243", "proceedings_title": null, "publisher": "", "title": "International Immunology", "volume": "28", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Innate-like function of memory Th17 cells for enhancing endotoxin-induced acute lung inflammation through IL-22.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mammalian genome is organized into submegabase-sized chromatin domains (CDs) including topologically associating domains, which have been identified using chromosome conformation capture-based methods. Single-nucleosome imaging in living mammalian cells has revealed subdiffusively dynamic nucleosome movement. It is unclear how single nucleosomes within CDs fluctuate and how the CD structure reflects the nucleosome movement. Here, we present a polymer model wherein CDs are characterized by fractal dimensions and the nucleosome fibers fluctuate in a viscoelastic medium with memory. We analytically show that the mean-squared displacement (MSD) of nucleosome fluctuations within CDs is subdiffusive. The diffusion coefficient and the subdiffusive exponent depend on the structural information of CDs. This analytical result enabled us to extract information from the single-nucleosome imaging data for HeLa cells. Our observation that the MSD is lower at the nuclear periphery region than the interior region indicates that CDs in the heterochromatin-rich nuclear periphery region are more compact than those in the euchromatin-rich interior region with respect to the fractal dimensions as well as the size. Finally, we evaluated that the average size of CDs is in the range of 100-500 nm and that the relaxation time of nucleosome movement within CDs is a few seconds. Our results provide physical and dynamic insights into the genome architecture in living cells.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Tadasu", "last_name": "Nozaki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Maeshima", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Togashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1005136" }, "pmcid": { "normalized": "PMC5072619" }, "pmid": { "normalized": "27764097" } }, "mesh": [ { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Chromatin Assembly and Disassembly", "descriptor_ui": "D042002", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Chemical", "descriptor_ui": "D008956", "major_topic": true }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Molecular Conformation", "descriptor_ui": "D008968", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Motion", "descriptor_ui": "D009038", "major_topic": false }, { "descriptor": "Nucleosomes", "descriptor_ui": "D009707", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "e1005136", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "12", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic Nucleosome Movement Provides Structural Information of Topological Chromatin Domains in Living Human Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the subgranular zone (SGZ) of the hippocampus, neurogenesis persists throughout life and is upregulated following ischemia. Accumulating evidence suggests that enhanced neurogenesis stimulated by ischemic injury contributes to recovery after stroke. However, the mechanisms underlying the upregulation of neurogenesis are unclear. We have demonstrated that a neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), exerts a wide range of effects on neural stem cells (NSCs) during neural development. Here, we examined the effects of endogenous and exogenous PACAP in adult NSCs of the SGZ. Immunostaining showed expression of the PACAP receptor PAC1R in nestin-positive NSCs of adult naive mice. PACAP injection into the lateral ventricle increased bromodeoxyuridine (BrdU)-positive proliferative cells in the SGZ. These data suggest that PACAP promoted the proliferation of NSCs. In global ischemia model mice, the number of BrdU-positive cells was increased in wild-type mice but not in PACAP heterozygous knockout mice. The BrdU-positive cells that increased in number after ischemia were immunopositive for SOX2, a marker of NSCs, and differentiated into NeuN-positive mature neurons at 4 weeks after ischemia. These findings suggest that PACAP contributes to the proliferation of NSCs and may be associated with recovery after brain injury.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Minako", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Nakamachi", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Ohtaki", "name": null }, { "creator_type": "author", "first_name": "Norimitsu", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Zhifang", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Tamotsu", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Shioda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12031-016-0731-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26910758" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Heterozygote", "descriptor_ui": "D006579", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Nestin", "descriptor_ui": "D064231", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": true }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051236", "major_topic": false }, { "descriptor": "SOXB1 Transcription Factors", "descriptor_ui": "D055748", "major_topic": false }, { "descriptor": "Stroke", "descriptor_ui": "D020521", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jun", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "270-279", "proceedings_title": null, "publisher": "", "title": "Journal of molecular neuroscience : MN", "volume": "59", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Is Involved in Adult Mouse Hippocampal Neurogenesis After Stroke.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Antisense RNA has emerged as a crucial regulator of opposite-strand protein-coding genes in the long noncoding RNA (lncRNA) category, but little is known about their dynamics and decay process in the context of a stress response. Antisense transcripts from the fission yeast fbp1 locus (fbp1-as) are expressed in glucose-rich conditions and anticorrelated with transcription of metabolic stress-induced lncRNA (mlonRNA) and mRNA on the sense strand during glucose starvation. Here, we investigate the localization and decay of antisense RNAs at fbp1 and other loci, and propose a model to explain the rapid switch between antisense and sense mlonRNA/mRNA transcription triggered by glucose starvation. We show that fbp1-as shares many features with mRNAs, such as a 5'-cap and poly(A)-tail, and that its decay partially depends upon Rrp6, a cofactor of the nuclear exosome complex involved in 3'-5' degradation of RNA. Fluorescence in situ hybridization and polysome fractionation show that the majority of remaining fbp1-as localizes to the cytoplasm and binds to polyribosomes in glucose-rich conditions. Furthermore, fbp1-as and antisense RNA at other stress-responsive loci are promptly degraded via the cotranslational nonsense-mediated decay (NMD) pathway. These results suggest NMD may potentiate the swift disappearance of antisense RNAs in response to cellular stress.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Atsuko", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Josephine", "last_name": "Galipon", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Toshifumi", "last_name": "Inada", "name": null }, { "creator_type": "author", "first_name": "Kunihiro", "last_name": "Ohta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.12443" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27723196" } }, "mesh": [ { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Fungal", "descriptor_ui": "D015966", "major_topic": true }, { "descriptor": "Genes, Fungal", "descriptor_ui": "D005800", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Ribosomes", "descriptor_ui": "D012270", "major_topic": false }, { "descriptor": "RNA Stability", "descriptor_ui": "D020871", "major_topic": false }, { "descriptor": "RNA, Antisense", "descriptor_ui": "D016372", "major_topic": false }, { "descriptor": "RNA, Fungal", "descriptor_ui": "D012331", "major_topic": false }, { "descriptor": "RNA, Long Noncoding", "descriptor_ui": "D062085", "major_topic": false }, { "descriptor": "Schizosaccharomyces", "descriptor_ui": "D012568", "major_topic": false }, { "descriptor": "Stress, Physiological", "descriptor_ui": "D013312", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1276-1289", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "21", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "RNA decay systems enhance reciprocal switching of sense and antisense transcripts in response to glucose starvation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Calpains are intracellular Ca(2+)-regulated cysteine proteases that are essential for various cellular functions. Mammalian conventional calpains (calpain-1 and calpain-2) modulate the structure and function of their substrates by limited proteolysis. Thus, it is critically important to determine the site(s) in proteins at which calpains cleave. However, the calpains' substrate specificity remains unclear, because the amino acid (aa) sequences around their cleavage sites are very diverse. To clarify calpains' substrate specificities, 84 20-mer oligopeptides, corresponding to P10-P10' of reported cleavage site sequences, were proteolyzed by calpains, and the catalytic efficiencies (kcat/Km) were globally determined by LC/MS. This analysis revealed 483 cleavage site sequences, including 360 novel ones. Thekcat/Kms for 119 sites ranged from 12.5-1,710 M(-1)s(-1) Although most sites were cleaved by both calpain-1 and -2 with a similarkcat/Km, sequence comparisons revealed distinct aa preferences at P9-P7/P2/P5'. The aa compositions of the novel sites were not statistically different from those of previously reported sites as a whole, suggesting calpains have a strict implicit rule for sequence specificity, and that the limited proteolysis of intact substrates is because of substrates' higher-order structures. Cleavage position frequencies indicated that longer sequences N-terminal to the cleavage site (P-sites) were preferred for proteolysis over C-terminal (P'-sites). Quantitative structure-activity relationship (QSAR) analyses using partial least-squares regression and >1,300 aa descriptors achievedkcat/Kmprediction withr= 0.834, and binary-QSAR modeling attained an 87.5% positive prediction value for 132 reported calpain cleavage sites independent of our model construction. These results outperformed previous calpain cleavage predictors, and revealed the importance of the P2, P3', and P4' sites, and P1-P2 cooperativity. Furthermore, using our binary-QSAR model, novel cleavage sites in myoglobin were identified, verifying our predictor. This study increases our understanding of calpain substrate specificities, and opens calpains to \"next-generation,\"i.e.activity-related quantitative and cooperativity-dependent analyses.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Fumiko", "last_name": "Shinkai-Ouchi", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ojima", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "duVerle", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Fujiko", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Doi", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Mamitsuka", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Sorimachi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/mcp.m115.053413" }, "pmcid": { "normalized": "PMC4824854" }, "pmid": { "normalized": "26796116" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Calpain", "descriptor_ui": "D002154", "major_topic": false }, { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Oligopeptides", "descriptor_ui": "D009842", "major_topic": false }, { "descriptor": "Proteolysis", "descriptor_ui": "D059748", "major_topic": false }, { "descriptor": "Quantitative Structure-Activity Relationship", "descriptor_ui": "D021281", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "1262-1280", "proceedings_title": null, "publisher": "", "title": "Molecular & cellular proteomics : MCP", "volume": "15", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Predictions of Cleavability of Calpain Proteolysis by Quantitative Structure-Activity Relationship Analysis Using Newly Determined Cleavage Sites and Catalytic Efficiencies of an Oligopeptide Array.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genetically Encoded Voltage Indicators (GEVIs) are powerful tools used to investigate neural activity in the brain. The spatiotemporal resolution of GEVIs is on a subcellular and millisecond scale, and is superior to that of the functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG). Further, while patch-clamp techniques record membrane voltage for tens of neurons simultaneously, GEVIs can do so for hundreds of neurons. It is important for neuroscientists to understand the pros and cons of GEVIs and to choose appropriate ones for their specific requirements. Here, we summarize the characteristics of currently available GEVIs based on voltage sensing mechanism and provide a guideline for selecting optimal GEVIs for specific applications.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shigenori", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cbpa.2016.05.023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27322400" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": true }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Rhodopsin", "descriptor_ui": "D012243", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Aug", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "95-100", "proceedings_title": null, "publisher": "", "title": "Current opinion in chemical biology", "volume": "33", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Current progress in genetically encoded voltage indicators for neural activity recording.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chd5 is an essential factor for neuronal differentiation and spermatogenesis and is a known tumor suppressor. H3K27me3 and H3K4un are modifications recognized by Chd5; however, it remains unclear how Chd5 remodels chromatin structure. We completely disrupted the Chd5 locus using the CRISPR-Cas9 system to generate a 52 kbp long deletion and analyzed Chd5 function in mouse embryonic stem cells. Our findings show that Chd5 represses murine endogenous retrovirus-L (MuERV-L/MERVL), an endogenous retrovirus-derived retrotransposon, by regulating H3K27me3 and H3.1/H3.2 function.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masayasu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Semba", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Kudo", "name": null }, { "creator_type": "author", "first_name": "Hidehisa", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Chikara", "last_name": "Meno", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Ichiyanagi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/jcb.25368" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26359639" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "DNA Helicases", "descriptor_ui": "D004265", "major_topic": false }, { "descriptor": "Endogenous Retroviruses", "descriptor_ui": "D020077", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mouse Embryonic Stem Cells", "descriptor_ui": "D000066450", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": true }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "780-792", "proceedings_title": null, "publisher": "", "title": "Journal of cellular biochemistry", "volume": "117", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Chd5 Regulates MuERV-L/MERVL Expression in Mouse Embryonic Stem Cells Via H3K27me3 Modification and Histone H3.1/H3.2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescence imaging of calcium ions (Ca(2+)) has become an essential technique for investigation of signaling pathways involving Ca(2+) as a second messenger. But, Ca(2+) signaling is involved in many biological phenomena, and therefore simultaneous visualization of Ca(2+) and other biomolecules (multicolor imaging) would be particularly informative. For this purpose, we set out to develop a fluorescent probe for Ca(2+) that would operate in a different color region (red) from that of probes for other molecules, many of which show green fluorescence, as exemplified by green fluorescent protein (GFP). We previously developed a red fluorescent probe for monitoring cytoplasmic Ca(2+) concentration, based on our established red fluorophore, TokyoMagenta (TM), but there remained room for improvement, especially as regards efficiency of introduction into cells. We considered that this issue was probably mainly due to limited water solubility of the probe. So, we designed and synthesized a red-fluorescent probe with improved water solubility. We confirmed that this Ca(2+) red-fluorescent probe showed high cell-membrane permeability with bright fluorescence. It was successfully applied to fluorescence imaging of not only live cells, but also brain slices, and should be practically useful for multicolor imaging studies of biological mechanisms.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Hirabayashi", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Egawa", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Shodai", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Ikegaya", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ceca.2016.06.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27349490" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Membrane Permeability", "descriptor_ui": "D002463", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ions", "descriptor_ui": "D007477", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Spectrophotometry, Ultraviolet", "descriptor_ui": "D013056", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "256-265", "proceedings_title": null, "publisher": "", "title": "Cell calcium", "volume": "60", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of practical red fluorescent probe for cytoplasmic calcium ions with greatly improved cell-membrane permeability.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epstein-Barr virus (EBV) establishes a lifelong latent infection in B lymphocytes and often is found in epithelial cells. Several lines of evidence indicate that viral transmission mediated by cell-to-cell contact is the dominant mode of infection by EBV for epithelial cells. However, its detailed molecular mechanism has not been fully elucidated. We investigated the role of host membrane trafficking machinery in this process. We have found that adhesion molecules critical for this process are expressed in EBV-positive and -negative Burkitt's lymphoma (BL) cells and multiple epithelial cell lines. Treatment with blocking antibodies against beta1 and beta2 integrin families and their ligands suppressed EBV transmission in a dose-dependent manner. We also confirmed that adhesion molecules are upregulated in co-cultured BL cells. Immunofluorescence staining revealed that the intracellular adhesion molecule 1 (ICAM-1) distributed to the cell surface and partially co-localized with recycling endosomes in co-cultured BL cells. Moreover, cell-to-cell EBV transmission was inhibited upon blocking endocytic recycling by expression of a dominant-negative form of a small GTPase Rab11 or by knockdown of Rab11, supporting the notion that the endocytic pathway-dependent trafficking of ICAM-1 to the cell surface of BL cells contributes to viral transmission by stabilizing cell-to-cell contact between the donor cells and recipient cells. Finally, we demonstrated that co-cultivation upregulated clathrin-mediated endocytosis in the recipient cells, allowing EBV to be internalized. Taken together, our findings demonstrate that EBV exploits host endocytic machinery in both donor and recipient cells, a process which is facilitated by cell-to-cell contact, thereby promoting successful viral transmission.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Asuka", "last_name": "Nanbo", "name": null }, { "creator_type": "author", "first_name": "Kunihiro", "last_name": "Kachi", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Yoshiyama", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1099/jgv.0.000605" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27655016" } }, "mesh": [ { "descriptor": "Burkitt Lymphoma", "descriptor_ui": "D002051", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": true }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Epstein-Barr Virus Infections", "descriptor_ui": "D020031", "major_topic": false }, { "descriptor": "Herpesvirus 4, Human", "descriptor_ui": "D004854", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Adhesion Molecule-1", "descriptor_ui": "D018799", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "2989-3006", "proceedings_title": null, "publisher": "", "title": "The Journal of general virology", "volume": "97", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Epstein-Barr virus exploits host endocytic machinery for cell-to-cell viral transmission rather than a virological synapse.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Fluorescent proteins have continued to shed light on cell biology since the cDNA of wild type green fluorescent protein was first isolated. Nowadays, these remarkable proteins are useful tools, not only in basic research, but also in clinical medicine. HIGHLIGHT: By taking advantage of fluorescent protein-based technologies, we identified a signaling network critical for influenza virus internalization and infection. In addition, we developed a highly sensitive biosensor for monitoring kinase activity that utilizes energy transfer between fluorescent proteins. This has led to a high-performance clinical test that enables the prediction of future therapeutic responses and the risk of acquired drug resistance for each individual patient before beginning molecular target therapy. CONCLUSION: Technologies that utilize fluorescent proteins, such as the biosensor presented here, should find increasing applications in clinical medicine.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.job.2016.07.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32512679" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Nov", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "113-119", "proceedings_title": null, "publisher": "", "title": "Journal of oral biosciences", "volume": "58", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Fluorescence bioimaging of intracellular signaling and its clinical application.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Exocrine glands, e.g., salivary and pancreatic glands, play an important role in digestive enzyme secretion, while endocrine glands, e.g., pancreatic islets, secrete hormones that regulate blood glucose levels. The dysfunction of these secretory organs immediately leads to various diseases, such as diabetes or Sjogren's syndrome, by poorly understood mechanisms. Gland-related diseases have been studied by optical microscopy (OM), and at higher resolution by transmission electron microscopy (TEM) of Epon embedded samples, which necessitates hydrophobic sample pretreatment. Here, we report the direct observation of tissue in aqueous solution by atmospheric scanning electron microscopy (ASEM). Salivary glands, lacrimal glands, and pancreas were fixed, sectioned into slabs, stained with phosphotungstic acid (PTA), and inspected in radical scavenger d-glucose solution from below by an inverted scanning electron microscopy (SEM), guided by optical microscopy from above to target the tissue substructures. A 2- to 3-microm specimen thickness was visualized by the SEM. In secretory cells, cytoplasmic vesicles and other organelles were clearly imaged at high resolution, and the former could be classified according to the degree of PTA staining. In islets of Langerhans, the microvascular system used as an outlet by the secretory cells was also clearly observed. Microvascular system is also critically involved in the onset of diabetic complications and was clearly visible in subcutaneous tissue imaged by ASEM. The results suggest the use of in-solution ASEM for histology and to study vesicle secretion systems. Further, the high-throughput of ASEM makes it a potential tool for the diagnosis of exocrine and endocrine-related diseases.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Toshiko", "last_name": "Yamazawa", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Chikara", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/jemt.22773" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27696606" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Harderian Gland", "descriptor_ui": "D006243", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Microscopy, Electron, Scanning", "descriptor_ui": "D008855", "major_topic": false }, { "descriptor": "Pancreas", "descriptor_ui": "D010179", "major_topic": true }, { "descriptor": "Salivary Glands", "descriptor_ui": "D012469", "major_topic": true }, { "descriptor": "Subcutaneous Tissue", "descriptor_ui": "D040521", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1179-1187", "proceedings_title": null, "publisher": "", "title": "Microscopy research and technique", "volume": "79", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Secretory glands and microvascular systems imaged in aqueous solution by atmospheric scanning electron microscopy (ASEM).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Antiangiogenic agents transiently normalize tumor vessel structure and improve vessel function, thereby providing a window of opportunity for enhancing the efficacy of chemotherapy or radiotherapy. Currently, there are no reliable predictors or markers reflecting this vessel normalization window during antiangiogenic therapy. Apelin, the expression of which is regulated by hypoxia, and which has well-described roles in tumor progression, is an easily measured secreted protein. Here, we show that apelin can be used as a marker for the vessel normalization window during antiangiogenic therapy. Mice bearing s.c. tumors resulting from inoculation of the colon adenocarcinoma cell line HT29 were treated with a single injection of bevacizumab, a mAb neutralizing vascular endothelial growth factor. Tumor growth, vessel density, pericyte coverage, tumor hypoxia, and small molecule delivery were determined at four different times after treatment with bevacizumab (days 1, 3, 5, and 8). Tumor growth and vessel density were significantly reduced after bevacizumab treatment, which also significantly increased tumor vessel maturity, and improved tumor hypoxia and small molecule delivery between days 3 and 5. These effects abated by day 8, suggesting that a time window for vessel normalization was opened between days 3 and 5 during bevacizumab treatment in this model. Apelin mRNA expression and plasma apelin levels decreased transiently at day 5 post-treatment, coinciding with vessel normalization. Thus, apelin is a potential indicator of the vessel normalization window during antiangiogenic therapy.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Li", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takara", "name": null }, { "creator_type": "author", "first_name": "Daishi", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.12836" }, "pmcid": { "normalized": "PMC4724822" }, "pmid": { "normalized": "26475217" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Angiogenesis Inhibitors", "descriptor_ui": "D020533", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apelin", "descriptor_ui": "D000073861", "major_topic": false }, { "descriptor": "Bevacizumab", "descriptor_ui": "D000068258", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cell Separation", "descriptor_ui": "D002469", "major_topic": false }, { "descriptor": "Colonic Neoplasms", "descriptor_ui": "D003110", "major_topic": false }, { "descriptor": "Enzyme-Linked Immunosorbent Assay", "descriptor_ui": "D004797", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": false }, { "descriptor": "HT29 Cells", "descriptor_ui": "D019073", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "36-44", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "107", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This article contains structure and pharmacological characteristics of melanocortin receptors (MCRs) related to research published in \"Characterization of melanocortin receptors from stingray Dasyatis akajei, a cartilaginous fish\" (Takahashi et al., 2016) [1]. The amino acid sequences of the stingray, D. akajei, MC1R, MC2R, MC3R, MC4R, and MC5R were aligned with the corresponding melanocortin receptor sequences from the elephant shark, Callorhinchus milii, the dogfish, Squalus acanthias, the goldfish, Carassius auratus, and the mouse, Mus musculus. These alignments provide the basis for phylogenetic analysis of these gnathostome melanocortin receptor sequences. In addition, the Japanese stingray melanocortin receptors were separately expressed in Chinese Hamster Ovary cells, and stimulated with stingray ACTH, alpha-MSH, beta-MSH, gamma-MSH, delta-MSH, and beta-endorphin. The dose response curves reveal the order of ligand selectivity for each stingray MCR.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Perry", "last_name": "Davis", "name": null }, { "creator_type": "author", "first_name": "Christina", "last_name": "Reinick", "name": null }, { "creator_type": "author", "first_name": "Kanta", "last_name": "Mizusawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Robert M.", "last_name": "Dores", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.dib.2016.04.050" }, "pmcid": { "normalized": "PMC4927774" }, "pmid": { "normalized": "27408924" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Jun", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "1670-1677", "proceedings_title": null, "publisher": "", "title": "Data in brief", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Data for amino acid alignment of Japanese stingray melanocortin receptors with other gnathostome melanocortin receptor sequences, and the ligand selectivity of Japanese stingray melanocortin receptors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "How symbioses between bacteria and aquatic animals influence food webs in freshwater ecosystems is a fundamental question in ecology. We investigated symbiosis between a crustacean zooplankton Daphnia magna and its dominant bacterial symbiont Limnohabitans, an abundant and globally distributed freshwater Betaproteobacteria. Aposymbiotic juvenile Daphnia were prepared and exposed to any of four Limnohabitans sp. - Limnohabitans strains DM1, 2KL-3, 2KL-7 and Limnohabitans planktonicus strain II-D5, all previously found in D. magna digestive tract or culture. Re-infected Daphnia were cultured until they produced the first clutch of juveniles. Limnohabitans strain DM1 and L. planktonicus strain II-D5 successfully re-infected Daphnia through single exposure at the first instar juvenile stage. In contrast to aposymbiotic Daphnia that produced non-viable juveniles, re-infected Daphnia produced viable juveniles and increased fecundity to levels of that of symbiotic Daphnia. Re-infected Daphnia did not increase their number of eggs nor growth rates. Limnohabitans strains 2KL-7 and 2KL-3 could not recover fecundity even in multiple exposures during culture. This study shows the functional evidence demonstrating that a single bacterium Limnohabitans regulates fecundity of the consumer Daphnia through symbiosis. Our results indicated that symbiotic relationship between major bacterioplankton and zooplankton is important for maintaining the population of zooplankton in freshwater ecosystems.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Saranya", "last_name": "Peerakietkhajorn", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Vojtech", "last_name": "Kasalicky", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/1462-2920.12919" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26014379" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Betaproteobacteria", "descriptor_ui": "D020562", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "Ecosystem", "descriptor_ui": "D017753", "major_topic": false }, { "descriptor": "Fertility", "descriptor_ui": "D005298", "major_topic": false }, { "descriptor": "Food Chain", "descriptor_ui": "D020387", "major_topic": false }, { "descriptor": "Fresh Water", "descriptor_ui": "D005618", "major_topic": false }, { "descriptor": "Symbiosis", "descriptor_ui": "D013559", "major_topic": true }, { "descriptor": "Zooplankton", "descriptor_ui": "D015048", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Sep", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "2366-2374", "proceedings_title": null, "publisher": "", "title": "Environmental microbiology", "volume": "18", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Betaproteobacteria Limnohabitans strains increase fecundity in the crustacean Daphnia magna: symbiotic relationship between major bacterioplankton and zooplankton in freshwater ecosystem.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "RATIONALE: The acetylcholinesterase inhibitors donepezil, galantamine, and rivastigmine are used for the treatment of Alzheimer's disease. We previously demonstrated that donepezil and galantamine differentially affect isolation rearing-induced prepulse inhibition (PPI) deficits and that this might be due to differential effects on brain muscarinic acetylcholine (mACh) receptor function in mice. OBJECTIVES: We examined the effects of rivastigmine on isolation rearing-induced PPI deficits, brain ACh levels, and mACh receptor function in mice. METHODS: Acoustic startle responses were measured in a startle chamber. Microdialysis was performed, and the levels of dopamine and ACh in the prefrontal cortex were measured. RESULTS: Rivastigmine (0.3 mg/kg) improved PPI deficits, and this improvement was antagonized by the mACh receptor antagonist telenzepine but not by the nicotinic ACh receptor antagonist mecamylamine. Rivastigmine increased extracellular ACh levels by approximately 2-3-fold, less than the increase produced by galantamine. Rivastigmine enhanced the effect of the mACh receptor agonist N-desmethylclozapine on prefrontal dopamine release, a marker of mACh receptor function, and this increase was blocked by telenzepine. In contrast, galantamine did not affect N-desmethylclozapine-induced dopamine release. Furthermore, rivastigmine did not affect cortical dopamine release induced by the serotonin1A receptor agonist osemozotan, suggesting that the effect of rivastigmine has specificity for mACh receptors. CONCLUSIONS: Taken together with our previous finding that marked increases in ACh levels are required for the PPI deficit improvement induced by galantamine, our present results suggest that rivastigmine improves isolation rearing-induced PPI deficits by increasing ACh levels and by concomitantly enhancing mACh receptor function.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Higashino", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Umeki", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Onaka", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00213-015-4123-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26518025" } }, "mesh": [ { "descriptor": "Acetylcholine", "descriptor_ui": "D000109", "major_topic": false }, { "descriptor": "Acoustic Stimulation", "descriptor_ui": "D000161", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain Chemistry", "descriptor_ui": "D001923", "major_topic": false }, { "descriptor": "Cholinesterase Inhibitors", "descriptor_ui": "D002800", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mecamylamine", "descriptor_ui": "D008464", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscarinic Antagonists", "descriptor_ui": "D018727", "major_topic": false }, { "descriptor": "Nicotinic Antagonists", "descriptor_ui": "D018733", "major_topic": false }, { "descriptor": "Pirenzepine", "descriptor_ui": "D010890", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Receptor, Serotonin, 5-HT1A", "descriptor_ui": "D044282", "major_topic": false }, { "descriptor": "Receptors, Muscarinic", "descriptor_ui": "D011976", "major_topic": false }, { "descriptor": "Reflex, Startle", "descriptor_ui": "D013216", "major_topic": false }, { "descriptor": "Rivastigmine", "descriptor_ui": "D000068836", "major_topic": false }, { "descriptor": "Social Isolation", "descriptor_ui": "D012934", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Feb", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "521-528", "proceedings_title": null, "publisher": "", "title": "Psychopharmacology", "volume": "233", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Rivastigmine improves isolation rearing-induced prepulse inhibition deficits via muscarinic acetylcholine receptors in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the fruitfly Drosophila melanogaster, circadian rhythms of locomotor activity under constant darkness are controlled by pacemaker neurons. To understand how behavioral rhythmicity is generated by the nervous system, it is essential to identify the output circuits from the pacemaker neurons. A recent study of Drosophila has suggested that pacemaker neurons project to mushroom body (MB) neurons, which are considered the memory center in Drosophila. MBs also regulate spontaneous locomotor activity without learning, suggesting that MB neuronal activity regulates behavioral rhythms. However, the importance of MBs in generating behavioral rhythmicity remains controversial because contradicting results have been reported as follows: (1) locomotor activity in MB-ablated flies is substantially rhythmic, but (2) activation of restricted neuronal populations including MB neurons induces arrhythmic locomotor activity. Here, we report that neurotransmission in MBs is required for behavioral rhythmicity. For adult-specific disruption of neurotransmission in MBs, we used the GAL80/GAL4/UAS ternary gene expression system in combination with the temperature-sensitive dynamin mutation shibire(ts1). Blocking of neurotransmission in GAL4-positive neurons including MB neurons induced arrhythmic locomotor activity, whereas this arrhythmicity was rescued by the MB-specific expression of GAL80. Our results indicate that MB signaling plays a key role in locomotor activity rhythms in Drosophila.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ikumi", "last_name": "Mabuchi", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Shoma", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kahori", "last_name": "Ienaga", "name": null }, { "creator_type": "author", "first_name": "Show", "last_name": "Inami", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2016.04.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27106579" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Darkness", "descriptor_ui": "D003624", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Dynamins", "descriptor_ui": "D034281", "major_topic": false }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": false }, { "descriptor": "Mushroom Bodies", "descriptor_ui": "D024521", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "25-33", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "111", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Mushroom body signaling is required for locomotor activity rhythms in Drosophila.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Our sleep is composed of rapid eye movement (REM) sleep and non-REM (NREM) sleep. REM sleep is the major source of dreams, whereas synchronous cortical oscillations, called slow waves, are observed during NREM sleep. Both stages are unique to certain vertebrate species, and therefore, REM and NREM sleep are thought to be involved in higher-order brain functions. While several studies have revealed the importance of NREM sleep in growth hormone secretion, memory consolidation and brain metabolite clearance, the functions of REM sleep are currently almost totally unknown. REM sleep functions cannot be easily indicated from classical REM sleep deprivation experiments, where animals are forced to wake up whenever they enter REM sleep, because such experiments produce extreme stress due to the stimuli and because REM sleep is under strong homeostatic regulation. To overcome these issues, we developed a novel transgenic mouse model in which REM sleep can be manipulated. Using these mice, we found that REM sleep enhances slow wave activity during the subsequent NREM sleep. Slow wave activity is known to contribute to memory consolidation and synaptic plasticity. Thus, REM sleep might be involved in higher-order brain functions through its role in enhancing slow wave activity.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuaki", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.11477/mf.1416200575" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27703108" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dreams", "descriptor_ui": "D004325", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Sleep Deprivation", "descriptor_ui": "D012892", "major_topic": false }, { "descriptor": "Sleep, REM", "descriptor_ui": "D012895", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "1205-1211", "proceedings_title": null, "publisher": "", "title": "Brain and nerve = Shinkei kenkyu no shinpo", "volume": "68", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "[The Function of REM Sleep: Implications from Transgenic Mouse Models].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Skin fibroblast heterogeneity is of growing interest due to its relevance in not only skin development but also cutaneous wound healing. However, the characterization of human dermal fibroblasts at a clonal level has not been accomplished and their functional heterogeneity remains poorly understood. OBJECTIVE: The aim of this study was to define the clonal heterogeneity of human dermal fibroblasts. METHODS: Isolated human dermal fibroblasts were clonally expanded and categorized by comprehensive phenotypic and gene expression profiling. RESULTS: Single fibroblasts were significantly multiplied and efficiently cloned without chromosomal abnormalities under hypoxic conditions. Individual clones were heterogeneous in their proliferative capacity, and gene expression profiling revealed differences in the expression of genes involved in extracellular matrix synthesis and degradation. Each cloned fibroblast also had different abilities in terms of collagen remodeling. All phenotypic and gene expression data were analyzed with Spearman's rank correlation, and fibroblasts were categorized into at least two functional clonal types. One was highly proliferative, while the other was less proliferative but had the ability to remodel the tissue architecture. The proliferative clones were predominant in infants, but decreased with physiological aging. CONCLUSION: This study provides strong evidence for the functional heterogeneity of human dermal fibroblasts at a clonal level, which has implications regarding skin repair and aging.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Chihiro", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Fujio", "last_name": "Toki", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Sayama", "name": null }, { "creator_type": "author", "first_name": "Emi K.", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Nanba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jdermsci.2016.01.009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26867959" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Child", "descriptor_ui": "D002648", "major_topic": false }, { "descriptor": "Child, Preschool", "descriptor_ui": "D002675", "major_topic": false }, { "descriptor": "Clone Cells", "descriptor_ui": "D002999", "major_topic": false }, { "descriptor": "Collagen", "descriptor_ui": "D003094", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infant", "descriptor_ui": "D007223", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Skin Aging", "descriptor_ui": "D015595", "major_topic": false }, { "descriptor": "Wound Healing", "descriptor_ui": "D014945", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 May", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "84-94", "proceedings_title": null, "publisher": "", "title": "Journal of dermatological science", "volume": "82", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Two clonal types of human skin fibroblasts with different potentials for proliferation and tissue remodeling ability.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mg(2+) is an essential cation to maintain cellular functions, and intracellular Mg(2+) concentration ([Mg(2+)]i) is regulated by Mg(2+) channels and transporters. In our previous study, we demonstrated that MPP(+) elicits Mg(2+) influx across the cell membrane and Mg(2+) mobilization from mitochondria, and the resulting [Mg(2+)]i is an important determinants of the cell viability in MPP(+) model of Parkinson's disease (PD). It indicates that cellular Mg(2+) transport is one of the important factors to determine the progress of PD. However, whether the expression levels of Mg(2+) transport proteins change in the progress of PD has still been obscure. In this study, we estimated the mRNA expression levels of Mg(2+) transport proteins upon the exposure to MPP(+). In thirteen Mg(2+) transport proteins examined, mRNA expression level of SLC41A2 was increased and that of ACDP2, NIPA1 and MMgT2 were decreased. Knockdown of SLC41A2, ACDP2 or NIPA1 accelerated the MPP(+)-induced cell degeneration, and overexpression attenuated it. The decrease in the mRNA expression levels of NIPA1 and MMgT2 were also elicited by rotenone, H2O2 and FCCP, indicating that mitochondrial dysfunction related to this down-regulation. The increase in that of SLC41A2 was induced by an uncoupler, FCCP, as well as MPP(+), suggesting that it is an intrinsic protection mechanism against depolarized mitochondrial membrane potential and/or cellular ATP depletion. Our results shown here indicate that alteration of Mg(2+) transport proteins is implicated in the MPP(+) model of PD, and it affects cell degeneration.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbamcr.2016.05.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27157538" } }, "mesh": [ { "descriptor": "1-Methyl-4-phenylpyridinium", "descriptor_ui": "D015655", "major_topic": false }, { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone", "descriptor_ui": "D002259", "major_topic": false }, { "descriptor": "Cation Transport Proteins", "descriptor_ui": "D027682", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": false }, { "descriptor": "Ion Transport", "descriptor_ui": "D017136", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Membrane Potential, Mitochondrial", "descriptor_ui": "D053078", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "MPTP Poisoning", "descriptor_ui": "D020267", "major_topic": false }, { "descriptor": "Nerve Degeneration", "descriptor_ui": "D009410", "major_topic": false }, { "descriptor": "Nerve Growth Factor", "descriptor_ui": "D020932", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Rotenone", "descriptor_ui": "D012402", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "1979-1984", "proceedings_title": null, "publisher": "", "title": "Biochimica et biophysica acta", "volume": "1863", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Altered expression of Mg(2+) transport proteins during Parkinson's disease-like dopaminergic cell degeneration in PC12 cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Activation of caspases is crucial for the execution of apoptosis. Although the caspase cascade associated with activation of the initiator caspase-8 (CASP8) has been investigated in molecular and biochemical detail, the physiological role of CASP8 is not fully understood. Here, we identified a two-pore domain potassium channel, tandem-pore domain halothane-inhibited K(+) channel 1 (THIK-1), as a novel CASP8 substrate. The intracellular region of THIK-1 was cleaved by CASP8 in apoptotic cells. Overexpression of THIK-1, but not its mutant lacking the CASP8-target sequence in the intracellular portion, accelerated cell shrinkage in response to apoptotic stimuli. In contrast, knockdown of endogenous THIK-1 by RNA interference resulted in delayed shrinkage and potassium efflux. Furthermore, a truncated THIK-1 mutant lacking the intracellular region, which mimics the form cleaved by CASP8, led to a decrease of cell volume of cultured cells without apoptotic stimulation and excessively promoted irregular development of Xenopus embryos. Taken together, these results indicate that THIK-1 is involved in the acceleration of cell shrinkage. Thus, we have demonstrated a novel physiological role of CASP8: creating a cascade that advances the cell to the next stage in the apoptotic process.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Sakamaki", "name": null }, { "creator_type": "author", "first_name": "Takahiro M.", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Sakata", "name": null }, { "creator_type": "author", "first_name": "Kiwamu", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Chiyo", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Nozawa", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Shinoda", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Haruyo", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Tamate", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Satou", "name": null }, { "creator_type": "author", "first_name": "Sang-Kee", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Koyamada", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sawasaki", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Ueno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbamcr.2016.08.010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27566292" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Caspase 8", "descriptor_ui": "D053181", "major_topic": false }, { "descriptor": "Cell Size", "descriptor_ui": "D048429", "major_topic": true }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MCF-7 Cells", "descriptor_ui": "D061986", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Potassium Channels, Tandem Pore Domain", "descriptor_ui": "D024683", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Interaction Domains and Motifs", "descriptor_ui": "D054730", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false }, { "descriptor": "Xenopus laevis", "descriptor_ui": "D014982", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "2766-2783", "proceedings_title": null, "publisher": "", "title": "Biochimica et biophysica acta", "volume": "1863", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Dysregulation of a potassium channel, THIK-1, targeted by caspase-8 accelerates cell shrinkage.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Amino-terminal enhancer of split (Aes) is a member of Groucho/Transducin-like enhancer (TLE) family. Aes is a recently found metastasis suppressor of colorectal cancer (CRC) that inhibits Notch signalling, and forms nuclear foci together with TLE1. Although some Notch-associated proteins are known to form subnuclear bodies, little is known regarding the dynamics or functions of these structures. Here, we show that Aes nuclear foci in CRC observed under an electron microscope are in a rather amorphous structure, lacking surrounding membrane. Investigation of their behaviour during the cell cycle by time-lapse cinematography showed that Aes nuclear foci dissolve during mitosis and reassemble after completion of cytokinesis. We have also found that heat shock cognate 70 (HSC70) is an essential component of Aes foci. Pharmacological inhibition of the HSC70 ATPase activity with VER155008 reduces Aes focus formation. These results provide insight into the understanding of Aes-mediated inhibition of Notch signalling.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiro", "last_name": "Itatani", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Kakizaki", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Okawa", "name": null }, { "creator_type": "author", "first_name": "Stefano", "last_name": "Stifani", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Yoshiharu", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "M. Mark", "last_name": "Taketo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jb/mvv077" }, "pmcid": { "normalized": "PMC4882644" }, "pmid": { "normalized": "26229111" } }, "mesh": [ { "descriptor": "Adenosine Triphosphatases", "descriptor_ui": "D000251", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Co-Repressor Proteins", "descriptor_ui": "D056970", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Cytokinesis", "descriptor_ui": "D048749", "major_topic": false }, { "descriptor": "HCT116 Cells", "descriptor_ui": "D045325", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HSC70 Heat-Shock Proteins", "descriptor_ui": "D050883", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Microscopy, Immunoelectron", "descriptor_ui": "D016253", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false }, { "descriptor": "Purine Nucleosides", "descriptor_ui": "D011684", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "133-140", "proceedings_title": null, "publisher": "", "title": "Journal of biochemistry", "volume": "159", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Characterization of Aes nuclear foci in colorectal cancer cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The canonical Wnt signaling pathway plays a major role in the regulation of embryogenesis and organogenesis, where signal strength-dependent cellular responses are of particular importance. To assess Wnt signal levels in individual cells, and to circumvent the integration site-dependent bias shown in previous Wnt reporter lines, we constructed a new Wnt signal reporter mouse line R26-WntVis. Heptameric TCF/LEF1 binding sequences were combined with a viral minimal promoter to confer a graded response to the reporter depending on Wnt signal strengths. The histone H2B-EGFP fusion protein was chosen as the fluorescent reporter to facilitate single-cell resolution analyses. This WntVis reporter gene was then inserted into the ROSA26 locus in an orientation opposite to that of the endogenous gene. The R26-WntVis allele was introduced into Wnt3a(-/-) and Wnt3a(vt/-) mutant mouse embryos and compared with wild-type embryos to assess its performance. The R26-WntVis reporter was activated in known Wnt-dependent tissues and responded in a graded fashion to signal intensity. This analysis also indicated that the major Wnt activity early in embryogenesis switched from Wnt3 to Wnt3a around E7.5. The R26-WntVis mouse line will be widely useful for the study of Wnt signal-dependent processes.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyonari", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Yasuhide", "last_name": "Furuta", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Kondoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.12364" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27030109" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Gastrula", "descriptor_ui": "D005775", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Wnt Proteins", "descriptor_ui": "D051153", "major_topic": false }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "661-669", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "21", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "R26-WntVis reporter mice showing graded response to Wnt signal levels.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This study tested the hypothesis that oocyte-derived paracrine factors (ODPFs) regulate miRNA expression in mouse granulosa cells. Expression of mmu-miR-322-5p (miR-322) was higher in mural granulosa cells (MGCs) than in cumulus cells of the Graafian follicles. The expression levels of miR-322 decreased when cumulus cells or MGCs were co-cultured with oocytes denuded of their cumulus cells. Inhibition of SMAD2/3 signaling by SB431542 increased miR-322 expression by cumulus-oocyte complexes (COCs). Moreover, the cumulus cells but not the MGCs in Bmp15–/–/Gdf9+/– (double-mutant) mice exhibited higher miR-322 expression than those of wild-type mice. Taken together, these results show that ODPFs suppress the expression of miR-322 in cumulus cells. Gene ontology analysis of putative miR-322 targets whose expression was detected in MGCs with RNA-sequencing suggested that multiple biological processes are affected by miR-322 in MGCs. These results demonstrate that ODPFs regulate miRNA expression in granulosa cells and that this regulation may participate in the differential control of cumulus cell versus MGC functions. Therefore, the ODPF-mediated regulation of cumulus cells takes place at both transcriptional and post-transcriptional levels.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Jun-ichi", "last_name": "SUMITOMO", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "EMORI", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "MATSUNO", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "UENO", "name": null }, { "creator_type": "author", "first_name": "Kurenai", "last_name": "KAWASAKI", "name": null }, { "creator_type": "author", "first_name": "Takaho A.", "last_name": "ENDO", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "SHIROGUCHI", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "FUJII", "name": null }, { "creator_type": "author", "first_name": "Kunihiko", "last_name": "NAITO", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "SUGIURA", "name": null } ], "identifiers": { "doi": { "normalized": "10.1262/jrd.2015-161" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27180925" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Morphogenetic Protein 15", "descriptor_ui": "D055430", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Cumulus Cells", "descriptor_ui": "D054885", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Granulosa Cells", "descriptor_ui": "D006107", "major_topic": false }, { "descriptor": "Growth Differentiation Factor 9", "descriptor_ui": "D055429", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Oocytes", "descriptor_ui": "D009865", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "393-399", "proceedings_title": null, "publisher": "", "title": "The Journal of Reproduction and Development", "volume": "62", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Mouse oocytes suppress miR-322-5p expression in ovarian granulosa cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Brugada syndrome (BrS) is an inherited lethal arrhythmic disorder characterized by syncope and sudden cardiac death from ventricular tachyarrhythmias. Here we identified a novel K817E mutation of SCN5A gene in a man with type 1 BrS electrocardiogram pattern using next-generation sequencing targeted for 73 cardiac disorder-related genes. SCN5A encodes the alpha-subunit of NaV1.5 voltage-gated Na(+) channel, and some of its mutations are linked to BrS. The proband had no mutation in any of the other arrhythmia-related genes sequenced. OBJECTIVE: We investigated whether the K817E mutation causes a functional change of NaV1.5 channel responsible for the BrS phenotype. METHODS: We compared the electrophysiological properties of the whole-cell currents mediated by wild-type and mutant channels heterologously expressed in human embryonic kidney 293 cells by using a voltage-clamp technique. RESULTS: The K817E mutation reduced the Na(+) current density by 39.0%-91.4% at membrane potentials from -55 to -5 mV. This reduction resulted from a ~24-mV positive shift in the voltage dependence of activation. The mutation also decelerated recovery from both fast and intermediate inactivation, whereas it had little effect on the cell surface expression, single-channel conductance, voltage-dependence of fast inactivation, entry into intermediate inactivation, use-dependent loss of channel availability, or closed-state inactivation. CONCLUSION: The K817E mutation of SCN5A gene leads to loss of function of NaV1.5 channel and may underlie the BrS phenotype of the proband.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Koshi", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Kohki", "last_name": "Nishide", "name": null }, { "creator_type": "author", "first_name": "Mario", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Mizumaki", "name": null }, { "creator_type": "author", "first_name": "Kunihiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.hrthm.2016.01.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26776555" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Asymptomatic Diseases", "descriptor_ui": "D058070", "major_topic": false }, { "descriptor": "Brugada Syndrome", "descriptor_ui": "D053840", "major_topic": true }, { "descriptor": "Electrocardiography", "descriptor_ui": "D004562", "major_topic": false }, { "descriptor": "Electrophysiologic Techniques, Cardiac", "descriptor_ui": "D022062", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "NAV1.5 Voltage-Gated Sodium Channel", "descriptor_ui": "D062554", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "1113-1120", "proceedings_title": null, "publisher": "", "title": "Heart rhythm", "volume": "13", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "SCN5A(K817E), a novel Brugada syndrome-associated mutation that alters the activation gating of NaV1.5 channel.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genetically modified pigs for biomedical applications have been mainly generated using the somatic cell nuclear transfer technique; however, this approach requires complex micromanipulation techniques and sometimes increases the risks of both prenatal and postnatal death by faulty epigenetic reprogramming of a donor somatic cell nucleus. As a result, the production of genetically modified pigs has not been widely applied. We provide a simple method for CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 gene editing in pigs that involves the introduction of Cas9 protein and single-guide RNA into in vitro fertilized zygotes by electroporation. The use of gene editing by electroporation of Cas9 protein (GEEP) resulted in highly efficient targeted gene disruption and was validated by the efficient production of Myostatin mutant pigs. Because GEEP does not require the complex methods associated with micromanipulation for somatic reprogramming, it has the potential for facilitating the genetic modification of pigs.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Fuminori", "last_name": "Tanihara", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Shengbin", "last_name": "Rao", "name": null }, { "creator_type": "author", "first_name": "Lanh Thi Kim", "last_name": "Do", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Onishi", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Chisato", "last_name": "Kosugi", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shoichiro", "last_name": "Sembon", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yasue", "name": null }, { "creator_type": "author", "first_name": "Munehide", "last_name": "Matsuhisa", "name": null }, { "creator_type": "author", "first_name": "Sumihare", "last_name": "Noji", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Fujimura", "name": null }, { "creator_type": "author", "first_name": "Dai-Ichiro", "last_name": "Fuchimoto", "name": null }, { "creator_type": "author", "first_name": "Takeshige", "last_name": "Otoi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.1600803" }, "pmcid": { "normalized": "PMC5023319" }, "pmid": { "normalized": "27652340" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Fertilization in Vitro", "descriptor_ui": "D005307", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Myostatin", "descriptor_ui": "D055435", "major_topic": false }, { "descriptor": "Nuclear Transfer Techniques", "descriptor_ui": "D053652", "major_topic": true }, { "descriptor": "RNA Editing", "descriptor_ui": "D017393", "major_topic": false }, { "descriptor": "Swine", "descriptor_ui": "D013552", "major_topic": false }, { "descriptor": "Zygote", "descriptor_ui": "D015053", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "e1600803", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "2", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Somatic cell reprogramming-free generation of genetically modified pigs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Over the past decades many researchers have made major contributions towards the development of genetically encoded (GE) fluorescent sensors derived from fluorescent proteins. GE sensors are now used to study biological phenomena by facilitating the measurement of biochemical behaviors at various scales, ranging from single molecules to single cells or even whole animals. Here, we review the historical development of GE fluorescent sensors and report on their current status. We specifically focus on the development strategies of the GE sensors used for measuring pH, ion concentrations (e.g., chloride and calcium), redox indicators, membrane potential, temperature, pressure, and molecular crowding. We demonstrate that these fluroescent protein-based sensors have a shared history of concepts and development strategies, and we highlight the most original concepts used to date. We believe that the understanding and application of these various concepts will pave the road for the development of future GE sensors and lead to new breakthroughs in bioimaging.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Arno", "last_name": "Germond", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12551-016-0195-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28510054" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Jun", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "121-138", "proceedings_title": null, "publisher": "", "title": "Biophysical Reviews", "volume": "8", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Design and development of genetically encoded fluorescent sensors to monitor intracellular chemical and physical parameters.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Arterial and venous blood gas analyses (BGAs) are essential to evaluate devices that measure biological oxygenation. The appropriate timing of blood sampling for BGA after respiratory rate (RR) change in animal experiments has not been reported. This study investigated the appropriate timing of blood sampling for BGA in ventilated rabbits and whether venous samples are an alternative to arterial samples. MATERIALS AND METHODS: Under general anesthesia, 14 rabbits (body weight, 3.02 +/- 0.09 kg) were ventilated and their RR was changed (40/min, 30/min, and 20/min). Blood was sampled through cervical arterial and venous catheters. Experiment 1: in seven rabbits, arterial BGA was measured at 0, 0.5, 1, 2, 3, 5, 10, 15, and 20 min after the RR change. Experiment 2: in seven different rabbits, simultaneous arterial and venous BGA were measured at 0, 2, 5, 10, 15, and 20 min after the RR change. RESULTS: Oxygen partial pressure (PO2) and saturation (SO2) of the arterial blood stabilized 0.5 min after the RR changed. In venous BGA, no index stabilized during observation. The arterial and venous values of the carbon dioxide partial pressure (PCO2) and pH had significant correlations (arterial PCO2 = 0.9316 x venous PCO2-4.4425 [r = 0.9178]; arterial pH = 1.0835 x venous pH-0.5795 [r = 0.9453]). CONCLUSIONS: In ventilated rabbits, arterial PO2 and SO2 stabilized in 0.5 min. No venous value stabilized after the RR change. Only the PCO2 and pH of venous samples may be an alternative to arterial samples under the defined formula.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kiguna", "last_name": "Sei", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Okawa", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Sasa", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Furuya", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jss.2016.08.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27884326" } }, "mesh": [ { "descriptor": "Anesthesia, General", "descriptor_ui": "D000768", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arteries", "descriptor_ui": "D001158", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Blood Gas Analysis", "descriptor_ui": "D001784", "major_topic": false }, { "descriptor": "Blood Specimen Collection", "descriptor_ui": "D001800", "major_topic": false }, { "descriptor": "Carbon Dioxide", "descriptor_ui": "D002245", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Respiration, Artificial", "descriptor_ui": "D012121", "major_topic": true }, { "descriptor": "Respiratory Rate", "descriptor_ui": "D056152", "major_topic": true }, { "descriptor": "Veins", "descriptor_ui": "D014680", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "325-336", "proceedings_title": null, "publisher": "", "title": "The Journal of surgical research", "volume": "206", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Appropriate timing of blood sampling for blood gas analysis in the ventilated rabbit.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Thymus-derived regulatory T cells (Tregs) are considered to be a distinct T-cell lineage that is genetically programmed and specialised for immunosuppression. This perspective is based on the key evidence that CD25+ Tregs emigrate to neonatal spleen a few days later than other T cells and that thymectomy of 3-day-old mice depletes Tregs only, causing autoimmune diseases. Although widely believed, the evidence has never been reproduced as originally reported, and some studies indicate that Tregs exist in neonates. Thus we examine the consequences of the controversial evidence, revisit the fundamental issues of Tregs and thereby reveal the overlooked relationship of T-cell activation and Foxp3-mediated control of the T-cell system. Here we provide a new model of Tregs and Foxp3, a feedback control perspective, which views Tregs as a component of the system that controls T-cell activation, rather than as a distinct genetically programmed lineage. This perspective provides new insights into the roles of self-reactivity, T cell–antigen-presenting cell interaction and T-cell activation in Foxp3-mediated immune regulation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Reiko J.", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/icb.2015.65" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26215792" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Feedback, Physiological", "descriptor_ui": "D025461", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Immunological", "descriptor_ui": "D018448", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false }, { "descriptor": "Thymus Gland", "descriptor_ui": "D013950", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "3-10", "proceedings_title": null, "publisher": "", "title": "Immunology and Cell Biology", "volume": "94", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Controversies concerning thymus-derived regulatory T cells: fundamental issues and a new perspective.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The crustacean hyperglycemic hormone (CHH) is one of the major hormones in crustaceans, and peptides belonging to the CHH superfamily have been found in diverse ecdysozoans. Although the basic function of CHH is to control energy metabolism, it also plays various roles in crustacean species, such as in molting and vitellogenesis. Here, we present the crystal structure of Pej-SGP-I-Gly, a partially active precursor of CHH from the kuruma prawn Marsupenaeus japonicus, which has an additional Gly residue in place of the C-terminal amide group of the mature Pej-SGP-I. The 1.6-angstrom crystal structure showed not only the common CHH superfamily scaffold comprising three alpha-helices, three disulfide bridges, and a hydrophobic core but also revealed that the C-terminal part has a variant backbone fold that is specific to Pej-SGP-I-Gly. The alpha-helix 4 of Pej-SGP-I-Gly was much longer than that of molt-inhibiting hormone (Pej-MIH) from the same species, and as a result, the following C-terminal helix, corresponding to alpha-helix 5 in MIH, was not formed. Unlike monomeric Pej-MIH, Pej-SGP-I-Gly forms a homodimer in the crystal structure via its unique alpha-helix 4. The unexpected dissimilar folds between Pej-SGP-I-Gly and Pej-MIH appear to be the result of their distinct C-terminal amino acid sequences. Variations in amino acid sequences and lengths and the resulting variety of backbone folds allow the C-terminal and sterically adjoining regions to confer different hormonal activities in diverse CHH superfamily members. DATABASE: Structural data are available in the PDB under the accession number 5B5I.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naoaki", "last_name": "Tsutsui", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Arisaka", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tanokura", "name": null }, { "creator_type": "author", "first_name": "Hiromichi", "last_name": "Nagasawa", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Nagata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/febs.13926" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27743429" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arthropod Proteins", "descriptor_ui": "D060829", "major_topic": false }, { "descriptor": "Crystallography, X-Ray", "descriptor_ui": "D018360", "major_topic": false }, { "descriptor": "Databases, Protein", "descriptor_ui": "D030562", "major_topic": false }, { "descriptor": "Disulfides", "descriptor_ui": "D004220", "major_topic": false }, { "descriptor": "Hydrogen Bonding", "descriptor_ui": "D006860", "major_topic": false }, { "descriptor": "Invertebrate Hormones", "descriptor_ui": "D007447", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Multigene Family", "descriptor_ui": "D005810", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Penaeidae", "descriptor_ui": "D033561", "major_topic": false }, { "descriptor": "Protein Domains", "descriptor_ui": "D000072417", "major_topic": false }, { "descriptor": "Protein Multimerization", "descriptor_ui": "D055503", "major_topic": false }, { "descriptor": "Protein Precursors", "descriptor_ui": "D011498", "major_topic": false }, { "descriptor": "Protein Structure, Secondary", "descriptor_ui": "D017433", "major_topic": false }, { "descriptor": "Sequence Homology, Amino Acid", "descriptor_ui": "D017386", "major_topic": false }, { "descriptor": "Thermodynamics", "descriptor_ui": "D013816", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec", "date_precision": "unknown", "issue": "23", "normalized_date": null, "pages": "4325-4339", "proceedings_title": null, "publisher": "", "title": "The FEBS journal", "volume": "283", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Crystal structure of a crustacean hyperglycemic hormone (CHH) precursor suggests structural variety in the C-terminal regions of CHH superfamily members.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The changes triggered by sperm-induced activation of oocytes, which are required for normal oocyte development, can be mediated by other agents, thereby inducing the parthenogenesis. In this study, we exposed porcine oocytes to 1 mM Ca-EDTA, a metal-ion chelator, at various intervals during 48 hr of in vitro maturation to determine the optimum period of Ca-EDTA treatment for parthenogenetic activation. When the oocytes were cultured with or without Ca-EDTA from 36 hr (post-12), 24 hr (post-24), 12 hr (post-36) and 0 hr (post-48) after the start of maturation culture, the blastocyst formation rates were significantly higher (P<0.05) in the post-24, post-36 and post-48 groups (3.3%, 4.0% and 2.6%, respectively) than those in the control group without treatment (0%). Furthermore, when the oocytes were cultured with Ca-EDTA for 0 hr (control), 12 hr (pre-12), 24 hr (pre-24), 36 hr (pre-36) and 48 hr (pre-48) from the start of maturation culture, the oocytes formed blastocysts only in the pre-36 and pre-48 groups (0.4% or 0.8%, respectively). Pronuclei (<66.7%) were observed only when the periods of Ca-EDTA treatment were more than 12 hr during maturation culture. In the control group, no pronuclei were detected. Our findings demonstrate that porcine immature oocytes can be parthenogenetically activated by Ca-EDTA treatment for at least 24 hr to 36 hr during maturation culture, leading to pronucleus formation followed by the formation of blastocysts.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "MORITA", "name": null }, { "creator_type": "author", "first_name": "Masayasu", "last_name": "TANIGUCHI", "name": null }, { "creator_type": "author", "first_name": "Fuminori", "last_name": "TANIHARA", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "ITO", "name": null }, { "creator_type": "author", "first_name": "Zhao", "last_name": "NAMULA", "name": null }, { "creator_type": "author", "first_name": "Lanh Thi Kim", "last_name": "DO", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "TAKAGI", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "TAKEMOTO", "name": null }, { "creator_type": "author", "first_name": "Takeshige", "last_name": "OTOI", "name": null } ], "identifiers": { "doi": { "normalized": "10.1292/jvms.15-0658" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26947170" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Culture Media", "descriptor_ui": "D003470", "major_topic": false }, { "descriptor": "Edetic Acid", "descriptor_ui": "D004492", "major_topic": false }, { "descriptor": "In Vitro Oocyte Maturation Techniques", "descriptor_ui": "D059471", "major_topic": false }, { "descriptor": "Oocytes", "descriptor_ui": "D009865", "major_topic": false }, { "descriptor": "Parthenogenesis", "descriptor_ui": "D010312", "major_topic": false }, { "descriptor": "Swine", "descriptor_ui": "D013552", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "1019-1023", "proceedings_title": null, "publisher": "", "title": "The Journal of Veterinary Medical Science", "volume": "78", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "The optimal period of Ca-EDTA treatment for parthenogenetic activation of porcine oocytes during maturation culture.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Spinocerebellar ataxia (SCA) is a genetically heterogeneous disease. To date, 36 dominantly inherited loci have been reported, and 31 causative genes have been identified. RESULTS: In this study, we analyzed a Japanese family with autosomal dominant SCA using linkage analysis and exome sequencing, and identified CACNA1G, which encodes the calcium channel CaV3.1, as a new causative gene. The same mutation was also found in another family with SCA. Although most patients exhibited the pure form of cerebellar ataxia, two patients showed prominent resting tremor in addition to ataxia. CaV3.1 is classified as a low-threshold voltage-dependent calcium channel (T-type) and is expressed abundantly in the central nervous system, including the cerebellum. The mutation p.Arg1715His, identified in this study, was found to be located at S4 of repeat IV, the voltage sensor of the CaV3.1. Electrophysiological analyses revealed that the membrane potential dependency of the mutant CaV3.1 transfected into HEK293T cells shifted toward a positive potential. We established induced pluripotent stem cells (iPSCs) from fibroblasts of the patient, and to our knowledge, this is the first report of successful differentiation from the patient-derived iPSCs into Purkinje cells. There was no significant difference in the differentiation status between control- and patient-derived iPSCs. CONCLUSIONS: To date, several channel genes have been reported as causative genes for SCA. Our findings provide important insights into the pathogenesis of SCA as a channelopathy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Morino", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Ohsawa", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Ohtake", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Otobe", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Kawakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13041-015-0180-4" }, "pmcid": { "normalized": "PMC4693440" }, "pmid": { "normalized": "26715324" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Age of Onset", "descriptor_ui": "D017668", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": false }, { "descriptor": "Calcium Channels, T-Type", "descriptor_ui": "D020747", "major_topic": false }, { "descriptor": "Exome", "descriptor_ui": "D059472", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Genes, Dominant", "descriptor_ui": "D005799", "major_topic": false }, { "descriptor": "Genetic Linkage", "descriptor_ui": "D008040", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Potentials", "descriptor_ui": "D008564", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Pedigree", "descriptor_ui": "D010375", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Spinocerebellar Ataxias", "descriptor_ui": "D020754", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Dec 29", "date_precision": "day", "issue": "", "normalized_date": "2015-12-29", "pages": "89", "proceedings_title": null, "publisher": "", "title": "Molecular brain", "volume": "8", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "A mutation in the low voltage-gated calcium channel CACNA1G alters the physiological properties of the channel, causing spinocerebellar ataxia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "GABAergic synaptic transmission regulates brain function by establishing the appropriate excitation-inhibition (E/I) balance in neural circuits. The structure and function of GABAergic synapses are sensitive to destabilization by impinging neurotransmitters. However, signaling mechanisms that promote the restorative homeostatic stabilization of GABAergic synapses remain unknown. Here, by quantum dot single-particle tracking, we characterize a signaling pathway that promotes the stability of GABAA receptor (GABAAR) postsynaptic organization. Slow metabotropic glutamate receptor signaling activates IP3 receptor-dependent calcium release and protein kinase C to promote GABAAR clustering and GABAergic transmission. This GABAAR stabilization pathway counteracts the rapid cluster dispersion caused by glutamate-driven NMDA receptor-dependent calcium influx and calcineurin dephosphorylation, including in conditions of pathological glutamate toxicity. These findings show that glutamate activates distinct receptors and spatiotemporal patterns of calcium signaling for opposing control of GABAergic synapses.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null }, { "creator_type": "author", "first_name": "Fumihiro", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Mark W.", "last_name": "Sherwood", "name": null }, { "creator_type": "author", "first_name": "Amulya Nidhi", "last_name": "Shrivastava", "name": null }, { "creator_type": "author", "first_name": "Misa", "last_name": "Arizono", "name": null }, { "creator_type": "author", "first_name": "Akitoshi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Kotomi", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Sabine", "last_name": "Levi", "name": null }, { "creator_type": "author", "first_name": "Antoine", "last_name": "Triller", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Mikoshiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2015.12.002" }, "pmcid": { "normalized": "PMC4700050" }, "pmid": { "normalized": "26711343" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "GABAergic Neurons", "descriptor_ui": "D059330", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Receptors, GABA-A", "descriptor_ui": "D011963", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Dec 29", "date_precision": "day", "issue": "12", "normalized_date": "2015-12-29", "pages": "2768-2780", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "13", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Bidirectional Control of Synaptic GABAAR Clustering by Glutamate and Calcium.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stem cells are pivotal for development and tissue homeostasis of multicellular animals, and the quest for a gene toolkit associated with the emergence of stem cells in a common ancestor of all metazoans remains a major challenge for evolutionary biology. We reconstructed the conserved gene repertoire of animal stem cells by transcriptomic profiling of totipotent archeocytes in the demosponge Ephydatia fluviatilis and by tracing shared molecular signatures with flatworm and Hydra stem cells. Phylostratigraphy analyses indicated that most of these stem-cell genes predate animal origin, with only few metazoan innovations, notably including several partners of the Piwi machinery known to promote genome stability. The ancestral stem-cell transcriptome is strikingly poor in transcription factors. Instead, it is rich in RNA regulatory actors, including components of the \"germ-line multipotency program\" and many RNA-binding proteins known as critical regulators of mammalian embryonic stem cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Alexandre", "last_name": "Alie", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Itsuro", "last_name": "Sugimura", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Manuel", "name": null }, { "creator_type": "author", "first_name": "Wakana", "last_name": "Sugano", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Nori", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Kiyokazu", "last_name": "Agata", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Funayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1514789112" }, "pmcid": { "normalized": "PMC4697369" }, "pmid": { "normalized": "26644562" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Genomic Instability", "descriptor_ui": "D042822", "major_topic": false }, { "descriptor": "Hydra", "descriptor_ui": "D006829", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Porifera", "descriptor_ui": "D011161", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Dec 22", "date_precision": "day", "issue": "51", "normalized_date": "2015-12-22", "pages": "E7093-7100", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "112", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "The ancestral gene repertoire of animal stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "F1-ATPase (F1) is a rotary motor protein that can efficiently convert chemical energy to mechanical work of rotation via fine coordination of its conformational motions and reaction sequences. Compared with reactant binding and product release, the ATP hydrolysis has relatively little contributions to the torque and chemical energy generation. To scrutinize possible roles of ATP hydrolysis, we investigate the detailed statistics of the catalytic dwells from high-speed single wild-type F1 observations. Here we report a small rotation during the catalytic dwell triggered by the ATP hydrolysis that is indiscernible in previous studies. Moreover, we find in freely rotating F1 that ATP hydrolysis is followed by the release of inorganic phosphate with low synthesis rates. Finally, we propose functional roles of the ATP hydrolysis as a key to kinetically unlock the subsequent phosphate release and promote the correct reaction ordering.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Chun-Biu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Rikiya", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Noji", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms10223" }, "pmcid": { "normalized": "PMC4703894" }, "pmid": { "normalized": "26678797" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Hydrolysis", "descriptor_ui": "D006868", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Molecular Motor Proteins", "descriptor_ui": "D020409", "major_topic": false }, { "descriptor": "Monte Carlo Method", "descriptor_ui": "D009010", "major_topic": false }, { "descriptor": "Phosphates", "descriptor_ui": "D010710", "major_topic": false }, { "descriptor": "Proton-Translocating ATPases", "descriptor_ui": "D006180", "major_topic": false }, { "descriptor": "Rotation", "descriptor_ui": "D012399", "major_topic": false }, { "descriptor": "Torque", "descriptor_ui": "D019415", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Dec 17", "date_precision": "day", "issue": "", "normalized_date": "2015-12-17", "pages": "10223", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "6", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "ATP hydrolysis assists phosphate release and promotes reaction ordering in F1-ATPase.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Prion diseases are fatal neurodegenerative diseases characterised by deposition of amyloid plaques containing abnormal prion protein aggregates (PrP(Sc)). This study aimed to evaluate the potential of radioiodinated flavonoid derivatives for single photon emission computed tomography (SPECT) imaging of PrP(Sc). In vitro binding assays using recombinant mouse PrP (rMoPrP) aggregates revealed that the 4-dimethylamino-substituted styrylchromone derivative (SC-NMe2) had higher in vitro binding affinity (Kd = 24.5 nM) and capacity (Bmax = 36.3 pmol/nmol protein) than three other flavonoid derivatives (flavone, chalcone, and aurone). Fluorescent imaging using brain sections from mouse-adapted bovine spongiform encephalopathy (mBSE)-infected mice demonstrated that SC-NMe2 clearly labelled PrP(Sc)-positive prion deposits in the mice brain. Two methoxy SC derivatives, SC-OMe and SC-(OMe)2, also showed high binding affinity for rMoPrP aggregates with Ki values of 20.8 and 26.6 nM, respectively. In vitro fluorescence and autoradiography experiments demonstrated high accumulation of [(125)I]SC-OMe and [(125)I]SC-(OMe)2 in prion deposit-rich regions of the mBSE-infected mouse brain. SPECT/computed tomography (CT) imaging and ex vivo autoradiography demonstrated that [(123)I]SC-OMe showed consistent brain distribution with the presence of PrP(Sc) deposits in the mBSE-infected mice brain. In conclusion, [(123)I]SC-OMe appears a promising SPECT radioligand for monitoring prion deposit levels in the living brain.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Fuchigami", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Haratake", "name": null }, { "creator_type": "author", "first_name": "Ryuichiro", "last_name": "Atarashi", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Nakagaki", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Ubagai", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Sakura", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Nakayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep18440" }, "pmcid": { "normalized": "PMC4680881" }, "pmid": { "normalized": "26669576" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "Cattle", "descriptor_ui": "D002417", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Encephalopathy, Bovine Spongiform", "descriptor_ui": "D016643", "major_topic": true }, { "descriptor": "Flavonoids", "descriptor_ui": "D005419", "major_topic": true }, { "descriptor": "Iodine Radioisotopes", "descriptor_ui": "D007457", "major_topic": true }, { "descriptor": "Isotope Labeling", "descriptor_ui": "D007553", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "PrPSc Proteins", "descriptor_ui": "D018620", "major_topic": false }, { "descriptor": "Radiography", "descriptor_ui": "D011859", "major_topic": false }, { "descriptor": "Tomography, Emission-Computed, Single-Photon", "descriptor_ui": "D015899", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Dec 16", "date_precision": "day", "issue": "", "normalized_date": "2015-12-16", "pages": "18440", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "5", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Characterisation of radioiodinated flavonoid derivatives for SPECT imaging of cerebral prion deposits.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The CNS contains many diverse neuronal subtypes, and most neurological diseases target specific subtypes. However, the mechanism of neuronal subtype specificity of disease phenotypes remains elusive. Although in vitro disease models employing human pluripotent stem cells (PSCs) have great potential to clarify the association of neuronal subtypes with disease, it is currently difficult to compare various PSC-derived subtypes. This is due to the limited number of subtypes whose induction is established, and different cultivation protocols for each subtype. Here, we report a culture system to control the regional identity of PSC-derived neurons along the anteroposterior (A-P) and dorsoventral (D-V) axes. This system was successfully used to obtain various neuronal subtypes based on the same protocol. Furthermore, we reproduced subtype-specific phenotypes of amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) by comparing the obtained subtypes. Therefore, our culture system provides new opportunities for modeling neurological diseases with PSCs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kent", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Takefumi", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Ibata", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Michisuke", "last_name": "Yuzaki", "name": null }, { "creator_type": "author", "first_name": "Wado", "last_name": "Akamatsu", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2015.10.005" }, "pmcid": { "normalized": "PMC4682123" }, "pmid": { "normalized": "26549851" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Amyotrophic Lateral Sclerosis", "descriptor_ui": "D000690", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Hedgehog Proteins", "descriptor_ui": "D053823", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Dec 8", "date_precision": "day", "issue": "6", "normalized_date": "2015-12-08", "pages": "1010-1022", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "5", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Controlling the Regional Identity of hPSC-Derived Neurons to Uncover Neuronal Subtype Specificity of Neurological Disease Phenotypes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The significance of kinetic analysis as a tool for understanding the reactivity and selectivity of organic reactions has recently been recognized. However, conventional simulation approaches that solve rate equations numerically are not amenable to multistep reaction profiles consisting of fast and slow elementary steps. Herein, we present an efficient and robust approach for evaluating the overall rate constants of multistep reactions via the recursive contraction of the rate equations to give the overall rate constants for the products and byproducts. This new method was applied to the Claisen rearrangement of allyl vinyl ether, as well as a substituted allyl vinyl ether. Notably, the profiles of these reactions contained 23 and 84 local minima, and 66 and 278 transition states, respectively. The overall rate constant for the Claisen rearrangement of allyl vinyl ether was consistent with the experimental value. The selectivity of the Claisen rearrangement reaction has also been assessed using a substituted allyl vinyl ether. The results of this study showed that the conformational entropy in these flexible chain molecules had a substantial impact on the overall rate constants. This new method could therefore be used to estimate the overall rate constants of various other organic reactions involving flexible molecules.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yosuke", "last_name": "Sumiya", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Nagahata", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Taketsugu", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Maeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jpca.5b09447" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26567633" } }, "mesh": [ { "descriptor": "Entropy", "descriptor_ui": "D019277", "major_topic": true }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Organic Chemicals", "descriptor_ui": "D009930", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Dec 3", "date_precision": "day", "issue": "48", "normalized_date": "2015-12-03", "pages": "11641-11649", "proceedings_title": null, "publisher": "", "title": "The journal of physical chemistry. A", "volume": "119", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Kinetic Analysis for the Multistep Profiles of Organic Reactions: Significance of the Conformational Entropy on the Rate Constants of the Claisen Rearrangement.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A sensitive bioluminogenic probe for highly reactive oxygen species (hROS), SO3 H-APL, was developed based on the concept of dual control of bioluminescence emission by means of bioluminescent enzyme-induced electron transfer (BioLeT) and modulation of cell-membrane permeability. This probe enables non-invasive visualization of physiologically relevant amounts of hROS generated deep inside the body of living rats for the first time. It is expected to serve as a practical analytical tool for investigating a wide range of biological functions of hROS in vivo. The design concept should be applicable to other in vivo bioluminogenic probes.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201507530" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26474404" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Luminescent Agents", "descriptor_ui": "D049408", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Transgenic", "descriptor_ui": "D055647", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Dec 1", "date_precision": "day", "issue": "49", "normalized_date": "2015-12-01", "pages": "14768-14771", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "54", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a Sensitive Bioluminogenic Probe for Imaging Highly Reactive Oxygen Species in Living Rats.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mammalian sleep comprises rapid eye movement (REM) sleep and non-REM (NREM) sleep. To functionally isolate from the complex mixture of neurons populating the brainstem pons those involved in switching between REM and NREM sleep, we chemogenetically manipulated neurons of a specific embryonic cell lineage in mice. We identified excitatory glutamatergic neurons that inhibit REM sleep and promote NREM sleep. These neurons shared a common developmental origin with neurons promoting wakefulness; both derived from a pool of proneural hindbrain cells expressing Atoh1 at embryonic day 10.5. We also identified inhibitory gamma-aminobutyric acid-releasing neurons that act downstream to inhibit REM sleep. Artificial reduction or prolongation of REM sleep in turn affected slow-wave activity during subsequent NREM sleep, implicating REM sleep in the regulation of NREM sleep.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Mitsuaki", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Kanuka", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Shigeyoshi", "last_name": "Itohara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.aad1023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26494173" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Brain Stem", "descriptor_ui": "D001933", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cell Separation", "descriptor_ui": "D002469", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Glutamates", "descriptor_ui": "D005971", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Pons", "descriptor_ui": "D011149", "major_topic": false }, { "descriptor": "Rhombencephalon", "descriptor_ui": "D012249", "major_topic": false }, { "descriptor": "Sleep, REM", "descriptor_ui": "D012895", "major_topic": false }, { "descriptor": "Wakefulness", "descriptor_ui": "D014851", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Nov 20", "date_precision": "day", "issue": "6263", "normalized_date": "2015-11-20", "pages": "957-961", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "350", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Cells of a common developmental origin regulate REM/non-REM sleep and wakefulness in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Melanopsin is involved in non-visual photoreception in mammals, but molecular characteristics underlying these non-visual functions are unclear.Results: Stability of the bond with the retinal chromophore is weakened and diversified in mammalian melanopsins.Conclusion: Mammalian melanopsins have acquired characteristics suited for their non-visual functions.Significance: The weaker retinal attachment in melanopsin may contribute to the functional tuning of non-visual photoreception in mammals.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hisao", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "David L.", "last_name": "Farrens", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Furutani", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m115.666305" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26416885" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Galago", "descriptor_ui": "D005701", "major_topic": false }, { "descriptor": "Genetic Variation", "descriptor_ui": "D014644", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lancelets", "descriptor_ui": "D064175", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Melanopsin", "descriptor_ui": "D000099210", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Oocytes", "descriptor_ui": "D009865", "major_topic": false }, { "descriptor": "Papio anubis", "descriptor_ui": "D048530", "major_topic": false }, { "descriptor": "Photoreceptor Cells, Vertebrate", "descriptor_ui": "D020419", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Protein Stability", "descriptor_ui": "D055550", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Retinal Ganglion Cells", "descriptor_ui": "D012165", "major_topic": false }, { "descriptor": "Retinal Pigments", "descriptor_ui": "D012168", "major_topic": false }, { "descriptor": "Retinaldehyde", "descriptor_ui": "D012172", "major_topic": false }, { "descriptor": "Rod Opsins", "descriptor_ui": "D017299", "major_topic": false }, { "descriptor": "Saimiri", "descriptor_ui": "D012453", "major_topic": false }, { "descriptor": "Schiff Bases", "descriptor_ui": "D012545", "major_topic": false }, { "descriptor": "Sequence Homology, Amino Acid", "descriptor_ui": "D017386", "major_topic": false }, { "descriptor": "Spiders", "descriptor_ui": "D013112", "major_topic": false }, { "descriptor": "Xenopus", "descriptor_ui": "D014981", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Nov 6", "date_precision": "day", "issue": "45", "normalized_date": "2015-11-06", "pages": "27176-27187", "proceedings_title": null, "publisher": "", "title": "The Journal of Biological Chemistry", "volume": "290", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Retinal Attachment Instability Is Diversified among Mammalian Melanopsins*.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Hydrogen sulfide (H2S) exhibits protective effects in various disease models including cerebral ischemia-reperfusion (I/R) injury. Nonetheless, mechanisms and identity of molecules responsible for neuroprotective effects of H2S remain incompletely defined. In the current study, we observed that thiosulfate, an oxidation product of H2S, mediates protective effects of an H2S donor compound sodium sulfide (Na2S) against neuronal I/R injury. METHODS AND RESULTS: We observed that thiosulfate in cell culture medium is not only required but also sufficient to mediate cytoprotective effects of Na2S against oxygen glucose deprivation and reoxygenation of human neuroblastoma cell line (SH-SY5Y) and murine primary cortical neurons. Systemic administration of sodium thiosulfate (STS) improved survival and neurological function of mice subjected to global cerebral I/R injury. Beneficial effects of STS, as well as Na2S, were associated with marked increase of thiosulfate, but not H2S, in plasma and brain tissues. These results suggest that thiosulfate is a circulating \"carrier\" molecule of beneficial effects of H2S. Protective effects of thiosulfate were associated with inhibition of caspase-3 activity by persulfidation at Cys163 in caspase-3. We discovered that an SLC13 family protein, sodium sulfate cotransporter 2 (SLC13A4, NaS-2), facilitates transport of thiosulfate, but not sulfide, across the cell membrane, regulating intracellular concentrations and thus mediating cytoprotective effects of Na2S and STS. CONCLUSIONS: The protective effects of H2S are mediated by thiosulfate that is transported across cell membrane by NaS-2 and exerts antiapoptotic effects via persulfidation of caspase-3. Given the established safety track record, thiosulfate may be therapeutic against ischemic brain injury.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Eizo", "last_name": "Marutani", "name": null }, { "creator_type": "author", "first_name": "Marina", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Tokuda", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Kai", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Shirozu", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Hayashida", "name": null }, { "creator_type": "author", "first_name": "Shizuko", "last_name": "Kosugi", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Kaneki", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Fumito", "last_name": "Ichinose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1161/jaha.115.002125" }, "pmcid": { "normalized": "PMC4845224" }, "pmid": { "normalized": "26546573" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anion Transport Proteins", "descriptor_ui": "D027321", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Brain Ischemia", "descriptor_ui": "D002545", "major_topic": false }, { "descriptor": "Caspase 3", "descriptor_ui": "D053148", "major_topic": false }, { "descriptor": "Cell Hypoxia", "descriptor_ui": "D015687", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cytoprotection", "descriptor_ui": "D019610", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Gestational Age", "descriptor_ui": "D005865", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neuroprotective Agents", "descriptor_ui": "D018696", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Reperfusion Injury", "descriptor_ui": "D015427", "major_topic": false }, { "descriptor": "Sulfate Transporters", "descriptor_ui": "D000076988", "major_topic": false }, { "descriptor": "Sulfites", "descriptor_ui": "D013447", "major_topic": false }, { "descriptor": "Symporters", "descriptor_ui": "D027981", "major_topic": false }, { "descriptor": "Thiosulfates", "descriptor_ui": "D013885", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Nov 6", "date_precision": "day", "issue": "11", "normalized_date": "2015-11-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of the American Heart Association", "volume": "4", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Thiosulfate Mediates Cytoprotective Effects of Hydrogen Sulfide Against Neuronal Ischemia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Kaifu", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Iwakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.18632/oncotarget.6043" }, "pmcid": { "normalized": "PMC4741427" }, "pmid": { "normalized": "26462156" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ankylosis", "descriptor_ui": "D000844", "major_topic": false }, { "descriptor": "Antigen Presentation", "descriptor_ui": "D017951", "major_topic": false }, { "descriptor": "Bone and Bones", "descriptor_ui": "D001842", "major_topic": false }, { "descriptor": "Bone Density", "descriptor_ui": "D015519", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": false }, { "descriptor": "Lectins, C-Type", "descriptor_ui": "D037181", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Oct 27", "date_precision": "day", "issue": "33", "normalized_date": "2015-10-27", "pages": "34051-34052", "proceedings_title": null, "publisher": "", "title": "Oncotarget", "volume": "6", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "DCIR in the \"osteo-immune\" system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent studies have revealed that cell competition can occur between normal and transformed epithelial cells; normal epithelial cells recognize the presence of the neighboring transformed cells and actively eliminate them from epithelial tissues. Here, we have established a brand-new high-throughput screening platform that targets cell competition. By using this platform, we have identified Rebeccamycin as a hit compound that specifically promotes elimination of RasV12-transformed cells from the epithelium, though after longer treatment it shows substantial cytotoxic effect against normal epithelial cells. Among several Rebeccamycin-derivative compounds, we have found that VC1-8 has least cytotoxicity against normal cells but shows the comparable effect on the elimination of transformed cells. This cell competition-promoting activity of VC1-8 is observed both in vitro and ex vivo. These data demonstrate that the cell competition-based screening is a promising tool for the establishment of a novel type of cancer preventive medicine.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hajime", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Matsumaru", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Maenaka", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Semba", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kon", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep15336" }, "pmcid": { "normalized": "PMC4612300" }, "pmid": { "normalized": "26480891" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carbazoles", "descriptor_ui": "D002227", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Cell Line, Transformed", "descriptor_ui": "D002461", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "Drug Screening Assays, Antitumor", "descriptor_ui": "D004354", "major_topic": true }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Genes, ras", "descriptor_ui": "D011905", "major_topic": true }, { "descriptor": "High-Throughput Screening Assays", "descriptor_ui": "D057166", "major_topic": true }, { "descriptor": "Intestinal Mucosa", "descriptor_ui": "D007413", "major_topic": false }, { "descriptor": "Small Molecule Libraries", "descriptor_ui": "D054852", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015 Oct 20", "date_precision": "day", "issue": "", "normalized_date": "2015-10-20", "pages": "15336", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "5", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "The cell competition-based high-throughput screening identifies small compounds that promote the elimination of RasV12-transformed cells from epithelia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer cells robustly expel lactate produced through enhanced glycolysis via monocarboxylate transporters (MCTs) and maintain alkaline intracellular pH. To develop a novel therapeutic strategy against multiple myeloma (MM), which still remains incurable, we explored the impact of perturbing a metabolism via inhibiting MCTs. All MM cells tested constitutively expressed MCT1 and MCT4, and most expressed MCT2. Lactate export was substantially suppressed to induce death along with lowering intracellular pH in MM cells by blockade of all three MCT molecules with alpha-cyano-4-hydroxy cinnamate (CHC) or the MCT1 and MCT2 inhibitor AR-C155858 in combination with MCT4 knockdown, although only partially by knockdown of each MCT. CHC lowered intracellular pH and severely curtailed lactate secretion even when combined with metformin, which further lowered intracellular pH and enhanced cytotoxicity. Interestingly, an ambient acidic pH markedly enhanced CHC-mediated cytotoxicity, suggesting preferential targeting of MM cells in acidic MM bone lesions. Furthermore, treatment with CHC suppressed hexokinase II expression and ATP production to reduce side populations and colony formation. Finally, CHC caused downregulation of homing receptor CXCR4 and abrogated SDF-1-induced migration. Targeting tumor metabolism by MCT blockade therefore may become an effective therapeutic option for drug-resistant MM cells with elevated glycolysis.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Derek James", "last_name": "Hanson", "name": null }, { "creator_type": "author", "first_name": "Shingen", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Amachi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Hiasa", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Teramachi", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Abe", "name": null } ], "identifiers": { "doi": { "normalized": "10.18632/oncotarget.5598" }, "pmcid": { "normalized": "PMC4741786" }, "pmid": { "normalized": "26384349" } }, "mesh": [ { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Coumaric Acids", "descriptor_ui": "D003373", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Metformin", "descriptor_ui": "D008687", "major_topic": false }, { "descriptor": "Molecular Targeted Therapy", "descriptor_ui": "D058990", "major_topic": false }, { "descriptor": "Monocarboxylate Transport Protein 1", "descriptor_ui": "D000099233", "major_topic": false }, { "descriptor": "Monocarboxylic Acid Transporters", "descriptor_ui": "D027501", "major_topic": false }, { "descriptor": "Multiple Myeloma", "descriptor_ui": "D009101", "major_topic": false }, { "descriptor": "Muscle Proteins", "descriptor_ui": "D009124", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Symporters", "descriptor_ui": "D027981", "major_topic": false }, { "descriptor": "Thiophenes", "descriptor_ui": "D013876", "major_topic": false }, { "descriptor": "Uracil", "descriptor_ui": "D014498", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Oct 20", "date_precision": "day", "issue": "32", "normalized_date": "2015-10-20", "pages": "33568-33586", "proceedings_title": null, "publisher": "", "title": "Oncotarget", "volume": "6", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Effective impairment of myeloma cells and their progenitors by blockade of monocarboxylate transportation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Measurement of Forster resonance energy transfer by fluorescence lifetime imaging microscopy (FLIM-FRET) is a powerful method for visualization of intracellular signaling activities such as protein-protein interactions and conformational changes of proteins. Here, we developed a dark green fluorescent protein (ShadowG) that can serve as an acceptor for FLIM-FRET. ShadowG is spectrally similar to monomeric enhanced green fluorescent protein (mEGFP) and has a 120-fold smaller quantum yield. When FRET from mEGFP to ShadowG was measured using an mEGFP-ShadowG tandem construct with 2-photon FLIM-FRET, we observed a strong FRET signal with low cell-to-cell variability. Furthermore, ShadowG was applied to a single-molecule FRET sensor to monitor a conformational change of CaMKII and of the light oxygen voltage (LOV) domain in HeLa cells. These sensors showed reduced cell-to-cell variability of both the basal fluorescence lifetime and response signal. In contrast to mCherry- or dark-YFP-based sensors, our sensor allowed for precise measurement of individual cell responses. When ShadowG was applied to a separate-type Ras FRET sensor, it showed a greater response signal than did the mCherry-based sensor. Furthermore, Ras activation and translocation of its effector ERK2 into the nucleus could be observed simultaneously. Thus, ShadowG is a promising FLIM-FRET acceptor.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Akihiro C. E.", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Nakahata", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Nabekura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep15334" }, "pmcid": { "normalized": "PMC4606784" }, "pmid": { "normalized": "26469148" } }, "mesh": [ { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinase Type 2", "descriptor_ui": "D054732", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Mutagenesis", "descriptor_ui": "D016296", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Protein Interaction Domains and Motifs", "descriptor_ui": "D054730", "major_topic": false }, { "descriptor": "Quantum Theory", "descriptor_ui": "D011789", "major_topic": false }, { "descriptor": "ras Proteins", "descriptor_ui": "D018631", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Red Fluorescent Protein", "descriptor_ui": "D000097573", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Oct 15", "date_precision": "day", "issue": "", "normalized_date": "2015-10-15", "pages": "15334", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "5", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "A dark green fluorescent protein as an acceptor for measurement of Forster resonance energy transfer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Monoacylglycerol lipase (MGL) is a major enzyme involved in degradation of the endocannabinoid 2-arachidonoylglycerol (2-AG). Selective inhibitors of MGL are regarded as promising analgesics and anticancer agents. To gain insight into the possible consequences of their prolonged administration for anesthetic action, the effects of several inhalational and intravenous anesthetics were tested in knockout mice lacking the MGL gene in the loss of righting reflex (LORR) assay. Sensitivity to inhalational and most intravenous anesthetics was not altered in knockout mice. However, compared with wild-type littermates, they showed increased sensitivity to the intravenous anesthetic propofol. Permanently elevated levels of 2-AG after MGL knockout are known to cause desensitization of cannabinoid (CB1) receptors, which have been advocated as possible mediators of propofol anesthesia. Therefore, increased sensitivity to propofol in knockout mice at first suggested that 2-AG may potentiate CB1 receptors despite their hypofunction in these animals. Pharmacologic inhibition of MGL also causes desensitization of CB1 receptors, so sensitivity to propofol was tested further in C57BL/6N mice pretreated chronically with the selective MGL inhibitor JZL 184. Contrary to the results in knockout mice, these animals showed drastically reduced sensitivity to propofol. The reason for increased sensitivity to propofol after MGL knockout remains unclear, but may result from changes occurring in these animals during development. However, our results in C57BL/6N mice pretreated with JZL 184 confirmed the role of CB1 receptors in propofol anesthesia advocated previously, and also suggest that prolonged use of MGL inhibitors may be associated with the development of resistance to propofol.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Andrey B.", "last_name": "Petrenko", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ejphar.2015.08.048" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26318148" } }, "mesh": [ { "descriptor": "Anesthetics, Intravenous", "descriptor_ui": "D018686", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arachidonic Acids", "descriptor_ui": "D001095", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Drug Resistance", "descriptor_ui": "D004351", "major_topic": true }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": false }, { "descriptor": "Glycerides", "descriptor_ui": "D005989", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Monoacylglycerol Lipases", "descriptor_ui": "D008994", "major_topic": false }, { "descriptor": "Propofol", "descriptor_ui": "D015742", "major_topic": false }, { "descriptor": "Receptor, Cannabinoid, CB1", "descriptor_ui": "D043884", "major_topic": false }, { "descriptor": "Reflex, Righting", "descriptor_ui": "D057897", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Oct 15", "date_precision": "day", "issue": "", "normalized_date": "2015-10-15", "pages": "268-273", "proceedings_title": null, "publisher": "", "title": "European journal of pharmacology", "volume": "765", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetic inactivation and prolonged pharmacologic inhibition of monoacylglycerol lipase have opposite effects on anesthetic sensitivity to propofol.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Animal bodies are shaped by skeletons, which are built inside the body by biomineralization of condensed mesenchymal cells in vertebrates [1, 2] and echinoderms [3, 4], or outside the body by apical secretion of extracellular matrices by epidermal cell layers in arthropods [5]. In each case, the skeletons' shapes are a direct reflection of the pattern of skeleton-producing cells [6]. Here we report a newly discovered mode of skeleton formation: assembly of sponges' mineralized skeletal elements (spicules) in locations distant from where they were produced. Although it was known that internal skeletons of sponges consist of spicules assembled into large pole-and-beam structures with a variety of morphologies [7-10], the spicule assembly process (i.e., how spicules become held up and connected basically in staggered tandem) and what types of cells act in this process remained unexplored. Here we found that mature spicules are dynamically transported from where they were produced and then pierce through outer epithelia, and their basal ends become fixed to substrate or connected with such fixed spicules. Newly discovered \"transport cells\" mediate spicule movement and the \"pierce\" step, and collagen-secreting basal-epithelial cells fix spicules to the substratum, suggesting that the processes of spiculous skeleton construction are mediated separately by specialized cells. Division of labor by manufacturer, transporter, and cementer cells, and iteration of the sequential mechanical reactions of \"transport,\" \"pierce,\" \"raise up,\" and \"cementation,\" allows construction of the spiculous skeleton spicule by spicule as a self-organized biological structure, with the great plasticity in size and shape required for indeterminate growth, and generating the great morphological diversity of individual sponges.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Sohei", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Kazushi", "last_name": "Arima", "name": null }, { "creator_type": "author", "first_name": "Kotoe", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Kurato", "last_name": "Mohri", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Inui", "name": null }, { "creator_type": "author", "first_name": "Wakana", "last_name": "Sugano", "name": null }, { "creator_type": "author", "first_name": "Hibiki", "last_name": "Koba", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Tamada", "name": null }, { "creator_type": "author", "first_name": "Yudai J.", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Kouji", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Miyuki", "last_name": "Arai-Shindo", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Kiyokazu", "last_name": "Agata", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Funayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2015.08.023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26387717" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cementation", "descriptor_ui": "D002484", "major_topic": false }, { "descriptor": "Collagen", "descriptor_ui": "D003094", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Minerals", "descriptor_ui": "D008903", "major_topic": false }, { "descriptor": "Porifera", "descriptor_ui": "D011161", "major_topic": false }, { "descriptor": "Skeleton", "descriptor_ui": "D012863", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Oct 5", "date_precision": "day", "issue": "19", "normalized_date": "2015-10-05", "pages": "2549-2554", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "25", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic Transport and Cementation of Skeletal Elements Build Up the Pole-and-Beam Structured Skeleton of Sponges.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Indium-tin-oxide (ITO) glass electrodes possess the properties of optical transparency and high electrical conductivity, which enables the electrical stimulation of cultured cells to be performed whilst also measuring the responses with fluorescent imaging techniques. However, the quantitative relationship between the intensity of the stimulating current and the cell response is unclear when using conventional methods that employ a separated configuration of counter and stimulation electrodes. NEW METHOD: A quantitative electrical current stimulation device without the use of a counter electrode was fabricated. RESULTS: Nerve growth factor (NGF)-induced differentiated PC12 cells were cultured on an ITO single glass electrode, and the Ca(2+) response to electrical stimuli was measured using fluorescent Ca(2+) imaging. ITO electrode devices with a width less than 0.1mm were found to evoke a Ca(2+) response in the PC12 cells. Subsequent variation in the length of the device in the range of 2-10mm was found to have little influence on the efficiency of the electric stimulus. We found that the stimulation of the cells was dependent on the electrical current, when greater than 60 muA, rather than on the Joule heat, regardless of the width and length of the conductive area. COMPARISON WITH EXISTING METHOD(S): Because of the cells directly in contact with the electrode, our device enables to stimulate the cells specifically, comparing with previous devices with the counter electrode. CONCLUSIONS: The ITO device without the use of a counter electrode is a useful tool for evaluating the quantitative neural excitability of cultured neurons.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Tanamoto", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Norihisa", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jneumeth.2015.07.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26185873" } }, "mesh": [ { "descriptor": "Aniline Compounds", "descriptor_ui": "D000814", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biophysics", "descriptor_ui": "D001703", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Electric Stimulation", "descriptor_ui": "D004558", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Membrane Potentials", "descriptor_ui": "D008564", "major_topic": false }, { "descriptor": "Microelectrodes", "descriptor_ui": "D008839", "major_topic": true }, { "descriptor": "Nerve Growth Factor", "descriptor_ui": "D020932", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false }, { "descriptor": "Tin Compounds", "descriptor_ui": "D017971", "major_topic": true }, { "descriptor": "Xanthenes", "descriptor_ui": "D014966", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Sep 30", "date_precision": "day", "issue": "", "normalized_date": "2015-09-30", "pages": "272-278", "proceedings_title": null, "publisher": "", "title": "Journal of neuroscience methods", "volume": "253", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Electrical stimulation of cultured neurons using a simply patterned indium-tin-oxide (ITO) glass electrode.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Acclimation from marine to dilute environments constitutes among the dramatic evolutionary transitions in the history of life. Such adaptations have evolved in multiple lineages, but studies of the blood/hemolymph homeostasis mechanisms are limited to those using evolutionarily advanced Deuterostome (chordates) and Ecdysozoa (crustaceans). Here, we examined hemolymph homeostasis in the advanced Lophotrochozoa/mollusc, the other unexplored taxa, and its possible regulation by the vasopressin/oxytocin superfamily peptides known to be implicated in fluid homeostasis in Chordata and Arthropoda. The hemolymph osmotic and ionic status in the euryhaline cephalopod (Octopus ocellatus) following transfer from 30-ppt normal seawater to 20 ppt salinity indicate hyperosmo- and hyperionoregulatory abilities for more than 1 week, as in crustaceans and teleost fish. While ventilation frequency decreased by 1 day, Na(+)/K(+)-ATPase activity, which has been generally implicated in ion transport, was induced in two of the eight posterior gills after 1 week. In addition, the octopuses were intravenously injected with 1 or 100 ng/g octopressin or cephalotocin, which are Octopus vasopressin/oxytocin orthologs. After 1 day, octopressin, but not cephalotocin, decreased the hemolymph osmolality and Ca concentrations, as well as urinary Na concentrations. These data provide evidence for possible parallel evolution in hyperionoregulatory mechanisms and coordination by conserved peptides.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Yudai", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Akada", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Minakata", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep14469" }, "pmcid": { "normalized": "PMC4585917" }, "pmid": { "normalized": "26403952" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": true }, { "descriptor": "Body Fluids", "descriptor_ui": "D001826", "major_topic": false }, { "descriptor": "Cephalopoda", "descriptor_ui": "D049830", "major_topic": false }, { "descriptor": "Gills", "descriptor_ui": "D005880", "major_topic": false }, { "descriptor": "Hemolymph", "descriptor_ui": "D006458", "major_topic": false }, { "descriptor": "Osmoregulation", "descriptor_ui": "D064587", "major_topic": true }, { "descriptor": "Osmosis", "descriptor_ui": "D009995", "major_topic": true }, { "descriptor": "Salinity", "descriptor_ui": "D054712", "major_topic": false }, { "descriptor": "Sodium-Potassium-Exchanging ATPase", "descriptor_ui": "D000254", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Sep 25", "date_precision": "day", "issue": "", "normalized_date": "2015-09-25", "pages": "14469", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "5", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Osmotic/ionic status of body fluids in the euryhaline cephalopod suggest possible parallel evolution of osmoregulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The complement system is important for the host defence against infection as well as for the development of inflammatory diseases. Here we show that C1q/TNF-related protein 6 (CTRP6; gene symbol C1qtnf6) expression is elevated in mouse rheumatoid arthritis (RA) models. C1qtnf6(-/-) mice are highly susceptible to induced arthritis due to enhanced complement activation, whereas C1qtnf6-transgenic mice are refractory. The Arthus reaction and the development of experimental autoimmune encephalomyelitis are also enhanced in C1qtnf6(-/-) mice and C1qtnf6(-/-) embryos are semi-lethal. We find that CTRP6 specifically suppresses the alternative pathway of the complement system by competing with factor B for C3(H2O) binding. Furthermore, treatment of arthritis-induced mice with intra-articular injection of recombinant human CTRP6 cures the arthritis. CTRP6 is expressed in human synoviocytes, and CTRP6 levels are increased in RA patients. These results indicate that CTRP6 is an endogenous complement regulator and could be used for the treatment of complement-mediated diseases.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masanori A.", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Kakuta", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Tomo", "last_name": "Yonezawa", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Tateishi", "name": null }, { "creator_type": "author", "first_name": "Harumichi", "last_name": "Ishigame", "name": null }, { "creator_type": "author", "first_name": "Rikio", "last_name": "Yabe", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Akimasa", "last_name": "Seno", "name": null }, { "creator_type": "author", "first_name": "Hsi-Hua", "last_name": "Chi", "name": null }, { "creator_type": "author", "first_name": "Yuriko", "last_name": "Hashiguchi", "name": null }, { "creator_type": "author", "first_name": "Riho", "last_name": "Kurata", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yang", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Masahira", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Shinobu", "last_name": "Saijo", "name": null }, { "creator_type": "author", "first_name": "Misao", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Teizo", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Sumida", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Iwakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms9483" }, "pmcid": { "normalized": "PMC4598845" }, "pmid": { "normalized": "26404464" } }, "mesh": [ { "descriptor": "Adipokines", "descriptor_ui": "D054392", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arthritis, Experimental", "descriptor_ui": "D001169", "major_topic": false }, { "descriptor": "Arthritis, Rheumatoid", "descriptor_ui": "D001172", "major_topic": false }, { "descriptor": "Arthus Reaction", "descriptor_ui": "D001183", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Collagen", "descriptor_ui": "D003094", "major_topic": false }, { "descriptor": "Complement C3-C5 Convertases", "descriptor_ui": "D050577", "major_topic": false }, { "descriptor": "Complement C3a", "descriptor_ui": "D015926", "major_topic": false }, { "descriptor": "Complement C5a", "descriptor_ui": "D015936", "major_topic": false }, { "descriptor": "Complement Pathway, Alternative", "descriptor_ui": "D003170", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Encephalomyelitis, Autoimmune, Experimental", "descriptor_ui": "D004681", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoprecipitation", "descriptor_ui": "D047468", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "Synovial Membrane", "descriptor_ui": "D013583", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Sep 25", "date_precision": "day", "issue": "", "normalized_date": "2015-09-25", "pages": "8483", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "6", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "CTRP6 is an endogenous complement regulator that can effectively treat induced arthritis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In breast cancer, the prognosis of human epidermal growth factor receptor 2 (HER2)-positive patients (20-25%) has been dramatically improved by the clinical application of the anti-HER2 antibody drugs trastuzumab and pertuzumab. However, the clinical outcomes of HER2-negative cases with a poor prognosis have not improved, and novel therapeutic antibody drugs or diagnostic molecular markers of prognosis are urgently needed. Here, we targeted protease-activated receptor 1 (PAR1) as a new biomarker for HER2-negative patients. The developed anti-PAR1 antibody inhibited PAR1 activation by matrix metalloprotease 1 and thereby prevented cancer-cell migration and invasion. To estimate PAR1 expression levels in HER2-negative patient tissues using the antibody, user-friendly immunohistochemistry with fluorescence nanoparticles or quantum dots (QDs) was developed. Previously, immunohistochemistry with QDs was affected by tissue autofluorescence, making quantitative measurement extremely difficult. We significantly improved the quantitative sensitivity of immunohistochemistry with QDs by using an autofluorescence-subtracted image and single-QD imaging. The immunohistochemistry showed that PAR1 expression was strongly correlated with relapse-free survival time in HER2-negative breast cancer patients. Therefore, the developed anti-PAR1 antibody is a strong candidate for use as an anticancer drug and a prognostic biomarker for HER2-negative patients.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kohsuke", "last_name": "Gonda", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Miyashita", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Ohuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep14322" }, "pmcid": { "normalized": "PMC4585722" }, "pmid": { "normalized": "26392299" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Diagnostic Imaging", "descriptor_ui": "D003952", "major_topic": false }, { "descriptor": "Erb-b2 Receptor Tyrosine Kinases", "descriptor_ui": "D018719", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Matrix Metalloproteinase 1", "descriptor_ui": "D020781", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Platelet Aggregation Inhibitors", "descriptor_ui": "D010975", "major_topic": false }, { "descriptor": "Postoperative Care", "descriptor_ui": "D011182", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Quantum Dots", "descriptor_ui": "D045663", "major_topic": true }, { "descriptor": "Receptor, PAR-1", "descriptor_ui": "D044463", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Sep 22", "date_precision": "day", "issue": "", "normalized_date": "2015-09-22", "pages": "14322", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "5", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Predictive diagnosis of the risk of breast cancer recurrence after surgery by single-particle quantum dot imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Self-incompatibility in the Brassicaceae is controlled by multiple haplotypes encoding the pollen ligand (S-locus protein 11, SP11, also known as S-locus cysteine-rich protein, SCR) and its stigmatic receptor (S-receptor kinase, SRK). A haplotype-specific interaction between SP11/SCR and SRK triggers the self-incompatibility response that leads to self-pollen rejection, but the signalling pathway remains largely unknown. Here we show that Ca(2+) influx into stigma papilla cells mediates self-incompatibility signalling. Using self-incompatible Arabidopsis thaliana expressing SP11/SCR and SRK, we found that self-pollination specifically induced an increase in cytoplasmic Ca(2+) ([Ca(2+)]cyt) in papilla cells. Direct application of SP11/SCR to the papilla cell protoplasts induced Ca(2+) increase, which was inhibited by D-(-)-2-amino-5-phosphonopentanoic acid (AP-5), a glutamate receptor channel blocker. An artificial increase in [Ca(2+)]cyt in papilla cells arrested wild-type (WT) pollen hydration. Treatment of papilla cells with AP-5 interfered with self-incompatibility, and Ca(2+) increase on the self-incompatibility response was reduced in the glutamate receptor-like channel (GLR) gene mutants. These results suggest that Ca(2+) influx mediated by GLR is the essential self-incompatibility response leading to self-pollen rejection.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Megumi", "last_name": "Iwano", "name": null }, { "creator_type": "author", "first_name": "Kanae", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Kakita", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Asano-Shimosato", "name": null }, { "creator_type": "author", "first_name": "Motoko", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Pulla", "last_name": "Kaothien-Nakayama", "name": null }, { "creator_type": "author", "first_name": "Tetsuyuki", "last_name": "Entani", "name": null }, { "creator_type": "author", "first_name": "Asaka", "last_name": "Kanatani", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Takehisa", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kunihiko", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Shiba", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Isogai", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Takayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nplants.2015.128" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27250681" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015 Sep 1", "date_precision": "day", "issue": "", "normalized_date": "2015-09-01", "pages": "15128", "proceedings_title": null, "publisher": "", "title": "Nature plants", "volume": "1", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Calcium signalling mediates self-incompatibility response in the Brassicaceae.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Leucine-rich repeat kinase 2 (LRRK2) is the causative molecule of the autosomal dominant hereditary form of Parkinson's disease (PD), PARK8, which was originally defined in a study of a Japanese family (the Sagamihara family) harboring the I2020T mutation in the kinase domain. Although a number of reported studies have focused on cell death mediated by mutant LRRK2, details of the pathogenetic effect of LRRK2 still remain to be elucidated. In the present study, to elucidate the mechanism of neurodegeneration in PD caused by LRRK2, we generated induced pluripotent stem cells (iPSC) derived from fibroblasts of PD patients with I2020T LRRK2 in the Sagamihara family. We found that I2020T mutant LRRK2 iPSC-derived neurons released less dopamine than control-iPSC-derived neurons. Furthermore, we demonstrated that patient iPSC-derived neurons had a lower phospho-AKT level than control-iPSC-derived neurons, and that the former showed an increased incidence of apoptosis relative to the controls. Interestingly, patient iPSC-derived neurons exhibited activation of glycogen synthase kinase-3beta (GSK-3beta) and high Tau phosphorylation. In addition, the postmortem brain of the patient from whom the iPSC had been established exhibited deposition of neurofibrillary tangles as well as increased Tau phosphorylation in neurons. These results suggest that I2020T LRRK2-iPSC could be a promising new tool for reproducing the pathology of PD in the brain caused by the I2020T mutation, and applicable as a model in studies of targeted therapeutics.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Nihira", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Uchino", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Wado", "last_name": "Akamatsu", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Ohyama", "name": null }, { "creator_type": "author", "first_name": "Masafuchi", "last_name": "Ryo", "name": null }, { "creator_type": "author", "first_name": "Mieko", "last_name": "Ogino", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Kazutoshi", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Yoshikuni", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Obata", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/hmg/ddv212" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26056228" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": false }, { "descriptor": "Caspase 3", "descriptor_ui": "D053148", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Glycogen Synthase Kinase 3", "descriptor_ui": "D038362", "major_topic": false }, { "descriptor": "Glycogen Synthase Kinase 3 beta", "descriptor_ui": "D000071679", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Leucine-Rich Repeat Serine-Threonine Protein Kinase-2", "descriptor_ui": "D000071158", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Sep 1", "date_precision": "day", "issue": "17", "normalized_date": "2015-09-01", "pages": "4879-4900", "proceedings_title": null, "publisher": "", "title": "Human molecular genetics", "volume": "24", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "I2020T mutant LRRK2 iPSC-derived neurons in the Sagamihara family exhibit increased Tau phosphorylation through the AKT/GSK-3beta signaling pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To clarify the function(s) of the herpes simplex virus 1 (HSV-1) major virion structural protein UL47 (also designated VP13/14), we screened cells overexpressing UL47 for UL47-binding cellular proteins. Tandem affinity purification of transiently expressed UL47 coupled with mass spectrometry-based proteomics technology and subsequent analyses showed that UL47 interacted with cell protein p32 in HSV-1-infected cells. Unlike in mock-infected cells, p32 accumulated at the nuclear rim in HSV-1-infected cells, and this p32 recruitment to the nuclear rim required UL47. p32 formed a complex(es) with HSV-1 proteins UL31, UL34, Us3, UL47, and/or ICP22 in HSV-1-infected cells. All these HSV-1 proteins were previously reported to be important for HSV-1 nuclear egress, in which nucleocapsids bud through the inner nuclear membrane (primary envelopment) and the enveloped nucleocapsids then fuse with the outer nuclear membrane (de-envelopment). Like viral proteins UL31, UL34, Us3, and UL47, p32 was detected in primary enveloped virions. p32 knockdown reduced viral replication and induced membranous invaginations adjacent to the nuclear rim containing primary enveloped virions and aberrant localization of UL31 and UL34 in punctate structures at the nuclear rim. These effects of p32 knockdown were reduced in the absence of UL47. Therefore, the effects of p32 knockdown in HSV-1 nuclear egress were similar to those of the previously reported mutation(s) in HSV-1 regulatory proteins for HSV-1 de-envelopment during viral nuclear egress. Collectively, these results suggested that p32 regulated HSV-1 de-envelopment and replication in a UL47-dependent manner.IMPORTANCE In this study, we have obtained data suggesting that (i) the HSV-1 major virion structural protein UL47 interacted with host cell protein p32 and mediated the recruitment of p32 to the nuclear rim in HSV-1-infected cells; (ii) p32 was a component of the HSV-1 nuclear egress complex (NEC), whose core components were UL31 and UL34; and (iii) p32 regulated HSV-1 de-envelopment during viral nuclear egress. It has been reported that p32 was a component of human cytomegalovirus NEC and was required for efficient disintegration of nuclear lamina, which has been thought to facilitate HSV-1 primary envelopment during viral nuclear egress. Thus, p32 appeared to be a core component of herpesvirus NECs, like UL31 and UL34 homologs in other herpesviruses, and to play multiple roles in herpesvirus nuclear egress.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Zhuoming", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kozuka-Hata", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01220-15" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26085152" } }, "mesh": [ { "descriptor": "Active Transport, Cell Nucleus", "descriptor_ui": "D021581", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Cytomegalovirus", "descriptor_ui": "D003587", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitochondrial Proteins", "descriptor_ui": "D024101", "major_topic": false }, { "descriptor": "Nuclear Envelope", "descriptor_ui": "D009685", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Nucleocapsid", "descriptor_ui": "D019251", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Fusion Proteins", "descriptor_ui": "D014760", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virus Assembly", "descriptor_ui": "D019065", "major_topic": false }, { "descriptor": "Virus Release", "descriptor_ui": "D057074", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Sep 1", "date_precision": "day", "issue": "17", "normalized_date": "2015-09-01", "pages": "8982-8998", "proceedings_title": null, "publisher": "", "title": "Journal of Virology", "volume": "89", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of Host Cell p32 in Herpes Simplex Virus 1 De-Envelopment during Viral Nuclear Egress.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescein is a representative green fluorophore that has been widely used as a scaffold of practically useful green fluorescent probes. Here, we report synthesis and characterization of a silicon-substituted fluorescein, i.e., 2-COOH TokyoMagenta (2-COOH TM), which is a fluorescein analogue in which the O atom at the 10' position of the xanthene moiety of fluorescein is replaced with a Si atom. This fluorescein analogue forms a spirolactone ring via intramolecular nucleophilic attack of the carboxylic group in a pH-dependent manner. Consequently, 2-COOH TM exhibits characteristic large pH-dependent absorption and fluorescence spectral changes: (1) 2-COOH TM is colorless at acidic pH, whereas fluorescein retains observable absorption and fluorescence even at acidic pH, and the absorption maximum is also shifted; (2) the absorption spectral change occurs above pH 7.0 for 2-COOH TM and below pH 7.0 for fluorescein; (3) 2-COOH TM shows a much sharper pH response than fluorescein because of its pKa inversion, i.e., pKa1 > pKa2. These features are also different from those of a compound without the carboxylic group, 2-Me TokyoMagenta (2-Me TM). Analysis of the chemical equilibrium between pH 3.0 and 11.0 disclosed that 2-COOH TM favors the colorless and nonfluorescent lactone form, compared with fluorescein. Substitution of Cl atoms at the 4' and 5' positions of the xanthene moiety of 2-COOH TM to obtain 2-COOH DCTM shifted the equilibrium so that the new derivative exists predominantly in the strongly fluorescent open form at physiological pH (pH 7.4). To demonstrate the practical utility of 2-COOH DCTM as a novel scaffold for red fluorescent probes, we employed it to develop a probe for beta-galactosidase.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Hirabayashi", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Takayanagi", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Toki", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Egawa", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.5b02331" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26237524" } }, "mesh": [ { "descriptor": "Fluorescein", "descriptor_ui": "D019793", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Photochemical Processes", "descriptor_ui": "D055668", "major_topic": false }, { "descriptor": "Silicon", "descriptor_ui": "D012825", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Sep 1", "date_precision": "day", "issue": "17", "normalized_date": "2015-09-01", "pages": "9061-9069", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "87", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Analysis of chemical equilibrium of silicon-substituted fluorescein and its application to develop a scaffold for red fluorescent probes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We present a mechanism of global reaction coordinate switching, namely, a phenomenon in which the reaction coordinate dynamically switches to another coordinate as the total energy of the system increases. The mechanism is based on global changes in the underlying phase space geometry caused by a switching of dominant unstable modes from the original reactive mode to another nonreactive mode in systems with more than 2 degrees of freedom. We demonstrate an experimental observability to detect a reaction coordinate switching in an ionization reaction of a hydrogen atom in crossed electric and magnetic fields. For this reaction, the reaction coordinate is a coordinate along which electrons escape and its switching changes the escaping direction from the direction of the electric field to that of the magnetic field and, thus, the switching can be detected experimentally by measuring the angle-resolved momentum distribution of escaping electrons.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Teramoto", "name": null }, { "creator_type": "author", "first_name": "Mikito", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hirohiko", "last_name": "Kono", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physrevlett.115.093003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26371648" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015 Aug 28", "date_precision": "day", "issue": "9", "normalized_date": "2015-08-28", "pages": "093003", "proceedings_title": null, "publisher": "", "title": "Physical review letters", "volume": "115", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Mechanism and Experimental Observability of Global Switching Between Reactive and Nonreactive Coordinates at High Total Energies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Integrin LFA-1 regulates immune cell adhesion and trafficking by binding to ICAM-1 upon chemokine stimulation. Integrin-mediated clutch formation between extracellular ICAM-1 and the intracellular actin cytoskeleton is important for cell adhesion. We applied single-molecule tracking analysis to LFA-1 and ICAM-1 in living cells to examine the ligand-binding kinetics and mobility of the molecular clutch under chemokine-induced physiological adhesion and Mn(2+)-induced tight adhesion. Our results show a transient LFA-1-mediated clutch formation that lasts a few seconds and leads to a transient lower-mobility is sufficient to promote cell adhesion. Stable clutch formation was observed for Mn(2+)-induced high affinity LFA-1, but was not required for physiological adhesion. We propose that fast cycling of the clutch formation by intermediate-affinity integrin enables dynamic cell adhesion and migration.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Munenori", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Miyanaga", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Kozuka", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Togashi", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Kinashi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2015.06.155" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26143530" } }, "mesh": [ { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Adhesion Molecule-1", "descriptor_ui": "D018799", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Lymphocyte Function-Associated Antigen-1", "descriptor_ui": "D016169", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Aug 21", "date_precision": "day", "issue": "2", "normalized_date": "2015-08-21", "pages": "459-466", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "464", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Integrin LFA-1 regulates cell adhesion via transient clutch formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The structural modification of dendritic spines plays a critical role in synaptic plasticity. CaMKII is a pivotal molecule involved in this process through both kinase-dependent and independent structural functions, but the respective contributions of these two functions to the synaptic plasticity remain unclear. We demonstrate that the transient interplay between the kinase and structural functions of CaMKII during the induction of synaptic plasticity temporally gates the activity-dependent modification of the actin cytoskeleton. Inactive CaMKII binds F-actin, thereby limiting access of actin-regulating proteins to F-actin and stabilizing spine structure. CaMKII-activating stimuli trigger dissociation of CaMKII from F-actin through specific autophosphorylation reactions within the F-actin binding region and permits F-actin remodeling by regulatory proteins followed by reassociation and restabilization. Blocking the autophosphorylation impairs both functional and structural plasticity without affecting kinase activity. These results underpin the importance of the interplay between the kinase and structural functions of CaMKII in defining a time window permissive for synaptic plasticity.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Karam", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Gurpreet", "last_name": "Lakhanpal", "name": null }, { "creator_type": "author", "first_name": "Hsiangmin E.", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Mustafa", "last_name": "Khan", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Mariko Kato", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Radhakrishnan", "last_name": "Narayanan", "name": null }, { "creator_type": "author", "first_name": "Thomas T.", "last_name": "Luyben", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Thomas A.", "last_name": "Blanpied", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Okamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2015.07.023" }, "pmcid": { "normalized": "PMC4548268" }, "pmid": { "normalized": "26291163" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinase Type 2", "descriptor_ui": "D054732", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Organ Culture Techniques", "descriptor_ui": "D009924", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Aug 19", "date_precision": "day", "issue": "4", "normalized_date": "2015-08-19", "pages": "813-826", "proceedings_title": null, "publisher": "", "title": "Neuron", "volume": "87", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "A Temporary Gating of Actin Remodeling during Synaptic Plasticity Consists of the Interplay between the Kinase and Structural Functions of CaMKII.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stimulus-specific adaptation (SSA) is considered to be the neural underpinning of habituation to frequent stimuli and novelty detection. However, neither the cellular mechanism underlying SSA nor the link between SSA-like neuronal plasticity and behavioral modulation is well understood. The wind-detection system in crickets is one of the best models for investigating the neural basis of SSA. We found that crickets exhibit stimulus-direction-specific adaptation in wind-elicited avoidance behavior. Repetitive air currents inducing this behavioral adaptation reduced firings to the stimulus and the amplitude of excitatory synaptic potentials in wind-sensitive giant interneurons (GIs) related to the avoidance behavior. Injection of a Ca(2+) chelator into GIs diminished both the attenuation of firings and the synaptic depression induced by the repetitive stimulation, suggesting that adaptation of GIs induced by this stimulation results in Ca(2+)-mediated modulation of postsynaptic responses, including postsynaptic short-term depression. Some types of GIs showed specific adaptation to the direction of repetitive stimuli, resulting in an alteration of their directional tuning curves. The types of GIs for which directional tuning was altered displayed heterogeneous direction selectivity in their Ca(2+) dynamics that was restricted to a specific area of dendrites. In contrast, other types of GIs with constant directionality exhibited direction-independent global Ca(2+) elevation throughout the dendritic arbor. These results suggest that depression induced by local Ca(2+) accumulation at repetitively activated synapses of key neurons underlies direction-specific behavioral adaptation. This input-selective depression mediated by heterogeneous Ca(2+) dynamics could confer the ability to detect novelty at the earliest stages of sensory processing in crickets. SIGNIFICANCE STATEMENT: Stimulus-specific adaptation (SSA) is considered to be the neural underpinning of habituation and novelty detection. We found that crickets exhibit stimulus-direction-specific adaptation in wind-elicited avoidance behavior. Repetitive air currents inducing this behavioral adaptation altered the directional selectivity of wind-sensitive giant interneurons (GIs) via direction-specific adaptation mediated by dendritic Ca(2+) elevation. The GIs for which directional tuning was altered displayed heterogeneous direction selectivity in their Ca(2+) dynamics and the transient increase in Ca(2+) evoked by the repeated puffs was restricted to a specific area of dendrites. These results suggest that depression induced by local Ca(2+) accumulation at repetitively activated synapses of key neurons underlies direction-specific behavioral adaptation. Our findings elucidate the subcellular mechanism underlying SSA-like neuronal plasticity related to behavioral adaptation.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroto", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.1378-15.2015" }, "pmcid": { "normalized": "PMC6605242" }, "pmid": { "normalized": "26290241" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Gryllidae", "descriptor_ui": "D006135", "major_topic": false }, { "descriptor": "Habituation, Psychophysiologic", "descriptor_ui": "D006185", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mechanotransduction, Cellular", "descriptor_ui": "D040542", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Sense Organs", "descriptor_ui": "D012679", "major_topic": false }, { "descriptor": "Sensory Receptor Cells", "descriptor_ui": "D011984", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Aug 19", "date_precision": "day", "issue": "33", "normalized_date": "2015-08-19", "pages": "11644-11655", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "35", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Direction-Specific Adaptation in Neuronal and Behavioral Responses of an Insect Mechanosensory System.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The lack of intravital imaging of axonal transport of mitochondria in the mammalian CNS precludes characterization of the dynamics of axonal transport of mitochondria in the diseased and aged mammalian CNS. Glaucoma, the most common neurodegenerative eye disease, is characterized by axon degeneration and the death of retinal ganglion cells (RGCs) and by an age-related increase in incidence. RGC death is hypothesized to result from disturbances in axonal transport and in mitochondrial function. Here we report minimally invasive intravital multiphoton imaging of anesthetized mouse RGCs through the sclera that provides sequential time-lapse images of mitochondria transported in a single axon with submicrometer resolution. Unlike findings from explants, we show that the axonal transport of mitochondria is highly dynamic in the mammalian CNS in vivo under physiological conditions. Furthermore, in the early stage of glaucoma modeled in adult (4-mo-old) mice, the number of transported mitochondria decreases before RGC death, although transport does not shorten. However, with increasing age up to 23-25 mo, mitochondrial transport (duration, distance, and duty cycle) shortens. In axons, mitochondria-free regions increase and lengths of transported mitochondria decrease with aging, although totally organized transport patterns are preserved in old (23- to 25-mo-old) mice. Moreover, axonal transport of mitochondria is more vulnerable to glaucomatous insults in old mice than in adult mice. These mitochondrial changes with aging may underlie the age-related increase in glaucoma incidence. Our method is useful for characterizing the dynamics of axonal transport of mitochondria and may be applied to other submicrometer structures in the diseased and aged mammalian CNS in vivo.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Takihara", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Inatani", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Eto", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Kreymerman", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Nagaya", "name": null }, { "creator_type": "author", "first_name": "Ayami", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Iwao", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Takamura", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Mineo", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Jeffrey L.", "last_name": "Goldberg", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Nabekura", "name": null }, { "creator_type": "author", "first_name": "Hidenobu", "last_name": "Tanihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1509879112" }, "pmcid": { "normalized": "PMC4547257" }, "pmid": { "normalized": "26240337" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axonal Transport", "descriptor_ui": "D001370", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Central Nervous System", "descriptor_ui": "D002490", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glaucoma", "descriptor_ui": "D005901", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Optic Nerve", "descriptor_ui": "D009900", "major_topic": false }, { "descriptor": "Photons", "descriptor_ui": "D017785", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Retinal Ganglion Cells", "descriptor_ui": "D012165", "major_topic": false }, { "descriptor": "Sclera", "descriptor_ui": "D012590", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Aug 18", "date_precision": "day", "issue": "33", "normalized_date": "2015-08-18", "pages": "10515-10520", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "112", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "In vivo imaging of axonal transport of mitochondria in the diseased and aged mammalian CNS.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Methanosarcina species pyrrolysyl-tRNA synthetase (PylRS) attaches Pyl to its cognate amber suppressor tRNA. The introduction of two mutations (Y384F and Y306A) into PylRS was previously shown to generate a mutant, designated LysZ-RS, that was able to attach N-benzyloxycarbonyl-L-lysine (LysZ) to its cognate tRNA. Despite the potential of LysZ derivatives, further LysZ-RS engineering has not been performed; consequently, we aimed to generate LysZ-RS mutants with improved LysZ incorporation activity through in vitro directed evolution. Using a liposome-based in vitro compartmentalization (IVC) approach, we screened a randomly mutagenized gene library of LysZ-RS and obtained a mutant that showed increased LysZ incorporation activity both in vitro and in vivo. The ease and high flexibility of liposome-based IVC should enable the evolution of not only LysZ-RS that can attach various LysZ derivatives but also of other enzymes involved in protein translation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Atsuko", "last_name": "Uyeda", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Yomo", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Hohsaka", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cbic.201500174" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26052693" } }, "mesh": [ { "descriptor": "Amino Acyl-tRNA Synthetases", "descriptor_ui": "D000604", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": true }, { "descriptor": "Gene Library", "descriptor_ui": "D015723", "major_topic": false }, { "descriptor": "Liposomes", "descriptor_ui": "D008081", "major_topic": false }, { "descriptor": "Lysine", "descriptor_ui": "D008239", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Sequence Analysis", "descriptor_ui": "D017421", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Aug 17", "date_precision": "day", "issue": "12", "normalized_date": "2015-08-17", "pages": "1797-1802", "proceedings_title": null, "publisher": "", "title": "Chembiochem : a European journal of chemical biology", "volume": "16", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Liposome-Based in Vitro Evolution of Aminoacyl-tRNA Synthetase for Enhanced Pyrrolysine Derivative Incorporation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell lines have been used for drug discovery as useful models of cancers; however, they do not recapitulate cancers faithfully, especially in the points of rapid growth rate and microenvironment independency. Consequently, the majority of conventional anti-cancer drugs are less sensitive to slow growing cells and do not target microenvironmental support, although most primary cancer cells grow slower than cell lines and depend on microenvironmental support. Here, we developed a novel high throughput drug screening system using patient-derived xenograft (PDX) cells of lymphoma that maintained primary cancer cell phenotype more than cell lines. The library containing 2613 known pharmacologically active substance and off-patent drugs were screened by this system. We could find many compounds showing higher cytotoxicity than conventional anti-tumor drugs. Especially, pyruvinium pamoate showed the highest activity and its strong anti-tumor effect was confirmed also in vivo. We extensively investigated its mechanism of action and found that it inhibited glutathione supply from stromal cells to lymphoma cells, implying the importance of the stromal protection from oxidative stress for lymphoma cell survival and a new therapeutic strategy for lymphoma. Our system introduces a primary cancer cell phenotype into cell-based phenotype screening and sheds new light on anti-cancer drug development.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Keiki", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kiyoi", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Naoe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep13054" }, "pmcid": { "normalized": "PMC4538400" }, "pmid": { "normalized": "26278963" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Drug Discovery", "descriptor_ui": "D055808", "major_topic": true }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interleukin Receptor Common gamma Subunit", "descriptor_ui": "D053631", "major_topic": false }, { "descriptor": "Lymphoma", "descriptor_ui": "D008223", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, SCID", "descriptor_ui": "D016513", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Pyrvinium Compounds", "descriptor_ui": "D011774", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Transplantation, Heterologous", "descriptor_ui": "D014183", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Aug 17", "date_precision": "day", "issue": "", "normalized_date": "2015-08-17", "pages": "13054", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "5", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Discovery of a drug targeting microenvironmental support for lymphoma cells by screening using patient-derived xenograft cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report the development of environmentally responsive fluorescent polymers. The reversible temperature-induced phase transition of copolymers composed of N-isopropylacrylamide and a fluorescent monomer based on the fluorescein (FL), coumarin (CO), rhodamine (RH), or dansyl (DA) skeleton was used as a molecular switch to control the fluorescence intensity. The poly(N-isopropylacrylamide) (PNIPAAm) chain showed an expanded coil conformation below the lower critical solution temperature (LCST) due to hydration, but it changed to a globular form above the LCST due to dehydration. Through the combination of a polarity-sensitive fluorophore with PNIPAAm, the synthetic fluorescent polymer displayed a response to external temperature, with the fluorescence strength dramatically changing close to the LCST. Additionally, the P(NIPAAm-co-FL) and P(NIPAAm-co-CO) polymers, containing fluorescein and coumarin groups, respectively, exhibited pH responsiveness. The environmental responsiveness of the reported polymers is derived directly from the PNIPAAm and fluorophore structures, thus allowing for the cellular uptake of the fluorescence copolymer by RAW264.7 cells to be temperature-controlled. Cellular uptake was suppressed below the LCST but enhanced above the LCST. Furthermore, the cellular uptake of both P(NIPAAm-co-CO) and P(NIPAAm-co-RH) conjugated with a fusogenic lipid, namely, l-alpha-phosphatidylethanolamine, dioleoyl (DOPE), was enhanced. Such lipid-conjugated fluorescence probes are expected to be useful as physiological indicators for intracellular imaging.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Arisa", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Jian", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Ayano", "name": null }, { "creator_type": "author", "first_name": "Hideko", "last_name": "Kanazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.biomac.5b00591" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26121103" } }, "mesh": [ { "descriptor": "Acrylamides", "descriptor_ui": "D000178", "major_topic": false }, { "descriptor": "Acrylic Resins", "descriptor_ui": "D000180", "major_topic": false }, { "descriptor": "Cell Tracking", "descriptor_ui": "D058948", "major_topic": true }, { "descriptor": "Coumarins", "descriptor_ui": "D003374", "major_topic": false }, { "descriptor": "Fluorescein", "descriptor_ui": "D019793", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": true }, { "descriptor": "Phase Transition", "descriptor_ui": "D044367", "major_topic": false }, { "descriptor": "Phosphatidylcholines", "descriptor_ui": "D010713", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Aug 10", "date_precision": "day", "issue": "8", "normalized_date": "2015-08-10", "pages": "2356-2362", "proceedings_title": null, "publisher": "", "title": "Biomacromolecules", "volume": "16", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Design of Environmentally Responsive Fluorescent Polymer Probes for Cellular Imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dominant mutations in Cu,Zn-superoxide dismutase (SOD1) cause a familial form of amyotrophic lateral sclerosis (ALS). A pathological hallmark of the familial ALS is the formation of mutant SOD1 aggregates, leading to the proposal that SOD1 gains toxicities through protein misfolding triggered by mutations. Nevertheless, molecular requirements for mutant SOD1 to acquire pathogenicity still remain obscure. Here, we show that Cys residues in SOD1 are essential to exerting toxicities of SOD1 in a Caenorhabditis elegans model. Exogenous expression of wild-type as well as pathogenic mutant SOD1 fused with a fluorescent protein in C. elegans resulted in the accumulation of disulfide-reduced SOD1 and retarded the worm's motility. In contrast, little effects of exogenously expressed SOD1 on the motility were observed when all four Cys residues in SOD1 were replaced with Ser. Taken together, we propose that deregulation of Cys chemistry in SOD1 proteins is involved in the pathogenesis of SOD1-related ALS.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mariko", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Shidara", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Kurosawa", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Nukina", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Furukawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2015.06.084" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26086102" } }, "mesh": [ { "descriptor": "Amyotrophic Lateral Sclerosis", "descriptor_ui": "D000690", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Superoxide Dismutase", "descriptor_ui": "D013482", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Aug 7", "date_precision": "day", "issue": "4", "normalized_date": "2015-08-07", "pages": "1196-1202", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "463", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Cysteine residues in Cu,Zn-superoxide dismutase are essential to toxicity in Caenorhabditis elegans model of amyotrophic lateral sclerosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In vivo toxicity evaluation using model organisms is an important step for the development of new drugs. Here, we report that Ciona intestinalis, a chordate invertebrate, is beneficial to drug toxicity evaluation for the following reasons: rapid embryonic and larval development, resemblance to vertebrates, ease of management, low cost, transparent body, and low risk of ethical issues. The dynamic phenotypic change of Ciona larvae during metamorphosis prompted us to examine the effect of cytotoxic drugs on its development by quantifying six toxicity endpoints: degenerated tail size, ampulla length, rotation of body axis, stomach size, heart rate, and body size. As a result, mitochondrial respiratory inhibitors, tubulin polymerization/depolymerization inhibitors, or DNA/RNA synthesis inhibitors showed distinct toxicity profiles against these six endpoints, but drugs with the same targets showed a similar toxicity profile in Ciona. Our results suggest Ciona is an effective animal model for profiling drug toxicity and exploring the mechanisms of drugs with unknown targets.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Mizotani", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Etsu", "last_name": "Tashiro", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Imoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2015.05.119" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26043689" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": false }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "Toxicity Tests", "descriptor_ui": "D018675", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Aug 7", "date_precision": "day", "issue": "4", "normalized_date": "2015-08-07", "pages": "656-660", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "463", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Evaluation of drug toxicity profiles based on the phenotypes of ascidian Ciona intestinalis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Previous studies suggest that dysfunction of neurotransmitter systems is associated with the pathology of autism in humans and the disease model rodents, but the precise mechanism is not known. Rodent offspring exposed prenatally to VPA shows autism-related behavioral abnormalities. The present study examined the effect of prenatal VPA exposure on brain monoamine neurotransmitter systems in male and female mice. The prenatal VPA exposure did not affect the levels of dopamine (DA), noradrenaline (NA), serotonin (5-HT) and their metabolites in the prefrontal cortex and striatum, while it significantly reduced methamphetamine (METH) (1.0 mg/kg)-induced hyperlocomotion in male offspring. In vivo microdialysis study demonstrated that prenatal VPA exposure attenuated METH-induced increases in extracellular DA levels in the prefrontal cortex, while it did not affect those in extracellular NA and 5-HT levels. Prenatal VPA exposure also decreased METH-induced c-Fos expression in the prefrontal cortex and the mRNA levels of DA D1 and D2 receptors in the prefrontal cortex. These effects of VPA were not observed in the striatum. In contrast to male offspring, prenatal VPA exposure did not affect METH-induced increases in locomotor activity and prefrontal DA levels and the D1 and D2 receptor mRNA levels in the prefrontal cortex in female offspring. These findings suggest that prenatal VPA exposure causes hypofunction of prefrontal DA system in a sex-dependent way.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Erika", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Katashiba", "name": null }, { "creator_type": "author", "first_name": "Atsuki", "last_name": "Taruta", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Higashino", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbr.2015.04.022" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25907743" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autistic Disorder", "descriptor_ui": "D001321", "major_topic": false }, { "descriptor": "Biogenic Monoamines", "descriptor_ui": "D015306", "major_topic": false }, { "descriptor": "Corpus Striatum", "descriptor_ui": "D003342", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Methamphetamine", "descriptor_ui": "D008694", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Prenatal Exposure Delayed Effects", "descriptor_ui": "D011297", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-fos", "descriptor_ui": "D016760", "major_topic": false }, { "descriptor": "Receptors, Dopamine", "descriptor_ui": "D011954", "major_topic": false }, { "descriptor": "Valproic Acid", "descriptor_ui": "D014635", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Aug 1", "date_precision": "day", "issue": "", "normalized_date": "2015-08-01", "pages": "39-47", "proceedings_title": null, "publisher": "", "title": "Behavioural brain research", "volume": "289", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Reduced prefrontal dopaminergic activity in valproic acid-treated mouse autism model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Poly(N-isopropylacrylamide) (PNIPAm) is one of the most widely studied temperature-responsive polymers among those that have been applied to biomaterials science and technology. Here, we investigated the importance of interactions between PNIPAm-based copolymers and biological factors. The effects of a series of major anionic electrolytes in biological environments and of human serum albumin (HSA) on the lower critical solution temperature (LCST) of homo-PNIPAm and PNIPAm copolymers were studied, using either a hydrophobic monomer or a cationic monomer. We synthesized P(NIPAm-co-BMA3%) with butyl methacrylate (BMA) as a hydrophobic monomer and P(NIPAm-co-DMAPAm2%) with N,N-dimethylaminopropyl acrylamide (DMAPAm) as a cationic monomer. The LCST of PNIPAm and P(NIPAm-co-DMAPAm2%) decreased with increasing salt concentrations, and the effects of anions on each polymer corresponded to the Hofmeister series. The LCST of P(NIPAm-co-DMAPAm2%) was greatly affected by anionic electrolytes compared with those of homo-PNIPAm and P(NIPAm-co-BMA3%). While the LCST of homo-PNIPAm was not affected by HSA, the LCST of P(NIPAm-co-DMAPAm2%) decreased non-linearly with increasing HSA concentrations. These effects were due to the electrostatic interactions between the positively charged polymer chains and the negatively charged HSA, as well as the stabilization of polymer aggregations with HSA. Under physiological buffer conditions, the LCST of P(NIPAm-co-DMAPAm2%) was not significantly affected by the HSA concentration. These results indicated that depending on the types of copolymers used for biological applications, it is necessary to take into account the effect of biological media while designing polymers.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Nagumo", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Funatsu", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Hideko", "last_name": "Kanazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.colsurfb.2015.05.032" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26057248" } }, "mesh": [ { "descriptor": "Acrylic Resins", "descriptor_ui": "D000180", "major_topic": false }, { "descriptor": "Anions", "descriptor_ui": "D000838", "major_topic": false }, { "descriptor": "Electrolytes", "descriptor_ui": "D004573", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Serum Albumin", "descriptor_ui": "D012709", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015 Aug 1", "date_precision": "day", "issue": "", "normalized_date": "2015-08-01", "pages": "299-304", "proceedings_title": null, "publisher": "", "title": "Colloids and surfaces. B, Biointerfaces", "volume": "132", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "The effects of anionic electrolytes and human serum albumin on the LCST of poly(N-isopropylacrylamide)-based temperature-responsive copolymers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The c-Jun N-terminal kinase (JNK) pathway is a dual-functional oncogenic signaling that exerts both anti- and pro-tumor activities. However, the mechanism by which JNK switches its oncogenic roles depending on different cellular contexts has been elusive. Here, using the Drosophila genetics, we show that hyperactive Ras acts as a signaling switch that converts JNK's role from anti- to pro-tumor signaling through the regulation of Hippo signaling activity. In the normal epithelium, JNK signaling antagonizes the Hippo pathway effector Yorkie (Yki) through elevation of Warts activity, thereby suppressing tissue growth. In contrast, in the presence of hyperactive Ras, JNK signaling enhances Yki activation by accumulating F-actin through the activity of the LIM domain protein Ajuba, thereby promoting tissue growth. We also find that the epidermal growth factor receptor (EGFR) signaling uses this Ras-mediated conversion of JNK signaling to promote tissue growth. Our observations suggest that Ras-mediated switch of the JNK pathway from anti- to pro-tumor signaling could play crucial roles in tumorigenesis as well as in normal development.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masato", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kizawa", "name": null }, { "creator_type": "author", "first_name": "Shizue", "last_name": "Ohsawa", "name": null }, { "creator_type": "author", "first_name": "Tatsushi", "last_name": "Igaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2015.05.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25967126" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Hippo Kinases", "descriptor_ui": "D000099317", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Imaginal Discs", "descriptor_ui": "D060227", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": true }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Protein Kinases", "descriptor_ui": "D011494", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "ras Proteins", "descriptor_ui": "D018631", "major_topic": false }, { "descriptor": "Trans-Activators", "descriptor_ui": "D015534", "major_topic": false }, { "descriptor": "YAP-Signaling Proteins", "descriptor_ui": "D000091102", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jul 15", "date_precision": "day", "issue": "2", "normalized_date": "2015-07-15", "pages": "162-171", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "403", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "JNK signaling is converted from anti- to pro-tumor pathway by Ras-mediated switch of Warts activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transmission electron microscopy (TEM) is used for three-dimensional (3-D) analysis of synaptic connections in neuroscience research. However, 3-D reconstruction of the synapses using serial ultrathin sections is a powerful but tedious approach requiring advanced technical skills. High-voltage electron microscopy (HVEM) allows examination of thicker sections of biological specimens due to the increased penetration of the more accelerated electrons, which is useful to analyze the 3-D structure of biological specimens. However, it is still difficult to visualize the neural networks and synaptic connections in 3-D using HVEM because of insufficient and non uniform heavy metal staining in the membranous structures in semi-thin sections. Here, we present the successful chemical 3-D neuroanatomy of the rat spinal dorsal horn at the ultrastructural level as a first step for effective synaptome analysis by applying a high-contrast en bloc staining method to immune-HVEM tomography. Our new approach made it possible to examine many itch-mediating synaptic connections and neural networks in the spinal cord simultaneously using HVEM tomography. This novel 3-D electron microscopy is very useful for the analysis of synaptic structure and the chemical neuroanatomy at the 3-D ultrastructural level.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Keita", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Takanami", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neulet.2015.05.031" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26007703" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microscopy, Electron, Transmission", "descriptor_ui": "D046529", "major_topic": false }, { "descriptor": "Posterior Horn Cells", "descriptor_ui": "D020671", "major_topic": false }, { "descriptor": "Pruritus", "descriptor_ui": "D011537", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jul 10", "date_precision": "day", "issue": "", "normalized_date": "2015-07-10", "pages": "86-91", "proceedings_title": null, "publisher": "", "title": "Neuroscience letters", "volume": "599", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Effective synaptome analysis of itch-mediating neurons in the spinal cord: A novel immunohistochemical methodology using high-voltage electron microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dendritic cell immunoreceptor (DCIR) is a C-type lectin receptor mainly expressed in DCs. Dcir (-/-) mice spontaneously develop autoimmune enthesitis and ankylosis accompanied by fibrocartilage proliferation and ectopic ossification. However, the mechanisms of new bone/cartilage formation in Dcir (-/-) mice remain to be elucidated. In this study, we show that DCIR maintains bone homeostasis by regulating IFN-gamma production under pathophysiological conditions. DCIR deficiency increased bone volume in femurs and caused aberrant ossification in joints, whereas these symptoms were abolished in Rag2(-/-)Dcir(-/-) mice. IFN-gamma-producing T cells accumulated in lymph nodes and joints of Dcir(-/-) mice, and purified Dcir(-/-) DCs enhanced IFN-gamma(+) T cell differentiation. The ankylotic changes and bone volume increase were suppressed in the absence of IFN-gamma. Thus, IFN-gamma is a positive chondrogenic and osteoblastogenic factor, and DCIR is a crucial regulator of bone metabolism; consequently, both factors are potential targets for therapies directed against bone metabolic diseases.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Kaifu", "name": null }, { "creator_type": "author", "first_name": "Rikio", "last_name": "Yabe", "name": null }, { "creator_type": "author", "first_name": "Akimasa", "last_name": "Seno", "name": null }, { "creator_type": "author", "first_name": "Soo-Hyun", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Fujikado", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Iwakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.4049/jimmunol.1500273" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25926676" } }, "mesh": [ { "descriptor": "Age Factors", "descriptor_ui": "D000367", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ankylosis", "descriptor_ui": "D000844", "major_topic": false }, { "descriptor": "Bone and Bones", "descriptor_ui": "D001842", "major_topic": false }, { "descriptor": "Bone Density", "descriptor_ui": "D015519", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Chondrocytes", "descriptor_ui": "D019902", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Interferon-gamma", "descriptor_ui": "D007371", "major_topic": false }, { "descriptor": "Lectins, C-Type", "descriptor_ui": "D037181", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Osteoblasts", "descriptor_ui": "D010006", "major_topic": false }, { "descriptor": "T-Lymphocyte Subsets", "descriptor_ui": "D016176", "major_topic": false }, { "descriptor": "X-Ray Microtomography", "descriptor_ui": "D055114", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jun 15", "date_precision": "day", "issue": "12", "normalized_date": "2015-06-15", "pages": "5681-5691", "proceedings_title": null, "publisher": "", "title": "Journal of immunology (Baltimore, Md. : 1950)", "volume": "194", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "DCIR maintains bone homeostasis by regulating IFN-gamma production in T cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: We produced fibroblast growth factor (FGF)-2-containing low-molecular-weight heparin (Fragmin)/protamine nanoparticles (FGF-2 + F/P NPs). The purpose of this study was to evaluate the effectiveness of the local administration of FGF-2 + F/P NPs on repairing crush syndrome (CS)-injured lesions after compression release using a nonlethal and reproducible CS injury rat model. MATERIALS AND METHODS: The hind limbs of the anesthetized rats were compressed for 6 h using 3.6 kg blocks, as previously described. The effects of administering FGF-2 + F/P NPs (group A), F/P NPs alone (group B), FGF-2 alone (group C), and saline (control; group D) were examined. Motor function, surface blood flow in the hind limbs, and the wet/dry weight ratio in the tibialis anterior muscle were examined for 1-28 d after the compression release. Histologic analyses were also performed. RESULTS: At the middle and late stages (3-28 d after the compression release), group A had higher scores in the motor function, improved blood flow, increased number of blood vessels, and faster recovered muscle tissue, compared with the other groups. There was no significant difference in enhanced edema in the tibialis anterior muscle among all groups. CONCLUSIONS: The local administration of FGF-2 + F/P NPs to a CS-injured lesion was effective in repairing damaged muscle tissue after compression release.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Takikawa", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Takabayashi", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Hidemi", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jss.2015.03.022" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25864985" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anticoagulants", "descriptor_ui": "D000925", "major_topic": false }, { "descriptor": "Crush Syndrome", "descriptor_ui": "D003444", "major_topic": false }, { "descriptor": "Dalteparin", "descriptor_ui": "D017985", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Drug Evaluation, Preclinical", "descriptor_ui": "D004353", "major_topic": false }, { "descriptor": "Drug Therapy, Combination", "descriptor_ui": "D004359", "major_topic": false }, { "descriptor": "Edema", "descriptor_ui": "D004487", "major_topic": false }, { "descriptor": "Fibroblast Growth Factor 2", "descriptor_ui": "D016222", "major_topic": false }, { "descriptor": "Injections, Intralesional", "descriptor_ui": "D015552", "major_topic": false }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": false }, { "descriptor": "Lower Extremity", "descriptor_ui": "D035002", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": false }, { "descriptor": "Neovascularization, Physiologic", "descriptor_ui": "D018919", "major_topic": false }, { "descriptor": "Protamines", "descriptor_ui": "D011479", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Regional Blood Flow", "descriptor_ui": "D012039", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jun 15", "date_precision": "day", "issue": "2", "normalized_date": "2015-06-15", "pages": "247-257", "proceedings_title": null, "publisher": "", "title": "The Journal of surgical research", "volume": "196", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Improved angiogenesis and healing in crush syndrome by fibroblast growth factor-2-containing low-molecular-weight heparin (Fragmin)/protamine nanoparticles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We examined the pancreatic function of p13 encoded by 1110001J03Rik, whose expression is decreased in pancreatic islets in high-fat-fed diabetic mice, by generating transgenic mice overexpressing p13 (p13-Tg) in pancreatic beta-cells. p13-Tg mice showed normal basal glucose metabolism; however, under high-fat feeding, these animals showed augmented glucose-induced first-phase and total insulin secretion, improved glucose disposal, greater islet area and increased mitotic insulin-positive cells. In addition, high-fat diet-induced 4-hydroxynonenal immunoreactivity, a reliable marker and causative agent of lipid peroxidative stress, was significantly decreased in p13-Tg mouse islets. These results indicate that p13 is a novel pancreatic factor exerting multiple beneficial effects against type 2 diabetes.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shintaro", "last_name": "Higashi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Katagi", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Soken", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Koumoto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hamagami", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Tomimoto", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Tadayasu", "last_name": "Ohkubo", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Onaka", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2015.04.074" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25912136" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 2", "descriptor_ui": "D003924", "major_topic": false }, { "descriptor": "Diet, High-Fat", "descriptor_ui": "D059305", "major_topic": true }, { "descriptor": "Insulin-Secreting Cells", "descriptor_ui": "D050417", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jun 12", "date_precision": "day", "issue": "4", "normalized_date": "2015-06-12", "pages": "612-617", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "461", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "p13 overexpression in pancreatic beta-cells ameliorates type 2 diabetes in high-fat-fed mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent use of the CRISPR/Cas9 system has dramatically reduced the time required to produce mutant mice, but the involvement of a time-consuming microinjection step still hampers its application for high-throughput genetic analysis. Here we developed a simple, highly efficient, and large-scale genome editing method, in which the RNAs for the CRISPR/Cas9 system are electroporated into zygotes rather than microinjected. We used this method to perform single-stranded oligodeoxynucleotide (ssODN)-mediated knock-in in mouse embryos. This method facilitates large-scale genetic analysis in the mouse.", "classifications": [ { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masakazu", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep11315" }, "pmcid": { "normalized": "PMC4463957" }, "pmid": { "normalized": "26066060" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": true }, { "descriptor": "Electroporation", "descriptor_ui": "D018274", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Zygote", "descriptor_ui": "D015053", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015 Jun 11", "date_precision": "day", "issue": "", "normalized_date": "2015-06-11", "pages": "11315", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "5", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Electroporation enables the efficient mRNA delivery into the mouse zygotes and facilitates CRISPR/Cas9-based genome editing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Inflammasome activation has been implicated in various inflammatory diseases including post-ischaemic inflammation after stroke. Inflammasomes mediate activation of caspase-1, which subsequently induces secretion of pro-inflammatory cytokines such as IL-1β and IL-18, as well as a form of cell death called pyroptosis. In this study, we report that Bruton's tyrosine kinase (BTK) is an essential component of the NLRP3 inflammasome, in which BTK physically interacts with ASC and NLRP3. Inhibition of BTK by pharmacological or genetic means severely impairs activation of the NLRP3 inflammasome. The FDA-approved BTK inhibitor ibrutinib (PCI-32765) efficiently suppresses infarct volume growth and neurological damage in a brain ischaemia/reperfusion model in mice. Ibrutinib inhibits maturation of IL-1β by suppressing caspase-1 activation in infiltrating macrophages and neutrophils in the infarcted area of ischaemic brain. Our study indicates that BTK is essential for NLRP3 inflammasome activation and could be a potent therapeutic target in ischaemic stroke.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shichita", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Ritsuko", "last_name": "Komine", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Rimpei", "last_name": "Morita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms8360" }, "pmcid": { "normalized": "PMC4490404" }, "pmid": { "normalized": "26059659" } }, "mesh": [ { "descriptor": "Agammaglobulinaemia Tyrosine Kinase", "descriptor_ui": "D000077329", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain Ischemia", "descriptor_ui": "D002545", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Inflammasomes", "descriptor_ui": "D058847", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "NLR Family, Pyrin Domain-Containing 3 Protein", "descriptor_ui": "D000071199", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Protein-Tyrosine Kinases", "descriptor_ui": "D011505", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jun 10", "date_precision": "day", "issue": "", "normalized_date": "2015-06-10", "pages": "7360", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "6", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Bruton's tyrosine kinase is essential for NLRP3 inflammasome activation and contributes to ischaemic brain injury.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Reduced motivation is an important marker of psychiatric disorders, including depression. We describe the female encounter test, a novel method of evaluating reward-seeking behavior in mice. METHODS: The test apparatus consists of three open chambers, formed with partitions that allow the animal to move freely from one chamber to another. A test male mouse is habituated in the apparatus, and subsequently a female and male mouse are introduced into a wire-mesh box in the left and right chamber, respectively. The time the test male mouse spends in the female or male area is measured for 10 min. RESULTS: All six strains of mice tested showed a significant preference for female encounters. The preference was observed in 7-30-week-old mice. The preference was blocked by castration of the resident male test mouse, and was not affected by the phase of the menstrual cycle of the female intruder. The preference was impaired in mouse models of depression, including social isolation-reared, corticosterone-treated, and lipopolysaccharide-treated mice. The impairment was alleviated by fluvoxamine in isolation-reared and lipopolysaccharide-treated mice, and it was improved by the metabotropic glutamate 2/3 receptor antagonist LY341495 in corticosterone-treated mice. Encounter with a female, but not male, mouse increased c-Fos expression in the nucleus accumbens shell of test male mice. Furthermore, both the preference and encounter-induced increases in c-Fos expression were blocked by dopamine D1 and D2 receptor antagonists. CONCLUSIONS: These findings indicate that motivation in adult male mice can be easily evaluated by quantitating female encounters.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Saki", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Onaka", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/ijnp/pyv062" }, "pmcid": { "normalized": "PMC4756727" }, "pmid": { "normalized": "26025781" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antidepressive Agents, Second-Generation", "descriptor_ui": "D018687", "major_topic": false }, { "descriptor": "Castration", "descriptor_ui": "D002369", "major_topic": false }, { "descriptor": "Choice Behavior", "descriptor_ui": "D002755", "major_topic": false }, { "descriptor": "Corticosterone", "descriptor_ui": "D003345", "major_topic": false }, { "descriptor": "Depressive Disorder", "descriptor_ui": "D003866", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Estrous Cycle", "descriptor_ui": "D030762", "major_topic": false }, { "descriptor": "Excitatory Amino Acid Antagonists", "descriptor_ui": "D018691", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluvoxamine", "descriptor_ui": "D016666", "major_topic": false }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Motivation", "descriptor_ui": "D009042", "major_topic": true }, { "descriptor": "Nucleus Accumbens", "descriptor_ui": "D009714", "major_topic": false }, { "descriptor": "Psychological Tests", "descriptor_ui": "D011581", "major_topic": true }, { "descriptor": "Reward", "descriptor_ui": "D012201", "major_topic": true }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": true }, { "descriptor": "Social Isolation", "descriptor_ui": "D012934", "major_topic": false }, { "descriptor": "Xanthenes", "descriptor_ui": "D014966", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 May 29", "date_precision": "day", "issue": "11", "normalized_date": "2015-05-29", "pages": "pyv062", "proceedings_title": null, "publisher": "", "title": "The international journal of neuropsychopharmacology", "volume": "18", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "The Female Encounter Test: A Novel Method for Evaluating Reward-Seeking Behavior or Motivation in Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We discovered that positively charged terbium complexes bearing 1,4,7,10-tetraazacyclododecane functionalized with amide ligands are highly sensitive to dynamic luminescence quenching by NAD(P)H. We exploited this phenomenon to establish a general time-resolved luminescence-based assay platform for sensitive detection of NAD(P)H-dependent enzyme activities.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c5cc01613d" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25879812" } }, "mesh": [ { "descriptor": "Amides", "descriptor_ui": "D000577", "major_topic": false }, { "descriptor": "Coordination Complexes", "descriptor_ui": "D056831", "major_topic": false }, { "descriptor": "Heterocyclic Compounds, 1-Ring", "descriptor_ui": "D006573", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Luminescence", "descriptor_ui": "D049449", "major_topic": false }, { "descriptor": "NADP", "descriptor_ui": "D009249", "major_topic": false }, { "descriptor": "Terbium", "descriptor_ui": "D013725", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 May 14", "date_precision": "day", "issue": "39", "normalized_date": "2015-05-14", "pages": "8319-8322", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "51", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Detection of NAD(P)H-dependent enzyme activity with dynamic luminescence quenching of terbium complexes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Molecular pathways regulating the development of arterial and venous endothelial cells (ECs) are now well established, but control of parallel arterial-venous alignment is unclear. Here we report that arterial-venous alignment in the skin is determined by apelin receptor (APJ) expression in venous ECs. One of the activators of APJ is apelin. We found that apelin is produced by arterial ECs during embryogenesis, induces chemotaxis of venous ECs, and promotes the production of secreted Frizzled-related protein 1 (sFRP1) by APJ(+) ECs. sFRP1 stimulates matrix metalloproteinase production by Ly6B.2(+) neutrophil-like cells located between the arteries and veins, resulting in remodeling of extracellular matrices to support venous displacement. Moreover, using apelin- or APJ-deficient mice, which exhibit arterial-venous disorganization, we found that arterial-venous alignment is involved in thermoregulation, possibly by regulating countercurrent heat exchange. We hypothesize that the evolution of parallel juxtapositional arterial-venous alignment was an adaptation to reduce body heat loss.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Daishi", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Weizhen", "last_name": "Jia", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Sonobe", "name": null }, { "creator_type": "author", "first_name": "Hirotsugu", "last_name": "Tsuchimochi", "name": null }, { "creator_type": "author", "first_name": "Mikiyasu", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Ralf H.", "last_name": "Adams", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Fukamizu", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2015.02.024" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25920569" } }, "mesh": [ { "descriptor": "Adipokines", "descriptor_ui": "D054392", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apelin", "descriptor_ui": "D000073861", "major_topic": false }, { "descriptor": "Apelin Receptors", "descriptor_ui": "D000075244", "major_topic": false }, { "descriptor": "Arteries", "descriptor_ui": "D001158", "major_topic": false }, { "descriptor": "Body Temperature Regulation", "descriptor_ui": "D001833", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Endothelium, Vascular", "descriptor_ui": "D004730", "major_topic": false }, { "descriptor": "Frizzled-Related Proteins", "descriptor_ui": "D000099274", "major_topic": false }, { "descriptor": "Glycoproteins", "descriptor_ui": "D006023", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neovascularization, Physiologic", "descriptor_ui": "D018919", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Veins", "descriptor_ui": "D014680", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 May 4", "date_precision": "day", "issue": "3", "normalized_date": "2015-05-04", "pages": "247-259", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "33", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "APJ Regulates Parallel Alignment of Arteries and Veins in the Skin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stress during developmental stage may cause psychological morbidities, and then the studies on stress are important in adolescent rodents. Restraint is used as a common stressor in rodents and the effects of restraint during the light cycle have been studied, but those of restraint during the dark cycle have not. The present study examined the effects of restraint during the light and dark cycles on anxiety behaviors in adolescent mice. Restraint for 3h during either the light or dark cycle impaired memory function in the fear conditioning test, but did not affect locomotor activity. In the elevated plus-maze test, restraint during the dark cycle reduced anxiety-like behaviors in mice. Repeated exposure to a 3-h period dark cycle restraint for 2 weeks had a similar anxiolytic-like effect. In contrast, restraint for 3h during the light cycle produced anxiety behavior in adolescent, but not adult, mice. The light cycle stress increased plasma corticosterone levels, and elevated c-Fos expression in the prefrontal cortex, paraventricular hypothalamic nucleus, basolateral amygdala and dentate gyrus, and enhanced serotonin turnover in the hippocampus and striatum, while the dark cycle stress did not. There was no difference in the stress-mediated reduction in pentobarbital-induced sleeping time between dark and light cycle restraint. These findings suggest that the anxiolytic effect of dark cycle restraint is mediated by corticosterone, serotonin or gamma-aminobutyric acid-independent mechanisms, although the anxiogenic effect of light cycle restraint is associated with changes in plasma corticosterone levels and serotonin turnover in specific brain regions.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Toratani", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Onaka", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbr.2015.02.010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25687845" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anxiety", "descriptor_ui": "D001007", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Conditioning, Psychological", "descriptor_ui": "D003213", "major_topic": false }, { "descriptor": "Corticosterone", "descriptor_ui": "D003345", "major_topic": false }, { "descriptor": "Darkness", "descriptor_ui": "D003624", "major_topic": true }, { "descriptor": "Exploratory Behavior", "descriptor_ui": "D005106", "major_topic": false }, { "descriptor": "Fear", "descriptor_ui": "D005239", "major_topic": false }, { "descriptor": "Hypnotics and Sedatives", "descriptor_ui": "D006993", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Pentobarbital", "descriptor_ui": "D010424", "major_topic": false }, { "descriptor": "Photoperiod", "descriptor_ui": "D017440", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-fos", "descriptor_ui": "D016760", "major_topic": false }, { "descriptor": "Restraint, Physical", "descriptor_ui": "D012149", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 May 1", "date_precision": "day", "issue": "", "normalized_date": "2015-05-01", "pages": "103-111", "proceedings_title": null, "publisher": "", "title": "Behavioural brain research", "volume": "284", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Anxiolytic-like effects of restraint during the dark cycle in adolescent mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Depression is a complex neuropsychiatric disorder with an unclear molecular etiology. Inflammatory cytokines and molecular intermediates (including prostaglandins) are suggested to be involved in depression; however, the roles of prostaglandins and their respective receptors are largely unknown in depression. Using genetic and pharmacological approaches, we show here that chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2), a second receptor for prostaglandin D2 (PGD2), mediates depression-related behavior in mice. CRTH2-deficient (CRTH2(-/-)) mice showed antidepressant-like activity in a chronic corticosterone treatment-induced depression. Consistent with this observation, the pharmacological inhibition of CRTH2 via the clinically available drug ramatroban also rescued abnormal social interaction and depression-related behavior in well-established models, including chronic corticosterone-, lipopolysaccharide-, and tumor-induced pathologically relevant depression models. Importantly, chronic stress via corticosterone treatment increased mRNA levels in PGD2-producing enzymes, such as cyclooxygenase-2 and lipocalin-type PGD2 synthase, in the brain. Furthermore, the activity of the hippocampal noradrenergic system but not the dopaminergic or serotonergic systems was increased in CRTH2(-/-) mice. Together with the observation that untreated CRTH2(-/-) mice showed antidepressant-like activity in the forced swim test, these results provide evidence that central CRTH2-mediated signaling is critically involved in depression-related behavior.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Onaka", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Haba", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Hyper", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Kanoh", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Kin-Ya", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "James A.", "last_name": "Waschek", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbr.2015.02.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25698598" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Carbazoles", "descriptor_ui": "D002227", "major_topic": false }, { "descriptor": "Central Nervous System Agents", "descriptor_ui": "D002491", "major_topic": false }, { "descriptor": "Chronic Disease", "descriptor_ui": "D002908", "major_topic": false }, { "descriptor": "Corticosterone", "descriptor_ui": "D003345", "major_topic": false }, { "descriptor": "Cyclooxygenase 2", "descriptor_ui": "D051546", "major_topic": false }, { "descriptor": "Depressive Disorder", "descriptor_ui": "D003866", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Intramolecular Oxidoreductases", "descriptor_ui": "D019746", "major_topic": false }, { "descriptor": "Lipocalins", "descriptor_ui": "D054834", "major_topic": false }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Norepinephrine", "descriptor_ui": "D009638", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Receptors, Immunologic", "descriptor_ui": "D011971", "major_topic": false }, { "descriptor": "Receptors, Prostaglandin", "descriptor_ui": "D011982", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": false }, { "descriptor": "Stress, Psychological", "descriptor_ui": "D013315", "major_topic": false }, { "descriptor": "Sulfonamides", "descriptor_ui": "D013449", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 May 1", "date_precision": "day", "issue": "", "normalized_date": "2015-05-01", "pages": "131-137", "proceedings_title": null, "publisher": "", "title": "Behavioural brain research", "volume": "284", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "CRTH2, a prostaglandin D2 receptor, mediates depression-related behavior in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydrogen sulfide (H2S), a toxic gas with the smell of rotten eggs, plays key roles in many physiological processes, including relaxation of vascular smooth muscles, mediation of neurotransmission, inhibition of insulin signaling, and regulation of inflammation. The most commonly used methods or detecting H2S are the methylene blue method and the electrode method, but these methods require destructive sampling, e.g., homogenization of biological samples. On the other hand, the fluorescence detection method has been widely used in biological studies to study the physiological roles of H2S, because this technology provides real-time, easy-to-use, nondestructive detection in live cells or tissues. Many selective fluorescent probes for H2S have been reported. Sulfane sulfur compounds contain divalent sulfur atoms bonded to other sulfur atom(s), as in persulfides (R-S-SH) and polysulfides (R-S-Sn-S-R). They are currently attracting increasing interest because one of the mechanisms of activity regulation of proteins by H2S is sulfhydration of cysteine residues (RSH --> RSSH). Since H2S and sulfane sulfur are redox partners, they are very likely to coexist in biological systems, and from a reactivity point-of-view, sulfane sulfur seems likely to be much more effective than H2S in S-sulfhydration. Therefore, sulfane sulfur may be involved in mediating at least some of the biological activities of H2S. In this review, we summarize recent work on fluorescent probes selective for H2S and/or sulfane sulfur, and we briefly review their applications to biological studies.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhito", "last_name": "Shimamoto", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.niox.2014.11.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25461270" } }, "mesh": [ { "descriptor": "Biotechnology", "descriptor_ui": "D001709", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Fluorometry", "descriptor_ui": "D005470", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Apr 30", "date_precision": "day", "issue": "", "normalized_date": "2015-04-30", "pages": "72-79", "proceedings_title": null, "publisher": "", "title": "Nitric oxide : biology and chemistry", "volume": "46", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Fluorescent probes for hydrogen sulfide (H2S) and sulfane sulfur and their applications to biological studies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Near-infrared (NIR) fluorescent probes based on the Forster resonance energy transfer (FRET) mechanism have various practical advantages, and their molecular design is generally based on the use of NIR dark quenchers, which are nonfluorescent dyes, as cleavable FRET acceptors. However, few NIR dark quenchers can quench fluorescence in the Cy7 region (over 780 nm). Here, we describe Si-rhodamine-based NIR dark quenchers (SiNQs), which show broad absorption covering this region. They are nonfluorescent independently of solvent polarity and pH, probably due to free rotation of the bond between the N atom and the xanthene moiety. SiNQs can easily be structurally modified to tune their water-solubility and absorption spectra, enabling flexible design of appropriate FRET pair for various NIR fluorescent dyes. To demonstrate the usefulness of SiNQs, we designed and synthesized a NIR fluorescent probe for matrix metalloproteinase (MMP) activity using SiNQ780. This probe 1 could detect MMP activity in vitro, in cultured cells and in a tumor-bearing mouse, in which the tumor was clearly visualized, by NIR fluorescence. We believe SiNQs will be useful for the development of a wide range of practical NIR fluorescent probes.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takuya", "last_name": "Myochin", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Shimpei", "last_name": "Iwaki", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.5b00246" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25764154" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Darkness", "descriptor_ui": "D003624", "major_topic": true }, { "descriptor": "Drug Design", "descriptor_ui": "D015195", "major_topic": true }, { "descriptor": "Drug Stability", "descriptor_ui": "D004355", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infrared Rays", "descriptor_ui": "D007259", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": false }, { "descriptor": "Silicon", "descriptor_ui": "D012825", "major_topic": false }, { "descriptor": "Solubility", "descriptor_ui": "D012995", "major_topic": false }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Apr 15", "date_precision": "day", "issue": "14", "normalized_date": "2015-04-15", "pages": "4759-4765", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "137", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a series of near-infrared dark quenchers based on Si-rhodamines and their application to fluorescent probes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescence live imaging has become an essential methodology in modern cell biology. However, fluorescence requires excitation light, which can sometimes cause potential problems, such as autofluorescence, phototoxicity, and photobleaching. Furthermore, combined with recent optogenetic tools, the light illumination can trigger their unintended activation. Because luminescence imaging does not require excitation light, it is a good candidate as an alternative imaging modality to circumvent these problems. The application of luminescence imaging, however, has been limited by the two drawbacks of existing luminescent protein probes, such as luciferases: namely, low brightness and poor color variants. Here, we report the development of bright cyan and orange luminescent proteins by extending our previous development of the bright yellowish-green luminescent protein Nano-lantern. The color change and the enhancement of brightness were both achieved by bioluminescence resonance energy transfer (BRET) from enhanced Renilla luciferase to a fluorescent protein. The brightness of these cyan and orange Nano-lanterns was approximately 20 times brighter than wild-type Renilla luciferase, which allowed us to perform multicolor live imaging of intracellular submicron structures. The rapid dynamics of endosomes and peroxisomes were visualized at around 1-s temporal resolution, and the slow dynamics of focal adhesions were continuously imaged for longer than a few hours without photobleaching or photodamage. In addition, we extended the application of these multicolor Nano-lanterns to simultaneous monitoring of multiple gene expression or Ca(2+) dynamics in different cellular compartments in a single cell.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" }, { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Akira", "last_name": "Takai", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Remi", "last_name": "Haruno", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Ohyanagi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1418468112" }, "pmcid": { "normalized": "PMC4394297" }, "pmid": { "normalized": "25831507" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Endosomes", "descriptor_ui": "D011992", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Focal Adhesions", "descriptor_ui": "D022001", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Luciferases, Renilla", "descriptor_ui": "D049410", "major_topic": false }, { "descriptor": "Luminescence", "descriptor_ui": "D049449", "major_topic": true }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Oligonucleotides", "descriptor_ui": "D009841", "major_topic": false }, { "descriptor": "Peroxisomes", "descriptor_ui": "D020675", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Renilla", "descriptor_ui": "D048790", "major_topic": false }, { "descriptor": "Vinculin", "descriptor_ui": "D016596", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Apr 7", "date_precision": "day", "issue": "14", "normalized_date": "2015-04-07", "pages": "4352-4356", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "112", "year": 2015 }, "ssbd": { "database": [ "ssbd-database-000043" ], "repository": [ "ssbd-repos-000043" ] }, "title": "Expanded palette of Nano-lanterns for real-time multicolor luminescence imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "MOTIVATION: Recent progress in live-cell imaging and modeling techniques has resulted in generation of a large amount of quantitative data (from experimental measurements and computer simulations) on spatiotemporal dynamics of biological objects such as molecules, cells and organisms. Although many research groups have independently dedicated their efforts to developing software tools for visualizing and analyzing these data, these tools are often not compatible with each other because of different data formats. RESULTS: We developed an open unified format, Biological Dynamics Markup Language (BDML; current version: 0.2), which provides a basic framework for representing quantitative biological dynamics data for objects ranging from molecules to cells to organisms. BDML is based on Extensible Markup Language (XML). Its advantages are machine and human readability and extensibility. BDML will improve the efficiency of development and evaluation of software tools for data visualization and analysis. AVAILABILITY AND IMPLEMENTATION: A specification and a schema file for BDML are freely available online at http://ssbd.qbic.riken.jp/bdml/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Tohsato", "name": null }, { "creator_type": "author", "first_name": "Kenneth H. L.", "last_name": "Ho", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/bioinformatics/btu767" }, "pmcid": { "normalized": "PMC4382901" }, "pmid": { "normalized": "25414366" } }, "mesh": [ { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Computer Graphics", "descriptor_ui": "D003196", "major_topic": true }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Databases, Factual", "descriptor_ui": "D016208", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Programming Languages", "descriptor_ui": "D011381", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true }, { "descriptor": "User-Computer Interface", "descriptor_ui": "D014584", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Apr 1", "date_precision": "day", "issue": "7", "normalized_date": "2015-04-01", "pages": "1044-1052", "proceedings_title": null, "publisher": "", "title": "Bioinformatics (Oxford, England)", "volume": "31", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Biological Dynamics Markup Language (BDML): an open format for representing quantitative biological dynamics data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bioluminescence imaging (BLI) has advantages for investigating biological phenomena in deep tissues of living animals, but few design strategies are available for functional bioluminescent substrates. We propose a new design strategy (designated as bioluminescent enzyme-induced electron transfer: BioLeT) for luciferin-based bioluminescence probes. Luminescence measurements of a series of aminoluciferin derivatives confirmed that bioluminescence can be controlled by means of BioLeT. Based on this concept, we developed bioluminescence probes for nitric oxide that enabled quantitative and sensitive detection even in vivo. Our design strategy should be applicable to develop a wide range of practically useful bioluminogenic probes.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hideo", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja511014w" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25761130" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Electron Transport", "descriptor_ui": "D004579", "major_topic": false }, { "descriptor": "Firefly Luciferin", "descriptor_ui": "D049454", "major_topic": false }, { "descriptor": "Luciferases, Firefly", "descriptor_ui": "D049409", "major_topic": false }, { "descriptor": "Luminescent Agents", "descriptor_ui": "D049408", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Apr 1", "date_precision": "day", "issue": "12", "normalized_date": "2015-04-01", "pages": "4010-4013", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "137", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "New class of bioluminogenic probe based on bioluminescent enzyme-induced electron transfer: BioLeT.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A-nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Nojiri", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Hosoda", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Tokudome", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Ishikane", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Otani", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Noriyoshi", "last_name": "Sawabata", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Nakagiri", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Funaki", "name": null }, { "creator_type": "author", "first_name": "Yukiyasu", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyonari", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Shioi", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Mikiya", "last_name": "Miyazato", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Meinoshin", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kangawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1417273112" }, "pmcid": { "normalized": "PMC4386325" }, "pmid": { "normalized": "25775533" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Atrial Natriuretic Factor", "descriptor_ui": "D009320", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Disease-Free Survival", "descriptor_ui": "D018572", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Kaplan-Meier Estimate", "descriptor_ui": "D053208", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Melanoma, Experimental", "descriptor_ui": "D008546", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Mar 31", "date_precision": "day", "issue": "13", "normalized_date": "2015-03-31", "pages": "4086-4091", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "112", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Systematic and simultaneous analysis of multiple cell types in the brain is becoming important, but such tools have not yet been adequately developed. Here, we aimed to generate a method for the specific fluorescent labeling of neurons and astrocytes, two major cell types in the brain, and we have developed lentiviral vectors to express the red fluorescent protein tdTomato in neurons and the enhanced green fluorescent protein (EGFP) in astrocytes. Importantly, both fluorescent proteins are fused to histone 2B protein (H2B) to confer nuclear localization to distinguish between single cells. We also constructed several expression constructs, including a tandem alignment of the neuron- and astrocyte-expression cassettes for simultaneous labeling. Introducing these vectors and constructs in vitro and in vivo resulted in cell type-specific and nuclear-localized fluorescence signals enabling easy detection and distinguishability of neurons and astrocytes. This tool is expected to be utilized for the simultaneous analysis of changes in neurons and astrocytes in healthy and diseased brains.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Wiebke", "last_name": "Schulze", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Kamo", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Camille", "last_name": "Farfan", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2015.02.073" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25721661" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Biochemistry", "descriptor_ui": "D001671", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Lentivirus", "descriptor_ui": "D016086", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Primary Cell Culture", "descriptor_ui": "D061251", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Mar 27", "date_precision": "day", "issue": "1", "normalized_date": "2015-03-27", "pages": "81-86", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "459", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Simultaneous neuron- and astrocyte-specific fluorescent marking.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A linear ubiquitin chain, which consists of ubiquitin molecules linked via their N- and C-termini, is formed by a linear ubiquitin chain assembly complex (LUBAC) composed of HOIP, HOIL-1L, and SHARPIN, and conjugation of a linear ubiquitin chain on the NF-kappaB essential modulator (NEMO) is deeply involved in NF-kappaB activation induced by various signals. Since abnormal activation of NF-kappaB is associated with inflammatory disease and malignancy, we searched for an inhibitor of LUBAC by high-throughput screening (HTS) with a Tb(3+)-fluorescein FRET system. As a result, we found that the fungal metabolite gliotoxin inhibits LUBAC selectively by binding to the RING-IBR-RING domain of HOIP, the catalytic center of LUBAC. Gliotoxin has been well-known as an inhibitor of NF-kappaB activation, though its action mechanism has remained elusive. Here, we show that gliotoxin inhibits signal-induced NF-kappaB activation by selectively inhibiting LUBAC-mediated linear ubiquitin chain formation.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Egashira", "name": null }, { "creator_type": "author", "first_name": "Nae", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Kirisako", "name": null }, { "creator_type": "author", "first_name": "Simon", "last_name": "Miller", "name": null }, { "creator_type": "author", "first_name": "Yoshiteru", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Tadahiko", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Shimonishi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Soichi", "last_name": "Wakatsuki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Iwai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/cb500653y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25494483" } }, "mesh": [ { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Fluorescein", "descriptor_ui": "D019793", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Gliotoxin", "descriptor_ui": "D005912", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "I-kappa B Kinase", "descriptor_ui": "D051550", "major_topic": false }, { "descriptor": "Immunosuppressive Agents", "descriptor_ui": "D007166", "major_topic": false }, { "descriptor": "Jurkat Cells", "descriptor_ui": "D019169", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Terbium", "descriptor_ui": "D013725", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Tumor Necrosis Factor-alpha", "descriptor_ui": "D014409", "major_topic": false }, { "descriptor": "Ubiquitin", "descriptor_ui": "D025801", "major_topic": false }, { "descriptor": "Ubiquitin-Protein Ligases", "descriptor_ui": "D044767", "major_topic": false }, { "descriptor": "Ubiquitination", "descriptor_ui": "D054875", "major_topic": false }, { "descriptor": "Ubiquitins", "descriptor_ui": "D014452", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Mar 20", "date_precision": "day", "issue": "3", "normalized_date": "2015-03-20", "pages": "675-681", "proceedings_title": null, "publisher": "", "title": "ACS chemical biology", "volume": "10", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Gliotoxin suppresses NF-kappaB activation by selectively inhibiting linear ubiquitin chain assembly complex (LUBAC).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Studies of temporal behaviors of protein association in living cells are crucially important for elucidating the fundamental roles and the mechanism of interactive coordination for cell activities. We developed a method for investigating the temporal alternation of a particular protein assembly using monomeric fluorescent proteins, fluorescent timers (FTs), of which the fluorescent color changes from blue to red over time. We identified a dissection site of the FTs, which allows complementation of the split FT fragments. The split fragments of each FT variant recovered their fluorescence and maintained inherent rates of the color changes upon the reassembly of the fragments in vitro. We applied this method to visualize the aggregation process of alpha-synuclein in living cells. The size of the aggregates with the temporal information was analyzed from ratio values of the blue and red fluorescence of the reconstituted FTs, from which the aggregation rates were evaluated. This method using the split FT fragments enables tracing and visualizing temporal alternations of various protein associations by single fluorescence measurements at a given time point.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ayari", "last_name": "Takamura", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ac504583t" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25679333" } }, "mesh": [ { "descriptor": "alpha-Synuclein", "descriptor_ui": "D051844", "major_topic": false }, { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Peptide Fragments", "descriptor_ui": "D010446", "major_topic": false }, { "descriptor": "Protein Multimerization", "descriptor_ui": "D055503", "major_topic": true }, { "descriptor": "Protein Structure, Secondary", "descriptor_ui": "D017433", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Mar 17", "date_precision": "day", "issue": "6", "normalized_date": "2015-03-17", "pages": "3366-3372", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "87", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Simultaneous time-lamination imaging of protein association using a split fluorescent timer protein.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During skeletal muscle differentiation, the activation of some tissue-specific genes occurs immediately while others are delayed. The molecular basis controlling temporal gene regulation is poorly understood. We show that the regulatory sequences, but not other regions of genes expressed at late times of myogenesis, are in close physical proximity in differentiating embryonic tissue and in differentiating culture cells, despite these genes being located on different chromosomes. Formation of these inter-chromosomal interactions requires the lineage-determinant MyoD and functional Brg1, the ATPase subunit of SWI/SNF chromatin remodeling enzymes. Ectopic expression of myogenin and a specific Mef2 isoform induced myogenic differentiation without activating endogenous MyoD expression. Under these conditions, the regulatory sequences of late gene loci were not in close proximity, and these genes were prematurely activated. The data indicate that the spatial organization of late genes contributes to temporal regulation of myogenic transcription by restricting late gene expression during the early stages of myogenesis.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Chandrashekara", "last_name": "Mallappa", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "John T.", "last_name": "Butler", "name": null }, { "creator_type": "author", "first_name": "Stephen P.", "last_name": "Baker", "name": null }, { "creator_type": "author", "first_name": "Jeanne B.", "last_name": "Lawrence", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Anthony N.", "last_name": "Imbalzano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nar/gkv046" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25653159" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chromatin Assembly and Disassembly", "descriptor_ui": "D042002", "major_topic": false }, { "descriptor": "Chromosomes, Mammalian", "descriptor_ui": "D033481", "major_topic": false }, { "descriptor": "DNA Helicases", "descriptor_ui": "D004265", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Histone Deacetylase 2", "descriptor_ui": "D056464", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle Development", "descriptor_ui": "D024510", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "MyoD Protein", "descriptor_ui": "D017570", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Regulatory Elements, Transcriptional", "descriptor_ui": "D050436", "major_topic": true }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Feb 27", "date_precision": "day", "issue": "4", "normalized_date": "2015-02-27", "pages": "2008-2021", "proceedings_title": null, "publisher": "", "title": "Nucleic Acids Research", "volume": "43", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatial re-organization of myogenic regulatory sequences temporally controls gene expression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Adult human mesenchymal stem/stromal cells (hMSCs) from bone marrow have been reported to exhibit beneficial effects on spinal cord injury (SCI). A neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP) is known to decrease neuronal cell death and inflammatory response after ischemia, SCI, and other neuronal disorders. Recently, we found that expression of the gene for mouse PACAP (Adcyap1) was greater in animals receiving hMSCs with neural injury such as ischemia. However, the association of PACAP with hMSCs to protect nerve cells against neural injuries is still unclear. METHODS: Wild-type and PACAP-gene-deficient (Adcyap1 (+/-) ) mice were subjected to spinal cord transection, and hMSCs (5 x 10(5) cells) were injected into the intervertebral spinal cord on day 1 post-operation (p.o.). Locomotor activity, injury volume, retention of hMSCs, mouse and human cytokine genes (which contribute to macrophage (MPhi) and microglial activation), and Adcyap1 were evaluated. RESULTS: hMSCs injected into wild-type mice improved locomotor activity and injury volume compared with vehicle-treated mice. In contrast, non-viable hMSCs injected into wild-type mice, and viable hMSCs injected into Adcyap1 (+/-) mice, did not. Wild-type mice injected with hMSCs exhibited increased Adcyap1 expression, and observed PACAP immunoreaction in neuron-like cells. Gene expression levels for IL-1, tumor necrosis factor alpha (TNFalpha), interleukin-10 (IL-10), and transforming growth factor beta (TGFbeta) decreased, while that for interleukin-4 (IL-4) increased, in hMSC-injected wild-type mice. In contrast, IL-1, TGFbeta, and IL-4 gene expression levels were all abolished in hMSC-injected Adcyap1 (+/-) mice on day 7 post-operation. Moreover, the mice-implanted hMSCs increased an alternative activating macrophage/microglial marker, arginase activity. The human gene profile indicated that hMSCs upregulated the gene of IL-4 and growth factors which were reported to enhance Adcyap1 expression. Finally, we demonstrated that hMSCs express human ADCYAP1 and its receptor gene after the inflammation-related interferon-gamma (IFNgamma) in vitro. CONCLUSIONS: These results suggest that hMSCs attenuate the deleterious effects of SCI by reducing associated inflammatory responses and enhancing IL-4 production. This effect could be mediated in part by cell-cell cross-talk involving the neuropeptide PACAP.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomomi", "last_name": "Tsumuraya", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Ohtaki", "name": null }, { "creator_type": "author", "first_name": "Dandan", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Hiraizumi", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Nakamachi", "name": null }, { "creator_type": "author", "first_name": "Zhifang", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Dohi", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Atsumi", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Shioda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12974-015-0252-5" }, "pmcid": { "normalized": "PMC4346126" }, "pmid": { "normalized": "25889720" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Transformed", "descriptor_ui": "D002461", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell- and Tissue-Based Therapy", "descriptor_ui": "D064987", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Interferon-gamma", "descriptor_ui": "D007371", "major_topic": false }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": false }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": false }, { "descriptor": "Mesenchymal Stem Cells", "descriptor_ui": "D059630", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I", "descriptor_ui": "D051237", "major_topic": false }, { "descriptor": "Spinal Cord Injuries", "descriptor_ui": "D013119", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Feb 22", "date_precision": "day", "issue": "", "normalized_date": "2015-02-22", "pages": "35", "proceedings_title": null, "publisher": "", "title": "Journal of neuroinflammation", "volume": "12", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Human mesenchymal stem/stromal cells suppress spinal inflammation in mice with contribution of pituitary adenylate cyclase-activating polypeptide (PACAP).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "At the initial stage of carcinogenesis, a mutation occurs in a single cell within a normal epithelial layer. We have previously shown that RasV12-transformed cells are apically extruded from the epithelium when surrounded by normal cells. However, the molecular mechanisms underlying this phenomenon remain elusive. Here, we demonstrate that Cav-1-containing microdomains and EPLIN (also known as LIMA1) are accumulated in RasV12-transformed cells that are surrounded by normal cells. We also show that knockdown of Cav-1 or EPLIN suppresses apical extrusion of RasV12-transformed cells, suggesting their positive role in the elimination of transformed cells from epithelia. EPLIN functions upstream of Cav-1 and affects its enrichment in RasV12-transformed cells that are surrounded by normal cells. Furthermore, EPLIN regulates non-cell-autonomous activation of myosin-II and protein kinase A (PKA) in RasV12-transformed cells. In addition, EPLIN substantially affects the accumulation of filamin A, a vital player in epithelial defense against cancer (EDAC), in the neighboring normal cells, and vice versa. These results indicate that EPLIN is a crucial regulator of the interaction between normal and transformed epithelial cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Atsuko", "last_name": "Ohoka", "name": null }, { "creator_type": "author", "first_name": "Mihoko", "last_name": "Kajita", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Ikenouchi", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Yako", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Kitamoto", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kon", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Ikegawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/jcs.163113" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25609711" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Butadienes", "descriptor_ui": "D002070", "major_topic": false }, { "descriptor": "Caveolae", "descriptor_ui": "D021941", "major_topic": false }, { "descriptor": "Caveolin 1", "descriptor_ui": "D051242", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "Chromones", "descriptor_ui": "D002867", "major_topic": false }, { "descriptor": "Contactin 1", "descriptor_ui": "D058967", "major_topic": false }, { "descriptor": "Cyclic AMP-Dependent Protein Kinases", "descriptor_ui": "D017868", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Filamins", "descriptor_ui": "D064448", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Microfilament Proteins", "descriptor_ui": "D008840", "major_topic": false }, { "descriptor": "Morpholines", "descriptor_ui": "D009025", "major_topic": false }, { "descriptor": "Myosin Type II", "descriptor_ui": "D024462", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Nitriles", "descriptor_ui": "D009570", "major_topic": false }, { "descriptor": "Phosphoinositide-3 Kinase Inhibitors", "descriptor_ui": "D000081082", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Feb 15", "date_precision": "day", "issue": "4", "normalized_date": "2015-02-15", "pages": "781-789", "proceedings_title": null, "publisher": "", "title": "Journal of cell science", "volume": "128", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "EPLIN is a crucial regulator for extrusion of RasV12-transformed cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transcription activator-like effector nucleases (TALENs) are artificial nucleases harboring a customizable DNA-binding domain and a FokI nuclease domain. The high specificity of the DNA-binding domain and the ease of design have enabled researchers to use TALENs for targeted mutagenesis in various organisms. Here, we report the development of TALEN-dependent targeted gene disruption in the crustacean Daphnia magna, the emerging model for ecological and toxicological genomics. First, a reporter transgene DsRed2 (EF1alpha-1::DsRed2) was targeted. Using the Golden Gate method with a GoldyTALEN scaffold, we constructed homodimeric and heterodimeric TALENs containing wild-type and ELD/KKR FokI domains. mRNAs that coded for either the customized homodimeric or heterodimeric TALENs were injected into one-cell-stage embryos. The high mortality of embryos injected with homodimeric TALEN mRNAs prevented us from detecting mutations. In contrast, embryos injected with heterodimeric TALEN mRNAs survived and 78%-87% of the adults lost DsRed2 fluorescence in a large portion of cells throughout the body. In addition, these adults produced non-fluorescent progenies, all of which carried mutations at the dsRed2 locus. We also tested heterodimeric TALENs targeted for the endogenous eyeless gene and found that biallelic mutations could be transmitted through germ line cells at a rate of up to 22%. Both somatic and heritable mutagenesis efficiencies of TALENs were higher than those of the CRISPR/Cas9 system that we recently developed. These results suggest that the TALEN system may efficiently induce heritable mutations into the target genes, which will further contribute to the progress of functional genomics in D. magna.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akiko", "last_name": "Naitou", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/bio.20149738" }, "pmcid": { "normalized": "PMC4359742" }, "pmid": { "normalized": "25681393" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015 Feb 13", "date_precision": "day", "issue": "3", "normalized_date": "2015-02-13", "pages": "364-369", "proceedings_title": null, "publisher": "", "title": "Biology open", "volume": "4", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Heterodimeric TALENs induce targeted heritable mutations in the crustacean Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular redox state is a critical factor for fundamental cellular functions, including regulation of the activities of various metabolic enzymes as well as ROS production and elimination. Genetically-encoded fluorescent redox sensors, such as roGFP (Hanson, G. T., et al. (2004)) and Redoxfluor (Yano, T., et al. (2010)), have been developed to investigate the redox state of living cells. However, these sensors are not useful in cells that contain, for example, other colored pigments. We therefore intended to obtain simpler redox sensor proteins, and have developed oxidation-sensitive fluorescent proteins called Oba-Q (oxidation balance sensed quenching) proteins. Our sensor proteins derived from CFP and Sirius can be used to monitor the intracellular redox state as their fluorescence is drastically quenched upon oxidation. These blue-shifted spectra of the Oba-Q proteins enable us to monitor various redox states in conjunction with other sensor proteins.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ichinose", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2014.12.095" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25592971" } }, "mesh": [ { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": false }, { "descriptor": "Glutathione Disulfide", "descriptor_ui": "D019803", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Fluid", "descriptor_ui": "D007424", "major_topic": false }, { "descriptor": "Mutagenesis", "descriptor_ui": "D016296", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Quantum Theory", "descriptor_ui": "D011789", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Feb 13", "date_precision": "day", "issue": "3", "normalized_date": "2015-02-13", "pages": "242-248", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "457", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Redox sensor proteins for highly sensitive direct imaging of intracellular redox state.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescence imaging is one of the most powerful techniques for visualizing temporal and spatial changes of biological phenomena in living cells, and many fluorescent probes have been developed. In particular, xanthene dyes such as fluorescein and rhodamines have favorable characteristics, such as high water solubility, high fluorescence quantum yield and high molar extinction coefficient, and they have been utilized as fluorescent cores for fluorescent probes working in the green to red wavelength region. Recently, silicon-substituted xanthene dyes such as 2,7-N,N,N',N'-tetramethyl-9-dimethyl-10-hydro-9-silaanthracene (TMDHS), Si-rhodamines and TokyoMagentas, in which the O atom at the 10-position of xanthene is replaced with a Si atom, have been developed as novel far-red to near-infrared fluorescent cores that retain the key advantages of the parent structures. Fluorescent probes based on them have opened up new possibilities for imaging biological processes in living cells. This minireview covers recent progress in silicon-substituted xanthene dyes, including representative applications for in vivo tumor imaging, triple-color imaging of neuronal activity, and super-resolution microscopy.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yu", "last_name": "Kushida", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c4an01172d" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25380094" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Silicon", "descriptor_ui": "D012825", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Feb 7", "date_precision": "day", "issue": "3", "normalized_date": "2015-02-07", "pages": "685-695", "proceedings_title": null, "publisher": "", "title": "The Analyst", "volume": "140", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Silicon-substituted xanthene dyes and their applications in bioimaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During cerebellar development, the main portion of the cerebellar plate neuroepithelium gives birth to Purkinje cells and interneurons, whereas the rhombic lip, the germinal zone at its dorsal edge, generates granule cells and cerebellar nuclei neurons. However, it remains elusive how these components cooperate to form the intricate cerebellar structure. Here, we found that a polarized cerebellar structure self-organizes in 3D human embryonic stem cell (ESC) culture. The self-organized neuroepithelium differentiates into electrophysiologically functional Purkinje cells. The addition of fibroblast growth factor 19 (FGF19) promotes spontaneous generation of dorsoventrally polarized neural-tube-like structures at the level of the cerebellum. Furthermore, addition of SDF1 and FGF19 promotes the generation of a continuous cerebellar plate neuroepithelium with rhombic-lip-like structure at one end and a three-layer cytoarchitecture similar to the embryonic cerebellum. Thus, human-ESC-derived cerebellar progenitors exhibit substantial self-organizing potential for generating a polarized structure reminiscent of the early human cerebellum at the first trimester.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2014.12.051" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25640179" } }, "mesh": [ { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Chemokine CXCL12", "descriptor_ui": "D054377", "major_topic": false }, { "descriptor": "Fibroblast Growth Factors", "descriptor_ui": "D005346", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Feb 3", "date_precision": "day", "issue": "4", "normalized_date": "2015-02-03", "pages": "537-550", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "10", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lineage potential is triggered by lineage-specific transcription factors in association with changes in the chromatin structure. Histone H3.3 variant is thought to play an important role in the regulation of lineage-specific genes. To elucidate the function of H3.3 in myogenic differentiation, we forced the expression of GFP-H3.1 to alter the balance between H3.1 and H3.3 in mouse C2C12 cells that could be differentiated into myotubes. GFP-H3.1 replaced H3.3 in the regulatory regions of skeletal muscle (SKM) genes and induced a decrease of H3K4 trimethylation (H3K4me3) and increase of H3K27 trimethylation (H3K27me3). Similar results were obtained by H3.3 knockdown. In contrast, MyoD-dependent H3.3 incorporation into SKM genes in fibroblasts induced an increase of H3K4me3 and H3K27me3. In mouse embryos, a bivalent modification of H3K4me3 and H3K27me3 was formed on H3.3-incorporated SKM genes before embryonic skeletal muscle differentiation. These results suggest that lineage potential is established through a selective incorporation of specific H3 variants that governs the balance of histone modifications.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Daijiro", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nar/gku1346" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25539924" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle Development", "descriptor_ui": "D024510", "major_topic": false }, { "descriptor": "Muscle Fibers, Skeletal", "descriptor_ui": "D018485", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jan 30", "date_precision": "day", "issue": "2", "normalized_date": "2015-01-30", "pages": "775-786", "proceedings_title": null, "publisher": "", "title": "Nucleic Acids Research", "volume": "43", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Incorporation of histone H3.1 suppresses the lineage potential of skeletal muscle.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydrogen sulfide (H2S) has multiple physiological roles, for example, in vasodilation and inflammation. It is a highly reactive gas under ambient conditions, so controllable H2S donors are required for studying its biological functions. Here, we describe the design, synthesis and application of a H2S donor (SPD-2) that utilizes xanthone photochemistry to control H2S release. H2S generation from SPD-2 was completely dependent on UVA-irradiation (325-385nm), as confirmed by methylene blue assay and by the use of a H2S-selective fluorescent probe. SPD-2 was confirmed to provide controlled H2S delivery in live cells, and should be suitable for various biological applications.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Ieda", "name": null }, { "creator_type": "author", "first_name": "Mitsuyasu", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Sasakura", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Hidehiko", "last_name": "Nakagawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bmcl.2014.11.084" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25499432" } }, "mesh": [ { "descriptor": "Drug Carriers", "descriptor_ui": "D004337", "major_topic": false }, { "descriptor": "Drug Discovery", "descriptor_ui": "D055808", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": false }, { "descriptor": "Photochemistry", "descriptor_ui": "D010777", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jan 15", "date_precision": "day", "issue": "2", "normalized_date": "2015-01-15", "pages": "175-178", "proceedings_title": null, "publisher": "", "title": "Bioorganic & medicinal chemistry letters", "volume": "25", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of photo-controllable hydrogen sulfide donor applicable in live cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Simple and regular anatomical structure is a hallmark of the cerebellar cortex. Parasagittally arrayed alternate expression of aldolase C/zebrin II in Purkinje cells (PCs) has been extensively studied, but surprisingly little is known about its functional significance. Here we found a precise structure-function relationship between aldolase C expression and synchrony of PC complex spike activities that reflect climbing fiber inputs to PCs. We performed two-photon calcium imaging in transgenic mice in which aldolase C compartments can be visualized in vivo, and identified highly synchronous complex spike activities among aldolase C-positive or aldolase C-negative PCs, but not across these populations. The boundary of aldolase C compartments corresponded to that of complex spike synchrony at single-cell resolution. Sensory stimulation evoked aldolase C compartment-specific complex spike responses and synchrony. This result further revealed the structure-function segregation. In awake animals, complex spike synchrony both within and between PC populations across the aldolase C boundary were enhanced in response to sensory stimuli, in a way that two functionally distinct PC ensembles are coactivated. These results suggest that PC populations characterized by aldolase C expression precisely represent distinct functional units of the cerebellar cortex, and these functional units can cooperate to process sensory information in awake animals.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.2170-14.2015" }, "pmcid": { "normalized": "PMC6605375" }, "pmid": { "normalized": "25589776" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Fructose-Bisphosphate Aldolase", "descriptor_ui": "D005634", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Organ Specificity", "descriptor_ui": "D009928", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jan 14", "date_precision": "day", "issue": "2", "normalized_date": "2015-01-14", "pages": "843-852", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "35", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Structure-function relationships between aldolase C/zebrin II expression and complex spike synchrony in the cerebellum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Amphiphilic hyaluronic acid (HA) derivatives bearing hydrophobic indocyanine green dye derivatives and hydrophilic poly(ethylene glycol) were synthesized through the use of condensation and copper-catalyzed click cyclization reactions. The amphiphilic HA derivatives dissolved in water and formed self-assemblies in which the near-infrared dyes were tightly packed and arranged to form dimers or H-aggregates. By irradiating an aqueous solution of HA derivatives with near-infrared light, photoacoustic signals were detected along with fluorescence emission. Self-assemblies consisting of HA derivatives could smoothly accumulate in tumor tissues by passive tumor targeting. By utilizing HA derivatives as a contrast agent, tumor sites were clearly visualized by optical imaging as well as by photoacoustic tomography.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/bm501438e" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25402751" } }, "mesh": [ { "descriptor": "Adjuvants, Immunologic", "descriptor_ui": "D000276", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Colonic Neoplasms", "descriptor_ui": "D003110", "major_topic": false }, { "descriptor": "Coloring Agents", "descriptor_ui": "D004396", "major_topic": false }, { "descriptor": "Contrast Media", "descriptor_ui": "D003287", "major_topic": true }, { "descriptor": "Hyaluronic Acid", "descriptor_ui": "D006820", "major_topic": false }, { "descriptor": "Indocyanine Green", "descriptor_ui": "D007208", "major_topic": false }, { "descriptor": "Infrared Rays", "descriptor_ui": "D007259", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasm Transplantation", "descriptor_ui": "D009368", "major_topic": false }, { "descriptor": "Photoacoustic Techniques", "descriptor_ui": "D061088", "major_topic": false }, { "descriptor": "Polyethylene Glycols", "descriptor_ui": "D011092", "major_topic": false }, { "descriptor": "Tomography", "descriptor_ui": "D014054", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jan 12", "date_precision": "day", "issue": "1", "normalized_date": "2015-01-12", "pages": "219-227", "proceedings_title": null, "publisher": "", "title": "Biomacromolecules", "volume": "16", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Near-infrared dye-conjugated amphiphilic hyaluronic acid derivatives as a dual contrast agent for in vivo optical and photoacoustic tumor imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Regulation of transcription elongation by RNA polymerase II (Pol II) is a key regulatory step in gene transcription. Recently, the little elongation complex (LEC)-which contains the transcription elongation factor ELL/EAF-was found to be required for the transcription of Pol II-dependent small nuclear RNA (snRNA) genes. Here we show that the human Mediator subunit MED26 plays a role in the recruitment of LEC to a subset of snRNA genes through direct interaction of EAF and the N-terminal domain (NTD) of MED26. Loss of MED26 in cells decreases the occupancy of LEC at a subset of snRNA genes and results in a reduction in their transcription. Our results suggest that the MED26-NTD functions as a molecular switch in the exchange of TBP-associated factor 7 (TAF7) for LEC to facilitate the transition from initiation to elongation during transcription of a subset of snRNA genes.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hidehisa", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Delnur", "last_name": "Anwar", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Chieri", "last_name": "Tomomori-Sato", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Amol", "last_name": "Ranjan", "name": null }, { "creator_type": "author", "first_name": "Chris W.", "last_name": "Seidel", "name": null }, { "creator_type": "author", "first_name": "Tadasuke", "last_name": "Tsukiyama", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Mizushima", "name": null }, { "creator_type": "author", "first_name": "Masayasu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Joan W.", "last_name": "Conaway", "name": null }, { "creator_type": "author", "first_name": "Ronald C.", "last_name": "Conaway", "name": null }, { "creator_type": "author", "first_name": "Shigetsugu", "last_name": "Hatakeyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms6941" }, "pmcid": { "normalized": "PMC4646223" }, "pmid": { "normalized": "25575120" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DNA Polymerase II", "descriptor_ui": "D004257", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mediator Complex", "descriptor_ui": "D056892", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Peptide Chain Elongation, Translational", "descriptor_ui": "D010441", "major_topic": true }, { "descriptor": "Point Mutation", "descriptor_ui": "D017354", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "RNA, Small Nuclear", "descriptor_ui": "D012342", "major_topic": false }, { "descriptor": "Sequence Homology, Amino Acid", "descriptor_ui": "D017386", "major_topic": false }, { "descriptor": "Sf9 Cells", "descriptor_ui": "D061987", "major_topic": false }, { "descriptor": "TATA-Binding Protein Associated Factors", "descriptor_ui": "D035381", "major_topic": false }, { "descriptor": "Transcription Factor TFIID", "descriptor_ui": "D035362", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015 Jan 9", "date_precision": "day", "issue": "", "normalized_date": "2015-01-09", "pages": "5941", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "6", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "MED26 regulates the transcription of snRNA genes through the recruitment of little elongation complex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have developed a novel solid-phase extraction (SPE) system utilizing a temperature-responsive polymer hydrogel-modified stationary phase. Aminopropyl silica beads (average diameter, 40 - 64 mum) were coated with poly(N-isopropylacrylamide) (PNIPAAm)-based thermo-responsive hydrogels. Butyl methacrylate (BMA) and N,N-dimethylaminopropyl acrylamide (DMAPAAm) were used as the hydrophobic and cationic monomers, respectively, and copolymerized with NIPAAm. To evaluate the use of this SPE cartridge for the analysis of drugs and proteins in biological fluids, we studied the separation of phenytoin and theophylline from human serum albumin (HSA) as a model system. The retention of the analytes in an exclusively aqueous eluent could be modulated by changing the temperature and salt content. These results indicated that this temperature-responsive SPE system can be applied to the pretreatment of biological samples for the measurement of serum drug levels.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Michiko", "last_name": "Akimaru", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Hideko", "last_name": "Kanazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.2116/analsci.31.881" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26353953" } }, "mesh": [ { "descriptor": "Acrylic Resins", "descriptor_ui": "D000180", "major_topic": false }, { "descriptor": "Analytic Sample Preparation Methods", "descriptor_ui": "D053000", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogels", "descriptor_ui": "D020100", "major_topic": false }, { "descriptor": "Hydrophobic and Hydrophilic Interactions", "descriptor_ui": "D057927", "major_topic": false }, { "descriptor": "Phenytoin", "descriptor_ui": "D010672", "major_topic": false }, { "descriptor": "Serum Albumin", "descriptor_ui": "D012709", "major_topic": false }, { "descriptor": "Silicon Dioxide", "descriptor_ui": "D012822", "major_topic": false }, { "descriptor": "Solid Phase Extraction", "descriptor_ui": "D052616", "major_topic": false }, { "descriptor": "Surface Properties", "descriptor_ui": "D013499", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": true }, { "descriptor": "Theophylline", "descriptor_ui": "D013806", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "9", "normalized_date": "2015", "pages": "881-886", "proceedings_title": null, "publisher": "", "title": "Analytical sciences : the international journal of the Japan Society for Analytical Chemistry", "volume": "31", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Temperature-responsive Solid-phase Extraction Column for Biological Sample Pretreatment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The absorption spectrum of light is known to be a \"molecular fingerprint\" that enables analysis of the molecular type and its amount. It would be useful to measure the absorption spectrum in single cell in order to investigate the cellular status. However, cells are too thin for their absorption spectrum to be measured. In this study, we developed an optical-cavity-enhanced absorption spectroscopic microscopy method for two-dimensional absorption imaging. The light absorption is enhanced by an optical cavity system, which allows the detection of the absorption spectrum with samples having an optical path length as small as 10 mum, at a subcellular spatial resolution. Principal component analysis of various types of cultured mammalian cells indicates absorption-based cellular diversity. Interestingly, this diversity is observed among not only different species but also identical cell types. Furthermore, this microscopy technique allows us to observe frozen sections of tissue samples without any staining and is capable of label-free biopsy. Thus, our microscopy method opens the door for imaging the absorption spectra of biological samples and thereby detecting the individuality of cells.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Minamikawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0125733" }, "pmcid": { "normalized": "PMC4423951" }, "pmid": { "normalized": "25950513" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Principal Component Analysis", "descriptor_ui": "D025341", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "5", "normalized_date": "2015", "pages": "e0125733", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "10", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Spectral fingerprinting of individual cells visualized by cavity-reflection-enhanced light-absorption microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Entrainment to light cycle is a prerequisite for circadian rhythms to set daily physiological events to occur at an appropriate time of day. In hemimetabolous insects, the photoreceptor molecule for photic entrainment is still unknown. Since the compound eyes are the only circadian photoreceptor in the cricket Gryllus bimaculatus, we have investigated the role of three opsin genes expressed there, opsin-Ultraviolet (opUV), opsin-Blue (opB), and opsin-Long Wave (opLW) encoding a green-sensitive opsin in photic entrainment. RESULTS: A daily rhythm was detected in mRNA expressions of opB and opLW but not of opUV gene. When photic entrainment of circadian locomotor rhythms was tested after injection of double-stranded RNA (dsRNA) of three opsin genes, no noticeable effects were found in opUV RNAi and opB RNAi crickets. In opLW RNAi crickets, however, some crickets lost photic entrainability and the remaining crickets re-entrained with significantly longer transient cycles to a phase-advanced light-dark cycle as compared to control crickets. Crickets often lost entrainability when treated doubly with dsRNAs of two opsin genes including opLW. CONCLUSION: These results show that green-sensitive OpLW is the major circadian photoreceptor molecule for photic entrainment of locomotor rhythms in the cricket G. bimaculatus. Our finding will lead to further investigation of the photic entrainment mechanism at molecular and cellular levels, which still remains largely unknown.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sayaka", "last_name": "Komada", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Kamae", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Kousuke", "last_name": "Tatewaki", "name": null }, { "creator_type": "author", "first_name": "Ehab", "last_name": "Hassaneen", "name": null }, { "creator_type": "author", "first_name": "Asm", "last_name": "Saifullah", "name": null }, { "creator_type": "author", "first_name": "Taishi", "last_name": "Yoshii", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Tomioka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s40851-015-0011-6" }, "pmcid": { "normalized": "PMC4657349" }, "pmid": { "normalized": "26605056" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "11", "proceedings_title": null, "publisher": "", "title": "Zoological letters", "volume": "1", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Green-sensitive opsin is the photoreceptor for photic entrainment of an insect circadian clock.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transcription Activator-Like Effector Nucleases (TALENs) offer versatile tools to engineer endogenous genomic loci in various organisms. We established a homologous recombination (HR)-based knock-in using TALEN in the crustacean Daphnia magna, a model for ecological and toxicological genomics. We constructed TALENs and designed the 67 bp donor insert targeting a point deletion in the eyeless mutant that shows eye deformities. Co-injection of the TALEN mRNA with donor DNA into eggs led to the precise integration of the donor insert in the germ line, which recovered eye deformities in offspring. The frequency of HR events in the germ line was 2% by using both plasmid and single strand oligo DNA with 1.5 kb and 80 nt homology to the target. Deficiency of ligase 4 involved in non-homologous end joining repair did not increase the HR efficiency. Our data represent efficient HR-based knock-in by TALENs in D. magna, which is a promising tool to understand Daphnia gene functions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep18312" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26674741" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "DNA Ligases", "descriptor_ui": "D011088", "major_topic": false }, { "descriptor": "DNA Restriction Enzymes", "descriptor_ui": "D004262", "major_topic": false }, { "descriptor": "Eye Abnormalities", "descriptor_ui": "D005124", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Genetic Engineering", "descriptor_ui": "D005818", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Homologous Recombination", "descriptor_ui": "D059765", "major_topic": true }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "5", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "TALEN-mediated homologous recombination in Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Using Raman spectral imaging, we visualized the cell state transition during differentiation and constructed hypothetical potential landscapes for attractors of cellular states on a state space composed of parameters related to the shape of the Raman spectra. As models of differentiation, we used the myogenic C2C12 cell line and mouse embryonic stem cells. Raman spectral imaging can validate the amounts and locations of multiple cellular components that describe the cell state such as proteins, nucleic acids, and lipids; thus, it can report the state of a single cell. Herein, we visualized the cell state transition during differentiation using Raman spectral imaging of cell nuclei in combination with principal component analysis. During differentiation, cell populations with a seemingly homogeneous cell state before differentiation showed heterogeneity at the early stage of differentiation. At later differentiation stages, the cells returned to a homogeneous cell state that was different from the undifferentiated state. Thus, Raman spectral imaging enables us to illustrate the disappearance and reappearance of an attractor in a differentiation landscape, where cells stochastically fluctuate between states at the early stage of differentiation.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Liang-da", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Machiyama", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep11358" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26079396" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle Development", "descriptor_ui": "D024510", "major_topic": false }, { "descriptor": "Myoblasts", "descriptor_ui": "D032446", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "5", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualizing the appearance and disappearance of the attractor of differentiation using Raman spectral imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Motile cilia and flagella rapidly propagate bending waves and produce water flow over the cell surface. Their function is important for the physiology and development of various organisms including humans. The movement is based on the sliding between outer doublet microtubules driven by axonemal dyneins, and is regulated by various axonemal components and environmental factors. For studies aiming to elucidate the mechanism of cilia/flagella movement and regulation, Chlamydomonas is an invaluable model organism that offers a variety of mutants. This chapter introduces standard methods for studying Chlamydomonas flagellar motility including analysis of swimming paths, measurements of swimming speed and beat frequency, motility reactivation in demembranated cells (cell models), and observation of microtubule sliding in disintegrating axonemes. Most methods may be easily applied to other organisms with slight modifications of the medium conditions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Ritsu", "last_name": "Kamiya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/bs.mcb.2014.12.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25837401" } }, "mesh": [ { "descriptor": "Axonemal Dyneins", "descriptor_ui": "D056444", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Chlamydomonas reinhardtii", "descriptor_ui": "D016825", "major_topic": false }, { "descriptor": "Cilia", "descriptor_ui": "D002923", "major_topic": false }, { "descriptor": "Dyneins", "descriptor_ui": "D004398", "major_topic": false }, { "descriptor": "Flagella", "descriptor_ui": "D005407", "major_topic": false }, { "descriptor": "Hydrodynamics", "descriptor_ui": "D057446", "major_topic": true }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "387-402", "proceedings_title": null, "publisher": "", "title": "Methods in cell biology", "volume": "127", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Axonemal motility in Chlamydomonas.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Post-translational histone modifications play a critical role in genome functions such as epigenetic gene regulation and genome maintenance. The tail of the histone H4 N-terminus contains several amino acids that can be acetylated and methylated. Some of these modifications are known to undergo drastic changes during the cell cycle. In this study, we generated a panel of mouse monoclonal antibodies against histone H4 modifications, including acetylation at K5, K8, K12, and K16, and different levels of methylation at K20. Their specificity was evaluated by ELISA and immunoblotting using synthetic peptide and recombinant proteins that harbor specific modifications or amino acid substitutions. Immunofluorescence confirmed the characteristic distributions of target modifications. An H4K5 acetylation (H4K5ac)-specific antibody CMA405 reacted with K5ac only when the neighboring K8 was unacetylated. This unique feature allowed us to detect newly assembled H4, which is diacetylated at K5 and K12, and distinguish it from hyperacetylated H4, where K5 and K8 are both acetylated. Chromatin immunoprecipiation combined with deep sequencing (ChIP-seq) revealed that acetylation of both H4K8 and H4K16 were enriched around transcription start sites. These extensively characterized and highly specific antibodies will be useful for future epigenetics and epigenome studies.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yoko", "last_name": "Hayashi-Takanaka", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Umehara", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Chikashi", "last_name": "Obuse", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Naohito", "last_name": "Nozaki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10577-015-9486-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26343042" } }, "mesh": [ { "descriptor": "Acetylation", "descriptor_ui": "D000107", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": true }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cell Line, Transformed", "descriptor_ui": "D002461", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Chromatin Immunoprecipitation", "descriptor_ui": "D047369", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoglobulin G", "descriptor_ui": "D007074", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "4", "normalized_date": "2015", "pages": "753-766", "proceedings_title": null, "publisher": "", "title": "Chromosome Research", "volume": "23", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Distribution of histone H4 modifications as revealed by a panel of specific monoclonal antibodies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genetically encoded fluorescence resonance energy transfer (FRET) biosensors have been successfully used to visualize protein activity in living cells. The sensitivity and accuracy of FRET measurements directly depend on biosensor folding efficiency, expression pattern, sensitivity, and dynamic range. Here, to improve the folding efficiency of the Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIalpha) FRET biosensor, we amplified the association domain of the CaMKIIalpha gene using error-prone polymerase chain reaction (PCR) and fused it to the N-terminus of mCherry in a bacterial expression vector. We also created an Escherichia coli expression library based on a previously reported fluorescent protein folding reporter method, and found a bright red fluorescent colony that contained the association domain with four mutations (F394L, I419V, A430T, and I434T). In vitro assays using the purified mutant protein confirmed improved folding kinetics of the downstream fluorescent protein, but not of the association domain itself. Furthermore, we introduced these mutations into the previously reported CaMKIIalpha FRET sensor and monitored its Ca2+/calmodulin-dependent activation in HeLa cells using 2-photon fluorescence lifetime imaging microscopy (2pFLIM), and found that the expression pattern and signal reproducibility of the mutant sensor were greatly improved without affecting the autophosphorylation function and incorporation into oligomeric CaMKIIalpha. We believe that our improved CaMKIIalpha FRET sensor would be useful in various types of cells and tissues, providing data with high accuracy and reproducibility. In addition, the method described here may also be applicable for improving the performance of all currently available FRET sensors.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akihiro C. E.", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Hiroshi K.", "last_name": "Maebashi", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Nakahata", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Nabekura", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0121109" }, "pmcid": { "normalized": "PMC4370617" }, "pmid": { "normalized": "25799407" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinase Type 2", "descriptor_ui": "D054732", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Protein Folding", "descriptor_ui": "D017510", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Red Fluorescent Protein", "descriptor_ui": "D000097573", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "3", "normalized_date": "2015", "pages": "e0121109", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "10", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a molecularly evolved, highly sensitive CaMKII FRET sensor with improved expression pattern.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Delay eyeblink conditioning, a cerebellum-dependent learning paradigm, has been applied to various mammalian species but not yet to monkeys. We therefore developed an accurate measuring system that we believe is the first system suitable for delay eyeblink conditioning in a monkey species (Macaca mulatta). Monkey eyeblinking was simultaneously monitored by orbicularis oculi electromyographic (OO-EMG) measurements and a high-speed camera-based tracking system built around a 1-kHz CMOS image sensor. A 1-kHz tone was the conditioned stimulus (CS), while an air puff (0.02 MPa) was the unconditioned stimulus. EMG analysis showed that the monkeys exhibited a conditioned response (CR) incidence of more than 60% of trials during the 5-day acquisition phase and an extinguished CR during the 2-day extinction phase. The camera system yielded similar results. Hence, we conclude that both methods are effective in evaluating monkey eyeblink conditioning. This system incorporating two different measuring principles enabled us to elucidate the relationship between the actual presence of eyelid closure and OO-EMG activity. An interesting finding permitted by the new system was that the monkeys frequently exhibited obvious CRs even when they produced visible facial signs of drowsiness or microsleep. Indeed, the probability of observing a CR in a given trial was not influenced by whether the monkeys closed their eyelids just before CS onset, suggesting that this memory could be expressed independently of wakefulness. This work presents a novel system for cognitive assessment in monkeys that will be useful for elucidating the neural mechanisms of implicit learning in nonhuman primates.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Haruyoshi", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Kirino", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0129828" }, "pmcid": { "normalized": "PMC4466547" }, "pmid": { "normalized": "26068663" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blinking", "descriptor_ui": "D001767", "major_topic": true }, { "descriptor": "Conditioning, Classical", "descriptor_ui": "D003214", "major_topic": true }, { "descriptor": "Electromyography", "descriptor_ui": "D004576", "major_topic": false }, { "descriptor": "Macaca mulatta", "descriptor_ui": "D008253", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": true }, { "descriptor": "Reaction Time", "descriptor_ui": "D011930", "major_topic": true }, { "descriptor": "Video Recording", "descriptor_ui": "D014741", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "6", "normalized_date": "2015", "pages": "e0129828", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "10", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Implicit Memory in Monkeys: Development of a Delay Eyeblink Conditioning System with Parallel Electromyographic and High-Speed Video Measurements.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The properties of a fluorous solvent extraction system for trivalent lanthanide metal ions are reported. A fluorinated extractant, 4,4,5,5,6,6,7,7,8,8,9,9,9-tridecafluoro-1-(2-thienyl)-1,3-nonanedione, and HFE-7200 (C4F9OC2H5) as the extraction solvent were chosen. With this fluorous extractant/solvent combination, higher extraction ratios and separation factors compared to a conventional organic solvent system (thenoyltrifluoroacetone in CHCl3) were achieved for 5 heavy lanthanide ions (Lu, Yb, Tm, Er and Ho). On the other hand, light lanthanide ions (Nd, Pr, Ce and La) are hardly extracted, therefore enabling the mutual separation of light lanthanides from middle or heavy lanthanide ions.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Etsuko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Iwasawa", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.2116/analsci.31.923" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26353959" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "9", "normalized_date": "2015", "pages": "923-928", "proceedings_title": null, "publisher": "", "title": "Analytical sciences : the international journal of the Japan Society for Analytical Chemistry", "volume": "31", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "A Fluorous Biphasic Solvent Extraction System for Lanthanides with a Fluorophilic beta-Diketone Type Extractant.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Recent genome projects of various animals have uncovered an unexpectedly large number of opsin genes, which encode protein moieties of photoreceptor molecules, in most animals. In visual systems, the biological meanings of this diversification are clear; multiple types of visual opsins with different spectral sensitivities are responsible for color vision. However, the significance of the diversification of non-visual opsins remains uncertain, in spite of the importance of understanding the molecular mechanism and evolution of varied non-visual photoreceptions. Results: Here, we investigated the diversification of the pineal photopigment parapinopsin, which serves as the UV-sensitive photopigment for the pineal wavelength discrimination in the lamprey, linking it with other pineal photoreception. Spectroscopic analyses of the recombinant pigments of the two teleost parapinopsins PP1 and PP2 revealed that PP1 is a UV-sensitive pigment, similar to lamprey parapinopsin, but PP2 is a blue-sensitive pigment, with an absorption maximum at 460–480 nm, showing the diversification of non-visual pigment with respect to spectral sensitivity. We also found that PP1 and PP2 exhibit mutually exclusive expressions in the pineal organs of three teleost species. By using transgenic zebrafish in which these parapinopsin-expressing cells are labeled, we found that PP1-expressing cells basically possess neuronal processes, which is consistent with their involvement in wavelength discrimination. Interestingly, however, PP2-expressing cells rarely possess neuronal processes, raising the possibility that PP2 could be involved in non-neural responses rather than neural responses. Furthermore, we found that PP2-expressing cells contain serotonin and aanat2, the key enzyme involved in melatonin synthesis from serotonin, whereas PP1-expressing cells do not contain either, suggesting that blue-sensitive PP2 is instead involved in light-regulation of melatonin secretion. Conclusions: In this paper, we have clearly shown the different molecular properties of duplicated non-visual opsins by demonstrating the diversification of parapinopsin with respect to spectral sensitivity. Moreover, we have shown a plausible link between the diversification and its physiological impact by discovering a strong candidate for the underlying pigment in light-regulated melatonin secretion in zebrafish; the diversification could generate a new contribution of parapinopsin to pineal photoreception. Current findings could also provide an opportunity to understand the “color” preference of non-visual photoreception. Electronic supplementary material: The online version of this article (doi:10.1186/s12915-015-0174-9) contains supplementary material, which is available to authorized users.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Kawano-Yamashita", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Kuraku", "name": null }, { "creator_type": "author", "first_name": "Shigeaki", "last_name": "Kosaka", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Tamotsu", "name": null }, { "creator_type": "author", "first_name": "Hisao", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Shichida", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12915-015-0174-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26370232" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": false }, { "descriptor": "Color Vision", "descriptor_ui": "D055253", "major_topic": false }, { "descriptor": "Fish Proteins", "descriptor_ui": "D029941", "major_topic": false }, { "descriptor": "Oncorhynchus mykiss", "descriptor_ui": "D017686", "major_topic": false }, { "descriptor": "Pineal Gland", "descriptor_ui": "D010870", "major_topic": false }, { "descriptor": "Rod Opsins", "descriptor_ui": "D017299", "major_topic": false }, { "descriptor": "Tetraodontiformes", "descriptor_ui": "D023721", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "", "proceedings_title": null, "publisher": "", "title": "BMC Biology", "volume": "13", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Diversification of non-visual photopigment parapinopsin in spectral sensitivity for diverse pineal functions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Photoacoustic tomography is a recently developed imaging modality that can provide high spatial-resolution images of hemoglobin distribution in tissues such as the breast. Because breast cancer is an angiogenesis-dependent type of malignancy, we evaluated the clinical acceptability of breast tissue images produced using our first prototype photoacoustic mammography (PAM) system in patients with known cancer. Post-excisionally, histological sections of the tumors were stained immunohistochemically (IHC) for CD31 (an endothelial marker) and carbonic anhydrase IX (CAIX) (a marker of hypoxia). Whole-slide scanning and image analyses were used to evaluate the tumor microvessel distribution pattern and to calculate the total vascular perimeter (TVP)/area for each lesion. In this clinical study, 42 lesions were primarily scanned using PAM preoperatively, three of which were reported to be benign and were excluded from statistical analysis. Images were produced for 29 out of 39 cancers (visibility rate = 74.4%) at the median depth of 26.5 (3.25-51.2) mm. Age, menopausal status, body mass index, history of neoadjuvant treatment, clinical stage and histological tumor angiogenesis markers did not seem to affect the visibility. The oxygen saturation level in all of the measured lesions was lower than in the subcutaneous counterpart vessels (Wilcoxon test, p value<0.001), as well as in the counterpart contralateral normal breast region of interest (ROI) (Wilcoxon test, p value = 0.001). Although the oxygen saturation level was not statistically significant between CAIX-positive vs. -negative cases, lesional TVP/area showed a positive correlation with the oxygen saturation level only in the group that had received therapy before PAM. In conclusion, the vascular and oxygenation data obtained by PAM have great potential for identifying functional features of breast tumors.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Elham", "last_name": "Fakhrejahani", "name": null }, { "creator_type": "author", "first_name": "Masae", "last_name": "Torii", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kitai", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Kanao", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Asao", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Iku", "last_name": "Yamaga", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Tomoharu", "last_name": "Sugie", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Haga", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Togashi", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Toi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0139113" }, "pmcid": { "normalized": "PMC4624636" }, "pmid": { "normalized": "26506106" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Diagnostic Imaging", "descriptor_ui": "D003952", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hemoglobins", "descriptor_ui": "D006454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mammary Neoplasms, Animal", "descriptor_ui": "D015674", "major_topic": false }, { "descriptor": "Mammography", "descriptor_ui": "D008327", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Photoacoustic Techniques", "descriptor_ui": "D061088", "major_topic": true }, { "descriptor": "Tomography, X-Ray Computed", "descriptor_ui": "D014057", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "10", "normalized_date": "2015", "pages": "e0139113", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "10", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical Report on the First Prototype of a Photoacoustic Tomography System with Dual Illumination for Breast Cancer Imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The periodontal ligament has a rich sensory nerve supply which originates from the trigeminal ganglion and trigeminal mesencephalic nucleus. Although various types of mechanoreceptors have been reported in the periodontal ligament, the Ruffini ending is an essential one. It is unknown whether the distribution of periodontal nerve fibers in deciduous teeth is identical to that in permanent teeth or not. Moreover, morphological changes in the distribution of periodontal nerve fibers during resorption of deciduous teeth and eruption of successional permanent teeth in diphyodont animals have not been reported in detail. Therefore, in this study, we examined changes in the distribution of periodontal nerve fibers in the cat during changes in dentition (i.e., deciduous, mixed and permanent dentition) by immunohistochemistry of protein gene product 9.5. During deciduous dentition, periodontal nerve fibers were concentrated at the apical portion, and sparsely distributed in the periodontal ligament of deciduous molars. During mixed dentition, the periodontal nerve fibers of deciduous molars showed degenerative profiles during resorption. In permanent dentition, the periodontal nerve fibers of permanent premolars, the successors of deciduous molars, increased in number. Similar to permanent premolars, the periodontal nerve fibers of permanent molars, having no predecessors, increased in number, and were densely present in the apical portion. The present results indicate that the distribution of periodontal nerve fibers in deciduous dentition is almost identical to that in permanent dentition although the number of periodontal nerve fibers in deciduous dentition was low. The sparse distribution of periodontal nerve fibers in deciduous dentition agrees with clinical evidence that children are less sensitive to tooth stimulation than adults.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Shiho", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Ebara", "name": null }, { "creator_type": "author", "first_name": "Kenzo", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Wakisaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0129826" }, "pmcid": { "normalized": "PMC4471154" }, "pmid": { "normalized": "26083023" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cats", "descriptor_ui": "D002415", "major_topic": false }, { "descriptor": "Dentition", "descriptor_ui": "D003817", "major_topic": false }, { "descriptor": "Mandible", "descriptor_ui": "D008334", "major_topic": false }, { "descriptor": "Nerve Fibers", "descriptor_ui": "D009412", "major_topic": false }, { "descriptor": "Periodontal Ligament", "descriptor_ui": "D010513", "major_topic": false }, { "descriptor": "Radiography", "descriptor_ui": "D011859", "major_topic": false }, { "descriptor": "Tooth, Deciduous", "descriptor_ui": "D014094", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "6", "normalized_date": "2015", "pages": "e0129826", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "10", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Changes in the Distribution of Periodontal Nerve Fibers during Dentition Transition in the Cat.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The neurohypophysial hormones, arginine vasotocin and isotocin, regulate both hydromineral balance and social behaviors in fish. In the amphibious mudskipper, Periophthalmus modestus, we previously found arginine-vasotocin-specific regulation of aggressive behavior, including migration of the submissive subordinate into water. This migration also implies the need for adaptation to dehydration. Here, we examined the effects of arginine vasotocin and isotocin administration on the amphibious behavior of individual mudskippers in vivo. The mudskippers remained in the water for an increased period of time after 1-8 h of intracerebroventricular (ICV) injection with 500 pg/g arginine vasotocin or isotocin. The 'frequency of migration' was decreased after ICV injection of arginine vasotocin or isotocin, reflecting a tendency to remain in the water. ICV injections of isotocin receptor antagonist with arginine vasotocin or isotocin inhibited all of these hormonal effects. In animals kept out of water, mRNA expression of brain arginine vasotocin and isotocin precursors increased 3- and 1.5-fold, respectively. Given the relatively wide distribution of arginine vasotocin fibres throughout the mudskipper brain, induction of arginine vasotocin and isotocin under terrestrial conditions may be involved also in the preference for an aquatic habitat as ligands for brain isotocin receptors.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Yudai", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Aoi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Hyodo", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Kagawa", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0134605" }, "pmcid": { "normalized": "PMC4521927" }, "pmid": { "normalized": "26230718" } }, "mesh": [ { "descriptor": "Adaptation, Physiological", "descriptor_ui": "D000222", "major_topic": false }, { "descriptor": "Amphibians", "descriptor_ui": "D000663", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arginine Vasopressin", "descriptor_ui": "D001127", "major_topic": false }, { "descriptor": "Fishes", "descriptor_ui": "D005399", "major_topic": false }, { "descriptor": "Injections, Intraventricular", "descriptor_ui": "D007276", "major_topic": false }, { "descriptor": "Oxytocin", "descriptor_ui": "D010121", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "7", "normalized_date": "2015", "pages": "e0134605", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "10", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Neurohypophysial Hormones Regulate Amphibious Behaviour in the Mudskipper Goby.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The rapid progress in advanced imaging technologies has expanded our toolbox for monitoring a variety of biological aspects in living subjects including human. In vivo radiological imaging using small chemical tracers, such as with positron emission tomography, represents an especially vital breakthrough in the efforts to improve our understanding of the complicated cascade of neurodegenerative disorders including Alzheimer's disease (AD), and it has provided the most reliable visible biomarkers for enabling clinical diagnosis. At the same time, in combination with genetically modified animal model systems, the most recent innovation of fluorescence imaging is helping establish diverse applications in basic neuroscience research, from single-molecule analysis to animal behavior manipulation, suggesting the potential utility of fluorescence technology for dissecting the detailed molecular-based consequence of AD pathophysiology. In this review, our primary focus is on a current update of PET radiotracers and fluorescence indicators beneficial for understanding the AD cascade, and discussion of the utility and pitfalls of those imaging modalities for future translational research applications. We will also highlight current cutting-edge genetic approaches and discuss how to integrate individual technologies for further potential innovations.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masafumi", "last_name": "Shimojo", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2015.00482" }, "pmcid": { "normalized": "PMC4686595" }, "pmid": { "normalized": "26733795" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "482", "proceedings_title": null, "publisher": "", "title": "Frontiers in neuroscience", "volume": "9", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Imaging Multimodalities for Dissecting Alzheimer's Disease: Advanced Technologies of Positron Emission Tomography and Fluorescence Imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Whole-tissue quantification at single-cell resolution has become an inevitable approach for further quantitative understanding of morphogenesis in organ development. The feasibility of the approach has been dramatically increased by recent technological improvements in optical tissue clearing and microscopy. However, the series of procedures required for this approach to lead to successful whole-tissue quantification is far from developed. To provide the appropriate procedure, we here show tips for each critical step of the entire process, including fixation for immunofluorescence, optical clearing, and digital image processing, using developing murine internal organs such as epididymis, kidney, and lung as an example. Through comparison of fixative solutions and of clearing methods, we found optimal conditions to achieve clearer deep-tissue imaging of specific immunolabeled targets and explain what methods result in vivid volume imaging. In addition, we demonstrated that three-dimensional digital image processing after optical clearing produces objective quantitative data for the whole-tissue analysis, focusing on the spatial distribution of mitotic cells in the epididymal tubule. The procedure for the whole-tissue quantification shown in this article should contribute to systematic measurements of cellular processes in developing organs, accelerating the further understanding of morphogenesis at the single cell level.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Adachi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0135343" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26258587" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Epididymis", "descriptor_ui": "D004822", "major_topic": false }, { "descriptor": "Fixatives", "descriptor_ui": "D005404", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Tissue Fixation", "descriptor_ui": "D016707", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "8", "normalized_date": "2015", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "10", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Procedures for the Quantification of Whole-Tissue Immunofluorescence Images Obtained at Single-Cell Resolution during Murine Tubular Organ Development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: The adrenomedullins (AMs) comprise a hormonal family in mammals and teleost fishes, with five members (AM1-5) found or predicted in most of the teleosts including Japanese medaka (Oryzias latipes). AM1 is known to have cardiovascular and osmoregulatory functions in mammals, but the roles of most AMs are yet to be determined. RESULTS: Using medaka, we first analyzed the tissue distribution of all five AM genes and found detectable expression in all tissues examined, with relatively high levels of AM3 and AM5 in the liver and kidney. To assess the osmoregulatory roles of these AMs, mRNA levels were examined in the brain (including the eyes), gill, liver, kidney and spleen of medaka one week after transfer from isotonic saline (11 ppt) to freshwater (0 ppt) or seawater (33 ppt). Expression of AM1 in the brain-eye increased in freshwater. The central level of AM4 (the paralog of AM1) decreased in seawater; the branchial level of AM4 decreased in freshwater and seawater, but the renal level increased in freshwater. The branchial level of AM2 increased in seawater, whereas the renal level decreased in freshwater and seawater. Expression of AM3, the AM2 paralog, decreased in the brain-eye of seawater-acclimated fish. Expression of AM5 in the brain-eye and kidney decreased in seawater. CONCLUSIONS: Except for branchial AM2, the members of AM family tend to be involved in promotion of hyper-osmoregulation and/or inhibition of hypo-osmoregulation, although each AM may play a distinct role during adaptation to different salinities.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Maho", "last_name": "Ogoshi", "name": null }, { "creator_type": "author", "first_name": "Kanoko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s40851-015-0012-5" }, "pmcid": { "normalized": "PMC4657274" }, "pmid": { "normalized": "26605057" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "12", "proceedings_title": null, "publisher": "", "title": "Zoological letters", "volume": "1", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Effect of environmental salinity on expression of adrenomedullin genes suggests osmoregulatory activity in the medaka, Oryzias latipes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The quantitative relationship between change in cell shape and ATP consumption is an unsolved problem in cell biology. In this study, a simultaneous imaging and image processing analysis allowed us to observe and quantify these relationships under physiological conditions, for the first time. We focused on two marginal regions of cells: the microtubule-rich ‘lamella’ and the actin-rich ‘peripheral structure’. Simultaneous imaging and correlation analysis revealed that microtubule dynamics cause lamellar shape change accompanying an increase in ATP level. Also, image processing and spatiotemporal quantification enabled to visualize a chronological change of the relationships between the protrusion length and ATP levels, and it suggested they are influencing each other. Furthermore, inhibition of microtubule dynamics diminished motility in the peripheral structure and the range of fluctuation of ATP level in the lamella. This work clearly demonstrates that cellular motility and morphology are regulated by ATP-related cooperative function between microtubule and actin dynamics.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Rika", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep16874" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26575097" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Cytoskeleton", "descriptor_ui": "D003599", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Space", "descriptor_ui": "D042541", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "5", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatiotemporal quantification of subcellular ATP levels in a single HeLa cell during changes in morphology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Low reactive level laser therapy (LLLT) is mainly focused on the activation of intracellular or extracellular chromophore and the initiation of cellular signaling by using low power lasers. Over the past forty years, it was realized that the laser therapy had the potential to improve wound healing and reduce pain and inflammation. In recent years, the term LLLT has become widely recognized in the field of regenerative medicine. In this review, we will describe the mechanisms of action of LLLT at a cellular level and introduce the application to mesenchymal stem cells and mesenchymal stromal cells (MSCs) therapies. Finally, our recent research results that LLLT enhanced the MSCs differentiation to osteoblast will also be described.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Okawa", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1155/2015/974864" }, "pmcid": { "normalized": "PMC4529981" }, "pmid": { "normalized": "26273309" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "974864", "proceedings_title": null, "publisher": "", "title": "Stem cells international", "volume": "2015", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Low Reactive Level Laser Therapy for Mesenchymal Stromal Cells Therapies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: The complex of Dock180/ELMO1 that functions as a bipartite guanine nucleotide exchange factor for Rac is essential for diverse physiological and pathological processes of cells such as cell migration, phagocytosis, and invasion of cancer cells. Among the Src-family tyrosine kinases (SFKs), it has been reported that Hck directly phosphorylates ELMO1, regulating phagocytosis by promoting activation of Rac1; however, the involvement of other SFKs in ELMO1 phosphorylation has remained unknown. Here, we identified novel tyrosine (Y) residues of ELMO1 phosphorylated by SFKs, and examined the effects on Rac1 activity, cell adhesion, spreading, and cell motility on extracellular matrix (ECM). Results: In this study, we unveiled that Src and Fyn can induce tyrosine phosphorylation of ELMO1 in in vivo and in vitro phosphorylation assays. Mutational analyses identified both Y720 and Y724 residues of ELMO1 as Src-mediated phosphorylation sites, preferentially on Y724. Single substitution of Y724 to Phe abrogated Rac1 activation triggered by Src. To elucidate the biological function of pY724, we established NIH3T3 cells stably expressing wild-type ELMO1 or its Y724F mutant together with Dock180. Among them, Y724-deficient cells exhibited a depletion of Rac1 activity with diminished phosphorylation of ELMO1 even upon the ECM-stimulation. It is noteworthy that NIH3T3 cells with ELMO1 Y724F were strikingly defective to promote cell spreading on fibronectin-coated dish, concomitantly exhibiting immature assemblies of actin stress fibers and focal adhesions. Eventually, ELMO1 Y724F significantly impaired cell migration. Conclusion: These results define that Src-mediated Y724 phosphorylation in ELMO1 plays a critical role for cell spreading via activation of Rac1, leading to promotion of cell migration. As the overexpression and/or hyperactivation of Src have been shown in a wide variety of human cancers, Src-mediated phosphorylation of Y724 in ELMO1 may regulate cancer cell adhesion to the ECM, invasion into surrounding tissues, and subsequent distant metastasis. Electronic supplementary material: The online version of this article (doi:10.1186/s12964-015-0113-y) contains supplementary material, which is available to authorized users.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Makino", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nishihara", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12964-015-0113-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26205662" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Point Mutation", "descriptor_ui": "D017354", "major_topic": false }, { "descriptor": "rac1 GTP-Binding Protein", "descriptor_ui": "D020830", "major_topic": false }, { "descriptor": "src-Family Kinases", "descriptor_ui": "D019061", "major_topic": false }, { "descriptor": "Tyrosine", "descriptor_ui": "D014443", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cell Communication and Signaling : CCS", "volume": "13", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Tyr724 phosphorylation of ELMO1 by Src is involved in cell spreading and migration via Rac1 activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In response to extracellular stimuli, cells display a variety of behaviors, including proliferation, differentiation, morphological changes and migration. The analysis of the spatiotemporal regulation of signal transduction in living cells is needed for a better understanding of such behaviors, and such investigations have been greatly accelerated by the development of fluorescent protein-based biosensors. Currently, by using these biosensors a range of molecular actions, including lipid metabolism, protein activation, and ion dynamics, can be visualized in living cells. We recently reported that intracellular calcium, with its relevant downstream signaling pathways consisting of the small GTPase Ras and the lipid kinase phoshoinositide-3-kinase (PI3K), can be exploited in an efficient incorporation of influenza A viruses into host cells via endocytosis using a set of biosensors based on fluorescent proteins and the principle of Forster resonance energy transfer. Here, we focus this review on fluorescent protein-based biosensors that have been utilized in our recent research reports.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Nanbo", "name": null }, { "creator_type": "author", "first_name": "Shin-Ya", "last_name": "Nishide", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.2116/analsci.31.267" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25864669" } }, "mesh": [ { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": true }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "4", "normalized_date": "2015", "pages": "267-274", "proceedings_title": null, "publisher": "", "title": "Analytical sciences : the international journal of the Japan Society for Analytical Chemistry", "volume": "31", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Fluorescent protein-based biosensors to visualize signal transduction beneath the plasma membrane.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Investigation of the rotational motion of a fluorescent probe tethered to a protein helps to elucidate the local properties of the solvent and protein near the conjugation site of the probe. In this study, we have developed an instrument for frequency-domain fluorescence (FDF) anisotropy measurements, and studied how the local properties around a protein, actin, can be elucidated from the rotational motion of a dye tethered to actin. Rhodamine 6G (R6G) was attached to Cys-374 using newly-synthesized R6G-maleimide with three different oligo(ethylene glycol) (OEG) linker lengths. The time-resolved anisotropy decay of R6G tethered to G-actin was revealed to be a combination of the two modes of the wobbling motion of R6G and the tumbling motion of G-actin. The rotational diffusion coefficient (RDC) of R6G wobbling was ~0.1 ns(-1) at 20 degrees C and increased with OEG linker length. The use of the three R6G-actin conjugates of different linker lengths was useful to not only figure out the linker length dependence of the rotational motion of R6G but also validate the analyses. In the presence of a cosolvent of glycerol, although the tumbling motion of G-actin was retarded in response to the bulk viscosity, the wobbling motion of R6G tethered to actin exhibited an increase of RDC as glycerol concentration increased. This finding suggests an intricate relationship between the fluid properties of the bulk solvent and the local environment around actin.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuichi", "last_name": "Wazawa", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.12.0_87" }, "pmcid": { "normalized": "PMC4736842" }, "pmid": { "normalized": "27493858" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "87-102", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "12", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Rotational motion of rhodamine 6G tethered to actin through oligo(ethylene glycol) linkers studied by frequency-domain fluorescence anisotropy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the last couple of decades, the spatial resolution in optical microscopy has increased to unprecedented levels by exploiting the fluorescence properties of the probe. At about the same time, Raman imaging techniques have emerged as a way to image inherent chemical information in a sample without using fluorescent probes. However, in many applications, the achievable resolution is limited to about half the wavelength of excitation light. Here we report the use of structured illumination to increase the spatial resolution of label-free spontaneous Raman microscopy, generating highly detailed spatial contrast from the ensemble of molecular information in the sample. Using structured line illumination in slit-scanning Raman microscopy, we demonstrate a marked improvement in spatial resolution and show the applicability to a range of samples, including both biological and inorganic chemical component mapping. This technique is expected to contribute towards greater understanding of chemical component distributions in organic and inorganic materials.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kozue", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Almar F.", "last_name": "Palonpon", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Liang-da", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms10095" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26626144" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "6", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Structured line illumination Raman microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pineal organs of lower vertebrates contain several kinds of photosensitive molecules, opsins that are suggested to be involved in different light-regulated physiological functions. We previously reported that parapinopsin is an ultraviolet (UV)-sensitive opsin that underlies hyperpolarization of the pineal photoreceptor cells of lower vertebrates to achieve pineal wavelength discrimination. Although, parapinopsin is phylogenetically close to vertebrate visual opsins, it exhibits a property similar to invertebrate visual opsins and melanopsin: the photoproduct of parapinopsin is stable and reverts to the original dark states, demonstrating the nature of bistable pigments. Therefore, it is of evolutionary interest to identify a phototransduction cascade driven by parapinopsin and to compare it with that in vertebrate visual cells. Here, we showed that parapinopsin is coupled to vertebrate visual G protein transducin in the pufferfish, zebrafish, and lamprey pineal organs. Biochemical analyses demonstrated that parapinopsins activated transducin in vitro in a light-dependent manner, similar to vertebrate visual opsins. Interestingly, transducin activation by parapinopsin was provoked and terminated by UV- and subsequent orange-lights irradiations, respectively, due to the bistable nature of parapinopsin, which could contribute to a wavelength-dependent control of a second messenger level in the cell as a unique optogenetic tool. Immunohistochemical examination revealed that parapinopsin was colocalized with Gt2 in the teleost, which possesses rod and cone types of transducin, Gt1, and Gt2. On the other hand, in the lamprey, which does not possess the Gt2 gene, in situ hybridization suggested that parapinopsin-expressing photoreceptor cells contained Gt1 type transducin GtS, indicating that lamprey parapinopsin may use GtS in place of Gt2. Because it is widely accepted that vertebrate visual opsins having a bleaching nature have evolved from non-bleaching opsins similar to parapinopsin, these results implied that ancestral bistable opsins might acquire coupling to the transducin-mediated cascade and achieve light-dependent hyperpolarizing response of the photoreceptor cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Emi", "last_name": "Kawano-Yamashita", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Hisao", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0141280" }, "pmcid": { "normalized": "PMC4619617" }, "pmid": { "normalized": "26492337" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibody Formation", "descriptor_ui": "D000917", "major_topic": false }, { "descriptor": "Fish Proteins", "descriptor_ui": "D029941", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Immunoenzyme Techniques", "descriptor_ui": "D007124", "major_topic": false }, { "descriptor": "Immunoglobulin G", "descriptor_ui": "D007074", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Lampreys", "descriptor_ui": "D007798", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pineal Gland", "descriptor_ui": "D010870", "major_topic": false }, { "descriptor": "Rod Opsins", "descriptor_ui": "D017299", "major_topic": false }, { "descriptor": "Tetraodontiformes", "descriptor_ui": "D023721", "major_topic": false }, { "descriptor": "Transducin", "descriptor_ui": "D015293", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "10", "normalized_date": "2015", "pages": "e0141280", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "10", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Activation of Transducin by Bistable Pigment Parapinopsin in the Pineal Organ of Lower Vertebrates.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Characterization of states, the essential components of the underlying energy landscapes, is one of the most intriguing subjects in single-molecule (SM) experiments due to the existence of noise inherent to the measurements. Here we present a method to extract the underlying state sequences from experimental SM time-series. Taking into account empirical error and the finite sampling of the time-series, the method extracts a steady-state network which provides an approximation of the underlying effective free energy landscape. The core of the method is the application of rate-distortion theory from information theory, allowing the individual data points to be assigned to multiple states simultaneously. We demonstrate the method's proficiency in its application to simulated trajectories as well as to experimental SM fluorescence resonance energy transfer (FRET) trajectories obtained from isolated agonist binding domains of the AMPA receptor, an ionotropic glutamate receptor that is prevalent in the central nervous system.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "J. Nicholas", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Chun-Biu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "David R.", "last_name": "Cooper", "name": null }, { "creator_type": "author", "first_name": "Christy F.", "last_name": "Landes", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep09174" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25779909" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "5", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Error-based Extraction of States and Energy Landscapes from Experimental Single-Molecule Time-Series.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Growing evidence indicates that the endocannabinoid system is important for the acquisition and/or extinction of learning and memory. However, it is unclear which endocannabinoid(s) play(s) a crucial role in these cognitive functions, especially memory extinction. To elucidate the physiological role of 2-arachidonoylglycerol (2-AG), a major endocannabinoid, in behavioral and cognitive functions, we conducted a comprehensive behavioral test battery in knockout (KO) mice deficient in monoacylglycerol lipase (MGL), the major hydrolyzing enzyme of 2-AG. We found age-dependent increases in spontaneous physical activity (SPA) in MGL KO mice. Next, we tested the MGL KO mice using 5 hippocampus-dependent learning paradigms (i.e., Morris water maze (MWM), contextual fear conditioning, novel object recognition test, trace eyeblink conditioning, and water-finding test). In the MWM, MGL KO mice showed normal acquisition of reference memory, but exhibited significantly faster extinction of the learned behavior. Moreover, they showed faster memory acquisition on the reversal-learning task of the MWM. In contrast, in the contextual fear conditioning, MGL KO mice tended to show slower memory extinction. In the novel object recognition and water-finding tests, MGL KO mice exhibited enhanced memory acquisition. Trace eyeblink conditioning was not altered in MGL KO mice throughout the acquisition and extinction phases. These results indicate that 2-AG signaling is important for hippocampus-dependent learning and memory, but its contribution is highly task-dependent.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Barbara", "last_name": "Cagniard", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Kirino", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnbeh.2015.00134" }, "pmcid": { "normalized": "PMC4451424" }, "pmid": { "normalized": "26082696" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "134", "proceedings_title": null, "publisher": "", "title": "Frontiers in behavioral neuroscience", "volume": "9", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Task-specific enhancement of hippocampus-dependent learning in mice deficient in monoacylglycerol lipase, the major hydrolyzing enzyme of the endocannabinoid 2-arachidonoylglycerol.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "There is growing evidence and a consensus in the field that most pediatric brain tumors originate from stem cells, of which radial glial cells constitute a subtype. Here we show that orthotopic transplantation of human radial glial (RG) cells to the subventricular zone of the 3rd ventricle--but not to other transplantation sites--of the brain in immunocompromised NOD-SCID mice, gives rise to tumors that have the hallmarks of CNS primitive neuroectodermal tumors (PNETs). The resulting mouse model strikingly recapitulates the phenotype of PNETs. Importantly, the observed tumorigenic transformation was accompanied by aspects of an epithelial to mesenchymal transition (EMT)-like process. It is also noteworthy that the tumors are highly invasive, and that they effectively recruit mouse endothelial cells for angiogenesis. These results are significant for several reasons. First, they show that malignant transformation of radial glial cells can occur in the absence of specific mutations or inherited genomic alterations. Second, they demonstrate that the same radial glial cells may either give rise to brain tumors or differentiate normally depending upon the microenvironment of the specific region of the brain to which the cells are transplanted. In addition to providing a prospect for drug screening and development of new therapeutic strategies, the resulting mouse model of PNETs offers an unprecedented opportunity to identify the cancer driving molecular alterations and the microenvironmental factors that are responsible for committing otherwise normal radial glial cells to a malignant phenotype.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Sergey", "last_name": "Malchenko", "name": null }, { "creator_type": "author", "first_name": "Simone Treiger", "last_name": "Sredni", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Jianping", "last_name": "Xie", "name": null }, { "creator_type": "author", "first_name": "Naira V.", "last_name": "Margaryan", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Rishi R.", "last_name": "Lulla", "name": null }, { "creator_type": "author", "first_name": "Richard E. B.", "last_name": "Seftor", "name": null }, { "creator_type": "author", "first_name": "Lauren M.", "last_name": "Pachman", "name": null }, { "creator_type": "author", "first_name": "Herbert Y.", "last_name": "Meltzer", "name": null }, { "creator_type": "author", "first_name": "Mary J. C.", "last_name": "Hendrix", "name": null }, { "creator_type": "author", "first_name": "Marcelo B.", "last_name": "Soares", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0121707" }, "pmcid": { "normalized": "PMC4380339" }, "pmid": { "normalized": "25826270" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Transplantation", "descriptor_ui": "D017690", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Mice, SCID", "descriptor_ui": "D016513", "major_topic": false }, { "descriptor": "Neuroectodermal Tumors, Primitive", "descriptor_ui": "D018242", "major_topic": false }, { "descriptor": "Neuroglia", "descriptor_ui": "D009457", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "3", "normalized_date": "2015", "pages": "e0121707", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "10", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "A mouse model of human primitive neuroectodermal tumors resulting from microenvironmentally-driven malignant transformation of orthotopically transplanted radial glial cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) exerts neurotrophic activities including modulation of synaptic plasticity and memory, hippocampal neurogenesis, and neuroprotection, most of which are shared with brain-derived neurotrophic factor (BDNF). Therefore, the aim of this study was to compare morphological effects of PACAP and BDNF on primary cultured hippocampal neurons. At days in vitro (DIV) 3, PACAP increased neurite length and number to similar levels by BDNF, but vasoactive intestinal polypeptide showed much lower effects. In addition, PACAP increased axon, but not dendrite, length, and soma size at DIV 3 similarly to BDNF. The PACAP antagonist PACAP6-38 completely blocked the PACAP-induced increase in axon, but not dendrite, length. Interestingly, the BDNF-induced increase in axon length was also inhibited by PACAP6-38, suggesting a mechanism involving PACAP signaling. K252a, a TrkB receptor inhibitor, inhibited axon outgrowth induced by PACAP and BDNF without affecting dendrite length. These results indicate that in primary cultured hippocampal neurons, PACAP shows morphological actions via its cognate receptor PAC1, stimulating neurite length and number, and soma size to a comparable extent as BDNF, and that the increase in total neurite length is ascribed to axon outgrowth.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Katsuya", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Kamo", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Higashi", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Hisae", "last_name": "Momosaki", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Vaudry", "name": null }, { "creator_type": "author", "first_name": "Hubert", "last_name": "Vaudry", "name": null }, { "creator_type": "author", "first_name": "Ludovic", "last_name": "Galas", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0120526" }, "pmcid": { "normalized": "PMC4373823" }, "pmid": { "normalized": "25807538" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Brain-Derived Neurotrophic Factor", "descriptor_ui": "D019208", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Receptor, trkB", "descriptor_ui": "D020813", "major_topic": false }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I", "descriptor_ui": "D051237", "major_topic": false }, { "descriptor": "Receptors, Vasoactive Intestinal Peptide, Type II", "descriptor_ui": "D051239", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Vasoactive Intestinal Peptide", "descriptor_ui": "D014660", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "3", "normalized_date": "2015", "pages": "e0120526", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "10", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "PACAP enhances axon outgrowth in cultured hippocampal neurons to a comparable extent as BDNF.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fever is a common response to inflammation and infection. The mechanism involves prostaglandin E2 (PGE2)-EP3 receptor signaling in the hypothalamus, which raises the set point of hypothalamic thermostat for body temperature, but the lipid metabolic pathway for pyretic PGE2 production remains unknown. To reveal the molecular basis of fever initiation, we examined lipopolysaccharides (LPS)-induced fever model in monoacylglycerol lipase (MGL)-deficient (Mgll-/-) mice, CB1 receptor-MGL compound-deficient (Cnr1-/-Mgll-/-) mice, cytosolic phospholipase A2alpha (cPLA2alpha)-deficient (Pla2g4a-/-) mice, and diacylglycerol lipase alpha (DGLalpha)-deficient (Dagla-/-) mice. Febrile reactions were abolished in Mgll-/- and Cnr1-/-Mgll-/- mice, whereas Cnr1-/-Mgll+/+, Pla2g4a-/- and Dagla-/- mice responded normally, demonstrating that MGL is a critical enzyme for fever, which functions independently of endocannabinoid signals. Intracerebroventricular administration of PGE2 caused fever similarly in Mgll-/- and wild-type control mice, suggesting a lack of pyretic PGE2 production in Mgll-/- hypothalamus, which was confirmed by lipidomics analysis. Normal blood cytokine responses after LPS administration suggested that MGL-deficiency does not affect pyretic cytokine productions. Diurnal body temperature profiles were normal in Mgll-/- mice, demonstrating that MGL is unrelated to physiological thermoregulation. In conclusion, MGL-dependent hydrolysis of endocannabinoid 2-arachidonoylglycerol is necessary for pyretic PGE2 production in the hypothalamus.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Kenij", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Suzumi M.", "last_name": "Tokuoka", "name": null }, { "creator_type": "author", "first_name": "Fumie", "last_name": "Hamano", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Shimizu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0133663" }, "pmcid": { "normalized": "PMC4511515" }, "pmid": { "normalized": "26196692" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arachidonic Acids", "descriptor_ui": "D001095", "major_topic": false }, { "descriptor": "Dinoprostone", "descriptor_ui": "D015232", "major_topic": false }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fever", "descriptor_ui": "D005334", "major_topic": false }, { "descriptor": "Glycerides", "descriptor_ui": "D005989", "major_topic": false }, { "descriptor": "Group IV Phospholipases A2", "descriptor_ui": "D054513", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Lipoprotein Lipase", "descriptor_ui": "D008071", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Monoacylglycerol Lipases", "descriptor_ui": "D008994", "major_topic": false }, { "descriptor": "Receptor, Cannabinoid, CB1", "descriptor_ui": "D043884", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "7", "normalized_date": "2015", "pages": "e0133663", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "10", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Fever Is Mediated by Conversion of Endocannabinoid 2-Arachidonoylglycerol to Prostaglandin E2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dendritic cell immunoreceptor (DCIR) is a C-type lectin receptor containing a carbohydrate recognition domain in its extracellular portion and an immunoreceptor tyrosine–based inhibitory motif, which transduces negative signals into cells, in its cytoplasmic portion. Previously, we showed that Dcir–/– mice spontaneously develop autoimmune diseases such as enthesitis and sialadenitis due to excess expansion of dendritic cells (DCs), suggesting that DCIR is critically important for the homeostasis of the immune system. In this report, we analyzed the role of DCIR in the development of experimental autoimmune encephalomyelitis (EAE), an autoimmune disease model for multiple sclerosis. We found that EAE was exacerbated in Dcir–/– mice associated with severe demyelination of the spinal cords. The number of infiltrated CD11c+ DCs and CD4+ T cells into spinal cords was increased in Dcir–/– mice. Recall proliferative response of lymph node cells was higher in Dcir–/– mice compared with wild-type mice. These observations suggest that DCIR is an important negative regulator of the immune system, and Dcir–/– mice should be useful for analyzing the roles of DCIR in an array of autoimmune diseases.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Akimasa", "last_name": "SENO", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "MARUHASHI", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "KAIFU", "name": null }, { "creator_type": "author", "first_name": "Rikio", "last_name": "YABE", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "FUJIKADO", "name": null }, { "creator_type": "author", "first_name": "Guangyu", "last_name": "MA", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "IKARASHI", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "KAKUTA", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "IWAKURA", "name": null } ], "identifiers": { "doi": { "normalized": "10.1538/expanim.14-0079" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26176030" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CD4-Positive T-Lymphocytes", "descriptor_ui": "D015496", "major_topic": false }, { "descriptor": "Demyelinating Diseases", "descriptor_ui": "D003711", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Encephalomyelitis, Autoimmune, Experimental", "descriptor_ui": "D004681", "major_topic": false }, { "descriptor": "Lectins, C-Type", "descriptor_ui": "D037181", "major_topic": false }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Multiple Sclerosis", "descriptor_ui": "D009103", "major_topic": false }, { "descriptor": "Receptors, Immunologic", "descriptor_ui": "D011971", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "2", "normalized_date": "2015", "pages": "109-119", "proceedings_title": null, "publisher": "", "title": "Experimental Animals", "volume": "64", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Exacerbation of experimental autoimmune encephalomyelitis in mice deficient for DCIR, an inhibitory C-type lectin receptor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: The selective incorporation of appropriate histone variants into chromatin is critical for the regulation of genome function. Although many histone variants have been identified, a complete list has not been compiled. Results: We screened mouse, rat and human genomes by in silico hybridization using canonical histone sequences. In the mouse genome, we identified 14 uncharacterized H3 genes, among which 13 are similar to H3.3 and do not have human or rat counterparts, and one is similar to human testis-specific H3 variant, H3T/H3.4, and had a rat paralog. Although some of these genes were previously annotated as pseudogenes, their tissue-specific expression was confirmed by sequencing the 3′-UTR regions of the transcripts. Certain new variants were also detected at the protein level by mass spectrometry. When expressed as GFP-tagged versions in mouse C2C12 cells, some variants were stably incorporated into chromatin and the genome-wide distributions of most variants were similar to that of H3.3. Moreover, forced expression of H3 variants in chromatin resulted in alternate gene expression patterns after cell differentiation. Conclusions: We comprehensively identified and characterized novel mouse H3 variant genes that encoded highly conserved amino acid sequences compared to known histone H3. We speculated that the diversity of H3 variants acquired after species separation played a role in regulating tissue-specific gene expression in individual species. Their biological relevance and evolutionary aspect involving pseudogene diversification will be addressed by further functional analysis. Electronic supplementary material: The online version of this article (doi:10.1186/s13072-015-0027-3) contains supplementary material, which is available to authorized users.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Keiichi I.", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13072-015-0027-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26388943" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "", "proceedings_title": null, "publisher": "", "title": "Epigenetics & Chromatin", "volume": "8", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Tissue-specific expression of histone H3 variants diversified after species separation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "MicroRNAs (miRNAs) have been reported to regulate the development of chemoresistance in many tumors. Stathmin 1 (STMN1) is a microtubule-depolymerizing molecule, involved in chemo-response; however, the mechanism of its regulation is unknown. Herein, the immunohistochemical study indicated significant upregulation of the STMN1 in the ovarian cancer tissues defined as resistant tumors compared with those defined as responsive tumors. STMN1 level elevated in the chemoresistant ovarian cancer cells, KF-TX, compared with the parental, KF, ones. Targeting STMN1 by siRNA restored taxane-sensitivity of KF-TX cells. Screening miRNA profiles from KF/KF-TX cellular set followed by bioinformatics-based prediction, revealed that miR-31 could be a possible regulator of STMN1. Down-modulation of miR-31 was verified by quantitative RT-PCR in the cellular set used. Overexpression of miR-31 in KF-TX cells (KF-TX-miR-31) significantly restored chemo-response and reduced STMN1 expression as well. STMN1 reduction-associated cellular characteristics such as enhanced microtubule polymerization and stability, as indicated by acetylated tubulin quantification, confocal visualization, and G2 phase delay, were observed in KF-TX-miR-31 cells, indicating the functional reduction of STMN1. miR-31 suppressed the luciferase activity in reporter construct containing the STMN1 3'-untranslated region (3'-UTR), confirming that miR-31 directly targets STMN1. miR-31 has therapeutic potency when introduced into ovarian cancer, in combination with taxane.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mohamed Kamel", "last_name": "Hassan", "name": null }, { "creator_type": "author", "first_name": "Hidemichi", "last_name": "Watari", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Mitamura", "name": null }, { "creator_type": "author", "first_name": "Zainab", "last_name": "Mohamed", "name": null }, { "creator_type": "author", "first_name": "Sherif F.", "last_name": "El-Khamisy", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Sakuragi", "name": null } ], "identifiers": { "doi": { "normalized": "10.18632/oncoscience.143" }, "pmcid": { "normalized": "PMC4394135" }, "pmid": { "normalized": "25897432" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "3", "normalized_date": "2015", "pages": "294-308", "proceedings_title": null, "publisher": "", "title": "Oncoscience", "volume": "2", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "P18/Stathmin1 is regulated by miR-31 in ovarian cancer in response to taxane.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mechanism by which extracellular molecules control serotonergic cell fate remains elusive. Recently, we showed that noggin, which inactivates bone morphogenetic proteins (BMPs), induces serotonergic differentiation of mouse embryonic (ES) and induced pluripotent stem cells with coordinated gene expression along the serotonergic lineage. Here, we created a rapid assay for serotonergic induction by generating knock-in ES cells expressing a naturally secreted Gaussia luciferase driven by the enhancer of Pet-1/Fev, a landmark of serotonergic differentiation. Using these cells, we performed candidate-based screening and identified BMP type I receptor kinase inhibitors LDN-193189 and DMH1 as activators of luciferase. LDN-193189 induced ES cells to express the genes encoding Pet-1, tryptophan hydroxylase 2, and the serotonin transporter, and increased serotonin release without altering dopamine release. In contrast, TGF-beta receptor inhibitor SB-431542 selectively inhibited serotonergic differentiation, without changing overall neuronal differentiation. LDN-193189 inhibited expression of the BMP signaling target gene Id, and induced the TGF-beta target gene Lefty, whereas the opposite effect was observed with SB-431542. This study thus provides a new tool to investigate serotonergic differentiation and suggests that inhibition of BMP type I receptors and concomitant activation of TGF-beta receptor signaling are implicated in serotonergic differentiation. Candidate-based screening for serotonergic induction using a rapid assay in mouse embryonic stem cells revealed that the bone morphogenetic protein (BMP) type I receptor kinase inhibitors selectively induce serotonergic differentiation, whereas the TGF-beta receptor inhibitor SB-431542 inhibits the differentiation. These results suggest that inhibition of BMP type I receptors and concomitant activation of transforming growth factor-beta (TGF-beta) receptor signaling are involved in the early trajectory of serotonergic differentiation.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Toi", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Saki", "last_name": "Kimoto", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Herbert Y.", "last_name": "Meltzer", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "James A.", "last_name": "Waschek", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Onaka", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/jnc.12999" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25421849" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzamides", "descriptor_ui": "D001549", "major_topic": false }, { "descriptor": "Bone Morphogenetic Protein Receptors, Type I", "descriptor_ui": "D052005", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Dioxoles", "descriptor_ui": "D004149", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pyrazoles", "descriptor_ui": "D011720", "major_topic": false }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": false }, { "descriptor": "Receptors, Transforming Growth Factor beta", "descriptor_ui": "D018125", "major_topic": false }, { "descriptor": "Serotonergic Neurons", "descriptor_ui": "D059326", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Feb", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "418-428", "proceedings_title": null, "publisher": "", "title": "Journal of neurochemistry", "volume": "132", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of the role of bone morphogenetic protein (BMP) and transforming growth factor-beta (TGF-beta) signaling in the trajectory of serotonergic differentiation in a rapid assay in mouse embryonic stem cells in vitro.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ultrasound elastography is a relatively new diagnostic technique for measuring the elasticity (hardness) of tissue. Eleven years have passed since the debut of elastography. Various elastography devices are currently being marketed by manufacturers under different names. Pancreatic elastography can be used not only with transabdominal ultrasonography but also with endoscopic ultrasonography, but some types of elastography are difficult to perform for the pancreas. These guidelines aim to classify the various types of elastography into two major categories depending on the differences in the physical quantity (strain, shear wave), and to present the evidence for pancreatic elastography and how to use pancreatic elastography in the present day. But the number of reports on ultrasound elastography for the pancreas is still small, and there are no reports on some elastography devices for the pancreas. Therefore, these guidelines do not recommend methods of imaging and analysis by elastography device.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Hirooka", "name": null }, { "creator_type": "author", "first_name": "Takamichi", "last_name": "Kuwahara", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Irisawa", "name": null }, { "creator_type": "author", "first_name": "Fumihide", "last_name": "Itokawa", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Sasahira", "name": null }, { "creator_type": "author", "first_name": "Natsuko", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10396-014-0571-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26576568" } }, "mesh": [ { "descriptor": "Elasticity Imaging Techniques", "descriptor_ui": "D054459", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Pancreas", "descriptor_ui": "D010179", "major_topic": false }, { "descriptor": "Practice Guidelines as Topic", "descriptor_ui": "D017410", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "151-174", "proceedings_title": null, "publisher": "", "title": "Journal of medical ultrasonics (2001)", "volume": "42", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "JSUM ultrasound elastography practice guidelines: pancreas.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "While previous studies and brain atlases divide the hypothalamus into many nuclei and areas, uncharacterised regions remain. Here, we report a new region in the mouse anterior hypothalamus (AH), a triangular-shaped perifornical area of the anterior hypothalamus (PeFAH) between the paraventricular hypothalamic nucleus and fornix, that abundantly expresses chondroitin sulfate proteoglycans (CSPGs). The PeFAH strongly stained with markers for chondroitin sulfate/CSPGs such as Wisteria floribunda agglutinin and antibodies against aggrecan and chondroitin 6 sulfate. Nissl-stained sections of the PeFAH clearly distinguished it as a region of comparatively low density compared to neighboring regions, the paraventricular nucleus and central division of the anterior hypothalamic area. Immunohistochemical and DNA microarray analyses suggested that PeFAH contains sparsely distributed calretinin-positive neurons and a compact cluster of enkephalinergic neurons. Neuronal tract tracing revealed that both enkephalin- and calretinin-positive neurons project to the lateral septum (LS), while the PeFAH receives input from calbindin-positive LS neurons. These results suggest bidirectional connections between the PeFAH and LS. Considering neuronal subtype and projection, part of PeFAH that includes a cluster of enkephalinergic neurons is similar to the rat perifornical nucleus and guinea pig magnocellular dorsal nucleus. Finally, we examined c-Fos expression after several types of stimuli and found that PeFAH neuronal activity was increased by psychological but not homeostatic stressors. These findings suggest that the PeFAH is a source of enkephalin peptides in the LS and indicate that bidirectional neural connections between these regions may participate in controlling responses to psychological stressors.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Noriko", "last_name": "Horii-Hayashi", "name": null }, { "creator_type": "author", "first_name": "Takayo", "last_name": "Sasagawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Nishi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/ejn.13024" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26205995" } }, "mesh": [ { "descriptor": "Aggression", "descriptor_ui": "D000374", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anterior Hypothalamic Nucleus", "descriptor_ui": "D007025", "major_topic": false }, { "descriptor": "Chondroitin Sulfate Proteoglycans", "descriptor_ui": "D011508", "major_topic": false }, { "descriptor": "Enkephalins", "descriptor_ui": "D004745", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-fos", "descriptor_ui": "D016760", "major_topic": false }, { "descriptor": "Restraint, Physical", "descriptor_ui": "D012149", "major_topic": false }, { "descriptor": "Septal Nuclei", "descriptor_ui": "D012686", "major_topic": false }, { "descriptor": "Stress, Psychological", "descriptor_ui": "D013315", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Sep", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "2322-2334", "proceedings_title": null, "publisher": "", "title": "The European journal of neuroscience", "volume": "42", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "A newly identified mouse hypothalamic area having bidirectional neural connections with the lateral septum: the perifornical area of the anterior hypothalamus rich in chondroitin sulfate proteoglycans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurons form exuberant synapses with target cells early in development. Then, necessary synapses are selectively strengthened whereas unnecessary connections are weakened and eventually eliminated during postnatal development. This process is known as synapse elimination and is a crucial step for shaping immature neural circuits into functionally mature versions. Accumulating evidence suggests that retrograde signaling from postsynaptic cells regulates synapse elimination, but the underlying mechanisms remain unknown. Here, we show that semaphorin3A (Sema3A) and semaphorin7A (Sema7A) mediate retrograde signals for elimination of redundant climbing fiber (CF) to Purkinje cell (PC) synapses in the developing cerebellum, a representative model of synapse elimination in the central nervous system. We picked up candidate retrograde signaling molecules that are expressed in PCs during the period of CF synapse elimination and the receptors of these candidate molecules that are present in CFs. We then assessed the effects of lentivirus-mediated RNAi-knockdown of these molecules on CF synapse elimination. By this systematic screening, we found that knockdown of Sema3A in PCs or its co-receptor, plexinA4 (PlxnA4), in CFs accelerated CF synapse elimination and decreased CF-mediated synaptic inputs. Conversely, knockdown of Sema7A in PCs or either of the two receptors for Sema7A, plexinC1 (PlxnC1) and integrinB1 (ItgB1), in CFs impaired CF synapse elimination. Importantly, the effect of Sema7A involves signaling by type 1 metabotropic glutamate receptor (mGluR1), a canonical pathway in PCs for the final stage of CF synapse elimination. These results demonstrate that specific semaphorins act as retrograde signaling molecules and regulate distinct processes of CF synapse elimination during postnatal cerebellar development.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Motokazu", "last_name": "Uchigashima", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Mikuni", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12311-014-0615-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25338972" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Feb", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "4-7", "proceedings_title": null, "publisher": "", "title": "Cerebellum (London, England)", "volume": "14", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Retrograde signaling for climbing fiber synapse elimination.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The World Federation for Ultrasound in Medicine and Biology (WFUMB) has produced these guidelines for the use of elastography techniques in liver disease. For each available technique, the reproducibility, results, and limitations are analyzed, and recommendations are given. Finally, recommendations based on the international literature and the findings of the WFUMB expert group are established as answers to common questions. The document has a clinical perspective and is aimed at assessing the usefulness of elastography in the management of liver diseases.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Giovanna", "last_name": "Ferraioli", "name": null }, { "creator_type": "author", "first_name": "Carlo", "last_name": "Filice", "name": null }, { "creator_type": "author", "first_name": "Laurent", "last_name": "Castera", "name": null }, { "creator_type": "author", "first_name": "Byung Ihn", "last_name": "Choi", "name": null }, { "creator_type": "author", "first_name": "Ioan", "last_name": "Sporea", "name": null }, { "creator_type": "author", "first_name": "Stephanie R.", "last_name": "Wilson", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Cosgrove", "name": null }, { "creator_type": "author", "first_name": "Christoph F.", "last_name": "Dietrich", "name": null }, { "creator_type": "author", "first_name": "Dominique", "last_name": "Amy", "name": null }, { "creator_type": "author", "first_name": "Jeffrey C.", "last_name": "Bamber", "name": null }, { "creator_type": "author", "first_name": "Richard", "last_name": "Barr", "name": null }, { "creator_type": "author", "first_name": "Yi-Hong", "last_name": "Chou", "name": null }, { "creator_type": "author", "first_name": "Hong", "last_name": "Ding", "name": null }, { "creator_type": "author", "first_name": "Andre", "last_name": "Farrokh", "name": null }, { "creator_type": "author", "first_name": "Mireen", "last_name": "Friedrich-Rust", "name": null }, { "creator_type": "author", "first_name": "Timothy J.", "last_name": "Hall", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Kathryn R.", "last_name": "Nightingale", "name": null }, { "creator_type": "author", "first_name": "Mark L.", "last_name": "Palmeri", "name": null }, { "creator_type": "author", "first_name": "Fritz", "last_name": "Schafer", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Kudo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ultrasmedbio.2015.03.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25800942" } }, "mesh": [ { "descriptor": "Elastic Modulus", "descriptor_ui": "D055119", "major_topic": false }, { "descriptor": "Elasticity Imaging Techniques", "descriptor_ui": "D054459", "major_topic": false }, { "descriptor": "Internationality", "descriptor_ui": "D038622", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Liver Cirrhosis", "descriptor_ui": "D008103", "major_topic": false }, { "descriptor": "Practice Guidelines as Topic", "descriptor_ui": "D017410", "major_topic": true }, { "descriptor": "Shear Strength", "descriptor_ui": "D033081", "major_topic": false }, { "descriptor": "Stress, Mechanical", "descriptor_ui": "D013314", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "1161-1179", "proceedings_title": null, "publisher": "", "title": "Ultrasound in medicine & biology", "volume": "41", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 3: liver.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Wnt signaling pathways are tightly regulated by ubiquitination, and dysregulation of these pathways promotes tumorigenesis. It has been reported that the ubiquitin ligase RNF43 plays an important role in frizzled-dependent regulation of the Wnt/β-catenin pathway. Here, we show that RNF43 suppresses both Wnt/β-catenin signaling and noncanonical Wnt signaling by distinct mechanisms. The suppression of Wnt/β-catenin signaling requires interaction between the extracellular protease-associated (PA) domain and the cysteine-rich domain (CRD) of frizzled and the intracellular RING finger domain of RNF43. In contrast, these N-terminal domains of RNF43 are not required for inhibition of noncanonical Wnt signaling, but interaction between the C-terminal cytoplasmic region of RNF43 and the PDZ domain of dishevelled is essential for this suppression. We further show the mechanism by which missense mutations in the extracellular portion of RNF43 identified in patients with tumors activate Wnt/β-catenin signaling. Missense mutations of RNF43 change their localization from the endosome to the endoplasmic reticulum (ER), resulting in the failure of frizzled-dependent suppression of Wnt/β-catenin signaling. However, these mutants retain the ability to suppress noncanonical Wnt signaling, probably due to interaction with dishevelled. RNF43 is also one of the potential target genes of Wnt/β-catenin signaling. Our results reveal the molecular role of RNF43 and provide an insight into tumorigenesis.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tadasuke", "last_name": "Tsukiyama", "name": null }, { "creator_type": "author", "first_name": "Akimasa", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Sayuri", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Shinada", "name": null }, { "creator_type": "author", "first_name": "Hidehisa", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Terry P.", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Shigetsugu", "last_name": "Hatakeyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/mcb.00159-15" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25825523" } }, "mesh": [ { "descriptor": "beta Catenin", "descriptor_ui": "D051176", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Cytoskeletal Proteins", "descriptor_ui": "D003598", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": false }, { "descriptor": "Endosomes", "descriptor_ui": "D011992", "major_topic": false }, { "descriptor": "Frizzled Receptors", "descriptor_ui": "D051157", "major_topic": false }, { "descriptor": "HCT116 Cells", "descriptor_ui": "D045325", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Hep G2 Cells", "descriptor_ui": "D056945", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MCF-7 Cells", "descriptor_ui": "D061986", "major_topic": false }, { "descriptor": "Mutation, Missense", "descriptor_ui": "D020125", "major_topic": false }, { "descriptor": "Oncogene Proteins", "descriptor_ui": "D015513", "major_topic": false }, { "descriptor": "RING Finger Domains", "descriptor_ui": "D054829", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Trans-Activators", "descriptor_ui": "D015534", "major_topic": false }, { "descriptor": "Ubiquitin-Protein Ligases", "descriptor_ui": "D044767", "major_topic": false }, { "descriptor": "Wnt Proteins", "descriptor_ui": "D051153", "major_topic": false }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jun", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "2007-2023", "proceedings_title": null, "publisher": "", "title": "Molecular and Cellular Biology", "volume": "35", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular Role of RNF43 in Canonical and Noncanonical Wnt Signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herpes simplex virus 1 (HSV-1) envelope glycoprotein H (gH) is important for viral entry into cells and nuclear egress of nucleocapsids. To clarify additional novel roles of gH during HSV-1 replication, host cell proteins that interact with gH were screened for by tandem affinity purification coupled with mass spectrometry-based proteomics in 293T cells transiently expressing gH. This screen identified 123 host cell proteins as potential gH interactors. Of these proteins, general control nonderepressive-1 (GCN1), a trans-acting positive effector of GCN2 kinase that regulates phosphorylation of the alpha subunit of translation initiation factor 2 (eIF2alpha), was subsequently confirmed to interact with gH in HSV-1-infected cells. eIF2alpha phosphorylation is known to downregulate protein synthesis, and various viruses have evolved mechanisms to prevent the accumulation of phosphorylated eIF2alpha in infected cells. Here, it was shown that GCN1 knockdown reduces phosphorylation of eIF2alpha in HSV-1-infected cells and that the gH-null mutation increases eIF2alpha in HSV-1-infected cells, whereas gH overexpression in the absence of other HSV-1 proteins reduces eIF2alpha phosphorylation. These findings suggest that GCN1 can regulate eIF2alpha phosphorylation in HSV-1-infected cells and that the GCN1-binding viral partner gH is necessary and sufficient to prevent the accumulation of phosphorylated eIF2alpha. Our database of 123 host cell proteins potentially interacting with gH will be useful for future studies aimed at unveiling further novel functions of gH and the roles of cellular proteins in HSV-1-infected cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hirohata", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kozuka-Hata", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/1348-0421.12255" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25808324" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chromatography, Affinity", "descriptor_ui": "D002846", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Eukaryotic Initiation Factor-2", "descriptor_ui": "D015852", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Interaction Maps", "descriptor_ui": "D060066", "major_topic": true }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false }, { "descriptor": "Trans-Activators", "descriptor_ui": "D015534", "major_topic": false }, { "descriptor": "Viral Envelope Proteins", "descriptor_ui": "D014759", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "331-337", "proceedings_title": null, "publisher": "", "title": "Microbiology and immunology", "volume": "59", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Interactome analysis of herpes simplex virus 1 envelope glycoprotein H.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescence nanoscopy has revolutionized our ability to visualize biological structures not resolvable by conventional microscopy. However, photodamage induced by intense light exposure has limited its use in live specimens. Here we describe Kohinoor, a fast-switching, positively photoswitchable fluorescent protein, and show that it has high photostability over many switching repeats. With Kohinoor, we achieved super-resolution imaging of live HeLa cells using biocompatible, ultralow laser intensity (0.004 J/cm(2)) in reversible saturable optical fluorescence transition (RESOLFT) nanoscopy.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Dhermendra K.", "last_name": "Tiwari", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Agetsuma", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nmeth.3362" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25894946" } }, "mesh": [ { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": true }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Nanotechnology", "descriptor_ui": "D036103", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "515-518", "proceedings_title": null, "publisher": "", "title": "Nature methods", "volume": "12", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "A fast- and positively photoswitchable fluorescent protein for ultralow-laser-power RESOLFT nanoscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Collective motion of keratinocytes is involved in morphogenesis, homeostasis, and wound healing of the epidermis. Yet how the collective motion of keratinocytes emerges from the behavior of individual cells is still largely unknown. OBJECTIVE: The aim of this study was to find the cellular behavior that links single and collective motion of keratinocytes. METHODS: We investigated the behavior of two-cell colonies of HaCaT keratinocytes by a combination of time-lapse imaging and image processing. RESULTS: The two-cell colonies of HaCaT cells were formed as a contacted pair of keratinocyte clones. Image analysis and cell culture experiments revealed that the rotational speed of two-cell colonies was positively associated with their proliferative capacity. alpha6 integrin was required for the rotational motion of two-cell keratinocyte colonies. We also confirmed that two-cell colonies of keratinocytes predominantly exhibited the rotational, but not translational, motion, two modes of motion in a contact pair of rotating objects. CONCLUSION: The rotational motion is the primary motion of two-cell keratinocyte colonies and its speed is positively associated with their proliferative capacity. This study suggests that the assembly of rotating keratinocytes generates the collective motion of proliferative keratinocytes during morphogenesis and wound healing of the epidermis.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sota", "last_name": "Tate", "name": null }, { "creator_type": "author", "first_name": "Matome", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Natsuki", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Emi K.", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Nanba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jdermsci.2015.05.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26126707" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Clone Cells", "descriptor_ui": "D002999", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Integrin alpha6", "descriptor_ui": "D039503", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": false }, { "descriptor": "Rotation", "descriptor_ui": "D012399", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Sep", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "194-202", "proceedings_title": null, "publisher": "", "title": "Journal of dermatological science", "volume": "79", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Rotation is the primary motion of paired human epidermal keratinocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: The purpose of this study is to evaluate the performance of a modified range point migration (RPM) method using a semi-broad transmit beam for fetal surface imaging. METHODS: The conventional RPM method depicts accurate images of target surfaces by estimating the reflection point on a target surface from the path length of plural transmit-and-receive element combinations. However, the conventional RPM method depicts false images when echoes from different targets are received simultaneously. For the elimination of false images in the employment of the RPM method, we propose a modified RPM method with a semi-broad transmit beam to decrease the number of targets in each measurement region. RESULTS: The modified RPM method depicted two acrylic cylinders of 2 cm in diameter with a root-mean-square error (RMSE) of 0.062 mm, where the RMSE of the migration method was 0.145 mm. The modified RPM method also succeeded in depicting a 7-month fetal phantom with a RMSE of 0.058 mm relative to a 3D image acquired using optical measurement. CONCLUSION: This study shows the potential of the modified RPM method in achieving accurate surface imaging of multiple targets using a semi-broad beam, indicating that the method is suitable for fetal surface imaging.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanimura", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10396-014-0574-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26578490" } }, "mesh": [ { "descriptor": "Fetus", "descriptor_ui": "D005333", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Phantoms, Imaging", "descriptor_ui": "D019047", "major_topic": true }, { "descriptor": "Ultrasonography, Prenatal", "descriptor_ui": "D016216", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "51-58", "proceedings_title": null, "publisher": "", "title": "Journal of medical ultrasonics (2001)", "volume": "42", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Accurate ultrasound imaging based on range point migration method for the depiction of fetal surface.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescent Ca(2+) reporters are widely used as readouts of neuronal activities. Here we designed R-CaMP2, a high-affinity red genetically encoded calcium indicator (GECI) with a Hill coefficient near 1. Use of the calmodulin-binding sequence of CaMKK-alpha and CaMKK-beta in lieu of an M13 sequence resulted in threefold faster rise and decay times of Ca(2+) transients than R-CaMP1.07. These features allowed resolving single action potentials (APs) and recording fast AP trains up to 20-40 Hz in cortical slices. Somatic and synaptic activities of a cortical neuronal ensemble in vivo were imaged with similar efficacy as with previously reported sensitive green GECIs. Combining green and red GECIs, we successfully achieved dual-color monitoring of neuronal activities of distinct cell types, both in the mouse cortex and in freely moving Caenorhabditis elegans. Dual imaging using R-CaMP2 and green GECIs provides a powerful means to interrogate orthogonal and hierarchical neuronal ensembles in vivo.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Atsuya", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Shin-ichiro", "last_name": "Horigane", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Ohkura", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Gengyo-Ando", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kamijo", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Takemoto-Kimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Bito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nmeth.3185" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25419959" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinase Kinase", "descriptor_ui": "D054737", "major_topic": false }, { "descriptor": "Calmodulin-Binding Proteins", "descriptor_ui": "D002148", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Indicators and Reagents", "descriptor_ui": "D007202", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Peptide Fragments", "descriptor_ui": "D010446", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "64-70", "proceedings_title": null, "publisher": "", "title": "Nature methods", "volume": "12", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Rational design of a high-affinity, fast, red calcium indicator R-CaMP2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nonmuscle myosin heavy chain IIA (NMHC-IIA) has been reported to function as a herpes simplex virus 1 (HSV-1) entry coreceptor by interacting with viral envelope glycoprotein B (gB). Vertebrates have three genetically distinct isoforms of the NMHC-II, designated NMHC-IIA, NMHC-IIB, and NMHC-IIC. COS cells, which are readily infected by HSV-1, do not express NMHC-IIA but do express NMHC-IIB. This observation prompted us to investigate whether NMHC-IIB might associate with HSV-1 gB and be involved in an HSV-1 entry like NMHC-IIA. In these studies, we show that (i) NMHC-IIB coprecipitated with gB in COS-1 cells upon HSV-1 entry; (ii) a specific inhibitor of myosin light chain kinase inhibited cell surface expression of NMHC-IIB in COS-1 cells upon HSV-1 entry as well as HSV-1 infection, as reported with NMHC-IIA; (iii) overexpression of mouse NMHC-IIB in IC21 cells significantly increased their susceptibility to HSV-1 infection; and (iv) knockdown of NMHC-IIB in COS-1 cells inhibited HSV-1 infection as well as cell-cell fusion mediated by HSV-1 envelope glycoproteins. These results supported the hypothesis that, like NMHC-IIA, NMHC-IIB associated with HSV-1 gB and mediated HSV-1 entry. IMPORTANCE: Herpes simplex virus 1 (HSV-1) was reported to utilize nonmuscle myosin heavy chain IIA (NMHC-IIA) as an entry coreceptor associating with gB. Vertebrates have three genetically distinct isoforms of NMHC-II. In these isoforms, NMHC-IIB is of special interest since it highly expresses in neuronal tissue, one of the most important cellular targets of HSV-1 in vivo. In this study, we demonstrated that the ability to mediate HSV-1 entry appeared to be conserved in NMHC-II isoforms. These results may provide an insight into the mechanism by which HSV-1 infects a wide variety of cell types in vivo.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hirohata", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.03079-14" }, "pmcid": { "normalized": "PMC4300746" }, "pmid": { "normalized": "25428876" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Immunoprecipitation", "descriptor_ui": "D047468", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nonmuscle Myosin Type IIB", "descriptor_ui": "D024501", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Receptors, Virus", "descriptor_ui": "D011991", "major_topic": false }, { "descriptor": "Viral Envelope Proteins", "descriptor_ui": "D014759", "major_topic": false }, { "descriptor": "Virus Internalization", "descriptor_ui": "D053586", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015 Feb", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "1879-1888", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "89", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Nonmuscle myosin heavy chain IIb mediates herpes simplex virus 1 entry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have recently found that isolation-reared mice show hyperactivity during an encounter with an intruder. However, it is not known whether encounter-induced hyperactivity may model some aspects of psychiatric disorders. The present study examined the pharmacological profile of encounter-induced hyperactivity in isolation-reared mice. Encounter-induced hyperactivity was reduced by acute administration of various antidepressants including the tricyclic antidepressant desipramine (10 mg/kg), the selective serotonin (5-HT) reuptake inhibitors fluvoxamine (10 mg/kg) and paroxetine (10 mg/kg), the 5-HT/noradrenaline reuptake inhibitors venlafaxine (10 mg/kg) and duloxetine (10 mg/kg), the antipsychotic drug risperidone (0.01 mg/kg), the 5-HT2 antagonist ritanserin (1 mg/kg), and the glucocorticoid receptor antagonist RU-43044 (30 mg/kg). The alpha2 adrenoceptor agonist clonidine (0.03 mg/kg) and the 5-HT4 receptor agonist BIMU8 (30 mg/kg) also reduced encounter-induced hyperactivity. The effect of desipramine was blocked by the alpha2 adrenoceptor antagonist idazoxan (0.3 mg/kg). The effect of fluvoxamine was blocked by the 5-HT4 receptor antagonist GR125487 (3 mg/kg), but not the 5-HT1A receptor antagonist WAY100635 (1 mg/kg), the 5-HT3 receptor antagonist azasetron (3 mg/kg), or the 5-HT6 receptor antagonist SB399885 (3 mg/kg). The effect of venlafaxine was blocked by the simultaneous administration of idazoxan (0.3 mg/kg) and GR125487 (3 mg/kg), but not by either compound alone. These findings suggest that encounter-induced hyperactivity in isolation-reared mice is a robust model for testing the pharmacological profile of antidepressants, although the range of antidepressants tested is limited and some non-antidepressants are also effective. The present study also shows a key role of alpha2 and 5-HT4 receptors in the antidepressant effect in this model.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Saki", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/fbp.0000000000000140" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25932719" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Outbred Strains", "descriptor_ui": "D021461", "major_topic": false }, { "descriptor": "Benzimidazoles", "descriptor_ui": "D001562", "major_topic": false }, { "descriptor": "Bridged Bicyclo Compounds, Heterocyclic", "descriptor_ui": "D019086", "major_topic": false }, { "descriptor": "Desipramine", "descriptor_ui": "D003891", "major_topic": false }, { "descriptor": "Duloxetine Hydrochloride", "descriptor_ui": "D000068736", "major_topic": false }, { "descriptor": "Fluvoxamine", "descriptor_ui": "D016666", "major_topic": false }, { "descriptor": "Hydroxycorticosteroids", "descriptor_ui": "D006889", "major_topic": false }, { "descriptor": "Idazoxan", "descriptor_ui": "D019329", "major_topic": false }, { "descriptor": "Indoles", "descriptor_ui": "D007211", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Neuropsychological Tests", "descriptor_ui": "D009483", "major_topic": false }, { "descriptor": "Oxazines", "descriptor_ui": "D010078", "major_topic": false }, { "descriptor": "Paroxetine", "descriptor_ui": "D017374", "major_topic": false }, { "descriptor": "Piperazines", "descriptor_ui": "D010879", "major_topic": false }, { "descriptor": "Psychotropic Drugs", "descriptor_ui": "D011619", "major_topic": false }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false }, { "descriptor": "Risperidone", "descriptor_ui": "D018967", "major_topic": false }, { "descriptor": "Ritanserin", "descriptor_ui": "D016713", "major_topic": false }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": true }, { "descriptor": "Social Isolation", "descriptor_ui": "D012934", "major_topic": false }, { "descriptor": "Sulfonamides", "descriptor_ui": "D013449", "major_topic": false }, { "descriptor": "Venlafaxine Hydrochloride", "descriptor_ui": "D000069470", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Oct", "date_precision": "unknown", "issue": "7 Spec No", "normalized_date": null, "pages": "681-690", "proceedings_title": null, "publisher": "", "title": "Behavioural pharmacology", "volume": "26", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Pharmacological profile of encounter-induced hyperactivity in isolation-reared mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent advances in nanoscopy, which breaks the diffraction barrier and can visualize structures smaller than the diffraction limit in cells, have encouraged biologists to investigate cellular processes at molecular resolution. Since nanoscopy depends not only on special optics but also on 'smart' photophysical properties of photocontrollable fluorescent probes, including photoactivatability, photoswitchability and repeated blinking, it is important for biologists to understand the advantages and disadvantages of fluorescent probes and to choose appropriate ones for their specific requirements. Here, we summarize the characteristics of currently available fluorescent probes based on both proteins and synthetic compounds applicable to nanoscopy and provide a guideline for selecting optimal probes for specific applications.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shin-Nosuke", "last_name": "Uno", "name": null }, { "creator_type": "author", "first_name": "Dhermendra K.", "last_name": "Tiwari", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jmicro/dfv037" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26152215" } }, "mesh": [ { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Staining and Labeling", "descriptor_ui": "D013194", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "263-277", "proceedings_title": null, "publisher": "", "title": "Microscopy (Oxford, England)", "volume": "64", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "A guide to use photocontrollable fluorescent proteins and synthetic smart fluorophores for nanoscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An increase in the ratio of cellular excitation to inhibition (E/I ratio) has been proposed to underlie the pathogenesis of neuropsychiatric disorders, such as autism spectrum disorders (ASD), obsessive-compulsive disorder (OCD), and Tourette's syndrome (TS). A proper E/I ratio is achieved via factors expressed in neuron and glia. In astrocytes, the glutamate transporter GLT1 is critical for regulating an E/I ratio. However, the role of GLT1 dysfunction in the pathogenesis of neuropsychiatric disorders remains unknown because mice with a complete deficiency of GLT1 exhibited seizures and premature death. Here, we show that astrocyte-specific GLT1 inducible knockout (GLAST(CreERT2/+)/GLT1(flox/flox), iKO) mice exhibit pathological repetitive behaviors including excessive and injurious levels of self-grooming and tic-like head shakes. Electrophysiological studies reveal that excitatory transmission at corticostriatal synapse is normal in a basal state but is increased after repetitive stimulation. Furthermore, treatment with an N-methyl-D-aspartate (NMDA) receptor antagonist memantine ameliorated the pathological repetitive behaviors in iKO mice. These results suggest that astroglial GLT1 has a critical role in controlling the synaptic efficacy at corticostriatal synapses and its dysfunction causes pathological repetitive behaviors.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tomomi", "last_name": "Aida", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Asami", "last_name": "Tanimura", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Iino", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Soma", "name": null }, { "creator_type": "author", "first_name": "Ning", "last_name": "Bai", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Wanpeng", "last_name": "Cui", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Aizawa", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Terumi", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Kenji F.", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Takayanagi", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Magdalena", "last_name": "Gotz", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Hirase", "name": null }, { "creator_type": "author", "first_name": "Kohichi", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/npp.2015.26" }, "pmcid": { "normalized": "PMC4915262" }, "pmid": { "normalized": "25662838" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Anxiety", "descriptor_ui": "D001007", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": false }, { "descriptor": "Cumulative Trauma Disorders", "descriptor_ui": "D012090", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Excitatory Amino Acid Transporter 1", "descriptor_ui": "D027341", "major_topic": false }, { "descriptor": "Excitatory Amino Acid Transporter 2", "descriptor_ui": "D027342", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Hyperalgesia", "descriptor_ui": "D006930", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nerve Degeneration", "descriptor_ui": "D009410", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Seizures", "descriptor_ui": "D012640", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jun", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "1569-1579", "proceedings_title": null, "publisher": "", "title": "Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology", "volume": "40", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Astroglial glutamate transporter deficiency increases synaptic excitability and leads to pathological repetitive behaviors in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Autophagy is one of two major bulk protein degradation systems and is conserved throughout eukaryotes. The protozoan Entamoeba histolytica, which is a human intestinal parasite, possesses a restricted set of autophagy-related (Atg) proteins compared with other eukaryotes and thus represents a suitable model organism for studying the minimal essential components and ancestral functions of autophagy. E. histolytica possesses two conjugation systems: Atg8 and Atg5/12, although a gene encoding Atg12 is missing in the genome. Atg8 is considered to be the central and authentic marker of autophagosomes, but recent studies have demonstrated that Atg8 is not exclusively involved in autophagy per se, but other fundamental mechanisms of vesicular traffic. To investigate this question in E. histolytica, we studied on Atg8 during the proliferative stage. Atg8 was constitutively expressed in both laboratory-maintained and recently established clinical isolates and appeared to be lipid-modified in logarithmic growth phase, suggesting a role of Atg8 in non-stress and proliferative conditions. These findings are in contrast to those for Entamoeba invadens, in which autophagy is markedly induced during an early phase of differentiation from the trophozoite into the cyst. The repression of Atg8 gene expression in En. histolytica by antisense small RNA-mediated transcriptional gene silencing resulted in growth retardation, delayed endocytosis and reduced acidification of endosomes and phagosomes. Taken together, these results suggest that Atg8 and the Atg8 conjugation pathway have some roles in the biogenesis of endosomes and phagosomes in this primitive eukaryote.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Karina", "last_name": "Picazarri", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Nakada-Tsukui", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Nozaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cmi.12453" }, "pmcid": { "normalized": "PMC4744732" }, "pmid": { "normalized": "25923949" } }, "mesh": [ { "descriptor": "Endosomes", "descriptor_ui": "D011992", "major_topic": false }, { "descriptor": "Entamoeba histolytica", "descriptor_ui": "D004748", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Organelle Biogenesis", "descriptor_ui": "D001678", "major_topic": true }, { "descriptor": "Phagosomes", "descriptor_ui": "D010588", "major_topic": false }, { "descriptor": "Protozoan Proteins", "descriptor_ui": "D015800", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "1510-1522", "proceedings_title": null, "publisher": "", "title": "Cellular microbiology", "volume": "17", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Atg8 is involved in endosomal and phagosomal acidification in the parasitic protist Entamoeba histolytica.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The simultaneous observation of multiple fluorescent proteins (FPs) by optical microscopy is revealing mechanisms by which proteins and organelles control a variety of cellular functions. Here we show the use of visible-light based two-photon excitation for simultaneously imaging multiple FPs. We demonstrated that multiple fluorescent targets can be concurrently excited by the absorption of two photons from the visible wavelength range and can be applied in multicolor fluorescence imaging. The technique also allows simultaneous single-photon excitation to offer simultaneous excitation of FPs across the entire range of visible wavelengths from a single excitation source. The calculation of point spread functions shows that the visible-wavelength two-photon excitation provides the fundamental improvement of spatial resolution compared to conventional confocal microscopy.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masahito", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Uegaki", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Yonemaru", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1117/1.jbo.20.10.101202" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26238663" } }, "mesh": [ { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Equipment Failure Analysis", "descriptor_ui": "D019544", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Enhancement", "descriptor_ui": "D007089", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence, Multiphoton", "descriptor_ui": "D036641", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "101202", "proceedings_title": null, "publisher": "", "title": "Journal of biomedical optics", "volume": "20", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Visible-wavelength two-photon excitation microscopy for fluorescent protein imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have recently identified a metastasis suppressor gene for colorectal cancer: AES/Aes, which encodes an endogenous inhibitor of NOTCH signaling. When Aes is knocked out in the adenomatous epithelium of intestinal polyposis mice, their tumors become malignant, showing marked submucosal invasion and intravasation. Here, we show that one of the genes induced by NOTCH signaling in colorectal cancer is DAB1/Dab1. Genetic depletion of DAB1 suppresses cancer invasion and metastasis in the NOTCH signaling-activated mice. DAB1 is phosphorylated by ABL tyrosine kinase, which activates ABL reciprocally. Consistently, inhibition of ABL suppresses cancer invasion in mice. Furthermore, we show that one of the targets of ABL is the RAC/RHOGEF protein TRIO, and that phosphorylation at its Tyr residue 2681 (pY2681) causes RHO activation in colorectal cancer cells. Its unphosphorylatable mutation TRIO Y2681F reduces RHOGEF activity and inhibits invasion of colorectal cancer cells. Importantly, TRIO pY2681 correlates with significantly poorer prognosis of patients with colorectal cancer after surgery. SIGNIFICANCE: These results indicate that TRIO pY2681 is one of the downstream effectors of NOTCH signaling activation in colorectal cancer, and can be a prognostic marker, helping to determine the therapeutic modality of patients with colorectal cancer.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null }, { "creator_type": "author", "first_name": "Yoshiro", "last_name": "Itatani", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Kakizaki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Terashima", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Katsuyama", "name": null }, { "creator_type": "author", "first_name": "Yoshiharu", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "M. Mark", "last_name": "Taketo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/2159-8290.cd-14-0595" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25432929" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Guanine Nucleotide Exchange Factors", "descriptor_ui": "D020662", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Phosphoproteins", "descriptor_ui": "D010750", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Rho Guanine Nucleotide Exchange Factors", "descriptor_ui": "D064067", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "198-211", "proceedings_title": null, "publisher": "", "title": "Cancer discovery", "volume": "5", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Promotion of colorectal cancer invasion and metastasis through activation of NOTCH-DAB1-ABL-RHOGEF protein TRIO.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The filter-feeding crustacean Daphnia is a key organism in freshwater ecosystems. Here, we report the effect of symbiotic bacteria on ecologically important life history traits, such as population dynamics and longevity, in Daphnia magna. By disinfection of the daphniid embryos with glutaraldehyde, aposymbiotic daphniids were prepared and cultured under bacteria-free conditions. Removal of bacteria from the daphniids was monitored by quantitative polymerase chain reaction for bacterial 16S rRNA gene. The population of aposymbiotic daphniids was reduced 10-folds compared with that of the control daphniids. Importantly, re-infection with symbiotic bacteria caused daphniids to regain bacteria and increase their fecundity to the level of the control daphniids, suggesting that symbiotic bacteria regulate Daphnia fecundity. To identify the species of symbiotic bacteria, 16S rRNA genes of bacteria in daphniids were sequenced. This revealed that 50% of sequences belonged to the Limnohabitans sp. of the Betaproteobacteria class and that the diversity of bacterial taxa was relatively low. These results suggested that symbiotic bacteria have a beneficial effect on D. magna, and that aposymbiotic Daphnia are useful tools in understanding the role of symbiotic bacteria in the environmental responses and evolution of their hosts.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Saranya", "last_name": "Peerakietkhajorn", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/1758-2229.12260" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25534397" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": false }, { "descriptor": "Bacterial Physiological Phenomena", "descriptor_ui": "D018407", "major_topic": true }, { "descriptor": "Betaproteobacteria", "descriptor_ui": "D020562", "major_topic": false }, { "descriptor": "Biota", "descriptor_ui": "D058448", "major_topic": false }, { "descriptor": "Comamonadaceae", "descriptor_ui": "D042621", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "DNA, Bacterial", "descriptor_ui": "D004269", "major_topic": false }, { "descriptor": "DNA, Ribosomal", "descriptor_ui": "D004275", "major_topic": false }, { "descriptor": "Fertility", "descriptor_ui": "D005298", "major_topic": false }, { "descriptor": "Fresh Water", "descriptor_ui": "D005618", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Population Density", "descriptor_ui": "D011156", "major_topic": false }, { "descriptor": "RNA, Ribosomal, 16S", "descriptor_ui": "D012336", "major_topic": false }, { "descriptor": "Sequence Analysis, DNA", "descriptor_ui": "D017422", "major_topic": false }, { "descriptor": "Symbiosis", "descriptor_ui": "D013559", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "364-372", "proceedings_title": null, "publisher": "", "title": "Environmental microbiology reports", "volume": "7", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Symbiotic bacteria contribute to increasing the population size of a freshwater crustacean, Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have previously reported that an adaptor protein CRK, including CRK-I and CRK-II, plays essential roles in the malignant potential of various aggressive human cancers, suggesting the validity of targeting CRK in molecular targeted therapy of a wide range of cancers. Nevertheless, the role of CRK in human bladder cancer with marked invasion, characterized by distant metastasis and poor prognosis, remains obscure. In the present study, immunohistochemistry indicated a striking enhancement of CRK-I/-II, but not CRK-like, in human bladder cancer tissues compared to normal urothelium. We established CRK-knockdown bladder cancer cells using 5637 and UM-UC-3, which showed a significant decline in cell migration, invasion, and proliferation. It is noteworthy that an elimination of CRK conferred suppressed phosphorylation of c-Met and the downstream scaffold protein Gab1 in a hepatocyte growth factor-dependent and -independent manner. In epithelial-mesenchymal transition-related molecules, E-cadherin was upregulated by CRK elimination, whereas N-cadherin, vimentin, and Zeb1 were downregulated. A similar effect was observed following treatment with c-Met inhibitor SU11274. Depletion of CRK significantly decreased cell proliferation of 5637 and UM-UC-3, consistent with reduced activity of ERK. An orthotopic xenograft model with bioluminescent imaging revealed that CRK knockdown significantly attenuated not only tumor volume but also the number of circulating tumor cells, resulted in a complete abrogation of metastasis. Taken together, this evidence uncovered essential roles of CRK in invasive bladder cancer through the hepatocyte growth factor/c-Met/CRK feedback loop for epithelial-mesenchymal transition induction. Thus, CRK might be a potent molecular target in bladder cancer, particularly for preventing metastasis, leading to the resolution of clinically longstanding critical issues.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryuji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Nako", "last_name": "Maishi", "name": null }, { "creator_type": "author", "first_name": "Takashige", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Taichi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Mishie", "last_name": "Tanino", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nishihara", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Hida", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Nobuo", "last_name": "Shinohara", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Nonomura", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.12662" }, "pmcid": { "normalized": "PMC4471787" }, "pmid": { "normalized": "25816892" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Epithelial-Mesenchymal Transition", "descriptor_ui": "D058750", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hepatocyte Growth Factor", "descriptor_ui": "D017228", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false }, { "descriptor": "Neoplastic Cells, Circulating", "descriptor_ui": "D009360", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-crk", "descriptor_ui": "D050737", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-met", "descriptor_ui": "D019859", "major_topic": false }, { "descriptor": "Urinary Bladder Neoplasms", "descriptor_ui": "D001749", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "709-717", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "106", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Adaptor protein CRK induces epithelial-mesenchymal transition and metastasis of bladder cancer cells through HGF/c-Met feedback loop.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have found that fluvoxamine-induced increases in prefrontal dopamine release are enhanced by adrenalectomy/castration and 5-HT1A receptors are involved in the enhancement. This study examined which 5-HT1A autoreceptors or postsynaptic receptor play a key role in the enhancement in mice. Adrenalectomy/castration-induced enhancement of fluvoxamine-induced increase in the dopamine release was not blocked by local perfusion with the 5-HT1A receptor antagonist WAY100635 (10 muM), while it was blocked by systemic administration of WAY100635 at low dose (0.1 mg/kg) which blocked preferentially autoreceptor-mediated responses. These finding suggests that 5-HT1A autoreceptors play a key role in the enhancement of prefrontal dopamine release.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Hiramatsu", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Watabe", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphs.2015.01.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25727963" } }, "mesh": [ { "descriptor": "Adrenalectomy", "descriptor_ui": "D000315", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Castration", "descriptor_ui": "D002369", "major_topic": true }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Fluvoxamine", "descriptor_ui": "D016666", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred Strains", "descriptor_ui": "D008815", "major_topic": false }, { "descriptor": "Piperazines", "descriptor_ui": "D010879", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false }, { "descriptor": "Receptor, Serotonin, 5-HT1A", "descriptor_ui": "D044282", "major_topic": false }, { "descriptor": "Selective Serotonin Reuptake Inhibitors", "descriptor_ui": "D017367", "major_topic": false }, { "descriptor": "Serotonin 5-HT1 Receptor Antagonists", "descriptor_ui": "D058829", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "232-235", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "127", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of the 5-HT1A autoreceptor in the enhancement of fluvoxamine-induced increases in prefrontal dopamine release by adrenalectomy/castration in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Influenza viruses present major challenges to public health, evident by the 2009 influenza pandemic. Highly pathogenic influenza virus infections generally coincide with early, high levels of inflammatory cytokines that some studies have suggested may be regulated in a strain-dependent manner. However, a comprehensive characterization of the complex dynamics of the inflammatory response induced by virulent influenza strains is lacking. Here, we applied gene co-expression and nonlinear regression analysis to time-course, microarray data developed from influenza-infected mouse lung to create mathematical models of the host inflammatory response. We found that the dynamics of inflammation-associated gene expression are regulated by an ultrasensitive-like mechanism in which low levels of virus induce minimal gene expression but expression is strongly induced once a threshold virus titer is exceeded. Cytokine assays confirmed that the production of several key inflammatory cytokines, such as interleukin 6 and monocyte chemotactic protein 1, exhibit ultrasensitive behavior. A systematic exploration of the pathways regulating the inflammatory-associated gene response suggests that the molecular origins of this ultrasensitive response mechanism lie within the branch of the Toll-like receptor pathway that regulates STAT1 phosphorylation. This study provides the first evidence of an ultrasensitive mechanism regulating influenza virus-induced inflammation in whole lungs and provides insight into how different virus strains can induce distinct temporal inflammation response profiles. The approach developed here should facilitate the construction of gene regulatory models of other infectious diseases.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Jason E.", "last_name": "Shoemaker", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fukuyama", "name": null }, { "creator_type": "author", "first_name": "Amie J.", "last_name": "Eisfeld", "name": null }, { "creator_type": "author", "first_name": "Dongming", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Sakabe", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Maemura", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Gorai", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Katsura", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Muramoto", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tokiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Fuji", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kawaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.ppat.1004856" }, "pmcid": { "normalized": "PMC4457877" }, "pmid": { "normalized": "26046528" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Influenza A Virus, H1N1 Subtype", "descriptor_ui": "D053118", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Orthomyxoviridae Infections", "descriptor_ui": "D009976", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false }, { "descriptor": "Virulence", "descriptor_ui": "D014774", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "e1004856", "proceedings_title": null, "publisher": "", "title": "PLoS pathogens", "volume": "11", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "An Ultrasensitive Mechanism Regulates Influenza Virus-Induced Inflammation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Arginine vasopressin (AVP) is a neurohypophysial hormone synthesized as a part of a prepropeptide precursor containing the signal peptide, AVP hormone, AVP-associated neurophysin II and copeptin in the hypothalamic neurosecretory neurons. A transgenic (Tg) rat line expressing the AVP-eGFP fusion gene has been generated. To establish the AVP-eGFP Tg rat as a unique model for an analysis of AVP dynamics in vivo, we first examined the in vivo molecular dynamics of the AVP-eGFP fusion gene, and then the release of GFP in response to physiological stimuli. Double immunoelectron microscopy demonstrated that GFP was specifically localized in neurosecretory vesicles of AVP neurons in this Tg rat. After stimulation of the posterior pituitary with high potassium we demonstrated the exocytosis of AVP neurosecretory vesicles containing GFP at the ultrastructural level. Biochemical analyses indicated that the AVP-eGFP fusion gene is subjected to in vivo post-translational modifications like the native AVP gene, and is packaged into neurosecretory vesicles as a fusion protein: copeptin1-14 -GFP. Moreover, GFP release into the circulating blood appeared to be augmented after osmotic stimulation, like native AVP. Thus, here we show for the first time the in vivo molecular processing of the AVP-eGFP fusion gene and stimulated secretion after osmotic stimulation in rats. Because GFP behaved like native AVP in the hypothalamo-pituitary axis, and in particular was released into the circulation in response to a physiological stimulus, the AVP-eGFP Tg rat model appears to be a powerful tool for analyzing neuroendocrine systems at the organismal level.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Keita", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Oti", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Katoh", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Ueta", "name": null }, { "creator_type": "author", "first_name": "John F.", "last_name": "Morris", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/febs.13291" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25846300" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arginine Vasopressin", "descriptor_ui": "D001127", "major_topic": false }, { "descriptor": "Exocytosis", "descriptor_ui": "D005089", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microscopy, Immunoelectron", "descriptor_ui": "D016253", "major_topic": false }, { "descriptor": "Osmolar Concentration", "descriptor_ui": "D009994", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Transgenic", "descriptor_ui": "D055647", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jul", "date_precision": "unknown", "issue": "13", "normalized_date": null, "pages": "2488-2499", "proceedings_title": null, "publisher": "", "title": "The FEBS journal", "volume": "282", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "In vivo processing and release into the circulation of GFP fusion protein in arginine vasopressin enhanced GFP transgenic rats: response to osmotic stimulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report habenular lateralization in a simple transgenic mouse model used for labeling a facet of neuronal activity history. A transgenic construct comprised of a zif268/egr1 immediate-early gene promoter and a gene for normal Venus fluorescent protein with a membrane tag converted promoter activity into long-life fluorescent proteins, which was thought to describe a facet of neuronal activity history by summing neuronal activity. In addition to mapping the immediate-early gene-immunopositive cells, this method helped demonstrate the functionality of the lateral habenular nucleus (LHb). During postnatal development, the LHb was activated between postnatal days 10 and 16. The water-immersion restraint stress also activated the LHb over a similar period. LHb activation was functionally lateralized, but had no directional bias at the population level. Moreover, the posterior LHb was activated in the early stage after the stress, while the anterior LHb was activated in the later stage. Our results indicate lateralization, maturation, and anteroposterior topography of the LHb during postnatal development and the stress response.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Ichijo", "name": null }, { "creator_type": "author", "first_name": "Michito", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Masahumi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2015.01.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25637311" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Early Growth Response Protein 1", "descriptor_ui": "D051766", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": false }, { "descriptor": "Functional Laterality", "descriptor_ui": "D007839", "major_topic": false }, { "descriptor": "Habenula", "descriptor_ui": "D019262", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Restraint, Physical", "descriptor_ui": "D012149", "major_topic": false }, { "descriptor": "Staining and Labeling", "descriptor_ui": "D013194", "major_topic": false }, { "descriptor": "Stress, Psychological", "descriptor_ui": "D013315", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jun", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "27-37", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "95", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Lateralization, maturation, and anteroposterior topography in the lateral habenula revealed by ZIF268/EGR1 immunoreactivity and labeling history of neuronal activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Endocannabinoids are lipid-derived messengers, and both their synthesis and breakdown are under tight spatiotemporal regulation. As retrograde signalling molecules, endocannabinoids are synthesized postsynaptically but activate presynaptic cannabinoid receptor 1 (CB1) receptors to inhibit neurotransmitter release. In turn, CB1-expressing inhibitory and excitatory synapses act as strategically placed control points for activity-dependent regulation of dynamically changing normal and pathological oscillatory network activity. Here, we highlight emerging principles of cannabinoid circuit control and plasticity, and discuss their relevance for epilepsy and related comorbidities. New insights into cannabinoid signalling may facilitate the translation of the recent interest in cannabis-related substances as antiseizure medications to evidence-based treatment strategies.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ivan", "last_name": "Soltesz", "name": null }, { "creator_type": "author", "first_name": "Bradley E.", "last_name": "Alger", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Sang-Hun", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "David M.", "last_name": "Lovinger", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Ohno-Shosaku", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nrn3937" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25891509" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Brain Waves", "descriptor_ui": "D058256", "major_topic": true }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": false }, { "descriptor": "Epilepsy", "descriptor_ui": "D004827", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Receptor, Cannabinoid, CB1", "descriptor_ui": "D043884", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "264-277", "proceedings_title": null, "publisher": "", "title": "Nature reviews. Neuroscience", "volume": "16", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Weeding out bad waves: towards selective cannabinoid circuit control in epilepsy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "What is the central question of this study? Pilocarpine stimulates salivary secretion via muscarinic ACh receptors (mAChRs), although the Ca(2+) -mobilizing effect of pilocarpine in salivary gland cells is extremely small. Therefore, we examined the effect of pilocarpine on Ca(2+) responses in submandibular gland cells and on secretion in vitro and in vivo. What is the main finding and its importance? Pilocarpine induces small Ca(2+) responses and reduces the effects of other mAChR agonists on Ca(2+) responses via its partial agonistic effects. These effects of pilocarpine on Ca(2+) responses in the submandibular gland were further established in vivo with a novel Ca(2+) imaging system and a genetically encoded Ca(2+) indicator. Pilocarpine stimulates salivary secretion via muscarinic ACh receptors (mAChRs), although the effect of pilocarpine on Ca(2+) responses in dispersed salivary gland cells is extremely small. Here, we demonstrate the effect of pilocarpine on Ca(2+) responses and salivary secretion in the rat submandibular gland (SMG). In fura-2-loaded SMG cells, the maximal effect of pilocarpine on [Ca(2+) ]i elevation was 16% of that of carbachol, and pilocarpine attenuated carbachol- and bethanechol (Bet)-induced [Ca(2+) ]i increases, indicating that pilocarpine acts as a partial agonist for mAChR-mediated Ca(2+) responses. The partial agonistic effect of pilocarpine on Ca(2+) dynamics in the SMG was also confirmed in live animals using the genetically encoded Ca(2+) indicator, YC-Nano50. Administration of pilocarpine (3 mg kg(-1) , i.p.) elicited a small increase in [Ca(2+) ]i in the SMG. Quantitative analyses demonstrated that resting [Ca(2+) ]i was approximately 37 nm, which was increased by pilocarpine (3 mg kg(-1) ) and Bet (10 mg kg(-1) ) to 44 and 69 nm, respectively. The inhibitory effects of pilocarpine on Bet-induced Ca(2+) responses were also elucidated in vivo. We further examined real-time changes in pilocarpine-induced SMG salivary secretion and showed that pilocarpine induced an extremely weak secretory response and reduced Bet-induced secretion. Unlike Ca(2+) responses, pilocarpine failed to reduce the effect of Bet on SMG blood flow. Our results demonstrate that pilocarpine acts as a partial agonist of mAChRs to induce weak salivary secretion that is correlated with small increases in [Ca(2+) ]i . Furthermore, pilocarpine exhibits an antagonistic effect on mAChR-induced Ca(2+) responses and salivary secretion.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Akihiro", "last_name": "Nezu", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Tojyo", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Tanimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1113/ep085110" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25886199" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bethanechol", "descriptor_ui": "D018723", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Carbachol", "descriptor_ui": "D002217", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Drug Partial Agonism", "descriptor_ui": "D054333", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Muscarinic Agonists", "descriptor_ui": "D018721", "major_topic": false }, { "descriptor": "Pilocarpine", "descriptor_ui": "D010862", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Receptors, Muscarinic", "descriptor_ui": "D011976", "major_topic": false }, { "descriptor": "Saliva", "descriptor_ui": "D012463", "major_topic": false }, { "descriptor": "Salivation", "descriptor_ui": "D012472", "major_topic": false }, { "descriptor": "Submandibular Gland", "descriptor_ui": "D013363", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "640-651", "proceedings_title": null, "publisher": "", "title": "Experimental physiology", "volume": "100", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Partial agonistic effects of pilocarpine on Ca(2+) responses and salivary secretion in the submandibular glands of live animals.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We studied the role of the Src SH3 domain in its dynamics at the cell membrane using site-directed mutagenesis and live cell imaging. Physiologically, cell proliferation and migration require the expression of Src family kinases. Hyperactivation of Src molecules has been detected in various cancer cells. Although the activation mechanism of Src has been intensively studied, the dynamics of Src at the cell membrane are still unclear. Although Src molecules also exist at various cellular locations, we found that activated Src molecules are mainly localized at peripheral cell adhesion sites. Src phosphorylation status and subdomain conformations are thought to regulate Src activation and translocation. In this study, we analyzed the single-molecule dynamics of wild-type Src and SH2- and SH3-mutated Src at the cell membrane. Introducing mutations in the SH3 domain resulted in reduced Src motility at the cell membrane, both inside and outside of focal adhesions. Disruption of the actin cytoskeleton resulted in less diffusive Src movement at the cell membrane. We demonstrate that, inside focal adhesions, the SH3 domain enhanced dissociation of Src from the adhesion site and disruption of the SH3 domain altered the distribution of Src at the cell membrane. Inside focal adhesions, kinase activity of Src was essential for the Src mobility reduction by SH3 domain mutation, suggesting that rapid mobility of Src at focal adhesions mediated by the SH3 domain is catalytic-activity-dependent. These findings show that the SH3 domain of Src governs the dynamics of Src at the cell membrane and may be involved in rapid signal transduction in cells.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Machiyama", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Sawada", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/febs.13404" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26258764" } }, "mesh": [ { "descriptor": "Amino Acid Substitution", "descriptor_ui": "D019943", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "CSK Tyrosine-Protein Kinase", "descriptor_ui": "D000081247", "major_topic": false }, { "descriptor": "Focal Adhesions", "descriptor_ui": "D022001", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Mutagenesis, Site-Directed", "descriptor_ui": "D016297", "major_topic": false }, { "descriptor": "Mutant Proteins", "descriptor_ui": "D050505", "major_topic": false }, { "descriptor": "Paxillin", "descriptor_ui": "D051419", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "src Homology Domains", "descriptor_ui": "D018909", "major_topic": false }, { "descriptor": "src-Family Kinases", "descriptor_ui": "D019061", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Oct", "date_precision": "unknown", "issue": "20", "normalized_date": null, "pages": "4034-4055", "proceedings_title": null, "publisher": "", "title": "The FEBS journal", "volume": "282", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "SH3 domain of c-Src governs its dynamics at focal adhesions and the cell membrane.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The breast section of these Guidelines and Recommendations for Elastography produced under the auspices of the World Federation of Ultrasound in Medicine and Biology (WFUMB) assesses the clinically used applications of all forms of elastography used in breast imaging. The literature on various breast elastography techniques is reviewed, and recommendations are made on evidence-based results. Practical advice is given on how to perform and interpret breast elastography for optimal results, with emphasis placed on avoiding pitfalls. Artifacts are reviewed, and the clinical utility of some artifacts is discussed. Both strain and shear wave techniques have been shown to be highly accurate in characterizing breast lesions as benign or malignant. The relationship between the various techniques is discussed, and recommended interpretation based on a BI-RADS-like malignancy probability scale is provided. This document is intended to be used as a reference and to guide clinical users in a practical way.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Richard G.", "last_name": "Barr", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Dominique", "last_name": "Amy", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Cosgrove", "name": null }, { "creator_type": "author", "first_name": "Andre", "last_name": "Farrokh", "name": null }, { "creator_type": "author", "first_name": "Fritz", "last_name": "Schafer", "name": null }, { "creator_type": "author", "first_name": "Jeffrey C.", "last_name": "Bamber", "name": null }, { "creator_type": "author", "first_name": "Laurent", "last_name": "Castera", "name": null }, { "creator_type": "author", "first_name": "Byung Ihn", "last_name": "Choi", "name": null }, { "creator_type": "author", "first_name": "Yi-Hong", "last_name": "Chou", "name": null }, { "creator_type": "author", "first_name": "Christoph F.", "last_name": "Dietrich", "name": null }, { "creator_type": "author", "first_name": "Hong", "last_name": "Ding", "name": null }, { "creator_type": "author", "first_name": "Giovanna", "last_name": "Ferraioli", "name": null }, { "creator_type": "author", "first_name": "Carlo", "last_name": "Filice", "name": null }, { "creator_type": "author", "first_name": "Mireen", "last_name": "Friedrich-Rust", "name": null }, { "creator_type": "author", "first_name": "Timothy J.", "last_name": "Hall", "name": null }, { "creator_type": "author", "first_name": "Kathryn R.", "last_name": "Nightingale", "name": null }, { "creator_type": "author", "first_name": "Mark L.", "last_name": "Palmeri", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Ioan", "last_name": "Sporea", "name": null }, { "creator_type": "author", "first_name": "Stephanie", "last_name": "Wilson", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Kudo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ultrasmedbio.2015.03.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25795620" } }, "mesh": [ { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Elastic Modulus", "descriptor_ui": "D055119", "major_topic": false }, { "descriptor": "Elasticity Imaging Techniques", "descriptor_ui": "D054459", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Internationality", "descriptor_ui": "D038622", "major_topic": false }, { "descriptor": "Mammography", "descriptor_ui": "D008327", "major_topic": false }, { "descriptor": "Practice Guidelines as Topic", "descriptor_ui": "D017410", "major_topic": true }, { "descriptor": "Radiology", "descriptor_ui": "D011871", "major_topic": false }, { "descriptor": "Shear Strength", "descriptor_ui": "D033081", "major_topic": false }, { "descriptor": "Stress, Mechanical", "descriptor_ui": "D013314", "major_topic": false }, { "descriptor": "Tensile Strength", "descriptor_ui": "D013718", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "1148-1160", "proceedings_title": null, "publisher": "", "title": "Ultrasound in medicine & biology", "volume": "41", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 2: breast.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bioimaging requires not only high sensitivity but also minimal invasiveness. Bioimaging using luminescent proteins is potentially free from problems such as photo-induced damage or an undesirable physical reaction to the sample, which are often caused by illumination with an external light required in fluorescence imaging. The recent development of several luminescent proteins and substrates have greatly improved the brightness of luminescence imaging, facilitating its application by many researchers. In this short review, we summarize recent advances in development of luminescent proteins, substrates, and indicators.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kenta", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cbpa.2015.05.029" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26094043" } }, "mesh": [ { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Drug Discovery", "descriptor_ui": "D055808", "major_topic": true }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Aug", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "46-51", "proceedings_title": null, "publisher": "", "title": "Current opinion in chemical biology", "volume": "27", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Recent progress in luminescent proteins development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This data article contains complementary figure and movies (Supplementary Movies 1-3) related to the research article entitled, \"Effective synaptome analysis of itch-mediating neurons in the spinal cord: a novel immunohistochemical methodology using high-voltage electron microscopy\" [7]. It is important to show the synaptic connections at the ultrastructural level to understand the neural circuit, which requires the three-dimensional (3-D) analyses in the electron microscopy. Here, we applied a new sample preparation method, a high-contrast en bloc staining according to the protocol of the National Center for Microscopy and Imaging Research (NCMIR), University of California, San Diego, CA, USA to high-voltage electron microscopy (HVEM) tomography in order to examine the 3-D chemical neuroanatomy of the rat spinal cord. Pre-embedding immunoelectron microscopy was used in this study. HVEM has an excellent potential to directly visualize the ultrastructures in semi-thin sections (~5 mum thick), and we have successfully visualized many itch-mediating synaptic connections and neural networks in the spinal cord using \"HVEM tomography\". Moreover, the methodology used in this study is simple and can be applied in multiple ways. This is an important contribution to ultrastructural investigations of the central nervous system in the present post-genomic age.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Keita", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Takanami", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.dib.2015.07.005" }, "pmcid": { "normalized": "PMC4539164" }, "pmid": { "normalized": "26288803" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015 Sep", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "566-570", "proceedings_title": null, "publisher": "", "title": "Data in brief", "volume": "4", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Three-dimensional visualization of multiple synapses in thick sections using high-voltage electron microscopy in the rat spinal cord.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Replacement of the herpes simplex virus 1 small capsid protein VP26 phosphorylation site Thr-111 with alanine reduced viral replication and neurovirulence to levels observed with the VP26 null mutation. This mutation reduced VP26 expression and mislocalized VP26 and its binding partner, the major capsid protein VP5, in the nucleus. VP5 mislocalization was also observed with the VP26 null mutation. Thus, we postulate that phosphorylation of VP26 at Thr-111 regulates VP26 function in vitro and in vivo.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kozuka-Hata", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00547-15" }, "pmcid": { "normalized": "PMC4442450" }, "pmid": { "normalized": "25810545" } }, "mesh": [ { "descriptor": "Amino Acid Substitution", "descriptor_ui": "D019943", "major_topic": false }, { "descriptor": "Capsid Proteins", "descriptor_ui": "D036022", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015 Jun", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "6141-6147", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "89", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Function of the Herpes Simplex Virus 1 Small Capsid Protein VP26 Is Regulated by Phosphorylation at a Specific Site.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A mutation in herpes simplex virus 1 dUTPase (vdUTPase), which precluded its phosphorylation at Ser-187, decreased viral neurovirulence and increased mutation frequency in progeny virus genomes in the brains of mice where endogenous cellular dUTPase activity was relatively low, and overexpression of cellular dUTPase restored viral neurovirulence and mutation frequency altered by the mutation. Thus, phosphorylation of vdUTPase appeared to regulate viral virulence and genome integrity by compensating for low cellular dUTPase activity in vivo. IMPORTANCE: Many DNA viruses encode a homolog of host cell dUTPases, which are known to function in accurate replication of cellular DNA genomes. The viral dUTPase activity has long been assumed to play a role in viral replication by preventing mutations in progeny virus genomes if cellular dUTPase activity was not sufficient. Here, we showed that a mutation in herpes simplex virus 1 dUTPase, which precluded its phosphorylation at Ser-187 and reduced its activity, decreased viral neurovirulence and increased mutation frequency in progeny virus genomes in the brains of mice where endogenous cellular dUTPase activity was relatively low. In contrast, overexpression of cellular dUTPase restored viral neurovirulence and mutation frequency altered by the mutation in the brains of mice. This is the first report, to our knowledge, directly showing that viral dUTPase activity regulates viral genome integrity and pathogenicity by compensating for insufficient cellular dUTPase activity in vivo.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.02497-14" }, "pmcid": { "normalized": "PMC4301107" }, "pmid": { "normalized": "25320299" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Central Nervous System", "descriptor_ui": "D002490", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genomic Instability", "descriptor_ui": "D042822", "major_topic": true }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mutant Proteins", "descriptor_ui": "D050505", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": true }, { "descriptor": "Pyrophosphatases", "descriptor_ui": "D011755", "major_topic": false }, { "descriptor": "Survival Analysis", "descriptor_ui": "D016019", "major_topic": false }, { "descriptor": "Viral Load", "descriptor_ui": "D019562", "major_topic": false }, { "descriptor": "Virulence", "descriptor_ui": "D014774", "major_topic": false }, { "descriptor": "Virulence Factors", "descriptor_ui": "D037521", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "241-248", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "89", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Phosphorylation of herpes simplex virus 1 dUTPase regulates viral virulence and genome integrity by compensating for low cellular dUTPase activity in the central nervous system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Parkinson's disease (PD) is a neurodegenerative disorder resulting from mitochondrial dysfunction in dopaminergic neurons. Mitochondria are believed to be responsible for cellular Mg(2)(+) homeostasis. Mg(2)(+) is indispensable for maintaining ordinal cellular functions, hence perturbation of the cellular Mg(2)(+) homeostasis may be responsible for the disorders of physiological functions and diseases including PD. However, the changes in intracellular Mg(2)(+) concentration ([Mg(2)(+)]i) and the role of Mg(2)(+) in PD have still been obscure. In this study, we investigated [Mg(2)(+)]i and its effect on neurodegeneration in the 1-methyl-4-phenylpyridinium (MPP(+)) model of PD in differentiated PC12 cells. Application of MPP(+) induced an increase in [Mg(2)(+)]i immediately via two different pathways: Mg(2)(+) release from mitochondria and Mg(2)(+) influx across cell membrane, and the increased [Mg(2)(+)]i sustained for more than 16 h after MPP(+) application. Suppression of Mg(2)(+) influx decreased the viability of the cells exposed to MPP(+). The cell viability correlated highly with [Mg(2)(+)]i. In the PC12 cells with suppressed Mg(2)(+) influx, ATP concentration decreased and the amount of reactive oxygen species (ROS) increased after an 8h exposure to MPP(+). Our results indicate that the increase in [Mg(2)(+)]i inhibited cellular ROS generation and maintained ATP production, which resulted in the protection from MPP(+) toxicity.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbamcr.2015.08.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26319097" } }, "mesh": [ { "descriptor": "1-Methyl-4-phenylpyridinium", "descriptor_ui": "D015655", "major_topic": false }, { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Parkinson Disease", "descriptor_ui": "D010300", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "3182-3191", "proceedings_title": null, "publisher": "", "title": "Biochimica et biophysica acta", "volume": "1853", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Intracellular magnesium level determines cell viability in the MPP(+) model of Parkinson's disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tumor progression is classically viewed as the Darwinian evolution of subclones that sequentially acquire genetic mutations and autonomously overproliferate. However, growing evidence suggests that tumor microenvironment and subclone heterogeneity contribute to non-autonomous tumor progression. Recent Drosophila studies revealed a common mechanism by which clones of genetically altered cells trigger non-autonomous overgrowth. Such \"oncogenic niche cells\" (ONCs) do not overgrow but instead stimulate neighbor overgrowth and metastasis. Establishment of ONCs depends on competition and cooperation between heterogeneous cell populations. This review characterizes diverse ONCs identified in Drosophila and describes the genetic basis of non-autonomous tumor progression. Similar mechanisms may contribute to mammalian cancer progression and recurrence.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masato", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "John", "last_name": "Vaughen", "name": null }, { "creator_type": "author", "first_name": "Tatsushi", "last_name": "Igaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.12816" }, "pmcid": { "normalized": "PMC4714670" }, "pmid": { "normalized": "26362609" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1651-1658", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "106", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Non-autonomous overgrowth by oncogenic niche cells: Cellular cooperation and competition in tumorigenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Previous studies have shown that inhibitors of the Na(+)/Ca(2+) exchanger (NCX) attenuate seizure activity in drug-induced epilepsy models, but the role of NCX in epilepsy is not fully understood. The present study examined the effects of pentylenetetrazole (PTZ)-induced kindling on the mRNA expression of NCX isoforms (NCX1, NCX2 and NCX3) in mouse brain. Chronic administration of PTZ at 40mg/kg resulted in kindling seizure development. It caused decreases in the mRNA levels of NCX1 and NCX2, but not NCX3, in the hippocampus. Changes in NCX isoform expression levels were not observed in the prefrontal cortex or striatum. Acute PTZ at 40mg/kg, which caused little seizure activity, also decreased NCX2, but not NCX1 mRNA levels in the hippocampus. These results suggest that down-regulation of hippocampal NCX1 expression is associated with PTZ-induced kindling seizure development.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takuya", "last_name": "Kawanai", "name": null }, { "creator_type": "author", "first_name": "Atsuki", "last_name": "Taruta", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Ooi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.eplepsyres.2015.06.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26220386" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Corpus Striatum", "descriptor_ui": "D003342", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Kindling, Neurologic", "descriptor_ui": "D007696", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Pentylenetetrazole", "descriptor_ui": "D010433", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "RNA Isoforms", "descriptor_ui": "D059368", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Seizures", "descriptor_ui": "D012640", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Sep", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "109-112", "proceedings_title": null, "publisher": "", "title": "Epilepsy research", "volume": "115", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Decreased expression of hippocampal Na(+)/Ca(2)(+) exchanger isoform-1 by pentylenetetrazole kindling in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Hirooka", "name": null }, { "creator_type": "author", "first_name": "Takamichi", "last_name": "Kuwahara", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Irisawa", "name": null }, { "creator_type": "author", "first_name": "Fumihide", "last_name": "Itokawa", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Sasahira", "name": null }, { "creator_type": "author", "first_name": "Natsuko", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10396-014-0595-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26576569" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "175", "proceedings_title": null, "publisher": "", "title": "Journal of medical ultrasonics (2001)", "volume": "42", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Erratum to: JSUM ultrasound elastography practice guidelines: pancreas.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Conventional diagnostic ultrasound images of the anatomy (as opposed to blood flow) reveal differences in the acoustic properties of soft tissues (mainly echogenicity but also, to some extent, attenuation), whereas ultrasound-based elasticity images are able to reveal the differences in the elastic properties of soft tissues (e.g., elasticity and viscosity). The benefit of elasticity imaging lies in the fact that many soft tissues can share similar ultrasonic echogenicities but may have different mechanical properties that can be used to clearly visualize normal anatomy and delineate pathologic lesions. Typically, all elasticity measurement and imaging methods introduce a mechanical excitation and monitor the resulting tissue response. Some of the most widely available commercial elasticity imaging methods are 'quasi-static' and use external tissue compression to generate images of the resulting tissue strain (or deformation). In addition, many manufacturers now provide shear wave imaging and measurement methods, which deliver stiffness images based upon the shear wave propagation speed. The goal of this review is to describe the fundamental physics and the associated terminology underlying these technologies. We have included a questions and answers section, an extensive appendix, and a glossary of terms in this manuscript. We have also endeavored to ensure that the terminology and descriptions, although not identical, are broadly compatible across the WFUMB and EFSUMB sets of guidelines on elastography (Bamber et al. 2013; Cosgrove et al. 2013).", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Kathryn R.", "last_name": "Nightingale", "name": null }, { "creator_type": "author", "first_name": "Mark L.", "last_name": "Palmeri", "name": null }, { "creator_type": "author", "first_name": "Timothy J.", "last_name": "Hall", "name": null }, { "creator_type": "author", "first_name": "Jeffrey C.", "last_name": "Bamber", "name": null }, { "creator_type": "author", "first_name": "Richard G.", "last_name": "Barr", "name": null }, { "creator_type": "author", "first_name": "Laurent", "last_name": "Castera", "name": null }, { "creator_type": "author", "first_name": "Byung Ihn", "last_name": "Choi", "name": null }, { "creator_type": "author", "first_name": "Yi-Hong", "last_name": "Chou", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Cosgrove", "name": null }, { "creator_type": "author", "first_name": "Christoph F.", "last_name": "Dietrich", "name": null }, { "creator_type": "author", "first_name": "Hong", "last_name": "Ding", "name": null }, { "creator_type": "author", "first_name": "Dominique", "last_name": "Amy", "name": null }, { "creator_type": "author", "first_name": "Andre", "last_name": "Farrokh", "name": null }, { "creator_type": "author", "first_name": "Giovanna", "last_name": "Ferraioli", "name": null }, { "creator_type": "author", "first_name": "Carlo", "last_name": "Filice", "name": null }, { "creator_type": "author", "first_name": "Mireen", "last_name": "Friedrich-Rust", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Fritz", "last_name": "Schafer", "name": null }, { "creator_type": "author", "first_name": "Ioan", "last_name": "Sporea", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Stephanie", "last_name": "Wilson", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Kudo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ultrasmedbio.2015.03.009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25805059" } }, "mesh": [ { "descriptor": "Elasticity Imaging Techniques", "descriptor_ui": "D054459", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Internationality", "descriptor_ui": "D038622", "major_topic": false }, { "descriptor": "Practice Guidelines as Topic", "descriptor_ui": "D017410", "major_topic": true }, { "descriptor": "Radiology", "descriptor_ui": "D011871", "major_topic": false }, { "descriptor": "Terminology as Topic", "descriptor_ui": "D009626", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "1126-1147", "proceedings_title": null, "publisher": "", "title": "Ultrasound in medicine & biology", "volume": "41", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 1: basic principles and terminology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although pituitary adenylate cyclase-activating polypeptide (PACAP) was described as a key vasoregulator in human skin, little is known about its expression in mouse skin. As it is important to investigate PACAP signaling in translational mouse dermatitis models, we determined its presence, regulation, and role in neurogenic and non-neurogenic cutaneous inflammatory mechanisms. The mRNA of PACAP and its specific receptor PAC1 was detected with real-time PCR in several skin regions at comparable levels. PACAP-38-immunoreactivity measured with radioimmunoassay was similar in plantar and dorsal paw skin and the ear but significantly smaller in the back skin. PACAP and PAC1 mRNA, as well as PACAP-38 and PAC1 protein expression, significantly increased in the plantar skin after intraplantar administration of capsaicin (50 mul, 100 mug ml(-1)), an agonist of the transient receptor potential vanilloid 1 (TRPV1) receptor, evoking chiefly neurogenic inflammation without inflammatory cell accumulation. Intraplantar complete Freund's adjuvant (CFA; 50 mul, 1 mg ml(-1)) also increased PACAP/PAC1 mRNA but not the PACAP peptide. Capsaicin-induced neurogenic paw edema, but not CFA-evoked non-neurogenic swelling, was significantly smaller in PACAP-deficient mice throughout a 24-hour period. To our knowledge, we provide previously unreported evidence for PACAP and PAC1 expression upregulation during skin inflammation of different mechanisms and for its pro-inflammatory function in neurogenic edema formation.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Zsuzsanna", "last_name": "Helyes", "name": null }, { "creator_type": "author", "first_name": "Jozsef", "last_name": "Kun", "name": null }, { "creator_type": "author", "first_name": "Nora", "last_name": "Dobrosi", "name": null }, { "creator_type": "author", "first_name": "Katalin", "last_name": "Sandor", "name": null }, { "creator_type": "author", "first_name": "Jozsef", "last_name": "Nemeth", "name": null }, { "creator_type": "author", "first_name": "Aniko", "last_name": "Perkecz", "name": null }, { "creator_type": "author", "first_name": "Erika", "last_name": "Pinter", "name": null }, { "creator_type": "author", "first_name": "Krisztina", "last_name": "Szabadfi", "name": null }, { "creator_type": "author", "first_name": "Balazs", "last_name": "Gaszner", "name": null }, { "creator_type": "author", "first_name": "Valeria", "last_name": "Tekus", "name": null }, { "creator_type": "author", "first_name": "Janos", "last_name": "Szolcsanyi", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Steinhoff", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Dora", "last_name": "Reglodi", "name": null }, { "creator_type": "author", "first_name": "Tamas", "last_name": "Biro", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/jid.2015.156" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25905588" } }, "mesh": [ { "descriptor": "Analysis of Variance", "descriptor_ui": "D000704", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Capsaicin", "descriptor_ui": "D002211", "major_topic": false }, { "descriptor": "Dermatitis", "descriptor_ui": "D003872", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neurogenic Inflammation", "descriptor_ui": "D020078", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Radioimmunoassay", "descriptor_ui": "D011863", "major_topic": false }, { "descriptor": "Random Allocation", "descriptor_ui": "D011897", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Statistics, Nonparametric", "descriptor_ui": "D018709", "major_topic": false }, { "descriptor": "Transcriptional Activation", "descriptor_ui": "D015533", "major_topic": false }, { "descriptor": "TRPV Cation Channels", "descriptor_ui": "D050916", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "2209-2218", "proceedings_title": null, "publisher": "", "title": "The Journal of investigative dermatology", "volume": "135", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Pituitary Adenylate Cyclase-Activating Polypeptide Is Upregulated in Murine Skin Inflammation and Mediates Transient Receptor Potential Vanilloid-1-Induced Neurogenic Edema.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Embryonic stem cell (ESC) pluripotency is maintained by core transcription factors (TFs). Although the expression of these TFs is well documented, their expression dynamics is poorly evaluated. Here, we visualized the dynamics of Nanog and Oct3/4 expression in ESC using fluorescent reporters and found that expression of these TFs change dramatically during culture.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Brit G.", "last_name": "David", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Taishi", "last_name": "Kakizuka", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbiosc.2014.09.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25441442" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nanog Homeobox Protein", "descriptor_ui": "D000071317", "major_topic": false }, { "descriptor": "Octamer Transcription Factor-3", "descriptor_ui": "D050814", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "SOXB1 Transcription Factors", "descriptor_ui": "D055748", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "406-409", "proceedings_title": null, "publisher": "", "title": "Journal of bioscience and bioengineering", "volume": "119", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Gene dynamics of core transcription factors for pluripotency in embryonic stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In diabetes mellitus, pituitary adenylate cyclase-activating polypeptide (PACAP) has insulinotropic and glucose-lowering properties. We previously demonstrated that transgenic mice overexpressing PACAP in pancreatic beta-cells (PACAP-Tg) show attenuated pancreatic islet hyperplasia and hyperinsulinemia in type 2 diabetic models. To explore the underlying mechanisms, here we crossed PACAP-Tg mice with lethal yellow agouti (KKAy) diabetic mice, and performed gene chip analysis of laser capture microdissected pancreatic islets from four F(1) offspring genotypes (wild-type, PACAP-Tg, KKAy, and PACAP-Tg:KKAy). We identified 1371 probes with >16-fold differences between at least one pair of genotypes, and classified the probes into five clusters with characteristic expression patterns. Gene ontology enrichment analysis showed that genes involved in the terms ribosome and intracellular organelles such as ribonucleoprotein complex, mitochondrion, and chromosome organization were significantly enriched in clusters characterized by up-regulated genes in PACAP-Tg:KKAy mice compared with KKAy mice. These results may provide insight into the mechanisms of diabetes that accompany islet hyperplasia and amelioration by PACAP.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuya", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Tomimoto", "name": null }, { "creator_type": "author", "first_name": "Soken", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hamagami", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrep.2015.06.006" }, "pmcid": { "normalized": "PMC5668656" }, "pmid": { "normalized": "29124161" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015 Jul", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "179-183", "proceedings_title": null, "publisher": "", "title": "Biochemistry and biophysics reports", "volume": "2", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparative gene expression profiles in pancreatic islets associated with agouti yellow mutation and PACAP overexpression in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tumor angiogenesis plays an important role in tumor progression and metastasis. Tumor endothelial cells (TECs) are a therapeutic target of antiangiogenic chemotherapy that was recently developed and is currently being investigated in the clinic with promising results. Low-dose chemotherapy, which is the long-term administration of relatively low doses of chemotherapeutic agents, has been proposed for targeting tumor angiogenesis in various types of cancers. Although the efficacy of low-dose chemotherapy has been confirmed in several clinical models, some studies show insufficient therapeutic effect for malignant cancers. As a possible mechanism of the treatment failure, it has been considered that tumor cells may acquire resistance to this therapy. However, drug resistance by TECs may also be due to another mechanism for resistance of tumor cells to low-dose chemotherapy. We reported elsewhere that TECs were resistant to the anticancer drug paclitaxel, which is a mitotic inhibitor, concomitant with P-glycoprotein up-regulation. Verapamil, a P-glycoprotein inhibitor, abrogated TEC resistance in vitro. Herein, we demonstrated that verapamil coadministration enhanced the effects of low-dose paclitaxel concomitant with inhibiting tumor angiogenesis in a preclinical in vivo mouse melanoma xenograft model. Furthermore, verapamil coadministration reduced lung metastasis. These results suggest that inhibiting P-glycoprotein in TECs may be a novel strategy for low-dose chemotherapy targeting TECs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Nako", "last_name": "Maishi", "name": null }, { "creator_type": "author", "first_name": "Noritaka", "last_name": "Ohga", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Hida", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Mohammad Towfik", "last_name": "Alam", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kawamoto", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Ohmura", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Chisaho", "last_name": "Torii", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Shindoh", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Hida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ajpath.2014.10.017" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25498238" } }, "mesh": [ { "descriptor": "Administration, Metronomic", "descriptor_ui": "D059250", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anti-Arrhythmia Agents", "descriptor_ui": "D000889", "major_topic": false }, { "descriptor": "Antineoplastic Agents, Phytogenic", "descriptor_ui": "D000972", "major_topic": false }, { "descriptor": "ATP Binding Cassette Transporter, Subfamily B", "descriptor_ui": "D018435", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Paclitaxel", "descriptor_ui": "D017239", "major_topic": false }, { "descriptor": "Verapamil", "descriptor_ui": "D014700", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "572-580", "proceedings_title": null, "publisher": "", "title": "The American journal of pathology", "volume": "185", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Inhibition of multidrug transporter in tumor endothelial cells enhances antiangiogenic effects of low-dose metronomic paclitaxel.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Rationale: An abundance of genetic and epidemiologic evidence as well as longitudinal neuroimaging data point to developmental origins for schizophrenia and other mental health disorders. Recent clinical studies indicate that microduplications of VIPR2, encoding the vasoactive intestinal peptide (VIP) receptor VPAC2, confer significant risk for schizophrenia and autism spectrum disorder. Lymphocytes from patients with these mutations exhibited higher VIPR2 gene expression and VIP responsiveness (cAMP induction), but mechanisms by which overactive VPAC2 signaling may lead to these psychiatric disorders are unknown. Objectives: We subcutaneously administered the highly-selective VPAC2 receptor agonist Ro 25-1553 to C57BL/6 mice from postnatal day 1 (P1) to P14 to determine if overactivation of VPAC2 receptor signaling during postnatal brain maturation affects synaptogenesis and selected behaviors. Results: Western blot analyses on P21 revealed significant reductions of synaptophysin and postsynaptic density protein 95 (PSD-95) in the prefrontal cortex, but not in the hippocampus in Ro 25-1553-treated mice. The same postnatally-restricted treatment resulted in a disruption in prepulse inhibition of the acoustic startle measured in adult mice. No effects were observed in open-field locomotor activity, sociability in the three-chamber social interaction test, or fear conditioning or extinction. Conclusion: Overactivation of the VPAC2 receptor in the postnatal mouse results in a reduction in synaptic proteins in the prefrontal cortex and selective alterations in prepulse inhibition. These findings suggest that the VIPR2-linkage to mental health disorders may be due in part to overactive VPAC2 receptor signaling during a critical time of synaptic maturation.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Michael C.", "last_name": "Condro", "name": null }, { "creator_type": "author", "first_name": "Yossan-Var", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Cristina A.", "last_name": "Ghiani", "name": null }, { "creator_type": "author", "first_name": "Christopher S.", "last_name": "Colwell", "name": null }, { "creator_type": "author", "first_name": "Jesse D.", "last_name": "Cushman", "name": null }, { "creator_type": "author", "first_name": "Michael S.", "last_name": "Fanselow", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "James A.", "last_name": "Waschek", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00213-014-3848-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25575489" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Disks Large Homolog 4 Protein", "descriptor_ui": "D000076122", "major_topic": false }, { "descriptor": "Fear", "descriptor_ui": "D005239", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Guanylate Kinases", "descriptor_ui": "D051528", "major_topic": false }, { "descriptor": "Interpersonal Relations", "descriptor_ui": "D007398", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Peptides, Cyclic", "descriptor_ui": "D010456", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Prepulse Inhibition", "descriptor_ui": "D065808", "major_topic": false }, { "descriptor": "Receptors, Vasoactive Intestinal Peptide, Type II", "descriptor_ui": "D051239", "major_topic": false }, { "descriptor": "Reflex, Startle", "descriptor_ui": "D013216", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Synaptophysin", "descriptor_ui": "D016708", "major_topic": false }, { "descriptor": "Vasoactive Intestinal Peptide", "descriptor_ui": "D014660", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jun", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "2181-2189", "proceedings_title": null, "publisher": "", "title": "Psychopharmacology", "volume": "232", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Reductions in synaptic proteins and selective alteration of prepulse inhibition in male C57BL/6 mice after postnatal administration of a VIP receptor (VIPR2) agonist.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The photoacoustic (PA) imaging by considering light propagation into image reconstruction process can provide quantitative information of photon absorbers, such as hemoglobin and exogenous dyes, and to improve their imaging contrasts. METHODS: A 2D image reconstruction of the distribution of the light absorption coefficient from the PA measurements with light source and ultrasound transducer placed at the identical position was tested. The PA pressures were formulated with the PA wave equation and the photon diffusion equation. The relation between the PA pressure and the absorption coefficient was linearized. The image reconstruction was carried out by minimizing the squared error between the measured and calculated PA signals. The l 1-norm of the reconstructed image was simultaneously minimized to improve the localization of the reconstructed target in the image. The image reconstruction with the l 1-norm minimization was compared to that with the Tikhonov regularization by numerical simulation and phantom experiment. In phantom experiment, an aqueous solution of the intralipid and the indocyanine green was used as the measured object. The PA probe had optical fiber for illumination and piezoelectric film for detection placed at the identical position. RESULTS: The l 1-norm minimization reconstructed more localized target than the Tikhonov regularization. CONCLUSIONS: The l 1-norm minimization is useful for the sparse PA image reconstruction.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinpei", "last_name": "Okawa", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.3978/j.issn.2223-4292.2014.11.22" }, "pmcid": { "normalized": "PMC4312303" }, "pmid": { "normalized": "25694957" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015 Feb", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "78-85", "proceedings_title": null, "publisher": "", "title": "Quantitative imaging in medicine and surgery", "volume": "5", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Image reconstruction of the absorption coefficients with l 1-norm minimization from photoacoustic measurements.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herpesviruses have evolved a unique mechanism for nucleocytoplasmic transport of nascent nucleocapsids: the nucleocapsids bud through the inner nuclear membrane (INM; primary envelopment), and the enveloped nucleocapsids then fuse with the outer nuclear membrane (de-envelopment). Little is known about the molecular mechanism of herpesviral de-envelopment. We show here that the knockdown of both CD98 heavy chain (CD98hc) and its binding partner beta1 integrin induced membranous structures containing enveloped herpes simplex virus 1 (HSV-1) virions that are invaginations of the INM into the nucleoplasm and induced aberrant accumulation of enveloped virions in the perinuclear space and in the invagination structures. These effects were similar to those of the previously reported mutation(s) in HSV-1 proteins gB, gH, UL31, and/or Us3, which were shown here to form a complex(es) with CD98hc in HSV-1-infected cells. These results suggested that cellular proteins CD98hc and beta1 integrin synergistically or independently regulated HSV-1 de-envelopment, probably by interacting directly and/or indirectly with these HSV-1 proteins. IMPORTANCE: Certain cellular and viral macromolecular complexes, such as Drosophila large ribonucleoprotein complexes and herpesvirus nucleocapsids, utilize a unique vesicle-mediated nucleocytoplasmic transport: the complexes acquire primary envelopes by budding through the inner nuclear membrane into the space between the inner and outer nuclear membranes (primary envelopment), and the enveloped complexes then fuse with the outer nuclear membrane to release de-enveloped complexes into the cytoplasm (de-envelopment). However, there is a lack of information on the molecular mechanism of de-envelopment fusion. We report here that HSV-1 recruited cellular fusion regulatory proteins CD98hc and beta1 integrin to the nuclear membrane for viral de-envelopment fusion. This is the first report of cellular proteins required for efficient de-envelopment of macromolecular complexes during their nuclear egress.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hirohata", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Zhuoming", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kozuka-Hata", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sagara", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00741-15" }, "pmcid": { "normalized": "PMC4505654" }, "pmid": { "normalized": "25995262" } }, "mesh": [ { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Fusion Regulatory Protein 1, Heavy Chain", "descriptor_ui": "D027282", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Integrin beta1", "descriptor_ui": "D019012", "major_topic": false }, { "descriptor": "Nuclear Envelope", "descriptor_ui": "D009685", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virus Uncoating", "descriptor_ui": "D057646", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015 Aug", "date_precision": "unknown", "issue": "15", "normalized_date": null, "pages": "7799-7812", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "89", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Herpes Simplex Virus 1 Recruits CD98 Heavy Chain and beta1 Integrin to the Nuclear Membrane for Viral De-Envelopment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tau accumulation in the brain is a pathologic hallmark of Alzheimer disease and other tauopathies. Quantitative visualization of tau pathology in humans can be a powerful method as a diagnostic aid and for monitoring potential therapeutic interventions. We established methods of PET quantification of tau pathology with (11)C-PBB3 (2-((1E,3E)-4-(6-((11)C-methylamino)pyridin-3-yl)buta-1,3-dienyl) benzo[d]thiazol-6-ol), considering its radiometabolite entering the brain. METHODS: Seven Alzheimer disease patients and 7 healthy subjects underwent dynamic (11)C-PBB3 PET scanning. Arterial blood was sampled to obtain the parent and metabolite input functions. Quantification of (11)C-PBB3 binding was performed using dual-input models that take the brain metabolite activity into consideration, traditional single-input models without such considerations, and the reference tissue model (MRTMO) and standardized uptake value ratio (SUVR). The cerebellar cortex was used as the reference tissue for all methods. RESULTS: The dual-input graphical models estimated binding parameter ([Formula: see text]) stably ( approximately 0.36 in high-binding regions). The MRTMO [Formula: see text] matched the corresponding [Formula: see text] by the dual-input graphical model (r(2) = 1.00). SUVR minus 1 correlated well with MRTMO [Formula: see text] (r(2) > 0.97). However, BPND by the single-input models did not correlate with [Formula: see text] by the dual-input graphical model (r(2) = 0.04). CONCLUSION: The dual-input graphical model [Formula: see text] is consistent with the reference tissue [Formula: see text] and SUVR-1, suggesting that these parameters can accurately quantify binding of (11)C-PBB3 despite the entry of its radiometabolites into the brain.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Ichise", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Ikoma", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Harumasa", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shinotoh", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Ming-Rong", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.2967/jnumed.115.160127" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26182966" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Aminopyridines", "descriptor_ui": "D000631", "major_topic": true }, { "descriptor": "Benzothiazoles", "descriptor_ui": "D052160", "major_topic": true }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Enhancement", "descriptor_ui": "D007089", "major_topic": false }, { "descriptor": "Image Interpretation, Computer-Assisted", "descriptor_ui": "D007090", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Positron-Emission Tomography", "descriptor_ui": "D049268", "major_topic": false }, { "descriptor": "Radiopharmaceuticals", "descriptor_ui": "D019275", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "1359-1365", "proceedings_title": null, "publisher": "", "title": "Journal of nuclear medicine : official publication, Society of Nuclear Medicine", "volume": "56", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "PET Quantification of Tau Pathology in Human Brain with 11C-PBB3.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have developed a small-molecular probe, consisting of cyclic RGD pentapeptides bearing a nitrobenzoxadiazole fluorophore at the 4'-residue, which detects integrin alphaVbeta3 activity in terms of fluorescence intensity decrease due to quenching of the fluorophore by interaction with tyrosine-122 at the binding site of the protein. This probe appears to be suitable for a practical, high-throughput fluorescence assay to screen small-molecular modulators of integrin activity.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Aoi", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c4cc05591h" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25376090" } }, "mesh": [ { "descriptor": "4-Chloro-7-nitrobenzofurazan", "descriptor_ui": "D009327", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Catalytic Domain", "descriptor_ui": "D020134", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Integrin alphaVbeta3", "descriptor_ui": "D039302", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": false }, { "descriptor": "Molecular Probes", "descriptor_ui": "D015335", "major_topic": false }, { "descriptor": "Oligopeptides", "descriptor_ui": "D009842", "major_topic": false }, { "descriptor": "Peptides, Cyclic", "descriptor_ui": "D010456", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": true } ], "publication": { "conference_name": null, "date": "2014 Dec 28", "date_precision": "day", "issue": "100", "normalized_date": "2014-12-28", "pages": "15894-15896", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "50", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Fluorometric assay of integrin activity with a small-molecular probe that senses the binding site microenvironment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Agonist stimulation induces different intracellular trafficking of endothelin receptors (ETA/BR) after internalization. The mechanism is unclear.Results: Stimulation induces ubiquitination, lysosomal targeting, and decreased cell surface ETBR levels. Non-ubiquitinated ETAR and ETBR mutant recycled to plasma membrane with smaller changes in the levels.Conclusion: Ubiquitination determines intracellular trafficking of endothelin receptors.Significance: ETBR ubiquitination fine tunes cellular responses to agonist by regulating cellular receptor levels.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Terada", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Tsunehito", "last_name": "Higashi", "name": null }, { "creator_type": "author", "first_name": "Prabha", "last_name": "Nepal", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Horiguchi", "name": null }, { "creator_type": "author", "first_name": "Sarita", "last_name": "Karki", "name": null }, { "creator_type": "author", "first_name": "Chizuru", "last_name": "Hatate", "name": null }, { "creator_type": "author", "first_name": "Akimasa", "last_name": "Hoshi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Mai", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Soichi", "last_name": "Miwa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m113.544171" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25381251" } }, "mesh": [ { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Endothelin-1", "descriptor_ui": "D019332", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lysosomes", "descriptor_ui": "D008247", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "rab GTP-Binding Proteins", "descriptor_ui": "D020691", "major_topic": false }, { "descriptor": "rab11 GTP-Binding Proteins", "descriptor_ui": "D000099193", "major_topic": false }, { "descriptor": "rab7 GTP-Binding Proteins", "descriptor_ui": "D000090802", "major_topic": false }, { "descriptor": "Receptor, Endothelin A", "descriptor_ui": "D044022", "major_topic": false }, { "descriptor": "Receptor, Endothelin B", "descriptor_ui": "D044023", "major_topic": false }, { "descriptor": "Ubiquitination", "descriptor_ui": "D054875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Dec 19", "date_precision": "day", "issue": "51", "normalized_date": "2014-12-19", "pages": "35283-35295", "proceedings_title": null, "publisher": "", "title": "The Journal of Biological Chemistry", "volume": "289", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Agonist-promoted Ubiquitination Differentially Regulates Receptor Trafficking of Endothelin Type A and Type B Receptors*.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Acrolein, a cytotoxic alpha,beta-unsaturated aldehyde and disease biomarker, was determined in plasma by means of a novel tethering strategy using Michael addition of the compound to a fluorescent dye, followed by immobilization of the product on microbeads via the aldehyde moiety. Elevation of blood acrolein was detected in mice treated with an anticancer agent cyclophosphamide, which releases acrolein upon activation. This method should be suitable for high-throughput diagnostic and clinical application.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masataka", "last_name": "Togashi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Kazuei", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Yasunobu", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c4cc02578d" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24944098" } }, "mesh": [ { "descriptor": "Acrolein", "descriptor_ui": "D000171", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Cyclophosphamide", "descriptor_ui": "D003520", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Dec 11", "date_precision": "day", "issue": "95", "normalized_date": "2014-12-11", "pages": "14946-14948", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "50", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Practical fluorescence detection of acrolein in human plasma via a two-step tethering approach.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Host factors required for viral replication are ideal drug targets because they are less likely than viral proteins to mutate under drug-mediated selective pressure. Although genome-wide screens have identified host proteins involved in influenza virus replication, limited mechanistic understanding of how these factors affect influenza has hindered potential drug development. We conducted a systematic analysis to identify and validate host factors that associate with influenza virus proteins and affect viral replication. After identifying over 1,000 host factors that coimmunoprecipitate with specific viral proteins, we generated a network of virus-host protein interactions based on the stage of the viral life cycle affected upon host factor downregulation. Using compounds that inhibit these host factors, we validated several proteins, notably Golgi-specific brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF1) and JAK1, as potential antiviral drug targets. Thus, virus-host interactome screens are powerful strategies to identify targetable host factors and guide antiviral drug development.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tokiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Jason E.", "last_name": "Shoemaker", "name": null }, { "creator_type": "author", "first_name": "Tiago J. S.", "last_name": "Lopes", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Yuriko", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kozuka-Hata", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Gorai", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Kuwahara", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Kiso", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Sakai-Tagawa", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Katsura", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Sugita", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fukuyama", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Gabriele", "last_name": "Neumann", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kawaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chom.2014.11.002" }, "pmcid": { "normalized": "PMC4451456" }, "pmid": { "normalized": "25464832" } }, "mesh": [ { "descriptor": "Antiviral Agents", "descriptor_ui": "D000998", "major_topic": false }, { "descriptor": "Drug Evaluation, Preclinical", "descriptor_ui": "D004353", "major_topic": false }, { "descriptor": "Guanine Nucleotide Exchange Factors", "descriptor_ui": "D020662", "major_topic": false }, { "descriptor": "Host-Pathogen Interactions", "descriptor_ui": "D054884", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Influenza, Human", "descriptor_ui": "D007251", "major_topic": false }, { "descriptor": "Janus Kinase 1", "descriptor_ui": "D053613", "major_topic": false }, { "descriptor": "Orthomyxoviridae", "descriptor_ui": "D009975", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Interaction Mapping", "descriptor_ui": "D025941", "major_topic": false }, { "descriptor": "Protein Interaction Maps", "descriptor_ui": "D060066", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Dec 10", "date_precision": "day", "issue": "6", "normalized_date": "2014-12-10", "pages": "795-805", "proceedings_title": null, "publisher": "", "title": "Cell host & microbe", "volume": "16", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Influenza virus-host interactome screen as a platform for antiviral drug development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chemiluminescence imaging can be performed without excitation light sources at various spatial levels ranging from a single cell to the whole body. Thus far, chemiluminescence imaging has been primarily performed with long exposure times because of weak signals, resulting in low temporal resolution. Recently, the brightest-known chemiluminescent proteins--Nano-lantern and Nano-lantern-based functional indicators--have been developed. Nano-lantern probes break the limitation of temporal resolution and enable chemiluminescence imaging of living samples such as cells, plants, and small animals at video rates. This unit describes one protocol for observation of a freely moving unshaved mouse transplanted with Nano-lantern-expressing tumor cells, and another for compatible use of optogenetic tools and a Nano-lantern calcium indicator. Both protocols utilize the synchronization of illumination and camera acquisition sessions, thereby enabling real-time chemiluminescence imaging.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/9780470559277.ch140168" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25445178" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Dec 1", "date_precision": "day", "issue": "4", "normalized_date": "2014-12-01", "pages": "221-236", "proceedings_title": null, "publisher": "", "title": "Current protocols in chemical biology", "volume": "6", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Real-time chemiluminescence imaging using nano-lantern probes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A common feature of autism spectrum disorder (ASD) is the impairment of motor control and learning, occurring in a majority of children with autism, consistent with perturbation in cerebellar function. Here we report alterations in motor behaviour and cerebellar synaptic plasticity in a mouse model (patDp/+) for the human 15q11-13 duplication, one of the most frequently observed genetic aberrations in autism. These mice show ASD-resembling social behaviour deficits. We find that in patDp/+ mice delay eyeblink conditioning--a form of cerebellum-dependent motor learning--is impaired, and observe deregulation of a putative cellular mechanism for motor learning, long-term depression (LTD) at parallel fibre-Purkinje cell synapses. Moreover, developmental elimination of surplus climbing fibres--a model for activity-dependent synaptic pruning--is impaired. These findings point to deficits in synaptic plasticity and pruning as potential causes for motor problems and abnormal circuit development in autism.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Claire", "last_name": "Piochon", "name": null }, { "creator_type": "author", "first_name": "Alexander D.", "last_name": "Kloth", "name": null }, { "creator_type": "author", "first_name": "Giorgio", "last_name": "Grasselli", "name": null }, { "creator_type": "author", "first_name": "Heather K.", "last_name": "Titley", "name": null }, { "creator_type": "author", "first_name": "Hisako", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Vivian", "last_name": "Wan", "name": null }, { "creator_type": "author", "first_name": "Dana H.", "last_name": "Simmons", "name": null }, { "creator_type": "author", "first_name": "Tahra", "last_name": "Eissa", "name": null }, { "creator_type": "author", "first_name": "Jin", "last_name": "Nakatani", "name": null }, { "creator_type": "author", "first_name": "Adriana", "last_name": "Cherskov", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takumi", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Samuel S.-H.", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Hansel", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms6586" }, "pmcid": { "normalized": "PMC4243533" }, "pmid": { "normalized": "25418414" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autistic Disorder", "descriptor_ui": "D001321", "major_topic": false }, { "descriptor": "Blinking", "descriptor_ui": "D001767", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "DNA Copy Number Variations", "descriptor_ui": "D056915", "major_topic": false }, { "descriptor": "Electrophysiology", "descriptor_ui": "D004594", "major_topic": false }, { "descriptor": "Learning", "descriptor_ui": "D007858", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Nov 24", "date_precision": "day", "issue": "", "normalized_date": "2014-11-24", "pages": "5586", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "5", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Gadolinium(III) ion (Gd(3+)) complexes are widely used as contrast agents in magnetic resonance imaging (MRI), and many attempts have been made to couple them to sensor moieties in order to visualize biological phenomena of interest inside the body. However, the low sensitivity of MRI has made it difficult to develop practical MRI contrast agents for in vivo imaging. We hypothesized that practical MRI contrast agents could be designed by targeting a specific biological environment, rather than a specific protein such as a receptor. To test this idea, we designed and synthesized a Gd(3+)-based MRI contrast agent, 2BDP3Gd, for visualizing atherosclerotic plaques by linking the Gd(3+)-complex to the lipophilic fluorophore BODIPY to stain lipid-rich environments. We found that 2BDP3Gd was selectively accumulated into lipid droplets of adipocytes at the cellular level. Atherosclerotic plaques in the aorta of Watanabe heritable hyperlipidemic (WHHL) rabbits were clearly visualized in T1-weighted MR images after intravenous injection of 2BDP3Gd in vivo.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shimpei", "last_name": "Iwaki", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Hokamura", "name": null }, { "creator_type": "author", "first_name": "Mikako", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Takehara", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Yamane", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Hirabayashi", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Kohsuke", "last_name": "Hagisawa", "name": null }, { "creator_type": "author", "first_name": "Kazuhide", "last_name": "Nakahara", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Mineno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Yasunobu", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Umemura", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c4ob01270d" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25186130" } }, "mesh": [ { "descriptor": "Adipocytes", "descriptor_ui": "D017667", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aorta", "descriptor_ui": "D001011", "major_topic": false }, { "descriptor": "Apolipoproteins E", "descriptor_ui": "D001057", "major_topic": false }, { "descriptor": "Boron Compounds", "descriptor_ui": "D001896", "major_topic": false }, { "descriptor": "Contrast Media", "descriptor_ui": "D003287", "major_topic": false }, { "descriptor": "Coordination Complexes", "descriptor_ui": "D056831", "major_topic": false }, { "descriptor": "Drug Design", "descriptor_ui": "D015195", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Gadolinium", "descriptor_ui": "D005682", "major_topic": false }, { "descriptor": "Injections, Intravenous", "descriptor_ui": "D007275", "major_topic": false }, { "descriptor": "Lipid Droplets", "descriptor_ui": "D066292", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Plaque, Atherosclerotic", "descriptor_ui": "D058226", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Nov 21", "date_precision": "day", "issue": "43", "normalized_date": "2014-11-21", "pages": "8611-8618", "proceedings_title": null, "publisher": "", "title": "Organic & biomolecular chemistry", "volume": "12", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "A design strategy for small molecule-based targeted MRI contrast agents: their application for detection of atherosclerotic plaques.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cellular differentiation proceeds along complicated pathways, even when it is induced by extracellular signaling molecules. One of the major reasons for this complexity is the highly multidimensional internal dynamics of cells, which sometimes causes apparently stochastic responses in individual cells to extracellular stimuli. Therefore, to understand cell differentiation, it is necessary to monitor the internal dynamics of cells at single-cell resolution. Here, we used a Raman and autofluorescence spectrum analysis of single cells to detect dynamic changes in intracellular molecular components. MCF-7 cells are a human cancer-derived cell line that can be induced to differentiate into mammary-gland-like cells with the addition of heregulin (HRG) to the culture medium. We measured the spectra in the cytoplasm of MCF-7 cells during 12 days of HRG stimulation. The Raman scattering spectrum, which was the major component of the signal, changed with time. A multicomponent analysis of the Raman spectrum revealed that the dynamics of the major components of the intracellular molecules, including proteins and lipids, changed cyclically along the differentiation pathway. The background autofluorescence signals of Raman scattering also provided information about the differentiation process. Using the total information from the Raman and autofluorescence spectra, we were able to visualize the pathway of cell differentiation in the multicomponent phase space.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shin-ichi", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Takanezawa", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Mitsui", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpj.2014.10.002" }, "pmcid": { "normalized": "PMC4241437" }, "pmid": { "normalized": "25418290" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MCF-7 Cells", "descriptor_ui": "D061986", "major_topic": false }, { "descriptor": "Neuregulin-1", "descriptor_ui": "D020890", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2014 Nov 18", "date_precision": "day", "issue": "10", "normalized_date": "2014-11-18", "pages": "2221-2229", "proceedings_title": null, "publisher": "", "title": "Biophysical journal", "volume": "107", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Raman and autofluorescence spectrum dynamics along the HRG-induced differentiation pathway of MCF-7 cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "How spatial and temporal information are integrated to determine the direction of cell migration remains poorly understood. Here, by precise microfluidics emulation of dynamic chemoattractant waves, we demonstrate that, in Dictyostelium, directional movement as well as activation of small guanosine triphosphatase Ras at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This 'rectification' of directional sensing occurs only at an intermediate range of wave speed and does not require phosphoinositide-3-kinase or F-actin. From modelling analysis, we show that rectification arises naturally in a single-layered incoherent feedforward circuit with zero-order ultrasensitivity. The required stimulus time-window predicts ~5 s transient for directional sensing response close to Ras activation and inhibitor diffusion typical for protein in the cytosol. We suggest that the ability of Dictyostelium cells to move only in the wavefront is closely associated with rectification of adaptive response combined with local activation and global inhibition.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms6367" }, "pmcid": { "normalized": "PMC4272253" }, "pmid": { "normalized": "25373620" } }, "mesh": [ { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false }, { "descriptor": "Microfluidics", "descriptor_ui": "D044085", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "ras Proteins", "descriptor_ui": "D018631", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Nov 6", "date_precision": "day", "issue": "", "normalized_date": "2014-11-06", "pages": "5367", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "5", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Rectified directional sensing in long-range cell migration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A single epithelial tubule undergoes morphogenesis to form a functional shape during the development of internal organs; however, the mechanical processes that are directed by the molecular signals regulating tubular morphogenesis are poorly understood. Here, axial tubular buckling triggered by cell proliferation is shown to drive the morphogenesis of murine epididymal tubules through mechanical interactions between the developing epithelial tubule and its surrounding tissues. Through immunofluorescence labeling and mathematical modeling, epididymal tubule shape formation is found to depend on two factors: cell proliferation area in the tubule and mechanical resistance from the tissues surrounding the tubule. Moreover, experimental perturbations of these two factors alter the shape of the epididymal tubule as predicted by the mathematical model, suggesting that the shape of the epididymal tubule spontaneously emerges through mechanical coupling between developing tissues instead of by growing according to a predetermined fate.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2014.09.041" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25437543" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": true }, { "descriptor": "Epididymis", "descriptor_ui": "D004822", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Inhibin-beta Subunits", "descriptor_ui": "D028322", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Nov 6", "date_precision": "day", "issue": "3", "normalized_date": "2014-11-06", "pages": "866-873", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Pattern formation of an epithelial tubule by mechanical instability during epididymal development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Yellow Cameleons are genetically encoded Ca2+ indicators in which cyan and yellow fluorescent proteins and calmodulin work together as a fluorescence (Forster) resonance energy transfer Ca2+-sensor probe. To achieve ultrasensitive Ca2+ imaging for low resting Ca2+ or small Ca2+ transients in various organs, we generated a transgenic mouse line expressing the highest-sensitive genetically encoded Ca2+ indicator (Yellow Cameleon-Nano 15) in the whole body. We then focused on the mechanism of exocytotic events mediated by intracellular Ca2+ signaling in acinar cells of the mice with an agonist and observed them by two-photon excitation microscopy. In the results, two-photon excitation imaging of Yellow Cameleon-Nano 15 successfully visualized intracellular Ca2+ concentration under stimulation with the agonist at nanomolar levels. This is the first demonstration for application of genetically encoded Ca2+ indicators to pancreatic acinar cells. We also simultaneously observed exocytotic events and an intracellular Ca2+ concentration under in vivo condition. Yellow Cameleon-Nano 15 mice are healthy and no significant deteriorative effect was observed on physiological response regarding the pancreatic acinar cells. The dynamic range of 165% was calculated from Rmax and Rmin values under in vivo condition. The mice will be useful for ultrasensitive Ca2+ imaging in vivo.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kajiura-Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Terumasa", "last_name": "Hibi", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Shigenori", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Nemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms151119971" }, "pmcid": { "normalized": "PMC4264150" }, "pmid": { "normalized": "25372943" } }, "mesh": [ { "descriptor": "Acetylcholine", "descriptor_ui": "D000109", "major_topic": false }, { "descriptor": "Acinar Cells", "descriptor_ui": "D061354", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Ionophores", "descriptor_ui": "D061207", "major_topic": false }, { "descriptor": "Calcium-Binding Proteins", "descriptor_ui": "D002135", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Exocytosis", "descriptor_ui": "D005089", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence, Multiphoton", "descriptor_ui": "D036641", "major_topic": false }, { "descriptor": "Pancreas", "descriptor_ui": "D010179", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Nov 3", "date_precision": "day", "issue": "11", "normalized_date": "2014-11-03", "pages": "19971-19986", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "15", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Ultrasensitive imaging of Ca2+ dynamics in pancreatic acinar cells of yellow cameleon-nano transgenic mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cytoplasmic dynein acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. However, the regulatory mechanism underlying release of dynactin bound cargoes from dynein motor remains largely unknown. Here we report that ADP-ribosylation factor-like 3 (Arl3) and dynein light chain LC8 induce dissociation of dynactin from dynein. Immunoprecipitation and microtubule pull-down assays revealed that Arl3(Q71L) and LC8 facilitated detachment of dynactin from dynein. We also demonstrated Arl3(Q71L) or LC8-mediated dynactin release from a dynein-dynactin complex through trace experiments using quantum dot (Qdot)-conjugated proteins. Furthermore, we disclosed interactions of Arl3 and LC8 with dynactin and dynein, respectively, by live-cell imaging. Finally, knockdown (KD) of Arl3 and LC8 by siRNA induced abnormal localizations of dynein, dynactin and related organelles. Our findings uncovered the surprising functional relevance of GTP-bound Arl3 and LC8 for the unloading regulation of dynactin-bound cargo from dynein motor.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mingyue", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Masami", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Hirotsune", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms6295" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25342295" } }, "mesh": [ { "descriptor": "ADP-Ribosylation Factors", "descriptor_ui": "D020727", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cytoplasmic Dyneins", "descriptor_ui": "D056445", "major_topic": false }, { "descriptor": "Dynactin Complex", "descriptor_ui": "D000072159", "major_topic": false }, { "descriptor": "Dyneins", "descriptor_ui": "D004398", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Microtubule-Associated Proteins", "descriptor_ui": "D008869", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Mutant Proteins", "descriptor_ui": "D050505", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Oct 24", "date_precision": "day", "issue": "", "normalized_date": "2014-10-24", "pages": "5295", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "5", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Arl3 and LC8 regulate dissociation of dynactin from dynein.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Caged compounds are useful tools for precise spatiotemporal modulation of cell functions, but in most cases uncaging requires ultraviolet (UV) light, which is cytotoxic and has limited tissue penetration. Therefore, caged compounds that can be activated by longer-wavelength light are required. Here we describe a novel photoelimination reaction of 4-aryloxy boron dipyrromethene (BODIPY) derivatives and show that BODIPY can function as a caging group for phenol groups. We developed a novel BODIPY-caged histamine compound, which is photoactivatable with blue-green visible light to stimulate cultured HeLa cells in a spatiotemporally well-controlled manner. This caging strategy is expected to be widely applicable to develop tools for probing various cellular functions.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/cb500525p" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25140990" } }, "mesh": [ { "descriptor": "Boron", "descriptor_ui": "D001895", "major_topic": false }, { "descriptor": "Boron Compounds", "descriptor_ui": "D001896", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Photons", "descriptor_ui": "D017785", "major_topic": true }, { "descriptor": "Porphobilinogen", "descriptor_ui": "D011162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Oct 17", "date_precision": "day", "issue": "10", "normalized_date": "2014-10-17", "pages": "2242-2246", "proceedings_title": null, "publisher": "", "title": "ACS chemical biology", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Boron dipyrromethene as a fluorescent caging group for single-photon uncaging with long-wavelength visible light.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The dysbindin-1 gene (DTNBP1: dystrobrevin binding protein 1) is a promising schizophrenia susceptibility gene, known to localize almost exclusively to neurons in the brain, and participates in the regulation of neurotransmitter release, membrane-surface receptor expression, and synaptic plasticity. Sandy mice, with spontaneous Dtnbp1 deletion, display behavioral abnormalities relevant to symptoms of schizophrenia. However, it remains unknown if dysbindin-1 gain-of-function is beneficial or detrimental. RESULTS: To answer this question and gain further insight into the pathophysiology and therapeutic potential of dysbindin-1, we developed transgenic mice expressing human DTNBP1 (Dys1A-Tg) and analyzed their behavioral phenotypes. Dys1A-Tg mice were born viable in the expected Mendelian ratios, apparently normal and fertile. Primary screening of behavior and function showed a marginal change in limb grasping in Dys1A-Tg mice. In addition, Dys1A-Tg mice exhibited increased hyperlocomotion after methamphetamine injection. Transcriptomic analysis identified several up- and down-regulated genes, including the immediate-early genes Arc and Egr2, in the prefrontal cortex of Dys1A-Tg mice. CONCLUSIONS: The present findings in Dys1A-Tg mice support the role of dysbindin-1 in psychiatric disorders. The fact that either overexpression (Dys1A-Tg) or underexpression (Sandy) of dysbindin-1 leads to behavioral alterations in mice highlights the functional importance of dysbindin-1 in vivo.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Onaka", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Takamura", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Umeda-Yano", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Mouri", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Mamiya", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Haba", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Matsuzaki", "name": null }, { "creator_type": "author", "first_name": "Taiichi", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Hidenaga", "last_name": "Yamamori", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yagasaki", "name": null }, { "creator_type": "author", "first_name": "Toshitaka", "last_name": "Nabeshima", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13041-014-0074-x" }, "pmcid": { "normalized": "PMC4201722" }, "pmid": { "normalized": "25298178" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": true }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Dysbindin", "descriptor_ui": "D000074765", "major_topic": false }, { "descriptor": "Dystrophin-Associated Proteins", "descriptor_ui": "D049029", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Methamphetamine", "descriptor_ui": "D008694", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Phencyclidine", "descriptor_ui": "D010622", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Oct 9", "date_precision": "day", "issue": "", "normalized_date": "2014-10-09", "pages": "74", "proceedings_title": null, "publisher": "", "title": "Molecular brain", "volume": "7", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Behavioral characterization of mice overexpressing human dysbindin-1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We previously found that juvenile pituitary adenylate cyclase-activating polypeptide (PACAP)-knockout (PACAP(-/-)) mice reared in an enriched environment (EE) for 4 weeks showed attenuated hyperactivity, jumping behavior, impairments in social interaction, and depression-like behavior. The present study examined the effects of EE on memory function and memory-related protein levels in PACAP(-/-) mice. Eight-week-old PACAP(-/-) mice displayed fear memory dysfunction in a contextual fear conditioning test and cognitive impairments in a novel object recognition test. Rearing of 4-week-old PACAP(-/-) mice in an EE for 4 weeks ameliorated these memory impairments. The beneficial effects of EE were also observed 2 weeks after a return to housing in a standard environment (SE). This suggests that the effects of EE on impaired memory are long-lasting. In both wild-type and PACAP(-/-) mice, EE increased the protein levels of the NMDA receptor NR2B subunit, phospho-ERK, phospho-CaMKII, and brain-derived neurotrophic factor (BDNF) in the hippocampus, and decreased neurotrophin-3 levels, whereas it did not affect nerve growth factor and glial cell-derived neurotrophic factor levels. Increased levels of NR2B, phospho-ERK, phospho-CaMKII and BDNF were not observed 2 weeks after a return to housing in a SE. These findings suggest that living in an EE engenders long-lasting reductions in memory impairments in PACAP(-/-) mice. The present study also implies that increases in hippocampal memory-related protein and BDNF levels are responsible for the beneficial effects of an EE, but not for the maintenance of these effects.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Ishihama", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbr.2014.07.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25014004" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain-Derived Neurotrophic Factor", "descriptor_ui": "D019208", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinase Type 2", "descriptor_ui": "D054732", "major_topic": false }, { "descriptor": "Conditioning, Psychological", "descriptor_ui": "D003213", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Fear", "descriptor_ui": "D005239", "major_topic": false }, { "descriptor": "Glial Cell Line-Derived Neurotrophic Factor", "descriptor_ui": "D051100", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Housing, Animal", "descriptor_ui": "D006799", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory Disorders", "descriptor_ui": "D008569", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Nerve Growth Factor", "descriptor_ui": "D020932", "major_topic": false }, { "descriptor": "Neurotrophin 3", "descriptor_ui": "D020933", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Random Allocation", "descriptor_ui": "D011897", "major_topic": false }, { "descriptor": "Receptors, N-Methyl-D-Aspartate", "descriptor_ui": "D016194", "major_topic": false }, { "descriptor": "Recognition, Psychology", "descriptor_ui": "D021641", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Oct 1", "date_precision": "day", "issue": "", "normalized_date": "2014-10-01", "pages": "269-278", "proceedings_title": null, "publisher": "", "title": "Behavioural brain research", "volume": "272", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "An enriched environment ameliorates memory impairments in PACAP-deficient mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydrogen sulfide (H(2)S) exerts a host of biological effects ranging from cytotoxicity to cytoprotection. Cytotoxicity of H(2)S in neurodegenerative diseases may be mediated by N-methyl-D-aspartate receptor (NMDAR) activation. To exploit cytoprotective effects of H(2)S while minimizing its toxicity, we synthesized a series of H(2)S-releasing NMDAR antagonists and examined their effects against 1-methyl-4-phenylpyridinium (MPP(+))-induced cell death, a cellular model of Parkinson's disease. We observed that cytoprotective effect of H(2)S-releasing NMDAR antagonists correlated with their ability to increase intracellular sulfane sulfur, but not H(2)S, levels. These studies suggest that H(2)S-donor compounds that increase intracellular sulfane sulfur are potentially useful neuroprotective agents against neurodegenerative diseases.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Eizo", "last_name": "Marutani", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Sasakura", "name": null }, { "creator_type": "author", "first_name": "Jifeng", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Xian", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Fumito", "last_name": "Ichinose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c4md00180j" }, "pmcid": { "normalized": "PMC4242466" }, "pmid": { "normalized": "25431645" } }, "mesh": [], "publication": { "conference_name": null, "date": "2014 Oct 1", "date_precision": "day", "issue": "10", "normalized_date": "2014-10-01", "pages": "1577-1583", "proceedings_title": null, "publisher": "", "title": "MedChemComm", "volume": "5", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Cytoprotective effects of hydrogen sulfide-releasing N-methyl-D-aspartate receptor antagonists are mediated by intracellular sulfane sulfur.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Teleost fishes are the major group of ray-finned fishes and represent more than one-half of the total number of vertebrate species. They have experienced in their evolution an additional third-round whole genome duplication just after the divergence of their lineage, which endowed them with an extra adaptability to invade various aquatic habitats. Thus their physiology is also extremely diverse compared with other vertebrate groups as exemplified by the many patterns of body fluid regulation or osmoregulation. The key osmoregulatory organ for teleosts, whose body fluid composition is similar to mammals, is the gill, where ions are absorbed from or excreted into surrounding waters of various salinities against concentration gradients. It has been shown that the underlying molecular physiology of gill ionocytes responsible for ion regulation is highly variable among species. This variability is also seen in the endocrine control of osmoregulation where some hormones have distinct effects on body fluid regulation in different teleost species. A typical example is atrial natriuretic peptide (ANP); ANP is secreted in response to increased blood volume and acts on various osmoregulatory organs to restore volume in rainbow trout as it does in mammals, but it is secreted in response to increased plasma osmolality, and specifically decreases NaCl, and not water, in the body of eels. The distinct actions of other osmoregulatory hormones such as growth hormone, prolactin, angiotensin II, and vasotocin among teleost species are also evident. We hypothesized that such diversity of ionocytes and hormone actions among species stems from their intrinsic differences in body fluid regulation that originated from their native habitats, either fresh water or seawater. In this review, we summarized remarkable differences in body fluid regulation and its endocrine control among teleost species, although the number of species is still limited to substantiate the hypothesis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshio", "last_name": "Takei", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Hiroi", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1152/ajpregu.00104.2014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24965789" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Atrial Natriuretic Factor", "descriptor_ui": "D009320", "major_topic": false }, { "descriptor": "Body Fluids", "descriptor_ui": "D001826", "major_topic": false }, { "descriptor": "Endocrine System", "descriptor_ui": "D004703", "major_topic": false }, { "descriptor": "Fishes", "descriptor_ui": "D005399", "major_topic": false }, { "descriptor": "Hormones", "descriptor_ui": "D006728", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Water-Electrolyte Balance", "descriptor_ui": "D014882", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Oct 1", "date_precision": "day", "issue": "7", "normalized_date": "2014-10-01", "pages": "R778-792", "proceedings_title": null, "publisher": "", "title": "American journal of physiology. Regulatory, integrative and comparative physiology", "volume": "307", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Diverse mechanisms for body fluid regulation in teleost fishes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In cerebellar Purkinje cell dendrites, heterosynaptic calcium signaling induced by the proximal climbing fiber (CF) input controls plasticity at distal parallel fiber (PF) synapses. The substrate and regulation of this long-range dendritic calcium signaling are poorly understood. Using high-speed calcium imaging, we examine the role of active dendritic conductances. Under basal conditions, CF stimulation evokes T-type calcium signaling displaying sharp proximodistal decrement. Combined mGluR1 receptor activation and depolarization, two activity-dependent signals, unlock P/Q calcium spikes initiation and propagation, mediating efficient CF signaling at distal sites. These spikes are initiated in proximal smooth dendrites, independently from somatic sodium action potentials, and evoke high-frequency bursts of all-or-none fast-rising calcium transients in PF spines. Gradual calcium spike burst unlocking arises from increasing inactivation of mGluR1-modulated low-threshold A-type potassium channels located in distal dendrites. Evidence for graded activity-dependent CF calcium signaling at PF synapses refines current views on cerebellar supervised learning rules.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yo", "last_name": "Otsu", "name": null }, { "creator_type": "author", "first_name": "Paikan", "last_name": "Marcaggi", "name": null }, { "creator_type": "author", "first_name": "Anne", "last_name": "Feltz", "name": null }, { "creator_type": "author", "first_name": "Philippe", "last_name": "Isope", "name": null }, { "creator_type": "author", "first_name": "Mihaly", "last_name": "Kollo", "name": null }, { "creator_type": "author", "first_name": "Zoltan", "last_name": "Nusser", "name": null }, { "creator_type": "author", "first_name": "Benjamin", "last_name": "Mathieu", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Tsujita", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Stephane", "last_name": "Dieudonne", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2014.08.035" }, "pmcid": { "normalized": "PMC4183427" }, "pmid": { "normalized": "25220810" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Ion Channel Gating", "descriptor_ui": "D015640", "major_topic": false }, { "descriptor": "Kv Channel-Interacting Proteins", "descriptor_ui": "D051605", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Organ Culture Techniques", "descriptor_ui": "D009924", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Oct 1", "date_precision": "day", "issue": "1", "normalized_date": "2014-10-01", "pages": "137-151", "proceedings_title": null, "publisher": "", "title": "Neuron", "volume": "84", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Activity-dependent gating of calcium spikes by A-type K+ channels controls climbing fiber signaling in Purkinje cell dendrites.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We introduce a step transition and state identification (STaSI) method for piecewise constant single-molecule data with a newly derived minimum description length equation as the objective function. We detect the step transitions using the Student’s t test and group the segments into states by hierarchical clustering. The optimum number of states is determined based on the minimum description length equation. This method provides comprehensive, objective analysis of multiple traces requiring few user inputs about the underlying physical models and is faster and more precise in determining the number of states than established and cutting-edge methods for single-molecule data analysis. Perhaps most importantly, the method does not require either time-tagged photon counting or photon counting in general and thus can be applied to a broad range of experimental setups and analytes.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Bo", "last_name": "Shuang", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Cooper", "name": null }, { "creator_type": "author", "first_name": "J. Nick", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Lydia", "last_name": "Kisley", "name": null }, { "creator_type": "author", "first_name": "Jixin", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Wenxiao", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Chun Biu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null }, { "creator_type": "author", "first_name": "Christy F.", "last_name": "Landes", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jz501435p" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25247055" } }, "mesh": [], "publication": { "conference_name": null, "date": "2014 Sep 18", "date_precision": "day", "issue": "18", "normalized_date": "2014-09-18", "pages": "3157-3161", "proceedings_title": null, "publisher": "", "title": "The Journal of Physical Chemistry Letters", "volume": "5", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Fast Step Transition and State Identification (STaSI) for Discrete Single-Molecule Data Analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Quantifying the interactions in dense colloidal fluids requires a properly designed order parameter. We present a modified bond-orientational order parameter, psī6, to avoid problems of the original definition of bond-orientational order parameter. The original bond-orientational order parameter can change discontinuously in time but our modified order parameter is free from the discontinuity and, thus, it is a suitable measure to quantify the dynamics of the bond-orientational ordering of the local surroundings. Here we analyze psī6 in a dense driven monodisperse quasi-two-dimensional colloidal fluids where a single particle is optically trapped at the center. The perturbation by the trapped and driven particle alters the structure and dynamics of the neighboring particles. This perturbation disturbs the flow and causes spatial and temporal distortion of the bond-orientational configuration surrounding each particle. We investigate spatio-temporal behavior of psī6 by a Wavelet transform that provides a time-frequency representation of the time series of psī6. It is found that particles that have high power in frequencies corresponding to the inverse of the timescale of perturbation undergo distortions of their packing configurations that result in cage breaking and formation dynamics. To gain insight into the dynamic structure of cage breaking and formation of bond-orientational ordering, we compare the cage breaking and formation dynamics with the underlying dynamical structure identified by Lagrangian Coherent Structures (LCSs) estimated from the finite-time Lyapunov exponent (FTLE) field. The LCSs are moving separatrices that effectively divide the flow into distinct regions with different dynamical behavior. It is shown that the spatial distribution of the FTLE field and the power of particles in the wavelet transform have positive correlation, implying that LCSs provide a dynamic structure that dominates the dynamics of cage breaking and formation of the colloidal fluids.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Preetom", "last_name": "Nag", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Teramoto", "name": null }, { "creator_type": "author", "first_name": "Chun-Biu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Joseph Z.", "last_name": "Terdik", "name": null }, { "creator_type": "author", "first_name": "Norbert F.", "last_name": "Scherer", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/1.4894866" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25217951" } }, "mesh": [ { "descriptor": "Colloids", "descriptor_ui": "D003102", "major_topic": false }, { "descriptor": "Hydrodynamics", "descriptor_ui": "D057446", "major_topic": false }, { "descriptor": "Mechanical Phenomena", "descriptor_ui": "D055595", "major_topic": false }, { "descriptor": "Rheology", "descriptor_ui": "D012212", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Sep 14", "date_precision": "day", "issue": "10", "normalized_date": "2014-09-14", "pages": "104907", "proceedings_title": null, "publisher": "", "title": "The Journal of chemical physics", "volume": "141", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Local-heterogeneous responses and transient dynamics of cage breaking and formation in colloidal fluids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Calumin is an endoplasmic reticulum (ER)-transmembrane protein, and little is known about its physiological roles. Here we showed that calumin homozygous mutant embryos die at embryonic days (E) 10.5-11.5. At mid-gestation, calumin was expressed predominantly in the yolk sac. Apoptosis was enhanced in calumin homozygous mutant yolk sacs at E9.5, pointing to a possible link to the embryonic lethality. Calumin co-immunoprecipitated with ERAD components such as p97, BIP, derlin-1, derlin-2 and VIMP, suggesting its involvement in ERAD. Indeed, calumin knockdown in HEK 293 cells resulted in ERAD being less efficient, as demonstrated by attenuation in both degradations of a misfolded alpha1-antitrypsin variant and the ER-to-cytosol dislocation of cholera toxin A1 subunit. In calumin homozygous mutant yolk sac endoderm cells, ER stress-associated alterations were observed, including lipid droplet accumulation, fragmentation of the ER and dissociation of ribosomes from the ER. In this context, the ER-overload response, assumed to be cytoprotective, was also triggered in the mutant endoderm cells, but seemed to fully counteract the excessive ER stress generated due to defective ERAD. Taken together, our findings suggested that calumin serves to maintain the yolk sac integrity through participation in the ERAD activity, contributing to embryonic development.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Komazaki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Matsubayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Daiju", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Kakizawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2014.06.024" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25009997" } }, "mesh": [ { "descriptor": "alpha 1-Antitrypsin", "descriptor_ui": "D000515", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cholera Toxin", "descriptor_ui": "D002772", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Endoderm", "descriptor_ui": "D004707", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum Stress", "descriptor_ui": "D059865", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum-Associated Degradation", "descriptor_ui": "D060746", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Protein Folding", "descriptor_ui": "D017510", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Yolk Sac", "descriptor_ui": "D015017", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Sep 1", "date_precision": "day", "issue": "1", "normalized_date": "2014-09-01", "pages": "33-43", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "393", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Contribution of calumin to embryogenesis through participation in the endoplasmic reticulum-associated degradation activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Monoacylglycerol lipase (MGL) is the main enzyme responsible for degradation of the endocannabinoid 2-arachidonoylglycerol (2-AG). Selective inhibitors of MGL have antinociceptive effects upon acute administration and, therefore, hold promise as analgesics. To gain insight into the possible consequences of their prolonged administration, genetically modified mice with the knocked-out MGL gene were tested in several models of acute (phasic, tonic) and chronic (inflammatory, neuropathic) pain. MGL knockout mice showed normal acute phasic pain perception (pain thresholds) and no alleviation of pain perception in models of inflammatory and neuropathic pain. However, compared with wild-type controls, they showed significantly augmented nociceptive behavior in models of acute somatic and visceral tonic pain (formalin and acetic acid tests). The observed proalgesic changes in perception of tonic pain in MGL knockouts could have resulted from desensitization of cannabinoid receptors (known to occur after genetic inactivation of MGL). Supporting this notion, chronic pretreatment with the selective CB1 receptor antagonist AM 251 (employed to re-sensitize cannabinoid receptors in MGL knockouts) resulted in normalization of their tonic pain-related behaviors. Similar augmentation of tonic pain-related behaviors was replicated in C57BL/6N mice pretreated chronically with the selective MGL inhibitor JZL 184 (employed to pharmacologically desensitize CB1 receptors). These findings imply that prolonged use of MGL inhibitors, at doses causing close to complete inhibition of MGL enzymatic activity, not only have no beneficial analgesic effects, they may lead to exacerbation of some types of pain (particularly those with a tonic component).", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Andrey B.", "last_name": "Petrenko", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbr.2014.05.063" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24906199" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arachidonic Acids", "descriptor_ui": "D001095", "major_topic": false }, { "descriptor": "Benzodioxoles", "descriptor_ui": "D052117", "major_topic": false }, { "descriptor": "Cannabinoid Receptor Modulators", "descriptor_ui": "D063385", "major_topic": false }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": false }, { "descriptor": "Glycerides", "descriptor_ui": "D005989", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred CBA", "descriptor_ui": "D008808", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neuralgia", "descriptor_ui": "D009437", "major_topic": false }, { "descriptor": "Pain", "descriptor_ui": "D010146", "major_topic": false }, { "descriptor": "Pain Threshold", "descriptor_ui": "D017288", "major_topic": false }, { "descriptor": "Phosphotransferases (Alcohol Group Acceptor)", "descriptor_ui": "D017853", "major_topic": false }, { "descriptor": "Piperidines", "descriptor_ui": "D010880", "major_topic": false }, { "descriptor": "Pyrazoles", "descriptor_ui": "D011720", "major_topic": false }, { "descriptor": "Receptor, Cannabinoid, CB1", "descriptor_ui": "D043884", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Sep 1", "date_precision": "day", "issue": "", "normalized_date": "2014-09-01", "pages": "51-58", "proceedings_title": null, "publisher": "", "title": "Behavioural brain research", "volume": "271", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Augmented tonic pain-related behavior in knockout mice lacking monoacylglycerol lipase, a major degrading enzyme for the endocannabinoid 2-arachidonoylglycerol.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A purpose-designed porphyrin-peptide hybrid effectively degraded amyloid beta monomer and oligomers associated with Alzheimer's disease. Degradation was achieved using light irradiation in the absence of any additives and under neutral conditions. Moreover, the hybrid effectively neutralized the cytotoxicity of amyloid beta in PC12 cells upon photoirradiation.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ayumi", "last_name": "Hirabayashi", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Kazunobu", "last_name": "Toshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c4cc03791j" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25012260" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Amyloid beta-Peptides", "descriptor_ui": "D016229", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Oligopeptides", "descriptor_ui": "D009842", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Peptide Fragments", "descriptor_ui": "D010446", "major_topic": false }, { "descriptor": "Photolysis", "descriptor_ui": "D010782", "major_topic": false }, { "descriptor": "Photosensitizing Agents", "descriptor_ui": "D017319", "major_topic": false }, { "descriptor": "Porphyrins", "descriptor_ui": "D011166", "major_topic": false }, { "descriptor": "Protein Multimerization", "descriptor_ui": "D055503", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Aug 28", "date_precision": "day", "issue": "67", "normalized_date": "2014-08-28", "pages": "9543-9546", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "50", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Photodegradation of amyloid beta and reduction of its cytotoxicity to PC12 cells using porphyrin derivatives.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Synapse elimination is crucial for precise neural circuit formation during postnatal development. We examined how relative differences in synaptic strengths among competing inputs and/or absolute synaptic strengths contribute to climbing fiber (CF) to Purkinje cell (PC) synapse elimination in the cerebellum. We generated mice with PC-selective deletion of stargazin (TARP gamma-2), the major AMPA receptor auxiliary subunit in PCs (gamma-2 PC-KO mice). Whereas relative differences between \"strong\" and \"weak\" CF-mediated postsynaptic response are preserved, absolute strengths of CF inputs are scaled down globally in PCs of gamma-2 PC-KO mice. Although the early phase of CF elimination is normal, dendritic translocation of the strongest CF and the late phase of CF elimination that requires Ca(2+)-dependent activation of Arc/Arg3.1 in PCs are both impaired in gamma-2 PC-KO mice. We conclude that, although relative differences in CF synaptic inputs are initially essential, proper synaptic scaling is crucial for accomplishing CF synapse elimination.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shinya", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Mikuni", "name": null }, { "creator_type": "author", "first_name": "Miwako", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2014.07.014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25127140" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Channels", "descriptor_ui": "D015220", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Cytoskeletal Proteins", "descriptor_ui": "D003598", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Receptors, AMPA", "descriptor_ui": "D018091", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Aug 21", "date_precision": "day", "issue": "4", "normalized_date": "2014-08-21", "pages": "1119-1129", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "8", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Global scaling down of excitatory postsynaptic responses in cerebellar Purkinje cells impairs developmental synapse elimination.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In this study, amphiphilic Janus-type polymers were synthesized via ring-opening metathesis polymerization (ROMP), multiple vicinal diol formation, and grafting of poly(ethylene glycol) monomethyl ether (mPEG). These amphiphilic polymers formed self-assemblies, which were a mixture of micelles and multimicellar aggregates, in water. By choosing suitable Janus-type polymers and irradiating an aqueous solution of polymers using a sonicator, either small micelles or large multimicellar aggregates were obtained selectively. Hydrophobic substituents controlled the aggregation-disaggregation behavior, leading to the formation of metastable self-assemblies by sonication. The formation of self-assemblies with a uniform size was affected by ultrasonic frequency, rather than power. In vivo optical tumor imaging revealed that the large-size multimicellar aggregates persisting for a long time in blood circulation slowly accumulated in tumor tissues. In contrast, the tumor site was rapidly, clearly visualized using the small-size micelles.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/smll.201400358" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24729486" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Crystallization", "descriptor_ui": "D003460", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "High-Energy Shock Waves", "descriptor_ui": "D019220", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": false }, { "descriptor": "Neoplasms, Experimental", "descriptor_ui": "D009374", "major_topic": false }, { "descriptor": "Particle Size", "descriptor_ui": "D010316", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Sonication", "descriptor_ui": "D013010", "major_topic": false }, { "descriptor": "Surface-Active Agents", "descriptor_ui": "D013501", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Aug 13", "date_precision": "day", "issue": "15", "normalized_date": "2014-08-13", "pages": "3119-3130", "proceedings_title": null, "publisher": "", "title": "Small (Weinheim an der Bergstrasse, Germany)", "volume": "10", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Sonication-induced formation of size-controlled self-assemblies of amphiphilic Janus-type polymers as optical tumor-imaging agents.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Molecular assemblies that change photoluminescence color in response to thermal or mechanical stimulation without dissociation into the monomeric states in water are described herein. A dumbbell-shaped amphiphilic compound forms micellar molecular assemblies in water and exhibits yellow photoluminescence derived from excimer formation of the luminescent core, which contains a 2,6-diethynylanthracene moiety. Annealing of the aqueous solution induces a photoluminescence color change from yellow to green (lambdaem, max =558-->525 nm). The same photoluminescence color change is also achieved by rubbing the yellow-photoluminescence-emitting molecular assemblies adsorbed on glass substrates with cotton wool in water. The observed green photoluminescence is ascribed to micelles that are distinct from the yellow-photoluminescence-emitting micelles, on the basis of transmission electron microscopy observations, atomic force microscopy observations, and dynamic light scattering measurements. We examined the relationship between the structure of the molecular assemblies and the photophysical properties of the anthracene derivative in water before and after thermal or mechanical stimulation and concluded that thermal or mechanical stimuli-induced slight changes of the molecular-assembled structures in the micelles result in the change in the photoluminescence color from yellow to green in water.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshimitsu", "last_name": "Sagara", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/chem.201403025" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25043342" } }, "mesh": [ { "descriptor": "Anthracenes", "descriptor_ui": "D000873", "major_topic": false }, { "descriptor": "Friction", "descriptor_ui": "D017276", "major_topic": false }, { "descriptor": "Luminescence", "descriptor_ui": "D049449", "major_topic": false }, { "descriptor": "Luminescent Agents", "descriptor_ui": "D049408", "major_topic": false }, { "descriptor": "Micelles", "descriptor_ui": "D008823", "major_topic": false }, { "descriptor": "Surface-Active Agents", "descriptor_ui": "D013501", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Aug 11", "date_precision": "day", "issue": "33", "normalized_date": "2014-08-11", "pages": "10397-10403", "proceedings_title": null, "publisher": "", "title": "Chemistry (Weinheim an der Bergstrasse, Germany)", "volume": "20", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Thermal or mechanical stimuli-induced photoluminescence color change of a molecular assembly composed of an amphiphilic anthracene derivative in water.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fibroblast growth factor-2 (FGF-2) plays a critical role in endothelial survival, proliferation, and angiogenesis and is localized on the cell membrane by binding to heparan sulfate proteoglycans. Here we established a neutralizing monoclonal antibody, 1B9B9, against FGF-2 using the rat medial iliac lymph node method. 1B9B9 blocked the binding of FGF-2 to its receptor, inhibiting FGF-2-induced proliferation and corresponding downstream signaling in endothelial cells. Treatment of human umbilical vein endothelial cells with 1B9B9 reduced the basal phosphorylation levels of Akt and MAPK. Furthermore, continued treatment with 1B9B9 induced cell death by apoptosis. Compared with FGF-2 knockdown, 1B9B9 significantly reduced cell survival. In addition, the combination of FGF-2 siRNA and 1B9B9 showed a synergistic effect. The data indicate that 1B9B9 established by the rat iliac lymph node method is a fully compatible neutralizing antibody.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masako", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shiota", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Kawamoto", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Azusa", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Osada-Oka", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Wanibuchi", "name": null }, { "creator_type": "author", "first_name": "Yasukatsu", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Iwao", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/mab.2013.0085" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25171006" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Antibodies, Neutralizing", "descriptor_ui": "D057134", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Enzyme-Linked Immunosorbent Assay", "descriptor_ui": "D004797", "major_topic": false }, { "descriptor": "Fibroblast Growth Factor 2", "descriptor_ui": "D016222", "major_topic": false }, { "descriptor": "Human Umbilical Vein Endothelial Cells", "descriptor_ui": "D061307", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Immunoprecipitation", "descriptor_ui": "D047468", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": false }, { "descriptor": "Oncogene Protein v-akt", "descriptor_ui": "D051058", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Aug 01", "date_precision": "day", "issue": "4", "normalized_date": "2014-08-01", "pages": "261-269", "proceedings_title": null, "publisher": "", "title": "Monoclonal Antibodies in Immunodiagnosis and Immunotherapy", "volume": "33", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Establishment of Neutralizing Rat Monoclonal Antibodies for Fibroblast Growth Factor-2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The origin and developmental mechanisms underlying coronary vessels are not fully elucidated. Here we show that myocardium-derived angiopoietin-1 (Ang1) is essential for coronary vein formation in the developing heart. Cardiomyocyte-specific Ang1 deletion results in defective formation of the subepicardial coronary veins, but had no significant effect on the formation of intramyocardial coronary arteries. The endothelial cells (ECs) of the sinus venosus (SV) are heterogeneous population, composed of APJ-positive and APJ-negative ECs. Among these, the APJ-negative ECs migrate from the SV into the atrial and ventricular myocardium in Ang1-dependent manner. In addition, Ang1 may positively regulate venous differentiation of the subepicardial APJ-negative ECs in the heart. Consistently, in vitro experiments show that Ang1 indeed promotes venous differentiation of the immature ECs. Collectively, our results indicate that myocardial Ang1 positively regulates coronary vein formation presumably by promoting the proliferation, migration and differentiation of immature ECs derived from the SV.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoh", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Nakaoka", "name": null }, { "creator_type": "author", "first_name": "Taichi", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Yamamizu", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Arima", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kataoka-Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kuniyasu", "last_name": "Ikeoka", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Masaki", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Jin-Sung", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yamagishi", "name": null }, { "creator_type": "author", "first_name": "Kinya", "last_name": "Otsu", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Yamauchi-Takihara", "name": null }, { "creator_type": "author", "first_name": "Gou Y.", "last_name": "Koh", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sakata", "name": null }, { "creator_type": "author", "first_name": "Jun K.", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Issei", "last_name": "Komuro", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms5552" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25072663" } }, "mesh": [ { "descriptor": "Angiopoietin-1", "descriptor_ui": "D042683", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Chimera", "descriptor_ui": "D002678", "major_topic": false }, { "descriptor": "Coronary Vessels", "descriptor_ui": "D003331", "major_topic": false }, { "descriptor": "DNA Primers", "descriptor_ui": "D017931", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Heart", "descriptor_ui": "D006321", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Polymerase Chain Reaction", "descriptor_ui": "D016133", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014-07-29", "date_precision": "day", "issue": "", "normalized_date": "2014-07-29", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "5", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Myocardium-derived angiopoietin-1 is essential for coronary vein formation in the developing heart.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell surfaces represent a platform through which extracellular signals that determine diverse cellular processes, including migration, division, adhesion, and phagocytosis, are transduced. Techniques to rapidly reconfigure the surface properties of living cells should thus offer the ability to harness these cellular functions. Although the molecular mechanism of phagocytosis is well characterized, the minimal molecular players that are sufficient to activate this elaborate process remain elusive. We developed and implemented a technique to present a molecule of interest at the cell surface in an inducible manner on a time scale of minutes. We simultaneously induced the cell surface display of the C2 domain of milk fat globule epidermal growth factor factor 8 (MFG-E8) and activated the intracellular small guanosine triphosphatase Rac, which stimulates actin polymerization at the cell periphery. The C2 domain binds to phosphatidylserine, a lipid exposed on the surface of apoptotic cells. By integrating the stimulation of these two processes, we converted HeLa cells into a phagocytic cell line that bound to and engulfed apoptotic human Jurkat cells. Inducing either the cell surface display of the C2 domain or activating Rac alone was not sufficient to stimulate phagocytosis, which suggests that attachment to the target cell and actin reorganization together constitute the minimal molecular events that are needed to induce phagocytosis. This cell surface display technique might be useful as part of a targeted, cell-based therapy in which unwanted cells with characteristic surface molecules could be rapidly consumed by engineered cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Onuma", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Takanari", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/scisignal.2005123" }, "pmcid": { "normalized": "PMC4136641" }, "pmid": { "normalized": "25028719" } }, "mesh": [ { "descriptor": "Antigens, Surface", "descriptor_ui": "D000954", "major_topic": false }, { "descriptor": "Cell Surface Display Techniques", "descriptor_ui": "D061505", "major_topic": false }, { "descriptor": "Cell Transdifferentiation", "descriptor_ui": "D054338", "major_topic": false }, { "descriptor": "Cell- and Tissue-Based Therapy", "descriptor_ui": "D064987", "major_topic": false }, { "descriptor": "Dimerization", "descriptor_ui": "D019281", "major_topic": false }, { "descriptor": "DNA Primers", "descriptor_ui": "D017931", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Jurkat Cells", "descriptor_ui": "D019169", "major_topic": false }, { "descriptor": "Milk Proteins", "descriptor_ui": "D008894", "major_topic": false }, { "descriptor": "Phagocytosis", "descriptor_ui": "D010587", "major_topic": false }, { "descriptor": "Phalloidine", "descriptor_ui": "D010590", "major_topic": false }, { "descriptor": "Phosphatidylserines", "descriptor_ui": "D010718", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "rac1 GTP-Binding Protein", "descriptor_ui": "D020830", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jul 15", "date_precision": "day", "issue": "334", "normalized_date": "2014-07-15", "pages": "rs4", "proceedings_title": null, "publisher": "", "title": "Science signaling", "volume": "7", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Rapidly rendering cells phagocytic through a cell surface display technique and concurrent Rac activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Astrocytes generate local calcium (Ca(2+)) signals that are thought to regulate their functions. Visualization of these signals in the intact brain requires an imaging method with high spatiotemporal resolution. Here, we describe such a method using transgenic mice expressing the ultrasensitive ratiometric Ca(2+) indicator yellow Cameleon-Nano 50 (YC-Nano50) in astrocytes. In these mice, we detected a unique pattern of Ca(2+) signals. These occur spontaneously, predominantly in astrocytic fine processes, but not the cell body. Upon sensory stimulation, astrocytes initially responded with Ca(2+) signals at fine processes, which then propagated to the cell body. These observations suggest that astrocytic fine processes function as a high-sensitivity detector of neuronal activities. Thus, the method provides a useful tool for studying the activity of astrocytes in brain physiology and pathology.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazunori", "last_name": "Kanemaru", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Kaname", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Nami", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Moritoh", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Hasuwa", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Mimura", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Masamitsu", "last_name": "Iino", "name": null }, { "creator_type": "author", "first_name": "Kenji F.", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2014.05.056" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24981861" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Calcium-Binding Proteins", "descriptor_ui": "D002135", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Somatosensory Cortex", "descriptor_ui": "D013003", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jul 10", "date_precision": "day", "issue": "1", "normalized_date": "2014-07-10", "pages": "311-318", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "8", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "In vivo visualization of subtle, transient, and local activity of astrocytes using an ultrasensitive Ca(2+) indicator.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In eukaryotic cilia and flagella, outer arm dyneins (OADs) are bound to axonemal doublet microtubules every 24 nm; however, how this regular arrangement is produced remains unknown. To approach this problem, we studied the properties of the OAD-docking complex (ODA-DC), a three-subunit complex that functions as the OAD-docking site on the doublet. Using recombinant ODA-DC, we found that the ODA-DC has an ∼24-nm-long ellipsoidal shape and cooperatively binds to the axoneme in an end-to-end manner. These and other results indicate that cooperative association of the ODA-DC underlies the periodic OAD arrangement at specific positions on the doublets. These findings provide insight into how the regular axonemal repeat structure is produced.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mikito", "last_name": "Owa", "name": null }, { "creator_type": "author", "first_name": "Akane", "last_name": "Furuta", "name": null }, { "creator_type": "author", "first_name": "Jiro", "last_name": "Usukura", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Arisaka", "name": null }, { "creator_type": "author", "first_name": "Stephen M.", "last_name": "King", "name": null }, { "creator_type": "author", "first_name": "George B.", "last_name": "Witman", "name": null }, { "creator_type": "author", "first_name": "Ritsu", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Wakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1403101111" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24979786" } }, "mesh": [ { "descriptor": "Axoneme", "descriptor_ui": "D054468", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Chromatography, Gel", "descriptor_ui": "D002850", "major_topic": false }, { "descriptor": "Dyneins", "descriptor_ui": "D004398", "major_topic": false }, { "descriptor": "Electrophoresis, Polyacrylamide Gel", "descriptor_ui": "D004591", "major_topic": false }, { "descriptor": "Electroporation", "descriptor_ui": "D018274", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": false }, { "descriptor": "Macromolecular Substances", "descriptor_ui": "D046911", "major_topic": false }, { "descriptor": "Microscopy, Electron", "descriptor_ui": "D008854", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Rosaniline Dyes", "descriptor_ui": "D012394", "major_topic": false }, { "descriptor": "Ultracentrifugation", "descriptor_ui": "D014461", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jul 1", "date_precision": "day", "issue": "26", "normalized_date": "2014-07-01", "pages": "9461-9466", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "111", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Cooperative binding of the outer arm-docking complex underlies the regular arrangement of outer arm dynein in the axoneme.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have developed an activatable photosensitizer capable of specifically inducing the death of beta-galactosidase-expressing cells in response to photoirradiation. By using a selenium-substituted rhodol scaffold bearing beta-galactoside as a targeting substituent, we designed and synthesized HMDESeR-betaGal, which has a non-phototoxic spirocyclic structure owing to the presence of the galactoside moiety. However, beta-galactosidase efficiently converted HMDESeR-betaGal into phototoxic HMDESeR, which exists predominantly in the open xanthene form. This structural change resulted in drastic recovery of visible-wavelength absorption and the ability to generate singlet oxygen ((1)O2). When HMDESeR-betaGal was applied to larval Drosophila melanogaster wing disks, which express beta-galactosidase only in the posterior region, photoirradiation induced cell death in the beta-galactosidase-expressing region with high specificity.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Obata", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201403221" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24848546" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "beta-Galactosidase", "descriptor_ui": "D001616", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": false }, { "descriptor": "Photosensitizing Agents", "descriptor_ui": "D017319", "major_topic": false }, { "descriptor": "Selenium", "descriptor_ui": "D012643", "major_topic": false }, { "descriptor": "Selenium Compounds", "descriptor_ui": "D018036", "major_topic": false }, { "descriptor": "Singlet Oxygen", "descriptor_ui": "D026082", "major_topic": false }, { "descriptor": "Thermodynamics", "descriptor_ui": "D013816", "major_topic": false }, { "descriptor": "Wings, Animal", "descriptor_ui": "D014921", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jun 23", "date_precision": "day", "issue": "26", "normalized_date": "2014-06-23", "pages": "6772-6775", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "53", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Selective ablation of beta-galactosidase-expressing cells with a rationally designed activatable photosensitizer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Giant unilamellar vesicles (GUVs) are vesicles>1 mum in diameter that provide an environment in which the effect of a confined reaction volume on intravesicular reactions can be investigated. By synthesizing EmrE, a multidrug transporter from Escherichia coli, as a model membrane protein using a reconstituted in vitro transcription-translation system inside GUVs, we investigated the effect of a confined volume on the synthesis and membrane integration of EmrE. Flow cytometry was used to analyze multiple properties of the vesicles and to quantify EmrE synthesis inside GUVs composed of only 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine. We found that EmrE was synthesized and integrated into the GUV membrane in its active form. We also found that the ratio of membrane-integrated EmrE to total synthesized EmrE increased with decreasing vesicle volume; this finding is explained by the effect of an increased surface-area-to-volume ratio in smaller vesicles. In vitro membrane synthesis inside GUVs is a useful approach to study quantitatively the properties of membrane proteins and their interaction with the membrane under cell-mimicking environments.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Haruka", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Yomo", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/sb400094c" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24328098" } }, "mesh": [ { "descriptor": "Acriflavine", "descriptor_ui": "D000167", "major_topic": false }, { "descriptor": "Antiporters", "descriptor_ui": "D017920", "major_topic": false }, { "descriptor": "Cell-Free System", "descriptor_ui": "D002474", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Escherichia coli Proteins", "descriptor_ui": "D029968", "major_topic": false }, { "descriptor": "Ethidium", "descriptor_ui": "D004996", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Phosphatidylcholines", "descriptor_ui": "D010713", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Unilamellar Liposomes", "descriptor_ui": "D053835", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jun 20", "date_precision": "day", "issue": "6", "normalized_date": "2014-06-20", "pages": "372-379", "proceedings_title": null, "publisher": "", "title": "ACS synthetic biology", "volume": "3", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "In vitro membrane protein synthesis inside cell-sized vesicles reveals the dependence of membrane protein integration on vesicle volume.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We herein present our experience to assess intraoperative confirmation of vascular patency with an uncooled infrared camera in extracranial-intracranial (EC-IC) bypass surgery. This camera had distinguishing characteristics, including its small size, light weight, and adequate temperature resolution (< 0.022 degrees). We used a simplified zoom germanium lens as a preliminary study to verify the potential of using this camera to assess the vascular flow of the end-to-side anastomosis model in rats. In addition, we evaluated the vascular flow in continuous clinical series using this infrared camera during EC-IC bypass in 14 patients (17 sides). This infrared camera offers real-time information on the vascular patency of end-to-side anastomosis vessels of all relevant diameters. The spatial resolution and image quality are satisfactory, and the procedure can be safely repeatable. We have shown that the infrared camera could be a new and feasible technology for intraoperative imaging of the vascular flow and is considered to be clinically useful during cerebrovascular surgery.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Otani", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Kanji", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Kojiro", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.2176/nmc.tn2012-0265" }, "pmcid": { "normalized": "PMC4533455" }, "pmid": { "normalized": "24201104" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebral Angiography", "descriptor_ui": "D002533", "major_topic": false }, { "descriptor": "Cerebral Revascularization", "descriptor_ui": "D002548", "major_topic": false }, { "descriptor": "Cerebrovascular Circulation", "descriptor_ui": "D002560", "major_topic": true }, { "descriptor": "Computer Systems", "descriptor_ui": "D003199", "major_topic": false }, { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Feasibility Studies", "descriptor_ui": "D005240", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Infrared Rays", "descriptor_ui": "D007259", "major_topic": false }, { "descriptor": "Intracranial Aneurysm", "descriptor_ui": "D002532", "major_topic": false }, { "descriptor": "Intracranial Arteriosclerosis", "descriptor_ui": "D002537", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Monitoring, Intraoperative", "descriptor_ui": "D016343", "major_topic": false }, { "descriptor": "Moyamoya Disease", "descriptor_ui": "D009072", "major_topic": false }, { "descriptor": "Photography", "descriptor_ui": "D010781", "major_topic": false }, { "descriptor": "Radiometry", "descriptor_ui": "D011874", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false }, { "descriptor": "Vascular Patency", "descriptor_ui": "D014654", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jun 17", "date_precision": "day", "issue": "6", "normalized_date": "2014-06-17", "pages": "502-506", "proceedings_title": null, "publisher": "", "title": "Neurologia medico-chirurgica", "volume": "54", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Uncooled infrared camera for the noninvasive visualization of the vascular flow in an anastomotic vessel during neurological surgery: technical note.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mammalian target of rapamycin (mTOR) has been implicated in human neurological diseases such as tuberous sclerosis complex (TSC), neurodegeneration, and autism. However, little is known about when and how mTOR is involved in the pathogenesis of these diseases, due to a lack of animal models that directly increase mTOR activity. Here, we generated transgenic mice expressing a gain-of-function mutant of mTOR in the forebrain in a temporally controlled manner. Selective activation of mTORC1 in embryonic stages induced cortical atrophy caused by prominent apoptosis of neuronal progenitors, associated with upregulation of HIF-1alpha. In striking contrast, activation of the mTORC1 pathway in adulthood resulted in cortical hypertrophy with fatal epileptic seizures, recapitulating human TSC. Activated mTORC1 in the adult cortex also promoted rapid accumulation of cytoplasmic inclusions and activation of microglial cells, indicative of progressive neurodegeneration. Our findings demonstrate that mTORC1 plays different roles in developmental and adult stages and contributes to human neurological diseases.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Kassai", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugaya", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Atsu", "last_name": "Aiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2014.04.048" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24857653" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Hypoxia-Inducible Factor 1, alpha Subunit", "descriptor_ui": "D051795", "major_topic": false }, { "descriptor": "Mechanistic Target of Rapamycin Complex 1", "descriptor_ui": "D000076222", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Microcephaly", "descriptor_ui": "D008831", "major_topic": false }, { "descriptor": "Microglia", "descriptor_ui": "D017628", "major_topic": false }, { "descriptor": "Multiprotein Complexes", "descriptor_ui": "D046912", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Prosencephalon", "descriptor_ui": "D016548", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "TOR Serine-Threonine Kinases", "descriptor_ui": "D058570", "major_topic": false }, { "descriptor": "Tuberous Sclerosis", "descriptor_ui": "D014402", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": true } ], "publication": { "conference_name": null, "date": "2014 Jun 12", "date_precision": "day", "issue": "5", "normalized_date": "2014-06-12", "pages": "1626-1639", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "7", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Selective activation of mTORC1 signaling recapitulates microcephaly, tuberous sclerosis, and neurodegenerative diseases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neural circuits are shaped by elimination of early-formed redundant synapses during postnatal development. Retrograde signaling from postsynaptic cells regulates synapse elimination. In this work, we identified semaphorins, a family of versatile cell recognition molecules, as retrograde signals for elimination of redundant climbing fiber to Purkinje cell synapses in developing mouse cerebellum. Knockdown of Sema3A, a secreted semaphorin, in Purkinje cells or its receptor in climbing fibers accelerated synapse elimination during postnatal day 8 (P8) to P18. Conversely, knockdown of Sema7A, a membrane-anchored semaphorin, in Purkinje cells or either of its two receptors in climbing fibers impaired synapse elimination after P15. The effect of Sema7A involves signaling by metabotropic glutamate receptor 1, a canonical pathway for climbing fiber synapse elimination. These findings define how semaphorins retrogradely regulate multiple processes of synapse elimination.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Motokazu", "last_name": "Uchigashima", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Mikuni", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Harumi", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Atsu", "last_name": "Aiba", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.1252514" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24831527" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, CD", "descriptor_ui": "D015703", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "Semaphorin-3A", "descriptor_ui": "D040121", "major_topic": false }, { "descriptor": "Semaphorins", "descriptor_ui": "D039961", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 May 30", "date_precision": "day", "issue": "6187", "normalized_date": "2014-05-30", "pages": "1020-1023", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "344", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Retrograde semaphorin signaling regulates synapse elimination in the developing mouse brain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Calcium ion (Ca2+) is an important second messenger implicated in the control of many different cellular processes in living organisms. Ca2+ is typically studied by direct visualization using chemically or genetically encoded indicators. A complementary, and perhaps more useful, approach involves direct manipulation of Ca2+ concentration; tools for this exist but are rather poorly developed compared to the indicators at least. Here, we report a photoactivatable Ca2+-releasing protein, photoactivatable Ca2+ releaser (PACR), made by the insertion of a photosensitive protein domain (LOV2) into a Ca2+ binding protein (calmodulin fused with the M13 peptide). As the PACR is genetically encoded, and unlike conventional optical control tools (e.g., channel rhodopsin) not membrane bound, we are able to restrict expression within the cell, to allow subcellular perturbation of Ca2+ levels. In whole animals, we are able to control the behavior of Caenorhabditis elegans with light by expressing the PACR only in the touch neuron.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Noritaka", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/cb400849n" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24625002" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calmodulin", "descriptor_ui": "D002147", "major_topic": false }, { "descriptor": "Cations, Divalent", "descriptor_ui": "D002413", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Protein Engineering", "descriptor_ui": "D015202", "major_topic": true }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 May 16", "date_precision": "day", "issue": "5", "normalized_date": "2014-05-16", "pages": "1197-1203", "proceedings_title": null, "publisher": "", "title": "ACS chemical biology", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Optical control of the Ca2+ concentration in a live specimen with a genetically encoded Ca2+-releasing molecular tool.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A switchlike response in nuclear factor-kappaB (NF-kappaB) activity implies the existence of a threshold in the NF-kappaB signaling module. We show that the CARD-containing MAGUK protein 1 (CARMA1, also called CARD11)-TAK1 (MAP3K7)-inhibitor of NF-kappaB (IkappaB) kinase-beta (IKKbeta) module is a switch mechanism for NF-kappaB activation in B cell receptor (BCR) signaling. Experimental and mathematical modeling analyses showed that IKK activity is regulated by positive feedback from IKKbeta to TAK1, generating a steep dose response to BCR stimulation. Mutation of the scaffolding protein CARMA1 at serine-578, an IKKbeta target, abrogated not only late TAK1 activity, but also the switchlike activation of NF-kappaB in single cells, suggesting that phosphorylation of this residue accounts for the feedback.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hisaaki", "last_name": "Shinohara", "name": null }, { "creator_type": "author", "first_name": "Marcelo", "last_name": "Behar", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Tomoharu", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Sanjo", "name": null }, { "creator_type": "author", "first_name": "Shiori", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Yumoto", "name": null }, { "creator_type": "author", "first_name": "Sewon", "last_name": "Ki", "name": null }, { "creator_type": "author", "first_name": "Shizuo", "last_name": "Akira", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Hoffmann", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kurosaki", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Okada-Hatakeyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.1250020" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24833394" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "CARD Signaling Adaptor Proteins", "descriptor_ui": "D053468", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chickens", "descriptor_ui": "D002645", "major_topic": false }, { "descriptor": "Feedback, Physiological", "descriptor_ui": "D025461", "major_topic": false }, { "descriptor": "Guanylate Cyclase", "descriptor_ui": "D006162", "major_topic": false }, { "descriptor": "I-kappa B Kinase", "descriptor_ui": "D051550", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinase 7", "descriptor_ui": "D000099151", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinases", "descriptor_ui": "D020930", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Receptors, Antigen, B-Cell", "descriptor_ui": "D011947", "major_topic": false }, { "descriptor": "Serine", "descriptor_ui": "D012694", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 May 16", "date_precision": "day", "issue": "6185", "normalized_date": "2014-05-16", "pages": "760-764", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "344", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Positive feedback within a kinase signaling complex functions as a switch mechanism for NF-kappaB activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Expression of CGS1, which codes for an enzyme of methionine biosynthesis, is feedback-regulated by mRNA degradation in response to S-adenosyl-L-methionine (AdoMet). In vitro studies revealed that AdoMet induces translation arrest at Ser-94, upon which several ribosomes stack behind the arrested one, and mRNA degradation occurs at multiple sites that presumably correspond to individual ribosomes in a stacked array. Despite the significant contribution of stacked ribosomes to inducing mRNA degradation, little is known about the ribosomes in the stacked array. Here, we assigned the peptidyl-tRNA species of the stacked second and third ribosomes to their respective codons and showed that they are arranged at nine-codon intervals behind the Ser-94 codon, indicating tight stacking. Puromycin reacts with peptidyl-tRNA in the P-site, releasing the nascent peptide as peptidyl-puromycin. This reaction is used to monitor the activity of the peptidyltransferase center (PTC) in arrested ribosomes. Puromycin reaction of peptidyl-tRNA on the AdoMet-arrested ribosome, which is stalled at the pre-translocation step, was slow. This limited reactivity can be attributed to the peptidyl-tRNA occupying the A-site at this step rather than to suppression of PTC activity. In contrast, puromycin reactions of peptidyl-tRNA with the stacked second and third ribosomes were slow but were not as slow as pre-translocation step ribosomes. We propose that the anticodon end of peptidyl-tRNA resides in the A-site of the stacked ribosomes and that the stacked ribosomes are stalled at an early step of translocation, possibly at the P/E hybrid state.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yui", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Yoshitomo", "last_name": "Kadokura", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Sotta", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Satake", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Onouchi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Naito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m113.526616" }, "pmcid": { "normalized": "PMC4007459" }, "pmid": { "normalized": "24652291" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Carbon-Oxygen Lyases", "descriptor_ui": "D019757", "major_topic": false }, { "descriptor": "Electrophoresis, Polyacrylamide Gel", "descriptor_ui": "D004591", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Peptide Chain Elongation, Translational", "descriptor_ui": "D010441", "major_topic": true }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "Puromycin", "descriptor_ui": "D011691", "major_topic": false }, { "descriptor": "Ribosomes", "descriptor_ui": "D012270", "major_topic": false }, { "descriptor": "RNA Stability", "descriptor_ui": "D020871", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "RNA, Plant", "descriptor_ui": "D018749", "major_topic": false }, { "descriptor": "RNA, Transfer, Amino Acyl", "descriptor_ui": "D012346", "major_topic": false }, { "descriptor": "S-Adenosylmethionine", "descriptor_ui": "D012436", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 May 2", "date_precision": "day", "issue": "18", "normalized_date": "2014-05-02", "pages": "12693-12704", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "289", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Ribosomes in a stacked array: elucidation of the step in translation elongation at which they are stalled during S-adenosyl-L-methionine-induced translation arrest of CGS1 mRNA.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Crush syndrome (CS) has been reported in disasters, terrorist incidents, and accidents, and the clinical and pathologic picture has gradually been clarified. Few lethal and reproducible animal models of CS with use of a quantitative load are available. A new model is needed to investigate pathologic and therapeutic aspects of this injury. MATERIALS AND METHODS: Using a device built from commercially available components, both hindlimbs of anesthetized rats were respectively compressed for 6 h using 3.6-kg blocks. The effects of trunk warming alone without compressed hindlimbs (Group A), non-warming at room temperature (Group B), whole-body warming including compressed hindlimbs (Group C), or warming of compressed hindlimbs alone (Group D) during compression were examined. Survival rates were compared and hematological and histologic analyses were performed at specific time points after compression release. RESULTS: Limb or whole-body warming significantly worsened the survival of rats. We found a much lower survival rate of 0%-10% in animals, in which the hindlimbs were warmed during compression (Groups C and D) at 12 h after compression release, compared with 90%-100% in animals without warming of the hindlimbs (Groups A and B). Groups C and D showed significantly enhanced hyperkalemia at >/=4 h after compression release and all blood samples from dead cases showed hyperkalemia (>10 mEq/L). CONCLUSIONS: We developed a new lethal and reproducible rat CS model with a quantitative load. This study found that warming of compressed limbs worsened the survival rate and significantly enhanced hyperkalemia, apparently leading to cardiac arrest.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takefumi", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Yoritsuna", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Tadaaki", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kanatani", "name": null }, { "creator_type": "author", "first_name": "Shoichi", "last_name": "Tachibana", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jss.2013.12.012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24679269" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Temperature", "descriptor_ui": "D001831", "major_topic": false }, { "descriptor": "Crush Syndrome", "descriptor_ui": "D003444", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "Hindlimb", "descriptor_ui": "D006614", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Potassium", "descriptor_ui": "D011188", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Survival Analysis", "descriptor_ui": "D016019", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": true } ], "publication": { "conference_name": null, "date": "2014 May 1", "date_precision": "day", "issue": "1", "normalized_date": "2014-05-01", "pages": "250-259", "proceedings_title": null, "publisher": "", "title": "The Journal of surgical research", "volume": "188", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Improved survival rate by temperature control at compression sites in rat model of crush syndrome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Systems-level identification and analysis of cellular circuits in the brain will require the development of whole-brain imaging with single-cell resolution. To this end, we performed comprehensive chemical screening to develop a whole-brain clearing and imaging method, termed CUBIC (clear, unobstructed brain imaging cocktails and computational analysis). CUBIC is a simple and efficient method involving the immersion of brain samples in chemical mixtures containing aminoalcohols, which enables rapid whole-brain imaging with single-photon excitation microscopy. CUBIC is applicable to multicolor imaging of fluorescent proteins or immunostained samples in adult brains and is scalable from a primate brain to subcellular structures. We also developed a whole-brain cell-nuclear counterstaining protocol and a computational image analysis pipeline that, together with CUBIC reagents, enable the visualization and quantification of neural activities induced by environmental stimulation. CUBIC enables time-course expression profiling of whole adult brains with single-cell resolution.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Etsuo A.", "last_name": "Susaki", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Tainaka", "name": null }, { "creator_type": "author", "first_name": "Dimitri", "last_name": "Perrin", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Kishino", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Tawara", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Onoe", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyonari", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Hiroki R.", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cell.2014.03.042" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24746791" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Callithrix", "descriptor_ui": "D002144", "major_topic": false }, { "descriptor": "Indicators and Reagents", "descriptor_ui": "D007202", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Neuroimaging", "descriptor_ui": "D059906", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Apr 24", "date_precision": "day", "issue": "3", "normalized_date": "2014-04-24", "pages": "726-739", "proceedings_title": null, "publisher": "", "title": "Cell", "volume": "157", "year": 2014 }, "ssbd": { "database": [ "ssbd-database-000048" ], "repository": [ "ssbd-repos-000048" ] }, "title": "Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Covalent attachment of mechanoresponsive luminescent organic or organometallic compounds to other materials is a promising approach to develop a wide variety of mechanoresponsive luminescent materials. Here, we report covalently linkable mechanoresponsive micelles that change their photoluminescence from yellow to green in response to mechanical stimulation under aqueous conditions. These micelles are composed of a dumbbell-shaped amphiphilic pyrene derivative having amine groups at the peripheral positions of its dendrons. Using a well-established cross-linker, the micelles were covalently linked via their peripheral amine groups to the surface of glass beads, polylactic acid (PLA) beads, and living cells under aqueous conditions. Vortexing of glass beads bearing the micelles in a glass vial filled with water caused a photoluminescence color change from yellow to green. PLA beads bearing the micelles showed no change in photoluminescence color under the same conditions. We ascribe this result to the lower density and stiffness of the PLA beads, because the color of the PLA beads changed on vortexing in the presence of bare glass beads. HeLa cells and HL-60 cells bearing the micelles showed no obvious photoluminescence color change under vortexing. The structure, photophysical properties, and mechanism of photoluminescence color change of the micellar assemblies were examined.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshimitsu", "last_name": "Sagara", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja412670g" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24571353" } }, "mesh": [ { "descriptor": "Glass", "descriptor_ui": "D005898", "major_topic": false }, { "descriptor": "HL-60 Cells", "descriptor_ui": "D018922", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lactic Acid", "descriptor_ui": "D019344", "major_topic": false }, { "descriptor": "Luminescence", "descriptor_ui": "D049449", "major_topic": true }, { "descriptor": "Micelles", "descriptor_ui": "D008823", "major_topic": false }, { "descriptor": "Particle Size", "descriptor_ui": "D010316", "major_topic": false }, { "descriptor": "Polyesters", "descriptor_ui": "D011091", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Pyrenes", "descriptor_ui": "D011721", "major_topic": false }, { "descriptor": "Surface Properties", "descriptor_ui": "D013499", "major_topic": false }, { "descriptor": "Surface-Active Agents", "descriptor_ui": "D013501", "major_topic": false }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Mar 19", "date_precision": "day", "issue": "11", "normalized_date": "2014-03-19", "pages": "4273-4280", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "136", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Covalent attachment of mechanoresponsive luminescent micelles to glasses and polymers in aqueous conditions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Poly(N-isopropylacrylamide) (PNIPAAm)-based temperature-responsive fluorescence polymer probes were developed using radical polymerization, with 3-mercaptopropionic acid as the chain-transfer agent, followed by activation of terminal carboxyl groups with N-hydroxysuccinimide and reaction with 5-aminofluorescein (FL). The lower critical solution temperatures (LCSTs) of the resulting fluorescent polymer probes differed depending on the copolymer composition, and had a sharp phase-transition (hydrophilic/hydrophobic) boundary at the LCST. The cellular uptakes of the fluorescent polymer probes were effectively suppressed below the LCST, and increased greatly above the LCST. In particular, the cellular uptake of a copolymer with N,N-dimethylaminopropylacrylamide, P(NIPAAm-co-DMAPAAm2%)-FL (LCST: 37.4 degrees C), can be controlled within only 1 degrees C near body temperature, which is suitable for biological applications. These results indicated that the cellular uptakes of thermoresponsive polymers could be accurately controlled by the temperature, and such polymers have potential applications in discriminating between normal and pathological cells, and in intracellular drug delivery systems with local hyperthermia.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Mirai", "last_name": "Shimamura", "name": null }, { "creator_type": "author", "first_name": "Minami", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Funatsu", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Ayano", "name": null }, { "creator_type": "author", "first_name": "Teruo", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Hideko", "last_name": "Kanazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/mz5000569" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35590521" } }, "mesh": [], "publication": { "conference_name": null, "date": "2014 Mar 18", "date_precision": "day", "issue": "3", "normalized_date": "2014-03-18", "pages": "281-285", "proceedings_title": null, "publisher": "", "title": "ACS macro letters", "volume": "3", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Temperature-Responsive Fluorescence Polymer Probes with Accurate Thermally Controlled Cellular Uptakes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The polarization of neurons, which mainly includes the differentiation of axons and dendrites, is regulated by cell-autonomous and non-cell-autonomous factors. In the developing central nervous system, neuronal development occurs in a heterogeneous environment that also comprises extracellular matrices, radial glial cells, and neurons. Although many cell-autonomous factors that affect neuronal polarization have been identified, the microenvironmental cues involved in neuronal polarization remain largely unknown. Here, we show that neuronal polarization occurs in a microenvironment in the lower intermediate zone, where the cell adhesion molecule transient axonal glycoprotein-1 (TAG-1) is expressed in cortical efferent axons. The immature neurites of multipolar cells closely contact TAG-1-positive axons and generate axons. Inhibition of TAG-1-mediated cell-to-cell interaction or its downstream kinase Lyn impairs neuronal polarization. These results show that the TAG-1-mediated cell-to-cell interaction between the unpolarized multipolar cells and the pioneering axons regulates the polarization of multipolar cells partly through Lyn kinase and Rac1.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Namba", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kibe", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Funahashi", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Nakamuta", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Sachi", "last_name": "Kozawa", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Shimoda", "name": null }, { "creator_type": "author", "first_name": "Kanako", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Yoshino", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Sakakibara", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Catherine", "last_name": "Faivre-Sarrailh", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Kozo", "last_name": "Kaibuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2013.12.015" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24559674" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Cell Adhesion Molecules, Neuronal", "descriptor_ui": "D015816", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": false }, { "descriptor": "Contactin 2", "descriptor_ui": "D058969", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "rac1 GTP-Binding Protein", "descriptor_ui": "D020830", "major_topic": false }, { "descriptor": "src-Family Kinases", "descriptor_ui": "D019061", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Feb 19", "date_precision": "day", "issue": "4", "normalized_date": "2014-02-19", "pages": "814-829", "proceedings_title": null, "publisher": "", "title": "Neuron", "volume": "81", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Pioneering axons regulate neuronal polarization in the developing cerebral cortex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Rhodopsin is a G-protein-coupled receptor, in which retinal chromophore acts as inverse-agonist or agonist depending on its configuration and protonation state. Photostimulation of rhodopsin results in a pH-dependent equilibrium between the active state (Meta-II) and its inactive precursor (Meta-I). Here, we monitored conformational changes of rhodopsin using a fluorescent probe Alexa594 at the cytoplasmic surface, which shows fluorescence increase upon the generation of active state, by single-molecule measurements. The fluorescence intensity of a single photoactivated rhodopsin molecule alternated between two states. Interestingly, such a fluorescence alternation was also observed for ligand-free rhodopsin (opsin), but not for dark-state rhodopsin. In addition, the pH-dependences of Meta-I/Meta-II equilibrium estimated by fluorescence measurements deviated notably from estimates based on absorption spectra, indicating that both Meta-I and Meta-II are mixtures of two conformers. Our observations indicate that rhodopsin molecules intrinsically adopt both active and inactive conformations, and the ligand retinal shifts the conformational equilibrium. These findings provide dynamical insights into the activation mechanisms of G-protein-coupled receptors.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Akimori", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Shichida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Imamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpj.2014.01.020" }, "pmcid": { "normalized": "PMC3945020" }, "pmid": { "normalized": "24559994" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cattle", "descriptor_ui": "D002417", "major_topic": false }, { "descriptor": "Guanosine Diphosphate", "descriptor_ui": "D006153", "major_topic": false }, { "descriptor": "Guanosine Triphosphate", "descriptor_ui": "D006160", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Rhodopsin", "descriptor_ui": "D012243", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Feb 18", "date_precision": "day", "issue": "4", "normalized_date": "2014-02-18", "pages": "915-924", "proceedings_title": null, "publisher": "", "title": "Biophysical journal", "volume": "106", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-molecule observation of the ligand-induced population shift of rhodopsin, a G-protein-coupled receptor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although the magnesium ion (Mg(2+)) is one of the most abundant divalent cations in cells and is known to play critical roles in many physiological processes, its mobilization and underlying mechanisms are still unknown. Here, we describe a novel fluorescent Mg(2+) probe, \"KMG-104-AsH\", composed of a highly selective fluorescent Mg(2+) probe, \"KMG-104\", and a fluorescence-recoverable probe, \"FlAsH\", bound specifically to a tetracysteine peptide tag (TCtag), which can be genetically incorporated into any protein. This probe was developed for molecular imaging of local changes in intracellular Mg(2+) concentration. KMG-104-AsH was synthesized, and its optical properties were investigated in solution. The fluorescence intensity of KMG-104-AsH (at lambda(em/max) = 540 nm) increases by more than 10-fold by binding to both the TCtag peptide and Mg(2+), and the probe is highly selective for Mg(2+) (K(d/Mg) = 1.7 mM, K(d/Ca) >> 100 mM). Application of the probe for imaging of Mg(2+) in HeLa cells showed that this FlAsH-type Mg(2+) sensing probe is membrane-permeable and binds specifically to tagged proteins, such as TCtag-actin and mKeima-TCtag targeted to the cytoplasm and the mitochondrial intermembrane space. KMG-104-AsH bound to TCtag responded to an increase in intracellular Mg(2+) concentration caused by the release of Mg(2+) from mitochondria induced by FCCP, a protonophore that eliminates the inner membrane potential of mitochondria. This probe is expected to be a strong tool for elucidating the dynamics and mechanisms of intracellular localization of Mg(2+).", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja410031n" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24447167" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": true }, { "descriptor": "Quinazolines", "descriptor_ui": "D011799", "major_topic": false }, { "descriptor": "Xanthenes", "descriptor_ui": "D014966", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Feb 12", "date_precision": "day", "issue": "6", "normalized_date": "2014-02-12", "pages": "2374-2381", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "136", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Design and synthesis of a FlAsH-type Mg2+ fluorescent probe for specific protein labeling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The metabotropic glutamate receptor subtype 1 (mGluR1, Grm1) in cerebellar Purkinje cells (PCs) is essential for motor coordination and motor learning. At the synaptic level, mGluR1 has a critical role in long-term synaptic depression (LTD) at parallel fiber (PF)-PC synapses, and in developmental elimination of climbing fiber (CF)-PC synapses. mGluR1a, a predominant splice variant in PCs, has a long carboxyl (C)-terminal domain that interacts with Homer scaffolding proteins. Cerebellar roles of the C-terminal domain at both synaptic and behavior levels remain poorly understood. To address this question, we introduced a short variant, mGluR1b, which lacks this domain into PCs of mGluR1-knock-out (KO) mice (mGluR1b-rescue mice). In mGluR1b-rescue mice, mGluR1b showed dispersed perisynaptic distribution in PC spines. Importantly, mGluR1b-rescue mice exhibited impairments in inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca(2+) release, CF synapse elimination, LTD induction, and delay eyeblink conditioning: they showed normal transient receptor potential canonical (TRPC) currents and normal motor coordination. In contrast, PC-specific rescue of mGluR1a restored all cerebellar defects of mGluR1-KO mice. We conclude that the long C-terminal domain of mGluR1a is required for the proper perisynaptic targeting of mGluR1, IP3R-mediated Ca(2+) release, CF synapse elimination, LTD, and motor learning, but not for TRPC currents and motor coordination.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Ohtani", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Fukaya", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kase", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Kassai", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Tatsumi", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Atsu", "last_name": "Aiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.3542-13.2014" }, "pmcid": { "normalized": "PMC6802745" }, "pmid": { "normalized": "24523559" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Immunoprecipitation", "descriptor_ui": "D047468", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Psychomotor Performance", "descriptor_ui": "D011597", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Feb 12", "date_precision": "day", "issue": "7", "normalized_date": "2014-02-12", "pages": "2702-2712", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "34", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "The synaptic targeting of mGluR1 by its carboxyl-terminal domain is crucial for cerebellar function.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2) is a second prostaglandin D2 receptor involved in mediating the allergic response; however, its central function is not yet known. Here, we demonstrate that central CRTH2 mediates emotional impairment. Lipopolysaccharide (LPS)-induced decreases in social interaction and novel exploratory behavior were observed in wild-type (CRTH2(+/+)) mice but not CRTH2-deficient (CRTH2(-/-)) mice, but both genotypes showed hypolocomotion and anorexia following LPS injection. Tumor (colon 26) inoculation, a more pathologically relevant model, induced decreases in social interaction and novel exploratory behavior in CRTH2(+/+), but not CRTH2(-/-) mice. In addition, the CRTH2 antagonists including clinically available ramatroban reversed impaired social interaction and novel exploratory behavior after either LPS or tumor inoculation in CRTH2(+/+) mice. Finally, LPS-induced c-Fos expression in the hypothalamic paraventricular nucleus (PVN) and central amygdala (CeA) was selectively abolished in CRTH2(-/-) mice. These results show that CRTH2 participates in LPS-induced emotional changes and activation in the PVN and CeA. Our study provides the first evidence that central CRTH2 regulates specific emotional behaviors, and that CRTH2 antagonism has potential as a therapeutic target for behavioral symptoms associated with tumors and infectious diseases.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ryota", "last_name": "Haba", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Onaka", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Kanoh", "name": null }, { "creator_type": "author", "first_name": "Hyper", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Risa", "last_name": "Takenaga", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Kin-ya", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.1407-13.2014" }, "pmcid": { "normalized": "PMC6802750" }, "pmid": { "normalized": "24523542" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Illness Behavior", "descriptor_ui": "D055809", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neoplasms, Experimental", "descriptor_ui": "D009374", "major_topic": false }, { "descriptor": "Receptors, Immunologic", "descriptor_ui": "D011971", "major_topic": false }, { "descriptor": "Receptors, Prostaglandin", "descriptor_ui": "D011982", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "Stress, Psychological", "descriptor_ui": "D013315", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Feb 12", "date_precision": "day", "issue": "7", "normalized_date": "2014-02-12", "pages": "2514-2523", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "34", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Central CRTH2, a second prostaglandin D2 receptor, mediates emotional impairment in the lipopolysaccharide and tumor-induced sickness behavior model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Jesus", "last_name": "Avila", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fneur.2014.00001" }, "pmcid": { "normalized": "PMC3889107" }, "pmid": { "normalized": "24454306" } }, "mesh": [], "publication": { "conference_name": null, "date": "2014 Jan 13", "date_precision": "day", "issue": "", "normalized_date": "2014-01-13", "pages": "1", "proceedings_title": null, "publisher": "", "title": "Frontiers in neurology", "volume": "5", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "\"Tau oligomers,\" what we know and what we don't know.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Androgens including testosterone, organize the nervous system as well as masculine external and internal genitalia during the perinatal period. Androgen organization involves promotion of masculine body features, usually by acting through androgen receptors (ARs). We have recently demonstrated that the gastrin-releasing peptide (GRP) system in the lumbar spinal cord also mediates spinal centers promoting penile reflexes during male sexual behavior in rats. Testosterone may induce sexual differentiation of this spinal GRP system during development and maintain its activation in adulthood. In the present study, we examined the role of ARs in the nervous system regulating the development of the sexually dimorphic GRP system. For this purpose, we used a conditional mouse line selectively lacking the AR gene in the nervous system. AR floxed males carrying (mutants) or not (controls) the nestin-Cre transgene were castrated in adulthood and supplemented with physiological amounts of testosterone. Loss of AR expression in the nervous system resulted in a significant decrease in the number of GRP neurons compared to control littermates. Consequently, the intensity of GRP axonal projections onto the lower lumbar and upper sacral spinal cord was greater in control males than in mutant males. These results suggest that ARs expressed in the nervous system play a significant role in the development of the GRP system in the male lumbar spinal cord. The AR-deletion mutation may attenuate sexual behavior and activity of mutant males via spinal GRP system-mediated neural mechanisms.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Clarisse", "last_name": "Marie-Luce", "name": null }, { "creator_type": "author", "first_name": "Kalina", "last_name": "Raskin", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Oti", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Sakina", "last_name": "Mhaouty-Kodja", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neulet.2013.10.068" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24211692" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Castration", "descriptor_ui": "D002369", "major_topic": false }, { "descriptor": "Cell Count", "descriptor_ui": "D002452", "major_topic": false }, { "descriptor": "Gastrin-Releasing Peptide", "descriptor_ui": "D019886", "major_topic": false }, { "descriptor": "Lumbosacral Region", "descriptor_ui": "D008161", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Mutant Strains", "descriptor_ui": "D008817", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Receptors, Androgen", "descriptor_ui": "D011944", "major_topic": false }, { "descriptor": "Sex Characteristics", "descriptor_ui": "D012727", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false }, { "descriptor": "Testosterone", "descriptor_ui": "D013739", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jan 13", "date_precision": "day", "issue": "", "normalized_date": "2014-01-13", "pages": "109-114", "proceedings_title": null, "publisher": "", "title": "Neuroscience letters", "volume": "558", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Androgen regulates development of the sexually dimorphic gastrin-releasing peptide neuron system in the lumbar spinal cord: evidence from a mouse line lacking androgen receptor in the nervous system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Rheumatoid arthritis (RA) is an autoimmune inflammatory disease exhibited most commonly in joints. We found that the expression of C1qtnf3, which encodes C1q/TNF-related protein 3 (CTRP3), was highly increased in two mouse RA models with different etiology. To elucidate the pathogenic roles of CTRP3 in the development of arthritis, we generated C1qtnf3(-/-) mice and examined the development of collagen-induced arthritis in these mice. We found that the incidence and severity score was higher in C1qtnf3(-/-) mice compared with wild-type (WT) mice. Histopathology of the joints was also more severe in C1qtnf3(-/-) mice. The levels of antibodies against type II collagen and pro-inflammatory cytokine mRNAs in C1qtnf3(-/-) mice were higher than WT mice. These observations indicate that CTRP3 plays an important role in the development of autoimmune arthritis, suggesting CTRP3 as a possible medicine to treat RA.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masanori A.", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Kakuta", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Akimasa", "last_name": "Seno", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shinobu", "last_name": "Saijo", "name": null }, { "creator_type": "author", "first_name": "Masahira", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Iwakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2013.11.040" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24269820" } }, "mesh": [ { "descriptor": "Adipokines", "descriptor_ui": "D054392", "major_topic": false }, { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arthritis, Experimental", "descriptor_ui": "D001169", "major_topic": false }, { "descriptor": "Arthritis, Rheumatoid", "descriptor_ui": "D001172", "major_topic": false }, { "descriptor": "Autoimmunity", "descriptor_ui": "D015551", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Collagen Type II", "descriptor_ui": "D024043", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Joints", "descriptor_ui": "D007596", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jan 3", "date_precision": "day", "issue": "1", "normalized_date": "2014-01-03", "pages": "42-48", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "443", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "CTRP3 plays an important role in the development of collagen-induced arthritis in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent advances in quantitative single-cell analysis revealed large diversity in gene expression levels between individual cells, which could affect the physiology and/or fate of each cell. In contrast, for most metabolites, the concentrations were only measureable as ensemble averages of many cells. In living cells, adenosine triphosphate (ATP) is a critically important metabolite that powers many intracellular reactions. Quantitative measurement of the absolute ATP concentration in individual cells has not been achieved because of the lack of reliable methods. In this study, we developed a new genetically-encoded ratiometric fluorescent ATP indicator “QUEEN”, which is composed of a single circularly-permuted fluorescent protein and a bacterial ATP binding protein. Unlike previous FRET-based indicators, QUEEN was apparently insensitive to bacteria growth rate changes. Importantly, intracellular ATP concentrations of numbers of bacterial cells calculated from QUEEN fluorescence were almost equal to those from firefly luciferase assay. Thus, QUEEN is suitable for quantifying the absolute ATP concentration inside bacteria cells. Finally, we found that, even for a genetically-identical Escherichia coli cell population, absolute concentrations of intracellular ATP were significantly diverse between individual cells from the same culture, by imaging QUEEN signals from single cells.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Yaginuma", "name": null }, { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Kazuhito V.", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Tomiyama", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kakizuka", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Noji", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Imamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep06522" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25283467" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Diagnostic Imaging", "descriptor_ui": "D003952", "major_topic": true }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "4", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Diversity in ATP concentrations in a single bacterial cell population revealed by quantitative single-cell imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "SLD5 is a member of the GINS complex composed of PSF1, PSF2, PSF3 and SLD5, playing a critical role in the formation of the DNA replication fork with CDC45 in yeast. Previously, we had isolated a PSF1 orthologue from a murine hematopoietic stem cell DNA library and were then able to identify orthologues of all the other GINS members by the yeast two hybrid approach using PSF1 as the bait. These GINS orthologues may also function in DNA replication in mammalian cells because they form tetrameric complexes as observed in yeast, and gene deletion mutants of both PSF1 and SLD5 result in a lack of epiblast proliferation and early embryonic lethality. However, we found that PSF1 is also involved in chromosomal segregation in M phase, consistent with recent suggestions that homologues of genes associated with DNA replication in lower organisms also regulate cellular events other than DNA replication in mammalian cells. Here we analyzed the function of SLD5 other than DNA replication and found that it is active in DNA damage and repair. Attenuation of SLD5 expression results in marked DNA damage in both normal cells and cancer cells, suggesting that it protects against DNA damage. Attenuation of SLD5 delays the DNA repair response and cell cycle restoration in normal cells but not in cancer cells. These findings suggest that SLD5 might represent a therapeutic target molecule acting at the level of tumor stromal cells rather than the cancerous cells themselves, because development of the tumor microenvironment could be delayed or disrupted by the suppression of its expression in the normal cell types within the tumor.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Zhi-Yuan", "last_name": "Gong", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Mohri", "name": null }, { "creator_type": "author", "first_name": "Yinglu", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0110483" }, "pmcid": { "normalized": "PMC4204874" }, "pmid": { "normalized": "25334017" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Cell Cycle Checkpoints", "descriptor_ui": "D059447", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": true }, { "descriptor": "DNA Repair", "descriptor_ui": "D004260", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Rad51 Recombinase", "descriptor_ui": "D051135", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "10", "normalized_date": "2014", "pages": "e110483", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "DNA damage enhanced by the attenuation of SLD5 delays cell cycle restoration in normal cells but not in cancer cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alzheimer's disease is a progressive dementia that is characterized by a loss of recent memory. Evidence has accumulated to support the hypothesis that synapses are critical storage sites for memory. However, it is still uncertain whether tau protein is involved in associative memory storage and whether tau is distributed in mature brain synapses. To address this question, we examined the synaptosomal distribution of tau protein in both JNPL3 transgenic mice expressing human P301L tau and non-transgenic littermates. The JNPL3 mouse line is known as one of the mouse models of human tauopathy that develop motor and behavioral deficits with intracellular tau aggregates in the spinal cord and brainstem. The phenotype of disease progression is highly dependent on strain background. In this study, we confirmed that male JNPL3 transgenic mice with C57BL/6J strain background showed neither any sign of motor deficits nor accumulation of hyperphosphorylated tau in the sarkosyl-insoluble fraction until 18 months of age. Subcellular fractionation analysis showed that both mouse tau and human P301L tau were present in the synaptosomal fraction. Those tau proteins were less-phosphorylated than tau in the cytosolic fraction. Human P301L tau was preferentially distributed in the synaptosomal fraction while mouse endogenous tau was more distributed in the cytosolic fraction. Interestingly, a human-specific tau band with phosphorylation at Ser199 and Ser396 was observed in the synaptosomal fraction of JNPL3 mice. This tau was not identical to either tau species in cytosolic fraction or a prominent hyperphosphorylated 64 kDa tau species that was altered to tau pathology. These results suggest that exogenous human P301L tau induces synaptosomal distribution of tau protein with a certain phosphorylation. Regulating the synaptosomal tau level might be a potential target for a therapeutic intervention directed at preventing neurodegeneration.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Miyuki", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fneur.2014.00026" }, "pmcid": { "normalized": "PMC3949102" }, "pmid": { "normalized": "24653715" } }, "mesh": [], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "26", "proceedings_title": null, "publisher": "", "title": "Frontiers in neurology", "volume": "5", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Biochemical Distribution of Tau Protein in Synaptosomal Fraction of Transgenic Mice Expressing Human P301L Tau.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Apoptosis is the programmed cell death which maintains the healthy survival/death balance in metazoan cells. Defect in apoptosis can cause cancer or autoimmunity, while enhanced apoptosis may cause degenerative diseases. The apoptotic signals contribute into safeguarding the genomic integrity while defective apoptosis may promote carcinogenesis. The apoptotic signals are complicated and they are regulated at several levels. The signals of carcinogenesis modulate the central control points of the apoptotic pathways, including inhibitor of apoptosis (IAP) proteins and FLICE-inhibitory protein (c-FLIP). The tumor cells may use some of several molecular mechanisms to suppress apoptosis and acquire resistance to apoptotic agents, for example, by the expression of antiapoptotic proteins such as Bcl-2 or by the downregulation or mutation of proapoptotic proteins such as BAX. In this review, we provide the main regulatory molecules that govern the main basic mechanisms, extrinsic and intrinsic, of apoptosis in normal cells. We discuss how carcinogenesis could be developed via defective apoptotic pathways or their convergence. We listed some molecules which could be targeted to stimulate apoptosis in different cancers. Together, we briefly discuss the development of some promising cancer treatment strategies which target apoptotic inhibitors including Bcl-2 family proteins, IAPs, and c-FLIP for apoptosis induction.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mohamed", "last_name": "Hassan", "name": null }, { "creator_type": "author", "first_name": "Hidemichi", "last_name": "Watari", "name": null }, { "creator_type": "author", "first_name": "Ali", "last_name": "AbuAlmaaty", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Sakuragi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1155/2014/150845" }, "pmcid": { "normalized": "PMC4075070" }, "pmid": { "normalized": "25013758" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "CASP8 and FADD-Like Apoptosis Regulating Protein", "descriptor_ui": "D053446", "major_topic": false }, { "descriptor": "Genes, bcl-2", "descriptor_ui": "D019254", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inhibitor of Apoptosis Proteins", "descriptor_ui": "D051034", "major_topic": false }, { "descriptor": "Molecular Targeted Therapy", "descriptor_ui": "D058990", "major_topic": true }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "150845", "proceedings_title": null, "publisher": "", "title": "BioMed research international", "volume": "2014", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Apoptosis and molecular targeting therapy in cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" }, { "id": "A03-2", "label": "Planned Research A03-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnmol.2014.00090" }, "pmcid": { "normalized": "PMC4243560" }, "pmid": { "normalized": "25505381" } }, "mesh": [], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "90", "proceedings_title": null, "publisher": "", "title": "Frontiers in molecular neuroscience", "volume": "7", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetically encoded Ca(2+) indicators; expanded affinity range, color hue and compatibility with optogenetics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mammals contain 1 melanopsin (Opn4) gene that is expressed in a subset of retinal ganglion cells to serve as a photopigment involved in non-image-forming vision such as photoentrainment of circadian rhythms. In contrast, most nonmammalian vertebrates possess multiple melanopsins that are distributed in various types of retinal cells; however, their functions remain unclear. We previously found that the lamprey has only 1 type of mammalian-like melanopsin gene, which is similar to that observed in mammals. Here we investigated the molecular properties and localization of melanopsin in the lamprey and other cyclostome hagfish retinas, which contribute to visual functions including image-forming vision and mainly to non-image-forming vision, respectively. We isolated 1 type of mammalian-like melanopsin cDNA from the eyes of each species. We showed that the recombinant lamprey melanopsin was a blue light-sensitive pigment and that both the lamprey and hagfish melanopsins caused light-dependent increases in calcium ion concentration in cultured cells in a manner that was similar to that observed for mammalian melanopsins. We observed that melanopsin was distributed in several types of retinal cells, including horizontal cells and ganglion cells, in the lamprey retina, despite the existence of only 1 melanopsin gene in the lamprey. In contrast, melanopsin was almost specifically distributed to retinal ganglion cells in the hagfish retina. Furthermore, we found that the melanopsin-expressing horizontal cells connected to the rhodopsin-containing short photoreceptor cells in the lamprey. Taken together, our findings suggest that in cyclostomes, the global distribution of melanopsin in retinal cells might not be related to the melanopsin gene number but to the extent of retinal contribution to visual function.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Lanfang", "last_name": "Sun", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Kawano-Yamashita", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Hisao", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Furutani", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0108209" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25251771" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DNA, Complementary", "descriptor_ui": "D018076", "major_topic": false }, { "descriptor": "Hagfishes", "descriptor_ui": "D006196", "major_topic": false }, { "descriptor": "Lampreys", "descriptor_ui": "D007798", "major_topic": false }, { "descriptor": "Melanopsin", "descriptor_ui": "D000099210", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Rod Opsins", "descriptor_ui": "D017299", "major_topic": false }, { "descriptor": "Vision, Ocular", "descriptor_ui": "D014785", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "9", "normalized_date": "2014", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Distribution of Mammalian-Like Melanopsin in Cyclostome Retinas Exhibiting a Different Extent of Visual Functions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In a variety of animal species, females hold a leading position in evaluating potential mating partners. The decision of virgin females to accept or reject a courting male is one of the most critical steps for mating success. In the fruitfly Drosophila melanogaster, however, the molecular and neuronal mechanisms underlying female receptivity are still poorly understood, particularly for virgin females. The Drosophila painless (pain) gene encodes a transient receptor potential (TRP) ion channel. We previously demonstrated that mutations in pain significantly enhance the sexual receptivity of virgin females and that pain expression in pain(GAL4) -positive neurons is necessary and sufficient for pain-mediated regulation of the virgin receptivity. Among the pain(GAL4) -positive neurons in the adult female brain, here we have found that insulin-producing cells (IPCs), a neuronal subset in the pars intercerebralis, are essential in virgin females for the regulation of sexual receptivity through Pain TRP channels. IPC-specific knockdown of pain expression or IPC ablation strongly enhanced female sexual receptivity as was observed in pain mutant females. When pain expression or neuronal activity was conditionally suppressed in adult IPCs, female sexual receptivity was similarly enhanced. Furthermore, both pain mutations and the conditional knockdown of pain expression in IPCs depressed female rejection behaviors toward courting males. Taken together, our results indicate that the Pain TRP channel in IPCs plays an important role in controlling the sexual receptivity of Drosophila virgin females by positively regulating female rejection behaviors during courtship.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hirono", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Shoma", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Show", "last_name": "Inami", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kitamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0088175" }, "pmcid": { "normalized": "PMC3913769" }, "pmid": { "normalized": "24505416" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Courtship", "descriptor_ui": "D003380", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Ion Channels", "descriptor_ui": "D007473", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Sexual Behavior, Animal", "descriptor_ui": "D012726", "major_topic": false }, { "descriptor": "Transient Receptor Potential Channels", "descriptor_ui": "D050051", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "2", "normalized_date": "2014", "pages": "e88175", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Insulin-producing cells regulate the sexual receptivity through the painless TRP channel in Drosophila virgin females.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ecdysteroids, known as molting hormones, play central roles in the onset of molting, metamorphosis, and reproduction in arthropods. The ecdysteroids stored in eggs also play an important role in embryogenesis. In insects, ecdysteroids are stored as phosphate esters, which are converted to an active form by ecdysteroid-phosphate phosphatase (EPPase). Although EPPase is believed to be widely conserved in the Ecdysozoa, little is known about its expression in clades other than Insecta. In this study, we cloned a putative EPPase gene from a small fresh water crustacean known as a water flea, Daphnia magna Straus (Cladocera: Daphniidae), and examined its expression during embryogenesis. The amino acid sequence of the putative crustacean EPPase cDNA showed high similarity to insect EPPase and human suppressor of T-cell receptor signaling-1. We also found that the D. magna EPPase was highly expressed during early embryogenesis; its expression rapidly decreased 6 h after oviposition. This timing corresponds to the onset of organogenesis in D. magna. The expression of EPPase could not be detected in diapaused eggs. This is the first report of an EPPase from crustaceans, and the results suggest that the function of EPPase is conserved between insects and crustaceans.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Miki", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jisesa/ieu043" }, "pmcid": { "normalized": "PMC5634057" }, "pmid": { "normalized": "25399434" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Phosphoric Monoester Hydrolases", "descriptor_ui": "D010744", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "181", "proceedings_title": null, "publisher": "", "title": "Journal of insect science (Online)", "volume": "14", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Early embryonic expression of a putative ecdysteroid-phosphate phosphatase in the water flea, Daphnia magna (Cladocera: Daphniidae).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "For many species, dyadic interaction during courtship and pair bonding engage intense emotional states that control approach or avoidance behavior. Previous studies have shown that one component of a common social brain network (SBN), dopaminergic areas, are highly engaged during male songbird courtship of females. We tested whether the level of activity in dopaminergic systems of both females and males during courtship is related to their level of affiliation. In order to objectively quantify affiliative behaviors, we developed a system for tracking the position of both birds during free interaction sessions. During a third successive daily interaction session, there was a range of levels of affiliation among bird pairs, as quantified by several position and movement parameters. Because both positive and negative social interactions were present, we chose to characterize affiliation strength by pair valence. As a potential neural system involved in regulating pair valence, the level of activity of the dopaminergic group A11 (within the central gray) was selectively reduced in females of positive valence pairs. Further, activation of non-dopaminergic neurons in VTA was negatively related to valence, with this relationship strongest in ventral VTA of females. Together, these results suggest that inhibition of fear or avoidance networks may be associated with development of close affiliation, and highlight the importance of negative as well as positive emotional states in the process of courtship, and in development of long-lasting social bonds.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mai", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Thomas M.", "last_name": "Poulsen", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Neal A.", "last_name": "Hessler", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnbeh.2014.00210" }, "pmcid": { "normalized": "PMC4052804" }, "pmid": { "normalized": "24966819" } }, "mesh": [], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "210", "proceedings_title": null, "publisher": "", "title": "Frontiers in behavioral neuroscience", "volume": "8", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Sexually dimorphic activation of dopaminergic areas depends on affiliation during courtship and pair formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Accumulating evidence from human genetic studies implicates the pituitary adenylate cyclase-activating polypeptide (PACAP) gene as a risk factor for psychiatric disorders, including schizophrenia and stress-related diseases. Mice with homozygous disruption of the PACAP gene display profound behavioral and neurological abnormalities that are ameliorated with the atypical antipsychotic and dopamine D2 and serotonin (5-HT)2 antagonist risperidone and the 5-HT2 receptor antagonist ritanserin; however, the underlying mechanisms remain unknown. Here, we investigated if PACAP heterozygous mutant (PACAP(+/-)) mice, which appear behaviorally normal, are vulnerable to aversive stimuli. PACAP(+/-) mice were administered a 5-HT2 receptor agonist, (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI), a hallucinogenic drug, and their responses were compared with the littermate wild-type mice. After DOI injection, PACAP(+/-) mice showed increased head-twitch responses, while their behavior was normal after saline. DOI induced deficits in sensorimotor gating, as determined by prepulse inhibition, specifically in PACAP(+/-) mice. However, other 5-HT2 receptor-dependent responses, such as corticosterone release and hypothermia, were similarly observed in PACAP(+/-) and wild-type mice. c-Fos expression analysis, performed in various brain regions, revealed that the DOI-induced increase in the number of c-Fos-positive cells was more pronounced in 5-HT2A receptor-negative cells in the somatosensory cortex in PACAP(+/-) mice compared with wild-type mice. These results indicate that PACAP(+/-) mice exhibit specific vulnerability to DOI-induced deficits in cortical sensory function, such as exaggerated head-twitch responses and sensorimotor gating deficits. Our findings provide insight into the neural mechanisms underlying impaired behavioral responses in which 5-HT2 receptors are implicated.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Hazama", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Uetsuki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Encho", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Dora", "last_name": "Reglodi", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Miyakawa", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0089153" }, "pmcid": { "normalized": "PMC3930680" }, "pmid": { "normalized": "24586556" } }, "mesh": [ { "descriptor": "Amphetamines", "descriptor_ui": "D000662", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Hallucinogens", "descriptor_ui": "D006213", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mothers", "descriptor_ui": "D009035", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-fos", "descriptor_ui": "D016760", "major_topic": false }, { "descriptor": "Receptors, Serotonin, 5-HT2", "descriptor_ui": "D044348", "major_topic": false }, { "descriptor": "Serotonin 5-HT2 Receptor Agonists", "descriptor_ui": "D058826", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "2", "normalized_date": "2014", "pages": "e89153", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Increased behavioral and neuronal responses to a hallucinogenic drug in PACAP heterozygous mutant mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The discovery of tau mutations in frontotemporal dementia has been a key event in neurodegenerative disease research. The rTg4510 mouse line expressing human tau with P301L FTDP-17-tau mutation has been established to understand the role of tau in neurodegeneration. Our histological analyses with tau antibodies and fluorescent tau ligands on rTg4510 mice revealed that tau oligomer formation was distinct from tangle formation. While in vivo imaging of mature tangles is now available, imaging biomarkers for tau oligomers would be useful for clarifying their roles in neurotoxicity and for diagnosing early-stage tau pathology.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Yan", "last_name": "Ren", "name": null }, { "creator_type": "author", "first_name": "Sarah", "last_name": "Ward", "name": null }, { "creator_type": "author", "first_name": "Lester I.", "last_name": "Binder", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Higuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3233/jad-132429" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24595194" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Early Diagnosis", "descriptor_ui": "D042241", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neurofibrillary Tangles", "descriptor_ui": "D016874", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "S91-96", "proceedings_title": null, "publisher": "", "title": "Journal of Alzheimer's disease : JAD", "volume": "40 Suppl 1", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Tau oligomers as potential targets for early diagnosis of tauopathy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Prolactin-releasing peptide (PrRP) is one of the RF-amide peptides and was originally identified in the bovine hypothalamus as a stimulator of prolactin (PRL) release. Independently, another RF-amide peptide was found in Japanese crucian carp and named Carassius-RFa (C-RFa), which shows high homology to PrRP and stimulates PRL secretion in teleost fish. Therefore, C-RFa has been recognized as fish PrRP. However, recent work has revealed that PrRP and C-RFa in non-mammalian vertebrates are encoded by separate genes originated through duplication of an ancestral gene. Indeed, both PrRP and C-RFa are suggested to exist in teleost, amphibian, reptile, and avian species. Therefore, we propose that non-mammalian PrRP (C-RFa) be renamed PrRP2. Despite a common evolutionary origin, PrRP2 appears to be a physiological regulator of PRL, whereas this is not a consistent role for PrRP itself. Further work revealed that the biological functions of PrRP and PrRP2 are not limited solely to PRL release, because they are also neuromodulators of several hypothalamus-pituitary axes and are involved in some brain circuits related to the regulation of food intake, stress, and cardiovascular functions. However, these actions appear to be different among vertebrates. For example, central injection of PrRP inhibits feeding behavior in rodents and teleosts, while it stimulates it in chicks. Therefore, both PrRP and PrRP2 have acquired diverse actions through evolution. In this review, we integrate the burgeoning information of structures, expression profiles, and multiple biological actions of PrRP in higher vertebrates, as well as those of PrRP2 in non-mammals.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fendo.2014.00170" }, "pmcid": { "normalized": "PMC4226156" }, "pmid": { "normalized": "25426099" } }, "mesh": [], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "170", "proceedings_title": null, "publisher": "", "title": "Frontiers in endocrinology", "volume": "5", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Functions of two distinct \"prolactin-releasing peptides\" evolved from a common ancestral gene.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Autophagy is an evolutionarily conserved mechanism for the gross disposal of intracellular proteins in mammalian cells and dysfunction in this pathway has been associated with human disease. Although the serine threonine kinase Akt is suggested to play a role in this process, little is known about the molecular mechanisms by which Akt induces autophagy. Using a yeast two-hybrid screen, Phafin2 (EAPF or PLEKHF2), a lysosomal protein with a unique structure of N-terminal PH (pleckstrin homology) domain and C-terminal FYVE (Fab 1, YOTB, Vac 1, and EEA1) domain was found to interact with Akt. A sucrose gradient fractionation experiment revealed that both Akt and Phafin2 co-existed in the same lysosome enriched fraction after autophagy induction. Confocal microscopic analysis and BiFC analysis demonstrated that both Akt and Phafin2 accumulate in the lysosome after induction of autophagy. BiFC analysis using PtdIns (3)P interaction defective mutant of Phafin2 demonstrated that lysosomal accumulation of the Akt-Phafin2 complex and subsequent induction of autophagy were lysosomal PtdIns (3)P dependent events. Furthermore, in murine macrophages, both Akt and Phafin2 were required for digestion of fluorescent bacteria and/or LPS-induced autophagy. Taken together, these findings establish that lysosomal accumulation of Akt and Phafin2 is a critical step in the induction of autophagy via an interaction with PtdIns (3)P.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mami", "last_name": "Matsuda-Lennikov", "name": null }, { "creator_type": "author", "first_name": "Futoshi", "last_name": "Suizu", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kohki", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Nagamine", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Iwanaga", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0079795" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24416124" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lysosomes", "descriptor_ui": "D008247", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Phosphatidylinositol Phosphates", "descriptor_ui": "D018129", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false }, { "descriptor": "Vesicular Transport Proteins", "descriptor_ui": "D033921", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "1", "normalized_date": "2014", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Lysosomal Interaction of Akt with Phafin2: A Critical Step in the Induction of Autophagy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Heat shock cognate protein 70 (Hsc70) acts as a molecular chaperone for the maintenance of intracellular proteins, which allows cancer cells to survive under proteotoxic stress. We attempted to use Hsc70 to identify key molecules in cancer cell survival. Here, we performed mass-spectrometry-based proteomics analysis utilizing affinity purification with anti-Hsc70 antibodies; as a result, 83 differentially expressed proteins were identified under stress conditions. This result implies that there was a change in the proteins with which Hsc70 interacted in response to stress. Among the proteins identified under both serum-depleted and 5-fluorouracil-treated conditions, Rab1A was identified as an essential molecule for cancer cell survival. Hsc70 interacted with Rab1A in a chaperone-dependent manner. In addition, Hsc70 knockdown decreased the level of Rab1A and increased the level of its ubiquitination under stress conditions, suggesting that Hsc70 prevented the degradation of Rab1A denatured by stress exposure. We also found that Rab1A knockdown induced cell death by inhibition of autophagosome formation. Rab1A may therefore contribute to overcoming proteotoxic insults, which allows cancer cells to survive under stress conditions. Analysis of Hsc70 interactors provided insight into changes of intracellular status. We expect further study of the Hsc70 interactome to provide a more comprehensive understanding of cancer cell physiology.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masako", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Saya", "last_name": "Mun", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Azusa", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Soichi", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yasukatsu", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Osada-Oka", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Wanibuchi", "name": null }, { "creator_type": "author", "first_name": "Masayo", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Tokihito", "last_name": "Yukimura", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shiota", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Iwao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0096785" }, "pmcid": { "normalized": "PMC4011886" }, "pmid": { "normalized": "24801886" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Fluorouracil", "descriptor_ui": "D005472", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "HSC70 Heat-Shock Proteins", "descriptor_ui": "D050883", "major_topic": false }, { "descriptor": "HT29 Cells", "descriptor_ui": "D019073", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Protein Array Analysis", "descriptor_ui": "D040081", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "rab1 GTP-Binding Proteins", "descriptor_ui": "D020761", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "5", "normalized_date": "2014", "pages": "e96785", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Hsc70 contributes to cancer cell survival by preventing Rab1A degradation under stress conditions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Since the first reports in 2001, great advances have been made towards the understanding of endocannabinoid-mediated synaptic modulation. Electrophysiological studies have revealed that one of the two major endocannabinoids, 2-arachidonoylglycerol (2-AG), is produced from membrane lipids upon postsynaptic Ca(2+) elevation and/or activation of Gq/11-coupled receptors, and released from postsynaptic neurons. The released 2-AG then acts retrogradely onto presynaptic cannabinoid CB1 receptors and induces suppression of neurotransmitter release either transiently or persistently. These forms of 2-AG-mediated retrograde synaptic modulation are functional throughout the brain. The other major endocannabinoid, anandamide, mediates a certain form of endocannabinoid-mediated long-term depression (LTD). Anandamide also functions as an agonist for transient receptor potential vanilloid receptor type 1 (TRPV1) and mediates endocannabinoid-independent and TRPV1-dependent forms of LTD. It has also been demonstrated that the endocannabinoid system itself is plastic, which can be either up- or down-regulated by experimental or environmental conditions. In this review, I will make an overview of the mechanisms underlying endocannabinoid-mediated synaptic modulation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.2183/pjab.90.235" }, "pmcid": { "normalized": "PMC4237895" }, "pmid": { "normalized": "25169670" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": false }, { "descriptor": "GTP-Binding Protein alpha Subunits, Gq-G11", "descriptor_ui": "D043802", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Long-Term Synaptic Depression", "descriptor_ui": "D036881", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false }, { "descriptor": "TRPV Cation Channels", "descriptor_ui": "D050916", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "7", "normalized_date": "2014", "pages": "235-250", "proceedings_title": null, "publisher": "", "title": "Proceedings of the Japan Academy. Series B, Physical and biological sciences", "volume": "90", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Control of synaptic function by endocannabinoid-mediated retrograde signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "System level understanding of the cell requires detailed description of the cell state, which is often characterized by the expression levels of proteins. However, understanding the cell state requires comprehensive information of the cell, which is usually obtained from a large number of cells and their disruption. In this study, we used Raman spectroscopy, which can report changes in the cell state without introducing any label, as a non-invasive method with single cell capability. Significant differences in Raman spectra were observed at the levels of both the cytosol and nucleus in different cell-lines from mouse, indicating that Raman spectra reflect differences in the cell state. Difference in cell state was observed before and after the induction of differentiation in neuroblastoma and adipocytes, showing that Raman spectra can detect subtle changes in the cell state. Cell state transitions during embryonic stem cell (ESC) differentiation were visualized when Raman spectroscopy was coupled with principal component analysis (PCA), which showed gradual transition in the cell states during differentiation. Detailed analysis showed that the diversity between cells are large in undifferentiated ESC and in mesenchymal stem cells compared with terminally differentiated cells, implying that the cell state in stem cells stochastically fluctuates during the self-renewal process. The present study strongly indicates that Raman spectral morphology, in combination with PCA, can be used to establish cells' fingerprints, which can be useful for distinguishing and identifying different cellular states.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Liang-da", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Yanagida", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0084478" }, "pmcid": { "normalized": "PMC3883674" }, "pmid": { "normalized": "24409302" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "1", "normalized_date": "2014", "pages": "e84478", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualizing cell state transition using Raman spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ontologies provide an important resource to integrate information. For developmental biology and comparative anatomy studies, ontologies of a species are used to formalize and annotate data that are related to anatomical structures, their lineage and timing of development. Here, we have constructed the first ontology for anatomy and asexual development (blastogenesis) of a bilaterian, the colonial tunicate Botryllus schlosseri. Tunicates, like Botryllus schlosseri, are non-vertebrates and the only chordate taxon species that reproduce both sexually and asexually. Their tadpole larval stage possesses structures characteristic of all chordates, i.e. a notochord, a dorsal neural tube, and gill slits. Larvae settle and metamorphose into individuals that are either solitary or colonial. The latter reproduce both sexually and asexually and these two reproductive modes lead to essentially the same adult body plan. The Botryllus schlosseri Ontology of Development and Anatomy (BODA) will facilitate the comparison between both types of development. BODA uses the rules defined by the Open Biomedical Ontologies Foundry. It is based on studies that investigate the anatomy, blastogenesis and regeneration of this organism. BODA features allow the users to easily search and identify anatomical structures in the colony, to define the developmental stage, and to follow the morphogenetic events of a tissue and/or organ of interest throughout asexual development. We invite the scientific community to use this resource as a reference for the anatomy and developmental ontology of B. schlosseri and encourage recommendations for updates and improvements.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Lucia", "last_name": "Manni", "name": null }, { "creator_type": "author", "first_name": "Fabio", "last_name": "Gasparini", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Katherine J.", "last_name": "Ishizuka", "name": null }, { "creator_type": "author", "first_name": "Lorenzo", "last_name": "Ricci", "name": null }, { "creator_type": "author", "first_name": "Stefano", "last_name": "Tiozzo", "name": null }, { "creator_type": "author", "first_name": "Ayelet", "last_name": "Voskoboynik", "name": null }, { "creator_type": "author", "first_name": "Delphine", "last_name": "Dauga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0096434" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24789338" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Ontologies", "descriptor_ui": "D064229", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": false }, { "descriptor": "Databases, Genetic", "descriptor_ui": "D030541", "major_topic": true }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false }, { "descriptor": "Urochordata", "descriptor_ui": "D014561", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "5", "normalized_date": "2014", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Ontology for the Asexual Development and Anatomy of the Colonial Chordate Botryllus schlosseri.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The water flea Daphnia magna has been used as an animal model in ecology, evolution, and environmental sciences. Thanks to the recent progress in Daphnia genomics, genetic information such as the draft genome sequence and expressed sequence tags (ESTs) is now available. To investigate the relationship between phenotypes and the available genetic information about Daphnia, some gene manipulation methods have been developed. However, a technique to induce targeted mutagenesis into Daphnia genome remains elusive. To overcome this problem, we focused on an emerging genome editing technique mediated by the clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR/Cas) system to introduce genomic mutations. In this study, we targeted a functionally conserved regulator of eye development, the eyeless gene in D. magna. When we injected Cas9 mRNAs and eyeless-targeting guide RNAs into eggs, 18-47% of the survived juveniles exhibited abnormal eye morphology. After maturation, up to 8.2% of the adults produced progenies with deformed eyes, which carried mutations in the eyeless loci. These results showed that CRISPR/Cas system could introduce heritable mutations into the endogenous eyeless gene in D. magna. This is the first report of a targeted gene knockout technique in Daphnia and will be useful in uncovering Daphnia gene functions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0098363" }, "pmcid": { "normalized": "PMC4039500" }, "pmid": { "normalized": "24878568" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Clustered Regularly Interspaced Short Palindromic Repeats", "descriptor_ui": "D064112", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "Eye", "descriptor_ui": "D005123", "major_topic": false }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Genetic Engineering", "descriptor_ui": "D005818", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Mutagenesis", "descriptor_ui": "D016296", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "RNA, Guide, CRISPR-Cas Systems", "descriptor_ui": "D000094704", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "5", "normalized_date": "2014", "pages": "e98363", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "CRISPR/Cas-mediated targeted mutagenesis in Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuo", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fncir.2014.00135" }, "pmcid": { "normalized": "PMC4226153" }, "pmid": { "normalized": "25426031" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "135", "proceedings_title": null, "publisher": "", "title": "Frontiers in neural circuits", "volume": "8", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Neural circuits: Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Over the past decade, great developments in optical microscopy have made this technology increasingly compatible with biological studies. Fluorescence microscopy has especially contributed to investigating the dynamic behaviors of live specimens and can now resolve objects with nanometer precision and resolution due to super-resolution imaging. Additionally, single particle tracking provides information on the dynamics of individual proteins at the nanometer scale both in vitro and in cells. Complementing advances in microscopy technologies has been the development of fluorescent probes. The quantum dot, a semi-conductor fluorescent nanoparticle, is particularly suitable for single particle tracking and super-resolution imaging. This article overviews the principles of single particle tracking and super resolution along with describing their application to the nanometer measurement/observation of biological systems when combined with quantum dot technologies.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fphys.2014.00273" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25120488" } }, "mesh": [], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Physiology", "volume": "5", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Nano-scale measurement of biomolecules by optical microscopy and semiconductor nanoparticles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Direct lineage conversion of adult cells is a promising approach for regenerative medicine. A major challenge of lineage conversion is to generate specific cell subtypes. The pancreatic islets contain three major hormone-secreting endocrine subtypes: insulin+ β-cells, glucagon+ α-cells, and somatostatin+ δ-cells. We previously reported that a combination of three transcription factors, Ngn3, Mafa, and Pdx1, directly reprograms pancreatic acinar cells to β-cells. We now show that acinar cells can be converted to δ-like and α-like cells by Ngn3 and Ngn3+Mafa respectively. Thus, three major islet endocrine subtypes can be derived by acinar reprogramming. Ngn3 promotes establishment of a generic endocrine state in acinar cells, and also promotes δ-specification in the absence of other factors. δ-specification is in turn suppressed by Mafa and Pdx1 during α- and β-cell induction. These studies identify a set of defined factors whose combinatorial actions reprogram acinar cells to distinct islet endocrine subtypes in vivo.DOI:http://dx.doi.org/10.7554/eLife.01846.001", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Weida", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Adrian", "last_name": "Zumsteg", "name": null }, { "creator_type": "author", "first_name": "Matthew", "last_name": "Shear", "name": null }, { "creator_type": "author", "first_name": "Christopher", "last_name": "Wright", "name": null }, { "creator_type": "author", "first_name": "Douglas A.", "last_name": "Melton", "name": null }, { "creator_type": "author", "first_name": "Qiao", "last_name": "Zhou", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.01846" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24714494" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cell Transdifferentiation", "descriptor_ui": "D054338", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Glucagon-Secreting Cells", "descriptor_ui": "D050416", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin-Secreting Cells", "descriptor_ui": "D050417", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Maf Transcription Factors, Large", "descriptor_ui": "D051473", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Pancreas, Exocrine", "descriptor_ui": "D046790", "major_topic": false }, { "descriptor": "Red Fluorescent Protein", "descriptor_ui": "D000097573", "major_topic": false }, { "descriptor": "Somatostatin-Secreting Cells", "descriptor_ui": "D019864", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Trans-Activators", "descriptor_ui": "D015534", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "3", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "In vivo reprogramming of pancreatic acinar cells to three islet endocrine subtypes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This study describes the sensitization mechanism to thermal stress by histone deacetylase inhibitors (HDACIs) in lung cancer cells and shows that Ku70, based on its acetylation status, mediates the protection of lung cancer from hyperthermia (42.5°C, 1-6 hrs). Ku70 regulates apoptosis by sequestering pro-apoptotic Bax. However, its role in thermal stress is not fully understood. The findings showed that, pre-treating lung cancer cells with HDACIs, nicotinamide (NM) or Trichostatin A (TsA) or both significantly enhanced hyperthermia-induced Bax-dependent apoptosis in PC-10 cells. We found that hyperthermia induces SirT-1, Sirtuin, upregulation but not HDAC6 or SirT-3, therefore transfection with dominant negative SirT-1 (Y/H) also eliminated the protection and resulted in more cell death by hyperthermia, in H1299 cells through Bax activation. Hyperthermia alone primed lung cancer cells to apoptosis without prominent death. After hyperthermia Bax was upregulated, Bcl-2 was downregulated, the Bax/Bcl-2 ratio was inversed and Bax/Bcl-2 heterodimer was dissociated. Although hyperthermia did not affect total Ku70 expression level, it stimulated Ku70 deacetylation, which in turn could bind more Bax in the PC-10 cells. These findings suggest an escape mechanism from hyperthermia-induced Bax activation. To verify the role of Ku70 in this protection mechanism, Ku70 was silenced by siRNA. Ku70 silencing significantly sensitized the lung cancer cells to hyperthermia. The Ku70 KD cells underwent cytotoxic G1 arrest and caspase-dependant apoptosis when compared to scrambled transfectants which showed only G2/M cytostatic arrest in the cell lines investigated, suggesting an additional cell cycle-dependent, novel, role of Ku70 in protection from hyperthermia. Taken together, our data show a Ku70-dependent protection mechanism from hyperthermia. Targeting Ku70 and/or its acetylation during hyperthermia may represent a promising therapeutic approach for lung cancer.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mohamed K.", "last_name": "Hassan", "name": null }, { "creator_type": "author", "first_name": "Hidemichi", "last_name": "Watari", "name": null }, { "creator_type": "author", "first_name": "Alaa-eldin", "last_name": "Salah-eldin", "name": null }, { "creator_type": "author", "first_name": "Ahmed S.", "last_name": "Sultan", "name": null }, { "creator_type": "author", "first_name": "Zainab", "last_name": "Mohamed", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Sakuragi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0094213" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24728004" } }, "mesh": [ { "descriptor": "Antigens, Nuclear", "descriptor_ui": "D034961", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "bcl-2-Associated X Protein", "descriptor_ui": "D051028", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Histone Deacetylase Inhibitors", "descriptor_ui": "D056572", "major_topic": false }, { "descriptor": "Hot Temperature", "descriptor_ui": "D006358", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydroxamic Acids", "descriptor_ui": "D006877", "major_topic": false }, { "descriptor": "Hyperthermia, Induced", "descriptor_ui": "D006979", "major_topic": false }, { "descriptor": "Ku Autoantigen", "descriptor_ui": "D000072200", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Niacinamide", "descriptor_ui": "D009536", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "4", "normalized_date": "2014", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Histone Deacetylase Inhibitors Sensitize Lung Cancer Cells to Hyperthermia: Involvement of Ku70/SirT-1 in Thermo-Protection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transient receptor potential (TRP) channels have attracted considerable attention because of their vital roles in primary sensory neurons, mediating responses to a wide variety of external environmental stimuli. However, much less is known about how TRP channels in the brain respond to intrinsic signals and are involved in neurophysiological processes that control complex behaviors. Painless (Pain) is the Drosophila TRP channel that was initially identified as a molecular sensor responsible for detecting noxious thermal and mechanical stimuli. Here, we review recent behavioral genetic studies demonstrating that Pain expressed in the brain plays a critical role in both innate and learned aspects of sexual behaviors. Several members of the TRP channel superfamily play evolutionarily conserved roles in sensory neurons as well as in other peripheral tissues. It is thus expected that brain TRP channels in vertebrates and invertebrates would have some common physiological functions. Studies of Pain in the Drosophila brain using a unique combination of genetics and physiological techniques should provide valuable insights into the fundamental principles concerning TRP channels expressed in the vertebrate and invertebrate brains.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shoma", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kitamoto", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnbeh.2014.00400" }, "pmcid": { "normalized": "PMC4251448" }, "pmid": { "normalized": "25520634" } }, "mesh": [], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "400", "proceedings_title": null, "publisher": "", "title": "Frontiers in behavioral neuroscience", "volume": "8", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Modulation of innate and learned sexual behaviors by the TRP channel Painless expressed in the fruit fly brain: behavioral genetic analysis and its implications.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Intraoperative thermographic confirmation of the extent of carotid plaque distribution using an uncooled infrared camera was assessed during carotid endarterectomy (CEA). METHODS: This camera was small, light, and provided high temperature resolution (<0.022 degrees), thus allowing detection of the changes in thermal radiation induced by surface temperature differences. RESULTS: Vascular flow of the artery appeared as a light color, and absence of flow as a dark color. Vascular re-flow was recognized as a bright color. Therefore, vascular flow could be evaluated using the uncooled infrared camera during CEA. The uncooled infrared camera offers real-time information on vascular patency and extent of plaque. Spatial resolution and image quality are satisfactory, and the procedure can be repeated easily and safely. CONCLUSION: We have shown that the uncooled infrared camera could be a new and feasible technology for intraoperative imaging of the vascular flow, and isconsidered to be clinically useful during CEA.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Otani", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Kojiro", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.4103/2152-7806.142034" }, "pmcid": { "normalized": "PMC4192904" }, "pmid": { "normalized": "25317359" } }, "mesh": [], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "144", "proceedings_title": null, "publisher": "", "title": "Surgical neurology international", "volume": "5", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Noninvasive thermographic visualization of the extent of carotid plaque distribution during carotid endarterectomy using an uncooled infrared camera.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Currently, in the era of post-genomics, immunology is facing a challenging problem to translate mutant phenotypes into gene functions based on high-throughput data, while taking into account the classifications and functions of immune cells, which requires new methods. Results: Here we propose a novel application of a multidimensional analysis, Canonical Correspondence Analysis (CCA), to reveal the molecular characteristics of undefined cells in terms of cellular differentiation programmes by analysing two transcriptomic datasets. Using two independent datasets, whether RNA-seq or microarray data, CCA successfully visualised the cross-level relationships between genes, cells, and differentiation programmes, and thereby identified the immunological features of mutant cells (Gata3-KO T cells and Stat3-KO T cells) in a data-oriented manner. With a new concept, differentiation variable, CCA provides an automatic classification of cell samples, which had a high sensitivity and a comparable performance to other classification methods. In addition, we elaborate how CCA results can be interpreted, and reveal the features of CCA in comparison with other visualisation techniques. Conclusions: CCA is a visualisation tool with a classification ability to reveal the cross-level relationships of genes, cells and differentiation programmes. This can be used for characterising the functional defect of cells of interest (e.g. mutant cells) in the context of cellular differentiation. The proposed approach fits with common hypothesis-oriented studies in immunology, and can be used for a wide range of molecular and genomic studies on cellular differentiation mechanisms. Electronic supplementary material: The online version of this article (doi:10.1186/1471-2164-15-1028) contains supplementary material, which is available to authorized users.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Reiko J.", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1471-2164-15-1028" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25428805" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Datasets as Topic", "descriptor_ui": "D066264", "major_topic": false }, { "descriptor": "GATA3 Transcription Factor", "descriptor_ui": "D050990", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": true }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "T-Lymphocyte Subsets", "descriptor_ui": "D016176", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "1", "normalized_date": "2014", "pages": "", "proceedings_title": null, "publisher": "", "title": "BMC Genomics", "volume": "15", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualisation of the T cell differentiation programme by Canonical Correspondence Analysis of transcriptomes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Acute lung injury is characterized by neutrophilic inflammation and increased lung permeability. Thiosulfate is a stable metabolite of hydrogen sulfide, a gaseous mediator that exerts antiinflammatory effects. Although sodium thiosulfate (STS) has been used as an antidote, the effect of STS on acute lung injury is unknown. The authors assessed the effects of STS on mice lung and vascular endothelial cells subjected to acute inflammation. METHODS: Lung injury was assessed in mice challenged with intratracheal lipopolysaccharide or subjected to cecal ligation and puncture with or without STS. Effects of STS on endothelial permeability and the production of inflammatory cytokines and reactive oxygen species were examined in cultured endothelial cells incubated with lipopolysaccharide or tumor necrosis factor-alpha. Levels of sulfide and sulfane sulfur were measured using novel fluorescence probes. RESULTS: STS inhibited lipopolysaccharide-induced production of cytokines (interleukin-6 [pg/ml]; 313+/-164, lipopolysaccharide; 79+/-27, lipopolysaccharide+STS [n=10]), lung permeability, histologic lung injury, and nuclear factor-kappaB activation in the lung. STS also prevented up-regulation of interleukin-6 in the mouse lung subjected to cecal ligation and puncture. In endothelial cells, STS increased intracellular levels of sulfide and sulfane sulfur and inhibited lipopolysaccharide or tumor necrosis factor-alpha-induced production of cytokines and reactive oxygen species. The beneficial effects of STS were associated with attenuation of the lipopolysaccharide-induced nuclear factor-kappaB activation through the inhibition of tumor necrosis factor receptor-associated factor 6 ubiquitination. CONCLUSIONS: STS exerts robust antiinflammatory effects in mice lung and vascular endothelium. The results suggest a therapeutic potential of STS in acute lung injury.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Eizo", "last_name": "Marutani", "name": null }, { "creator_type": "author", "first_name": "Hae-sook", "last_name": "Shin", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Xian", "name": null }, { "creator_type": "author", "first_name": "Fumito", "last_name": "Ichinose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/aln.0000000000000456" }, "pmcid": { "normalized": "PMC4237715" }, "pmid": { "normalized": "25260144" } }, "mesh": [ { "descriptor": "Acute Lung Injury", "descriptor_ui": "D055371", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antioxidants", "descriptor_ui": "D000975", "major_topic": false }, { "descriptor": "Cecum", "descriptor_ui": "D002432", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Thiosulfates", "descriptor_ui": "D013885", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "1248-1257", "proceedings_title": null, "publisher": "", "title": "Anesthesiology", "volume": "121", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Sodium thiosulfate attenuates acute lung injury in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The oxidation of cysteine in mammalian cells occurs by two routes: a highly regulated direct oxidation pathway in which the first step is catalyzed by cysteine dioxygenase (CDO) and by desulfhydration-oxidation pathways in which the sulfur is released in a reduced oxidation state. To assess the effect of a lack of CDO on production of hydrogen sulfide (H2S) and thiosulfate (an intermediate in the oxidation of H2S to sulfate) and to explore the roles of both cystathionine γ-lyase (CTH) and cystathionine β-synthase (CBS) in cysteine desulfhydration by liver, we investigated the metabolism of cysteine in hepatocytes isolated from Cdo1-null and wild-type mice. Hepatocytes from Cdo1-null mice produced more H2S and thiosulfate than did hepatocytes from wild-type mice. The greater flux of cysteine through the cysteine desulfhydration reactions catalyzed by CTH and CBS in hepatocytes from Cdo1-null mice appeared to be the consequence of their higher cysteine levels, which were due to the lack of CDO and hence lack of catabolism of cysteine by the cysteinesulfinate-dependent pathways. Both CBS and CTH appeared to contribute substantially to cysteine desulfhydration, with estimates of 56 % by CBS and 44 % by CTH in hepatocytes from wild-type mice, and 63 % by CBS and 37 % by CTH in hepatocytes from Cdo1-null mice.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Halina", "last_name": "Jurkowska", "name": null }, { "creator_type": "author", "first_name": "Heather B.", "last_name": "Roman", "name": null }, { "creator_type": "author", "first_name": "Lawrence L.", "last_name": "Hirschberger", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Sasakura", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Jakub", "last_name": "Krijt", "name": null }, { "creator_type": "author", "first_name": "Martha H.", "last_name": "Stipanuk", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00726-014-1700-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24609271" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Cysteine Dioxygenase", "descriptor_ui": "D050558", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Thiosulfates", "descriptor_ui": "D013885", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "1353-1365", "proceedings_title": null, "publisher": "", "title": "Amino acids", "volume": "46", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Primary hepatocytes from mice lacking cysteine dioxygenase show increased cysteine concentrations and higher rates of metabolism of cysteine to hydrogen sulfide and thiosulfate.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Elevated expression of human hyperphosphorylated tau is associated with neuronal loss and white matter (WM) pathology in Alzheimer's disease (AD) and related neurodegenerative disorders. Using in vivo diffusion tensor magnetic resonance imaging (DT-MRI) at 11.1 Tesla we measured age-related alterations in WM diffusion anisotropy indices in a mouse model of human tauopathy (rTg4510) and nontransgenic (nonTg) control mice at the age of 2.5, 4.5, and 8 months. Similar to previous DT-MRI studies in AD subjects, 8-month-old rTg4510 mice showed lower fractional anisotropy (FA) values in WM structures than nonTg. The low WM FA in rTg4510 mice was observed in the genu and splenium of the corpus callosum, anterior commissure, fimbria, and internal capsule and was associated with a higher radial diffusivity than nonTg. Interestingly, rTg4510 mice showed lower estimates for the mode of anisotropy than controls at 2.5 months suggesting that changes in this diffusivity metric are detectable at an early stage preceding severe tauopathy. Immunogold electron microscopy partly supports our diffusion tensor imaging findings. At the age of 4 months, rTg4510 mice show axonal tau inclusions and unmyelinated processes. At later ages (12 months and 14 months) we observed inclusions in myelin sheath, axons, and unmyelinated processes, and a \"disorganized\" pattern of myelinated fiber arrangement with enlarged inter-axonal spaces in rTg4510 but not in nonTg mice. Our data support a role for the progression of tau pathology in reduced WM integrity measured by DT-MRI. Further in vivo DT-MRI studies in the rTg4510 mouse should help better discern the detailed mechanisms of reduced FA and anisotropy mode, and the specific role of tau during neurodegeneration.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Naruhiko", "last_name": "Sahara", "name": null }, { "creator_type": "author", "first_name": "Pablo D.", "last_name": "Perez", "name": null }, { "creator_type": "author", "first_name": "Wen-Lang", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Dennis W.", "last_name": "Dickson", "name": null }, { "creator_type": "author", "first_name": "Yan", "last_name": "Ren", "name": null }, { "creator_type": "author", "first_name": "Huadong", "last_name": "Zeng", "name": null }, { "creator_type": "author", "first_name": "Jada", "last_name": "Lewis", "name": null }, { "creator_type": "author", "first_name": "Marcelo", "last_name": "Febo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neurobiolaging.2013.12.009" }, "pmcid": { "normalized": "PMC4729397" }, "pmid": { "normalized": "24411290" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anisotropy", "descriptor_ui": "D016880", "major_topic": false }, { "descriptor": "Corpus Callosum", "descriptor_ui": "D003337", "major_topic": false }, { "descriptor": "Diffusion Tensor Imaging", "descriptor_ui": "D056324", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neurodegenerative Diseases", "descriptor_ui": "D019636", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Tauopathies", "descriptor_ui": "D024801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "1364-1374", "proceedings_title": null, "publisher": "", "title": "Neurobiology of aging", "volume": "35", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Age-related decline in white matter integrity in a mouse model of tauopathy: an in vivo diffusion tensor magnetic resonance imaging study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hippocampal sharp waves (SWs)/ripples represent the reactivation of neurons involved in recently acquired memory and are crucial for memory consolidation. By labeling active cells with fluorescent protein under the control of an immediate-early gene promoter, we found that neurons that had been activated while mice explored a novel environment were preferentially reactivated during spontaneous SWs in hippocampal slices in vitro. During SWs, the reactivated neurons received strong excitatory synaptic inputs as opposed to a globally tuned network balance between excitation and inhibition.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mika", "last_name": "Mizunuma", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Norimoto", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Tao", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Egawa", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Hioki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Matsuki", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Ikegaya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nn.3674" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24633127" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Exploratory Behavior", "descriptor_ui": "D005106", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genes, Immediate-Early", "descriptor_ui": "D017781", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Random Allocation", "descriptor_ui": "D011897", "major_topic": false }, { "descriptor": "Synaptic Potentials", "descriptor_ui": "D055366", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "503-505", "proceedings_title": null, "publisher": "", "title": "Nature neuroscience", "volume": "17", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Unbalanced excitability underlies offline reactivation of behaviorally activated neurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We recently showed that prenatal exposure to valproic acid (VPA) in mice causes autism-like behavioral abnormalities, including social interaction deficits, anxiety-like behavior and spatial learning disability, in male offspring. In the present study, we examined the effect of prenatal VPA on cognitive function and whether the effect is improved by chronic treatment with VPA and sodium butyrate, histone deacetylase inhibitors. In addition, we examined whether the cognitive dysfunction is associated with hippocampal dendritic morphological changes. Mice given prenatal exposure to VPA exhibited novel object recognition deficits at 9 weeks of age, and that the impairment was blocked by chronic (5-week) treatment with VPA (30 mg/kg/d, i.p.) or sodium butyrate (1.2g/kg/d, i.p.) starting at 4 weeks of age. In agreement with the behavioral findings, the mice prenatally exposed to VPA showed a decrease in dendritic spine density in the hippocampal CA1 region, and the spine loss was attenuated by chronic treatment with sodium butyrate or VPA. Furthermore, acute treatment with sodium butyrate, but not VPA, significantly increased acetylation of histone H3 in the hippocampus at 30 min, suggesting the difference in the mechanism for the effects of chronic VPA and sodium butyrate. These findings suggest that prenatal VPA-induced cognitive dysfunction is associated with changes in hippocampal dendritic spine morphology.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Kawanai", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Erika", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.pbb.2014.08.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25240644" } }, "mesh": [ { "descriptor": "Acetylation", "descriptor_ui": "D000107", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autistic Disorder", "descriptor_ui": "D001321", "major_topic": false }, { "descriptor": "Butyric Acid", "descriptor_ui": "D020148", "major_topic": false }, { "descriptor": "CA1 Region, Hippocampal", "descriptor_ui": "D056547", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "Exploratory Behavior", "descriptor_ui": "D005106", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Histone Deacetylase Inhibitors", "descriptor_ui": "D056572", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Prenatal Exposure Delayed Effects", "descriptor_ui": "D011297", "major_topic": false }, { "descriptor": "Valproic Acid", "descriptor_ui": "D014635", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Nov", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "43-49", "proceedings_title": null, "publisher": "", "title": "Pharmacology, biochemistry, and behavior", "volume": "126", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Chronic treatment with valproic acid or sodium butyrate attenuates novel object recognition deficits and hippocampal dendritic spine loss in a mouse model of autism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Unlike in vitro protein dynamics, intracellular protein dynamics are intricately regulated by protein-protein interactions or interactions between proteins and other cellular components, including nucleic acids, the plasma membrane and the cytoskeleton. Alteration of these dynamics plays a crucial role in physiological phenomena such as gene expression and cell division. Live-cell imaging via microscopy with the inherent properties of fluorescent proteins, i.e. photobleaching and photoconversion, or fluorescence correlation spectroscopy, provides insight into the movement of proteins and their interactions with cellular components. This article reviews techniques based on photo-induced changes in the physicochemical properties of fluorescent proteins to measure protein dynamics inside living cells, and it also discusses the strengths and weaknesses of these techniques.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jmicro/dfu033" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25268018" } }, "mesh": [ { "descriptor": "Cells", "descriptor_ui": "D002477", "major_topic": false }, { "descriptor": "Fluorescence Recovery After Photobleaching", "descriptor_ui": "D036681", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Photobleaching", "descriptor_ui": "D038761", "major_topic": true }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "403-408", "proceedings_title": null, "publisher": "", "title": "Microscopy (Oxford, England)", "volume": "63", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative measurement of intracellular protein dynamics using photobleaching or photoactivation of fluorescent proteins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The CCAAT/enhancer-binding protein (C/EBP)beta belongs to the C/EBP family of proteins that possesses a basic leucine zipper DNA-binding domain. These proteins bind DNA by dimerization and play a role in the transcriptional regulation of various cells. There are six different types of C/EBPs, and some form isoforms through the use of alternative translation initiation sites. The functional analysis of the C/EBP family is therefore difficult to achieve. Here we report on the production of specific monoclonal antibodies against mouse C/EBPbeta using a rat medial iliac lymph node method. Immunoblotting using C/EBPbeta monoclonal antibodies identified two types of isoforms, while immunostaining revealed a subnuclear localization for C/EBPbeta. Use of this antibody should contribute to the further elucidation of the transcriptional regulatory function of C/EBPbeta.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/mab.2013.0069" }, "pmcid": { "normalized": "PMC3935365" }, "pmid": { "normalized": "24555934" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "CCAAT-Enhancer-Binding Protein-beta", "descriptor_ui": "D022782", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hybridomas", "descriptor_ui": "D006825", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Inbred WKY", "descriptor_ui": "D011921", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Feb", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "34-37", "proceedings_title": null, "publisher": "", "title": "Monoclonal antibodies in immunodiagnosis and immunotherapy", "volume": "33", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Production of a monoclonal antibody for C/EBPbeta: the subnuclear localization of C/EBPbeta in mouse L929 cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurons form exuberant synapses with target cells early in development. Then, necessary synapses are strengthened whereas unnecessary connections are weakened and eventually eliminated during postnatal development. This process, known as synapse elimination, is widely believed to be a crucial step for shaping immature neural circuits into functionally mature versions. In the neonatal mouse cerebellum, each Purkinje cell is innervated by multiple climbing fibers (CFs). Their synaptic strengths are initially uniform but a single CF strengthens relative to the other CFs during the first postnatal week. Then the weaker CFs are eliminated during the second postnatal week. Similar developmental changes occur in several other synapses including the neuromuscular junction and the projection from the retina to the lateral geniculate nucleus (LGN). Recent studies have clarified that synapse elimination consists of multiple phases that involve distinct types of neural activity and/or molecular mechanisms.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25200578" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "1069-1077", "proceedings_title": null, "publisher": "", "title": "Brain and nerve = Shinkei kenkyu no shinpo", "volume": "66", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "[Cellular and molecular mechanisms of synapse elimination in the Mammalian brain].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: Photoacoustic tomography can image the hemoglobin distribution and oxygenation state inside tissue with high spatial resolution. The purpose of this study is to investigate its clinical usefulness for diagnosis of breast cancer and evaluation of therapeutic response in relation to other diagnostic modalities. MATERIALS AND METHODS: Using a prototype machine for photoacoustic mammography (PAM), 27 breast tumor lesions, including 21 invasive breast cancer (IBC), five ductal carcinoma in situ (DCIS), and one phyllodes tumor, were measured. Nine out of twenty-one IBC patients had received primary systemic therapy (PST). RESULTS: Eight out of twelve IBC without PST were visible. Notably, detection was possible in all five cases with DCIS, whereas it was not in one case with phyllodes tumor. Seven out of nine IBC with PST were assigned as visible in spite of decreased size of tumor after PST. The mean value of hemoglobin saturation in the visible lesions was 78.6 %, and hemoglobin concentration was 207 muM. The tumor images of PAM were comparable to those of magnetic resonance imaging (MRI). CONCLUSIONS: It is suggested that PAM can image tumor vascularity and oxygenation, which may be useful for diagnosis and characterization of breast cancer.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kitai", "name": null }, { "creator_type": "author", "first_name": "Masae", "last_name": "Torii", "name": null }, { "creator_type": "author", "first_name": "Tomoharu", "last_name": "Sugie", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Kanao", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Toi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12282-012-0363-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22484692" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Carcinoma, Intraductal, Noninfiltrating", "descriptor_ui": "D002285", "major_topic": false }, { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hemoglobins", "descriptor_ui": "D006454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Mammography", "descriptor_ui": "D008327", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Photoacoustic Techniques", "descriptor_ui": "D061088", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Mar", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "146-153", "proceedings_title": null, "publisher": "", "title": "Breast cancer (Tokyo, Japan)", "volume": "21", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Photoacoustic mammography: initial clinical results.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Staphylococcus aureus is a clinically important bacterium that is commensal in both humans and animals. Bacteriophage (phage) attachment to the host bacterial surface is an important process during phage infection, which involves interactions between phage receptor-binding proteins and host receptor molecules. However, little information is available on the receptor-binding protein of S. aureus phages. S. aureus virulent phages S24-1 and S13' (family Podoviridae, genus AHJD-like viruses) were isolated from sewage. In the present study, we investigated the receptor-binding protein of AHJD-like viruses using phage S24-1. First, based on a comparative genomic analysis of phages S24-1 and S13', open reading frame 16 (ORF16) of phage S24-1 was speculated to be the receptor-binding protein, which possibly determines the host range. Second, we demonstrated that this was the receptor-binding protein of phage S24-1. Third, our study suggested that wall teichoic acids in the cell walls of S. aureus are the main receptor molecules for ORF16 and phage S24-1. Finally, the C-terminal region of ORF16 may be essential for binding to S. aureus. These results strongly suggest that ORF16 of phage S24-1 and its homologs may be the receptor-binding proteins of AHJD-like viruses.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jumpei", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Iyo", "last_name": "Takemura-Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Ujihara", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Hanaki", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Daibata", "name": null }, { "creator_type": "author", "first_name": "Shigenobu", "last_name": "Matsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/mbo3.166" }, "pmcid": { "normalized": "PMC3996573" }, "pmid": { "normalized": "24591378" } }, "mesh": [ { "descriptor": "DNA, Viral", "descriptor_ui": "D004279", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Open Reading Frames", "descriptor_ui": "D016366", "major_topic": false }, { "descriptor": "Podoviridae", "descriptor_ui": "D017902", "major_topic": false }, { "descriptor": "Receptors, Virus", "descriptor_ui": "D011991", "major_topic": false }, { "descriptor": "Sequence Analysis, DNA", "descriptor_ui": "D017422", "major_topic": false }, { "descriptor": "Sewage", "descriptor_ui": "D012722", "major_topic": false }, { "descriptor": "Staphylococcus aureus", "descriptor_ui": "D013211", "major_topic": false }, { "descriptor": "Staphylococcus Phages", "descriptor_ui": "D013204", "major_topic": false }, { "descriptor": "Teichoic Acids", "descriptor_ui": "D013682", "major_topic": false }, { "descriptor": "Virus Attachment", "descriptor_ui": "D053585", "major_topic": true } ], "publication": { "conference_name": null, "date": "2014 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "257-270", "proceedings_title": null, "publisher": "", "title": "MicrobiologyOpen", "volume": "3", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "In silico analysis of AHJD-like viruses, Staphylococcus aureus phages S24-1 and S13', and study of phage S24-1 adsorption.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "One of the two major endocannabinoids, 2-arachidonoylglycerol (2-AG), serves as a retrograde messenger at various types of synapses throughout the brain. Upon postsynaptic activation, 2-AG is released immediately after de novo synthesis, activates presynaptic CB1 cannabinoid receptors, and transiently suppresses neurotransmitter release. When CB1 receptor activation is combined with some other factors such as presynaptic activity, the suppression is converted to a long-lasting form. Whereas 2-AG primarily transmits a rapid, transient, point-to-point retrograde signal, the other major endocannabinoid, anandamide, may function as a relatively slow retrograde or non-retrograde signal or as an agonist of the vanilloid receptor. The endocannabinoid system can be up- or down-regulated by a variety of physiological and environmental factors including stress, which might be clinically important.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takako", "last_name": "Ohno-Shosaku", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.conb.2014.03.017" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24747340" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arachidonic Acids", "descriptor_ui": "D001095", "major_topic": false }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": false }, { "descriptor": "Glycerides", "descriptor_ui": "D005989", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Neurological", "descriptor_ui": "D008959", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Polyunsaturated Alkamides", "descriptor_ui": "D053284", "major_topic": false }, { "descriptor": "Receptor, Cannabinoid, CB1", "descriptor_ui": "D043884", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Dec", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "1-8", "proceedings_title": null, "publisher": "", "title": "Current opinion in neurobiology", "volume": "29", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Endocannabinoid-mediated retrograde modulation of synaptic transmission.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cortical efferent and afferent fibers are arranged in a stereotyped pattern in the intermediate zone (IZ). Here, we studied the mechanism of axonal pathway formation by identifying a molecule that is expressed in a subset of cortical axons in the rat. We found that T-cadherin (T-cad), a member of the cadherin family, is expressed in deep-layer cell axons projecting to subcortical structures, but not in upper layer callosal axons projecting to the contralateral cortex. Ectopic expression of T-cad in upper layer cells induced axons to project toward subcortical structures via the upper part of the IZ. Moreover, the axons of deep-layer cells in which T-cad expression was suppressed by RNAi projected towards the contralateral cortex via an aberrant route. These results suggest that T-cad is involved in axonal pathway formation in the developing cortex.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Hayano", "name": null }, { "creator_type": "author", "first_name": "Hong", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Shigemi", "last_name": "Norioka", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.108290" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25468941" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": false }, { "descriptor": "Electrophoresis, Polyacrylamide Gel", "descriptor_ui": "D004591", "major_topic": false }, { "descriptor": "Electroporation", "descriptor_ui": "D018274", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Neocortex", "descriptor_ui": "D019579", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "Sequence Analysis, Protein", "descriptor_ui": "D020539", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Dec", "date_precision": "unknown", "issue": "24", "normalized_date": null, "pages": "4784-4793", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "141", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "The role of T-cadherin in axonal pathway formation in neocortical circuits.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Enzyme-dead mutations in the herpes simplex virus 1 UL12 gene that abolished its endo- and exonuclease activities only slightly reduced viral replication in cell cultures. However, the UL12 null mutation significantly reduced viral replication, suggesting that a UL12 function(s) unrelated to its nuclease activities played a major role in viral replication. In contrast, the enzyme-dead mutations significantly reduced viral neurovirulence in mice, suggesting that UL12 nuclease activities were critical for viral pathogenesis in vivo.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hikaru", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Mugitani", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Zhuoming", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Shumpei", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.03621-13" }, "pmcid": { "normalized": "PMC3911558" }, "pmid": { "normalized": "24335305" } }, "mesh": [ { "descriptor": "Deoxyribonucleases", "descriptor_ui": "D003851", "major_topic": false }, { "descriptor": "DNA Primers", "descriptor_ui": "D017931", "major_topic": false }, { "descriptor": "DNA, Recombinant", "descriptor_ui": "D004274", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virulence", "descriptor_ui": "D014774", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Feb", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "2359-2364", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "88", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of the nuclease activities encoded by herpes simplex virus 1 UL12 in viral replication and neurovirulence.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Astrocytes produce a complex repertoire of Ca2+ events that coordinate their major functions. The principle of Ca2+ events integration in astrocytes, however, is unknown. Here we analyze whole Ca2+ events, which were defined as spatiotemporally interconnected transient Ca2+ increases. Using such analysis in single hippocampal astrocytes in culture and in slices we found that spreads and durations of Ca2+ events follow power law distributions, a fingerprint of scale-free systems. A mathematical model demonstrated that such Ca2+ dynamics can arise from intracellular inositol-3-phosphate diffusion. The power law exponent (alpha) was decreased by activation of metabotropic glutamate receptors (mGluRs) either by specific receptor agonist or by low frequency stimulation of glutamatergic fibers in hippocampal slices. Decrease in alpha indicated an increase in proportion of large Ca2+ events. Notably, mGluRs activation did not increase the frequency of whole Ca2+ events. This result suggests that neuronal activity does not trigger new Ca2+ events in astrocytes (detectable by our methods), but modulates the properties of existing ones. Thus, our results provide a new perspective on how astrocyte responds to neuronal activity by changing its Ca2+ dynamics, which might further affect local network by triggering release of gliotransmitters and by modulating local blood flow.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yu-Wei", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Xiaofang", "last_name": "Tang", "name": null }, { "creator_type": "author", "first_name": "Misa", "last_name": "Arizono", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null }, { "creator_type": "author", "first_name": "Pei-Yu", "last_name": "Shih", "name": null }, { "creator_type": "author", "first_name": "Yulia", "last_name": "Dembitskaya", "name": null }, { "creator_type": "author", "first_name": "Victor", "last_name": "Kazantsev", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Shigeyoshi", "last_name": "Itohara", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Mikoshiba", "name": null }, { "creator_type": "author", "first_name": "Alexey", "last_name": "Semyanov", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ceca.2013.12.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24484772" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Methoxyhydroxyphenylglycol", "descriptor_ui": "D008734", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "119-129", "proceedings_title": null, "publisher": "", "title": "Cell calcium", "volume": "55", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatiotemporal calcium dynamics in single astrocytes and its modulation by neuronal activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Leucine-rich repeat kinase 2 (LRRK2) has been identified as the causal molecule for autosomal-dominant Parkinson's disease (PD). Experimental evidence indicates that LRRK2 may play an important role in the pathology induced by abnormal phosphorylation of tau. In the present study, we demonstrated that LRRK2 directly associates with GSK-3beta, and that this interaction enhances the kinase activity of GSK-3beta. Furthermore, we found that LRRK2-mediated activation of GSK-3beta induces high phosphorylation of tau at Ser396 in SH-SY5Y cells. From our present findings, we conclude that LRRK2 may function as a novel enhancer for GSK-3beta and as a physiological regulator of neurite outgrowth and axonal transport through regulation of the GSK-3beta-mediated phosphorylation of tau at the cellular level. Since LRRK2 is detected in tau-positive inclusions in brain tissue affected by various neurodegenerative disorders, including PD, LRRK2-stimulated phosphorylation of tau by GSK-3beta may be involved in development of pathological features in the initial stage of PD.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Kagiya", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Ichikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/febs.12579" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24165324" } }, "mesh": [ { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Glycogen Synthase Kinase 3", "descriptor_ui": "D038362", "major_topic": false }, { "descriptor": "Glycogen Synthase Kinase 3 beta", "descriptor_ui": "D000071679", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoprecipitation", "descriptor_ui": "D047468", "major_topic": false }, { "descriptor": "Leucine-Rich Repeat Serine-Threonine Protein Kinase-2", "descriptor_ui": "D000071158", "major_topic": false }, { "descriptor": "Neuroblastoma", "descriptor_ui": "D009447", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "3-13", "proceedings_title": null, "publisher": "", "title": "The FEBS journal", "volume": "281", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Leucine-rich repeat kinase 2 regulates tau phosphorylation through direct activation of glycogen synthase kinase-3beta.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Most animal opsin-based pigments are typical G protein-coupled receptors (GPCR) and consist of a protein moiety, opsin, and 11-cis retinal as a chromophore. More than several thousand opsins have been identified from a wide variety of animals, which have multiple opsin genes. Accumulated evidence reveals the molecular property of opsin-based pigments, particularly non-conventional visual pigments including non-visual pigments. Opsin-based pigments are generally a bistable pigment having two stable and photointerconvertible states and therefore are bleach-resistant and reusable, unlike vertebrate visual pigments which become bleached. The opsin family contains Gt-coupled, Gq-coupled, Go-coupled, Gs-coupled, Gi-coupled, and Gi/Go-coupled opsins, indicating the existence of a large diversity of light-driven GPCR-signaling cascades. It is suggested that these molecular properties might contribute to different physiologies. In addition, various opsin based-pigments, especially nonconventional visual pigments having different molecular characteristics would facilitate the design and development of promising optogenetic tools for modulating GPCR-signaling, which is involved in a wide variety of physiological responses. We here introduce molecular and functional properties of various kinds of opsins and discuss their physiological function and also their potentials for optogenetic applications. This article is part of a Special Issue entitled: Retinal proteins - you can teach an old dog new tricks.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbabio.2013.09.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24041647" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Invertebrates", "descriptor_ui": "D007448", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Light Signal Transduction", "descriptor_ui": "D055537", "major_topic": true }, { "descriptor": "Opsins", "descriptor_ui": "D055355", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": true }, { "descriptor": "Protein Stability", "descriptor_ui": "D055550", "major_topic": false }, { "descriptor": "Retinaldehyde", "descriptor_ui": "D012172", "major_topic": false }, { "descriptor": "Structure-Activity Relationship", "descriptor_ui": "D013329", "major_topic": false }, { "descriptor": "Vertebrates", "descriptor_ui": "D014714", "major_topic": false }, { "descriptor": "Vision, Ocular", "descriptor_ui": "D014785", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "710-716", "proceedings_title": null, "publisher": "", "title": "Biochimica et biophysica acta", "volume": "1837", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Diversity of animal opsin-based pigments and their optogenetic potential.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular signaling inside living cells is controlled by the specific localization of biomolecules, including proteins, with timescales ranging from milliseconds to several hours. To elucidate the related spatial and temporal signal processes, development of optical probes for cellular events is a challenging task in present studies. Herein, we describe recent advances in the basic design of the optical probes, which have been inspired by luminescent creatures, and their practical application to visualize intracellular events in living cells and animals. A discussion of different probe designs reveals their benefits and shortcomings.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/tcr.201402001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24946730" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": true }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Enzymes", "descriptor_ui": "D004798", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Protein Interaction Maps", "descriptor_ui": "D060066", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "Xenopus laevis", "descriptor_ui": "D014982", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jun", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "492-501", "proceedings_title": null, "publisher": "", "title": "Chemical record (New York, N.Y.)", "volume": "14", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Methods of split reporter reconstitution for the analysis of biomolecules.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The caspases, a family of cysteine proteases, play multiple roles in apoptosis, inflammation, and cellular differentiation. Caspase-8 (Casp8), which was first identified in humans, functions as an initiator caspase in the apoptotic signaling mediated by cell-surface death receptors. To understand the evolution of function in the Casp8 protein family, casp8 orthologs were identified from a comprehensive range of vertebrates and invertebrates, including sponges and cnidarians, and characterized at both the gene and protein levels. Some introns have been conserved from cnidarians to mammals, but both losses and gains have also occurred; a new intron arose during teleost evolution, whereas in the ascidian Ciona intestinalis, the casp8 gene is intronless and is organized in an operon with a neighboring gene. Casp8 activities are near ubiquitous throughout the animal kingdom. Exogenous expression of a representative range of nonmammalian Casp8 proteins in cultured mammalian cells induced cell death, implying that these proteins possess proapoptotic activity. The cnidarian Casp8 proteins differ considerably from their bilaterian counterparts in terms of amino acid residues in the catalytic pocket, but display the same substrate specificity as human CASP8, highlighting the complexity of spatial structural interactions involved in enzymatic activity. Finally, it was confirmed that the interaction with an adaptor molecule, Fas-associated death domain protein, is also evolutionarily ancient. Thus, despite structural diversity and cooption to a variety of new functions, the ancient origins and near ubiquitous distribution of this activity across the animal kingdom emphasize the importance and utility of Casp8 as a central component of the metazoan molecular toolkit.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Sakamaki", "name": null }, { "creator_type": "author", "first_name": "Kouhei", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Satou", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Funayama", "name": null }, { "creator_type": "author", "first_name": "Masami", "last_name": "Nozaki", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Yajima", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Mayura", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Michi", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Haruna", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Andrew Y.", "last_name": "Gracey", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Tomii", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Gotoh", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Akasaka", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sawasaki", "name": null }, { "creator_type": "author", "first_name": "David J.", "last_name": "Miller", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/molbev/msu260" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25205508" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Annelida", "descriptor_ui": "D000845", "major_topic": false }, { "descriptor": "Anthozoa", "descriptor_ui": "D037421", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": true }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Caspase 8", "descriptor_ui": "D053181", "major_topic": false }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Fish Proteins", "descriptor_ui": "D029941", "major_topic": false }, { "descriptor": "Fishes", "descriptor_ui": "D005399", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Mytilus", "descriptor_ui": "D049878", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Planarians", "descriptor_ui": "D010932", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "3282-3301", "proceedings_title": null, "publisher": "", "title": "Molecular biology and evolution", "volume": "31", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "The apoptotic initiator caspase-8: its functional ubiquity and genetic diversity during animal evolution.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Ascidian larval epidermal sensory neurons (ESNs) each extend a single cilium into the outer body structure, or tunic, to form a unique external sensory network, the ASNET (ascidian dendritic network in tunic). The functions of ESNs and the ASNET are unknown, though it has been suggested that they play important roles in swimming larvae. In this study, we used transgenic larva expressing the photoconvertible protein Kaede pan-neuronally to identify the orientation and morphology of single ESN external processes within the ASNET. RESULTS: When individual ESN cell bodies were UV-irradiated, the photoconverted Kaede protein diffused into the external processes that projected to the edge of the tunic, indicating that these processes are cytoplasmically connected to the cell bodies of ESNs. We were, therefore, able to comprehensively catalog the morphology and orientation of each ESN external process. Most trunk ESNs appeared to extend neurites to the palp, but no processes were observed to emanate from palp neurons. ESN processes differed systematically in their morphology and orientation, suggesting that the ASNET is formed in a regulated, non-random fashion. CONCLUSIONS: This study reveals the organization of ESN sensory fields in the ascidian larval tunic.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takatoshi D.", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/dvdy.24169" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25073890" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": true }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Peripheral Nervous System", "descriptor_ui": "D017933", "major_topic": false }, { "descriptor": "Sensory Receptor Cells", "descriptor_ui": "D011984", "major_topic": false }, { "descriptor": "Urochordata", "descriptor_ui": "D014561", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "1362-1373", "proceedings_title": null, "publisher": "", "title": "Developmental dynamics : an official publication of the American Association of Anatomists", "volume": "243", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Comprehensive morphological analysis of individual peripheral neuron dendritic arbors in ascidian larvae using the photoconvertible protein Kaede.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The aim of this study was to reveal the background to the image variations in strain elastography (strain imaging [SI]) depending on the manner of manipulation (compression magnitude) during elasticity image (EI) acquisition. Thirty patients with 33 breast lesions who had undergone surgery followed by SI assessment in vivo were analyzed. An analytical approach to tissue elasticity based on the stress-elastic modulus (Young's modulus) relationship was adopted. Young's moduli were directly measured ex vivo in surgical specimens ranging from 2.60 kPa (fat) to 16.08 kPa (invasive carcinoma) under the weak-stress condition (<0.2-0.4 kPa, which corresponds to the appropriate \"light touch\" technique in SI investigation. The contrast (ratio) of lesion to fat in elasticity ex vivo gradually decreased as the stress applied increased (around 1.0 kPa) on the background of significant non-linearity of the breast tissue. Our results indicate that the differences in non-linearity in elasticity between the different tissues within the breast under minimal stress conditions are closely related to the variation in EI quality. The significance of the \"pre-load compression\" concept in tissue elasticity evaluation is recognized. Non-linearity of elasticity is an essential attribute of living subjects and could provide useful information having a considerable impact on clinical diagnosis in quantitative ultrasound elastography.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Umemoto", "name": null }, { "creator_type": "author", "first_name": "Ei", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Mitake", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ultrasmedbio.2014.02.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24802305" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Breast", "descriptor_ui": "D001940", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Breast Neoplasms, Male", "descriptor_ui": "D018567", "major_topic": false }, { "descriptor": "Elastic Modulus", "descriptor_ui": "D055119", "major_topic": false }, { "descriptor": "Elasticity Imaging Techniques", "descriptor_ui": "D054459", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Ultrasonography, Mammary", "descriptor_ui": "D016217", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "1755-1768", "proceedings_title": null, "publisher": "", "title": "Ultrasound in medicine & biology", "volume": "40", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Ex vivo and in vivo assessment of the non-linearity of elasticity properties of breast tissues for quantitative strain elastography.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ecdysone is a hormone known to play a pivotal role in crustaceans and insects. In order to evaluate the ecdysone activities in the environment and within the organism, we have developed a biomonitoring Daphnia strain by introducing a reporter gene. In this study, the ecdysone response element was inserted in the upstream region of a reporter gene, and the DNA construct was injected into Daphnia eggs. The expression of the reporter gene was detected during the early embryonic development stage. In addition, when the eggs expressing the reporter gene were exposed to ecdysone, there was enhanced expression of the reporter gene at detectable levels, while the presence of an antagonist led to its downregulation. These results suggested that this system could be potentially developed for monitoring ecdysone activities in media.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Miki", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.marenvres.2013.11.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24296240" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Environmental Monitoring", "descriptor_ui": "D004784", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Receptors, Steroid", "descriptor_ui": "D011987", "major_topic": false }, { "descriptor": "Response Elements", "descriptor_ui": "D020218", "major_topic": false }, { "descriptor": "Zygote", "descriptor_ui": "D015053", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Feb", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "118-122", "proceedings_title": null, "publisher": "", "title": "Marine environmental research", "volume": "93", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualization of ecdysteroid activity using a reporter gene in the crustacean, Daphnia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Ionizing irradiation is an effective treatment for malignant glioma (MG); however, a higher rate of recurrence with more aggressive phenotypes is a vital issue. Although epithelial-mesenchymal transition (EMT) is involved in irradiation-induced cancer progression, the role for such phenotypic transition in MG remains unknown. METHODS: To investigate the mechanism of irradiation-dependent tumor progression in MG, we performed immunohistochemistry (IHC) and qRT-PCR using primary and recurrent MG specimens, MG cell lines, and primary culture cells of MG. siRNA technique was used for MG cell lines. RESULTS: In 22 cases of clinically recurrent MG, the expression of the mesenchymal markers vimentin and CD44 was found to be increased by IHC. In paired identical MG of 7 patients, the expression of collagen, MMPs, and YKL-40 were also elevated in the recurrent MGs, suggesting the The Cancer Genome Atlas-based mesenchymal subtype. Among EMT regulators, sustained elevation of Snail was observed in MG cells at 21 days after irradiation. Cells exhibited an upregulation of migration, invasion, numbers of focal adhesion, and MMP-2 production, and all of these mesenchymal features were abrogated by Snail knockdown. Intriguingly, phosphorylation of ERK1/2 and GSK-3beta were increased after irradiation in a Snail-dependent manner, and TGF-beta was elevated in both fibroblasts and macrophages but not in MG cells after irradiation. It was noteworthy that irradiated cells also expressed stemness features such as SOX2 expression and tumor-forming potential in vivo. CONCLUSIONS: We here propose a novel concept of glial-mesenchymal transition after irradiation in which the sustained Snail expression plays an essential role.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Roshan", "last_name": "Mahabir", "name": null }, { "creator_type": "author", "first_name": "Mishie", "last_name": "Tanino", "name": null }, { "creator_type": "author", "first_name": "Aiman", "last_name": "Elmansuri", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Taichi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Tamio", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nishihara", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Shirato", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/neuonc/not239" }, "pmcid": { "normalized": "PMC3984547" }, "pmid": { "normalized": "24357458" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain Neoplasms", "descriptor_ui": "D001932", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Epithelial-Mesenchymal Transition", "descriptor_ui": "D058750", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glioma", "descriptor_ui": "D005910", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Mutant Strains", "descriptor_ui": "D008817", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Snail Family Transcription Factors", "descriptor_ui": "D000071250", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "671-685", "proceedings_title": null, "publisher": "", "title": "Neuro-oncology", "volume": "16", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Sustained elevation of Snail promotes glial-mesenchymal transition after irradiation in malignant glioma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Us3 is a serine-threonine protein kinase that is encoded by herpes simplex virus 1 (HSV-1). In experimental animal models of HSV infection, peripheral and intracranial inoculations can be used to study viral pathogenicity in peripheral sites (e.g., eyes and vagina) and central nervous systems (CNSs), respectively. In addition, peripheral inoculation can be used to investigate this virus' ability to invade the CNS (neuroinvasiveness) from peripheral sites. HSV-1 Us3 has previously been shown to be critical for viral pathogenicity in both peripheral sites and CNSs of mice. However, the role of HSV-1 Us3 in viral neuroinvasiveness has not yet been elucidated. In the present study, the yields of a Us3 null mutant virus and its repaired virus in the eyes, trigeminal ganglia, and brains of mice following ocular inoculation were examined. It was found that, although the repaired virus appeared in the brains of mice 3 days after infection, peak replication occurring 7 days after infection, no viral replication of the Us3 null mutant virus was detectable. These findings indicate that HSV-1 Us3 plays a crucial role in the ability of the virus to invade the brain from the eyes. Thus, HSV-1 Us3 is a significant neuroinvasiveness factor in vivo.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/1348-0421.12108" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24200420" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Eye", "descriptor_ui": "D005123", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Order", "descriptor_ui": "D023061", "major_topic": false }, { "descriptor": "Genome, Viral", "descriptor_ui": "D016679", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Trigeminal Ganglion", "descriptor_ui": "D012668", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "31-37", "proceedings_title": null, "publisher": "", "title": "Microbiology and immunology", "volume": "58", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of herpes simplex virus 1 Us3 in viral neuroinvasiveness.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herpesviruses have evolved a unique mechanism for nuclear egress of nascent progeny nucleocapsids: the nucleocapsids bud through the inner nuclear membrane into the perinuclear space between the inner and outer nuclear membranes (primary envelopment), and enveloped nucleocapsids then fuse with the outer nuclear membrane to release nucleocapsids into the cytoplasm (de-envelopment). We have shown that the herpes simplex virus 1 (HSV-1) major virion structural protein UL47 (or VP13/VP14) is a novel regulator for HSV-1 nuclear egress. In particular, we demonstrated the following: (i) UL47 formed a complex(es) with HSV-1 proteins UL34, UL31, and/or Us3, which have all been reported to be critical for viral nuclear egress, and these viral proteins colocalized at the nuclear membrane in HSV-1-infected cells; (ii) the UL47-null mutation considerably reduced primary enveloped virions in the perinuclear space although capsids accumulated in the nucleus; and (iii) UL47 was detected in primary enveloped virions in the perinuclear space by immunoelectron microscopy. These results suggested that UL47 promoted HSV-1 primary envelopment, probably by interacting with the critical HSV-1 regulators for viral nuclear egress and by modulating their functions. IMPORTANCE: Like other herpesviruses, herpes simplex virus 1 (HSV-1) has evolved a vesicle-mediated nucleocytoplasmic transport mechanism for nuclear egress of nascent progeny nucleocapsids. Although previous reports identified and characterized several HSV-1 and cellular proteins involved in viral nuclear egress, complete details of HSV-1 nuclear egress remain to be elucidated. In this study, we have presented data suggesting (i) that the major HSV-1 virion structural protein UL47 (or VP13/VP14) formed a complex with known viral regulatory proteins critical for viral nuclear egress and (ii) that UL47 played a regulatory role in HSV-1 primary envelopment. Thus, we identified UL47 as a novel regulator for HSV-1 nuclear egress.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Zhuoming", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sagara", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kawaoka", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00137-14" }, "pmcid": { "normalized": "PMC3993843" }, "pmid": { "normalized": "24522907" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Interaction Mapping", "descriptor_ui": "D025941", "major_topic": true }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Viral Fusion Proteins", "descriptor_ui": "D014760", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virus Release", "descriptor_ui": "D057074", "major_topic": true } ], "publication": { "conference_name": null, "date": "2014 May", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "4657-4667", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "88", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Herpes simplex virus 1 UL47 interacts with viral nuclear egress factors UL31, UL34, and Us3 and regulates viral nuclear egress.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The water flea Daphnia is a new model organism for ecological, evolutionary, and toxicological genomics. Detailed functional analysis of genes newly discovered through genomic approaches often requires overexpression of the identified protein. In the present study, we report the microinjection of in vitro-synthesized RNAs into the eggs as a method for overexpressing ubiquitous proteins in Daphnia magna. We injected a 1.3-kb mRNA that coded for the red fluorescent protein (DsRed2) flanked by UTRs from the ubiquitously expressed elongation factor 1alpha-1 (EF1alpha-1) into D. magna embryos. DsRed2 fluorescence in the embryos was measured 24 h after microinjection. Unexpectedly, the reporter RNA containing the 522-bp full-length EF1alpha-1 3' UTR failed to induce fluorescence. To assess reporter expression, the length of the 3' UTR that potentially contained negative regulatory elements of protein expression, including AU-rich regions and Musashi binding elements, was serially reduced from the 3' end. Assessing all injected RNA alternatives, mRNA containing the first 60 bp of the 3' UTR gave rise to the highest fluorescence, 14 times the Daphnia auto-fluorescence. In contrast, mRNA lacking the entire 3' UTR hardly induced any change in fluorescence intensity. This is the first evaluation of UTRs of mRNAs delivered into Daphnia embryos by microinjection for overexpressing proteins. The mRNA with truncated 3' UTRs of Daphnia EF1alpha-1 will be useful not only for gain-of-function analyses but also for labeling proteins and organelles with fluorescent proteins in Daphnia.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kerstin", "last_name": "Torner", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00438-014-0830-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24585253" } }, "mesh": [ { "descriptor": "3' Untranslated Regions", "descriptor_ui": "D020413", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "DNA, Recombinant", "descriptor_ui": "D004274", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Microinjections", "descriptor_ui": "D008845", "major_topic": false }, { "descriptor": "Nucleic Acid Conformation", "descriptor_ui": "D009690", "major_topic": false }, { "descriptor": "Ovum", "descriptor_ui": "D010063", "major_topic": false }, { "descriptor": "Peptide Elongation Factor 1", "descriptor_ui": "D020648", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Sequence Analysis, DNA", "descriptor_ui": "D017422", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "707-715", "proceedings_title": null, "publisher": "", "title": "Molecular genetics and genomics : MGG", "volume": "289", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Optimization of mRNA design for protein expression in the crustacean Daphnia magna.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Cigarette smoking is a known risk factor for arteriosclerosis. In atheromatous plaques, vascular smooth muscle cells (VSMCs) display a phenotype that is different from the contractile type under normal conditions. Nicotine is the major pharmacological agent in cigarette smoke. However, any direct effect of nicotine on VSMCs remains uncertain. Because nicotine promotes VSMC migration, its phenotype may change due to nicotine. APPROACH AND RESULTS: We used human aorta primary smooth muscle cells (HuAoSMCs), differentiated with transforming growth factor-beta, to investigate changes in the protein levels of differentiation markers and in the activity of mitogen-activated protein kinases (MAPKs) after exposure to 0.1 muM of nicotine for 48 h. After nicotine exposure, the protein levels of myosin II 10 (2.93-fold) and beta-actin (1.66-fold), synthetic type markers, were increased. In contrast, the levels of the contractile type markers, myosin II 11 (0.63-fold), high-molecular-weight caldesmon (0.40-fold) and SM22 (0.66-fold), which concern differentiated VSMC, were decreased. Moreover, nicotine exposure induced enhanced activation of p38 MAPK (1.30-fold) and extracellular signal-regulated kinase (1.91-fold). These results indicated that the phenotype of HuAoSMCs had changed to a synthetic-like type because of nicotine exposure. Thus, nicotine is one factor that can alter protein expression of differentiation markers in VSMCs. Besides, the increase of intracellular Ca(2+) levels suggested that these effects of nicotine were mediated through nicotinic acetylcholine receptors. CONCLUSION: Nicotine has already been reported to promote VSMC migration from the tunica media to atheromatous plaques in the vascular intima. This phenomenon may occur because nicotine directly induces VSMC transformation from contractile type to synthetic-like type via nicotinic acetylcholine receptors and G protein-coupled receptors.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shinji", "last_name": "Yoshiyama", "name": null }, { "creator_type": "author", "first_name": "Zhenyi", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Okagaki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Kohama", "name": null }, { "creator_type": "author", "first_name": "Ritsuko", "last_name": "Nasu-Kawaharada", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Noriyasu", "last_name": "Ohshima", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Nakamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.atherosclerosis.2014.10.019" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25463075" } }, "mesh": [ { "descriptor": "Aorta", "descriptor_ui": "D001011", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calmodulin-Binding Proteins", "descriptor_ui": "D002148", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Muscle Contraction", "descriptor_ui": "D009119", "major_topic": false }, { "descriptor": "Muscle, Smooth, Vascular", "descriptor_ui": "D009131", "major_topic": false }, { "descriptor": "Myocytes, Smooth Muscle", "descriptor_ui": "D032389", "major_topic": false }, { "descriptor": "Nicotine", "descriptor_ui": "D009538", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Receptors, Nicotinic", "descriptor_ui": "D011978", "major_topic": false }, { "descriptor": "Smoking", "descriptor_ui": "D012907", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false }, { "descriptor": "Tunica Media", "descriptor_ui": "D017540", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Dec", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "464-470", "proceedings_title": null, "publisher": "", "title": "Atherosclerosis", "volume": "237", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Nicotine exposure alters human vascular smooth muscle cell phenotype from a contractile to a synthetic type.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INI1/hSNF5/BAF47, which has an SNF5 domain, belongs to the SWI/SNF family. This family is known as ATP-dependent regulators of gene expression by remodeling chromatin structure during cell differentiation. However, the detailed function of INI1/hSNF5/BAF47 is unclear. Here we report the generation of a specific monoclonal antibody for INI1/hSNF5/BAF47 by the mouse iliac lymph node method. The obtained antibody recognized two isoforms of INI1/hSNF5/BAF47 in immunoblotting and precisely recognized the nuclear localization of INI1/hSNF5/BAF47 in immunostaining. This antibody can contribute to further elucidation of the mechanisms of gene expression regulation by INI1/hSNF5/BAF47 during cell differentiation.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Masayasu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yuuki", "last_name": "Kuniyoshi", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Semba", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Sugahara", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/mab.2013.0065" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24555937" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Chromosomal Proteins, Non-Histone", "descriptor_ui": "D002868", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Glutathione Transferase", "descriptor_ui": "D005982", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hybridomas", "descriptor_ui": "D006825", "major_topic": false }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "SMARCB1 Protein", "descriptor_ui": "D000071796", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Feb", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "49-51", "proceedings_title": null, "publisher": "", "title": "Monoclonal antibodies in immunodiagnosis and immunotherapy", "volume": "33", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of a monoclonal antibody for INI1/hSNF5/BAF47.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Substrate elasticity is a potent regulator of the cell state. Soft substrates have been shown to promote the homogeneous self-renewal of mouse embryonic stem cells through the down-regulation of cell-matrix tractions. We therefore investigated whether soft substrates promote the reprogramming of somatic cells into induced pluripotent stem (iPS) cells. After retroviral infection with five factors, Oct3/4, Klf4, Sox2, Lin28 and Nanog, mouse embryonic fibroblasts (MEFs) were cultured on several artificial substrates of varying elasticity and examined for the expression of pluripotency genes. When MEFs were cultured on soft (<0.1 kPa) polyacrylamide gels coated with gelatin, the expressions of Nanog and Oct3/4 genes were higher than in cells cultured on rigid plastic dishes ( approximately 10(6) kPa). The same result was obtained at higher elasticity (0.5 kPa) for adult human dermal fibroblasts (HDFa). We also examined whether reprogramming could be enhanced on soft substrates without exogenous gene introduction, finding that cells cultured on soft substrates in the presence of chemicals known to promote cell reprogramming exhibited up-regulated stem cell markers. These results suggest that controlling the substrate stiffness can enhance the initiation of cell reprogramming, which may lead to effective and reproducible iPS cell production.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Sayaka", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kawauchi", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbiosc.2013.11.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24360205" } }, "mesh": [ { "descriptor": "Acrylamides", "descriptor_ui": "D000178", "major_topic": false }, { "descriptor": "Adult Stem Cells", "descriptor_ui": "D053687", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Culture Media", "descriptor_ui": "D003470", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": true }, { "descriptor": "Hardness", "descriptor_ui": "D006244", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Kruppel-Like Factor 4", "descriptor_ui": "D000090062", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nanog Homeobox Protein", "descriptor_ui": "D000071317", "major_topic": false }, { "descriptor": "Octamer Transcription Factor-3", "descriptor_ui": "D050814", "major_topic": false }, { "descriptor": "rho-Associated Kinases", "descriptor_ui": "D054460", "major_topic": false }, { "descriptor": "SOXB1 Transcription Factors", "descriptor_ui": "D055748", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "749-755", "proceedings_title": null, "publisher": "", "title": "Journal of bioscience and bioengineering", "volume": "117", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Culturing of mouse and human cells on soft substrates promote the expression of stem cell markers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "UNLABELLED: In order to investigate the novel function(s) of the herpes simplex virus 1 (HSV-1) immediate early protein ICP22, we screened for ICP22-binding proteins in HSV-1-infected cells. Our results were as follows. (i) Tandem affinity purification of ICP22 from infected cells, coupled with mass spectrometry-based proteomics and subsequent analyses, demonstrates that ICP22 forms a complex(es) with the HSV-1 proteins UL31, UL34, UL47 (or VP13/14), and/or Us3. All these proteins were previously reported to be important for viral egress through the nuclear membrane. (ii) ICP22 colocalizes with UL31 and UL34 at the nuclear membrane in wild-type HSV-1-infected cells. (iii) The UL31-null mutation prevents the targeting of ICP22 to the nuclear membrane. (iv) The ICP22-null mutation resulted in UL31 and UL34 being mislocalized in the endoplasmic reticulum (in addition to the nuclear membrane) and significantly reduced numbers of primary enveloped virions in the perinuclear space, although capsids accumulated in the nuclei. Collectively, these results suggest that (i) ICP22 interacts with HSV-1 regulators of nuclear egress, including UL31, UL34, UL47, and Us3 in HSV-1-infected cells; (ii) UL31 mediates the recruitment and anchorage of ICP22 at the nuclear membrane; and (iii) ICP22 plays a regulatory role in HSV-1 primary envelopment, probably by interacting with and regulating UL31 and UL34. Here we report a previously unknown function for ICP22 in the regulation of HSV-1 nuclear egress. IMPORTANCE: The herpes simplex virus 1 (HSV-1) immediate early protein ICP22 is recognized primarily as a regulator of viral gene expression. In this study, we show that ICP22 interacts with the HSV-1 proteins UL31 and UL34, which play crucial roles at the nuclear membrane in HSV-1 primary envelopment during viral nuclear egress. We also demonstrate that UL31 is required for the targeting of ICP22 to the nuclear membrane and that ICP22 is required for the correct localization of UL31 and/or UL34. Furthermore, we confirm that ICP22 is required for efficient HSV-1 primary envelopment during viral nuclear egress. Thus, we report, for the first time, that ICP22 plays a regulatory role in HSV-1 nuclear egress.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Zhuoming", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kozuka-Hata", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01057-14" }, "pmcid": { "normalized": "PMC4054440" }, "pmid": { "normalized": "24741100" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Chromatography, Affinity", "descriptor_ui": "D002846", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immediate-Early Proteins", "descriptor_ui": "D017874", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Nuclear Envelope", "descriptor_ui": "D009685", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization", "descriptor_ui": "D019032", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virion", "descriptor_ui": "D014771", "major_topic": false }, { "descriptor": "Virus Assembly", "descriptor_ui": "D019065", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jul", "date_precision": "unknown", "issue": "13", "normalized_date": null, "pages": "7445-7454", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "88", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of herpes simplex virus 1 immediate early protein ICP22 in viral nuclear egress.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herpes simplex virus 1 (HSV-1) encodes Us3 protein kinase, which is critical for viral pathogenicity in both mouse peripheral sites (e.g., eyes and vaginas) and in the central nervous systems (CNS) of mice after intracranial and peripheral inoculations, respectively. Whereas some Us3 substrates involved in Us3 pathogenicity in peripheral sites have been reported, those involved in Us3 pathogenicity in the CNS remain to be identified. We recently reported that Us3 phosphorylated HSV-1 dUTPase (vdUTPase) at serine 187 (Ser-187) in infected cells, and this phosphorylation promoted viral replication by regulating optimal enzymatic activity of vdUTPase. In the present study, we show that the replacement of vdUTPase Ser-187 by alanine (S187A) significantly reduced viral replication and virulence in the CNS of mice following intracranial inoculation and that the phosphomimetic substitution at vdUTPase Ser-187 in part restored the wild-type viral replication and virulence. Interestingly, the S187A mutation in vdUTPase had no effect on viral replication and pathogenic effects in the eyes and vaginas of mice after ocular and vaginal inoculation, respectively. Similarly, the enzyme-dead mutation in vdUTPase significantly reduced viral replication and virulence in the CNS of mice after intracranial inoculation, whereas the mutation had no effect on viral replication and pathogenic effects in the eyes and vaginas of mice after ocular and vaginal inoculation, respectively. These observations suggested that vdUTPase was one of the Us3 substrates responsible for Us3 pathogenicity in the CNS and that the CNS-specific virulence of HSV-1 involved strict regulation of vdUTPase activity by Us3 phosphorylation.IMPORTANCE Herpes simplex virus 1 (HSV-1) encodes a viral protein kinase Us3 which is critical for pathogenicity both in peripheral sites and in the central nervous systems (CNS) of mice following peripheral and intracranial inoculations, respectively. Whereas some Us3 substrates involved in Us3 pathogenicity in peripheral sites have been reported, those involved in Us3 pathogenicity in the CNS remain to be identified. Here, we report that Us3 phosphorylation of viral dUTPase (vdUTPase) at serine 187 (Ser-187), which has been shown to promote the vdUTPase activity, appears to be critical for viral virulence in the CNS but not for pathogenic effects in peripheral sites. Since HSV proteins critical for viral virulence in the CNS are, in almost all cases, also involved in viral pathogenicity at peripheral sites, this phosphorylation event is a unique report of a specific mechanism involved in HSV-1 virulence in the CNS.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.03300-13" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24352467" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Central Nervous System", "descriptor_ui": "D002490", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genome, Viral", "descriptor_ui": "D016679", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Pyrophosphatases", "descriptor_ui": "D011755", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virulence", "descriptor_ui": "D014774", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Mar", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "2775-2785", "proceedings_title": null, "publisher": "", "title": "Journal of Virology", "volume": "88", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Phosphorylation of a Herpes Simplex Virus 1 dUTPase by a Viral Protein Kinase, Us3, Dictates Viral Pathogenicity in the Central Nervous System but Not at the Periphery.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The herpes simplex virus 1 (HSV-1) UL12 protein (pUL12) is a nuclease that is critical for viral replication in vitro and neurovirulence in vivo. In this study, mass spectrometric analysis of pUL12 and phosphate-affinity SDS-polyacrylamide gel electrophoresis analysis identified tyrosine at pUL12 residue 371 (Tyr-371) as a pUL12 phosphorylation site: Tyr-371 is conserved in pUL12 homologs in herpesviruses in all Herpesviridae subfamilies. Replacement of Tyr-371 with phenylalanine (Y371F) in pUL12 (i) abolished its exonuclease activity in HSV-1-infected Vero, HEL, and A549 cells, (ii) reduced viral replication, cell-cell spread, and pUL12 expression in infected cells in a cell type-dependent manner, (iii) led to aberrant subcellular localization of pUL12 in infected cells in a cell type-dependent manner, and (iv) reduced HSV-1 neurovirulence in mice. The effects of the pUL12 Y371F mutation in cell cultures and mice were similar to those of a nuclease-dead double mutation in pUL12, although the Y371F mutation reduced viral replication severalfold more than the nuclease-dead double mutation in a cell type- and multiplicity-of-infection-dependent manner. Replacement of Tyr-371 with glutamic acid, which mimics constitutive phosphorylation, restored the wild-type phenotype in cell cultures and mice. These results suggested that phosphorylation of pUL12 Tyr-371 was essential for pUL12 to express its nuclease activity in HSV-1-infected cells and that this phosphorylation promoted viral replication and cell-cell spread in cell cultures and neurovirulence in mice mainly by upregulating pUL12 nuclease activity and, in part, by regulating the subcellular localization and expression of pUL12 in HSV-1-infected cells. IMPORTANCE: Herpesviruses encode a considerable number of enzymes for their replication. Like cellular enzymes, the viral enzymes need to be properly regulated in infected cells. Although the functional aspects of herpesvirus enzymes have gradually been clarified, information on how most of these enzymes are regulated in infected cells is lacking. In the present study, we report that the enzymatic activity of the herpes simplex virus 1 alkaline nuclease pUL12 was regulated by phosphorylation of pUL12 Tyr-371 in infected cells and that this phosphorylation promoted viral replication and cell-cell spread in cell cultures and neurovirulence in mice, mainly by upregulating pUL12 nuclease activity. Interestingly, pUL12 and tyrosine at pUL12 residue 371 appeared to be conserved in all herpesviruses in the family Herpesviridae, raising the possibility that the herpesvirus pUL12 homologs may also be regulated by phosphorylation of the conserved tyrosine residue.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hikaru", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Mugitani", "name": null }, { "creator_type": "author", "first_name": "Yukie", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kozuka-Hata", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01634-14" }, "pmcid": { "normalized": "PMC4178857" }, "pmid": { "normalized": "24991005" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Deoxyribonucleases", "descriptor_ui": "D003851", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Tyrosine", "descriptor_ui": "D014443", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Sep", "date_precision": "unknown", "issue": "18", "normalized_date": null, "pages": "10624-10634", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "88", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "The UL12 protein of herpes simplex virus 1 is regulated by tyrosine phosphorylation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Calcium imaging of individual neurons is widely used for monitoring their activity in vitro and in vivo. Synthetic fluorescent calcium indicator dyes are commonly used, but the resulting calcium signals sometimes suffer from a low signal-to-noise ratio (SNR). Therefore, it is difficult to detect signals caused by single action potentials (APs) particularly from neurons in vivo. Here we showed that a recently developed calcium indicator dye, Cal-520, is sufficiently sensitive to reliably detect single APs both in vitro and in vivo. In neocortical neurons, calcium signals were linearly correlated with the number of APs, and the SNR was > 6 for in vitro slice preparations and > 1.6 for in vivo anesthetised mice. In cerebellar Purkinje cells, dendritic calcium transients evoked by climbing fiber inputs were clearly observed in anesthetised mice with a high SNR and fast decay time. These characteristics of Cal-520 are a great advantage over those of Oregon Green BAPTA-1, the most commonly used calcium indicator dye, for monitoring the activity of individual neurons both in vitro and in vivo.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mayumi", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Atsuya", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/ejn.12476" }, "pmcid": { "normalized": "PMC4232931" }, "pmid": { "normalized": "24405482" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": false }, { "descriptor": "Aniline Compounds", "descriptor_ui": "D000814", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Fluoresceins", "descriptor_ui": "D005452", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Neocortex", "descriptor_ui": "D019579", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Pyramidal Cells", "descriptor_ui": "D017966", "major_topic": false }, { "descriptor": "Signal-To-Noise Ratio", "descriptor_ui": "D059629", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jun", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "1720-1728", "proceedings_title": null, "publisher": "", "title": "The European journal of neuroscience", "volume": "39", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "A highly sensitive fluorescent indicator dye for calcium imaging of neural activity in vitro and in vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ecological developmental biology (eco-devo) explores the mechanistic relationships between the processes of individual development and environmental factors. Recent studies imply that some of these relationships have deep evolutionary origins, and may even predate the divergences of the simplest extant animals, including cnidarians and sponges. Development of these early diverging metazoans is often sensitive to environmental factors, and these interactions occur in the context of conserved signaling pathways and mechanisms of tissue homeostasis whose detailed molecular logic remain elusive. Efficient methods for transgenesis in cnidarians together with the ease of experimental manipulation in cnidarians and sponges make them ideal models for understanding causal relationships between environmental factors and developmental mechanisms. Here, we identify major questions at the interface between animal evolution and development and outline a road map for research aimed at identifying the mechanisms that link environmental factors to developmental mechanisms in early diverging metazoans.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Thomas C. G.", "last_name": "Bosch", "name": null }, { "creator_type": "author", "first_name": "Maja", "last_name": "Adamska", "name": null }, { "creator_type": "author", "first_name": "René", "last_name": "Augustin", "name": null }, { "creator_type": "author", "first_name": "Tomislav", "last_name": "Domazet-Loso", "name": null }, { "creator_type": "author", "first_name": "Sylvain", "last_name": "Foret", "name": null }, { "creator_type": "author", "first_name": "Sebastian", "last_name": "Fraune", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Funayama", "name": null }, { "creator_type": "author", "first_name": "Juris", "last_name": "Grasis", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Hatta", "name": null }, { "creator_type": "author", "first_name": "Bert", "last_name": "Hobmayer", "name": null }, { "creator_type": "author", "first_name": "Kotoe", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Klimovich", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Manuel", "name": null }, { "creator_type": "author", "first_name": "Chuya", "last_name": "Shinzato", "name": null }, { "creator_type": "author", "first_name": "Uli", "last_name": "Technau", "name": null }, { "creator_type": "author", "first_name": "Seungshic", "last_name": "Yum", "name": null }, { "creator_type": "author", "first_name": "David J.", "last_name": "Miller", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/bies.201400065" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25205353" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": true }, { "descriptor": "Cnidaria", "descriptor_ui": "D003063", "major_topic": false }, { "descriptor": "Ecosystem", "descriptor_ui": "D017753", "major_topic": false }, { "descriptor": "Extinction, Biological", "descriptor_ui": "D053476", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Gene-Environment Interaction", "descriptor_ui": "D059647", "major_topic": true }, { "descriptor": "Life Cycle Stages", "descriptor_ui": "D008018", "major_topic": false }, { "descriptor": "Metamorphosis, Biological", "descriptor_ui": "D008675", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Porifera", "descriptor_ui": "D011161", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1185-1194", "proceedings_title": null, "publisher": "", "title": "BioEssays : news and reviews in molecular, cellular and developmental biology", "volume": "36", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "How do environmental factors influence life cycles and development? An experimental framework for early-diverging metazoans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We recently reported that herpes simplex virus 1 (HSV-1) protein kinase Us3 phosphorylated viral dUTPase (vdUTPase) at serine 187 (Ser-187) to upregulate its enzymatic activity, which promoted HSV-1 replication in human neuroblastoma SK-N-SH cells but not in human carcinoma HEp-2 cells. In the present study, we showed that endogenous cellular dUTPase activity in SK-N-SH cells was significantly lower than that in HEp-2 cells and that overexpression of cellular dUTPase in SK-N-SH cells increased the replication of an HSV-1 mutant with an alanine substitution for Ser-187 (S187A) in vdUTPase to the wild-type level. In addition, we showed that knockdown of cellular dUTPase in HEp-2 cells significantly reduced replication of the mutant vdUTPase (S187A) virus but not that of wild-type HSV-1. Furthermore, the replacement of Ser-187 in vdUTPase with aspartic acid, which mimics constitutive phosphorylation, and overexpression of cellular dUTPase restored viral replication to the wild-type level in cellular dUTPase knockdown HEp-2 cells. These results indicated that sufficient dUTPase activity was required for efficient HSV-1 replication and supported the hypothesis that Us3 phosphorylation of vdUTPase Ser-187 upregulated vdUTPase activity in host cells with low cellular dUTPase activity to produce efficient viral replication.virus. Importance: It has long been assumed that dUTPase activity is important for replication of viruses encoding a dUTPase and that the viral dUTPase (vdUTPase) activity was needed if host cell dUTPase activity was not sufficient for efficient viral replication. In the present study, we showed that the S187A mutation in HSV-1 vdUTPase, which impaired its enzymatic activity, reduced viral replication in SK-N-SH cells, which have low endogenous cellular dUTPase activity, and that overexpression of cellular dUTPase restored viral replication to the wild-type level. We also showed that knockdown of cellular dUTPase in HEp-2 cells, which have higher dUTPase activity than do SK-N-SH cells, reduced replication of HSV-1 with the vdUTPase mutation but had no effect on wild-type virus replication. This is the first report, to our knowledge, directly showing that dUTPase activity is critical for efficient viral replication and that vdUTPase compensates for low host cell dUTPase activity to produce efficient viral replication.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hirohata", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00603-14" }, "pmcid": { "normalized": "PMC4097765" }, "pmid": { "normalized": "24760895" } }, "mesh": [ { "descriptor": "Amino Acid Substitution", "descriptor_ui": "D019943", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutant Proteins", "descriptor_ui": "D050505", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": true }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Pyrophosphatases", "descriptor_ui": "D011755", "major_topic": false }, { "descriptor": "Serine", "descriptor_ui": "D012694", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": true } ], "publication": { "conference_name": null, "date": "2014 Jul", "date_precision": "unknown", "issue": "14", "normalized_date": null, "pages": "7776-7785", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "88", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Phosphorylation of herpes simplex virus 1 dUTPase upregulated viral dUTPase activity to compensate for low cellular dUTPase activity for efficient viral replication.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We present a novel scheme to extract a multiscale state space network (SSN) from single-molecule time series. The multiscale SSN is a type of hidden Markov model that takes into account both multiple states buried in the measurement and memory effects in the process of the observable whenever they exist. Most biological systems function in a nonstationary manner across multiple timescales. Combined with a recently established nonlinear time series analysis based on information theory, a simple scheme is proposed to deal with the properties of multiscale and nonstationarity for a discrete time series. We derived an explicit analytical expression of the autocorrelation function in terms of the SSN. To demonstrate the potential of our scheme, we investigated single-molecule time series of dissociation and association kinetics between epidermal growth factor receptor (EGFR) on the plasma membrane and its adaptor protein Ash/Grb2 (Grb2) in an in vitro reconstituted system. We found that our formula successfully reproduces their autocorrelation function for a wide range of timescales (up to 3 s), and the underlying SSNs change their topographical structure as a function of the timescale; while the corresponding SSN is simple at the short timescale (0.033-0.1 s), the SSN at the longer timescales (0.1 s to ~3 s) becomes rather complex in order to capture multiscale nonstationary kinetics emerging at longer timescales. It is also found that visiting the unbound form of the EGFR-Grb2 system approximately resets all information of history or memory of the process.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tahmina", "last_name": "Sultana", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Morimatsu", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Teramoto", "name": null }, { "creator_type": "author", "first_name": "Chun-Biu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/1.4848719" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24387402" } }, "mesh": [ { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "GRB2 Adaptor Protein", "descriptor_ui": "D051380", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Markov Chains", "descriptor_ui": "D008390", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Dec 28", "date_precision": "day", "issue": "24", "normalized_date": "2013-12-28", "pages": "245101", "proceedings_title": null, "publisher": "", "title": "The Journal of chemical physics", "volume": "139", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Non-Markovian properties and multiscale hidden Markovian network buried in single molecule time series.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Infection by a given pathogen results in stimulation of multiple classes of innate receptors in a cell, leading to activation of distinct signaling pathways. However, these pathways are not always beneficial to immune response against the pathogen. This study shows that, on infection by pathogenic bacterium Listeria monocytogenes, Toll-like receptor (TLR) pathways suppress type I IFN gene induction that is mediated by stimulator of IFN genes. Type I IFNs are critical for antiviral immunity but detrimental to macrophage bactericidal activity. The TLR pathways selectively suppress IFN regulatory factor 3, an essential transcription factor for type I IFN gene induction, through induction/activation of mitogen-activated protein kinase phosphatases, revealing a unique mechanism of beneficial innate signaling interference against bacterial infection.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hideo", "last_name": "Negishi", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Matsuki", "name": null }, { "creator_type": "author", "first_name": "Nobuyasu", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Hana", "last_name": "Sarashina", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Fukazawa", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Taguchi-Atarashi", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Ikushima", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Yanai", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Kenya", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Shun’ichiro", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Yongliang", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Hongbo", "last_name": "Chi", "name": null }, { "creator_type": "author", "first_name": "Richard A.", "last_name": "Flavell", "name": null }, { "creator_type": "author", "first_name": "Tadatsugu", "last_name": "Taniguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1320145110" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24248350" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Colony-Forming Units Assay", "descriptor_ui": "D003114", "major_topic": false }, { "descriptor": "Dual Specificity Phosphatase 1", "descriptor_ui": "D054638", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Immunoprecipitation", "descriptor_ui": "D047468", "major_topic": false }, { "descriptor": "Interferon Regulatory Factor-3", "descriptor_ui": "D050838", "major_topic": false }, { "descriptor": "Interferon Type I", "descriptor_ui": "D007370", "major_topic": false }, { "descriptor": "Listeria monocytogenes", "descriptor_ui": "D008089", "major_topic": false }, { "descriptor": "Listeriosis", "descriptor_ui": "D008088", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Multiprotein Complexes", "descriptor_ui": "D046912", "major_topic": false }, { "descriptor": "Myeloid Differentiation Factor 88", "descriptor_ui": "D053594", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Toll-Like Receptors", "descriptor_ui": "D051193", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Dec 3", "date_precision": "day", "issue": "49", "normalized_date": "2013-12-03", "pages": "19884-19889", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "110", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Beneficial innate signaling interference for antibacterial responses by a Toll-like receptor–mediated enhancement of the MKP-IRF3 axis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A lipid second messenger, phosphatidylinositol (3,4,5)-trisphosphate (PIP3), is a signaling molecule that mediates central cellular events, such as growth, motility, and development by activating downstream proteins. Although functions of various PIP3 binding partners have been unveiled, the various roles of PIP3 have not been resolved thoroughly because of limitations of PIP3 analysis. Herein, we describe a novel method for the analysis of relative PIP3 amount based on spontaneous complementation of split luciferase fragments. An N-terminal fragment of a luciferase was located on the plasma membrane (LucN-pm). A C-terminal fragment of a luciferase fused with PIP3 binding units, pleckstrin homology domains (PHDs) of the general receptor for phosphoinositides 1 (GRP1), was expressed in cytosol (PP-LucC). In response to PIP3 production, PP-LucC was brought to the plasma membrane and colocalized with LucN-pm. The LucN-pm and PP-LucC reconstituted spontaneously to form an active luciferase, producing bioluminescence recovery. We obtained bioluminescence signals corresponding to relative PIP3 amounts successfully upon stimulation with an agonist. We also demonstrated that the probes were applied for a high-throughput screening format and for monitoring of PIP3 production on the plasma membrane by bioluminescence. This method enables further study of PIP3 and supports versatile applications related to the PIP3 amount.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Lingzhi", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nasu", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kanno", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ac402278f" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24195761" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CHO Cells", "descriptor_ui": "D016466", "major_topic": false }, { "descriptor": "Cricetulus", "descriptor_ui": "D003412", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Phosphatidylinositol Phosphates", "descriptor_ui": "D018129", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Dec 3", "date_precision": "day", "issue": "23", "normalized_date": "2013-12-03", "pages": "11352-11359", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "85", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Bioluminescent probes to analyze ligand-induced phosphatidylinositol 3,4,5-trisphosphate production with split luciferase complementation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Let it shine: New hypoxia-sensitive fluorescent probes were developed; they consist of a rhodamine moiety with an azo group directly conjugated to the fluorophore. Because of an ultrafast conformational change around the NN bond, the compounds are nonfluorescent under normoxia. However, under hypoxia, the azo group is reduced, and a strongly fluorescent rhodamine derivative is released.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Wen", "last_name": "Piao", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Fengyi", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Shodai", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Kushida", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Morokuma", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201305784" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24127124" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Azo Compounds", "descriptor_ui": "D001391", "major_topic": false }, { "descriptor": "Cell Hypoxia", "descriptor_ui": "D015687", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Microsomes, Liver", "descriptor_ui": "D008862", "major_topic": false }, { "descriptor": "Quantum Theory", "descriptor_ui": "D011789", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Dec 2", "date_precision": "day", "issue": "49", "normalized_date": "2013-12-02", "pages": "13028-13032", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "52", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of azo-based fluorescent probes to detect different levels of hypoxia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "G-protein-coupled receptors (GPCRs) may form heteromeric complexes and cooperatively mediate cellular responses. Although heteromeric GPCR complexes are suggested to occur in many neurons, their contribution to neuronal function remains unclear. We address this question using two GPCRs expressed in cerebellar Purkinje cells: adenosine A1 receptor (A1R), which regulates neurotransmitter release and neuronal excitability in central neurons, and type-1 metabotropic glutamate receptor (mGluR1), which mediates cerebellar long-term depression, a form of synaptic plasticity crucial for cerebellar motor learning. We examined interaction between these GPCRs by immunocytochemical, biochemical, and Forster resonance energy transfer analyses in cultured mouse Purkinje cells and heterologous expression cells. These analyses revealed that the GPCRs closely colocalized and formed heteromeric complexes on the cell surfaces. Furthermore, our electrophysiological analysis showed that CSF levels (40-400 nm) of adenosine or synthetic A1R agonists with comparable potencies blocked mGluR1-mediated long-term depression of the postsynaptic glutamate-responsiveness (glu-LTD) of cultured Purkinje cells. A similar dose of the A1R agonist decreased the ligand affinity of mGluR1 and did not affect depolarization-induced Ca(2+) influx, which is an essential factor in inducing glu-LTD. The A1R agonist did not affect glu-LTD mimicked by direct activation of protein kinase C. These results suggest that A1R blocked glu-LTD by decreasing the ligand sensitivity of mGluR1, but not the coupling efficacy from mGluR1 to the intracellular signaling cascades. These findings provide a new insight into neuronal GPCR signaling and demonstrate a novel regulatory mechanism of synaptic plasticity.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Kamikubo", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Shimomura", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Kashiyama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Kenkichi", "last_name": "Fukurotani", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.5567-12.2013" }, "pmcid": { "normalized": "PMC6618803" }, "pmid": { "normalized": "24259587" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bicuculline", "descriptor_ui": "D001640", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Energy Transfer", "descriptor_ui": "D004735", "major_topic": false }, { "descriptor": "Excitatory Amino Acid Antagonists", "descriptor_ui": "D018691", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neuroprotective Agents", "descriptor_ui": "D018696", "major_topic": false }, { "descriptor": "Quinoxalines", "descriptor_ui": "D011810", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Receptor, Adenosine A1", "descriptor_ui": "D043682", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false }, { "descriptor": "Sodium Channel Blockers", "descriptor_ui": "D026941", "major_topic": false }, { "descriptor": "Tetrodotoxin", "descriptor_ui": "D013779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Nov 20", "date_precision": "day", "issue": "47", "normalized_date": "2013-11-20", "pages": "18661-18671", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "33", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Functional cooperation of metabotropic adenosine and glutamate receptors regulates postsynaptic plasticity in the cerebellum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Axon guidance involves multiple second messenger signal transduction pathways. Although each signal transduction pathway has been characterized, only a few studies have examined crosstalk between these cascades. Here, we applied a simultaneous second messenger imaging method to the growth cone and demonstrated correlations between cAMP, cGMP, and Ca(2+). The levels of cAMP and cGMP in non-stimulated freely extending growth cones showed a negative correlation without delay. Although there was no direct correlation between cAMP and Ca(2+), examination of cross correlations using small time windows showed frequent switching behavior from negative to positive and vice versa. Furthermore, spatially asymmetric cAMP and cGMP signals in freely deviating growth cones were visualized directly. These results indicate that we succeed in relating second messenger crosstalk to growth cone deviation and extension, and also indicate the possibility of predicting axon guidance from this second messenger crosstalk.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takahiko", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Nagase", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep03118" }, "pmcid": { "normalized": "PMC3814829" }, "pmid": { "normalized": "24176909" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Growth Cones", "descriptor_ui": "D020439", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Second Messenger Systems", "descriptor_ui": "D015290", "major_topic": true } ], "publication": { "conference_name": null, "date": "2013 Nov 1", "date_precision": "day", "issue": "", "normalized_date": "2013-11-01", "pages": "3118", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "3", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Crosstalk between second messengers predicts the motility of the growth cone.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Migratory cells, including mammalian leukocytes and Dictyostelium, use G-protein-coupled receptor (GPCR) signaling to regulate MAPK/ERK, PI3K, TORC2/AKT, adenylyl cyclase and actin polymerization, which collectively direct chemotaxis. Upon ligand binding, mammalian GPCRs are phosphorylated at cytoplasmic residues, uncoupling G-protein pathways, but activating other pathways. However, connections between GPCR phosphorylation and chemotaxis are unclear. In developing Dictyostelium, secreted cAMP serves as a chemoattractant, with extracellular cAMP propagated as oscillating waves to ensure directional migratory signals. cAMP oscillations derive from transient excitatory responses of adenylyl cyclase, which then rapidly adapts. We have studied chemotactic signaling in Dictyostelium that express non-phosphorylatable cAMP receptors and show through chemotaxis modeling, single-cell FRET imaging, pure and chimeric population wavelet quantification, biochemical analyses and TIRF microscopy, that receptor phosphorylation is required to regulate adenylyl cyclase adaptation, long-range oscillatory cAMP wave production and cytoskeletal actin response. Phosphorylation defects thus promote hyperactive actin polymerization at the cell periphery, misdirected pseudopodia and the loss of directional chemotaxis. Our data indicate that chemoattractant receptor phosphorylation is required to co-regulate essential pathways for migratory cell polarization and chemotaxis. Our results significantly extend the understanding of the function of GPCR phosphorylation, providing strong evidence that this evolutionarily conserved mechanism is required in a signal attenuation pathway that is necessary to maintain persistent directional movement of Dictyostelium, neutrophils and other migratory cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Joseph A.", "last_name": "Brzostowski", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Orr", "last_name": "Rozov", "name": null }, { "creator_type": "author", "first_name": "Xin-hua", "last_name": "Liao", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Carole A.", "last_name": "Parent", "name": null }, { "creator_type": "author", "first_name": "Alan R.", "last_name": "Kimmel", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/jcs.122952" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23902692" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false }, { "descriptor": "Mechanistic Target of Rapamycin Complex 2", "descriptor_ui": "D000076225", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 1", "descriptor_ui": "D019950", "major_topic": false }, { "descriptor": "Multiprotein Complexes", "descriptor_ui": "D046912", "major_topic": false }, { "descriptor": "Phosphatidylinositol 3-Kinases", "descriptor_ui": "D019869", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protozoan Proteins", "descriptor_ui": "D015800", "major_topic": false }, { "descriptor": "Receptors, Cyclic AMP", "descriptor_ui": "D011953", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "TOR Serine-Threonine Kinases", "descriptor_ui": "D058570", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Oct 15", "date_precision": "day", "issue": "20", "normalized_date": "2013-10-15", "pages": "4614-4626", "proceedings_title": null, "publisher": "", "title": "Journal of Cell Science", "volume": "126", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Phosphorylation of chemoattractant receptors regulates chemotaxis, actin reorganization and signal relay.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Electron-rich cycloparaphenyleneacetylenes as well as their twin \"glasses-like\" conjugates form stable complexes with fullerenes.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Senda", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kowada", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c3cc42561d" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23715441" } }, "mesh": [], "publication": { "conference_name": null, "date": "2013 Oct 14", "date_precision": "day", "issue": "80", "normalized_date": "2013-10-14", "pages": "9092-9094", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "49", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Electron-rich carbon nanorings as macrocyclic hosts for fullerenes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: The neovascular form of age-related macular degeneration (AMD) is characterized by the growth of abnormal new blood vessels from the choroid, termed choroidal neovascularization (CNV). The origin of the new vessels in CNV, however, has not been elucidated fully to our knowledge. The purpose of this study is to identify vascular endothelial side population (SP) cells in the preexisting choroidal vessels, and investigate their potential role in AMD. METHODS: We made single cell suspensions of freshly isolated mouse choroidal, retinal, and brain tissue by enzymatic digestion. Vascular endothelial SP cells were isolated using flow cytometry based on the ability to efflux the DNA-binding dye, Hoechst 33342, via ATP-binding cassette (ABC) transporters. RESULTS: In the choroid, 2.8% of CD31(+)CD45(-) vascular endothelial cells (ECs) showed a typical SP staining pattern. They were not bone marrow-derived and possessed high colony-forming capacity in vitro. They proliferated during laser-induced CNV in vivo. In contrast, stereotypic SP staining pattern was not observed in retinal and brain ECs. Retinal and brain EC-SP cells included increased SP populations with less colony-forming capacity within the SP compartment, because they contained cells with and without proliferative potential. The latter still could efflux the dye due to high levels of ABC transporters, such as ABCB1a, ABCC4, and ABCC6. CONCLUSIONS: The EC-SP cells in the choroid may represent vessel-residing endothelial stem/progenitor cells contributing mainly to angiogenesis, and may be useful for augmenting vascular regeneration or for developing new antiangiogenic therapy in AMD.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taku", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takara", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Sakimoto", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1167/iovs.13-12342" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24022013" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "ATP-Binding Cassette Transporters", "descriptor_ui": "D018528", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Choroid", "descriptor_ui": "D002829", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Endothelium, Vascular", "descriptor_ui": "D004730", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Macular Degeneration", "descriptor_ui": "D008268", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "Retinal Neovascularization", "descriptor_ui": "D015861", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Oct 11", "date_precision": "day", "issue": "10", "normalized_date": "2013-10-11", "pages": "6686-6693", "proceedings_title": null, "publisher": "", "title": "Investigative ophthalmology & visual science", "volume": "54", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of vascular endothelial side population cells in the choroidal vessels and their potential role in age-related macular degeneration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report, for the first time, the saturated excitation (SAX) of fluorescent proteins for subdiffraction-limited imaging of living cells in three-dimensions. To achieve saturation, a bright yellow and green fluorescent protein (Venus and EGFP) that exhibits a strong nonlinear fluorescence response to the high excitation intensity at the laser focus is used. Harmonic demodulation of the fluorescence signal produced by a modulated excitation light extracts the nonlinear fluorescence signals. After constructing the image from the nonlinear components, we obtain fluorescence images of living cells with spatial resolution beyond the diffraction limit. We also applied linear deconvolution to SAX microscopy and found it effective in further enhancing the contrast of small intracellular structures in the SAX image, confirming the expansion of the optical transfer function in SAX microscopy.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masahito", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1098/rsfs.2013.0007" }, "pmcid": { "normalized": "PMC3915824" }, "pmid": { "normalized": "24511385" } }, "mesh": [], "publication": { "conference_name": null, "date": "2013 Oct 6", "date_precision": "day", "issue": "5", "normalized_date": "2013-10-06", "pages": "20130007", "proceedings_title": null, "publisher": "", "title": "Interface focus", "volume": "3", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Saturated excitation of fluorescent proteins for subdiffraction-limited imaging of living cells in three dimensions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: For the analysis of spatio-temporal dynamics, various automated processing methods have been developed for nuclei segmentation. These methods tend to be complex for segmentation of images with crowded nuclei, preventing the simple reapplication of the methods to other problems. Thus, it is useful to evaluate the ability of simple methods to segment images with various degrees of crowded nuclei. RESULTS: Here, we selected six simple methods from various watershed based and local maxima detection based methods that are frequently used for nuclei segmentation, and evaluated their segmentation accuracy for each developmental stage of the Caenorhabditis elegans. We included a 4D noise filter, in addition to 2D and 3D noise filters, as a pre-processing step to evaluate the potential of simple methods as widely as possible. By applying the methods to image data between the 50- to 500-cell developmental stages at 50-cell intervals, the error rate for nuclei detection could be reduced to 3 s to pull it again. We found two types of task-related cells in the mice: cells whose peak activities occurred during lever pulls (pull cells) and cells whose peak activities occurred after the end of lever pulls. The activity of pull cells was strongly associated with lever-pull duration. In ∼40% of imaged fields, functional clusterings were temporally detected during the lever pulls. Spatially, there were ∼70-μm-scale clusters that consisted of more than four pull cells in ∼50% of the fields. Ensemble and individual activities of pull cells within the cluster more accurately predicted lever movement trajectories than activities of pull cells outside the cluster. This was likely because clustered pull cells were more often active in the individual trials than pull cells outside the cluster. This higher fidelity of activity was related to higher trial-to-trial correlations of activities of pairs within the cluster. We propose that strong recurrent network clusters may represent the execution of voluntary movements.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Riichiro", "last_name": "Hira", "name": null }, { "creator_type": "author", "first_name": "Fuki", "last_name": "Ohkubo", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Isomura", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Matsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.2550-12.2013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23345214" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain Mapping", "descriptor_ui": "D001931", "major_topic": false }, { "descriptor": "Electromyography", "descriptor_ui": "D004576", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Motor Cortex", "descriptor_ui": "D009044", "major_topic": false }, { "descriptor": "Movement", "descriptor_ui": "D009068", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Jan 23", "date_precision": "day", "issue": "4", "normalized_date": "2013-01-23", "pages": "1377-1390", "proceedings_title": null, "publisher": "", "title": "The Journal of Neuroscience", "volume": "33", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatiotemporal Dynamics of Functional Clusters of Neurons in the Mouse Motor Cortex during a Voluntary Movement.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Sung Bae", "last_name": "Kim", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ac3031724" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23134415" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": true }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": true } ], "publication": { "conference_name": null, "date": "2013 Jan 15", "date_precision": "day", "issue": "2", "normalized_date": "2013-01-15", "pages": "590-609", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "85", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Advances in fluorescence and bioluminescence imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "It has long been held that cortisol, a glucocorticoid in many vertebrates, performs glucocorticoid and mineralocorticoid actions in the teleost fish since it lacks aldosterone. However, in addition to the counterparts of tetrapod mineralocorticoid receptors (MRs), 11-deoxycorticosterone (DOC) has been recently identified as a specific endogenous ligand for the MRs in teleosts. Here, we point out the minor role of mineralocorticoid signaling (i.e., DOC-MR) in the osmoregulation compared with those of glucocorticoid signaling (i.e., cortisol-glucocorticoid receptor [GR]), and review the current findings on the physiological roles of the DOC-MR in teleosts. Cortisol promotes both freshwater and seawater adaptation via the GRs in the osmoregulatory organs such as gills and gastrointestinal tracts, but the expressions of MR mRNA are abundant in the brains especially in the key components of the stress axis and cerebellums. Together with the behavioral effects of intracerebroventricular injection with DOC, the MR is suggested to play an important role in the brain dependent behaviors. Since the abundant expression of central MRs has been reported also in higher vertebrates and the MR is thought to be ancestral to the GR, the role of MR in fish might reflect the principal and original function of corticosteroid signaling. Functional evolution of corticosteroid systems is summarized and areas in need of research like our on-going experiments with MR-knockout medaka are outlined.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hideya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ygcen.2012.11.016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23220000" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fishes", "descriptor_ui": "D005399", "major_topic": false }, { "descriptor": "Glucocorticoids", "descriptor_ui": "D005938", "major_topic": false }, { "descriptor": "Receptors, Mineralocorticoid", "descriptor_ui": "D018161", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Water-Electrolyte Balance", "descriptor_ui": "D014882", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Jan 15", "date_precision": "day", "issue": "", "normalized_date": "2013-01-15", "pages": "223-228", "proceedings_title": null, "publisher": "", "title": "General and comparative endocrinology", "volume": "181", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "The role of 'mineralocorticoids' in teleost fish: relative importance of glucocorticoid signaling in the osmoregulation and 'central' actions of mineralocorticoid receptor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Leucine-rich repeat kinase 2 (LRRK2) is the molecule responsible for autosomal-dominant Parkinson's disease (PD), PARK8, but the etiologic effects of its mutation remain unknown. In the present study, we investigated a novel mechanism for the neurodegeneration induced by I2020T mutant LRRK2. Using native gel electrophoresis and immunoprecipitation, we found that wild-type (WT) LRRK2 formed a heterodimer with I2020T LRRK2 in transfected cells, and that the heterodimer exhibited a markedly lower intracellular protein level than the WT/WT-homodimer. An increased amount of I2020T LRRK2 decreased the protein level of co-transfected WT LRRK2. A pulse-chase experiment revealed that the intracellular protein lifetime of WT LRRK2 was shortened by co-transfection with I2020T LRRK2. These results suggest that I2020T LRRK2 enhances the intracellular degradation of WT LRRK2 through WT/I2020T-heterodimer formation. Overexpression of WT LRRK2 in HEK293 cells increased the phosphorylation level of Akt1 (S473), a possible physiological substrate of LRRK2, and made cells resistant to hydrogen peroxide-induced apoptosis. However, both Akt1 phosphorylation and apoptosis resistance were reduced in WT/I2020T-expressing cells in comparison with WT/WT-expressing cells. Reduction of Akt1 phosphorylation and apoptosis resistance were also evident when a neuroblastoma SH-SY5Y clone overexpressing WT LRRK2 was transfected with the I2020T LRRK2. Altogether, these results suggest that the I2020T mutation enhances the intracellular degradation of LRRK2 through WT/I2020T-heterodimer formation, leading to reduced Akt1 phosphorylation and diminished protectivity against apoptosis. Our findings suggest the possibility of a dominant-negative mechanism of neurodegeneration in PD caused by I2020T LRRK2 mutation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Obata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2012.11.113" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23220480" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoprecipitation", "descriptor_ui": "D047468", "major_topic": false }, { "descriptor": "Leucine-Rich Repeat Serine-Threonine Protein Kinase-2", "descriptor_ui": "D000071158", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Parkinson Disease", "descriptor_ui": "D010300", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Multimerization", "descriptor_ui": "D055503", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Jan 11", "date_precision": "day", "issue": "2", "normalized_date": "2013-01-11", "pages": "560-566", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "430", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Dominant-negative effects of LRRK2 heterodimers: a possible mechanism of neurodegeneration in Parkinson's disease caused by LRRK2 I2020T mutation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have synthesized and evaluated a series of hydroxymethyl rhodamine derivatives and found an intriguing difference of intramolecular spirocyclization behavior: the acetylated derivative of hydroxymethyl rhodamine green (Ac-HMRG) exists as a closed spirocyclic structure in aqueous solution at physiological pH, whereas HMRG itself takes an open nonspirocyclic structure. Ac-HMRG is colorless and nonfluorescent, whereas HMRG is strongly fluorescent. On the basis of these findings, we have developed a general design strategy to obtain highly sensitive fluorescence probes for proteases and glycosidases, by replacing the acetyl group of Ac-HMRG with a substrate moiety of the target enzyme. Specific cleavage of the substrate moiety in the nonfluorescent probe by the target enzyme generates a strong fluorescence signal. To confirm the validity and flexibility of our strategy, we designed and synthesized fluorescence probes for leucine aminopeptidase (Leu-HMRG), fibroblast activation protein (Ac-GlyPro-HMRG), and beta-galactosidase (betaGal-HMRG). All of these probes were almost nonfluorescent due to the formation of spirocyclic structure, but were converted efficiently to highly fluorescent HMRG by the target enzymes. We confirmed that the probes can be used in living cells. These probes offer great practical advantages, including high sensitivity and rapid response (due to regulation of fluorescence at a single reactive site), as well as resistance to photobleaching, and are expected to be useful for a range of biological and pathological investigations.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masayo", "last_name": "Sakabe", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Asanuma", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Ryu J.", "last_name": "Iwatate", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja309688m" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23205758" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "beta-Galactosidase", "descriptor_ui": "D001616", "major_topic": false }, { "descriptor": "Cattle", "descriptor_ui": "D002417", "major_topic": false }, { "descriptor": "Cyclization", "descriptor_ui": "D003500", "major_topic": false }, { "descriptor": "Endopeptidases", "descriptor_ui": "D010450", "major_topic": false }, { "descriptor": "Fibroblast Activation Protein Alpha", "descriptor_ui": "D000099167", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Gelatinases", "descriptor_ui": "D018093", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Leucyl Aminopeptidase", "descriptor_ui": "D007931", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": false }, { "descriptor": "Serine Endopeptidases", "descriptor_ui": "D012697", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Spiro Compounds", "descriptor_ui": "D013141", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Jan 9", "date_precision": "day", "issue": "1", "normalized_date": "2013-01-09", "pages": "409-414", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "135", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Rational design of highly sensitive fluorescence probes for protease and glycosidase based on precisely controlled spirocyclization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Deep sequencing approaches, such as chromatin immunoprecipitation by sequencing (ChIP-seq), have been successful in detecting transcription factor-binding sites and histone modification in the whole genome. An approach for comparing two different ChIP-seq data would be beneficial for predicting unknown functions of a factor. We propose a model to represent co-localization of two different ChIP-seq data. We showed that a meaningful overlapping signal and a meaningless background signal can be separated by this model. We applied this model to compare ChIP-seq data of RNA polymerase II C-terminal domain (CTD) serine 2 phosphorylation with a large amount of peak-called data, including ChIP-seq and other deep sequencing data in the Encyclopedia of DNA Elements (ENCODE) project, and then extracted factors that were related to RNA polymerase II CTD serine 2 in HeLa cells. We further analyzed RNA polymerase II CTD serine 7 phosphorylation, of which their function is still unclear in HeLa cells. Our results were characterized by the similarity of localization for transcription factor/histone modification in the ENCODE data set, and this suggests that our model is appropriate for understanding ChIP-seq data for factors where their function is unknown.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Odawara", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Yoshimi", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Chikashi", "last_name": "Obuse", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Sakata", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nar/gks1010" }, "pmcid": { "normalized": "PMC3592427" }, "pmid": { "normalized": "23125363" } }, "mesh": [ { "descriptor": "Chromatin Immunoprecipitation", "descriptor_ui": "D047369", "major_topic": true }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": true }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": true }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "RNA Polymerase II", "descriptor_ui": "D012319", "major_topic": false }, { "descriptor": "Serine", "descriptor_ui": "D012694", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false }, { "descriptor": "Transcription Initiation Site", "descriptor_ui": "D024363", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Jan 7", "date_precision": "day", "issue": "1", "normalized_date": "2013-01-07", "pages": "54-62", "proceedings_title": null, "publisher": "", "title": "Nucleic acids research", "volume": "41", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "A co-localization model of paired ChIP-seq data using a large ENCODE data set enables comparison of multiple samples.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: Adrenomedullin (ADM) has been shown to take part in physiological and pathological angiogenesis. The purpose of this study was to investigate whether ADM signaling is involved in choroidal neovascularization (CNV) using a mouse model. METHODS AND RESULTS: CNV was induced by laser photocoagulation in 8-week-old C57BL/6 mice. ADM mRNA expression significantly increased following treatment, peaking 4 days thereafter. The expression of ADM receptor (ADM-R) components (CRLR, RAMP2 and RAMP 3) was higher in CD31(+)CD45(-) endothelial cells (ECs) than CD31(-)CD45(-) non-ECs. Inflammatory stimulation upregulated the expression of ADM not only in cell lines but also in cells in primary cultures of the choroid/retinal pigment epithelium complex. Supernatants from TNFalpha-treated macrophage cell lines potentiated the proliferation of ECs and this was partially suppressed by an ADM antagonist, ADM (22-52). Intravitreous injection of ADM (22-52) or ADM neutralizing monoclonal antibody (mAb) after laser treatment significantly reduced the size of CNV compared with vehicle-treated controls (p<0.01). CONCLUSIONS: ADM signaling is involved in laser-induced CNV formation, because both an ADM antagonist and ADM mAb significantly inhibited it. Suppression of ADM signaling might be a valuable alternative treatment for CNV associated with age-related macular degeneration.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Susumu", "last_name": "Sakimoto", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Kamei", "name": null }, { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Daishi", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0058096" }, "pmcid": { "normalized": "PMC3592925" }, "pmid": { "normalized": "23520487" } }, "mesh": [ { "descriptor": "Adrenomedullin", "descriptor_ui": "D053607", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Neutralizing", "descriptor_ui": "D057134", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Choroidal Neovascularization", "descriptor_ui": "D020256", "major_topic": false }, { "descriptor": "Culture Media, Conditioned", "descriptor_ui": "D017077", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": false }, { "descriptor": "Leukocyte Common Antigens", "descriptor_ui": "D017493", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Macular Degeneration", "descriptor_ui": "D008268", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Platelet Endothelial Cell Adhesion Molecule-1", "descriptor_ui": "D019408", "major_topic": false }, { "descriptor": "Receptor Activity-Modifying Protein 2", "descriptor_ui": "D058263", "major_topic": false }, { "descriptor": "Receptor Activity-Modifying Protein 3", "descriptor_ui": "D058264", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Tumor Necrosis Factor-alpha", "descriptor_ui": "D014409", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "3", "normalized_date": "2013", "pages": "e58096", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "8", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "An angiogenic role for adrenomedullin in choroidal neovascularization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent insulinotropic G-protein-coupled receptor ligand, for which morphoregulative roles in pancreatic islets have recently been suggested. Here, we evaluated the effects of pancreatic overexpression of PACAP on morphometric changes of islets in a severe type II diabetes model. Following cross-breeding of obese-diabetic model KKA(y) mice with mice overexpressing PACAP in their pancreatic beta-cells, the resulting KKA(y) mice with or without PACAP transgene (PACAP/+:A(y)/+ or A(y)/+ mice) were fed with a high-fat diet up to the age of 11 months. Pancreatic sections from 5- to 11-month-old littermates were examined. Histomorphometric analyses revealed significant suppression of islet mass expansion in PACAP/+:A(y)/+ mice compared with A(y)/+ mice at 11 months, but no significant difference between PACAP/+ and +/+ (wild-type) mice, as previously reported. The suppressed islet mass in PACAP/+:A(y)/+ mice was due to a decrease in islet density but not islet size. In addition, the density of tiny islets (<0.001 mm(2)) and of insulin-positive clusters in ductal structures were markedly decreased in PACAP/+:A(y)/+ mice compared with A(y)/+ mice at 5 months of age. In contrast, PACAP overexpression caused no significant effects on the level of aldehyde-fuchsin reagent staining (a measure of beta-cell granulation) or the volume and localization of glucagon-positive cells in the pancreas. These results support previously reported inhibitory effects of PACAP on pancreatic islet mass expansion, and suggest it has persistent suppressive effects on pancreatic islet density which may be related with ductal cell-associated islet neogenesis in type II diabetes.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Higashi", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fendo.2013.00027" }, "pmcid": { "normalized": "PMC3593608" }, "pmid": { "normalized": "23483824" } }, "mesh": [], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "", "normalized_date": "2013", "pages": "27", "proceedings_title": null, "publisher": "", "title": "Frontiers in endocrinology", "volume": "4", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "PACAP Inhibits beta-cell Mass Expansion in a Mouse Model of Type II Diabetes: Persistent Suppressive Effects on Islet Density.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chromophore-assisted light inactivation (CALI) is a powerful technique for acute perturbation of biomolecules in a spatio-temporally defined manner in living specimen with reactive oxygen species (ROS). Whereas a chemical photosensitizer including fluorescein must be added to specimens exogenously and cannot be restricted to particular cells or sub-cellular compartments, a genetically-encoded photosensitizer, KillerRed, can be controlled in its expression by tissue specific promoters or subcellular localization tags. Despite of this superiority, KillerRed hasn't yet become a versatile tool because its dimerization tendency prevents fusion with proteins of interest. Here, we report the development of monomeric variant of KillerRed (SuperNova) by direct evolution using random mutagenesis. In contrast to KillerRed, SuperNova in fusion with target proteins shows proper localization. Furthermore, unlike KillerRed, SuperNova expression alone doesn't perturb mitotic cell division. Supernova retains the ability to generate ROS, and hence promote CALI-based functional analysis of target proteins overcoming the major drawbacks of KillerRed.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kiwamu", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Donald", "last_name": "Fu", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Ippei", "last_name": "Kotera", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Horiuchi", "name": null }, { "creator_type": "author", "first_name": "Kiichi", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Tokiyoshi", "last_name": "Ayabe", "name": null }, { "creator_type": "author", "first_name": "Fuyuhiko", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep02629" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24043132" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Chromophore-Assisted Light Inactivation", "descriptor_ui": "D061885", "major_topic": true }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Molecular Weight", "descriptor_ui": "D008970", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "", "normalized_date": "2013", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "3", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "SuperNova, a monomeric photosensitizing fluorescent protein for chromophore-assisted light inactivation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Populations of cells often switch states as a group to cope with environmental changes such as nutrient availability and cell density. Although the gene circuits that underlie the switches are well understood at the level of single cells, the ways in which such circuits work in concert among many cells to support group-level switches are not fully explored. Experimental studies of microbial quorum sensing show that group-level changes in cellular states occur in either a graded or an all-or-none fashion. Here, we show through numerical simulations and mathematical analysis that these behaviors generally originate from two distinct forms of bistability. The choice of bistability is uniquely determined by a dimensionless parameter that compares the synthesis and the transport of the inducing molecules. The role of the parameter is universal, such that it not only applies to the autoinducing circuits typically found in bacteria but also to the more complex gene circuits involved in transmembrane receptor signaling. Furthermore, in gene circuits with negative feedback, the same dimensionless parameter determines the coherence of group-level transitions from quiescence to a rhythmic state. The set of biochemical parameters in bacterial quorum-sensing circuits appear to be tuned so that the cells can use either type of transition. The design principle identified here serves as the basis for the analysis and control of cellular collective decision making.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1003110" }, "pmcid": { "normalized": "PMC3694814" }, "pmid": { "normalized": "23825937" } }, "mesh": [ { "descriptor": "Cell Biology", "descriptor_ui": "D003585", "major_topic": true }, { "descriptor": "Decision Making", "descriptor_ui": "D003657", "major_topic": true }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "6", "normalized_date": "2013", "pages": "e1003110", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "9", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "A design principle of group-level decision making in cell populations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: The gene doublesex (dsx) is known as a key factor regulating genetic sex determination in many organisms. We previously identified two dsx genes (DapmaDsx1 and DapmaDsx2) from a freshwater branchiopod crustacean, Daphnia magna, which are expressed in males but not in females. D. magna produces males by parthenogenesis in response to environmental cues (environmental sex determination) and we showed that DapmaDsx1 expression during embryonic stages is responsible for the male trait development. The D. magna dsx genes are thought to have arisen by a cladoceran-specific duplication; therefore, to investigate evolutionary conservation of sex specific expression of dsx genes and to further assess their functions in the environmental sex determination, we searched for dsx homologs in four closely related cladoceran species. Results: We identified homologs of both dsx genes from, D. pulex, D. galeata, and Ceriodaphnia dubia, yet only a single dsx gene was found from Moina macrocopa. The deduced amino acid sequences of all 9 dsx homologs contained the DM and oligomerization domains, which are characteristic for all arthropod DSX family members. Molecular phylogenetic analysis suggested that the dsx gene duplication likely occurred prior to the divergence of these cladoceran species, because that of the giant tiger prawn Penaeus monodon is rooted ancestrally to both DSX1 and DSX2 of cladocerans. Therefore, this result also suggested that M. macrocopa lost dsx2 gene secondarily. Furthermore, all dsx genes identified in this study showed male-biased expression levels, yet only half of the putative 5’ upstream regulatory elements are preserved in D. magna and D. pulex. Conclusions: The all dsx genes of five cladoceran species examined had similar amino acid structure containing highly conserved DM and oligomerization domains, and exhibited sexually dimorphic expression patterns, suggesting that these genes may have similar functions for environmental sex determination in cladocerans.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Toyota", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Miyagawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Miyakawa", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Shigeto", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Ogino", "name": null }, { "creator_type": "author", "first_name": "Chizue", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Norihisa", "last_name": "Tatarazako", "name": null }, { "creator_type": "author", "first_name": "Susanne", "last_name": "Paland", "name": null }, { "creator_type": "author", "first_name": "Craig", "last_name": "Jackson", "name": null }, { "creator_type": "author", "first_name": "John K.", "last_name": "Colbourne", "name": null }, { "creator_type": "author", "first_name": "Taisen", "last_name": "Iguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1471-2164-14-239" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23575357" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arthropod Proteins", "descriptor_ui": "D060829", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Cladocera", "descriptor_ui": "D033361", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "Conserved Sequence", "descriptor_ui": "D017124", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Duplication", "descriptor_ui": "D020440", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Molecular Sequence Annotation", "descriptor_ui": "D058977", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Sex Characteristics", "descriptor_ui": "D012727", "major_topic": false }, { "descriptor": "Species Specificity", "descriptor_ui": "D013045", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "", "normalized_date": "2013", "pages": "239", "proceedings_title": null, "publisher": "", "title": "BMC Genomics", "volume": "14", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular cloning of doublesex genes of four cladocera (water flea) species.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genetically encoded fluorescent indicators for bioimaging are powerful tools for visualizing biological phenomena in specified cell types or cellular compartments. However, available gene promoters or localization sequences are not applicable for visualizing all expression events. Furthermore, a visualization technique focusing on single cells or cellular compartments is required for characterizing specific cellular properties including individuality of cells in the cell population. To address these limitations, we developed a genetically encoded caged Ca(2+) indicator for which expression timing and location could be controlled. This indicator, PA-TNXL, comprises a Ca(2+)-binding protein and troponin between a photoactivatable FRET donor (PA-GFP) and a FRET quencher (dim variant of YFP). Ultraviolet irradiation activates the FRET Ca(2+) indicator. Using this indicator, we successfully imaged Ca(2+) dynamics in a given set of HeLa cells and cultured hippocampal neurons. This technology can be applied for developing other photoactivatable indicators, thereby opening a new area of biological research.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep01398" }, "pmcid": { "normalized": "PMC3593221" }, "pmid": { "normalized": "23474844" } }, "mesh": [ { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Troponin", "descriptor_ui": "D014336", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "", "normalized_date": "2013", "pages": "1398", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "3", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Highlighted Ca(2)(+) imaging with a genetically encoded 'caged' indicator.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A critical function of singing by male songbirds is to attract a female mate. Previous studies have suggested that the anterior forebrain system is involved in this courtship behavior. Neural activity in this system, including the striatal Area X, is strikingly dependent on the function of male singing. When males sing to attract a female bird rather than while alone, less variable neural activity results in less variable song spectral features, which may be attractive to the female. These characteristics of neural activity and singing thus may reflect a male's motivation for courtship. Here, we compared the variability of neural activity and song features between courtship singing directed to a female with whom a male had previously formed a pair-bond or to other females. Surprisingly, across all units, there was no clear tendency for a difference in variability of neural activity or song features between courtship of paired females, nonpaired females, or dummy females. However, across the population of recordings, there was a significant relationship between the relative variability of syllable frequency and neural activity: when syllable frequency was less variable to paired than nonpaired females, neural activity was also less variable (and vice-versa). These results show that the lower variability of neural activity and syllable frequency during directed singing is not a binary distinction from undirected singing, but can vary in intensity, possibly related to the relative preference of a male for his singing target.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mai", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Thomas M.", "last_name": "Poulsen", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Neal A.", "last_name": "Hessler", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0081725" }, "pmcid": { "normalized": "PMC3843691" }, "pmid": { "normalized": "24312344" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Courtship", "descriptor_ui": "D003380", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Finches", "descriptor_ui": "D046369", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Motivation", "descriptor_ui": "D009042", "major_topic": false }, { "descriptor": "Pair Bond", "descriptor_ui": "D010152", "major_topic": false }, { "descriptor": "Prosencephalon", "descriptor_ui": "D016548", "major_topic": false }, { "descriptor": "Vocalization, Animal", "descriptor_ui": "D014828", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "11", "normalized_date": "2013", "pages": "e81725", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "8", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Singing-related activity in anterior forebrain of male zebra finches reflects courtship motivation for target females.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescent protein-based indicators for intracellular environment conditions such as pH and ion concentrations are commonly used to study the status and dynamics of living cells. Despite being an important factor in many biological processes, the development of an indicator for the physicochemical state of water, such as pressure, viscosity and temperature, however, has been neglected. We here found a novel mutation that dramatically enhances the pressure dependency of the yellow fluorescent protein (YFP) by inserting several glycines into it. The crystal structure of the mutant showed that the tyrosine near the chromophore flipped toward the outside of the beta-can structure, resulting in the entry of a few water molecules near the chromophore. In response to changes in hydrostatic pressure, a spectrum shift and an intensity change of the fluorescence were observed. By measuring the fluorescence of the YFP mutant, we succeeded in measuring the intracellular pressure change in living cell. This study shows a new strategy of design to engineer fluorescent protein indicators to sense hydrostatic pressure.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Imada", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Fumiyoshi", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Takamitsu J.", "last_name": "Morikawa", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Yanagida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0073212" }, "pmcid": { "normalized": "PMC3754940" }, "pmid": { "normalized": "24014139" } }, "mesh": [ { "descriptor": "Amino Acid Substitution", "descriptor_ui": "D019943", "major_topic": true }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Glycine", "descriptor_ui": "D005998", "major_topic": false }, { "descriptor": "Hydrostatic Pressure", "descriptor_ui": "D006874", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Mutation, Missense", "descriptor_ui": "D020125", "major_topic": true } ], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "8", "normalized_date": "2013", "pages": "e73212", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "8", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Glycine insertion makes yellow fluorescent protein sensitive to hydrostatic pressure.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Endocannabinoids are small signaling lipids, with 2-arachidonoylglycerol (2-AG) implicated in modulating axonal growth and synaptic plasticity. The concept of short-range extracellular signaling by endocannabinoids is supported by the lack of trans-synaptic 2-AG signaling in mice lacking sn-1-diacylglycerol lipases (DAGLs), synthesizing 2-AG. Nevertheless, how far endocannabinoids can spread extracellularly to evoke physiological responses at CB1 cannabinoid receptors (CB1Rs) remains poorly understood. Here, we first show that cholinergic innervation of CA1 pyramidal cells of the hippocampus is sensitive to the genetic disruption of 2-AG signaling in DAGLα null mice. Next, we exploit a hybrid COS-7-cholinergic neuron co-culture system to demonstrate that heterologous DAGLα overexpression spherically excludes cholinergic growth cones from 2-AG-rich extracellular environments, and minimizes cell-cell contact in vitro. CB1R-mediated exclusion responses lasted 3 days, indicating sustained spherical 2-AG availability. Overall, these data suggest that extracellular 2-AG concentrations can be sufficient to activate CB1Rs along discrete spherical boundaries to modulate neuronal responsiveness.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Erik", "last_name": "Keimpema", "name": null }, { "creator_type": "author", "first_name": "Alán", "last_name": "Alpár", "name": null }, { "creator_type": "author", "first_name": "Fiona", "last_name": "Howell", "name": null }, { "creator_type": "author", "first_name": "Katarzyna", "last_name": "Malenczyk", "name": null }, { "creator_type": "author", "first_name": "Carl", "last_name": "Hobbs", "name": null }, { "creator_type": "author", "first_name": "Yasmin L.", "last_name": "Hurd", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Patrick", "last_name": "Doherty", "name": null }, { "creator_type": "author", "first_name": "Tibor", "last_name": "Harkany", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep02093" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23806960" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arachidonic Acids", "descriptor_ui": "D001095", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": false }, { "descriptor": "Glycerides", "descriptor_ui": "D005989", "major_topic": false }, { "descriptor": "Lipoprotein Lipase", "descriptor_ui": "D008071", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "", "normalized_date": "2013", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "3", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Diacylglycerol lipase α manipulation reveals developmental roles for intercellular endocannabinoid signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cerebellar cortex has an elaborate rostrocaudal organization comprised of numerous microzones. Purkinje cells (PCs) in the same microzone show synchronous activity of complex spikes (CSs) evoked by excitatory inputs from climbing fibers (CFs) that arise from neurons in the inferior olive (IO). The synchronous CS activity is considered to depend on electrical coupling among IO neurons and anatomical organization of the olivo-cerebellar projection. To determine how the CF-PC wiring contributes to the formation of microzone, we examined the synchronous CS activities between neighboring PCs in the glutamate receptor delta2 knockout (GluD2 KO) mouse in which exuberant surplus CFs make ectopic innervations onto distal dendrites of PCs. We performed in vivo two-photon calcium imaging for PC populations to detect CF inputs. Neighboring PCs in GluD2 KO mice showed higher synchrony of calcium transients than those in wild-type (control) mice. Moreover, the synchrony in GluD2 KO mice hardly declined with mediolateral separation between PCs up to ~200 mum, which was in marked contrast to the falloff of the synchrony in control mice. The enhanced synchrony was only partially affected by the blockade of gap junctional coupling. On the other hand, transverse CF collaterals in GluD2 KO mice extended beyond the border of microzone and formed locally clustered ectopic synapses onto dendrites of neighboring PCs. Furthermore, PCs in GluD2 KO mice exhibited clustered firing (Cf), the characteristic CF response that was not found in PCs of wild-type mice. Importantly, Cf was often associated with localized calcium transients in distal dendrites of PCs, which are likely to contribute to the enhanced synchrony of calcium signals in GluD2 KO mice. Thus, our results indicate that CF signals in GluD2 KO mice propagate across multiple microzones, and that proper formation of longitudinal olivo-cerebellar projection is essential for the spatiotemporal organization of CS activity in the cerebellum.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Miki", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fncir.2013.00130" }, "pmcid": { "normalized": "PMC3747314" }, "pmid": { "normalized": "23970854" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Receptors, Glutamate", "descriptor_ui": "D017470", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "", "normalized_date": "2013", "pages": "130", "proceedings_title": null, "publisher": "", "title": "Frontiers in neural circuits", "volume": "7", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Disruption of cerebellar microzonal organization in GluD2 (GluRdelta2) knockout mouse.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Catechins, flavanols found at high levels in green tea, have received significant attention due to their potential health benefits related to cancer, autoimmunity and metabolic disease, but little is known about the mechanisms by which these compounds affect cellular behavior. Here, we assess whether the model organism Dictyostelium discoideum is a useful tool with which to characterize the effects of catechins. Epigallocatechin gallate (EGCG), the most abundant and potent catechin in green tea, has significant effects on the Dictyostelium life cycle. In the presence of EGCG aggregation is delayed, cells do not stream and development is typically stalled at the loose aggregate stage. The developmental effects very likely result from defects in motility, as EGCG reduces both random movement and chemotaxis of Dictyostelium amoebae. These results suggest that catechins and their derivatives may be useful tools with which to better understand cell motility and development in Dictyostelium and that this organism is a useful model to further characterize the activities of catechins.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kyle J.", "last_name": "McQuade", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "April N.", "last_name": "Ilacqua", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0059275" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23516620" } }, "mesh": [ { "descriptor": "Catechin", "descriptor_ui": "D002392", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "3", "normalized_date": "2013", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "8", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "The Green Tea Catechin Epigallocatechin Gallate (EGCG) Blocks Cell Motility, Chemotaxis and Development in Dictyostelium discoideum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Photodynamic therapy (PDT) involves the administration of a photosensitizer, followed by local irradiation of tumor tissues using a laser of an appropriate wavelength to activate the photosensitizer. Since multiple cellular signaling cascades are concomitantly activated in cancer cells exposed to the photodynamic effect, understanding the responses of cancer cells to PDT will aid in the development of new interventions. This review describes the possible cell-death signaling pathways initiated by PDT. In addition, we describe our latest findings regarding the induction of expression of miRNAs specific to apoptosis in cancer cells and the induction of antitumor immunity following PDT against cancer cells. A more detailed understanding of the molecular mechanisms related to PDT will potentially improve long-term survival of PDT treated patients.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Okawa", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1260/2040-2295.4.1.87" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23502251" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Photochemotherapy", "descriptor_ui": "D010778", "major_topic": false }, { "descriptor": "Photosensitizing Agents", "descriptor_ui": "D017319", "major_topic": false }, { "descriptor": "Singlet Oxygen", "descriptor_ui": "D026082", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "1", "normalized_date": "2013", "pages": "87-108", "proceedings_title": null, "publisher": "", "title": "Journal of healthcare engineering", "volume": "4", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Responses of cancer cells induced by photodynamic therapy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: A drug delivery system specifically targeting endothelial cells (ECs) in tumors is required to prevent normal blood vessels from being damaged by angiogenesis inhibitors. The purpose of this study was to investigate whether apelin, a ligand for APJ expressed in ECs when angiogenesis is taking place, can be used for targeting drug delivery to ECs in tumors. METHODS AND RESULTS: Uptake of apelin via APJ stably expressed in NIH-3T3 cells was investigated using TAMRA (fluorescent probe)-conjugated apelin. Both long and short forms of apelin (apelin 36 and apelin 13) were taken up, the latter more effectively. To improve efficacy of apelin- liposome conjugates, we introduced cysteine, with its sulfhydryl group, to the C terminus of apelin 13, resulting in the generation of apelin 14. In turn, apelin 14 was conjugated to rhodamine-encapsulating liposomes and administered to tumor-bearing mice. In the tumor microenvironment, we confirmed that liposomes were incorporated into the cytoplasm of ECs. In contrast, apelin non-conjugated liposomes were rarely found in the cytoplasm of ECs. Moreover, non-specific uptake of apelin-conjugated liposomes was rarely detected in other normal organs. CONCLUSIONS: ECs in normal organs express little APJ; however, upon hypoxic stimulation, such as in tumors, ECs start to express APJ. The present study suggests that apelin could represent a suitable tool to effectively deliver drugs specifically to ECs within tumors.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kawahara", "name": null }, { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takara", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0065499" }, "pmcid": { "normalized": "PMC3682998" }, "pmid": { "normalized": "23799018" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Apelin Receptors", "descriptor_ui": "D000075244", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Colonic Neoplasms", "descriptor_ui": "D003110", "major_topic": false }, { "descriptor": "Drug Screening Assays, Antitumor", "descriptor_ui": "D004354", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Liposomes", "descriptor_ui": "D008081", "major_topic": false }, { "descriptor": "Melanoma, Experimental", "descriptor_ui": "D008546", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neoplasm Transplantation", "descriptor_ui": "D009368", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "6", "normalized_date": "2013", "pages": "e65499", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "8", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Tumor endothelial cell-specific drug delivery system using apelin-conjugated liposomes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Shaping functional neural circuits in developing brain involves activity-dependent refinement of early-formed redundant synapses. In the developing cerebellum, a one-to-one connection between a climbing fibre (CF) and a Purkinje cell (PC) is established by selective strengthening of a single CF followed by elimination of surplus CFs. Here we investigate developmental changes in CF-mediated responses in PCs by using in vivo whole-cell recordings and two-photon Ca(2+) imaging. We show that each neonatal PC receives temporally clustered inputs from multiple CFs and temporal integration of these inputs is required to induce burst spiking and Ca(2+) rise in PCs. Importantly, a single CF input closest to PC's spike output is selectively strengthened during postnatal development. This spike timing-dependent selective strengthening is much less prominent in PC-selective P/Q-type voltage-dependent Ca(2+) channel knockout mice. Thus, spike timing- and Ca(2+)-dependent plasticity appears to underlie the selection of a single 'winner' CF and the establishment of mature CF-PC connections.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Hisako", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms3732" }, "pmcid": { "normalized": "PMC3868216" }, "pmid": { "normalized": "24225482" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "", "normalized_date": "2013", "pages": "2732", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "4", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Spike timing-dependent selective strengthening of single climbing fibre inputs to Purkinje cells during cerebellar development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Various viruses enter host cells via endocytosis, but the molecular mechanisms underlying the specific internalization pathways remain unclear. Here we show that influenza A viruses (IAVs) enter cells via redundant pathways of clathrin-mediated and clathrin-independent endocytosis, with intracellular Ca(2+) having a central role in regulation of both pathways by activating a signalling axis comprising RhoA, Rho-kinase, phosphatidylinositol 4-phosphate 5-kinase (PIP5K) and phospholipase C (PLC). IAV infection induces oscillations in the cytosolic Ca(2+) concentration of host cells, the prevention of which markedly attenuates virus internalization and infection. The small GTPase RhoA is found both to function downstream of the virus-induced Ca(2+) response and itself to induce Ca(2+) oscillations in a manner dependent on Rho-kinase and subsequent PIP5K-PLC signalling. This signalling circuit regulates both clathrin-mediated and clathrin-independent endocytosis during virus infection and seems to constitute a key mechanism for regulation of IAV internalization and infection.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Nanbo", "name": null }, { "creator_type": "author", "first_name": "Tomoe", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Tadaaki", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms3763" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24434940" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Influenza A virus", "descriptor_ui": "D009980", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phosphoinositide Phospholipase C", "descriptor_ui": "D054801", "major_topic": false }, { "descriptor": "Phosphotransferases (Alcohol Group Acceptor)", "descriptor_ui": "D017853", "major_topic": false }, { "descriptor": "rhoA GTP-Binding Protein", "descriptor_ui": "D020742", "major_topic": false }, { "descriptor": "Virus Internalization", "descriptor_ui": "D053586", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "", "normalized_date": "2013", "pages": "2763", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "4", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "A Ca(2+)-dependent signalling circuit regulates influenza A virus internalization and infection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neural circuits in neonatal animals contain numerous redundant synapses that are functionally immature. During the postnatal period, unnecessary synapses are eliminated while functionally important synapses become stronger and mature. The climbing fiber (CF) to the Purkinje cell (PC) synapse is a representative model for the analysis of postnatal refinement of neuronal circuits in the central nervous system. PCs are initially innervated by multiple CFs with similar strengths around postnatal day 3 (P3). Only a single CF is selectively strengthened during P3–P7 (functional differentiation), and the strengthened CF undergoes translocation from soma to dendrites of PCs from P9 on (dendritic translocation). Following the functional differentiation, supernumerary CF synapses on the soma are eliminated, which proceeds in two distinct phases: the early phase from P7 to around P11 and the late phase from around P12 to P17. Here, we review our current understanding of cellular and molecular mechanisms of CF synapse elimination in the developing cerebellum.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00018-013-1405-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23811844" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Neurological", "descriptor_ui": "D008959", "major_topic": false }, { "descriptor": "Nerve Fibers", "descriptor_ui": "D009412", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "24", "normalized_date": "2013", "pages": "4667-4680", "proceedings_title": null, "publisher": "", "title": "Cellular and Molecular Life Sciences", "volume": "70", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Synapse elimination in the developing cerebellum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Green fluorescent protein and its relatives have shed their light on a wide range of biological problems. To date, with a color palette consisting of fluorescent proteins with different spectra, researchers can \"paint\" living cells as they desire. Moreover, sophisticated biosensors engineered to contain single or multiple fluorescent proteins, including FRET-based biosensors, spatiotemporally unveil molecular mechanisms underlying physiological processes. Although such molecules have contributed considerably to basic research, their abilities to be used in applied life sciences have yet to be fully explored. Here, we review the molecular bases of fluorescent proteins and fluorescent protein-based biosensors and focus on approaches aimed at applying such proteins to the clinic.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Nakada", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/b978-0-12-386932-6.00008-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23244794" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": true }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ions", "descriptor_ui": "D007477", "major_topic": false }, { "descriptor": "Leukemia, Myelogenous, Chronic, BCR-ABL Positive", "descriptor_ui": "D015464", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Tyrosine", "descriptor_ui": "D014443", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "", "normalized_date": "2013", "pages": "313-348", "proceedings_title": null, "publisher": "", "title": "Progress in molecular biology and translational science", "volume": "113", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Fluorescent protein-based biosensors and their clinical applications.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The understanding of pathological processes is based on the comparison between physiological and pathological conditions, and transcriptomic analysis has been extensively applied to various diseases for this purpose. However, the way in which the transcriptomic data of pathological cells relate to the transcriptomes of normal cellular counterparts has not been fully explored, and may provide new and unbiased insights into the mechanisms of these diseases. To achieve this, it is necessary to develop a method to simultaneously analyse components across different levels, namely genes, normal cells, and diseases. Here we propose a multidimensional method that visualises the cross-level relationships between these components at three different levels based on transcriptomic data of physiological and pathological processes, by adapting Canonical Correspondence Analysis, which was developed in ecology and sociology, to microarray data (CCA on Microarray data, CCAM). Using CCAM, we have analysed transcriptomes of haematological disorders and those of normal haematopoietic cell differentiation. First, by analysing leukaemia data, CCAM successfully visualised known relationships between leukaemia subtypes and cellular differentiation, and their characteristic genes, which confirmed the relevance of CCAM. Next, by analysing transcriptomes of myelodysplastic syndromes (MDS), we have shown that CCAM was effective in both generating and testing hypotheses. CCAM showed that among MDS patients, high-risk patients had transcriptomes that were more similar to those of both haematopoietic stem cells (HSC) and megakaryocyte-erythroid progenitors (MEP) than low-risk patients, and provided a prognostic model. Collectively, CCAM reveals hidden relationships between pathological and physiological processes and gene expression, providing meaningful clinical insights into haematological diseases, and these could not be revealed by other univariate and multivariate methods. Furthermore, CCAM was effective in identifying candidate genes that are correlated with cellular phenotypes of interest. We expect that CCAM will benefit a wide range of medical fields.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Reiko J.", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Sugiman", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0053544" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23301083" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Antigens, CD34", "descriptor_ui": "D018952", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Hematologic Diseases", "descriptor_ui": "D006402", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunophenotyping", "descriptor_ui": "D016130", "major_topic": false }, { "descriptor": "Leukemia", "descriptor_ui": "D007938", "major_topic": false }, { "descriptor": "Myelodysplastic Syndromes", "descriptor_ui": "D009190", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Proportional Hazards Models", "descriptor_ui": "D016016", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "1", "normalized_date": "2013", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "8", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualising the Cross-Level Relationships between Pathological and Physiological Processes and Gene Expression: Analyses of Haematological Diseases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Detection and elimination of virus-infected cells by CD8(+) cytotoxic T lymphocytes (CTLs) depends on recognition of virus-derived peptides presented by major histocompatibility complex class I (MHC-I) molecules on the surface of infected cells. In the present study, we showed that inactivation of the activity of viral kinase Us3 encoded by herpes simplex virus 1 (HSV-1), the etiologic agent of several human diseases and a member of the alphaherpesvirinae, significantly increased cell surface expression of MHC-I, thereby augmenting CTL recognition of infected cells in vitro. Overexpression of Us3 by itself had no effect on cell surface expression of MHC-I and Us3 was not able to phosphorylate MHC-I in vitro, suggesting that Us3 indirectly downregulated cell surface expression of MHC-I in infected cells. We also showed that inactivation of Us3 kinase activity induced significantly more HSV-1-specific CD8(+) T cells in mice. Interestingly, depletion of CD8(+) T cells in mice significantly increased replication of a recombinant virus encoding a kinase-dead mutant of Us3, but had no effect on replication of a recombinant virus in which the kinase-dead mutation was repaired. These results indicated that Us3 kinase activity is required for efficient downregulation of cell surface expression of MHC-I and mediates evasion of HSV-1-specific CD8(+) T cells. Our results also raised the possibility that evasion of HSV-1-specific CD8(+) T cells by HSV-1 Us3-mediated inhibition of MHC-I antigen presentation might in part contribute to viral replication in vivo.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takahiko", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Suenaga", "name": null }, { "creator_type": "author", "first_name": "Ayuko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyono", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Arase", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0072050" }, "pmcid": { "normalized": "PMC3741198" }, "pmid": { "normalized": "23951282" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigen Presentation", "descriptor_ui": "D017951", "major_topic": false }, { "descriptor": "Antigens, Viral", "descriptor_ui": "D000956", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Order", "descriptor_ui": "D023061", "major_topic": false }, { "descriptor": "Genome, Viral", "descriptor_ui": "D016679", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Histocompatibility Antigens Class I", "descriptor_ui": "D015395", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Killer Cells, Natural", "descriptor_ui": "D007694", "major_topic": false }, { "descriptor": "Lymphocyte Depletion", "descriptor_ui": "D008212", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "T-Lymphocytes, Cytotoxic", "descriptor_ui": "D013602", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "8", "normalized_date": "2013", "pages": "e72050", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "8", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Us3 kinase encoded by herpes simplex virus 1 mediates downregulation of cell surface major histocompatibility complex class I and evasion of CD8+ T cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular composition and the distribution of bio-molecules play central roles in the specification of cell fates and morphogenesis during embryogenesis. Consequently, investigation of changes in the expression and distribution of bio-molecules, especially mRNAs and proteins, is an important challenge in developmental biology. Raman spectroscopic imaging, a non-invasive and label-free technique, allows simultaneous imaging of the intracellular composition and distribution of multiple bio-molecules. In this study, we explored the application of Raman spectroscopic imaging in the whole Ciona intestinalis embryo during development. Analysis of Raman spectra scattered from C. intestinalis embryos revealed a number of localized patterns of high Raman intensity within the embryo. Based on the observed distribution of bio-molecules, we succeeded in identifying the location and structure of differentiated muscle and endoderm within the whole embryo, up to the tailbud stage, in a label-free manner. Furthermore, during cell differentiation, we detected significant differences in cell state between muscle/endoderm daughter cells and daughter cells with other fates that had divided from the same mother cells; this was achieved by focusing on the Raman intensity of single Raman bands at 1002 or 1526 cm(-1), respectively. This study reports the first application of Raman spectroscopic imaging to the study of identifying and characterizing differentiating tissues in a whole chordate embryo. Our results suggest that Raman spectroscopic imaging is a feasible label-free technique for investigating the developmental process of the whole embryo of C. intestinalis.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuru J.", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0071739" }, "pmcid": { "normalized": "PMC3748111" }, "pmid": { "normalized": "23977129" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Endoderm", "descriptor_ui": "D004707", "major_topic": false }, { "descriptor": "Muscles", "descriptor_ui": "D009132", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Staining and Labeling", "descriptor_ui": "D013194", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "8", "normalized_date": "2013", "pages": "e71739", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "8", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Raman spectroscopic imaging of the whole Ciona intestinalis embryo during development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Detecting biclusters from expression data is useful, since biclusters are coexpressed genes under only part of all given experimental conditions. We present a software called SiBIC, which from a given expression dataset, first exhaustively enumerates biclusters, which are then merged into rather independent biclusters, which finally are used to generate gene set networks, in which a gene set assigned to one node has coexpressed genes. We evaluated each step of this procedure: 1) significance of the generated biclusters biologically and statistically, 2) biological quality of merged biclusters, and 3) biological significance of gene set networks. We emphasize that gene set networks, in which nodes are not genes but gene sets, can be more compact than usual gene networks, meaning that gene set networks are more comprehensible. SiBIC is available at http://utrecht.kuicr.kyoto-u.ac.jp:8080/miami/faces/index.jsp.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kei-ichiro", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Ichigaku", "last_name": "Takigawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Mamitsuka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0082890" }, "pmcid": { "normalized": "PMC3875427" }, "pmid": { "normalized": "24386124" } }, "mesh": [ { "descriptor": "Data Mining", "descriptor_ui": "D057225", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": true }, { "descriptor": "Internet", "descriptor_ui": "D020407", "major_topic": true }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true } ], "publication": { "conference_name": null, "date": "2013", "date_precision": "year", "issue": "12", "normalized_date": "2013", "pages": "e82890", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "8", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "SiBIC: a web server for generating gene set networks based on biclusters obtained by maximal frequent itemset mining.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In diffuse liver disease, it is extremely important to make an accurate diagnosis of liver fibrosis prior to determining indications for therapy or predicting treatment outcome and malignant potential. Although liver biopsy has long been the gold standard in the diagnosis of liver fibrosis, it is still an invasive method. In addition, the sampling error is an intrinsic problem of liver biopsy. Non-invasive serological methods for the diagnosis of liver fibrosis can be affected by factors unrelated to the liver. Recently, after the introduction of FibroScan, it became possible to measure liver fibrosis directly and non-invasively by elastography, which has attracted attention as a non-invasive imaging diagnostic tool for liver fibrosis. In addition, real-time tissue elastography is currently being used to conduct clinical trials at many institutions. Moreover, virtual touch quantification enables the observation of liver stiffness at any location by simply observing B-mode images. Furthermore, the recently developed ShearWave elastography visualizes liver stiffness on a color map. Elastography is thought to be useful for all types of diffuse liver diseases. Because of its association with portal hypertension and liver carcinogenesis, elastography is expected to function as a novel prognostic tool for liver disease. Although various elastographic devices have been developed by multiple companies, each device has its own measurement principle, method, and outcome, creating confusion in clinical settings. Therefore, it is extremely important to understand the characteristics of each device in advance. The objective of this guideline, which describes the characteristics of each device based on the latest knowledge, is for all users to be able to make the correct diagnosis of hepatic fibrosis by ultrasound elastography.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Kudo", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Fuminori", "last_name": "Moriyasu", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Iijima", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Tateishi", "name": null }, { "creator_type": "author", "first_name": "Norihisa", "last_name": "Yada", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Morikawa", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Hirooka", "name": null }, { "creator_type": "author", "first_name": "Yasukiyo", "last_name": "Sumino", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kumada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10396-013-0460-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27277450" } }, "mesh": [], "publication": { "conference_name": null, "date": "2013 Oct", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "325-357", "proceedings_title": null, "publisher": "", "title": "Journal of medical ultrasonics (2001)", "volume": "40", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "JSUM ultrasound elastography practice guidelines: liver.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "It is widely accepted that robust invasion of tumor-associated macrophages resembling M2 macrophage correlates with disease aggressiveness by affecting cancer cell invasion, metastasis, and angiogenesis. Many chemokines that induce migration of macrophages have been identified during inflammatory responses; however, further precise analysis of macrophage migration in the tumor microenvironment is required. Here, we analyzed the function of galectin-3 (Gal-3; gene LGALS3, alias Gal3) for macrophage chemotaxis using Gal3(-/-) mice as hosts, and a tumor allograft model. We engineered a concentration gradient of Gal-3 produced by the tumor. In this model, we found that macrophage infiltration was enhanced in tumors developing in these Gal3(-/-) mice relative to the Gal3(+/+) animals. This was accompanied by enhanced tumor angiogenesis and tumor growth in Gal3(-/-) mice. We found that macrophages of the M2 phenotype were dominant in infiltrates in the Gal3(-/-) mice and that they expressed only low levels of Gal-3. Gal3 knockdown by siRNA in macrophages resulted in enhanced chemotaxis. These data suggest that M2-like macrophages migrate into the tumor along a Gal-3 gradient and that high-level Gal-3 expression in the tumor results in acceleration of angiogenesis and tumor growth. Therefore, Gal-3 could be a potential target for the development of new treatments to inhibit tumor growth.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Weizhen", "last_name": "Jia", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Daishi", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ajpath.2013.01.017" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23499465" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Marrow Cells", "descriptor_ui": "D001854", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Galectin 3", "descriptor_ui": "D037502", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neoplasm Transplantation", "descriptor_ui": "D009368", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "1821-1831", "proceedings_title": null, "publisher": "", "title": "The American journal of pathology", "volume": "182", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Galectin-3 accelerates M2 macrophage infiltration and angiogenesis in tumors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Major questions about stem cell systems include what type(s) of stem cells are involved (unipotent/totipotent/pluripotent/multipotent stem cells) and how the self-renewal and differentiation of stem cells are regulated. Sponges, the sister group of all other animals and probably the earliest branching multicellular lineage of extant animals, are thought to possess totipotent stem cells. This review introduces what is known about the stem cells in sponges based on histological studies and also on recent molecular biological studies that have started to reveal the molecular and cellular mechanisms of the stem cell system in sponges (mainly in demosponges). The currently proposed model of the stem cell system in demosponges is described, and the possible applicability of this model to other classes of sponges is discussed. Finally, a possible scenario of the evolution of stem cells, including how migrating stem cells arose in the urmetazoan (the last common ancestor of metazoans) and the evolutionary origin of germ line cells in the urbilaterian (the last common ancestor of bilaterians), are discussed.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Noriko", "last_name": "Funayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00427-012-0417-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23053625" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Porifera", "descriptor_ui": "D011161", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": true } ], "publication": { "conference_name": null, "date": "2013 Mar", "date_precision": "unknown", "issue": "1-2", "normalized_date": null, "pages": "23-38", "proceedings_title": null, "publisher": "", "title": "Development genes and evolution", "volume": "223", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "The stem cell system in demosponges: suggested involvement of two types of cells: archeocytes (active stem cells) and choanocytes (food-entrapping flagellated cells).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ten years have passed since the first elastography application: Real-time Tissue Elastography. Now there are several elastography applications in existence. The Quality Control Research Team of The Japan Association of Breast and Thyroid Sonology (JABTS) and the Breast Elasticity Imaging Terminology and Diagnostic Criteria Subcommittee, Terminology and Diagnostic Criteria Committee of the Japan Society of Ultrasonics in Medicine (JSUM) have advocated breast elastography classifications for exact knowledge and good clinical use. We suggest two types of classifications: the technical classification and the classification for interpretation. The technical classification has been created to use vibration energy and to make images, and also shows how to obtain a good elastic image. The classification for interpretation has been prepared on the basis of interpretation of evidence in this decade. Finally, we describe the character and specificity of each vender equipment. We expect the present guidelines to be useful for many physicians and examiners throughout the world.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Katsutoshi", "last_name": "Enokido", "name": null }, { "creator_type": "author", "first_name": "Tokiko", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Tsunoda", "name": null }, { "creator_type": "author", "first_name": "Etsuo", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Umemoto", "name": null }, { "creator_type": "author", "first_name": "Ei", "last_name": "Ueno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10396-013-0457-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27277451" } }, "mesh": [], "publication": { "conference_name": null, "date": "2013 Oct", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "359-391", "proceedings_title": null, "publisher": "", "title": "Journal of medical ultrasonics (2001)", "volume": "40", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "JSUM ultrasound elastography practice guidelines: breast.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Abstract Objective: The purpose of this study was to measure intracellular reactive oxygen species (ROS) production after laser irradiation in various types of cells. BACKGROUND DATA: ROS are considered to be the key secondary messengers produced by low-level laser therapy (LLLT). Although various mechanisms for the effects of LLLT have been proposed, and intracellular ROS were indicated as the one of the key factors, direct measurement of intracellular ROS of several types of cells after different wavelength lasers irradiation has not been reported. MATERIALS AND METHODS: Various types of cells were used in this study: mouse preadipocytes (3T3-L1), prechondrocytes (ATDC5), myoblasts (C2C12), mesenchymal stromal cells (KUSA-A1), lung cancer cells (LLC), insulinoma cells (MIN6), fibroblasts (NIH-3T3), human cervix adenocarcinoma cells (HeLa), macrophages differentiated from lymphocytes (THP-1) after treatment with phorbol ester, and rat basophilic leukemia cells (RBL-2H3). Cells were irradiated with a blue laser (wavelength: 405 nm), a red laser (wavelength: 664 nm) or a near infrared laser (wavelength: 808 nm) at 100 mW/cm(2) for 60 or 120 sec. Intracellular ROS levels were measured by fluorometric assay using the intracellular ROS probe, CM-H2DCFDA in a flow cytometer. RESULTS: After a blue laser irradiation, intracellular ROS levels were increased in all types of cells. In contrast, intracellular ROS generation was not observed after irradiation with a red laser or near-infrared laser. CONCLUSIONS: Potential sources of intracellular ROS were excited by blue laser irradiation, resulting in ROS production within cells. Although the low-level intracellular ROS should be generated after a red or a near-infrared laser irradiation, the only high level intracellular ROS were detected by the ROS probe used in this study. As ROS are considered to be key secondary messengers, the specific functional regulation of cells by laser irradiation will be studied in a future study.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kushibiki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Okawa", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/pho.2012.3361" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23390956" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Radiation", "descriptor_ui": "D004307", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Low-Level Light Therapy", "descriptor_ui": "D028022", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "95-104", "proceedings_title": null, "publisher": "", "title": "Photomedicine and laser surgery", "volume": "31", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Blue laser irradiation generates intracellular reactive oxygen species in various types of cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ten years have passed since the first commercial equipment for elastography was released; since then clinical utility has been demonstrated. Nowadays, most manufacturers offer an elastography option. The most widely available commercial elastography methods are based on strain imaging, which uses external tissue compression and generates images of the resulting tissue strain. However, imaging methods differ slightly among manufacturers, which results in different image characteristics, for example, spatial and temporal resolution, and different recommended measurement conditions. In addition, many manufacturers have recently provided a shear wave-based method, providing stiffness images based on shear wave propagation speed. Each method of elastography is designed on the basis of assumptions of measurement conditions and tissue properties. Thus, we need to know the basic principles of elastography methods and the physics of tissue elastic properties to enable appropriate use of each piece of equipment and to obtain more precise diagnostic information from elastography. From this perspective, the basic section of this guideline aims to support practice of ultrasound elastography.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10396-013-0490-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27277449" } }, "mesh": [], "publication": { "conference_name": null, "date": "2013 Oct", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "309-323", "proceedings_title": null, "publisher": "", "title": "Journal of medical ultrasonics (2001)", "volume": "40", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "JSUM ultrasound elastography practice guidelines: basics and terminology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In germ cells, early embryos, and stem cells of animals, PIWI-interacting RNAs (piRNAs) have an important role in silencing retrotransposons, which are vicious genomic parasites, through transcriptional and post-transcriptional mechanisms. To examine whether the piRNA pathway can be used to silence genes of interest in germ cells, we have generated knock-in mice in which a foreign DNA fragment was inserted into a region generating pachytene piRNAs. The knock-in sequence was transcribed, and the resulting RNA was processed to yield piRNAs in postnatal testes. When reporter genes possessing a sequence complementary to portions of the knock-in sequence were introduced, they were greatly repressed after the time of pachytene piRNA generation. This repression mainly occurred at the post-transcriptional level, as degradation of the reporter RNAs was accelerated. Our results show that the piRNA pathway can be used as a tool for sequence-specific gene silencing in germ cells and support the idea that the piRNA generating regions serve as traps for retrotransposons, enabling the host cell to generate piRNAs against active retrotransposons.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Hoki", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Shirane", "name": null }, { "creator_type": "author", "first_name": "Yufeng", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Ichiiyanagi", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Kuramochi-Miyagawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Asao", "last_name": "Fujiyama", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Oginuma", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Sado", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Sasaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/gr.137224.112" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23132912" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Gene Silencing", "descriptor_ui": "D020868", "major_topic": true }, { "descriptor": "Gene Targeting", "descriptor_ui": "D018390", "major_topic": true }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Genetic Loci", "descriptor_ui": "D056426", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "RNA Processing, Post-Transcriptional", "descriptor_ui": "D012323", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "292-299", "proceedings_title": null, "publisher": "", "title": "Genome Research", "volume": "23", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Targeted gene silencing in mouse germ cells by insertion of a homologous DNA into a piRNA generating locus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During animal development, cells undergo dynamic changes in position and gene expression. A collection of quantitative information about morphological dynamics under a wide variety of gene perturbations would provide a rich resource for understanding the molecular mechanisms of development. Here, we created a database, the Worm Developmental Dynamics Database (http://so.qbic.riken.jp/wddd/), which stores a collection of quantitative information about cell division dynamics in early Caenorhabditis elegans embryos with single genes silenced by RNA-mediated interference. The information contains the three-dimensional coordinate values of the outlines of nuclear regions and the dynamics of the outlines over time. The database provides free access to 50 sets of quantitative data for wild-type embryos and 136 sets of quantitative data for RNA-mediated interference embryos corresponding to 72 of the 97 essential embryonic genes on chromosome III. The database also provides sets of four-dimensional differential interference contrast microscopy images on which the quantitative data were based. The database will provide a novel opportunity for the development of computational methods to obtain fresh insights into the mechanisms of development. The quantitative information and microscopy images can be synchronously viewed through a web browser, which is designed for easy access by experimental biologists.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Eru", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Oguro", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Urai", "name": null }, { "creator_type": "author", "first_name": "Ryoko", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Kuramochi", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nar/gks1107" }, "pmcid": { "normalized": "PMC3531189" }, "pmid": { "normalized": "23172286" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Databases, Genetic", "descriptor_ui": "D030541", "major_topic": true }, { "descriptor": "Genes, Helminth", "descriptor_ui": "D017238", "major_topic": false }, { "descriptor": "Internet", "descriptor_ui": "D020407", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Jan", "date_precision": "unknown", "issue": "Database issue", "normalized_date": null, "pages": "D732-737", "proceedings_title": null, "publisher": "", "title": "Nucleic acids research", "volume": "41", "year": 2013 }, "ssbd": { "database": [ "ssbd-database-000002" ], "repository": [ "ssbd-repos-000002" ] }, "title": "WDDD: Worm Developmental Dynamics Database.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mathematical modeling is a promising approach to reveal disease-related regulatory mechanisms. This article gives an overview of how mathematical modeling can increase our understanding of skin disease, addressing both its benefits and challenges. We discuss the importance of strong links among experiments, mathematical modeling, and data analysis in order to effectively use the modeling approach to advance skin research in the postgenomic era. Investigative dermatologists are needed to drive and orient this cross-disciplinary research to address fundamental problems in skin biology and disease.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Reiko J.", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/jid.2013.69" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23514928" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dermatitis, Atopic", "descriptor_ui": "D003876", "major_topic": false }, { "descriptor": "Dermatology", "descriptor_ui": "D003880", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune System", "descriptor_ui": "D007107", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Skin Physiological Phenomena", "descriptor_ui": "D012879", "major_topic": true } ], "publication": { "conference_name": null, "date": "2013 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "1472-1478", "proceedings_title": null, "publisher": "", "title": "The Journal of investigative dermatology", "volume": "133", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Skin disease modeling from a mathematical perspective.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Normally hyperbolic invariant manifolds (NHIMs) are well-known organizing centers of the dynamics in the phase space of a nonlinear system. Locating such manifolds in systems far from symmetric or integrable, however, has been an outstanding challenge. Here, we develop an automated detection method for codimension-one NHIMs in autonomous dynamical systems. Our method utilizes Stationary Lagrangian Coherent Structures (SLCSs), which are hypersurfaces satisfying one of the necessary conditions of a hyperbolic LCS, and are also quasi-invariant in a well-defined sense. Computing SLCSs provides a quick way to uncover NHIMs with high accuracy. As an illustration, we use SLCSs to locate two-dimensional stable and unstable manifolds of hyperbolic periodic orbits in the classic ABC flow, a three-dimensional solution of the steady Euler equations.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Teramoto", "name": null }, { "creator_type": "author", "first_name": "George", "last_name": "Haller", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/1.4824314" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24387546" } }, "mesh": [ { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": true }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": true } ], "publication": { "conference_name": null, "date": "2013 Dec", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "043107", "proceedings_title": null, "publisher": "", "title": "Chaos (Woodbury, N.Y.)", "volume": "23", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Detecting invariant manifolds as stationary Lagrangian coherent structures in autonomous dynamical systems.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genetically encoded calcium ion (Ca(2+)) indicators have become very useful and widely used tools for Ca(2+) imaging, not only in cellular models, but also in living organisms. However, the in vivo and in situ characterization of these indicators is tedious and time consuming, and it does not provide information regarding the suitability of an indicator for particular experimental environments. Thus, initial in vitro evaluation of these tools is typically performed to determine their properties. In this review, we examined the properties of dynamic range, affinity, selectivity, and kinetics for Ca(2+) indicators. Commonly used strategies for evaluating these properties are presented. This article is part of a Special Issue entitled: 12th European Symposium on Calcium.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Vadim", "last_name": "Perez Koldenkova", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbamcr.2013.01.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23352808" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Indicators and Reagents", "descriptor_ui": "D007202", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "1787-1797", "proceedings_title": null, "publisher": "", "title": "Biochimica et biophysica acta", "volume": "1833", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetically encoded Ca(2+) indicators: properties and evaluation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During the past decade, several novel fluorescence microscopy techniques have emerged that achieve incredible spatial and temporal resolution beyond the diffraction limit. These microscopy techniques depend on altered optical setups, unique fluorescent probes, or post-imaging analysis. Many of these techniques also depend strictly on the use of unique fluorescent proteins (FPs) with special photoswitching properties. These photoswitchable FPs are capable of switching between two states in response to light. All localization precision and patterned illumination techniques-such as photo-activation localization microscopy, stochastic optical reconstruction microscopy, reversible saturable optically linear transitions, and saturated structured illumination microscopy-take advantage of these inherent switching properties to achieve superior spatial resolution. This review provides extensive analysis of the positive and negative aspects of photoswitchable FPs, highlighting their application in diffraction-unlimited imaging and suggesting the most suitable fluorescent proteins for superresolution imaging.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Dhermendra K.", "last_name": "Tiwari", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12064" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23635320" } }, "mesh": [ { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Optics and Photonics", "descriptor_ui": "D055095", "major_topic": false }, { "descriptor": "Stochastic Processes", "descriptor_ui": "D013269", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 May", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "491-507", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "55", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Smart fluorescent proteins: innovation for barrier-free superresolution imaging in living cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Angiogenesis is tightly associated with the outgrowth of adipose tissue, leading to obesity, which is a risk factor for type 2 diabetes and hypertension, mainly because expanding adipose tissue requires an increased nutrient supply from blood vessels. Therefore, induction of vessel abnormality by adipokines has been well-studied, whereas how altered vascular function promotes obesity is relatively unexplored. Also, surviving Prox1 heterozygous mice have shown abnormal lymphatic patterning and adult-onset obesity, indicating that accumulation of adipocytes could be closely linked with lymphatic function. Here, we propose a new antiobesity strategy based on enhancement of lymphatic and blood vessel integrity with apelin. Apelin knockout (KO) mice fed a high-fat diet (HFD) showed an obese phenotype associated with abnormal lymphatic and blood vessel enlargement. Fatty acids present in the HFD induced hyperpermeability of endothelial cells, causing adipocyte differentiation, whereas apelin promoted vascular stabilization. Moreover, treatment of apelin KO mice with a selective cyclooxygenase-2 inhibitor, celecoxib, that were fed an HFD improved vascular function and also attenuated obesity. Finally, apelin transgenic mice showed decreased subcutaneous adipose tissue attributable to inhibition of HFD-induced hyperpermeability of vessels. These results indicate that apelin inhibits HFD-induced obesity by enhancing vessel integrity. Apelin could serve as a therapeutic target for treating obesity and related diseases.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mika", "last_name": "Sawane", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kajiya", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.2337/db12-0604" }, "pmcid": { "normalized": "PMC3661640" }, "pmid": { "normalized": "23378608" } }, "mesh": [ { "descriptor": "Adipocytes", "descriptor_ui": "D017667", "major_topic": false }, { "descriptor": "Adipokines", "descriptor_ui": "D054392", "major_topic": false }, { "descriptor": "Adipose Tissue", "descriptor_ui": "D000273", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apelin", "descriptor_ui": "D000073861", "major_topic": false }, { "descriptor": "Blood Vessels", "descriptor_ui": "D001808", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cyclooxygenase 2 Inhibitors", "descriptor_ui": "D052246", "major_topic": false }, { "descriptor": "Diet, High-Fat", "descriptor_ui": "D059305", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Lymphatic Vessels", "descriptor_ui": "D042601", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "1970-1980", "proceedings_title": null, "publisher": "", "title": "Diabetes", "volume": "62", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Apelin inhibits diet-induced obesity by enhancing lymphatic and blood vessel integrity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell-cell interactions within the tumour microenvironment have crucial roles in epithelial tumorigenesis. Using Drosophila genetics, we show that the oncoprotein Src controls tumour microenvironment by Jun N-terminal kinase (JNK)-dependent regulation of the Hippo pathway. Clones of cells with elevated Src expression activate the Rac-Diaphanous and Ras-mitogen-activated protein kinase (MAPK) pathways, which cooperatively induce F-actin accumulation, thereby leading to activation of the Hippo pathway effector Yorkie (Yki). Simultaneously, Src activates the JNK pathway, which antagonizes the autonomous Yki activity and causes propagation of Yki activity to neighbouring cells, resulting in the overgrowth of surrounding tissue. Our data provide a mechanism to explain how oncogenic mutations regulate tumour microenvironment through cell-cell communication.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masato", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Tatsushi", "last_name": "Igaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/embor.2012.185" }, "pmcid": { "normalized": "PMC3537139" }, "pmid": { "normalized": "23196366" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Hippo Kinases", "descriptor_ui": "D000099317", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": false }, { "descriptor": "MAP Kinase Kinase 4", "descriptor_ui": "D048670", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "src-Family Kinases", "descriptor_ui": "D019061", "major_topic": false }, { "descriptor": "Trans-Activators", "descriptor_ui": "D015534", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false }, { "descriptor": "YAP-Signaling Proteins", "descriptor_ui": "D000091102", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "65-72", "proceedings_title": null, "publisher": "", "title": "EMBO reports", "volume": "14", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Src controls tumorigenesis via JNK-dependent regulation of the Hippo pathway in Drosophila.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Metabotropic glutamate 2/3 (mGlu2/3) receptor antagonists have an antidepressant-like effect, but the exact mechanism still remains unclear. This study examined the effects of mGlu2/3 receptor antagonists in chronic corticosterone-treated mice which could be used as an animal model of depression. In the forced swim test, the mGlu2/3 receptor antagonists MGS0039 (1.0 mg/kg, i.p.) and LY341495 (0.3 mg/kg, i.p) significantly reduced the increased immobility time of mice pretreated with corticosterone (20 mg/kg, s.c.) for 21 days, while desipramine (30 mg/kg, i.p.) and fluoxetine (30 mg/kg, i.p.) did not. The antidepressant-like effect of LY341495 was not blocked by the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor antagonist NBQX (10 mg/kg, i.p.). Systemic administration of LY341495 did not affect basal release of glutamate, dopamine or serotonin in the prefrontal cortex of the control or chronic corticosterone-treated mice. Chronic corticosterone markedly enhanced high K(+)-induced release of dopamine, but not serotonin or glutamate, in the prefrontal cortex. This neurochemical change was blocked by systemic administration of MGS0039 and LY341495, but not desipramine or fluoxetine. These results suggest that chronic corticosterone-treated mice could be used as an animal model of treatment-resistant depression. This study also suggests that the prefrontal dopaminergic system is involved in the antidepressant-like effect of mGlu2/3 receptor antagonists in the chronic corticosterone-induced depression model.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Hiramatsu", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Onoe", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Chaki", "name": null }, { "creator_type": "author", "first_name": "Atsuro", "last_name": "Nakazato", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuropharm.2012.09.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23022081" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antidepressive Agents", "descriptor_ui": "D000928", "major_topic": false }, { "descriptor": "Corticosterone", "descriptor_ui": "D003345", "major_topic": false }, { "descriptor": "Depression", "descriptor_ui": "D003863", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Excitatory Amino Acid Antagonists", "descriptor_ui": "D018691", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Feb", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "29-38", "proceedings_title": null, "publisher": "", "title": "Neuropharmacology", "volume": "65", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabotropic glutamate 2/3 receptor antagonists improve behavioral and prefrontal dopaminergic alterations in the chronic corticosterone-induced depression model in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report a new type of UV-excitable red/NIR-emissive fluorescent dyads (PKF series). Conjugation of a pyrene and a novel bright red/near-infrared (NIR) fluorophore resulted in large quasi-Stokes shift while retaining intense fluorescence emission and sharp spectral bands. Labeling of PKF dyads to biomolecules was performed by means of introduction of a succinimidyl ester. Simultaneous Ca(2+)/albumin dual-color intracellular imaging by PKF in combination with fura-2 (UV-excitable/VIS-emissive Ca(2+) indicator) reveals its usefulness as a new bioimaging tool.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Umezawa", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10895-013-1227-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23700213" } }, "mesh": [ { "descriptor": "Albumins", "descriptor_ui": "D000418", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": true }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Fura-2", "descriptor_ui": "D016257", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Pyrenes", "descriptor_ui": "D011721", "major_topic": false }, { "descriptor": "Ultraviolet Rays", "descriptor_ui": "D014466", "major_topic": true } ], "publication": { "conference_name": null, "date": "2013 Sep", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "1007-1018", "proceedings_title": null, "publisher": "", "title": "Journal of fluorescence", "volume": "23", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of UV-excitable red and near-infrared fluorescent labels and their application for simultaneous multicolor bioimaging by single-wavelength excitation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Most viruses possess strategies to circumvent host immune responses. The measles virus (MV) nonstructural C protein suppresses the interferon response, thereby allowing efficient viral growth, but its detailed mechanism has been unknown. We identified Shc Src homology 2 domain-binding protein 1 (SHCBP1) as one of the host proteins interacting with the C protein. Knockdown of SHCBP1 using a short-hairpin RNA greatly reduced MV growth. SHCBP1 was found to be required for viral RNA synthesis in the minigenome assay and to bind to the MV phosphoprotein, a subunit of the viral RNA polymerase. A stretch of 12 amino acid residues in the C protein were sufficient for SHCBP1 binding, and the peptide containing these 12 residues could suppress MV RNA synthesis, like the full-length C protein. The central region of SHCBP1 was found to bind to the C protein, as well as the phosphoprotein, but the two viral proteins did not compete for SHCBP1 binding. Our results indicate that the C protein modulates MV RNA polymerase activity by binding to the host protein SHCBP1. SHCBP1 may be exploited as a target of antiviral compounds.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Yanagi", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Ohno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00714-13" }, "pmcid": { "normalized": "PMC3754092" }, "pmid": { "normalized": "23804634" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "DNA-Directed RNA Polymerases", "descriptor_ui": "D012321", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Host-Pathogen Interactions", "descriptor_ui": "D054884", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Measles virus", "descriptor_ui": "D008459", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "RNA, Viral", "descriptor_ui": "D012367", "major_topic": false }, { "descriptor": "Shc Signaling Adaptor Proteins", "descriptor_ui": "D055765", "major_topic": false }, { "descriptor": "Two-Hybrid System Techniques", "descriptor_ui": "D020798", "major_topic": false }, { "descriptor": "Viral Nonstructural Proteins", "descriptor_ui": "D017361", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Sep", "date_precision": "unknown", "issue": "17", "normalized_date": null, "pages": "9633-9642", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "87", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Measles virus nonstructural C protein modulates viral RNA polymerase activity by interacting with host protein SHCBP1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reactivity boundaries that divide the origin and destination of trajectories are of crucial importance to reveal the mechanism of reactions, which was recently found to exist robustly even at high energies for index 1 saddles [Phys. Rev. Lett. 105, 048304 (2010)]. Here we revisit the concept of the reactivity boundary and propose a more general definition that can involve a single reaction associated with a bottleneck composed of higher-index saddles and/or several saddle points with different indices, where the normal form theory, based on expansion around a single stationary point, does not work. We numerically demonstrate the reactivity boundary by using a reduced model system of the H(5)(+) cation where the proton exchange reaction takes place through a bottleneck composed of two index 2 saddle points and two index 1 saddle points. The cross section of the reactivity boundary in the reactant region of the phase space reveals which initial conditions are effective in making the reaction happen and thus sheds light on the reaction mechanism.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yutaka", "last_name": "Nagahata", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Teramoto", "name": null }, { "creator_type": "author", "first_name": "Chun-Biu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.88.042923" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24229265" } }, "mesh": [], "publication": { "conference_name": null, "date": "2013 Oct", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "042923", "proceedings_title": null, "publisher": "", "title": "Physical review. E, Statistical, nonlinear, and soft matter physics", "volume": "88", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Reactivity boundaries for chemical reactions associated with higher-index and multiple saddles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Purkinje cells in the cerebellum are unique neurons that generate local and global Ca(2+) signals in response to two types of excitatory inputs, parallel fiber and climbing fiber, respectively. The spatiotemporal distribution and interaction of these synaptic inputs produce complex patterns of Ca(2+) dynamics in the Purkinje cell dendrites. The Ca(2+) signals originate from Ca(2+) influx through voltage-gated Ca(2+) channels and Ca(2+) release from intracellular stores that are mediated by the metabotropic glutamate receptor signaling pathway. These Ca(2+) signals are essential for the induction of various forms of synaptic plasticity and for controlling the input-output relationship of Purkinje cells. In this article we review Ca(2+) signaling in Purkinje cell dendrites.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neunet.2012.08.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22985934" } }, "mesh": [ { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Nov", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "11-17", "proceedings_title": null, "publisher": "", "title": "Neural networks : the official journal of the International Neural Network Society", "volume": "47", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Dendritic calcium signaling in cerebellar Purkinje cell.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "p53 is a critical factor in the cellular response to a broad range of stress factors through its ability to regulate various cellular pathways. In this study, tandem affinity purification of transiently expressed herpes simplex virus 1 (HSV-1) regulatory protein ICP22 coupled with mass spectrometry-based proteomics technology and subsequent analyses showed that ICP22 interacted with p53 in HSV-1-infected cells. In p53(-/-) cells, replication of wild-type HSV-1 was reduced compared to that in parental p53(+/+) cells, indicating that p53 had a positive effect on HSV-1 replication. In contrast, the levels of viral replication of an ICP22-null mutant virus were similar in both p53(-/-) and p53(+/+) cells. At 2 h postinfection, the level of expression of ICP27, an essential viral regulatory protein, in p53(-/-) cells infected with wild-type HSV-1 or the ICP22-null mutant virus was lower than in p53(+/+) cells. In contrast, at 18 h postinfection, the level of expression of ICP0, a critical viral regulatory protein, in p53(-/-) cells infected with the ICP22-null mutant virus was higher than in p53(+/+) cells, although the levels of ICP0 expression in p53(-/-) and p53(+/+) cells infected with wild-type HSV-1 were almost identical. These results suggested that p53 overall promoted HSV-1 replication and that p53 played both positive and negative roles in HSV-1 replication: upregulating ICP27 expression very early in infection and downregulating ICP0 expression later in infection, which was antagonized by ICP22.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Hikaru", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kozuka-Hata", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01581-13" }, "pmcid": { "normalized": "PMC3754062" }, "pmid": { "normalized": "23785201" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Viral", "descriptor_ui": "D015967", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Host-Pathogen Interactions", "descriptor_ui": "D054884", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immediate-Early Proteins", "descriptor_ui": "D017874", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Interaction Mapping", "descriptor_ui": "D025941", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false }, { "descriptor": "Ubiquitin-Protein Ligases", "descriptor_ui": "D044767", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": true } ], "publication": { "conference_name": null, "date": "2013 Aug", "date_precision": "unknown", "issue": "16", "normalized_date": null, "pages": "9323-9332", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "87", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Roles of p53 in herpes simplex virus 1 replication.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reactivity boundaries that divide the destination and the origin of trajectories are of crucial importance to reveal the mechanism of reactions. We investigate whether such reactivity boundaries can be extracted for higher index saddles in terms of a nonlinear canonical transformation successful for index-one saddles by using a model system with an index-two saddle. It is found that the true reactivity boundaries do not coincide with those extracted by the transformation taking into account a nonlinearity in the region of the saddle even for small perturbations, and the discrepancy is more pronounced for the less repulsive direction of the index-two saddle system. The present result indicates an importance of the global properties of the phase space to identify the reactivity boundaries, relevant to the question of what reactant and product are in phase space, for saddles with index more than one.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yutaka", "last_name": "Nagahata", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Teramoto", "name": null }, { "creator_type": "author", "first_name": "Chun-Biu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.87.062817" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23848739" } }, "mesh": [], "publication": { "conference_name": null, "date": "2013 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "062817", "proceedings_title": null, "publisher": "", "title": "Physical review. E, Statistical, nonlinear, and soft matter physics", "volume": "87", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Reactivity boundaries to separate the fate of a chemical reaction associated with an index-two saddle.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Identifying the neuronal ensembles that respond to specific stimuli and mapping their projection patterns in living animals are fundamental challenges in neuroscience. To this end, we engineered a synthetic promoter, the enhanced synaptic activity-responsive element (E-SARE), that drives neuronal activity-dependent gene expression more potently than other existing immediate-early gene promoters. Expression of a drug-inducible Cre recombinase downstream of E-SARE enabled imaging of neuronal populations that respond to monocular visual stimulation and tracking of their long-distance thalamocortical projections in living mice. Targeted cell-attached recordings and calcium imaging of neurons in sensory cortices revealed that E-SARE reporter expression correlates with sensory-evoked neuronal activity at the single-cell level and is highly specific to the type of stimuli presented to the animals. This activity-dependent promoter can expand the repertoire of genetic approaches for high-resolution anatomical and functional analysis of neural circuits.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Kanzo", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kamijo", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Takemoto-Kimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Okuno", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Ohki", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Bito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nmeth.2559" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23852453" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Dependovirus", "descriptor_ui": "D000229", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Geniculate Bodies", "descriptor_ui": "D005829", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Integrases", "descriptor_ui": "D019426", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Molecular Biology", "descriptor_ui": "D008967", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Photic Stimulation", "descriptor_ui": "D010775", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Response Elements", "descriptor_ui": "D020218", "major_topic": true }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Visual Cortex", "descriptor_ui": "D014793", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "889-895", "proceedings_title": null, "publisher": "", "title": "Nature methods", "volume": "10", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Functional labeling of neurons and their projections using the synthetic activity-dependent promoter E-SARE.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A wide range of cellular developmental processes employ intercellular signaling via the Delta/Notch lateral inhibitory pathway to achieve stable spatial patterning. Recent genetic experiments have shown the importance of Delta/Notch lateral inhibition for regulating the number of tip cells in the tracheal primary branching of Drosophila. To examine the role of Delta/Notch regulation in the tip-cell selection, we analyzed a mathematical model of a simple lateral inhibitory system having input signals. Mathematical and numerical analyses revealed that the lateral inhibition did not amplify the signal difference between neighboring cells over the parameter ranges in which the spatial pattern of tip selection was realized. We also show that the number of tip cells becomes less affected by a fluctuation of the input gradient signal as the lateral inhibition becomes stronger. In addition, we demonstrate that the lateral inhibitory regulation enhances the robustness of the tip-cell selection compared with a system regulated by self-inhibition, an alternative means of inhibitory regulation. These results suggest that the lateral inhibition promotes the robustness of tip-cell selection in the tracheal development of Drosophila.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Yoh", "last_name": "Iwasa", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpj.2012.11.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23260057" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Trachea", "descriptor_ui": "D014132", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Dec 19", "date_precision": "day", "issue": "12", "normalized_date": "2012-12-19", "pages": "2549-2559", "proceedings_title": null, "publisher": "", "title": "Biophysical Journal", "volume": "103", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Mathematical Study of the Role of Delta/Notch Lateral Inhibition during Primary Branching of Drosophila Trachea Development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Long-term stable ratiometric fluorescent optical pH sensors (optodes) based on double sol-gel silica layers are prepared with the first layer embedding two types of quantum dots (QDs) and the second layer embedding light-absorbing pH indicators. The sensors are fabricated by a simple general sol-gel spin-coating method. The resulting double-layer pH optodes are designed as having long Stokes shift as well as ratiometric fluorescence emission response to pH in aqueous solutions of varying pH values. This optode has high durability against continuous light exposure, even under severe acidic condition (1 M HCl), and the storage stability is over a period of more than 6 months. These results indicate that the double-layer ratiometric fluorescence-based pH optode allows for long-term pH sensing. When two pH indicators of different pK(a) values with an optimized mixing ratio are embedded into the second layer, a double-layer pH optode with reproducible linear response in a wide pH range of over 6 pH units (from pH 4 to 10) can be designed and fabricated.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ac302178z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23163876" } }, "mesh": [], "publication": { "conference_name": null, "date": "2012 Dec 18", "date_precision": "day", "issue": "24", "normalized_date": "2012-12-18", "pages": "10650-10656", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "84", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Highly durable double sol-gel layer ratiometric fluorescent pH optode based on the combination of two types of quantum dots and absorbing pH indicators.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Considerable evidence has demonstrated that transient receptor potential (TRP) channels play vital roles in sensory neurons, mediating responses to various environmental stimuli. In contrast, relatively little is known about how TRP channels exert their effects in the central nervous system to control complex behaviors. This is also true for the Drosophila TRP channel encoded by painless (pain). The Pain TRP channel is expressed in a subset of sensory neurons and involved in behavioral responses to thermal, chemical, and mechanical stimuli. Its physiological roles in brain neurons, however, remain largely elusive. Using multiple mutant alleles and tranformants for pain, here we demonstrate that the brain-expressed Pain TRP channel is required for long-term memory (LTM), but not for short-lasting memory, induced by courtship conditioning in adult males. The courtship LTM phenotype in pain mutants was rescued by expressing wild-type pain temporarily, prior to conditioning, in adult flies. In addition, targeted expression of painRNAi in either the mushroom bodies (MBs) or insulin-producing cells (IPCs) resulted in defective courtship LTM. These results indicate that the Pain TRP channels in the MBs and IPCs control neuronal plasticity that is required for the formation of a certain type of long-lasting associative memory in Drosophila.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Shoma", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ishimoto", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kitamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/lm.029041.112" }, "pmcid": { "normalized": "PMC3533128" }, "pmid": { "normalized": "23247253" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Central Nervous System", "descriptor_ui": "D002490", "major_topic": false }, { "descriptor": "Courtship", "descriptor_ui": "D003380", "major_topic": true }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Ion Channels", "descriptor_ui": "D007473", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": false }, { "descriptor": "Mushroom Bodies", "descriptor_ui": "D024521", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Dec 17", "date_precision": "day", "issue": "1", "normalized_date": "2012-12-17", "pages": "34-40", "proceedings_title": null, "publisher": "", "title": "Learning & memory (Cold Spring Harbor, N.Y.)", "volume": "20", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Significance of the centrally expressed TRP channel painless in Drosophila courtship memory.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During embryogenesis, chordates pass through a tailbud stage in which the larval tail is formed. Since acquisition of a tadpole-like tail during tailbud stage is one of the key events in the evolution of chordates, understanding the anatomy of the tailbud stage chordate embryo is of special interest. In this study, to understand comprehensively the anatomy of the tailbud embryo at single-cell-level, real microscopic image stacks of the tailbud embryo in Ciona intestinalis were reconstructed into a 3D computer model. This comprehensive 3D model of the ascidian tailbud embryo was based on real images of confocal laser scanning microscope (CLSM) and therefore, cell shape, location and cell arrangement reflect real geometries of the tailbud embryo. We found that the tailbud embryo consists of 1579 cells, including 836 epidermal cells, 228 cells in the central nervous system, 218 mesenchymal cells, four trunk ventral cells, two B/B(⁎)8.11 cells, 36 muscle cells, 40 notochord cells, four primordial germ cells, and 199 endodermal cells. Moreover, we identified for the first time two populations of previously undefined cells (a total of 12 cells) in Ciona: one located in the lateral trunk and the other located under the tail dorsal epidermis. This information provides a first step for understanding how the body plan of the chordate tailbud embryo formed and evolved.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuru J.", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2012.09.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23022659" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": true }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Tail", "descriptor_ui": "D013623", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Dec 15", "date_precision": "day", "issue": "2", "normalized_date": "2012-12-15", "pages": "274-284", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "372", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Three-dimensional anatomy of the Ciona intestinalis tailbud embryo at single-cell resolution.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Using macrophages overexpressing or reducing SNAP-23, this study shows that SNAP-23 is implicated in phagosome formation and maturation, presumably by mediating SNARE-based membrane traffic. Indeed, a conformational change in SNAP-23 structure based on FRET signal is observed on the phagosome membrane of cells overexpressing the lysosomal SNARE VAMP7.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Chiye", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Seisuke", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Yoh", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Ge-Hong", "last_name": "Sun-Wada", "name": null }, { "creator_type": "author", "first_name": "Ikuo", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Kiyotaka", "last_name": "Hatsuzawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1091/mbc.e12-01-0069" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23087210" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Lysosomes", "descriptor_ui": "D008247", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "NADPH Oxidases", "descriptor_ui": "D019255", "major_topic": false }, { "descriptor": "Phagocytosis", "descriptor_ui": "D010587", "major_topic": false }, { "descriptor": "Phagosomes", "descriptor_ui": "D010588", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Qa-SNARE Proteins", "descriptor_ui": "D050765", "major_topic": false }, { "descriptor": "Qb-SNARE Proteins", "descriptor_ui": "D050766", "major_topic": false }, { "descriptor": "Qc-SNARE Proteins", "descriptor_ui": "D050767", "major_topic": false }, { "descriptor": "R-SNARE Proteins", "descriptor_ui": "D050683", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "Vacuolar Proton-Translocating ATPases", "descriptor_ui": "D025262", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Dec 15", "date_precision": "day", "issue": "24", "normalized_date": "2012-12-15", "pages": "4849-4863", "proceedings_title": null, "publisher": "", "title": "Molecular Biology of the Cell", "volume": "23", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "SNAP-23 regulates phagosome formation and maturation in macrophages.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Jdp2 is an AP-1 family transcription factor that regulates the epigenetic status of histones. Previous in vitro studies revealed that Jdp2 is involved in osteoclastogenesis. However, the roles of Jdp2 in vivo and its pleiotropic functions are largely unknown. Here we generated Jdp2(-/-) mice and discovered its crucial roles not only in bone metabolism but also in differentiation of neutrophils. Jdp2(-/-) mice exhibited osteopetrosis resulting from impaired osteoclastogenesis. Jdp2(-/-) neutrophils were morphologically normal but had impaired surface expression of Ly6G, bactericidal function, and apoptosis. We also found that ATF3 was an inhibitor of neutrophil differentiation and that Jdp2 directly suppresses its expression via inhibition of histone acetylation. Strikingly, Jdp2(-/-) mice were highly susceptible to Staphylococcus aureus and Candida albicans infection. Thus, Jdp2 plays pivotal roles in in vivo bone homeostasis and host defense by regulating osteoclast and neutrophil differentiation.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kenta", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Fukasaka", "name": null }, { "creator_type": "author", "first_name": "Alexis", "last_name": "Vandenbon", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Saitoh", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Kazunari K.", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Daron", "last_name": "Standley", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Shizuo", "last_name": "Akira", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.immuni.2012.08.022" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23200825" } }, "mesh": [ { "descriptor": "Activating Transcription Factor 3", "descriptor_ui": "D051700", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, Ly", "descriptor_ui": "D000950", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Bone and Bones", "descriptor_ui": "D001842", "major_topic": false }, { "descriptor": "Candidiasis", "descriptor_ui": "D002177", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neutrophils", "descriptor_ui": "D009504", "major_topic": false }, { "descriptor": "Osteoclasts", "descriptor_ui": "D010010", "major_topic": false }, { "descriptor": "Osteopetrosis", "descriptor_ui": "D010022", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Staphylococcal Infections", "descriptor_ui": "D013203", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Dec 14", "date_precision": "day", "issue": "6", "normalized_date": "2012-12-14", "pages": "1024-1036", "proceedings_title": null, "publisher": "", "title": "Immunity", "volume": "37", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "The transcription factor Jdp2 controls bone homeostasis and antibacterial immunity by regulating osteoclast and neutrophil differentiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report a fully reversible off-on fluorescence probe for hypoxia. The design employs QSY-21 as a Forster resonance energy transfer (FRET) acceptor and cyanine dye Cy5 as a FRET donor, based on our finding that QSY-21 undergoes one-electron bioreduction to the radical under hypoxia, with an absorbance decrease at 660 nm. At that point, FRET can no longer occur, and the dye becomes strongly fluorescent. Upon recovery of normoxia, the radical is immediately reoxidized to QSY-21, with loss of fluorescence due to restoration of FRET. We show that this probe, RHyCy5, can monitor repeated hypoxia-normoxia cycles in live cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shodai", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Wen", "last_name": "Piao", "name": null }, { "creator_type": "author", "first_name": "Yuriko", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Kamachi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja310049d" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23157219" } }, "mesh": [ { "descriptor": "Anthraquinones", "descriptor_ui": "D000880", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypoxia", "descriptor_ui": "D000860", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Nucleotides", "descriptor_ui": "D009711", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": false }, { "descriptor": "Rosaniline Dyes", "descriptor_ui": "D012394", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Dec 5", "date_precision": "day", "issue": "48", "normalized_date": "2012-12-05", "pages": "19588-19591", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "134", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Reversible off-on fluorescence probe for hypoxia and imaging of hypoxia-normoxia cycles in live cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In addition to its established function in the regulation of circadian rhythms, the Drosophila gene period (per) also plays an important role in processing long-term memory (LTM). Here, we used courtship conditioning as a learning paradigm and revealed that (1) overexpression and knocking down of per in subsets of brain neurons enhance and suppress LTM, respectively, and (2) suppression of synaptic transmission during memory retrieval in the same neuronal subsets leads to defective LTM. Further analysis strongly suggests that the brain region critical for per-dependent LTM regulation is the fan-shaped body, which is involved in sleep-induced enhancement of courtship LTM.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Show", "last_name": "Inami", "name": null }, { "creator_type": "author", "first_name": "Shoma", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kitamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/lm.028092.112" }, "pmcid": { "normalized": "PMC3506976" }, "pmid": { "normalized": "23154928" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Courtship", "descriptor_ui": "D003380", "major_topic": true }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory, Long-Term", "descriptor_ui": "D057567", "major_topic": false }, { "descriptor": "Mushroom Bodies", "descriptor_ui": "D024521", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Period Circadian Proteins", "descriptor_ui": "D056950", "major_topic": false }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Nov 15", "date_precision": "day", "issue": "12", "normalized_date": "2012-11-15", "pages": "571-574", "proceedings_title": null, "publisher": "", "title": "Learning & memory (Cold Spring Harbor, N.Y.)", "volume": "19", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Fan-shaped body neurons are involved in period-dependent regulation of long-term courtship memory in Drosophila.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "For quantitative analysis of nanoparticle diffusions and submicro-environments in living cells, use of newly synthesized silica-based fluorescent nanoparticle (Si-FNP) as a standard nanoprobe is successfully demonstrated. The appropriate characteristics of a standard probe were fully analyzed in vitro by single molecule detection, transmission electron microscopy, and dynamic light scattering. Using fluorescence correlation analysis in single living cells, we quantitatively compared the diffusional properties of the standard Si-FNP with a diameter of 50 nm, peptide coated Si-FNP, streptavidin coated Qdot, and GFP molecule which have different sizes and surface properties. The result demonstrates that the standard Si-FNP without coat is minimally trapped in the vesicles in the process of cellular endocytosis. Interestingly, a large proportion of Si-FNP introduced into the cells by electroporation diffuses freely in the cells during a cell cycle suggesting free diffusing NPs are hardly trapped in the vesicles. The simple but highly sensitive method will provide insight into strategies to understanding the hydrodynamic process of nanoparticle delivery into living cells as well as the cellular microenvironment in the view of submicro-size.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Chan Gi", "last_name": "Pack", "name": null }, { "creator_type": "author", "first_name": "Mi Ryoung", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Eunju Lee", "last_name": "Tae", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Kyung Hee", "last_name": "Byun", "name": null }, { "creator_type": "author", "first_name": "Jun Sung", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jconrel.2012.07.036" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22922061" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Electroporation", "descriptor_ui": "D018274", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": false }, { "descriptor": "Fluorescein-5-isothiocyanate", "descriptor_ui": "D016650", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": false }, { "descriptor": "Peptide Fragments", "descriptor_ui": "D010446", "major_topic": false }, { "descriptor": "Quantum Dots", "descriptor_ui": "D045663", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": false }, { "descriptor": "Silicon Dioxide", "descriptor_ui": "D012822", "major_topic": false }, { "descriptor": "Streptavidin", "descriptor_ui": "D019809", "major_topic": false }, { "descriptor": "tat Gene Products, Human Immunodeficiency Virus", "descriptor_ui": "D054322", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Nov 10", "date_precision": "day", "issue": "3", "normalized_date": "2012-11-10", "pages": "315-321", "proceedings_title": null, "publisher": "", "title": "Journal of controlled release : official journal of the Controlled Release Society", "volume": "163", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Microenvironments and different nanoparticle dynamics in living cells revealed by a standard nanoparticle.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Spatial regulation of tyrosine phosphorylation is important for many aspects of cell biology. However, phosphotyrosine accounts for less than 1% of all phosphorylated substrates, and it is typically a very transient event in vivo. These factors complicate the identification of key tyrosine kinase substrates, especially in the context of their extraordinary spatial organization. Here, we describe an approach to identify tyrosine kinase substrates based on their subcellular distribution from within cells. This method uses an unnatural amino acid-modified Src homology 2 (SH2) domain that is expressed within cells and can covalently trap phosphotyrosine proteins on exposure to light. This SH2 domain-based photoprobe was targeted to cellular structures, such as the actin cytoskeleton, mitochondria, and cellular membranes, to capture tyrosine kinase substrates unique to each cellular region. We demonstrate that RhoA, one of the proteins associated with actin, can be phosphorylated on two tyrosine residues within the switch regions, suggesting that phosphorylation of these residues might modulate RhoA signaling to the actin cytoskeleton. We conclude that expression of SH2 domains within cellular compartments that are capable of covalent phototrapping can reveal the spatial organization of tyrosine kinase substrates that are likely to be important for the regulation of subcellular structures.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Uezu", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Cosmo D.", "last_name": "del Vescovo", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Dario", "last_name": "Diviani", "name": null }, { "creator_type": "author", "first_name": "Scott H.", "last_name": "Soderling", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1207358109" }, "pmcid": { "normalized": "PMC3491470" }, "pmid": { "normalized": "23027962" } }, "mesh": [ { "descriptor": "Cell Compartmentation", "descriptor_ui": "D002451", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Phosphoproteins", "descriptor_ui": "D010750", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Phosphotyrosine", "descriptor_ui": "D019000", "major_topic": false }, { "descriptor": "src Homology Domains", "descriptor_ui": "D018909", "major_topic": true }, { "descriptor": "Subcellular Fractions", "descriptor_ui": "D013347", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Oct 23", "date_precision": "day", "issue": "43", "normalized_date": "2012-10-23", "pages": "E2929-2938", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "109", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Modified SH2 domain to phototrap and identify phosphotyrosine proteins from subcellular sites within cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We examined growth of euryhaline Japanese medaka (Oryzias latipes) after transfer to freshwater or seawater from isotonic saline. Growth was unaffected by the different salinities for 1 week, but the body weight increase and BMI of fish kept in freshwater for 2-3 weeks were significantly higher than those in the isotonic controls. These results may reflect the usual habitat of this species. To assess the basis for the difference in growth, energetics and the hepatic stress axis were evaluated 1 week after the transfer. Unexpectedly, despite the higher growth rate, the rate of routine oxygen consumption was significantly higher in freshwater. Plasma cortisol levels in freshwater were significantly higher than those in seawater, and the mRNA levels of the glucocorticoid receptor (GR1) in the liver were significantly lower in freshwater and seawater, compared to that in isotonic saline. Branchial Na(+)/K(+)-ATPase activities were also reduced significantly in freshwater and seawater, compared to that in isotonic saline. The higher levels of hepatic GR1 expression and branchial Na(+)/K(+)-ATPase activity in isotonic salinity than those in freshwater and seawater for 1 week may account for the lower growth rate under the isotonic condition. After 3 weeks, however, the Na(+)/K(+)-ATPase activity in seawater was significantly higher than that in freshwater. No significant difference in growth rate between freshwater and seawater groups indicates that medaka is a good model for studies of hypo- and hyperosmotic adaptations, since osmoregulation is not strongly associated with size and growth.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Maho", "last_name": "Ogoshi", "name": null }, { "creator_type": "author", "first_name": "Kanoko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Toshitaka", "last_name": "Ikeuchi", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ygcen.2012.05.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22613673" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fresh Water", "descriptor_ui": "D005618", "major_topic": false }, { "descriptor": "Hydrocortisone", "descriptor_ui": "D006854", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Oryzias", "descriptor_ui": "D009990", "major_topic": false }, { "descriptor": "Receptors, Glucocorticoid", "descriptor_ui": "D011965", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Salinity", "descriptor_ui": "D054712", "major_topic": false }, { "descriptor": "Seawater", "descriptor_ui": "D012623", "major_topic": false }, { "descriptor": "Sodium-Potassium-Exchanging ATPase", "descriptor_ui": "D000254", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Sep 1", "date_precision": "day", "issue": "2", "normalized_date": "2012-09-01", "pages": "175-179", "proceedings_title": null, "publisher": "", "title": "General and comparative endocrinology", "volume": "178", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Growth, energetics and the cortisol-hepatic glucocorticoid receptor axis of medaka (Oryzias latipes) in various salinities.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Heregulin (HRG) belongs to the family of EGFs and activates the receptor proteins ErbB3 and ErbB4 in a variety of cell types to regulate cell fate. The interactions between HRG and ErbB3/B4 are important to the pathological mechanisms underlying schizophrenia and some cancers. Here, we observed the reaction kinetics between fluorescently labeled single HRG molecules and ErbB3/B4 on the surfaces of MCF-7 human breast cancer cells. The equilibrium association and the dissociation from equilibrium were also measured using single-molecule imaging techniques. The unitary association processes mirrored the EGF and ErbB1 interactions in HeLa cells [Teramura Y, et al. (2006) EMBO J 25:4215–4222], suggesting that the predimerization of the receptors, followed by intermediate formation (between the first and second ligand-binding events to a receptor dimer), accelerated the formation of doubly liganded signaling dimers of the receptor molecules. However, the dissociation analysis suggested that the first HRG dissociation from the doubly liganded dimer was rapid, but the second dissociation from the singly liganded dimer was slow. The dissociation rate constant from the liganded monomer was intermediate. The dynamic changes in the association and dissociation kinetics in relation to the dimerization of ErbB displayed negative cooperativity, which resulted in apparent low- and high-affinity sites of HRG association on the cell surface.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Saeki", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Okada-Hatakeyama", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1200464109" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22891299" } }, "mesh": [ { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Dimerization", "descriptor_ui": "D019281", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Models, Chemical", "descriptor_ui": "D008956", "major_topic": false }, { "descriptor": "Neuregulin-1", "descriptor_ui": "D020890", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Receptor, ErbB-3", "descriptor_ui": "D020893", "major_topic": false }, { "descriptor": "Receptor, ErbB-4", "descriptor_ui": "D066247", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Aug 28", "date_precision": "day", "issue": "35", "normalized_date": "2012-08-28", "pages": "13984-13989", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "109", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamically varying interactions between heregulin and ErbB proteins detected by single-molecule analysis in living cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Near-infrared (NIR) fluorescence probes are especially useful for simple and noninvasive in vivo imaging inside the body because of low autofluorescence and high tissue transparency in the NIR region compared with other wavelength regions. However, existing NIR fluorescence probes for matrix metalloproteinases (MMPs), which are tumor, atherosclerosis, and inflammation markers, have various disadvantages, especially as regards sensitivity. Here, we report a novel design strategy to obtain a NIR fluorescence probe that is rapidly internalized by free diffusion and well retained intracellularly after activation by extracellular MMPs. We designed and synthesized four candidate probes, each consisting of a cell permeable or nonpermeable NIR fluorescent dye as a Forster resonance energy transfer (FRET) donor linked to the NIR dark quencher BHQ-3 as a FRET acceptor via a MMP substrate peptide. We applied these probes for detection of the MMP activity of cultured HT-1080 cells, which express MMP2 and MT1-MMP, by fluorescence microscopy. Among them, the probe incorporating BODIPY650/665, BODIPY-MMP, clearly visualized the MMP activity as an increment of fluorescence inside the cells. We then applied this probe to a mouse xenograft tumor model prepared with HT-1080 cells. Following intratumoral injection of the probe, MMP activity could be visualized for much longer with BODIPY-MMP than with the probe containing SulfoCy5, which is cell impermeable and consequently readily washed out of the tissue. This simple design strategy should be applicable to develop a range of sensitive, rapidly responsive NIR fluorescence probes not only for MMP activity, but also for other proteases.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takuya", "last_name": "Myochin", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja303931b" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22830429" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Boron Compounds", "descriptor_ui": "D001896", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Membrane Permeability", "descriptor_ui": "D002463", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Matrix Metalloproteinases", "descriptor_ui": "D020782", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Porphobilinogen", "descriptor_ui": "D011162", "major_topic": false }, { "descriptor": "Whole Body Imaging", "descriptor_ui": "D051598", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Aug 22", "date_precision": "day", "issue": "33", "normalized_date": "2012-08-22", "pages": "13730-13737", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "134", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Design strategy for a near-infrared fluorescence probe for matrix metalloproteinase utilizing highly cell permeable boron dipyrromethene.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We developed an organotypic coculture preparation allowing fast and efficient identification of molecules that regulate developmental synapse elimination in the mammalian brain. This coculture consists of a cerebellar slice obtained from rat or mouse at postnatal day 9 (P9) or P10 and a medullary explant containing the inferior olive dissected from rat at embryonic day 15. We verified that climbing fibers (CFs), the axons of inferior olivary neurons, formed functional synapses onto Purkinje cells (PCs) in the cerebellum of cocultures. PCs were initially reinnervated by multiple CFs with similar strengths. Surplus CFs were eliminated subsequently, and the remaining CFs became stronger. These changes are similar to those occurring in developing cerebellum in vivo. Importantly, the changes in CF innervations in cocultures involved the same molecules required for CF synapse elimination in vivo, including NMDA receptor, type 1 metabotropic glutamate receptor and glutamate receptor delta2 (GluRdelta2). We demonstrate that gain- and loss-of-function analyses can be efficiently performed by lentiviral-mediated overexpression and RNAi-induced knockdown of GluRdelta2. Using this approach, we identified neuroligin-2 as a novel molecule that promotes CF synapse elimination in postsynaptic PCs. Thus, our coculture preparation will greatly facilitate the elucidation of molecular mechanisms of synapse elimination.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Mikuni", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.1097-12.2012" }, "pmcid": { "normalized": "PMC6703771" }, "pmid": { "normalized": "22915109" } }, "mesh": [ { "descriptor": "Age Factors", "descriptor_ui": "D000367", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Biophysics", "descriptor_ui": "D001703", "major_topic": false }, { "descriptor": "Cell Adhesion Molecules, Neuronal", "descriptor_ui": "D015816", "major_topic": false }, { "descriptor": "Cell Line, Transformed", "descriptor_ui": "D002461", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Electric Stimulation", "descriptor_ui": "D004558", "major_topic": false }, { "descriptor": "Electroporation", "descriptor_ui": "D018274", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Excitatory Amino Acid Agents", "descriptor_ui": "D018683", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Medulla Oblongata", "descriptor_ui": "D008526", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Nerve Fibers", "descriptor_ui": "D009412", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Organ Culture Techniques", "descriptor_ui": "D009924", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Receptors, Glutamate", "descriptor_ui": "D017470", "major_topic": false }, { "descriptor": "Receptors, N-Methyl-D-Aspartate", "descriptor_ui": "D016194", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "Statistics, Nonparametric", "descriptor_ui": "D018709", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Aug 22", "date_precision": "day", "issue": "34", "normalized_date": "2012-08-22", "pages": "11657-11670", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "32", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Organotypic coculture preparation for the study of developmental synapse elimination in mammalian brain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Various biological events including muscle contraction and vesicle transport can be described as a mechanical process. Many of the corresponding proteins are thus required to generate or sense a force. Here we describe a strain-sensitive yellow fluorescent protein (YFP) recombinant that can detect the intramolecular strains these proteins experience.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c2cc32541a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22751284" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Kinesins", "descriptor_ui": "D016547", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "Protein Engineering", "descriptor_ui": "D015202", "major_topic": true }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Aug 14", "date_precision": "day", "issue": "63", "normalized_date": "2012-08-14", "pages": "7871-7873", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "48", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Engineering strain-sensitive yellow fluorescent protein.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We present a simple microfluidic method to generate high-density femotoliter-sized microreactor arrays within microfluidic channels. In general, we designed a main channel with many small chambers built into its walls. After sequentially infusing aqueous solution and organic solvent from a single tube into the device, aqueous droplets are confined in the chambers by the solvent flow. The generated reactors are small and stable enough for carrying out ultrasensitive biochemical assays at single molecule levels. As a demonstration, in this paper, we optically observed hydrolysis activity of beta-galactosidase enzymatic molecules in the reactor arrays at single molecule levels. Further, this method has the following advantages: (1) the droplets are observable immediately after formation and (2) its simple procedure is sufficiently robust such that even handy infusion of the preloaded solutions is reproducible. We believe our method provides a platform attractive to a variety of single molecule studies and sensing applications such as clinical diagnostics.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Takeuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ac301204v" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22789021" } }, "mesh": [ { "descriptor": "beta-Galactosidase", "descriptor_ui": "D001616", "major_topic": false }, { "descriptor": "Dimethylpolysiloxanes", "descriptor_ui": "D004129", "major_topic": false }, { "descriptor": "Enzyme Assays", "descriptor_ui": "D057075", "major_topic": false }, { "descriptor": "Hydrolysis", "descriptor_ui": "D006868", "major_topic": false }, { "descriptor": "Microfluidic Analytical Techniques", "descriptor_ui": "D046210", "major_topic": false }, { "descriptor": "Nanotechnology", "descriptor_ui": "D036103", "major_topic": false }, { "descriptor": "Solvents", "descriptor_ui": "D012997", "major_topic": false }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Aug 7", "date_precision": "day", "issue": "15", "normalized_date": "2012-08-07", "pages": "6346-6350", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "84", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of femtoliter reactor arrays within a microfluidic channel for biochemical analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The endocannabinoid 2-arachidonoylglycerol (2-AG) mediates retrograde synaptic suppression. Although the mechanisms of 2-AG production are well characterized, how 2-AG is degraded is less clearly understood. Here we found that expression of the 2-AG hydrolyzing enzyme monoacylglycerol lipase (MGL) was highly heterogeneous in the cerebellum, being rich within parallel fiber (PF) terminals, weak in Bergman glia (BG), and absent in other synaptic terminals. Despite this highly selective MGL expression pattern, 2-AG-mediated retrograde suppression was significantly prolonged at not only PF-Purkinje cell (PC) synapses but also climbing fiber-PC synapses in granule cell-specific MGL knockout (MGL-KO) mice whose cerebellar MGL expression was confined to the BG. Virus-mediated expression of MGL into the BG of global MGL-KO mice significantly shortened 2-AG-mediated retrograde suppression at PF-PC synapses. Furthermore, contribution of MGL to termination of 2-AG signaling depended on the distance from MGL-rich PFs to inhibitory synaptic terminals. Thus, 2-AG is degraded in a synapse-type independent manner by MGL present in PFs and the BG. The results of the present study strongly suggest that MGL regulates 2-AG signaling rather broadly within a certain range of neural tissue, although MGL expression is heterogeneous and limited to a subset of nerve terminals and astrocytes.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Asami", "last_name": "Tanimura", "name": null }, { "creator_type": "author", "first_name": "Motokazu", "last_name": "Uchigashima", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Mikuni", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1204404109" }, "pmcid": { "normalized": "PMC3409771" }, "pmid": { "normalized": "22783023" } }, "mesh": [ { "descriptor": "Analysis of Variance", "descriptor_ui": "D000704", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arachidonic Acids", "descriptor_ui": "D001095", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cannabinoid Receptor Modulators", "descriptor_ui": "D063385", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "DNA Primers", "descriptor_ui": "D017931", "major_topic": false }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": true }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Glycerides", "descriptor_ui": "D005989", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Monoacylglycerol Lipases", "descriptor_ui": "D008994", "major_topic": false }, { "descriptor": "Neuroglia", "descriptor_ui": "D009457", "major_topic": false }, { "descriptor": "Polymerase Chain Reaction", "descriptor_ui": "D016133", "major_topic": false }, { "descriptor": "Proteolysis", "descriptor_ui": "D059748", "major_topic": true }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jul 24", "date_precision": "day", "issue": "30", "normalized_date": "2012-07-24", "pages": "12195-12200", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "109", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Synapse type-independent degradation of the endocannabinoid 2-arachidonoylglycerol after retrograde synaptic suppression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Atg9-containing vesicles assemble to the preautophagosomal structure and eventually are incorporated into the autophagosomal outer membrane.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hayashi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Kakuta", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Sekito", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Kondo-Kakuta", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Kinjo", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Ohsumi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1083/jcb.201202061" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22826123" } }, "mesh": [ { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": false }, { "descriptor": "Autophagy-Related Proteins", "descriptor_ui": "D000071183", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Golgi Apparatus", "descriptor_ui": "D006056", "major_topic": false }, { "descriptor": "Intracellular Membranes", "descriptor_ui": "D007425", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Phagosomes", "descriptor_ui": "D010588", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae", "descriptor_ui": "D012441", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae Proteins", "descriptor_ui": "D029701", "major_topic": false }, { "descriptor": "Starvation", "descriptor_ui": "D013217", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jul 23", "date_precision": "day", "issue": "2", "normalized_date": "2012-07-23", "pages": "219-233", "proceedings_title": null, "publisher": "", "title": "The Journal of Cell Biology", "volume": "198", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Atg9 vesicles are an important membrane source during early steps of autophagosome formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Ca2+ microdomains regulate many essential physiological events.Results: IP3-evoked Ca2+ microdomains in histamine-stimulated intact HeLa cells were visualized using a total internal reflection fluorescence microscope.Conclusion: Ca2+ microdomains in intact cells are generated from spatially distributed multiple channel clusters, rather than a single tight cluster.Significance: The results provide a basic understanding of the spatiotemporal signal regulations of Ca2+ microdomain formation in living cells.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hideki", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Michikawa", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Mikoshiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m111.311399" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22637479" } }, "mesh": [ { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Fluorescence Polarization", "descriptor_ui": "D005454", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inositol 1,4,5-Trisphosphate", "descriptor_ui": "D015544", "major_topic": false }, { "descriptor": "Inositol 1,4,5-Trisphosphate Receptors", "descriptor_ui": "D053496", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jul 13", "date_precision": "day", "issue": "29", "normalized_date": "2012-07-13", "pages": "24563-24572", "proceedings_title": null, "publisher": "", "title": "The Journal of Biological Chemistry", "volume": "287", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Cooperative and Stochastic Calcium Releases from Multiple Calcium Puff Sites Generate Calcium Microdomains in Intact HeLa Cells*.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Optical highlighters are photoactivatable fluorescent molecules that exhibit pronounced changes in their spectral properties in response to irradiation with light of a specific wavelength and intensity. Here, we present a novel design strategy for a new class of caged BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) fluorophores, based on the use of photoremovable protecting groups (PRPGs) with high reduction potentials that serve as both a photosensitive unit and a fluorescence quencher via photoinduced electron transfer (PeT). 2,6-Dinitrobenzyl (DNB)-caged BODIPY was efficiently photoactivated, with activation ratios exceeding 600-fold in aqueous solutions. We then combined this photoactivatable fluorophore with a SNAP (mutant of O(6)-alkylguanine DNA alkyltransferase) ligand to obtain a small-molecule-based optical highlighter for visualization of protein dynamics, using the well-established SNAP tag technology. As proof of concept, we demonstrate spatiotemporal imaging of the fusion protein of epidermal growth factor receptor (EGFR) with SNAP tag in living cells. We also demonstrate highlighting of cells of interest in live zebrafish embryos, using the fusion protein of histone 2A with SNAP tag.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tomonori", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Claudia", "last_name": "Campos", "name": null }, { "creator_type": "author", "first_name": "Marcos", "last_name": "Gonzalez-Gaitan", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja212125w" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22694089" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Boron Compounds", "descriptor_ui": "D001896", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "O(6)-Methylguanine-DNA Methyltransferase", "descriptor_ui": "D019853", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Photochemical Processes", "descriptor_ui": "D055668", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jul 11", "date_precision": "day", "issue": "27", "normalized_date": "2012-07-11", "pages": "11153-11160", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "134", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Highly activatable and environment-insensitive optical highlighters for selective spatiotemporal imaging of target proteins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mika", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Jie", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Kojima-Aikawa", "name": null }, { "creator_type": "author", "first_name": "Bengt", "last_name": "Mannervik", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Shuto", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Ralf", "last_name": "Morgenstern", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Abe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cbic.201200242" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22689392" } }, "mesh": [ { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Fluorine", "descriptor_ui": "D005461", "major_topic": false }, { "descriptor": "Glutathione Transferase", "descriptor_ui": "D005982", "major_topic": false }, { "descriptor": "Magnetic Resonance Spectroscopy", "descriptor_ui": "D009682", "major_topic": true }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jul 9", "date_precision": "day", "issue": "10", "normalized_date": "2012-07-09", "pages": "1428-1432", "proceedings_title": null, "publisher": "", "title": "Chembiochem : a European journal of chemical biology", "volume": "13", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Universal caging group for the in-cell detection of glutathione transferase applied to 19F NMR and bioluminogenic probes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell differentiation is mediated by lineage-determining transcription factors. We show that chromodomain helicase DNA-binding domain 2 (Chd2), a SNF2 chromatin remodelling enzyme family member, interacts with MyoD and myogenic gene regulatory sequences to specifically mark these loci via deposition of the histone variant H3.3 prior to cell differentiation. Directed and genome-wide analysis of endogenous H3.3 incorporation demonstrates that knockdown of Chd2 prevents H3.3 deposition at differentiation-dependent, but not housekeeping, genes and inhibits myogenic gene activation. The data indicate that MyoD determines cell fate and facilitates differentiation-dependent gene expression through Chd2-dependent deposition of H3.3 at myogenic loci prior to differentiation.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Daijiro", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Odawara", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Yoshimi", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Kumamaru", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Saiwai", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Tsubota", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurumizaka", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Anthony N.", "last_name": "Imbalzano", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/emboj.2012.136" }, "pmcid": { "normalized": "PMC3395093" }, "pmid": { "normalized": "22569126" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Genetic Loci", "descriptor_ui": "D056426", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle Development", "descriptor_ui": "D024510", "major_topic": true }, { "descriptor": "MyoD Protein", "descriptor_ui": "D017570", "major_topic": false }, { "descriptor": "Transcriptional Activation", "descriptor_ui": "D015533", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jun 29", "date_precision": "day", "issue": "13", "normalized_date": "2012-06-29", "pages": "2994-3007", "proceedings_title": null, "publisher": "", "title": "The EMBO journal", "volume": "31", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Chd2 interacts with H3.3 to determine myogenic cell fate.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": ": In our previous study, we introduced a combination methodology of Fluorescence Correlation Spectroscopy (FCS) and Transmission Electron Microscopy (TEM), which is powerful to investigate the effect of intracellular environment to biochemical reaction processes. Now, we developed a reconstruction method of realistic simulation spaces based on our TEM images. Interactive raytracing visualization of this space allows the perception of the overall 3D structure, which is not directly accessible from 2D TEM images. Simulation results show that the diffusion in such generated structures strongly depends on image post-processing. Frayed structures corresponding to noisy images hinder the diffusion much stronger than smooth surfaces from denoised images. This means that the correct identification of noise or structure is significant to reconstruct appropriate reaction environment in silico in order to estimate realistic behaviors of reactants in vivo. Static structures lead to anomalous diffusion due to the partial confinement. In contrast, mobile crowding agents do not lead to anomalous diffusion at moderate crowding levels. By varying the mobility of these non-reactive obstacles (NRO), we estimated the relationship between NRO diffusion coefficient (Dnro) and the anomaly in the tracer diffusion (alpha). For Dnro=21.96 to 44.49 mum2/s, the simulation results match the anomaly obtained from FCS measurements. This range of the diffusion coefficient from simulations is compatible with the range of the diffusion coefficient of structural proteins in the cytoplasm. In addition, we investigated the relationship between the radius of NRO and anomalous diffusion coefficient of tracers by the comparison between different simulations. The radius of NRO has to be 58 nm when the polymer moves with the same diffusion speed as a reactant, which is close to the radius of functional protein complexes in a cell.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Noriko", "last_name": "Hiroi1", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Klann", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Iba", "name": null }, { "creator_type": "author", "first_name": "Pablo de", "last_name": "Heras Ciechomski", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Tabira", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Okuhara", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kubojima", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Robin", "last_name": "Mange", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Unger", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Funahashi", "name": null }, { "creator_type": "author", "first_name": "Heinz", "last_name": "Koeppl", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1687-4153-2012-7" }, "pmcid": { "normalized": "PMC3698665" }, "pmid": { "normalized": "22734658" } }, "mesh": [], "publication": { "conference_name": null, "date": "2012 Jun 26", "date_precision": "day", "issue": "1", "normalized_date": "2012-06-26", "pages": "7", "proceedings_title": null, "publisher": "", "title": "EURASIP journal on bioinformatics & systems biology", "volume": "2012", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "From microscopy data to in silico environments for in vivo-oriented simulations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have developed a novel red fluorescent dye, 2Me SiR600 (lambda(em)=613 nm), in which the O atom of Rhodamine Green at the 10 position of the xanthene moiety is replaced with a Si atom, as a scaffold for probes to detect protease activity with extremely high S/N ratio. As proof of concept, we designed and synthesized probes for caspase-3 activity (Z-DEVD-SiR600) and leucine aminopeptidase activity (Leu-SiR600). Caspase-3-mediated cleavage of Z-DEVD-SiR600 resulted in a large bathochromic shift (93 nm) of the absorption maximum and a 432-fold fluorescence enhancement.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yu", "last_name": "Kushida", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bmcl.2012.04.114" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22607681" } }, "mesh": [ { "descriptor": "Caspase 3", "descriptor_ui": "D053148", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Leucyl Aminopeptidase", "descriptor_ui": "D007931", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Silicon", "descriptor_ui": "D012825", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jun 15", "date_precision": "day", "issue": "12", "normalized_date": "2012-06-15", "pages": "3908-3911", "proceedings_title": null, "publisher": "", "title": "Bioorganic & medicinal chemistry letters", "volume": "22", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Red fluorescent scaffold for highly sensitive protease activity probes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Subcellular localization and dynamics of mRNAs control various physiological functions in living cells. A novel technique for visualizing endogenous mRNAs in living cells is necessary for investigation of the spatiotemporal movement of mRNAs. A pumilio homology domain of human pumilio 1 (PUM-HD) is a useful RNA binding protein as a tool for mRNA recognition because the domain can be modified to bind a specific 8-base sequence of target mRNA. In this study, we designed PUM-HD to match the sequence of beta-actin mRNA and developed an mRNA probe consisting of two PUM-HD mutants flanking full-length enhanced green fluorescent protein (EGFP). Fluorescence microscopy with the probe in living cells revealed that the probe was labeled precisely with the beta-actin mRNA in cytosol. Fluorescent spots from the probe were colocalized with microtubules and moved directionally in living cells. The PUM-HD mutants conjugated with full-length EGFP can enable visualization of beta-actin mRNA localization and dynamics in living cells.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Asumi", "last_name": "Inaguma", "name": null }, { "creator_type": "author", "first_name": "Toshimichi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/cb200474a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22387832" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Molecular Probes", "descriptor_ui": "D015335", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jun 15", "date_precision": "day", "issue": "6", "normalized_date": "2012-06-15", "pages": "999-1005", "proceedings_title": null, "publisher": "", "title": "ACS chemical biology", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Fluorescent probes for imaging endogenous beta-actin mRNA in living cells using fluorescent protein-tagged pumilio.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In this report, we demonstrate that an optic cup structure can form by self-organization in human ESC culture. The human ESC-derived optic cup is much larger than the mouse ESC-derived one, presumably reflecting the species differences. The neural retina in human ESC culture is thick and spontaneously curves in an apically convex manner, which is not seen in mouse ESC culture. In addition, human ESC-derived neural retina grows into multilayered tissue containing both rods and cones, whereas cone differentiation is rare in mouse ESC culture. The accumulation of photoreceptors in human ESC culture can be greatly accelerated by Notch inhibition. In addition, we show that an optimized vitrification method enables en bloc cryopreservation of stratified neural retina of human origin. This storage method at an intermediate step during the time-consuming differentiation process provides a versatile solution for quality control in large-scale preparation of clinical-grade retinal tissues.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tokushige", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Kiyotoshi", "last_name": "Sekiguchi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shigenobu", "last_name": "Yonemura", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stem.2012.05.009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22704518" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Eye", "descriptor_ui": "D005123", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": true }, { "descriptor": "Regenerative Medicine", "descriptor_ui": "D044968", "major_topic": false }, { "descriptor": "Retinal Neurons", "descriptor_ui": "D055351", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jun 14", "date_precision": "day", "issue": "6", "normalized_date": "2012-06-14", "pages": "771-785", "proceedings_title": null, "publisher": "", "title": "Cell stem cell", "volume": "10", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Self-formation of optic cups and storable stratified neural retina from human ESCs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We present a novel design strategy for near-infrared (NIR) fluorescence probes utilizing dye-protein interaction as a trigger for fluorescence enhancement. The design principle involves modification of a polymethine dye with cleavable functional groups that reduce the dye's protein-binding affinity. When these functional groups are removed by specific interaction with the target enzymes, the dye's protein affinity is restored, protein binding occurs, and the dye's fluorescence is strongly enhanced. To validate this strategy, we first designed and synthesized an alkaline phosphatase (ALP) sensor by introducing phosphate into the squarylium dye scaffold; this sensor was able to detect ALP-labeled secondary antibodies in Western blotting analysis. Second, we synthesized a probe for beta-galactosidase (widely used as a reporter of gene expression) by means of beta-galactosyl substitution of the squarylium scaffold; this sensor was able to visualize beta-galactosidase activity both in vitro and in vivo. Our strategy should be applicable to obtain NIR fluorescence probes for a wide range of target enzymes.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Daihi", "last_name": "Oushiki", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Makiya", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ac300061a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22482531" } }, "mesh": [ { "descriptor": "Alkaline Phosphatase", "descriptor_ui": "D000469", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "beta-Galactosidase", "descriptor_ui": "D001616", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Quantum Theory", "descriptor_ui": "D011789", "major_topic": false }, { "descriptor": "Spectroscopy, Near-Infrared", "descriptor_ui": "D019265", "major_topic": true } ], "publication": { "conference_name": null, "date": "2012 May 15", "date_precision": "day", "issue": "10", "normalized_date": "2012-05-15", "pages": "4404-4410", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "84", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Near-infrared fluorescence probes for enzymes based on binding affinity modulation of squarylium dye scaffold.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A novel palladium- and copper-catalyzed one-pot multicomponent synthesis of hetero alpha,alpha'-dimers of heterocycles via Sonogashira coupling and double cyclization cascade involving imine formation has been developed. This reaction cascade proceeded under mild conditions, providing a powerful synthetic tool for the assembly of pi-conjugated systems with a combination of palladium-catalyzed post-direct C-H bond arylations.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takahiko", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ol300718x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22533860" } }, "mesh": [], "publication": { "conference_name": null, "date": "2012 May 4", "date_precision": "day", "issue": "9", "normalized_date": "2012-05-04", "pages": "2296-2299", "proceedings_title": null, "publisher": "", "title": "Organic letters", "volume": "14", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Pd- and Cu-catalyzed one-pot multicomponent synthesis of hetero alpha,alpha'-dimers of heterocycles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The posttranslational regulation of mammalian clock proteins has been assigned a time-keeping function, but seems to have more essential roles. Here we show that c-Jun N-terminal kinase (JNK), identified by inhibitor screening of BMAL1 phosphorylation at Ser 520/Thr 527/Ser 592, confers dynamic regulation on the clock. Knockdown of JNK1 and JNK2 abrogates BMAL1 phosphorylation and lengthens circadian period in fibroblasts. Mice deficient for neuron-specific isoform JNK3 have altered behavioural rhythms, with longer free-running period and compromised phase shifts to light. The locomotor rhythms are insensitive to intensity variance of constant light, deviating from Aschoff's rule. Thus, JNK regulates a core characteristic of the circadian clock by controlling the oscillation speed and the phase in response to light.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hikari", "last_name": "Yoshitane", "name": null }, { "creator_type": "author", "first_name": "Sato", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Kiyomichi", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Shin-ya", "last_name": "Nishide", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyota", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Shinozaki", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Matsuki", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Doi", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Fukada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/embor.2012.37" }, "pmcid": { "normalized": "PMC3343351" }, "pmid": { "normalized": "22441692" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "ARNTL Transcription Factors", "descriptor_ui": "D056930", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Circadian Clocks", "descriptor_ui": "D057906", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Immunoprecipitation", "descriptor_ui": "D047468", "major_topic": false }, { "descriptor": "JNK Mitogen-Activated Protein Kinases", "descriptor_ui": "D048031", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 10", "descriptor_ui": "D048057", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 8", "descriptor_ui": "D048055", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 9", "descriptor_ui": "D048056", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 May 1", "date_precision": "day", "issue": "5", "normalized_date": "2012-05-01", "pages": "455-461", "proceedings_title": null, "publisher": "", "title": "EMBO reports", "volume": "13", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "JNK regulates the photic response of the mammalian circadian clock.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Functional neural circuit formation during development involves massive elimination of redundant synapses. In the cerebellum, one-to-one connection from excitatory climbing fiber (CF) to Purkinje cell (PC) is established by elimination of early-formed surplus CFs. This process depends on glutamatergic excitatory inputs, but contribution of GABAergic transmission remains unclear. Here, we demonstrate impaired CF synapse elimination in mouse models with diminished GABAergic transmission by mutation of a single allele for the GABA synthesizing enzyme GAD67, by conditional deletion of GAD67 from PCs and GABAergic interneurons or by pharmacological inhibition of cerebellar GAD activity. The impaired CF synapse elimination was rescued by enhancing GABA(A) receptor sensitivity in the cerebellum by locally applied diazepam. Our electrophysiological and Ca2+ imaging data suggest that GABA(A) receptor-mediated inhibition onto the PC soma from molecular layer interneurons influences CF-induced Ca2+ transients in the soma and regulates CF synapse elimination from postnatal day 10 (P10) to around P16.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hisako", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yuchio", "last_name": "Yanagawa", "name": null }, { "creator_type": "author", "first_name": "Kunihiko", "last_name": "Obata", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2012.02.032" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22542190" } }, "mesh": [ { "descriptor": "Agatoxins", "descriptor_ui": "D060848", "major_topic": false }, { "descriptor": "Age Factors", "descriptor_ui": "D000367", "major_topic": false }, { "descriptor": "Analysis of Variance", "descriptor_ui": "D000704", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Bicuculline", "descriptor_ui": "D001640", "major_topic": false }, { "descriptor": "Biophysical Phenomena", "descriptor_ui": "D055592", "major_topic": false }, { "descriptor": "Biophysics", "descriptor_ui": "D001703", "major_topic": false }, { "descriptor": "Calbindins", "descriptor_ui": "D064026", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Channels", "descriptor_ui": "D015220", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Chromones", "descriptor_ui": "D002867", "major_topic": false }, { "descriptor": "Cytochromes c", "descriptor_ui": "D045304", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Diazepam", "descriptor_ui": "D003975", "major_topic": false }, { "descriptor": "Electric Stimulation", "descriptor_ui": "D004558", "major_topic": false }, { "descriptor": "Excitatory Amino Acid Antagonists", "descriptor_ui": "D018691", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "GABA Modulators", "descriptor_ui": "D018757", "major_topic": false }, { "descriptor": "GABA-A Receptor Antagonists", "descriptor_ui": "D058787", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Glutamate Decarboxylase", "descriptor_ui": "D005968", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Membrane Potentials", "descriptor_ui": "D008564", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Microscopy, Electron, Transmission", "descriptor_ui": "D046529", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Neurotoxins", "descriptor_ui": "D009498", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Phospholipase C beta", "descriptor_ui": "D054799", "major_topic": false }, { "descriptor": "Protein Kinase C", "descriptor_ui": "D011493", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Quinoxalines", "descriptor_ui": "D011810", "major_topic": false }, { "descriptor": "Receptors, Glutamate", "descriptor_ui": "D017470", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false }, { "descriptor": "S100 Calcium Binding Protein G", "descriptor_ui": "D064030", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Vesicular Inhibitory Amino Acid Transport Proteins", "descriptor_ui": "D050495", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Apr 26", "date_precision": "day", "issue": "2", "normalized_date": "2012-04-26", "pages": "384-396", "proceedings_title": null, "publisher": "", "title": "Neuron", "volume": "74", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "GABAergic inhibition regulates developmental synapse elimination in the cerebellum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Leucine-rich repeat kinase 2 (LRRK2) is the gene responsible for autosomal-dominant Parkinson's disease (PD), PARK8, but the mechanism by which LRRK2 mutations cause neuronal dysfunction remains unknown. In the present study, we investigated for the first time a transgenic (TG) mouse strain expressing human LRRK2 with an I2020T mutation in the kinase domain, which had been detected in the patients of the original PARK8 family. RESULTS: The TG mouse expressed I2020T LRRK2 in dopaminergic (DA) neurons of the substantia nigra, ventral tegmental area, and olfactory bulb. In both the beam test and rotarod test, the TG mice exhibited impaired locomotive ability in comparison with their non-transgenic (NTG) littermates. Although there was no obvious loss of DA neurons in either the substantia nigra or striatum, the TG brain showed several neurological abnormalities such as a reduced striatal dopamine content, fragmentation of the Golgi apparatus in DA neurons, and an increased degree of microtubule polymerization. Furthermore, the tyrosine hydroxylase-positive primary neurons derived from the TG mouse showed an increased frequency of apoptosis and had neurites with fewer branches and decreased outgrowth in comparison with those derived from the NTG controls. CONCLUSIONS: The I2020T LRRK2 TG mouse exhibited impaired locomotive ability accompanied by several dopaminergic neuron abnormalities. The TG mouse should provide valuable clues to the etiology of PD caused by the LRRK2 mutation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Sayuri", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Miyajima", "name": null }, { "creator_type": "author", "first_name": "Sadahiro", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Obata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1750-1326-7-15" }, "pmcid": { "normalized": "PMC3467184" }, "pmid": { "normalized": "22534020" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Dopaminergic Neurons", "descriptor_ui": "D059290", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leucine-Rich Repeat Serine-Threonine Protein Kinase-2", "descriptor_ui": "D000071158", "major_topic": false }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Parkinson Disease", "descriptor_ui": "D010300", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Apr 25", "date_precision": "day", "issue": "", "normalized_date": "2012-04-25", "pages": "15", "proceedings_title": null, "publisher": "", "title": "Molecular neurodegeneration", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "The I2020T Leucine-rich repeat kinase 2 transgenic mouse exhibits impaired locomotive ability accompanied by dopaminergic neuron abnormalities.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hypoxia occurs in various diseases, including cancer, ischemia, and acute and chronic vascular diseases. Here we describe the design and synthesis of the first hypoxia-sensitive MRI contrast agents, SAGds. SAGds showed a pH-dependent r(1) relaxivity change associated with intramolecular chelation of the nitrogen atom of the sulfonamide moiety to the Gd(3+) center. There was a correlation between the pK(a) of the r(1) relaxivity change and the sum of the Hammett sigma constants of substituents on the aromatic ring. Among the synthesized compounds, 4NO(2)2MeOSAGd was selectively reduced to the amine by rat liver microsomes under hypoxic conditions, resulting in a 1.8-fold increment of the r(1) relaxivity owing to the change in pK(a) of the arylsulfonamide moiety. This enhancement of the r(1) relaxivity could be clearly detected in T(1)-weighted MR images. Thus, 4NO(2)2MeOSAGd is a 'smart' MRI contrast agent for the detection of hypoxia under physiological conditions.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shimpei", "last_name": "Iwaki", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Wen", "last_name": "Piao", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bmcl.2012.02.071" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22424977" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Contrast Media", "descriptor_ui": "D003287", "major_topic": false }, { "descriptor": "Gadolinium", "descriptor_ui": "D005682", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Hypoxia", "descriptor_ui": "D000860", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": true }, { "descriptor": "Microsomes, Liver", "descriptor_ui": "D008862", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Apr 15", "date_precision": "day", "issue": "8", "normalized_date": "2012-04-15", "pages": "2798-2802", "proceedings_title": null, "publisher": "", "title": "Bioorganic & medicinal chemistry letters", "volume": "22", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of hypoxia-sensitive Gd3+-based MRI contrast agents.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Metabotropic glutamate receptor (mGluR)-dependent calcium ion (Ca(2)+) signaling in astrocytic processes regulates synaptic transmission and local blood flow essential for brain function. However, because of difficulties in imaging astrocytic processes, the subcellular spatial organization of mGluR-dependent Ca(2)+ signaling is not well characterized and its regulatory mechanism remains unclear. Using genetically encoded Ca(2)+ indicators, we showed that despite global stimulation by an mGluR agonist, astrocyte processes intrinsically exhibited a marked enrichment of Ca(2)+ responses. Immunocytochemistry indicated that these polarized Ca(2)+ responses could be attributed to increased density of surface mGluR5 on processes relative to the soma. Single-particle tracking of surface mGluR5 dynamics revealed a membrane barrier that blocked the movement of mGluR5 between the processes and the soma. Overexpression of mGluR or expression of its carboxyl terminus enabled diffusion of mGluR5 between the soma and the processes, disrupting the polarization of mGluR5 and of mGluR-dependent Ca(2)+ signaling. Together, our results demonstrate an mGluR5-selective diffusion barrier between processes and soma that compartmentalized mGluR Ca(2)+ signaling in astrocytes and may allow control of synaptic and vascular activity in specific subcellular domains.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Misa", "last_name": "Arizono", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Fumihiro", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Matsu-Ura", "name": null }, { "creator_type": "author", "first_name": "Akitoshi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Mark W.", "last_name": "Sherwood", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Mikoshiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/scisignal.2002498" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22472649" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Calmodulin", "descriptor_ui": "D002147", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Diffusion", "descriptor_ui": "D004058", "major_topic": false }, { "descriptor": "Excitatory Amino Acid Agonists", "descriptor_ui": "D018690", "major_topic": false }, { "descriptor": "Fluorescence Recovery After Photobleaching", "descriptor_ui": "D036681", "major_topic": false }, { "descriptor": "Glycine", "descriptor_ui": "D005998", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Quantum Dots", "descriptor_ui": "D045663", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Receptor, Metabotropic Glutamate 5", "descriptor_ui": "D064529", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Resorcinols", "descriptor_ui": "D012118", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Apr 3", "date_precision": "day", "issue": "218", "normalized_date": "2012-04-03", "pages": "ra27", "proceedings_title": null, "publisher": "", "title": "Science signaling", "volume": "5", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Receptor-selective diffusion barrier enhances sensitivity of astrocytic processes to metabotropic glutamate receptor stimulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have designed and synthesized a reversible near-infrared (NIR) fluorescence probe, 2-Me TeR, for reactive oxygen species (ROS), utilizing the redox properties of the tellurium (Te) atom. 2-Me TeR is oxidized to fluorescent 2-Me TeOR by various ROS, while the generated 2-Me TeOR is quickly reduced in the presence of glutathione to regenerate 2-Me TeR. This redox-induced reversible NIR-fluorescence response of 2-Me TeR allowed us to detect the endogenous production of ROS and subsequent homeostatic recovery of the intracellular reductive environment in hydrogen peroxide-stimulated HL-60 cells. This probe is expected to be useful for monitoring the dynamics of ROS production continuously in vivo.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Koide", "name": null }, { "creator_type": "author", "first_name": "Mitsuyasu", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Abo", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c2cc18011a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22344329" } }, "mesh": [ { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Infrared Rays", "descriptor_ui": "D007259", "major_topic": false }, { "descriptor": "Molecular Probe Techniques", "descriptor_ui": "D015336", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Mar 25", "date_precision": "day", "issue": "25", "normalized_date": "2012-03-25", "pages": "3091-3093", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "48", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "A reversible near-infrared fluorescence probe for reactive oxygen species based on Te-rhodamine.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have developed a series of novel near-infrared (NIR) wavelength-excitable fluorescent dyes, SiR-NIRs, by modifying the Si-rhodamine scaffold to obtain emission in the range suitable for in vivo imaging. Among them, SiR680 and SiR700 showed sufficiently high quantum efficiency in aqueous media. Both antibody-bound and free dye exhibited high tolerance to photobleaching in aqueous solution. Subcutaneous xenograft tumors were successfully visualized in a mouse tumor model using SiR700-labeled anti-tenascin-C (TN-C) antibody, SiR700-RCB1. SiR-NIRs are expected to be useful as labeling agents for in vivo imaging studies including multicolor imaging, and also as scaffolds for NIR fluorescence probes.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Koide", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Wen", "last_name": "Piao", "name": null }, { "creator_type": "author", "first_name": "Moriaki", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Nae", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja210375e" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22390359" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Diagnostic Imaging", "descriptor_ui": "D003952", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasms, Experimental", "descriptor_ui": "D009374", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": true }, { "descriptor": "Silicon Dioxide", "descriptor_ui": "D012822", "major_topic": true }, { "descriptor": "Spectroscopy, Near-Infrared", "descriptor_ui": "D019265", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Mar 21", "date_precision": "day", "issue": "11", "normalized_date": "2012-03-21", "pages": "5029-5031", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "134", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of NIR fluorescent dyes based on Si-rhodamine for in vivo imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lipopolysaccharide (LPS) produces a series of systemic and psychiatric changes called sickness behavior. In the present study, we characterized the LPS-induced decrease in novel object exploratory behaviors in BALB/c mice. As already reported, LPS (0.3-5 mug/mouse) induced dose- and time-dependent decreases in locomotor activity, food intake, social interaction, and exploration for novel objects, and an increase in immobility in the forced-swim test. Although the decrease in locomotor activity was ameliorated by 10h postinjection, novel object exploratory behaviors remained decreased at 24h and were observed even with the lowest dose of LPS. In an object exploration test, LPS shortened object exploration time but did not affect moving time or the frequency of object exploration. Although pre-exposure to the same object markedly decreased the duration of exploration and LPS did not change this reduction, LPS significantly impaired the exploration of a novel object that replaced the familiar one. LPS did not affect anxiety-like behaviors in open-field and elevated plus-maze tests. An LPS-induced increase in the number of c-Fos-immunoreactive cells was observed in several brain regions within 6h of LPS administration, but the number of cells quickly returned to control levels, except in the central amygdala where the increase continued for 24h. These results suggest that LPS most prominently affects object exploratory behaviors by impairing cognition and/or motivation including continuous attention and curiosity toward objects, and that this may be associated with activation of brain nuclei such as the central amygdala.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ryota", "last_name": "Haba", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Onaka", "name": null }, { "creator_type": "author", "first_name": "Hyper", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Risa", "last_name": "Takenaga", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbr.2011.12.027" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22209851" } }, "mesh": [ { "descriptor": "Amygdala", "descriptor_ui": "D000679", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cognition Disorders", "descriptor_ui": "D003072", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Exploratory Behavior", "descriptor_ui": "D005106", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Hindlimb Suspension", "descriptor_ui": "D019417", "major_topic": false }, { "descriptor": "Illness Behavior", "descriptor_ui": "D055809", "major_topic": false }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": false }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Motivation", "descriptor_ui": "D009042", "major_topic": false }, { "descriptor": "Swimming", "descriptor_ui": "D013550", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Mar 17", "date_precision": "day", "issue": "2", "normalized_date": "2012-03-17", "pages": "423-431", "proceedings_title": null, "publisher": "", "title": "Behavioural brain research", "volume": "228", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Lipopolysaccharide affects exploratory behaviors toward novel objects by impairing cognition and/or motivation in mice: Possible role of activation of the central amygdala.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Skeletal muscle undergoes complicated differentiation steps that include cell-cycle arrest, cell fusion, and maturation, which are controlled through sequential expression of transcription factors. During muscle differentiation, remodeling of the epigenetic landscape is also known to take place on a large scale, determining cell fate. In an attempt to determine the extent of epigenetic remodeling during muscle differentiation, we characterized the plasticity of the chromatin structure using C2C12 myoblasts. Differentiation of C2C12 cells was induced by lowering the serum concentration after they had reached full confluence, resulting in the formation of multi-nucleated myotubes. Upon induction of differentiation, the nucleus size decreased whereas the aspect ratio increased, indicating the presence of force on the nucleus during differentiation. Movement of the nucleus was also suppressed when differentiation was induced, indicating that the plasticity of chromatin changed upon differentiation. To evaluate the histone dynamics during differentiation, FRAP experiment was performed, which showed an increase in the immobile fraction of histone proteins when differentiation was induced. To further evaluate the change in the histone dynamics during differentiation, FCS was performed, which showed a decrease in histone mobility on differentiation. We here show that the plasticity of chromatin decreases upon differentiation, which takes place in a stepwise manner, and that it can be used as an index for the differentiation stage during myogenesis using the state diagram developed with the parameters obtained in this study.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kawauchi", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Tsukasaki", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2012.01.091" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22306010" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Chromatin Assembly and Disassembly", "descriptor_ui": "D042002", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle Development", "descriptor_ui": "D024510", "major_topic": false }, { "descriptor": "Myoblasts, Skeletal", "descriptor_ui": "D032448", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Feb 24", "date_precision": "day", "issue": "4", "normalized_date": "2012-02-24", "pages": "742-747", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "418", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Chromatin plasticity as a differentiation index during muscle differentiation of C2C12 myoblasts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vasculogenesis, the in-situ assembly of angioblast or endothelial progenitor cells (EPCs), may persist into adult life, contributing to new blood vessel formation. However, EPCs are scattered throughout newly developed blood vessels and cannot be solely responsible for vascularization. Here, we identify an endothelial progenitor/stem-like population located at the inner surface of preexisting blood vessels using the Hoechst method in which stem cell populations are identified as side populations. This population is dormant in the steady state but possesses colony-forming ability, produces large numbers of endothelial cells (ECs) and when transplanted into ischaemic lesions, restores blood flow completely and reconstitutes de-novo long-term surviving blood vessels. Moreover, although surface markers of this population are very similar to conventional ECs, and they reside in the capillary endothelium sub-population, the gene expression profile is completely different. Our results suggest that this heterogeneity of stem-like ECs will lead to the identification of new targets for vascular regeneration therapy.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Sakimoto", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/emboj.2011.465" }, "pmcid": { "normalized": "PMC3280559" }, "pmid": { "normalized": "22179698" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Vessels", "descriptor_ui": "D001808", "major_topic": false }, { "descriptor": "Endothelium, Vascular", "descriptor_ui": "D004730", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infant, Newborn", "descriptor_ui": "D007231", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Feb 15", "date_precision": "day", "issue": "4", "normalized_date": "2012-02-15", "pages": "842-855", "proceedings_title": null, "publisher": "", "title": "The EMBO journal", "volume": "31", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification and characterization of a resident vascular stem/progenitor cell population in preexisting blood vessels.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The principal eyes of jumping spiders have a unique retina with four tiered photoreceptor layers, on each of which light of different wavelengths is focused by a lens with appreciable chromatic aberration. We found that all photoreceptors in both the deepest and second-deepest layers contain a green-sensitive visual pigment, although green light is only focused on the deepest layer. This mismatch indicates that the second-deepest layer always receives defocused images, which contain depth information of the scene in optical theory. Behavioral experiments revealed that depth perception in the spider was affected by the wavelength of the illuminating light, which affects the amount of defocus in the images resulting from chromatic aberration. Therefore, we propose a depth perception mechanism based on how much the retinal image is defocused.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Hisao", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Shinjiro", "last_name": "Saeki", "name": null }, { "creator_type": "author", "first_name": "Kunio", "last_name": "Isono", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Shichida", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Michiyo", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Arikawa", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.1211667" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22282813" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cues", "descriptor_ui": "D003463", "major_topic": false }, { "descriptor": "Depth Perception", "descriptor_ui": "D003867", "major_topic": false }, { "descriptor": "Fixation, Ocular", "descriptor_ui": "D005403", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": false }, { "descriptor": "Opsins", "descriptor_ui": "D055355", "major_topic": false }, { "descriptor": "Photoreceptor Cells, Invertebrate", "descriptor_ui": "D017956", "major_topic": false }, { "descriptor": "Predatory Behavior", "descriptor_ui": "D011235", "major_topic": false }, { "descriptor": "Spiders", "descriptor_ui": "D013112", "major_topic": false }, { "descriptor": "Vision, Ocular", "descriptor_ui": "D014785", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jan 27", "date_precision": "day", "issue": "6067", "normalized_date": "2012-01-27", "pages": "469-471", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "335", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Depth perception from image defocus in a jumping spider.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the adult cerebellum, each Purkinje cell (PC) is innervated by a single climbing fiber (CF) in proximal dendrites and 105-106 parallel fibers (PFs) in distal dendrites. This organized wiring is established postnatally through heterosynaptic competition between PFs and CFs and homosynaptic competition among multiple CFs. Using PC-specific Cav2.1 knock-out mice (PC-Cav2.1 KO mice), we have demonstrated recently that postsynaptic Cav2.1 plays a key role in the homosynaptic competition by promoting functional strengthening and dendritic translocation of single “winner” CFs. Here, we report that Cav2.1 in PCs, but not in granule cells, is also essential for the heterosynaptic competition. In PC-Cav2.1 KO mice, the extent of CF territory was limited to the soma and basal dendrites, whereas PF territory was expanded reciprocally. Consequently, the proximal somatodendritic domain of PCs displayed hyperspiny transformation and fell into chaotic innervation by multiple CFs and numerous PFs. PC-Cav2.1 KO mice also displayed patterned degeneration of PCs, which occurred preferentially in aldolase C/zebrin II-negative cerebellar compartments. Furthermore, the mutually complementary expression of phospholipase Cβ3 (PLCβ3) and PLCβ4 was altered such that their normally sharp boundary was blurred in the PCs of PC-Cav2.1 KO mice. This blurring was caused by an impaired posttranscriptional downregulation of PLCβ3 in PLCβ4-dominant PCs during the early postnatal period. A similar alteration was noted in the banded expression of the glutamate transporter EAAT4 in PC-Cav2.1 KO mice. Therefore, Cav2.1 in PCs is essential for competitive synaptic wiring, cell survival, and the establishment of precise boundaries and reciprocity of biochemical compartments in PCs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Miwako", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Usui", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.2755-11.2012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22279216" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Calcium Channels, N-Type", "descriptor_ui": "D020864", "major_topic": false }, { "descriptor": "Cell Compartmentation", "descriptor_ui": "D002451", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Organ Culture Techniques", "descriptor_ui": "D009924", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jan 25", "date_precision": "day", "issue": "4", "normalized_date": "2012-01-25", "pages": "1311-1328", "proceedings_title": null, "publisher": "", "title": "The Journal of Neuroscience", "volume": "32", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Cav2.1 in Cerebellar Purkinje Cells Regulates Competitive Excitatory Synaptic Wiring, Cell Survival, and Cerebellar Biochemical Compartmentalization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Synaptic inputs on dendrites are nonlinearly converted to action potential outputs, yet the spatiotemporal patterns of dendritic activation remain to be elucidated at single-synapse resolution. In rodents, we optically imaged synaptic activities from hundreds of dendritic spines in hippocampal and neocortical pyramidal neurons ex vivo and in vivo. Adjacent spines were frequently synchronized in spontaneously active networks, thereby forming dendritic foci that received locally convergent inputs from presynaptic cell assemblies. This precise subcellular geometry manifested itself during N-methyl-D-aspartate receptor-dependent circuit remodeling. Thus, clustered synaptic plasticity is innately programmed to compartmentalize correlated inputs along dendrites and may reify nonlinear synaptic integration.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Naoya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Mark", "last_name": "Mayford", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Matsuki", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Ikegaya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.1210362" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22267814" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CA3 Region, Hippocampal", "descriptor_ui": "D056654", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Organ Culture Techniques", "descriptor_ui": "D009924", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Pyramidal Cells", "descriptor_ui": "D017966", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Receptors, N-Methyl-D-Aspartate", "descriptor_ui": "D016194", "major_topic": false }, { "descriptor": "Somatosensory Cortex", "descriptor_ui": "D013003", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jan 20", "date_precision": "day", "issue": "6066", "normalized_date": "2012-01-20", "pages": "353-356", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "335", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Locally synchronized synaptic inputs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Steroid hormones easily cross the blood-brain barrier because of their physicochemical lipid solubility. The hormones act through nuclear receptor-mediated mechanisms and modulate gene transcription. In contrast to their genomic actions, the non-genomic rapid action of steroid hormones, acting via various types of membrane-associated receptors, reveals pharmacological properties that are distinct from the actions of the intracellular nuclear receptors. As a result, non-genomic rapid actions have gained increased scientific interest. However, insight into the phylogenic and/or comparative actions of steroids in the brain is still poorly understood. In this review, we summarize recent findings concerning the rapid, non-genomic signaling of steroid hormones in the vertebrate central nervous system, and we discuss (using a comparative view from fish to mammals) recently published data regarding the mechanism underlying physiology and behavior.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Nishi", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Takanami", "name": null }, { "creator_type": "author", "first_name": "Maho", "last_name": "Ogoshi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Kawata", "name": null } ], "identifiers": { "doi": { "normalized": "10.2741/3970" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22201787" } }, "mesh": [ { "descriptor": "Adrenal Cortex Hormones", "descriptor_ui": "D000305", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Gonadal Steroid Hormones", "descriptor_ui": "D012739", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": false }, { "descriptor": "Models, Neurological", "descriptor_ui": "D008959", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Nervous System", "descriptor_ui": "D009420", "major_topic": false }, { "descriptor": "Neurotransmitter Agents", "descriptor_ui": "D018377", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Steroids", "descriptor_ui": "D013256", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jan 1", "date_precision": "day", "issue": "3", "normalized_date": "2012-01-01", "pages": "996-1019", "proceedings_title": null, "publisher": "", "title": "Frontiers in bioscience (Landmark edition)", "volume": "17", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Rapid signaling of steroid hormones in the vertebrate nervous system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mechanisms for the evolution of convergent behavioral traits are largely unknown. Vocal learning is one such trait that evolved multiple times and is necessary in humans for the acquisition of spoken language. Among birds, vocal learning is evolved in songbirds, parrots, and hummingbirds. Each time similar forebrain song nuclei specialized for vocal learning and production have evolved. This finding led to the hypothesis that the behavioral and neuroanatomical convergences for vocal learning could be associated with molecular convergence. We previously found that the neural activity-induced gene dual specificity phosphatase 1 (dusp1) was up-regulated in non-vocal circuits, specifically in sensory-input neurons of the thalamus and telencephalon; however, dusp1 was not up-regulated in higher order sensory neurons or motor circuits. Here we show that song motor nuclei are an exception to this pattern. The song nuclei of species from all known vocal learning avian lineages showed motor-driven up-regulation of dusp1 expression induced by singing. There was no detectable motor-driven dusp1 expression throughout the rest of the forebrain after non-vocal motor performance. This pattern contrasts with expression of the commonly studied activity-induced gene egr1, which shows motor-driven expression in song nuclei induced by singing, but also motor-driven expression in adjacent brain regions after non-vocal motor behaviors. In the vocal non-learning avian species, we found no detectable vocalizing-driven dusp1 expression in the forebrain. These findings suggest that independent evolutions of neural systems for vocal learning were accompanied by selection for specialized motor-driven expression of the dusp1 gene in those circuits. This specialized expression of dusp1 could potentially lead to differential regulation of dusp1-modulated molecular cascades in vocal learning circuits.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Haruhito", "last_name": "Horita", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Wan-chun", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Erich D.", "last_name": "Jarvis", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Wada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0042173" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22876306" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Birds", "descriptor_ui": "D001717", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Dual Specificity Phosphatase 1", "descriptor_ui": "D054638", "major_topic": false }, { "descriptor": "Early Growth Response Protein 1", "descriptor_ui": "D051766", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": true }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "High Vocal Center", "descriptor_ui": "D053400", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Singing", "descriptor_ui": "D063346", "major_topic": false }, { "descriptor": "Verbal Learning", "descriptor_ui": "D014706", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "8", "normalized_date": "2012", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Specialized Motor-Driven dusp1 Expression in the Song Systems of Multiple Lineages of Vocal Learning Birds.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The use of fluorescent proteins has revolutionized our understanding of biological processes. However, the requirement for external illumination precludes their universal application to the study of biological processes in all tissues. Although light can be created by chemiluminescence, light emission from existing chemiluminescent probes is too weak to use this imaging modality in situations when fluorescence cannot be used. Here we report the development of the brightest luminescent protein to date, Nano-lantern, which is a chimera of enhanced Renilla luciferase and Venus, a fluorescent protein with high bioluminescence resonance energy transfer efficiency. Nano-lantern allows real-time imaging of intracellular structures in living cells with spatial resolution equivalent to fluorescence and sensitive tumour detection in freely moving unshaved mice. We also create functional indicators based on Nano-lantern that can image Ca(2+), cyclic adenosine monophosphate and adenosine 5'-triphosphate dynamics in environments where the use of fluorescent indicators is not feasible. These luminescent proteins allow visualization of biological phenomena at previously unseen single-cell, organ and whole-body level in animals and plants.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kenta", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Y.-F.", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Hatsugai", "name": null }, { "creator_type": "author", "first_name": "Yuriko", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Hashida", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms2248" }, "pmcid": { "normalized": "PMC3535334" }, "pmid": { "normalized": "23232392" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Cells", "descriptor_ui": "D002477", "major_topic": false }, { "descriptor": "Chloroplasts", "descriptor_ui": "D002736", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": true }, { "descriptor": "Luciferases, Renilla", "descriptor_ui": "D049410", "major_topic": false }, { "descriptor": "Luminescence", "descriptor_ui": "D049449", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Nanostructures", "descriptor_ui": "D049329", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": true }, { "descriptor": "Whole Body Imaging", "descriptor_ui": "D051598", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "", "normalized_date": "2012", "pages": "1262", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "3", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Luminescent proteins for high-speed single-cell and whole-body imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The activity-dependent modulation of GABA-A receptor (GABA(A)R) clustering at synapses controls inhibitory synaptic transmission. Several lines of evidence suggest that gephyrin, an inhibitory synaptic scaffold protein, is a critical factor in the regulation of GABA(A)R clustering during inhibitory synaptic plasticity induced by neuronal excitation. In this study, we tested this hypothesis by studying relative gephyrin dynamics and GABA(A)R declustering during excitatory activity. Surprisingly, we found that gephyrin dispersal is not essential for GABA(A)R declustering during excitatory activity. In cultured hippocampal neurons, quantitative immunocytochemistry showed that the dispersal of synaptic GABA(A)Rs accompanied with neuronal excitation evoked by 4-aminopyridine (4AP) or N-methyl-D-aspartic acid (NMDA) precedes that of gephyrin. Single-particle tracking of quantum dot labeled-GABA(A)Rs revealed that excitation-induced enhancement of GABA(A)R lateral mobility also occurred before the shrinkage of gephyrin clusters. Physical inhibition of GABA(A)R lateral diffusion on the cell surface and inhibition of a Ca(2+) dependent phosphatase, calcineurin, completely eliminated the 4AP-induced decrease in gephyrin cluster size, but not the NMDA-induced decrease in cluster size, suggesting the existence of two different mechanisms of gephyrin declustering during activity-dependent plasticity, a GABA(A)R-dependent regulatory mechanism and a GABA(A)R-independent one. Our results also indicate that GABA(A)R mobility and clustering after sustained excitatory activity is independent of gephyrin.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Fumihiro", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null }, { "creator_type": "author", "first_name": "Misa", "last_name": "Arizono", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Fukatsu", "name": null }, { "creator_type": "author", "first_name": "Antoine", "last_name": "Triller", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Mikoshiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0036148" }, "pmcid": { "normalized": "PMC3338568" }, "pmid": { "normalized": "22563445" } }, "mesh": [ { "descriptor": "4-Aminopyridine", "descriptor_ui": "D015761", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "N-Methylaspartate", "descriptor_ui": "D016202", "major_topic": false }, { "descriptor": "Quantum Dots", "descriptor_ui": "D045663", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Receptors, GABA-A", "descriptor_ui": "D011963", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "4", "normalized_date": "2012", "pages": "e36148", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Gephyrin-independent GABA(A)R mobility and clustering during plasticity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Optical microscopy is one of the most contributive tools for cell biology in the past decades. Many microscopic techniques with various functions have been developed to date, i.e., phase contrast microscopy, differential interference contrast (DIC) microscopy, confocal microscopy, two photon microscopy, superresolution microscopy, etc. However, person who is in charge of an experiment has to select one of the several microscopic techniques to achieve an experimental goal, which makes the biological assay time-consuming and expensive. To solve this problem, we have developed a microscopic system with various functions in one instrument based on the optical Fourier transformation with a lens system for detection while focusing on applicability and user-friendliness for biology. The present instrument can arbitrarily modulate the pupil function with a micro mirror array on the Fourier plane of the optical pathway for detection. We named the present instrument DiMPS (Distinct optical Modulated Pupil function System). The DiMPS is compatible with conventional fluorescent probes and illumination equipment, and gives us a Fourier-filtered image, a pseudo-relief image, and a deep focus depth. Furthermore, DiMPS achieved a resolution enhancement (pseudo-superresolution) of 110 nm through the subtraction of two images whose pupil functions are independently modulated. In maximum, the spatial and temporal resolution was improved to 120 nm and 2 ms, respectively. Since the DiMPS is based on relay optics, it can be easily combined with another microscopic instrument such as confocal microscope, and provides a method for multi-color pseudo-superresolution. Thus, the DiMPS shows great promise as a flexible optical microscopy technique in biological research fields.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Tsukasaki", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Saitoh", "name": null }, { "creator_type": "author", "first_name": "Shizuo", "last_name": "Akira", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Yanagida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0044028" }, "pmcid": { "normalized": "PMC3433489" }, "pmid": { "normalized": "22962597" } }, "mesh": [ { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Fourier Analysis", "descriptor_ui": "D005583", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": true }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": true }, { "descriptor": "Pupil", "descriptor_ui": "D011680", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "9", "normalized_date": "2012", "pages": "e44028", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Distinct modulated pupil function system for real-time imaging of living cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Hypofunction of the glutamate N-Methyl-d-aspartate (NMDA) receptor has been implicated in the pathophysiology of schizophrenia. p250GAP is a brain-enriched NMDA receptor-interacting RhoGAP. p250GAP is involved in spine morphology, and spine morphology has been shown to be altered in the post-mortem brains of patients with schizophrenia. Schizotypal personality disorder has a strong familial relationship with schizophrenia. Several susceptibility genes for schizophrenia have been related to schizotypal traits. Methods: We first investigated the association of eight linkage disequilibrium-tagging single-nucleotide polymorphisms (SNPs) that cover the p250GAP gene with schizophrenia in a Japanese sample of 431 schizophrenia patients and 572 controls. We then investigated the impact of the risk genetic variant in the p250GAP gene on schizotypal personality traits in 180 healthy subjects using the Schizotypal Personality Questionnaire. Results: We found a significant difference in genotype frequency between the patients and the controls in rs2298599 (χ2 = 17.6, p = 0.00015). The minor A/A genotype frequency of rs2298599 was higher in the patients (18%) than in the controls (9%) (χ2 = 15.5, p = 0.000083). Moreover, we found that subjects with the rs2298599 risk A/A genotype, compared with G allele carriers, had higher scores of schizotypal traits (F1,178 = 4.08, p = 0.045), particularly the interpersonal factor (F1,178 = 5.85, p = 0.017). Discussion: These results suggest that a genetic variation in the p250GAP gene might increase susceptibility not only for schizophrenia but also for schizotypal personality traits. We concluded that the p250GAP gene might be a new candidate gene for susceptibility to schizophrenia.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Ohi", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Takeya", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Hidenaga", "last_name": "Yamamori", "name": null }, { "creator_type": "author", "first_name": "Motoyuki", "last_name": "Fukumoto", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Umeda-Yano", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Iwase", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kazui", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Takeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0035696" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22530067" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "GTPase-Activating Proteins", "descriptor_ui": "D020690", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Linkage Disequilibrium", "descriptor_ui": "D015810", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Risk", "descriptor_ui": "D012306", "major_topic": false }, { "descriptor": "Schizophrenia", "descriptor_ui": "D012559", "major_topic": false }, { "descriptor": "Schizotypal Personality Disorder", "descriptor_ui": "D012569", "major_topic": false }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "4", "normalized_date": "2012", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "The p250GAP Gene Is Associated with Risk for Schizophrenia and Schizotypal Personality Traits.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The water flea, Daphnia, has been the subject of study in ecology, evolution, and environmental sciences for decades. Over the last few years, expressed sequence tags and a genome sequence have been determined. In addition, functional approaches of overexpression and gene silencing based on microinjection of RNAs into eggs have been established. However, the transient nature of these approaches prevents us from analyzing gene functions in later stages of development. To overcome this limitation, transgenesis would become a key tool. Here we report establishment of a transgenic line using microinjection of plasmid into Daphnia magna eggs. The green fluorescent protein (GFP) gene fused with the D. magna histone H2B gene under the control of a promoter/enhancer region of the elongation factor 1alpha-1 (EF1alpha-1) gene, EF1alpha-1::H2B-GFP, was used as a reporter providing high resolution visualization of active chromatin. Transgenic lines were obtained from 0.67% of the total fertile adults that survived the injections. One of the transgenic animals, which exhibited fluorescence in the nuclei of cells during embryogenesis and oogenesis, had two copies of EF1alpha-1::H2B-GFP in a head-to-tail array. This is the first report of a transgenesis technique in Daphnia and, together with emerging genome sequences, will be useful for advancing knowledge of the molecular biology of Daphnia.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0045318" }, "pmcid": { "normalized": "PMC3445449" }, "pmid": { "normalized": "23028929" } }, "mesh": [ { "descriptor": "3' Untranslated Regions", "descriptor_ui": "D020413", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Blotting, Southern", "descriptor_ui": "D015139", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "9", "normalized_date": "2012", "pages": "e45318", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Genomic integration and germline transmission of plasmid injected into crustacean Daphnia magna eggs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide acting as a neurotransmitter, neuromodulator, or neurotrophic factor. PACAP is widely expressed throughout the brain and exerts its functions through the PACAP-specific receptor (PAC1). Recent studies reveal that genetic variants of the PACAP and PAC1 genes are associated with mental disorders, and several behavioral abnormalities of PACAP knockout (KO) mice are reported. However, an insufficient number of backcrosses was made using PACAP KO mice on the C57BL/6J background due to their postnatal mortality. To elucidate the effects of PACAP on neuropsychiatric function, the PACAP gene was knocked out in F1 hybrid mice (C57BL/6J × 129SvEv) for appropriate control of the genetic background. The PACAP KO mice were then subjected to a behavioral test battery. PACAP deficiency had no significant effects on neurological screen. As shown previously, the mice exhibited significantly increased locomotor activity in a novel environment and abnormal anxiety-like behavior, while no obvious differences between genotypes were shown in home cage (HC) activity. In contrast to previous reports, the PACAP KO mice showed normal prepulse inhibition (PPI) and slightly decreased depression-like behavior. Previous study demonstrates that the social interaction (SI) in a resident-intruder test was decreased in PACAP KO mice. On the other hand, we showed that PACAP KO mice exhibited increased SI in Crawley's three-chamber social approach test, although PACAP KO had no significant impact on SI in a HC. PACAP KO mice also exhibited mild performance deficit in working memory in an eight-arm radial maze (RM) and the T-maze (TM), while they did not show any significant abnormalities in the left-right discrimination task in the TM. These results suggest that PACAP has an important role in the regulation of locomotor activity, social behavior, anxiety-like behavior and, potentially, working memory.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Satoko", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Takao", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Tanda", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Miyakawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnbeh.2012.00058" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23060763" } }, "mesh": [], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "", "normalized_date": "2012", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Behavioral Neuroscience", "volume": "6", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Comprehensive behavioral analysis of pituitary adenylate cyclase-activating polypeptide (PACAP) knockout mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIM: Tumor necrosis factor receptor 1 (TNFR1) participates importantly in arterial inflammation in genetically altered mice; however it remains undetermined whether a selective TNFR1 antagonist inhibits arterial inflammation and intimal hyperplasia. This study aimed to determine the effect and mechanism of a novel TNFR1 antagonist in the suppression of arterial inflammation. METHODS: We investigated intimal hyperplasia in IL-1 receptor antagonist-deficient mice two weeks after inducing femoral artery injury in an external vascular cuff model. All mice received intraperitoneal injections of TNFR1 antagonist (PEG-R1antTNF) or normal saline twice daily for 14 days. RESULTS: PEG-R1antTNF treatment yielded no adverse systemic effects, and we observed no significant differences in serum cholesterol or blood pressure in either group; however, selective PEG-R1antTNF treatment significantly reduced intimal hyperplasia (19,671+/-4,274 vs. 11,440+/-3,292 microm(2); p=0.001) and the intima/media ratio (1.86+/-0.43 vs. 1.34+/-0.36; p=0.029), compared with saline injection. Immunostaining revealed that PEG-R1antTNF inhibits Nuclear factor-kappaB (NF-kappaB), suppressing smooth muscle cell (SMC) proliferation and decreasing chemokine and adhesion molecule expression, and thus decreasing intimal hyperplasia and inflammation. CONCLUSIONS: Our data suggest that PEG-R1antTNF suppresses SMC proliferation and inflammation by inhibiting NF-kappaB. This study highlights the potential therapeutic benefit of selective TNFR1 antagonist therapy in preventing intimal hyperplasia and arterial inflammation.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Manabu", "last_name": "Kitagaki", "name": null }, { "creator_type": "author", "first_name": "Kikuo", "last_name": "Isoda", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Kamada", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Tsunoda", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Tomiharu", "last_name": "Niida", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Kujiraoka", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Ishigami", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Ohsuzu", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kikuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.5551/jat.9746" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22146239" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arteritis", "descriptor_ui": "D001167", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Endothelium, Vascular", "descriptor_ui": "D004730", "major_topic": false }, { "descriptor": "Human Umbilical Vein Endothelial Cells", "descriptor_ui": "D061307", "major_topic": false }, { "descriptor": "Hyperplasia", "descriptor_ui": "D006965", "major_topic": false }, { "descriptor": "Immunoenzyme Techniques", "descriptor_ui": "D007124", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Muscle, Smooth, Vascular", "descriptor_ui": "D009131", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Peptide Fragments", "descriptor_ui": "D010446", "major_topic": false }, { "descriptor": "Peptide Library", "descriptor_ui": "D019151", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "Receptors, Interleukin-1", "descriptor_ui": "D017472", "major_topic": false }, { "descriptor": "Receptors, Tumor Necrosis Factor, Type I", "descriptor_ui": "D047888", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Tumor Necrosis Factor-alpha", "descriptor_ui": "D014409", "major_topic": false }, { "descriptor": "Tunica Intima", "descriptor_ui": "D017539", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "1", "normalized_date": "2012", "pages": "36-46", "proceedings_title": null, "publisher": "", "title": "Journal of atherosclerosis and thrombosis", "volume": "19", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Novel TNF-alpha receptor 1 antagonist treatment attenuates arterial inflammation and intimal hyperplasia in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Isolation-induced abnormal behaviors are useful animal models for assessing potential anti-psychotic drugs. This study examined the effect of MGS0028, a selective metabotropic glutamate 2/3 receptor agonist, on abnormal behaviors such as hyperactivity, aggression, and deficits of prepulse inhibition in isolation-reared mice. MGS0028 attenuated hyperactivity and aggressive behaviors in isolation-reared mice. The agonist also reversed isolation rearing-induced deficits of prepulse inhibition. On the other hand, MGS0028 did not affect locomotor activity and prepulse inhibition in group-reared mice. These results suggest that the metabotropic glutamate 2/3 receptor agonist, MGS0028, is a potential compound for the treatment of psychiatric disorders.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Chaki", "name": null }, { "creator_type": "author", "first_name": "Atsuro", "last_name": "Nakazato", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Onoe", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/jphs.11200sc" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22293290" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antipsychotic Agents", "descriptor_ui": "D014150", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Bridged Bicyclo Compounds", "descriptor_ui": "D001643", "major_topic": false }, { "descriptor": "Dicarboxylic Acids", "descriptor_ui": "D003998", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false }, { "descriptor": "Reflex, Startle", "descriptor_ui": "D013216", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "2", "normalized_date": "2012", "pages": "295-298", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "118", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "The selective metabotropic glutamate 2/3 receptor agonist MGS0028 reverses isolation rearing-induced abnormal behaviors in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Environmental stresses lower the efficiency of photosynthesis and sometimes cause irreversible damage to plant functions. When spinach thylakoids and Photosystem II membranes were illuminated with excessive visible light (100–1,000 µmol photons m−1 s−1) for 10 min at either 20°C or 30°C, the optimum quantum yield of Photosystem II decreased as the light intensity and temperature increased. Reactive oxygen species and endogenous cationic radicals produced through a photochemical reaction at and/or near the reaction center have been implicated in the damage to the D1 protein. Here we present evidence that lipid peroxidation induced by the illumination is involved in the damage to the D1 protein and the subunits of the light-harvesting complex of Photosystem II. This is reasoned from the results that considerable lipid peroxidation occurred in the thylakoids in the light, and that lipoxygenase externally added in the dark induced inhibition of Photosystem II activity in the thylakoids, production of singlet oxygen, which was monitored by electron paramagnetic resonance spin trapping, and damage to the D1 protein, in parallel with lipid peroxidation. Modification of the subunits of the light-harvesting complex of Photosystem II by malondialdehyde as well as oxidation of the subunits was also observed. We suggest that mainly singlet oxygen formed through lipid peroxidation under light stress participates in damaging the Photosystem II subunits.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tiffanie", "last_name": "Chan", "name": null }, { "creator_type": "author", "first_name": "Yurika", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Pavel", "last_name": "Pospíšil", "name": null }, { "creator_type": "author", "first_name": "Nobuyoshi", "last_name": "Nijo", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Taninaka", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Nanba", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Yoshioka-Nishimura", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Mizusawa", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Yasusi", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0052100" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23300595" } }, "mesh": [ { "descriptor": "Electron Spin Resonance Spectroscopy", "descriptor_ui": "D004578", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Light-Harvesting Protein Complexes", "descriptor_ui": "D045342", "major_topic": false }, { "descriptor": "Lipid Peroxidation", "descriptor_ui": "D015227", "major_topic": false }, { "descriptor": "Malondialdehyde", "descriptor_ui": "D008315", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Photosynthesis", "descriptor_ui": "D010788", "major_topic": false }, { "descriptor": "Photosystem II Protein Complex", "descriptor_ui": "D045332", "major_topic": false }, { "descriptor": "Singlet Oxygen", "descriptor_ui": "D026082", "major_topic": false }, { "descriptor": "Spinacia oleracea", "descriptor_ui": "D018724", "major_topic": false }, { "descriptor": "Thylakoids", "descriptor_ui": "D020524", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "12", "normalized_date": "2012", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Quality Control of Photosystem II: Lipid Peroxidation Accelerates Photoinhibition under Excessive Illumination.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Leucine-rich repeat kinase 2 (LRRK2), a large protein kinase containing multi-functional domains, has been identified as the causal molecule for autosomal-dominant Parkinson's disease (PD). In the present study, we demonstrated for the first time that (i) LRRK2 interacts with tau in a tubulin-dependent manner; (ii) LRRK2 directly phosphorylates tubulin-associated tau, but not free tau; (iii) LRRK2 phosphorylates tau at Thr181 as one of the target sites; and (iv) The PD-associated LRRK2 mutations, G2019S and I2020T, elevated the degree of tau-phosphorylation. These results provide direct proof that tau is a physiological substrate for LRRK2. Furthermore, we revealed that LRRK2-mediated phosphorylation of tau reduces its tubulin-binding ability. Our results suggest that LRRK2 plays an important role as a physiological regulator for phosphorylation-mediated dissociation of tau from microtubules, which is an integral aspect of microtubule dynamics essential for neurite outgrowth and axonal transport.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Takatoshi", "last_name": "Yabata", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Minori", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Obata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0030834" }, "pmcid": { "normalized": "PMC3267742" }, "pmid": { "normalized": "22303461" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leucine-Rich Repeat Serine-Threonine Protein Kinase-2", "descriptor_ui": "D000071158", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Neurites", "descriptor_ui": "D016501", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Sus scrofa", "descriptor_ui": "D034421", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false }, { "descriptor": "Tubulin", "descriptor_ui": "D014404", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "1", "normalized_date": "2012", "pages": "e30834", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "LRRK2 phosphorylates tubulin-associated tau but not the free molecule: LRRK2-mediated regulation of the tau-tubulin association and neurite outgrowth.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Molecular imaging employing fluorescent proteins has been widely used to highlight specific reactions or processes in various fields of the life sciences. Despite extensive improvements of the fluorescent tag, this technology is still limited in the study of molecular events in the extracellular milieu. This is partly due to the presence of cysteine in the fluorescent proteins. These proteins almost cotranslationally form disulfide bonded oligomers when expressed in the endoplasmic reticulum (ER). Although single molecule photobleaching analysis showed that these oligomers were not fluorescent, the fluorescent monomer form often showed aberrant behavior in folding and motion, particularly when fused to cysteine-containing cargo. Therefore we investigated whether it was possible to eliminate the cysteine without losing the brightness. By site-saturated mutagenesis, we found that the cysteine residues in fluorescent proteins could be replaced with specific alternatives while still retaining their brightness. cf(cysteine-free)SGFP2 showed significantly reduced restriction of free diffusion in the ER and marked improvement of maturation when fused to the prion protein. We further applied this approach to TagRFP family proteins and found a set of mutations that obtains the same level of brightness as the cysteine-containing proteins. The approach used in this study to generate new cysteine-free fluorescent tags should expand the application of molecular imaging to the extracellular milieu and facilitate its usage in medicine and biotechnology.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takahisa", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Seisuke", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Chiye", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Ebana", "name": null }, { "creator_type": "author", "first_name": "Tsunehito", "last_name": "Higashi", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kiyotaka", "last_name": "Hatsuzawa", "name": null }, { "creator_type": "author", "first_name": "Ikuo", "last_name": "Wada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0037551" }, "pmcid": { "normalized": "PMC3359384" }, "pmid": { "normalized": "22649538" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Mutagenesis, Site-Directed", "descriptor_ui": "D016297", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "Photobleaching", "descriptor_ui": "D038761", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Prions", "descriptor_ui": "D011328", "major_topic": false }, { "descriptor": "Protein Engineering", "descriptor_ui": "D015202", "major_topic": false }, { "descriptor": "Sequence Analysis, DNA", "descriptor_ui": "D017422", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "5", "normalized_date": "2012", "pages": "e37551", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of cysteine-free fluorescent proteins for the oxidative environment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Activation of caspases is crucial for the execution of apoptosis. Although the caspase cascade associated with activation of the initiator caspase-8 (CASP8) has been investigated in molecular and biochemical detail, the dynamics of CASP8 activation are not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: We have established a biosensor based on fluorescence resonance energy transfer (FRET) for visualizing apoptotic signals associated with CASP8 activation at the single-cell level. Our dual FRET (dual-FRET) system, comprising a triple fusion fluorescent protein, enabled us to simultaneously monitor the activation of CASP8 and its downstream effector, caspase-3 (CASP3) in single live cells. With the dual-FRET-based biosensor, we detected distinct activation patterns of CASP8 and CASP3 in response to various apoptotic stimuli in mammalian cells, resulting in the positive feedback amplification of CASP8 activation. We reproduced these observations by in vitro reconstitution of the cascade, with a recombinant protein mixture that included procaspases. Furthermore, using a plasma membrane-bound FRET-based biosensor, we captured the spatiotemporal dynamics of CASP8 activation by the diffusion process, suggesting the focal activation of CASP8 is sufficient to propagate apoptotic signals through death receptors. CONCLUSIONS: Our new FRET-based system visualized the activation process of both initiator and effector caspases in a single apoptotic cell and also elucidated the necessity of an amplification loop for full activation of CASP8.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Katsuya", "last_name": "Kominami", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sawasaki", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Tsujimura", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Yashima", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Sunaga", "name": null }, { "creator_type": "author", "first_name": "Masateru", "last_name": "Tsuchimochi", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Koyamada", "name": null }, { "creator_type": "author", "first_name": "Yaeta", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Manabe", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Sakamaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0050218" }, "pmcid": { "normalized": "PMC3503975" }, "pmid": { "normalized": "23185580" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Caspase 3", "descriptor_ui": "D053148", "major_topic": false }, { "descriptor": "Caspase 8", "descriptor_ui": "D053181", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Enzyme Precursors", "descriptor_ui": "D004792", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "11", "normalized_date": "2012", "pages": "e50218", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "In vivo imaging of hierarchical spatiotemporal activation of caspase-8 during apoptosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The pineal-related organs of lower vertebrates have the ability to discriminate different wavelengths of light. This wavelength discrimination is achieved through antagonistic light responses to UV or blue and visible light. Previously, we demonstrated that parapinopsin underlies the UV reception in the lamprey pineal organ and identified parapinopsin genes in teleosts and frogs of which the pineal-related organs were reported to discriminate light. In this study, we report the first identification of parapinopsin in the reptile lineage and show its expression in the parietal eye of the green iguana. Spectroscopic analysis revealed that iguana parapinopsin is a UV-sensitive pigment, similar to lamprey parapinopsin. Interestingly, immunohistochemical analyses using antibodies specific to parapinopsin and parietopsin, a parietal eye green-sensitive pigment, revealed that parapinopsin and parietopsin are colocalized in the outer segments of the parietal eye photoreceptor cells in iguanas. These results strongly suggest that parapinopsin underlies the wavelength discrimination involving UV reception in the iguana parietal eye. The current findings support the idea that parapinopsin is a common photopigment underlying the UV-sensitivity in wavelength discrimination of the pineal-related organs found from lampreys to reptiles.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Seiji", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Kawano-Yamashita", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0039003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22720013" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "DNA Primers", "descriptor_ui": "D017931", "major_topic": false }, { "descriptor": "Eye", "descriptor_ui": "D005123", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Iguanas", "descriptor_ui": "D007076", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Pineal Gland", "descriptor_ui": "D010870", "major_topic": false }, { "descriptor": "Polymerase Chain Reaction", "descriptor_ui": "D016133", "major_topic": false }, { "descriptor": "Rod Opsins", "descriptor_ui": "D017299", "major_topic": false }, { "descriptor": "Ultraviolet Rays", "descriptor_ui": "D014466", "major_topic": true } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "6", "normalized_date": "2012", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Expression of UV-Sensitive Parapinopsin in the Iguana Parietal Eyes and Its Implication in UV-Sensitivity in Vertebrate Pineal-Related Organs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Like all mammalian cells, normal adult chondrocytes have a limited replicative life span, which decreases with age. To facilitate the therapeutic use of chondrocytes from older donors, a method is needed to prolong their life span. Methods: We transfected chondrocytes with hTERT or GRP78 and cultured them in a 3-dimensional atelocollagen honeycomb-shaped scaffold with a membrane seal. Then, we measured the amount of nuclear DNA and glycosaminoglycans (GAGs) and the expression level of type II collagen as markers of cell proliferation and extracellular matrix formation, respectively, in these cultures. In addition, we allografted this tissue-engineered cartilage into osteochondral defects in old rabbits to assess their repair activity in vivo. Results: Our results showed different degrees of differentiation in terms of GAG content between chondrocytes from old and young rabbits. Chondrocytes that were cotransfected with hTERT and GRP78 showed higher cellular proliferation and expression of type II collagen than those of nontransfected chondrocytes, regardless of the age of the cartilage donor. In addition, the in vitro growth rates of hTERT- or GRP78-transfected chondrocytes were higher than those of nontransfected chondrocytes, regardless of donor age. In vivo, the tissue-engineered cartilage implants exhibited strong repairing activity, maintained a chondrocyte-specific phenotype, and produced extracellular matrix components. Conclusions: Focal gene delivery to aged articular chondrocytes exhibited strong repairing activity and may be therapeutically useful for articular cartilage regeneration.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masato", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Shin-ya", "name": null }, { "creator_type": "author", "first_name": "Jeong Ik", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Nagatoshi", "last_name": "Kaneshiro", "name": null }, { "creator_type": "author", "first_name": "Genya", "last_name": "Mitani", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Tahara", "name": null }, { "creator_type": "author", "first_name": "Joji", "last_name": "Mochida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1471-2474-13-51" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22472071" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cartilage Diseases", "descriptor_ui": "D002357", "major_topic": false }, { "descriptor": "Cartilage, Articular", "descriptor_ui": "D002358", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": true }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chondrocytes", "descriptor_ui": "D019902", "major_topic": false }, { "descriptor": "Chondrogenesis", "descriptor_ui": "D020219", "major_topic": false }, { "descriptor": "Collagen", "descriptor_ui": "D003094", "major_topic": false }, { "descriptor": "Collagen Type II", "descriptor_ui": "D024043", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "DNA Replication", "descriptor_ui": "D004261", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum Chaperone BiP", "descriptor_ui": "D000091342", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glycosaminoglycans", "descriptor_ui": "D006025", "major_topic": false }, { "descriptor": "Heat-Shock Proteins", "descriptor_ui": "D006360", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Patella", "descriptor_ui": "D010329", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": true }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Telomerase", "descriptor_ui": "D019098", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Tissue Culture Techniques", "descriptor_ui": "D046509", "major_topic": false }, { "descriptor": "Tissue Scaffolds", "descriptor_ui": "D054457", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "", "normalized_date": "2012", "pages": "51", "proceedings_title": null, "publisher": "", "title": "BMC Musculoskeletal Disorders", "volume": "13", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Human telomerase reverse transcriptase and glucose-regulated protein 78 increase the life span of articular chondrocytes and their repair potential.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nod-like receptors (NLRs) comprise a large family of intracellular pattern- recognition receptors. Members of the NLR family assemble into large multiprotein complexes, termed the inflammasomes. The NLR family, pyrin domain-containing 3 (NLRP3) is triggered by a diverse set of molecules and signals, and forms the NLRP3 inflammasome. Recent studies have indicated that both DNA and RNA viruses stimulate the NLRP3 inflammasome, leading to the secretion of interleukin 1 beta (IL-1beta) and IL-18 following the activation of caspase-1. We previously demonstrated that the proton-selective ion channel M2 protein of influenza virus activates the NLRP3 inflammasome. However, the precise mechanism by which NLRP3 recognizes viral infections remains to be defined. Here, we demonstrate that encephalomyocarditis virus (EMCV), a positive strand RNA virus of the family Picornaviridae, activates the NLRP3 inflammasome in mouse dendritic cells and macrophages. Although transfection with RNA from EMCV virions or EMCV-infected cells induced robust expression of type I interferons in macrophages, it failed to stimulate secretion of IL-1beta. Instead, the EMCV viroporin 2B was sufficient to cause inflammasome activation in lipopolysaccharide-primed macrophages. While cells untransfected or transfected with the gene encoding the EMCV non-structural protein 2A or 2C expressed NLRP3 uniformly throughout the cytoplasm, NLRP3 was redistributed to the perinuclear space in cells transfected with the gene encoding the EMCV 2B or influenza virus M2 protein. 2B proteins of other picornaviruses, poliovirus and enterovirus 71, also caused the NLRP3 redistribution. Elevation of the intracellular Ca(2+) level, but not mitochondrial reactive oxygen species and lysosomal cathepsin B, was important in EMCV-induced NLRP3 inflammasome activation. Chelation of extracellular Ca(2+) did not reduce virus-induced IL-1beta secretion. These results indicate that EMCV activates the NLRP3 inflammasome by stimulating Ca(2+) flux from intracellular storages to the cytosol, and highlight the importance of viroporins, transmembrane pore-forming viral proteins, in virus-induced NLRP3 inflammasome activation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Yanagi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ichinohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.ppat.1002857" }, "pmcid": { "normalized": "PMC3415442" }, "pmid": { "normalized": "22916014" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cardiovirus Infections", "descriptor_ui": "D018188", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Encephalomyocarditis virus", "descriptor_ui": "D004686", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammasomes", "descriptor_ui": "D058847", "major_topic": false }, { "descriptor": "Interleukin-18", "descriptor_ui": "D020382", "major_topic": false }, { "descriptor": "Interleukin-1beta", "descriptor_ui": "D053583", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "NLR Family, Pyrin Domain-Containing 3 Protein", "descriptor_ui": "D000071199", "major_topic": false }, { "descriptor": "RNA, Viral", "descriptor_ui": "D012367", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virion", "descriptor_ui": "D014771", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "8", "normalized_date": "2012", "pages": "e1002857", "proceedings_title": null, "publisher": "", "title": "PLoS pathogens", "volume": "8", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Encephalomyocarditis virus viroporin 2B activates NLRP3 inflammasome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the two-cell stage embryos of Caenorhabditis elegans, the contact surface of the two blastomeres forms a curve that bulges from the AB blastomere to the P1 blastomere. This curve is a consequence of the high intracellular hydrostatic pressure of AB compared with that of P1. However, the higher pressure in AB is intriguing because AB has a larger volume than P1. In soap bubbles, which are a widely used model of cell shape, a larger bubble has lower pressure than a smaller bubble. Here, we reveal that the higher pressure in AB is mediated by its higher cortical tension. The cell fusion experiments confirmed that the curvature of the contact surface is related to the pressure difference between the cells. Chemical and genetic interferences showed that the pressure difference is mediated by actomyosin. Fluorescence imaging indicated that non-muscle myosin is enriched in the AB cortex. The cell killing experiments provided evidence that AB but not P1 is responsible for the pressure difference. Computer simulation clarified that the cell-to-cell heterogeneity of cortical tensions is indispensable for explaining the pressure difference. This study demonstrates that heterogeneity in surface tension results in significant deviations of cell behavior compared to simple soap bubble models, and thus must be taken into consideration in understanding cell shape within embryos.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0030224" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22253922" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Actomyosin", "descriptor_ui": "D000205", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": true }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": false }, { "descriptor": "Cell Size", "descriptor_ui": "D048429", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Extracellular Space", "descriptor_ui": "D005110", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Muscles", "descriptor_ui": "D009132", "major_topic": false }, { "descriptor": "Pressure", "descriptor_ui": "D011312", "major_topic": false }, { "descriptor": "Surface Tension", "descriptor_ui": "D013500", "major_topic": false }, { "descriptor": "Ultraviolet Rays", "descriptor_ui": "D014466", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "1", "normalized_date": "2012", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell-to-Cell Heterogeneity in Cortical Tension Specifies Curvature of Contact Surfaces in Caenorhabditis elegans Embryos.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dendritic spines, small bulbous postsynaptic compartments emanating from neuronal dendrites, have been thought to serve as basic units of memory storage. Despite their small size (~0.1 femtoliter), thousands of species of proteins exist in the spine, including receptors, channels, scaffolding proteins and signaling enzymes. Biochemical signaling mediated by these molecules leads to morphological and functional plasticity of dendritic spines, and ultimately learning and memory in the brain. Here, we review new insights into the mechanisms underlying spine plasticity brought about by recent advances in imaging techniques to monitor molecular events in single dendritic spines. The activity of each protein displays a specific spatiotemporal pattern, coordinating downstream events at different microdomains to change the function and morphology of dendritic spines.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Yasuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.tins.2011.12.002" }, "pmcid": { "normalized": "PMC3306839" }, "pmid": { "normalized": "22222350" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cytoskeleton", "descriptor_ui": "D003599", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "135-143", "proceedings_title": null, "publisher": "", "title": "Trends in neurosciences", "volume": "35", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Postsynaptic signaling during plasticity of dendritic spines.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Interactions between astrocytes and endothelial cells (ECs) are crucial for retinal vascular formation. Astrocytes induce migration and proliferation of ECs via their production of vascular endothelial growth factor (VEGF) and, conversely, ECs induce maturation of astrocytes possibly by the secretion of leukemia inhibitory factor (LIF). Together with the maturation of astrocytes, this finalizes angiogenesis. Thus far, the mechanisms triggering LIF production in ECs are unclear. Here we show that apelin, a ligand for the endothelial receptor APJ, induces maturation of astrocytes mediated by the production of LIF from ECs. APJ (Aplnr)- and Apln-deficient mice show delayed angiogenesis; however, aberrant overgrowth of endothelial networks with immature astrocyte overgrowth was induced. When ECs were stimulated with apelin, LIF expression was upregulated and intraocular injection of LIF into APJ-deficient mice suppressed EC and astrocyte overgrowth. These data suggest an involvement of apelin/APJ in the maturation process of retinal angiogenesis.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Susumu", "last_name": "Sakimoto", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Kamei", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Nobuhito", "last_name": "Goda", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Fukamizu", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.072330" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22357924" } }, "mesh": [ { "descriptor": "Adipokines", "descriptor_ui": "D054392", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apelin", "descriptor_ui": "D000073861", "major_topic": false }, { "descriptor": "Apelin Receptors", "descriptor_ui": "D000075244", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Leukemia Inhibitory Factor", "descriptor_ui": "D053605", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Apr", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "1327-1335", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "139", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "A role for endothelial cells in promoting the maturation of astrocytes through the apelin/APJ system in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Embryonic stem (ES) cells have been successfully used over the past decade to generate specific types of neuronal cells. In addition to its value for regenerative medicine, ES cell culture also provides versatile experimental systems for analyzing early neural development. These systems are complimentary to conventional animal models, particularly because they allow unique constructive (synthetic) approaches, for example, step-wise addition of components. Here we review the ability of ES cells to generate not only specific neuronal populations but also functional neural tissues by recapitulating microenvironments in early mammalian development. In particular, we focus on cerebellar neurogenesis from mouse ES cells, and explain the basic ideas for positional information and self-formation of polarized neuroepithelium. Basic research on developmental signals has fundamentally contributed to substantial progress in stem cell technology. We also discuss how in vitro model systems using ES cells can shed new light on the mechanistic understanding of organogenesis, taking an example of recent progress in self-organizing histogenesis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1440-169x.2012.01329.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22404483" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neural Tube", "descriptor_ui": "D054259", "major_topic": false }, { "descriptor": "Neuroepithelial Cells", "descriptor_ui": "D046569", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stem Cell Niche", "descriptor_ui": "D055153", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Apr", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "349-357", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "54", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "In vitro recapitulation of neural development using embryonic stem cells: from neurogenesis to histogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Studies on genetically modified mice for investigating the role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the brain have revealed a previously uncharacterized function of this neuropeptidergic signaling in the regulation of psychomotor behaviors. In addition, recent clinical studies investigating single nucleotide polymorphisms and copy number variations in the PACAP and its receptor genes have associated the variations with major psychiatric disorders and stress-dependent mental disorders. Here, I briefly review these recent advances in the field and make this an opportunity to consider future direction of research.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22834101" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Psychomotor Performance", "descriptor_ui": "D011597", "major_topic": false }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051236", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2012 Jun", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "133-137", "proceedings_title": null, "publisher": "", "title": "Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology", "volume": "32", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "[Psychiatric implications of PACAP signaling pathway].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Three-dimensional (3-D) analysis of anatomical ultrastructures is important in biological research. However, 3-D image analysis on exact serial sets of ultra-thin sections from biological specimens is very difficult to achieve, and limited information can be obtained by 3-D reconstruction from these sections due to the small area that can be reconstructed. On the other hand, the high-penetration power of electrons by an ultra-high accelerating voltage enables thick sections of biological specimens to be examined. High-voltage electron microscopy (HVEM) is particularly useful for 3-D analysis of the central nervous system because considerably thick sections can be observed at the ultrastructure level. Here, we applied HVEM tomography assisted by light microscopy to a study of the 3-D chemical neuroanatomy of the rat lower spinal cord annotated by double-labeling immunohistochemistry. This powerful methodology is useful for studying molecular and/or chemical neuroanatomy at the 3-D ultrastructural level.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Oti", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00418-012-0976-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22688675" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": true }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microscopy, Electron", "descriptor_ui": "D008854", "major_topic": true }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Oct", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "693-697", "proceedings_title": null, "publisher": "", "title": "Histochemistry and cell biology", "volume": "138", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Three-dimensional evaluation of the spinal local neural network revealed by the high-voltage electron microscopy: a double immunohistochemical study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A hallmark of stem cells is the ability to sustainably generate stem cells themselves (self-renew) as well as differentiated cells. Although a full understanding of this ability will require clarifying underlying the primordial molecular and cellular mechanisms, how stem cells maintain their stem state and their population in the evolutionarily oldest extant multicellular organisms, sponges, is poorly understood. Here, we report the identification of the first stem cell-specific gene in demosponges, a homolog of Musashi (an evolutionarily conserved RNA binding protein that regulates the stem cell state in various organisms). EflMsiA, a Musashi paralog, is specifically expressed in stem cells (archeocytes) in the freshwater sponge Ephydatia fluviatilis. EflMsiA protein is localized predominantly in the nucleus, with a small fraction in the cytoplasm, in archeocytes. When archeocytes enter M-phase, EflMsiA protein diffuses into the cytoplasm, probably because of the breakdown of the nuclear membrane. In the present study, the existence of two types of M-phase archeocytes [(M)-archeocytes] was revealed by a precise analysis of the expression levels of EflMsiA mRNA and protein. In Type I (M)-archeocytes, presumably archeocytes undergoing self-renewal, the expression levels of EflMsiA mRNA and protein were high. In Type II (M)-archeocytes, presumably archeocytes committed to differentiate (committed archeocytes), the expression levels of EflMsiA mRNA and protein were about 60% and 30% lower than those in Type I (M)-archeocytes. From these results, archeocytes can be molecularly defined for the first time as EflMsiA-mRNA-expressing cells. Furthermore, these findings shed light on the mode of cell division of archeocytes and suggest that archeocytes divide symmetrically for both self-renewal and differentiation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuko", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Nakatsukasa", "name": null }, { "creator_type": "author", "first_name": "Alexandre", "last_name": "Alie", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Kiyokazu", "last_name": "Agata", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Funayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.mod.2012.03.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22464976" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle Checkpoints", "descriptor_ui": "D059447", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Organ Specificity", "descriptor_ui": "D009928", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Porifera", "descriptor_ui": "D011161", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Mar-Jun", "date_precision": "unknown", "issue": "1-4", "normalized_date": null, "pages": "24-37", "proceedings_title": null, "publisher": "", "title": "Mechanisms of development", "volume": "129", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "The active stem cell specific expression of sponge Musashi homolog EflMsiA suggests its involvement in maintaining the stem cell state.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cerebellar Purkinje cells (PCs) of newborn rodents are innervated by multiple climbing fibers (CFs). During the first postnatal week, single CFs are strengthened relative to other CFs on the somata of individual PCs. Then, the strengthened CFs undergo translocation to PC dendrites after P9. Elimination of the weaker CFs occurs in two distinct steps, namely the early phase from P7 to around P12 and the late phase from about P12 to around P17. Our previous study demonstrates that CF synapse elimination is severely impaired in null mutant mice lacking Ca(v)2.1, a pore-forming component of P/Q-type voltage-dependent Ca(2+) channel (VDCC). To examine the contribution of postsynaptic P/Q-type VDCC to postnatal rearrangement of CFs, we generated mice with PC-selective deletion of Ca(v)2.1 (PC-Ca(v)2.1 KO). We made whole-cell recordings from PCs in cerebellar slices and examined CF-mediated excitatory postsynaptic currents. We found that PC-Ca(v)2.1 KO PCs had severe defects in selective strengthening of single CFs during the first postnatal week and subsequent CF synapse elimination from P7. Moreover, our morphological analysis revealed that multiple CFs abnormally underwent translocation to PC dendrites in PC-Ca(v)2.1 KO mice. These results indicate that Ca(2+) influx through P/Q-type VDCC into PCs is crucial for selective strengthening of single CFs, early phase elimination and selective translocation of single strengthened CFs to PC dendrites.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12311-011-0337-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22194041" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Calcium Channels, P-Type", "descriptor_ui": "D020865", "major_topic": false }, { "descriptor": "Calcium Channels, Q-Type", "descriptor_ui": "D020907", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Nerve Fibers", "descriptor_ui": "D009412", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jun", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "449-450", "proceedings_title": null, "publisher": "", "title": "Cerebellum (London, England)", "volume": "11", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Activity-dependent maturation of climbing fiber to Purkinje cell synapses during postnatal cerebellar development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mechanisms by which tumor microenvironments modulate nucleic acid–mediated innate immunity remain unknown. Here we identify the receptor TIM-3 as key in circumventing the stimulatory effects of nucleic acids in tumor immunity. Tumor-associated dendritic cells (DCs) in mouse tumors and patients with cancer had high expression of TIM-3. DC-derived TIM-3 suppressed innate immune responses through the recognition of nucleic acids by Toll-like receptors and cytosolic sensors via a galectin-9-independent mechanism. In contrast, TIM-3 interacted with the alarmin HMGB1 to interfere with the recruitment of nucleic acids into DC endosomes and attenuated the therapeutic efficacy of DNA vaccination and chemotherapy by diminishing the immunogenicity of nucleic acids released from dying tumor cells. Our findings define a mechanism whereby tumor microenvironments suppress antitumor immunity mediated by nucleic acids.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shigeki", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Muhammad", "last_name": "Baghdadi", "name": null }, { "creator_type": "author", "first_name": "Hisaya", "last_name": "Akiba", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Yoshiyama", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Hirotoshi", "last_name": "Dosaka-Akita", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Jacob V.", "last_name": "Gorman", "name": null }, { "creator_type": "author", "first_name": "John D.", "last_name": "Colgan", "name": null }, { "creator_type": "author", "first_name": "Mitsuomi", "last_name": "Hirashima", "name": null }, { "creator_type": "author", "first_name": "Toshimitsu", "last_name": "Uede", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Takaoka", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Yagita", "name": null }, { "creator_type": "author", "first_name": "Masahisa", "last_name": "Jinushi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ni.2376" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22842346" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": false }, { "descriptor": "Enzyme-Linked Immunosorbent Assay", "descriptor_ui": "D004797", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Hepatitis A Virus Cellular Receptor 2", "descriptor_ui": "D000072597", "major_topic": false }, { "descriptor": "HMGB1 Protein", "descriptor_ui": "D024243", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": true }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Immunologic Surveillance", "descriptor_ui": "D007157", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Nucleic Acids", "descriptor_ui": "D009696", "major_topic": false }, { "descriptor": "Receptors, Pattern Recognition", "descriptor_ui": "D051192", "major_topic": false }, { "descriptor": "Receptors, Virus", "descriptor_ui": "D011991", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "832-842", "proceedings_title": null, "publisher": "", "title": "Nature immunology", "volume": "13", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Tumor-infiltrating DCs suppress nucleic acid–mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Synovial sarcoma is an obstinate, high-grade malignancy because of its modest responses to radiotherapy and chemotherapy; the identification of effective therapeutics for this sarcoma is therefore necessary. Inhibition of Src family kinases (SFKs) suppresses the proliferation of synovial sarcoma cells in vitro, as we have previously reported. In this study, to validate the efficacy of Src inhibition in vivo, we employed SU6656, which was originally identified as a specific SFK inhibitor. SU6656 treatment significantly impaired the growth of established, existing tumours formed by synovial sarcoma cells in mice. Tumour cell invasion into the surrounding tissues was also abolished by SU6656. It is noteworthy that SU6656 but not PP2 induced a defect in cleavage furrow formation during cytokinesis, resulting in G2/M accumulation and subsequent apoptosis. Intriguingly, SU6656 abrogated the catalytic activities of Aurora kinases and led to the down-regulation of phosphorylated histone H3 coincidently with p53 accumulation, as did the Aurora kinase inhibitor VX-680. Structural comparison indicated an extensive similarity between the catalytic domains of SFKs and Aurora kinases. The structural analysis also revealed the potential binding mode of SU6656 to the ATP-binding cleft of Aurora B via four hydrogen bonds. SU6656 prevented angiogenesis within the tumours by attenuating vascular endothelial growth factor (VEGF) production by tumour cells and the subsequent chemotaxis of endothelial cells; these effects were the result of the inhibition of SFKs but not Aurora kinases. Based on these results, we hereby report a novel property of SU6656 as a dual inhibitor of SFKs and Aurora kinases, the suppression of both of which effectively abrogates tumour development and the progression of synovial sarcoma in vivo.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryuta", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Toyoyuki", "last_name": "Ose", "name": null }, { "creator_type": "author", "first_name": "Chikashi", "last_name": "Obuse", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Maenaka", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ejca.2011.12.028" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22244830" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aurora Kinase B", "descriptor_ui": "D064107", "major_topic": false }, { "descriptor": "Aurora Kinases", "descriptor_ui": "D064127", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Indoles", "descriptor_ui": "D007211", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Sarcoma, Synovial", "descriptor_ui": "D013584", "major_topic": false }, { "descriptor": "src-Family Kinases", "descriptor_ui": "D019061", "major_topic": false }, { "descriptor": "Sulfonamides", "descriptor_ui": "D013449", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Oct", "date_precision": "unknown", "issue": "15", "normalized_date": null, "pages": "2417-2430", "proceedings_title": null, "publisher": "", "title": "European journal of cancer (Oxford, England : 1990)", "volume": "48", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Simultaneous inhibition of Src and Aurora kinases by SU6656 induces therapeutic synergy in human synovial sarcoma growth, invasion and angiogenesis in vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22746059" } }, "mesh": [ { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Genes, abl", "descriptor_ui": "D016313", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia, Myelogenous, Chronic, BCR-ABL Positive", "descriptor_ui": "D015464", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Molecular Targeted Therapy", "descriptor_ui": "D058990", "major_topic": true }, { "descriptor": "Reagent Kits, Diagnostic", "descriptor_ui": "D011933", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "359-365", "proceedings_title": null, "publisher": "", "title": "Seikagaku. The Journal of Japanese Biochemical Society", "volume": "84", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "[Visualization of intracellular signaling and its application to assessment of response to molecular target drugs].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "For high range resolution ultrasonographic vascular imaging, we apply frequency domain interferometry with the Capon method to a single frame of in-phase and quadrature (IQ) data acquired using a commercial ultrasonographic device with a 7.5 MHz linear array probe. In order to tailor the adaptive beam forming algorithm for ultrasonography we employ four techniques: frequency averaging, whitening, radio-frequency data oversampling, and the moving average. The proposed method had a range resolution of 0.05 mm in an ideal condition, and experimentally detected the boundary couple 0.17 mm apart, where the boundary couple was indistinguishable from a single boundary utilizing a B-mode image. Further, this algorithm could depict a swine femoral artery with a range beam width of 0.054 mm and an estimation error for the vessel wall thickness of 0.009 mm, whereas using a conventional method the range beam width and estimation error were 0.182 and 0.021 mm, respectively. The proposed method requires 7.7 s on a mobile PC with a single CPU for a 1x3 cm region of interest. These findings indicate the potential of the proposed method for the improvement of range resolution in ultrasonography without deterioration in temporal resolution, resulting in enhanced detection of vessel stenosis.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Kousuke", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Motoi", "last_name": "Kudo", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1109/tmi.2011.2170847" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21984496" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Constriction, Pathologic", "descriptor_ui": "D003251", "major_topic": false }, { "descriptor": "Femoral Artery", "descriptor_ui": "D005263", "major_topic": false }, { "descriptor": "Image Enhancement", "descriptor_ui": "D007089", "major_topic": false }, { "descriptor": "Image Interpretation, Computer-Assisted", "descriptor_ui": "D007090", "major_topic": false }, { "descriptor": "Interferometry", "descriptor_ui": "D007368", "major_topic": false }, { "descriptor": "Peripheral Arterial Disease", "descriptor_ui": "D058729", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Swine", "descriptor_ui": "D013552", "major_topic": false }, { "descriptor": "Ultrasonography", "descriptor_ui": "D014463", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "417-429", "proceedings_title": null, "publisher": "", "title": "IEEE transactions on medical imaging", "volume": "31", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "High range resolution ultrasonographic vascular imaging using frequency domain interferometry with the Capon method.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Extracellular signal-regulated kinase (ERK) is a key factor in the widely used signaling cascade of phosphorylation-dephosphorylation cycles and plays pivotal roles in many aspects of biological processes. Experimental studies in yeast and in Drosophila embryo have suggested that the phosphorylation and spatial localization of ERK are influenced by the level of its downstream substrates. However, the mechanism, through which these substrates control properties of ERK signaling, has been unclear. I propose a mass-action kinetic model of ERK cycle with its substrate, and demonstrate that the substrate can modulate the ERK activity by directly interacting with ERK. The model shows that the addition of substrate controls the level of ERK phosphorylation positively or negatively, depending on the balance between dissociation constants of ERK-substrate interaction and properties of ERK cyclic signaling in the absence of the substrate. In addition, by considering cellular compartments, cytosol and nucleus, the substrate can lead to nuclear accumulation of ERK, suggesting that the substrate can act as a nuclear anchor of ERK. The model gives a possible mechanism that can account for substrate-mediated modulation of ERK signaling.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.mbs.2012.05.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22705338" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Oct", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "207-212", "proceedings_title": null, "publisher": "", "title": "Mathematical biosciences", "volume": "239", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "A kinetic model of ERK cyclic pathway on substrate control.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In this review, we describe technology and use of single-fluorophore imaging and detection in living cells with regard to application in systems biology and medicine. Because all biological reactions occur under aqueous conditions, the realization of single-fluorophore imaging using an optical microscope has led to the direct observation of biological molecules at work. Today, we can observe single molecules in individual living cells and even higher multicellular organisms. Using single-molecule imaging, we can determine the absolute values of kinetic and dynamic parameters of molecular reactions as a whole and during fluctuations and distribution. In addition, identification of the coordinate of single molecules has enabled super-localization techniques to virtually improve spatial resolution of optical microscopy. Single-molecule detection that depends on point detection instead of imaging is also useful in detecting concentrations, diffusive movements, and molecular interactions in living cells, especially in the cytoplasm. The precise and absolute values of positional, kinetic, and dynamic parameters that are determined by single-molecule imaging and detection in living cells constitute valuable data on unitary biological reactions, because they are obtained without destroying the integrity of complex cellular systems. Moreover, most parameters that are determined by single-molecule measurements can be substituted directly into equations that describe kinetic and dynamic models in systems biology and medicine.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Chan-Gi", "last_name": "Pack", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Kayo", "last_name": "Hibino", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/wsbm.161" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21913339" } }, "mesh": [ { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": false }, { "descriptor": "Nanotechnology", "descriptor_ui": "D036103", "major_topic": false }, { "descriptor": "Photons", "descriptor_ui": "D017785", "major_topic": false }, { "descriptor": "Systems Biology", "descriptor_ui": "D049490", "major_topic": true } ], "publication": { "conference_name": null, "date": "2012 Mar-Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "183-192", "proceedings_title": null, "publisher": "", "title": "Wiley interdisciplinary reviews. Systems biology and medicine", "volume": "4", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Live cell single-molecule detection in systems biology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have developed a new simple method to induce serotonergic neurons from embryonic stem (ES) and induced pluripotent stem cells. When ES or induced pluripotent stem cells were cultured on a thick gel layer of Matrigel, most colonies extended TuJ1-positive neurites. We found that noggin, a known antagonist of bone morphogenic protein, induces ES cells to express genes involved in serotonergic differentiation, such as Nkx2.2, Pet-1, Sonic hedgehog, tryptophan hydroxylase 2, and serotonin transporter, as well as increases high potassium-induced release of serotonin. To concentrate serotonergic neurons, ES cells carrying Pet-1-enhancer-driven enhanced green fluorescent protein were differentiated and sorted into about 80% pure cultures of serotonergic neurons. Whole cell voltage-clamp recordings showed a voltage-dependent current in dissociated neurons. This simplified method provides an alternative option for serotonergic differentiation of pluripotent stem cells and will likely contribute a deeper understanding regarding the nature of serotonergic neurons and open new therapeutic perspectives for the treatment of psychiatric disorders.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Takai", "name": null }, { "creator_type": "author", "first_name": "Kikuko", "last_name": "Shinohara", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Tominaga-Yoshino", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Toi", "name": null }, { "creator_type": "author", "first_name": "Kouji", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1471-4159.2012.07724.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22404309" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Morphogenetic Protein 4", "descriptor_ui": "D055415", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Collagen", "descriptor_ui": "D003094", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Drug Combinations", "descriptor_ui": "D004338", "major_topic": false }, { "descriptor": "Electric Stimulation", "descriptor_ui": "D004558", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Homeobox Protein Nkx-2.2", "descriptor_ui": "D000090322", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Laminin", "descriptor_ui": "D007797", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Noggin Protein", "descriptor_ui": "D000099176", "major_topic": false }, { "descriptor": "Organ Culture Techniques", "descriptor_ui": "D009924", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Proteoglycans", "descriptor_ui": "D011509", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "RNA, Untranslated", "descriptor_ui": "D022661", "major_topic": false }, { "descriptor": "Serotonergic Neurons", "descriptor_ui": "D059326", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transduction, Genetic", "descriptor_ui": "D014161", "major_topic": false }, { "descriptor": "Tubulin", "descriptor_ui": "D014404", "major_topic": false }, { "descriptor": "Tyrosine 3-Monooxygenase", "descriptor_ui": "D014446", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jul", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "81-93", "proceedings_title": null, "publisher": "", "title": "Journal of neurochemistry", "volume": "122", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "A simplified method to generate serotonergic neurons from mouse embryonic stem and induced pluripotent stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: The purpose of this study is to improve the calcification depiction ability in ultrasonography using correlation of echoes with a modified Wiener filter. METHODS: The waveform of an ultrasound pulse changes when it passes through the location of a calcification. Since the change in echo waveform caused by a calcification decreases the correlation of waveforms in adjacent scan lines, we have proposed a calcification depiction method using the decorrelation of echoes. However, the low signal-to-noise ratio of echoes also decreases the correlation of the echoes. In this study, we employ the correlation of echoes with a modified Wiener filter to suppress the effect of noise, as an indicator of a calcification. RESULTS: The proposed calcification indicator depicted copper cylindrical rods 0.2 mm in size at a depth of 2 cm with a sensitivity of 80% and a positive predictive value of 80%, despite being hardly depicted at all on B-mode ultrasound imaging. CONCLUSION: This study suggests the potential of the proposed method to improve the performance of calcification depiction by ultrasound devices.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10396-012-0354-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27278972" } }, "mesh": [], "publication": { "conference_name": null, "date": "2012 Jul", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "127-135", "proceedings_title": null, "publisher": "", "title": "Journal of medical ultrasonics (2001)", "volume": "39", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Small calcification indicator in ultrasonography using correlation of echoes with a modified Wiener filter.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Apelin is a bioactive peptide with diverse physiological actions on many tissues mediated by its interaction with its specific receptor APJ. Since the identification of apelin and APJ in 1998, pleiotropic roles of the apelin/APJ system have been elucidated in different tissues and organs, including modulation of the cardiovascular system, fluid homeostasis, metabolic pathway and vascular formation. In blood vessels, apelin and APJ expression are spatiotemporally regulated in endothelial cells (ECs) during angiogenesis. In vitro analysis revealed that the apelin/APJ system regulates angiogenesis by the induction of proliferation, migration and cord formation of cultured ECs. Moreover, apelin seems to stabilize cell-cell junctions of ECs. In addition, genetically engineered mouse models suggest that apelin/APJ regulates vascular stabilization and maturation in physiological and pathological angiogenesis. In this review, we summarize the current understanding of the apelin/APJ system for vascular formation and maturation.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jb/mvs071" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22745157" } }, "mesh": [ { "descriptor": "Adipokines", "descriptor_ui": "D054392", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apelin", "descriptor_ui": "D000073861", "major_topic": false }, { "descriptor": "Apelin Receptors", "descriptor_ui": "D000075244", "major_topic": false }, { "descriptor": "Blood Vessels", "descriptor_ui": "D001808", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Neovascularization, Physiologic", "descriptor_ui": "D018919", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Aug", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "125-131", "proceedings_title": null, "publisher": "", "title": "Journal of biochemistry", "volume": "152", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Biology of the apelin-APJ axis in vascular formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The serotonin 5-HT(7) receptor has been linked to various psychiatric disorders, including schizophrenia, anxiety and depression, and is antagonized by antipsychotics such as risperidone, clozapine and lurasidone. In this study, we examined whether inhibiting the 5-HT(7) receptor could reverse behavioral abnormalities in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP), an experimental mouse model for psychiatric disorders such as schizophrenia. The selective 5-HT(7) antagonist SB-269970 effectively suppressed abnormal jumping behavior in PACAP-deficient mice. SB-269970 tended to alleviate the higher immobility in the forced swim test in PACAP-deficient mice, although SB-269970 reduced the immobility also in wild-type mice. In addition, we found that mutant mice had impaired performance in the Y-maze test, which was reversed by SB-269970. In the mutant mouse brain, 5-HT(7) protein expression did not differ from wild-type mice. In primary embryonic hippocampal neurons, the 5-HT(7) agonist AS19 increased neurite length and number. Furthermore, SB-269970 significantly inhibited the increase in neurite extension mediated by the 5-HT(1A/7) agonist 8-OH-DPAT. These results indicate that 5-HT(7) receptor blockade ameliorates psychomotor and cognitive deficits in PACAP-deficient mice, providing additional evidence that the 5-HT(7) receptor is a rational target for the treatment of psychiatric disorders.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Minako", "last_name": "Tajiri", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Hazama", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12031-012-9861-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22843252" } }, "mesh": [ { "descriptor": "8-Hydroxy-2-(di-n-propylamino)tetralin", "descriptor_ui": "D017371", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antipsychotic Agents", "descriptor_ui": "D014150", "major_topic": false }, { "descriptor": "Cell Count", "descriptor_ui": "D002452", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Drug Evaluation, Preclinical", "descriptor_ui": "D004353", "major_topic": false }, { "descriptor": "Exploratory Behavior", "descriptor_ui": "D005106", "major_topic": false }, { "descriptor": "Freezing Reaction, Cataleptic", "descriptor_ui": "D046352", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Hyperkinesis", "descriptor_ui": "D006948", "major_topic": false }, { "descriptor": "Maze Learning", "descriptor_ui": "D018782", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Neurologic Mutants", "descriptor_ui": "D008818", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Neurites", "descriptor_ui": "D016501", "major_topic": false }, { "descriptor": "Phenols", "descriptor_ui": "D010636", "major_topic": false }, { "descriptor": "Physical Endurance", "descriptor_ui": "D010807", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Pyrazoles", "descriptor_ui": "D011720", "major_topic": false }, { "descriptor": "Receptors, Serotonin", "descriptor_ui": "D011985", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false }, { "descriptor": "Serotonin Antagonists", "descriptor_ui": "D012702", "major_topic": false }, { "descriptor": "Serotonin Receptor Agonists", "descriptor_ui": "D017366", "major_topic": false }, { "descriptor": "Sulfonamides", "descriptor_ui": "D013449", "major_topic": false }, { "descriptor": "Tetrahydronaphthalenes", "descriptor_ui": "D013764", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Nov", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "473-481", "proceedings_title": null, "publisher": "", "title": "Journal of molecular neuroscience : MN", "volume": "48", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Serotonin 5-HT(7) receptor blockade reverses behavioral abnormalities in PACAP-deficient mice and receptor activation promotes neurite extension in primary embryonic hippocampal neurons: therapeutic implications for psychiatric disorders.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "It is widely accepted that blood vessels in the tumor microenvironment are immature because mural cell (MC) adhesion to endothelial cells (ECs) is broadly lacking. Hyperpermeability of the tumor vasculature then results in interstitial hypertension that mitigates against penetration of anticancer drugs into the depths of the tumor. It has been suggested that treatment with angiogenesis inhibitors normalizes blood vessels, resulting in restoration of normal permeability and improved drug delivery. However, recent reports suggest that cancer cell invasion is induced from the edge of the tumor into peripheral areas after treatment with angiogenesis inhibitors. Therefore, it is important to assess the status of blood vessels in the fibrous cap at the tumor rim after antiangiogenesis therapy. In the present study, we found that mature blood vessels in which ECs are covered with MCs are present in the fibrous cap. After treatment with angiogenesis inhibitors, immature blood vessels were destroyed and vascular function was significantly improved, but maturing blood vessels in which ECs were covered with MCs remained visible. These maturing blood vessels showed a less dilated character after treatment with the angiogenesis inhibitors. It is widely accepted that well-matured blood vessels are sheathed in extracellular matrix (ECM) and that cancer cells migrate along tracks made of ECM collagen fibers. Therefore, our data indicate the importance of destroying maturing blood vessels outside the tumor parenchyma to prevent cancer cell invasion.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takara", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kawahara", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1349-7006.2011.02157.x" }, "pmcid": { "normalized": "PMC7713628" }, "pmid": { "normalized": "22098620" } }, "mesh": [ { "descriptor": "Angiogenesis Inhibitors", "descriptor_ui": "D020533", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal, Humanized", "descriptor_ui": "D061067", "major_topic": false }, { "descriptor": "Bevacizumab", "descriptor_ui": "D000068258", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "HT29 Cells", "descriptor_ui": "D019073", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Neoplasms, Experimental", "descriptor_ui": "D009374", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "433-438", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "103", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Changes in blood vessel maturation in the fibrous cap of the tumor rim.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cutaneous lymphatic system plays a major role in tissue fluid homeostasis and inflammation of the skin. Although several lymphangiogenic factors are known to be involved in the formation of lymphatic vessels, the molecular mechanisms that maintain lymphatic integrity and control the functional drainage of interstitial fluid and resolution of inflammation remain unknown. Here we show that angiopoietin-1 (Ang1) enhances lymphatic integrity and function during inflammation. Ang1 transgenic mice under the control of keratin-14 (K14-Ang1) showed attenuated edema formation and inflammation after UV B (UVB) exposure. After UVB irradiation, blood vascular permeability was inhibited in K14-Ang1 mice compared with wild-type (WT) mice. Moreover, lymphatic vessels of WT mice were markedly enlarged and leaky in inflamed skin, whereas K14-Ang1 mice showed relatively contracted lymphatic vessels together with enhanced lymphatic vascularization. Expression of endothelial-specific tight junction molecules claudin-5 and zonula occludens protein 1 (ZO-1) was strongly down-regulated in the inflamed lymphatic vessels of UVB-exposed WT mice, whereas down-regulation of both claudin-5 and ZO-1 was blocked in UVB-exposed K14-Ang1 mice. In vitro studies revealed that the stability of lymphatic endothelial cells was enhanced in the presence of Ang1, presumably via up-regulation of claudin-5, as well as ZO-1. Claudin-5 knockdown markedly increased the permeability of lymphatic endothelial cells. Overall, our data strongly support the idea that Ang1/Tie2 signaling promotes lymphatic integrity by modulating tight junction molecule expression during inflammation.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kajiya", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Sawane", "name": null }, { "creator_type": "author", "first_name": "Yuuko", "last_name": "Matsumoto-Okazaki", "name": null }, { "creator_type": "author", "first_name": "Haruyo", "last_name": "Yamanishi", "name": null }, { "creator_type": "author", "first_name": "Mikio", "last_name": "Furuse", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ajpath.2011.11.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22200616" } }, "mesh": [ { "descriptor": "Angiopoietin-1", "descriptor_ui": "D042683", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Claudin-5", "descriptor_ui": "D062507", "major_topic": false }, { "descriptor": "Claudins", "descriptor_ui": "D057167", "major_topic": false }, { "descriptor": "Edema", "descriptor_ui": "D004487", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Lymphangitis", "descriptor_ui": "D008205", "major_topic": false }, { "descriptor": "Lymphatic Vessels", "descriptor_ui": "D042601", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Otitis Externa", "descriptor_ui": "D010032", "major_topic": false }, { "descriptor": "Receptor, TIE-2", "descriptor_ui": "D042787", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Tight Junctions", "descriptor_ui": "D019108", "major_topic": false }, { "descriptor": "Ultraviolet Rays", "descriptor_ui": "D014466", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "1273-1282", "proceedings_title": null, "publisher": "", "title": "The American journal of pathology", "volume": "180", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Promotion of lymphatic integrity by angiopoietin-1/Tie2 signaling during inflammation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Inadequate compensatory insulin secretion is observed during the development of type 2 diabetes and deteriorates over time in a manner that is difficult to reverse. Here, we found that plasma glucose levels in genetically diabetic KKA(y) mice fed a high-fat diet were markedly increased in young mice. However, the levels started to decrease at 22 weeks of age and returned to normal levels at around 40 weeks of age. These changes were accompanied by a marked increase in insulin levels from week 25 onwards. Decreased energy intake and suppressed fat pad accumulation were observed at 44-45 weeks of age compared with those at 19-22 weeks of age. beta cell-specific overexpression of pituitary adenylate cyclase-activating polypeptide (PACAP), an insulinotropic neuropeptide, decreased the insulin levels required to compensate for hyperglycemia. Glucose disposal was significantly enhanced despite impaired insulin sensitivity in 41-44-week-old A(y) mice without or with PACAP overexpression. In conclusion, the present results provide further evidence that PACAP is involved in the regulation of hyperinsulinemia and islet hyperplasia in type 2 diabetes. Our results also indicate that A(y) mice fed a high-fat diet constitute an animal model suitable to study compensatory islet hyperplasia.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Arimori", "name": null }, { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Hamagami", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12031-012-9758-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22477644" } }, "mesh": [ { "descriptor": "Agouti Signaling Protein", "descriptor_ui": "D054366", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Glucose", "descriptor_ui": "D001786", "major_topic": false }, { "descriptor": "Body Weight", "descriptor_ui": "D001835", "major_topic": false }, { "descriptor": "Crosses, Genetic", "descriptor_ui": "D003433", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 2", "descriptor_ui": "D003924", "major_topic": false }, { "descriptor": "Diet, High-Fat", "descriptor_ui": "D059305", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Energy Intake", "descriptor_ui": "D002149", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Hyperinsulinism", "descriptor_ui": "D006946", "major_topic": false }, { "descriptor": "Hyperphagia", "descriptor_ui": "D006963", "major_topic": false }, { "descriptor": "Hyperplasia", "descriptor_ui": "D006965", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Insulin Resistance", "descriptor_ui": "D007333", "major_topic": false }, { "descriptor": "Insulin Secretion", "descriptor_ui": "D000078790", "major_topic": false }, { "descriptor": "Intra-Abdominal Fat", "descriptor_ui": "D050152", "major_topic": false }, { "descriptor": "Islets of Langerhans", "descriptor_ui": "D007515", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Mutant Strains", "descriptor_ui": "D008817", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Organ Size", "descriptor_ui": "D009929", "major_topic": false }, { "descriptor": "Pancreas", "descriptor_ui": "D010179", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Nov", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "647-653", "proceedings_title": null, "publisher": "", "title": "Journal of molecular neuroscience : MN", "volume": "48", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Compensatory recovery of blood glucose levels in KKA(y) mice fed a high-fat diet: insulin-sparing effects of PACAP overexpression in beta cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Multilayered, core/shell nanoprobes (MQQ-probe) based on magnetic nanoparticles (MNPs) and quantum dots (QDs) have been successfully developed for multimodality tumor imaging. This MQQ-probe contains Fe(3)O(4) MNPs, visible-fluorescent QDs (600 nm emission) and near infrared-fluorescent QDs (780 nm emission) in multiple silica layers. The fabrication of the MQQ-probe involves the synthesis of a primer Fe(3)O(4) MNPs/SiO(2) core by a reverse microemulsion method. The MQQ-probe can be used both as a fluorescent probe and a contrast reagent of magnetic resonance imaging. For breast cancer tumor imaging, anti-HER2 (human epidermal growth factor receptor 2) antibody was conjugated to the surface of the MQQ-probe. The specific binding of the antibody conjugated MQQ-probe to the surface of human breast cancer cells (KPL-4) was confirmed by fluorescence microscopy and fluorescence-activated cell sorting analysis in vitro. Due to the high tissue permeability of near-infrared (NIR) light, NIR fluorescence imaging of the tumor mice (KPL-4 cells transplanted) was conducted by using the anti-HER2 antibody conjugated MQQ-probe. In vivo multimodality images of breast tumors were successfully taken by NIR fluorescence and T(2)-weighted magnetic resonance. Antibody conjugated MQQ-probes have great potential to use for multimodality imaging of cancer tumors in vitro and in vivo.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Qiang", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Nakane", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Miyuki", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Yoshichika", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kohsuke", "last_name": "Gonda", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Ohuchi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Jin", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.biomaterials.2012.07.051" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22906608" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Diagnostic Imaging", "descriptor_ui": "D003952", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": false }, { "descriptor": "Nanotechnology", "descriptor_ui": "D036103", "major_topic": false }, { "descriptor": "Quantum Dots", "descriptor_ui": "D045663", "major_topic": true } ], "publication": { "conference_name": null, "date": "2012 Nov", "date_precision": "unknown", "issue": "33", "normalized_date": null, "pages": "8486-8494", "proceedings_title": null, "publisher": "", "title": "Biomaterials", "volume": "33", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Multilayered, core/shell nanoprobes based on magnetic ferric oxide particles and quantum dots for multimodality imaging of breast cancer tumors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This study describes a conditional RNA interference system that enabled the knockdown of essential mitotic genes along with high-resolution live microscopy. Loss-of-function analyses of augmin and γ-TuRC constitute a proof of principle and provide insight into acentrosomal microtubule formation during plant mitosis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Nakaoka", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Ryuta", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Tomioka", "name": null }, { "creator_type": "author", "first_name": "Chikashi", "last_name": "Obuse", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Hiwatashi", "name": null }, { "creator_type": "author", "first_name": "Gohta", "last_name": "Goshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1105/tpc.112.098509" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22505727" } }, "mesh": [ { "descriptor": "Anaphase", "descriptor_ui": "D000705", "major_topic": false }, { "descriptor": "Bryopsida", "descriptor_ui": "D019068", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Genes, Plant", "descriptor_ui": "D017343", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Plant Proteins", "descriptor_ui": "D010940", "major_topic": false }, { "descriptor": "Plants, Genetically Modified", "descriptor_ui": "D030821", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": true }, { "descriptor": "Spindle Apparatus", "descriptor_ui": "D008941", "major_topic": false }, { "descriptor": "Tubulin", "descriptor_ui": "D014404", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "1478-1493", "proceedings_title": null, "publisher": "", "title": "The Plant Cell", "volume": "24", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "An Inducible RNA Interference System in Physcomitrella patens Reveals a Dominant Role of Augmin in Phragmoplast Microtubule Generation[W][OA].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Many chemical reactions, including those of biological importance, take place in thermally fluctuating environments. Compared to isolated systems, there arise markedly different features due to the effects of energy dissipation through friction and stochastic driving by random forces reflecting the fluctuation of the environment. Investigation of how robustly the system reacts under the influence of thermal fluctuation, and elucidating the role of thermal fluctuation in the reaction are significant subjects in the study of chemical reactions. In this article, we start with overviewing the generalized Langevin equation (GLE), which has long been used and continues to be a powerful tool to describe a system surrounded by a thermal environment. It has been also generalized further to treat a nonstationary environment, in which the conventional fluctuation-dissipation theorem no longer holds. Then, within the framework of the Langevin equation we present a method recently developed to extract a new reaction coordinate that is decoupled from all the other coordinates in the region of a rank-one saddle linking the reactant and the product. The reaction coordinate is buried in nonlinear couplings among the original coordinates under the influence of stochastic random force. It was ensured that the sign of this new reaction coordinate (= a nonlinear functional of the original coordinates, velocities, friction, and random force) at any instant is sufficient to determine in which region, the reactant or the product, the system finally arrives. We also discuss how one can extend the method to extract such a coordinate from the GLE framework in stationary and nonstationary environments, where memory effects exist in dynamics of the reaction.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c1cp22504a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22048614" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Models, Chemical", "descriptor_ui": "D008956", "major_topic": true }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": true } ], "publication": { "conference_name": null, "date": "2011 Dec 28", "date_precision": "day", "issue": "48", "normalized_date": "2011-12-28", "pages": "21217-21229", "proceedings_title": null, "publisher": "", "title": "Physical chemistry chemical physics : PCCP", "volume": "13", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Why and how do systems react in thermally fluctuating environments?", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We present a novel design strategy for off/on fluorescent probes suitable for selective two-step labeling of proteins. To validate this strategy, we designed and synthesized an off/on fluorescent probe, 1-Ni(2+), which targets a cysteine-modified hexahistidine (His) tag. The probe consists of dichlorofluorescein conjugated with nitrilotriacetic acid (NTA)-Ni(2+) as the His-tag recognition site and a 2,4-dinitrophenyl ether moiety, which quenches the probe's fluorescence by photoinduced electron transfer (PeT) from the excited fluorophore to the 2,4-dinitrophenyl ether (donor-excited PeT; d-PeT) and also has reactivity with cysteine. His-tag recognition by the NTA-Ni(2+) moiety is followed by removal of the 2,4-dinitrophenyl ether quencher by proximity-enhanced reaction with the cysteine residue of the modified tag; this results in a marked fluorescence increase. Addition of His-tag peptide bearing a cysteine residue to aqueous probe solution resulted in about 20-fold fluorescence increment within 10 min, which is the largest fluorescence enhancement so far obtained with a visible light-excitable fluorescent probe for a His-based peptide tag. Further, we successfully visualized CysHis(6)-peptide tethered to microbeads without any washing step. The probe also showed a large fluorescence increment in the presence of His(6)Cys-tagged enhanced blue fluorescent protein (EBFP), but not His(6)-tagged EBFP. We consider this system is superior to large fluorescence tags (e.g., green fluorescent protein: 27 kDa), which can perturb protein folding, trafficking and function, and also to existing small tags, which generally show little fluorescence increase upon target recognition and therefore require a washout step. This strategy should also be applicable to other tags.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Hirabayashi", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Shimonishi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/chem.201102664" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22106092" } }, "mesh": [ { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Nickel", "descriptor_ui": "D009532", "major_topic": false }, { "descriptor": "Nitrilotriacetic Acid", "descriptor_ui": "D009571", "major_topic": false }, { "descriptor": "Oligopeptides", "descriptor_ui": "D009842", "major_topic": false }, { "descriptor": "Organometallic Compounds", "descriptor_ui": "D009942", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Dec 23", "date_precision": "day", "issue": "52", "normalized_date": "2011-12-23", "pages": "14763-14771", "proceedings_title": null, "publisher": "", "title": "Chemistry (Weinheim an der Bergstrasse, Germany)", "volume": "17", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Selective two-step labeling of proteins with an off/on fluorescent probe.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In this study, amphiphilic brush-like copolymers conjugated with short alkyl or long polymeric chains of various lengths are synthesized using ring-opening metathesis polymerization (ROMP) of substituted norbornadiene monomers followed by chemical transformations. These amphiphilic copolymers form spherical self-assemblies in aqueous media with diameters of 132-244 nm. The low critical aggregation concentration of these assemblies (2.5 x 10(-3) -1.4 x 10(-5) g/L) indicates that they are quite stable in dilute conditions. An appropriate length of polymer side chain that conjugates the polymer backbone with a hydrophobic ICG (indocyanine green) moiety enhanced the fluorescence intensities of these self-assemblies in aqueous solution as well as in tumor-bearing mice. A longer side chain conjugated with tumor targeting agents could significantly affect the tumor specificity of self-assemblies to a greater extent. The self-assemblies bearing hydrophilic tumor targeting agents, such as a glucosamine molecule and a cyclic RGD (arginine-glycine-asparatic acid) peptide, accumulated in tumor tissues with high selectivity, while those having a hydrophobic targeting agent, such as folate moieties, accumulated in tumor sites with low selectivity. The results demonstrated here unambiguously indicate that the fluorescence intensity and tumor specificity of self-assemblies are strongly affected by the length of side chains that conjugate with dyes and targeting agents.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Oride", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kuramochi", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/smll.201101637" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22038685" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Diagnostic Imaging", "descriptor_ui": "D003952", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Folic Acid", "descriptor_ui": "D005492", "major_topic": false }, { "descriptor": "Glucosamine", "descriptor_ui": "D005944", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Oligopeptides", "descriptor_ui": "D009842", "major_topic": false }, { "descriptor": "Polymerization", "descriptor_ui": "D058105", "major_topic": true }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Dec 16", "date_precision": "day", "issue": "24", "normalized_date": "2011-12-16", "pages": "3536-3547", "proceedings_title": null, "publisher": "", "title": "Small (Weinheim an der Bergstrasse, Germany)", "volume": "7", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Influence of side chain length on fluorescence intensity of ROMP-based polymeric nanoparticles and their tumor specificity in in-vivo tumor imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In early postnatal development, perisomatic innervation of cerebellar Purkinje cells (PCs) switches from glutamatergic climbing fibers (CFs) to GABAergic basket cell fibers (BFs). Here we examined the switching process in C57BL/6 mice. At postnatal day 7 (P7), most perisomatic synapses were formed by CFs on to somatic spines. The density of CF–spine synapses peaked at P9, when pericellular nest around PCs by CFs was most developed, and CF–spine synapses constituted 88% of the total perisomatic synapses. Thereafter, CF–spine synapses dropped to 63% at P12, 6% at P15, and <1% at P20, whereas BF synapses increased reciprocally. During the switching period, a substantial number of BF synapses existed as BF–spine synapses (37% of the total perisomatic synapses at P15), and free spines surrounded by BFs or Bergmann glia also emerged. By P20, BF–spine synapses and free spines virtually disappeared, and BF–soma synapses became predominant (88%), thus attaining the adult pattern of perisomatic innervation. Parallel with the presynaptic switching, postsynaptic receptor phenotype also switched from glutamatergic to GABAergic. In the active switching period, particularly at P12, fragmental clusters of AMPA-type glutamate receptor were juxtaposed with those of GABAA receptor. When examined with serial ultrathin sections, immunogold labeling for glutamate and GABAA receptors was often clustered beneath single BF terminals. These results suggest that a considerable fraction of somatic spines is succeeded from CFs to BFs and Bergmann glia in the early postnatal period, and that the switching of postsynaptic receptor phenotypes mainly proceeds under the coverage of BF terminals.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Miwako", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Kohtarou", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Haruyuki", "last_name": "Tatsumi", "name": null }, { "creator_type": "author", "first_name": "Yoshiro", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.2396-11.2011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22114262" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Nerve Fibers", "descriptor_ui": "D009412", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Nov 23", "date_precision": "day", "issue": "47", "normalized_date": "2011-11-23", "pages": "16916-16927", "proceedings_title": null, "publisher": "", "title": "The Journal of Neuroscience", "volume": "31", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Developmental Switching of Perisomatic Innervation from Climbing Fibers to Basket Cell Fibers in Cerebellar Purkinje Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Gadolinium ion (Gd(3+)) complexes are commonly used as magnetic resonance imaging (MRI) contrast agents to enhance signals in T(1)-weighted MR images. Recently, several methods to achieve cell-permeation of Gd(3+) complexes have been reported, but more general and efficient methodology is needed. In this report, we describe a novel method to achieve cell permeation of Gd(3+) complexes by using hydrophobic fluorescent dyes as a cell-permeability-enhancing unit. We synthesized Gd(3+) complexes conjugated with boron dipyrromethene (BDP-Gd) and Cy7 dye (Cy7-Gd), and showed that these conjugates can be introduced efficiently into cells. To examine the relationship between cell permeability and dye structure, we further synthesized a series of Cy7-Gd derivatives. On the basis of MR imaging, flow cytometry, and ICP-MS analysis of cells loaded with Cy7-Gd derivatives, highly hydrophobic and nonanionic dyes were effective for enhancing cell permeation of Gd(3+) complexes. Furthermore, the behavior of these Cy7-Gd derivatives was examined in mice. Thus, conjugation of hydrophobic fluorescent dyes appears to be an effective approach to improve the cell permeability of Gd(3+) complexes, and should be applicable for further development of Gd(3+)-based MRI contrast agents.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takehiro", "last_name": "Yamane", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Miyashita", "name": null }, { "creator_type": "author", "first_name": "Yasunobu", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/bc200127t" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21985057" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carbocyanines", "descriptor_ui": "D002232", "major_topic": false }, { "descriptor": "Contrast Media", "descriptor_ui": "D003287", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Gadolinium", "descriptor_ui": "D005682", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrophobic and Hydrophilic Interactions", "descriptor_ui": "D057927", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Nov 16", "date_precision": "day", "issue": "11", "normalized_date": "2011-11-16", "pages": "2227-2236", "proceedings_title": null, "publisher": "", "title": "Bioconjugate chemistry", "volume": "22", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Method for enhancing cell penetration of Gd3+-based MRI contrast agents by conjugation with hydrophobic fluorescent dyes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydrogen sulfide (H(2)S) has recently been identified as a biological response modifier. Here, we report the design and synthesis of a novel fluorescence probe for H(2)S, HSip-1, utilizing azamacrocyclic copper(II) ion complex chemistry to control the fluorescence. HSip-1 showed high selectivity and high sensitivity for H(2)S, and its potential for biological applications was confirmed by employing it for fluorescence imaging of H(2)S in live cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Sasakura", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Norihiro", "last_name": "Shibuya", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja207851s" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21999237" } }, "mesh": [ { "descriptor": "Copper", "descriptor_ui": "D003300", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Organometallic Compounds", "descriptor_ui": "D009942", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Nov 16", "date_precision": "day", "issue": "45", "normalized_date": "2011-11-16", "pages": "18003-18005", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "133", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a highly selective fluorescence probe for hydrogen sulfide.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Blood vessels are mainly composed of intraluminal endothelial cells (ECs) and mural cells adhering to the ECs on their basal side. Immature blood vessels lacking mural cells are leaky; thus, the process of mural cell adhesion to ECs is indispensable for stability of the vessels during physiological angiogenesis. However, in the tumor microenvironment, although some blood vessels are well-matured, the majority is immature. Because mural cell adhesion to ECs also has a marked anti-apoptotic effect, angiogenesis inhibitors that destroy immature blood vessels may not affect mature vessels showing more resistance to apoptosis. Activation of Tie2 receptor tyrosine kinase expressed in ECs mediates pro-angiogenic effects via the induction of EC migration but also facilitates vessel maturation via the promotion of cell adhesion between mural cells and ECs. Therefore, inhibition of Tie2 has the advantage of completely inhibiting angiogenesis. Here, we isolated a novel small molecule Tie2 kinase inhibitor, identified as 2-methoxycinnamaldehyde (2-MCA). We found that 2-MCA inhibits both sprouting angiogenesis and maturation of blood vessels, resulting in inhibition of tumor growth. Our results suggest a potent clinical benefit of disrupting these two using Tie2 inhibitors.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Daishi", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Sakimoto", "name": null }, { "creator_type": "author", "first_name": "Weizhen", "last_name": "Jia", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2011.10.053" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22033407" } }, "mesh": [ { "descriptor": "Acrolein", "descriptor_ui": "D000171", "major_topic": false }, { "descriptor": "Angiogenesis Inhibitors", "descriptor_ui": "D020533", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "HCT116 Cells", "descriptor_ui": "D045325", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Receptor, TIE-2", "descriptor_ui": "D042787", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Nov 11", "date_precision": "day", "issue": "1", "normalized_date": "2011-11-11", "pages": "174-180", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "415", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "2-Methoxycinnamaldehyde inhibits tumor angiogenesis by suppressing Tie2 activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The adenohypophysis (anterior pituitary) is a major centre for systemic hormones. At present, no efficient stem-cell culture for its generation is available, partly because of insufficient knowledge about how the pituitary primordium (Rathke's pouch) is induced in the embryonic head ectoderm. Here we report efficient self-formation of three-dimensional adenohypophysis tissues in an aggregate culture of mouse embryonic stem (ES) cells. ES cells were stimulated to differentiate into non-neural head ectoderm and hypothalamic neuroectoderm in adjacent layers within the aggregate, and treated with hedgehog signalling. Self-organization of Rathke's-pouch-like three-dimensional structures occurred at the interface of these two epithelia, as seen in vivo, and various endocrine cells including corticotrophs and somatotrophs were subsequently produced. The corticotrophs efficiently secreted adrenocorticotropic hormone in response to corticotrophin releasing hormone and, when grafted in vivo, these cells rescued the systemic glucocorticoid level in hypopituitary mice. Thus, functional anterior pituitary tissue self-forms in ES cell culture, recapitulating local tissue interactions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hidetaka", "last_name": "Suga", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kadoshima", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Minaguchi", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Ohgushi", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Soen", "name": null }, { "creator_type": "author", "first_name": "Tokushige", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Wataya", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Miyoshi", "name": null }, { "creator_type": "author", "first_name": "Shigenobu", "last_name": "Yonemura", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Oiso", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nature10637" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22080957" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Ectoderm", "descriptor_ui": "D004475", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Endocrine Cells", "descriptor_ui": "D055098", "major_topic": false }, { "descriptor": "Hypopituitarism", "descriptor_ui": "D007018", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pituitary Gland, Anterior", "descriptor_ui": "D010903", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Nov 9", "date_precision": "day", "issue": "7375", "normalized_date": "2011-11-09", "pages": "57-62", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "480", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Self-formation of functional adenohypophysis in three-dimensional culture.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "It has long been held that cortisol, a glucocorticoid in many vertebrates, carries out both glucocorticoid and mineralocorticoid actions in teleost fish. However, 11-deoxycorticosterone (DOC) has been identified as a specific endogenous ligand for the teleostean mineralocorticoid receptor (MR). Furthermore, the expressions of MR mRNA are modest in the osmoregulatory organs, but considerably higher in the brain of most teleosts. These recent findings suggest that the mineralocorticoid system (DOC/MR) may carry out some behavioral functions in fish. To test this possibility, we examined the effects of cortisol and DOC administration in the amphibious behavior in mudskipper (Periophthalmus modestus) in vivo. It was found that mudskippers remained in the water for an increased period of time when they were immersed into 5 muM DOC or cortisol for 8h. Additionally, an exposure to 25 muM DOC for 4 to 8 h caused a decreased migratory frequency of mudskippers to the water, reflected a tendency to remain in the water. It was further observed that after 8 h of intracerebroventricular (ICV) injection with 0.3 pmol DOC or cortisol the staying period in the water increased in fish. The migratory frequency was decreased after ICV DOC injection which indicated that fishes stayed in the water. Concurrent ICV injections of cortisol with RU486 [a specific glucocorticoid-receptor (GR) antagonist] inhibited only the partial effects of cortisol. Together with no changes in the plasma DOC concentrations under terrestrial conditions, these results indicate the involvement of brain MRs as cortisol receptors in the preference for an aquatic habitat of mudskippers. Although the role of GR signaling cannot be excluded in the aquatic preference, our data further suggest that the MR may play an important role in the brain dependent behaviors of teleost fish.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ojima", "name": null }, { "creator_type": "author", "first_name": "Maho", "last_name": "Ogoshi", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.physbeh.2011.06.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21683725" } }, "mesh": [ { "descriptor": "Analysis of Variance", "descriptor_ui": "D000704", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Desoxycorticosterone", "descriptor_ui": "D003900", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Fishes", "descriptor_ui": "D005399", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Hydrocortisone", "descriptor_ui": "D006854", "major_topic": false }, { "descriptor": "Receptors, Mineralocorticoid", "descriptor_ui": "D018161", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Water-Electrolyte Balance", "descriptor_ui": "D014882", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Oct 24", "date_precision": "day", "issue": "5", "normalized_date": "2011-10-24", "pages": "923-928", "proceedings_title": null, "publisher": "", "title": "Physiology & behavior", "volume": "104", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Corticosteroids stimulate the amphibious behavior in mudskipper: potential role of mineralocorticoid receptors in teleost fish.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Cellular function is regulated by the balance of stringently regulated amounts of mRNA. Previous reports revealed that RNA polymerase II (RNAPII), which transcribes mRNA, can be classified into the pausing state and the active transcription state according to the phosphorylation state of RPB1, the catalytic subunit of RNAPII. However, genome-wide association between mRNA expression level and the phosphorylation state of RNAPII is unclear. While the functional importance of pausing genes is clear, such as in mouse Embryonic Stem cells for differentiation, understanding this association is critical for distinguishing pausing genes from active transcribing genes in expression profiling data, such as microarrays and RNAseq. Therefore, we examined the correlation between the phosphorylation of RNAPII and mRNA expression levels using a combined analysis by ChIPseq and RNAseq. RESULTS: We first performed a precise quantitative measurement of mRNA by performing an optimized calculation in RNAseq. We then visualized the recruitment of various phosphorylated RNAPIIs, such as Ser2P and Ser5P. A combined analysis using optimized RNAseq and ChIPseq for phosphorylated RNAPII revealed that mRNA levels correlate with the various phosphorylation states of RNAPII. CONCLUSIONS: We demonstrated that the amount of mRNA is precisely reflected by the phased phosphorylation of Ser2 and Ser5. In particular, even the most \"pausing\" genes, for which only Ser5 is phosphorylated, were detectable at a certain level of mRNA. Our analysis indicated that the complexity of quantitative regulation of mRNA levels could be classified into three categories according to the phosphorylation state of RNAPII.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Odawara", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Yoshimi", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1471-2164-12-516" }, "pmcid": { "normalized": "PMC3209707" }, "pmid": { "normalized": "22011111" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Chromatin Immunoprecipitation", "descriptor_ui": "D047369", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": true }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "RNA Polymerase II", "descriptor_ui": "D012319", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Oct 20", "date_precision": "day", "issue": "", "normalized_date": "2011-10-20", "pages": "516", "proceedings_title": null, "publisher": "", "title": "BMC genomics", "volume": "12", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "The classification of mRNA expression levels by the phosphorylation state of RNAPII CTD based on a combined genome-wide approach.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have developed a red-emitting fluorescent K(+) probe, B3TAC, which also shows a wavelength shift upon binding to K(+). The probe was synthesized by conjugating a cryptand-based chelator, 2-triazacryptand [2,2,3]-1-(2-methoxyethoxy)benzene (TAC), to position 3 of the BODIPY fluorophore through a styryl linker. In water-acetonitrile mixed solvent, it responded to K(+) in the physiological concentration range with high selectivity over Na(+) and other metal ions. B3TAC is potentially useful for measuring cellular K(+) ion concentration, as well as for simple, naked-eye detection of K(+) in solution.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tomoya", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bmcl.2011.08.056" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21906942" } }, "mesh": [ { "descriptor": "Boron Compounds", "descriptor_ui": "D001896", "major_topic": false }, { "descriptor": "Colorimetry", "descriptor_ui": "D003124", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Ions", "descriptor_ui": "D007477", "major_topic": false }, { "descriptor": "Potassium", "descriptor_ui": "D011188", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Oct 15", "date_precision": "day", "issue": "20", "normalized_date": "2011-10-15", "pages": "6090-6093", "proceedings_title": null, "publisher": "", "title": "Bioorganic & medicinal chemistry letters", "volume": "21", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a potassium ion-selective fluorescent sensor based on 3-styrylated BODIPY.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report a novel near-infrared fluorescent calcium probe (KFCA), which has good optical properties such as intense NIR fluorescence emission (670 nm, QY: 0.24), excellent ON/OFF ratio (120-fold), and good wavelength-compatibility with visible-light-emissive fluorophores (Fluo-4, DsRed2), and which is applicable for real-time dual-colour intracellular Ca(2+) imaging.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akihiro", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Umezawa", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c1cc14045k" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21837350" } }, "mesh": [ { "descriptor": "Boron Compounds", "descriptor_ui": "D001896", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Color", "descriptor_ui": "D003116", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infrared Rays", "descriptor_ui": "D007259", "major_topic": true }, { "descriptor": "Intracellular Space", "descriptor_ui": "D042541", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Optical Phenomena", "descriptor_ui": "D055620", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Oct 7", "date_precision": "day", "issue": "37", "normalized_date": "2011-10-07", "pages": "10407-10409", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "47", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "A near-infrared fluorescent calcium probe: a new tool for intracellular multicolour Ca2+ imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We studied the photobleaching of a library of boron dipyrromethene (BODIPY) derivatives with a range of electron densities, and found that the photobleaching rate is influenced by the electron-withdrawing capacity of the substituents. Electron-deficient BODIPYs generated less singlet oxygen, were less reactive to singlet oxygen, and were highly resistant to photobleaching. We confirmed the utility of one of these fluorophores, 2,6-diCO(2)R-BDP, for visualizing EGF receptor dynamics in cells expressing an SNAP-tagged EGF receptor.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Daihi", "last_name": "Oushiki", "name": null }, { "creator_type": "author", "first_name": "Aoi", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Miyamura", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Mineno", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c1cc13367e" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21818482" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Boron Compounds", "descriptor_ui": "D001896", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": false }, { "descriptor": "Photobleaching", "descriptor_ui": "D038761", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Sep 28", "date_precision": "day", "issue": "36", "normalized_date": "2011-09-28", "pages": "10055-10057", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "47", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Rational design of boron dipyrromethene (BODIPY)-based photobleaching-resistant fluorophores applicable to a protein dynamics study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To improve optical imaging of Ca(2+) and to make available a distinct color window for multicolor imaging, we designed and synthesized CaSiR-1, a far-red to near-infrared fluorescence probe for Ca(2+), using Si-rhodamine (SiR) as the fluorophore and the well-known Ca(2+) chelator BAPTA. This wavelength region is advantageous, affording higher tissue penetration, lower background autofluorescence, and lower phototoxicity in comparison with the UV to visible range. CaSiR-1 has a high fluorescence off/on ratio of over 1000. We demonstrate its usefulness for multicolor fluorescence imaging of action potentials (visualized as increases in intracellular Ca(2+)) in brain slices loaded with sulforhodamine 101 (red color; specific for astrocytes) that were prepared from transgenic mice in which some neurons expressed green fluorescent protein.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takahiro", "last_name": "Egawa", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Koide", "name": null }, { "creator_type": "author", "first_name": "Sakiko", "last_name": "Ujita", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Ikegaya", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Matsuki", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja205809h" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21827169" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cations, Divalent", "descriptor_ui": "D002413", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Spectroscopy, Near-Infrared", "descriptor_ui": "D019265", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Sep 14", "date_precision": "day", "issue": "36", "normalized_date": "2011-09-14", "pages": "14157-14159", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "133", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a far-red to near-infrared fluorescence probe for calcium ion and its application to multicolor neuronal imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yasunori", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Kazunobu", "last_name": "Toshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/asia.201100421" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21780295" } }, "mesh": [ { "descriptor": "Amyloid beta-Peptides", "descriptor_ui": "D016229", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzothiazoles", "descriptor_ui": "D052160", "major_topic": false }, { "descriptor": "Fullerenes", "descriptor_ui": "D037741", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Peptide Fragments", "descriptor_ui": "D010446", "major_topic": false }, { "descriptor": "Photolysis", "descriptor_ui": "D010782", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Thiazoles", "descriptor_ui": "D013844", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Sep 5", "date_precision": "day", "issue": "9", "normalized_date": "2011-09-05", "pages": "2312-2315", "proceedings_title": null, "publisher": "", "title": "Chemistry, an Asian journal", "volume": "6", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Inhibition of amyloid beta aggregation and cytotoxicity by photodegradation using a designed fullerene derivative.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have developed the first highly selective fluorescence probe for alkaline phosphatase (ALP), TG-mPhos. This probe shows selectivity for ALP over protein tyrosine phosphatase and protein serine/threonine phosphatase. Our previously developed TG-Phos, which has a phenolic phosphate linkage in place of the alcoholic phosphate linkage of TG-mPhos, lacks this selectivity. TG-mPhos should enable precise fluorescence imaging of ALP activity in biological applications.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuyasu", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bmcl.2011.03.070" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21482108" } }, "mesh": [ { "descriptor": "Alkaline Phosphatase", "descriptor_ui": "D000469", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Photochemistry", "descriptor_ui": "D010777", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Sep 1", "date_precision": "day", "issue": "17", "normalized_date": "2011-09-01", "pages": "5088-5091", "proceedings_title": null, "publisher": "", "title": "Bioorganic & medicinal chemistry letters", "volume": "21", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a highly selective fluorescence probe for alkaline phosphatase.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nucleotide pyrophosphatases/phosphodiesterases (NPPs) are ubiquitous membrane-associated or secreted ectoenzymes that have a role in regulating extracellular nucleotide and phospholipid metabolism. Among the members of the NPP family, NPP1 and -3 act on nucleotides such as ATP, while NPP2, -6, and -7 act on phospholipids such as lysophosphatidylcholine and sphingomyelin. NPP6, a recently characterized NPP family member, is a choline-specific glycerophosphodiester phosphodiesterase, but its functions remain to be analyzed, partly due to the lack of highly sensitive activity assay systems and practical inhibitors. Here we report synthesis of novel NPP6 fluorescence probes, TG-mPC and its analogues TG-mPC(3)C, TG-mPC(5)C, TG-mPENE, TG-mPEA, TG-mPhos, TG-mPA, TG-mPMe, and TG-mPPr. Among the seven NPPs, only NPP6 hydrolyzed TG-mPC, TG-mPC(3)C, and TG-mPENE. TG-mPC was hydrolyzed in the cell lysate from NPP6-transfected cells, but not control cells, showing that it is suitable for use in cell-based NPP6 assays. We also examined the usefulness of TG-mPC as a fluorescence imaging probe. We further applied TG-mPC to carry out high-throughput NPP6 inhibitor screening and found several NPP6-selective inhibitors in a library of about 80,000 compounds. Through structure-activity relationship (SAR) analysis, we identified a potent and selective NPP6 inhibitor with an IC(50) value of 0.21 muM. Our NPP6-selective fluorescence probe, TG-mPC, and the inhibitor are expected to be useful to elucidate the biological function of NPP6.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuyasu", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Okudaira", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yuuta", "last_name": "Fujikawa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Junken", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja201028t" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21721554" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lysophospholipase", "descriptor_ui": "D008245", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "Phosphoric Diester Hydrolases", "descriptor_ui": "D010727", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Structure-Activity Relationship", "descriptor_ui": "D013329", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Aug 10", "date_precision": "day", "issue": "31", "normalized_date": "2011-08-10", "pages": "12021-12030", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "133", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Fluorescence probe for lysophospholipase C/NPP6 activity and a potent NPP6 inhibitor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We present a simple method to form free-standing lipid membranes on arrayed microchambers (>100). The formed membranes are perpendicular to an imaging plane with control of solute concentration on each side of the membranes. This platform let us quantitatively detect membrane transport of non-charged fluorescent molecules, induced by membrane proteins.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Takeuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c1lc20334g" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21701764" } }, "mesh": [ { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Lipids", "descriptor_ui": "D008055", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Membranes, Artificial", "descriptor_ui": "D008567", "major_topic": true }, { "descriptor": "Microarray Analysis", "descriptor_ui": "D046228", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Aug 7", "date_precision": "day", "issue": "15", "normalized_date": "2011-08-07", "pages": "2485-2487", "proceedings_title": null, "publisher": "", "title": "Lab on a chip", "volume": "11", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Microfluidic lipid membrane formation on microchamber arrays.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "LRRK2 is the causal molecule for autosomal-dominant familial Parkinson's disease, although its true function, including its physiological substrates, remains unknown. Here, using in vitro kinase assay with recombinant proteins, we demonstrated for the first time that LRRK2 directly phosphorylates Akt1, a central molecule involved in signal transduction for cell survival and prevention of apoptosis. Ser473, one of two amino acids essential for Akt1 activation, was the target site for LRRK2. A knockdown experiment using intact cells also demonstrated LRRK2-mediated phosphorylation of Akt1 (Ser473), suggesting that Akt1 is a convincing candidate for the physiological substrate of LRRK2. The disease-associated mutations, R1441C, G2019S, and I2020T, exhibited reduced interaction with, and phosphorylation of, Akt1, suggesting one possible mechanism for the neurodegeneration caused by LRRK2 mutations.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Obata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.febslet.2011.05.044" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21658387" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leucine-Rich Repeat Serine-Threonine Protein Kinase-2", "descriptor_ui": "D000071158", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Parkinson Disease", "descriptor_ui": "D010300", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jul 21", "date_precision": "day", "issue": "14", "normalized_date": "2011-07-21", "pages": "2165-2170", "proceedings_title": null, "publisher": "", "title": "FEBS letters", "volume": "585", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "LRRK2 directly phosphorylates Akt1 as a possible physiological substrate: impairment of the kinase activity by Parkinson's disease-associated mutations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular Ca(2+) levels play a crucial role in the control of ATP synthesis. However, the spatiotemporal correlation between ATP and Ca(2+) remains unclear due to the inability to visualize these factors within same individual cells. A Forster resonance energy transfer (FRET)-based fluorescent ATP probe, named ATeam, was recently developed for ATP imaging in single living cells. However, the spectra of cyan fluorescent protein (CFP) and yellow fluorescent protein (YFP) used as the FRET donor and the acceptor, respectively, significantly overlap with the ultraviolet-excitable Ca(2+) probe, fura-2. In the present work, we developed new red-shifted ATP probes, GO-ATeams, in which green fluorescent protein (GFP) and orange fluorescent protein (OFP) was used as the FRET pair to minimize spectral overlap with the fura-2 emission. The dynamics of intracellular Ca(2+) and mitochondrial ATP levels in single histamine-stimulated HeLa cells were successfully visualized by using fura-2 and GO-ATeam. The experiments showed that histamine induced increases of both intracellular Ca(2+) and mitochondrial ATP levels. The increment of mitochondrial ATP levels was proportional to that of Ca(2+). This finding suggests that cellular Ca(2+) levels might precisely control mitochondrial ATP synthesis in response to the increased ATP consumption triggered by Ca(2+). In addition, GO-ATeam has several advantages over the original ATeam. The GO-ATeam signal was more stable against acidification, which would allow ATP imaging inside acidic intracellular compartments. Also, the GO-ATeam excitation wavelength is much less phototoxic to cells, making the probe suitable for long-time observation.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Noji", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/cb100313n" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21488691" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Antimetabolites", "descriptor_ui": "D000963", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Deoxyglucose", "descriptor_ui": "D003847", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Fura-2", "descriptor_ui": "D016257", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Histamine", "descriptor_ui": "D006632", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jul 15", "date_precision": "day", "issue": "7", "normalized_date": "2011-07-15", "pages": "709-715", "proceedings_title": null, "publisher": "", "title": "ACS chemical biology", "volume": "6", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Ca(2)(+) regulation of mitochondrial ATP synthesis visualized at the single cell level.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Single mRNA imaging in live cells is a useful technique to elucidate its precise localization and dynamics. We developed a method for visualizing endogenous mRNAs in living cells with single molecule sensitivity using genetically encoded probes. An RNA-binding protein of human PUMILIO1 (PUM-HD) was used for recognizing base sequences of a target mRNA, beta-actin mRNA. Two PUM-HDs were modified by amino acid mutations to bind specifically to tandem 8-base sequences of the target mRNA. Because each PUM-HD was connected with amino- and carboxyl-terminal fragments of enhanced green fluorescent protein (EGFP), the probes emit fluorescence by reconstitution of EGFP fragments upon binding to beta-actin mRNAs. The EGFP reconstituted on the mRNAs was monitored with a total internal reflection fluorescence microscope. Results show that each fluorescent spot in live cells represented a single beta-actin mRNA and that distinct spatial and temporal movement of the individual beta-actin mRNAs was visualized. We also estimated the average velocity of the movement of the single mRNAs along microtubules in live cells. This method is widely applicable to tracking various mRNAs of interest in the native state of living cells with single-mRNA sensitivity.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Toshimichi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Asumi", "last_name": "Inaguma", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ac2009405" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21634804" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cytosol", "descriptor_ui": "D003600", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jul 15", "date_precision": "day", "issue": "14", "normalized_date": "2011-07-15", "pages": "5708-5714", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "83", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualization of nonengineered single mRNAs in living cells using genetically encoded fluorescent probes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydrogen peroxide is believed to play a role in cellular signal transduction by reversible oxidation of proteins. Here, we report the design and synthesis of a novel fluorescence probe for hydrogen peroxide, utilizing a photoinduced electron transfer strategy based on benzil chemistry to control the fluorescence. The practical value of this highly sensitive and selective fluorescence probe, NBzF, was confirmed by its application to imaging of hydrogen peroxide generation in live RAW 264.7 macrophages. NBzF was also employed for live cell imaging of hydrogen peroxide generated as a signaling molecule in A431 human epidermoid carcinoma cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Abo", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja203521e" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21692459" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Electron Transport", "descriptor_ui": "D004579", "major_topic": false }, { "descriptor": "Fluoresceins", "descriptor_ui": "D005452", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jul 13", "date_precision": "day", "issue": "27", "normalized_date": "2011-07-13", "pages": "10629-10637", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "133", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a highly sensitive fluorescence probe for hydrogen peroxide.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Oride", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kuramochi", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201101005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21656616" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Phosphorylcholine", "descriptor_ui": "D010767", "major_topic": false }, { "descriptor": "Polyethylene Glycols", "descriptor_ui": "D011092", "major_topic": false }, { "descriptor": "Polymethacrylic Acids", "descriptor_ui": "D011109", "major_topic": false }, { "descriptor": "Spectroscopy, Near-Infrared", "descriptor_ui": "D019265", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jul 11", "date_precision": "day", "issue": "29", "normalized_date": "2011-07-11", "pages": "6567-6570", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "50", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "High-contrast fluorescence imaging of tumors in vivo using nanoparticles of amphiphilic brush-like copolymers produced by ROMP.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Firefly luciferase is widely used as a reporter gene in assays to study gene expression, gene delivery, and so on because of its extremely high signal-to-noise ratio. The availability of a range of bioluminogenic substrates would greatly extend the applicability of the luciferin-luciferase system. Herein, we describe a design concept for functional bioluminogenic substrates based on the aminoluciferin (AL) scaffold, together with a convenient, high-yield method for synthesizing N-alkylated ALs. We confirmed the usefulness of ALs as bioluminogenic substrates by synthesizing three probes. The first was a conjugate of AL with glutamate, Glu-AL. When Glu-AL, the first membrane-impermeable bioluminogenic substrate of luciferases, was applied to cells transfected with luciferase, luminescence was not observed; that is, by using Glu-AL, we can distinguish between intracellular and extracellular events. The second was Cy5-AL, which consisted of Cy5, a near-infrared (NIR) cyanine fluorescent dye, and AL, and emitted NIR light. When Cy5-AL reacted with luciferase, luminescence derived from Cy5 was observed as a result of bioluminescence resonance energy transfer (BRET) from AL to Cy5. The NIR emission wavelength would allow a signal to be observed from deeper tissues in bioluminescence in vivo imaging. The third was biotin-DEVD-AL (DEVD = the amino acid sequence Asp-Glu-Val-Asp), which employed a caspase-3 substrate peptide as a switch to control the accessibility of the substrate to luciferase, and could detect the activity of caspase-3 in a time-dependent manner. This generalized design strategy should be applicable to other proteases. Our results indicate that the AL scaffold is appropriate for a range of functional luminophores and represents a useful alternative substrate to luciferin.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hideo", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/asia.201000873" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21416616" } }, "mesh": [ { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Biotin", "descriptor_ui": "D001710", "major_topic": false }, { "descriptor": "Caspase 3", "descriptor_ui": "D053148", "major_topic": false }, { "descriptor": "Firefly Luciferin", "descriptor_ui": "D049454", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Luciferases, Firefly", "descriptor_ui": "D049409", "major_topic": false }, { "descriptor": "Spectroscopy, Near-Infrared", "descriptor_ui": "D019265", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jul 4", "date_precision": "day", "issue": "7", "normalized_date": "2011-07-04", "pages": "1800-1810", "proceedings_title": null, "publisher": "", "title": "Chemistry, an Asian journal", "volume": "6", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Aminoluciferins as functional bioluminogenic substrates of firefly luciferase.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The absorption and emission wavelengths of group 14 pyronines and rhodamines, which contain silicon, germanium, or tin at the 10 position of the xanthene chromophore, showed large bathochromic shifts compared to the original rhodamines, owing to stabilization of the LUMO energy levels by sigma*-pi* conjugation between group 14 atom-C (methyl) sigma* orbitals and a pi* orbital of the fluorophore. These group 14 pyronines and rhodamines retain the advantages of the original rhodamines, including high quantum efficiency in aqueous media (Phi(fl) = 0.3-0.45), tolerance to photobleaching, and high water solubility. Group 14 rhodamines have higher values of reduction potential than other NIR light-emitting original rhodamines, and therefore, we speculated their NIR fluorescence could be controlled through the photoinduced electron transfer (PeT) mechanism. Indeed, we found that the fluorescence quantum yield (Phi(fl)) of Si-rhodamine (SiR) and Ge-rhodamine (GeR) could be made nearly equal to zero, and the threshold level for fluorescence on/off switching lies at around 1.3-1.5 V for the SiRs. This is about 0.1 V lower than in the case of TokyoGreens, in which the fluorophore is well established to be effective for PeT-based probes. That is to say, the fluorescence of SiR and GeR can be drastically activated by more than 100-fold through a PeT strategy. To confirm the validity of this strategy for developing NIR fluorescence probes, we employed this approach to design two kinds of novel fluorescence probes emitting in the far-red to NIR region, i.e., a series of pH-sensors for use in acidic environments and a Zn(2+) sensor. We synthesized these probes and confirmed that they work well.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Koide", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/cb1002416" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21375253" } }, "mesh": [ { "descriptor": "Chemical Phenomena", "descriptor_ui": "D055598", "major_topic": false }, { "descriptor": "Electrochemistry", "descriptor_ui": "D004563", "major_topic": false }, { "descriptor": "Electron Transport", "descriptor_ui": "D004579", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Photosensitizing Agents", "descriptor_ui": "D017319", "major_topic": false }, { "descriptor": "Pyronine", "descriptor_ui": "D011754", "major_topic": false }, { "descriptor": "Quantum Theory", "descriptor_ui": "D011789", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": false }, { "descriptor": "Solubility", "descriptor_ui": "D012995", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Spectrophotometry, Ultraviolet", "descriptor_ui": "D013056", "major_topic": false }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false }, { "descriptor": "Zinc", "descriptor_ui": "D015032", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jun 17", "date_precision": "day", "issue": "6", "normalized_date": "2011-06-17", "pages": "600-608", "proceedings_title": null, "publisher": "", "title": "ACS chemical biology", "volume": "6", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Evolution of group 14 rhodamines as platforms for near-infrared fluorescence probes utilizing photoinduced electron transfer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neural circuits are initially redundant but rearranged through activity-dependent synapse elimination during postnatal development. This process is crucial for shaping mature neural circuits and for proper brain function. At birth, Purkinje cells (PCs) in the cerebellum are innervated by multiple climbing fibers (CFs) with similar synaptic strengths. During postnatal development, a single CF is selectively strengthened in each PC through synaptic competition, the strengthened single CF undergoes translocation to a PC dendrite, and massive elimination of redundant CF synapses follows. To investigate the cellular mechanisms of this activity-dependent synaptic refinement, we generated mice with PC-selective deletion of the Ca(v)2.1 P/Q-type Ca(2+) channel, the major voltage-dependent Ca(2+) channel in PCs. In the PC-selective Ca(v)2.1 knockout mice, Ca(2+) transients induced by spontaneous CF inputs are markedly reduced in PCs in vivo. Not a single but multiple CFs were equally strengthened in each PC from postnatal day 5 (P5) to P8, multiple CFs underwent translocation to PC dendrites, and subsequent synapse elimination until around P12 was severely impaired. Thus, P/Q-type Ca(2+) channels in postsynaptic PCs mediate synaptic competition among multiple CFs and trigger synapse elimination in developing cerebellum.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Tsujita", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Hee-Sup", "last_name": "Shin", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1101488108" }, "pmcid": { "normalized": "PMC3116426" }, "pmid": { "normalized": "21628556" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Channels, N-Type", "descriptor_ui": "D020864", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Nerve Fibers", "descriptor_ui": "D009412", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jun 14", "date_precision": "day", "issue": "24", "normalized_date": "2011-06-14", "pages": "9987-9992", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "108", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Postsynaptic P/Q-type Ca2+ channel in Purkinje cell mediates synaptic competition and elimination in developing cerebellum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "2-Arachidonoylglycerol (2-AG) is the endocannabinoid that mediates retrograde suppression of neurotransmission in the brain. In the present study, we investigated the 2-AG signaling system at mossy cell (MC)–granule cell (GC) synapses in the mouse dentate gyrus, an excitatory recurrent circuit where endocannabinoids are thought to suppress epileptogenesis. First, we showed by electrophysiology that 2-AG produced by diacylglycerol lipase α (DGLα) mediated both depolarization-induced suppression of excitation and its enhancement by group I metabotropic glutamate receptor activation at MC–GC synapses, as they were abolished in DGLα-knock-out mice. Immunohistochemistry revealed that DGLα was enriched in the neck portion of GC spines forming synapses with MC terminals, whereas cannabinoid CB1 receptors accumulated in the terminal portion of MC axons. On the other hand, the major 2-AG-degrading enzyme, monoacylglycerol lipase (MGL), was absent at MC–GC synapses but was expressed in astrocytes and some inhibitory terminals. Serial electron microscopy clarified that a given GC spine was innervated by a single MC terminal and also contacted nonsynaptically by other MC terminals making synapses with other GC spines in the neighborhood. MGL-expressing elements, however, poorly covered GC spines, amounting to 17% of the total surface of GC spines by astrocytes and 4% by inhibitory terminals. Our findings provide a basis for 2-AG-mediated retrograde suppression of MC–GC synaptic transmission and also suggest that 2-AG released from activated GC spines is readily accessible to nearby MC–GC synapses by escaping from enzymatic degradation. This molecular–anatomical configuration will contribute to adjust network activity in the dentate gyrus after enhanced excitation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Motokazu", "last_name": "Uchigashima", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Miwako", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Asami", "last_name": "Tanimura", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.5665-10.2011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21613483" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arachidonic Acids", "descriptor_ui": "D001095", "major_topic": false }, { "descriptor": "Dentate Gyrus", "descriptor_ui": "D018891", "major_topic": false }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": false }, { "descriptor": "Glycerides", "descriptor_ui": "D005989", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mossy Fibers, Hippocampal", "descriptor_ui": "D019599", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 May 25", "date_precision": "day", "issue": "21", "normalized_date": "2011-05-25", "pages": "7700-7714", "proceedings_title": null, "publisher": "", "title": "The Journal of Neuroscience", "volume": "31", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular and Morphological Configuration for 2-Arachidonoylglycerol-Mediated Retrograde Signaling at Mossy Cell–Granule Cell Synapses in the Dentate Gyrus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Two-photon (2P) uncaging of caged neurotransmitters can efficiently stimulate individual synapses and is widely used to characterize synaptic functions in brain slice preparations. Here we extended 2P uncaging to neocortical pyramidal neurons in adult mice in vivo where caged glutamate was applied from the pial surface. To validate the methodology, we applied a small fluorescent probe using the same method, and confirmed that its concentrations were approximately homogenous up to 200 mum below the cortical surface, and that the extracellular space of the neocortex was as large as 22%. In fact, in vivo whole-cell recording revealed that 2P glutamate uncaging could elicit transient currents (2pEPSCs) very similar to excitatory postsynaptic currents (EPSCs). A spatial resolution of glutamate uncaging was 0.6-0.8 mum up to the depth of 200 mum, and in vivo 2P uncaging was able to stimulate single identified spines. Automated three-dimensional (3-D) mapping of such 2pEPSCs which covered the surfaces of dendritic branches revealed that functional AMPA receptor expression was stable and proportional to spine volume.Moreover, in vivo 2P Ca2+ imaging and uncaging suggested that the amplitudes of glutamate-induced Ca2+ transients were inversely proportional to spine volume. Thus, the key structure-function relationships hold in dendritic spines in adult neocortex in vivo, as in young hippocampal slice preparations. In vivo 2P uncaging will be a powerful tool to investigate properties of synapses in the neocortex.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Nagaoka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Graham C. R.", "last_name": "Ellis-Davies", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Matsuzaki", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Kasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1113/jphysiol.2011.207100" }, "pmcid": { "normalized": "PMC3115818" }, "pmid": { "normalized": "21486811" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Extracellular Space", "descriptor_ui": "D005110", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neocortex", "descriptor_ui": "D019579", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Pyramidal Cells", "descriptor_ui": "D017966", "major_topic": false }, { "descriptor": "Receptors, AMPA", "descriptor_ui": "D018091", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 May 15", "date_precision": "day", "issue": "Pt 10", "normalized_date": "2011-05-15", "pages": "2447-2457", "proceedings_title": null, "publisher": "", "title": "The Journal of physiology", "volume": "589", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "In vivo two-photon uncaging of glutamate revealing the structure-function relationships of dendritic spines in the neocortex of adult mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mutations of the myosin Va gene cause the neurological diseases Griscelli syndrome type 1 and Elejalde syndrome in humans and dilute phenotypes in rodents. To understand the pathophysiological mechanisms underlying the neurological disorders in myosin Va diseases, we conducted an integrated analysis at the molecular, cellular, electrophysiological, and behavioral levels using the dilute-neurological (d-n) mouse mutant. These mice manifest an ataxic gait and clonic seizures during postnatal development, but the neurological disorders are ameliorated in adulthood. We found that smooth endoplasmic reticulum (SER) rarely extended into the dendritic spines of Purkinje cells (PCs) of young d-n mice, and there were few, if any, IP3 receptors. Moreover, long-term depression (LTD) at parallel fiber–PC synapses was abolished, consistent with our previous observations in juvenile lethal dilute mutants. Young d-n mice exhibited severe impairment of cerebellum-dependent motor learning. In contrast, adult d-n mice showed restoration of motor learning and LTD, and these neurological changes were associated with accumulation of SER and IP3 receptors in some PC spines and the expression of myosin Va proteins in the PCs. RNA interference-mediated repression of myosin Va caused a reduction in the number of IP3 receptor-positive spines in cultured PCs. These findings indicate that myosin Va function is critical for subsequent processes in localization of SER and IP3 receptors in PC spines, LTD, and motor learning. Interestingly, d-n mice had defects of motor coordination from young to adult ages, suggesting that the role of myosin Va in PC spines is not sufficient for motor coordination.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mariko", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Naohide", "last_name": "Hirashima", "name": null }, { "creator_type": "author", "first_name": "Yoshiharu", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Takagishi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.5651-10.2011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21508232" } }, "mesh": [ { "descriptor": "Analysis of Variance", "descriptor_ui": "D000704", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Conditioning, Classical", "descriptor_ui": "D003214", "major_topic": false }, { "descriptor": "Conditioning, Eyelid", "descriptor_ui": "D003215", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Electrophysiology", "descriptor_ui": "D004594", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum, Smooth", "descriptor_ui": "D018871", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Inositol 1,4,5-Trisphosphate Receptors", "descriptor_ui": "D053496", "major_topic": false }, { "descriptor": "Learning", "descriptor_ui": "D007858", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Neurologic Mutants", "descriptor_ui": "D008818", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Myosin Heavy Chains", "descriptor_ui": "D018995", "major_topic": false }, { "descriptor": "Myosin Type V", "descriptor_ui": "D024701", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Rotarod Performance Test", "descriptor_ui": "D045442", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Apr 20", "date_precision": "day", "issue": "16", "normalized_date": "2011-04-20", "pages": "6067-6078", "proceedings_title": null, "publisher": "", "title": "The Journal of Neuroscience", "volume": "31", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "A Role for Myosin Va in Cerebellar Plasticity and Motor Learning: A Possible Mechanism Underlying Neurological Disorder in Myosin Va Disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A far-red to near-infrared (NIR) fluorescence probe, MMSiR, based on Si-rhodamine, was designed and synthesized for sensitive and selective detection of HOCl in real time. MMSiR and its oxidized product SMSiR have excellent properties, including pH-independence of fluorescence, high resistance to autoxidation and photobleaching, and good tissue penetration of far-red to NIR fluorescence emission. The value of MMSiR was confirmed by real-time imaging of phagocytosis using a fluorescence microscope. wsMMSiR, a more hydrophilic derivative of MMSiR, permitted effective in vivo imaging of HOCl generation in a mouse peritonitis model. This probe is expected to be a useful tool for investigating the wide range of biological functions of HOCl.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Koide", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja111470n" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21443186" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Hypochlorous Acid", "descriptor_ui": "D006997", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Neutrophils", "descriptor_ui": "D009504", "major_topic": false }, { "descriptor": "Phagocytosis", "descriptor_ui": "D010587", "major_topic": false }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": false }, { "descriptor": "Silicon Compounds", "descriptor_ui": "D017655", "major_topic": false }, { "descriptor": "Swine", "descriptor_ui": "D013552", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Apr 20", "date_precision": "day", "issue": "15", "normalized_date": "2011-04-20", "pages": "5680-5682", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "133", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of an Si-rhodamine-based far-red to near-infrared fluorescence probe selective for hypochlorous acid and its applications for biological imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We present a design strategy for fluorescence probes with a high off/on activation ratio in the red wavelength region, based on a novel fluorescein analogue in which the O atom at the 10 position of the xanthene chromophore is replaced with a Si atom. To demonstrate the usefulness of this strategy, we designed and synthesized a red-fluorescent probe for beta-galactosidase, and showed that it works in live HEK293 cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takahiro", "last_name": "Egawa", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Koide", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c1cc00078k" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21359330" } }, "mesh": [ { "descriptor": "beta-Galactosidase", "descriptor_ui": "D001616", "major_topic": false }, { "descriptor": "Fluoresceins", "descriptor_ui": "D005452", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Silicon", "descriptor_ui": "D012825", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Xanthenes", "descriptor_ui": "D014966", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Apr 14", "date_precision": "day", "issue": "14", "normalized_date": "2011-04-14", "pages": "4162-4164", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "47", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a fluorescein analogue, TokyoMagenta, as a novel scaffold for fluorescence probes in red region.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Rho family of GTPases have important roles in the morphogenesis of the dendritic spines of neurons in the brain and synaptic plasticity by modulating the organization of the actin cytoskeleton. Here we used two-photon fluorescence lifetime imaging microscopy to monitor the activity of two Rho GTPases-RhoA and Cdc42-in single dendritic spines undergoing structural plasticity associated with long-term potentiation in CA1 pyramidal neurons in cultured slices of rat hippocampus. When long-term volume increase was induced in a single spine using two-photon glutamate uncaging, RhoA and Cdc42 were rapidly activated in the stimulated spine. These activities decayed over about five minutes, and were then followed by a phase of persistent activation lasting more than half an hour. Although active RhoA and Cdc42 were similarly mobile, their activity patterns were different. RhoA activation diffused out of the stimulated spine and spread over about 5 microm along the dendrite. In contrast, Cdc42 activation was restricted to the stimulated spine, and exhibited a steep gradient at the spine necks. Inhibition of the Rho-Rock pathway preferentially inhibited the initial spine growth, whereas the inhibition of the Cdc42-Pak pathway blocked the maintenance of sustained structural plasticity. RhoA and Cdc42 activation depended on Ca(2+)/calmodulin-dependent kinase (CaMKII). Thus, RhoA and Cdc42 relay transient CaMKII activation to synapse-specific, long-term signalling required for spine structural plasticity.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Hong", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Yasuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nature09823" }, "pmcid": { "normalized": "PMC3105377" }, "pmid": { "normalized": "21423166" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinase Type 2", "descriptor_ui": "D054732", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "GTPase-Activating Proteins", "descriptor_ui": "D020690", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Learning", "descriptor_ui": "D007858", "major_topic": false }, { "descriptor": "Long-Term Potentiation", "descriptor_ui": "D017774", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Phosphoproteins", "descriptor_ui": "D010750", "major_topic": false }, { "descriptor": "Pyramidal Cells", "descriptor_ui": "D017966", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "rho GTP-Binding Proteins", "descriptor_ui": "D020741", "major_topic": false }, { "descriptor": "rhoA GTP-Binding Protein", "descriptor_ui": "D020742", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Apr 7", "date_precision": "day", "issue": "7341", "normalized_date": "2011-04-07", "pages": "100-104", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "472", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Local, persistent activation of Rho GTPases during plasticity of single dendritic spines.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Squid can rapidly change the chromatic patterns on their body. The patterns are created by the expansion and retraction of chromatophores. The chromatophore consists of a central pigment-containing cell surrounded by radial muscles that are controlled by motor neurons located in the central nervous system (CNS). In this study we used semi-intact squid (Sepioteuthis lessoniana) displaying centrally controlled natural patterns to analyze spatial and temporal activities of chromatophores located on the dorsal mantle skin. We found that chromatophores oscillated with miniature expansions/retractions at various frequencies, even when the chromatic patterns appear macroscopically stable. The frequencies of this miniature oscillation differed between \"feature\" and \"background\" areas of chromatic patterns. Higher frequencies occurred in feature areas, whereas lower frequencies were detected in background areas. We also observed synchronization of the oscillation during chromatic pattern expression. The expansion size of chromatophores oscillating at high frequency correlated with the number of synchronized chromatophores but not the oscillation frequency. Miniature oscillations were not observed in denervated chromatophores. These results suggest that miniature oscillations of chromatophores are driven by motor neuronal activities in the CNS and that frequency and synchrony of this oscillation determine the chromatic pattern and the expansion size, respectively.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mamiko", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0018244" }, "pmcid": { "normalized": "PMC3069962" }, "pmid": { "normalized": "21483763" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cell Count", "descriptor_ui": "D002452", "major_topic": false }, { "descriptor": "Cell Size", "descriptor_ui": "D048429", "major_topic": false }, { "descriptor": "Chromatophores", "descriptor_ui": "D002856", "major_topic": false }, { "descriptor": "Decapodiformes", "descriptor_ui": "D049832", "major_topic": false }, { "descriptor": "Pigmentation", "descriptor_ui": "D010858", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Apr 1", "date_precision": "day", "issue": "4", "normalized_date": "2011-04-01", "pages": "e18244", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "6", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Chromatophore activity during natural pattern expression by the squid Sepioteuthis lessoniana: contributions of miniature oscillation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The generalized Langevin equation (GLE) is extended to the case of nonstationary bath. The derivation starts with the Hamiltonian equation of motion of the total system including the bath, without any assumption on the form of Hamiltonian or the distribution of the initial condition. Then the projection operator formulation is utilized to obtain a low-dimensional description of the system dynamics surrounded by the nonstationary bath modes. In contrast to the ordinary GLE, the mean force becomes a time-dependent function of the position and the velocity of the system. The friction kernel is found to depend on both the past and the current times, in contrast to the stationary case where it only depends on their difference. The fluctuation-dissipation theorem, which relates the statistical property of the random force to the friction kernel, is also derived for general nonstationary cases. The resulting equation of motion is as simple as the ordinary GLE, and is expected to give a powerful framework to analyze the dynamics of the system surrounded by a nonstationary bath.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/1.3561065" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21428648" } }, "mesh": [], "publication": { "conference_name": null, "date": "2011 Mar 21", "date_precision": "day", "issue": "11", "normalized_date": "2011-03-21", "pages": "114523", "proceedings_title": null, "publisher": "", "title": "The Journal of chemical physics", "volume": "134", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Derivation of the generalized Langevin equation in nonstationary environments.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "RATIONALE: Grb2-associated binder (Gab) docking proteins, consisting of Gab1, Gab2, and Gab3, have crucial roles in growth factor-dependent signaling. Various proangiogenic growth factors regulate angiogenesis and endothelial function. However, the roles of Gab proteins in angiogenesis remain elusive. OBJECTIVE: To elucidate the role of Gab proteins in postnatal angiogenesis. METHODS AND RESULTS: Endothelium-specific Gab1 knockout (Gab1ECKO) mice were viable and showed no obvious defects in vascular development. Therefore, we analyzed a hindlimb ischemia (HLI) model of control, Gab1ECKO, or conventional Gab2 knockout (Gab2KO) mice. Intriguingly, impaired blood flow recovery and necrosis in the operated limb was observed in all of Gab1ECKO, but not in control or Gab2KO mice. Among several proangiogenic growth factors, hepatocyte growth factor (HGF) induced the most prominent tyrosine phosphorylation of Gab1 and subsequent complex formation of Gab1 with SHP2 (Src homology-2-containing protein tyrosine phosphatase 2) and phosphatidylinositol 3-kinase subunit p85 in human endothelial cells (ECs). Gab1-SHP2 complex was required for HGF-induced migration and proliferation of ECs via extracellular signal-regulated kinase (ERK)1/2 pathway and for HGF-induced stabilization of ECs via ERK5. In contrast, Gab1-p85 complex regulated activation of AKT and contributed partially to migration of ECs after HGF stimulation. Microarray analysis demonstrated that HGF upregulated angiogenesis-related genes such as KLF2 (Kruppel-like factor 2) and Egr1 (early growth response 1) via Gab1-SHP2 complex in human ECs. In Gab1ECKO mice, gene transfer of vascular endothelial growth factor, but not HGF, improved blood flow recovery and ameliorated limb necrosis after HLI. CONCLUSION: Gab1 is essential for postnatal angiogenesis after ischemia via HGF/c-Met signaling.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Wataru", "last_name": "Shioyama", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Nakaoka", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Taniyama", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Sonobe", "name": null }, { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Yoh", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Fujio", "name": null }, { "creator_type": "author", "first_name": "Mikiyasu", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Yamauchi-Takihara", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Kodama", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Issei", "last_name": "Komuro", "name": null } ], "identifiers": { "doi": { "normalized": "10.1161/circresaha.110.232223" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21293003" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": true }, { "descriptor": "Arteries", "descriptor_ui": "D001158", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Class Ia Phosphatidylinositol 3-Kinase", "descriptor_ui": "D058543", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Endothelium, Vascular", "descriptor_ui": "D004730", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Hepatocyte Growth Factor", "descriptor_ui": "D017228", "major_topic": false }, { "descriptor": "Hindlimb", "descriptor_ui": "D006614", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ischemia", "descriptor_ui": "D007511", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Phosphoproteins", "descriptor_ui": "D010750", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Regional Blood Flow", "descriptor_ui": "D012039", "major_topic": false }, { "descriptor": "SH2 Domain-Containing Protein Tyrosine Phosphatases", "descriptor_ui": "D054593", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Tyrosine", "descriptor_ui": "D014443", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Mar 18", "date_precision": "day", "issue": "6", "normalized_date": "2011-03-18", "pages": "664-675", "proceedings_title": null, "publisher": "", "title": "Circulation research", "volume": "108", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Docking protein Gab1 is an essential component of postnatal angiogenesis after ischemia via HGF/c-met signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Novel ratiometric, near-infrared fluorescent pH probes with various pK(a) values have been designed and synthesized on the basis of aminocyanine bearing a diamine moiety, and their photochemical properties were evaluated. Under acidic conditions, these pH probes showed a 46- to 83-nm red shift of the absorption maximum. This change is sufficiently large to permit their use as ratiometric pH probes, and is reversible, whereas monoamine-substituted aminocyanines showed irreversible changes because of their instability under acidic conditions. Furthermore, the pK(a) values of these probes can be predicted from the calculated pK(a) values of the diamine moieties, obtained from the SciFinder database. This design strategy is very simple and flexible, and should be applicable to develop NIR pH probes for various applications.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takuya", "last_name": "Myochin", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Kiyose", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja1063058" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21341656" } }, "mesh": [ { "descriptor": "Diamines", "descriptor_ui": "D003959", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Spectroscopy, Near-Infrared", "descriptor_ui": "D019265", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Mar 16", "date_precision": "day", "issue": "10", "normalized_date": "2011-03-16", "pages": "3401-3409", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "133", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Rational design of ratiometric near-infrared fluorescent pH probes with various pKa values, based on aminocyanine.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nonlinear reaction dynamics through a rank-one saddle is investigated for many-particle system with spatial rotation. Based on the recently developed theories of the phase space geometry in the saddle region, we present a theoretical framework to incorporate the spatial rotation which is dynamically coupled with the internal vibrational motions through centrifugal and Coriolis interactions. As an illustrative simple example, we apply it to isomerization reaction of HCN with some nonzero total angular momenta. It is found that no-return transition state (TS) and a set of impenetrable reaction boundaries to separate the \"past\" and \"future\" of trajectories can be identified analytically under rovibrational couplings. The three components of the angular momentum are found to have distinct effects on the migration of the \"anchor\" of the TS and the reaction boundaries through rovibrational couplings and anharmonicities in vibrational degrees of freedom. This method provides new insights in understanding the origin of a wide class of reactions with nonzero angular momentum.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/1.3554906" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21361536" } }, "mesh": [], "publication": { "conference_name": null, "date": "2011 Feb 28", "date_precision": "day", "issue": "8", "normalized_date": "2011-02-28", "pages": "084304", "proceedings_title": null, "publisher": "", "title": "The Journal of chemical physics", "volume": "134", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Phase space geometry of dynamics passing through saddle coupled with spatial rotation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Protease-activated receptor 1 (PAR1) is a member of the G-protein coupled receptors that are proteolytically activated by serine proteases. Recent studies suggest a definite contribution of PAR1 to brain functions, including learning and memory. However, cellular mechanisms by which PAR1 activation influences neuronal activity are not well understood. Here we show that PAR1 activation drives retrograde endocannabinoid signaling and thereby regulates synaptic transmission. In cultured hippocampal neurons from rat, PAR1 activation by thrombin or PAR1-specific peptide agonists transiently suppressed inhibitory transmission at cannabinoid-sensitive, but not cannabinoid-insensitive, synapses. The PAR1-induced suppression of synaptic transmission was accompanied by an increase in paired-pulse ratio, and was blocked by a cannabinoid CB(1) receptor antagonist. The PAR1-induced suppression was blocked by pharmacological inhibition of postsynaptic diacylglycerol lipase (DGL), a key enzyme for biosynthesis of the major endocannabinoid 2-arachidonoylglycerol (2-AG), and was absent in knock-out mice lacking the alpha isoform of DGL. The PAR1-induced IPSC suppression remained intact under the blockade of metabotropic glutamate receptors and was largely resistant to the treatment that blocked Ca(2+) elevation in glial cells following PAR1 activation, which excludes the major contribution of glial PAR1 in IPSC suppression. We conclude that activation of neuronal PAR1 triggers retrograde signaling mediated by 2-AG, which activates presynaptic CB(1) receptors and suppresses transmitter release at hippocampal inhibitory synapses.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Hashimotodani", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Ohno-Shosaku", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.6000-10.2011" }, "pmcid": { "normalized": "PMC6623775" }, "pmid": { "normalized": "21414931" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arachidonic Acids", "descriptor_ui": "D001095", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cannabinoid Receptor Modulators", "descriptor_ui": "D063385", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glycerides", "descriptor_ui": "D005989", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neurotransmitter Agents", "descriptor_ui": "D018377", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Receptor, Cannabinoid, CB1", "descriptor_ui": "D043884", "major_topic": false }, { "descriptor": "Receptor, PAR-1", "descriptor_ui": "D044463", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Feb 23", "date_precision": "day", "issue": "8", "normalized_date": "2011-02-23", "pages": "3104-3109", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "31", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Neuronal protease-activated receptor 1 drives synaptic retrograde signaling mediated by the endocannabinoid 2-arachidonoylglycerol.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "2-Arachidonoylglycerol (2-AG) is the endocannabinoid that mediates retrograde suppression of synaptic transmission in the brain. 2-AG is synthesized in activated postsynaptic neurons by sn-1-specific diacylglycerol lipase (DGL), binds to presynaptic cannabinoid CB1 receptors, suppresses neurotransmitter release, and is degraded mainly by monoacylglycerol lipase (MGL). In the basolateral amygdala complex, it has been demonstrated that CB1 is particularly enriched in axon terminals of cholecystokinin (CCK)-positive GABAergic interneurons, induces short- and long-term depression at inhibitory synapses, and is involved in extinction of fear memory. Here, we clarified a unique molecular convergence of DGLα, CB1, and MGL at specific inhibitory synapses in the basal nucleus (BA), but not lateral nucleus, of the basolateral amygdala. The synapses, termed invaginating synapses, consisted of conventional symmetrical contact and unique perisynaptic invagination of nerve terminals into perikarya. At invaginating synapses, DGLα was preferentially recruited to concave somatic membrane of postsynaptic pyramidal neurons, whereas invaginating presynaptic terminals highly expressed CB1, MGL, and CCK. No such molecular convergence was seen for flat perisomatic synapses made by parvalbumin-positive interneurons. On the other hand, DGLα and CB1 were expressed weakly at axospinous excitatory synapses. Consistent with these morphological data, thresholds for DGLα-mediated depolarization-induced retrograde suppression were much lower for inhibitory synapses than for excitatory synapses in BA pyramidal neurons. Moreover, depolarization-induced suppression was readily saturated for inhibition, but never for excitation. These findings suggest that perisomatic inhibition by invaginating synapses is a key target of 2-AG-mediated control of the excitability of BA pyramidal neurons.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takayuki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Motokazu", "last_name": "Uchigashima", "name": null }, { "creator_type": "author", "first_name": "Miwako", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Istvan", "last_name": "Katona", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1012875108" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21282604" } }, "mesh": [ { "descriptor": "Amygdala", "descriptor_ui": "D000679", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arachidonic Acids", "descriptor_ui": "D001095", "major_topic": false }, { "descriptor": "Cannabinoid Receptor Modulators", "descriptor_ui": "D063385", "major_topic": false }, { "descriptor": "Cholecystokinin", "descriptor_ui": "D002766", "major_topic": false }, { "descriptor": "Electrophysiology", "descriptor_ui": "D004594", "major_topic": false }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": true }, { "descriptor": "Glycerides", "descriptor_ui": "D005989", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "In Situ Hybridization, Fluorescence", "descriptor_ui": "D017404", "major_topic": false }, { "descriptor": "Lipoprotein Lipase", "descriptor_ui": "D008071", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Microscopy, Electron", "descriptor_ui": "D008854", "major_topic": false }, { "descriptor": "Microscopy, Immunoelectron", "descriptor_ui": "D016253", "major_topic": false }, { "descriptor": "Monoacylglycerol Lipases", "descriptor_ui": "D008994", "major_topic": false }, { "descriptor": "Neural Inhibition", "descriptor_ui": "D009433", "major_topic": false }, { "descriptor": "Pyramidal Tracts", "descriptor_ui": "D011712", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Feb 15", "date_precision": "day", "issue": "7", "normalized_date": "2011-02-15", "pages": "3059-3064", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "108", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Unique inhibitory synapse with particularly rich endocannabinoid signaling machinery on pyramidal neurons in basal amygdaloid nucleus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stimulatory and inhibitory co-receptors play fundamental roles in the regulation of the immune system. We describe a new mouse model of spontaneous autoimmune disease. Activation-induced cytidine deaminase-linked autoimmunity (aida) mice harbor a loss-of-function mutation in the gene encoding lymphocyte activation gene 3 (LAG-3), an inhibitory co-receptor. Although LAG-3 deficiency alone did not induce autoimmunity in nonautoimmune-prone mouse strains, it induced lethal myocarditis in BALB/c mice deficient for the gene encoding the inhibitory co-receptor programmed cell death 1 (PD-1). In addition, LAG-3 deficiency alone accelerated type 1 diabetes mellitus in nonobese diabetic mice. These results demonstrate that LAG-3 acts synergistically with PD-1 and/or other immunoregulatory genes to prevent autoimmunity in mice.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Taku", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Il-mi", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Jian", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Nakaki", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Sidonia", "last_name": "Fagarasan", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Tomoo", "last_name": "Eto", "name": null }, { "creator_type": "author", "first_name": "Kyoji", "last_name": "Hioki", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Honjo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1084/jem.20100466" }, "pmcid": { "normalized": "PMC3039848" }, "pmid": { "normalized": "21300912" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, CD", "descriptor_ui": "D015703", "major_topic": false }, { "descriptor": "Antigens, Surface", "descriptor_ui": "D000954", "major_topic": false }, { "descriptor": "Apoptosis Regulatory Proteins", "descriptor_ui": "D051017", "major_topic": false }, { "descriptor": "Autoimmunity", "descriptor_ui": "D015551", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 1", "descriptor_ui": "D003922", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "DNA Primers", "descriptor_ui": "D017931", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Lymphocyte Activation Gene 3 Protein", "descriptor_ui": "D000093322", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Microsatellite Repeats", "descriptor_ui": "D018895", "major_topic": false }, { "descriptor": "Myocarditis", "descriptor_ui": "D009205", "major_topic": false }, { "descriptor": "Polymorphism, Restriction Fragment Length", "descriptor_ui": "D012150", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Feb 14", "date_precision": "day", "issue": "2", "normalized_date": "2011-02-14", "pages": "395-407", "proceedings_title": null, "publisher": "", "title": "The Journal of experimental medicine", "volume": "208", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Questions of how the nature of a reaction coordinate that dominates the reaction ceases to exist and whether some new features emerge as an increase of total energy of systems are investigated for many degrees of freedom Hamiltonian systems. As a model system, a hydrogen atom in crossed electric and magnetic fields is scrutinized. It is shown that, when the total energy increases, the reaction coordinate no longer dominates the reaction as did at the lower energies. In turn, a new reaction coordinate emerges, connecting totally different reactant and product states. Furthermore, depending on which parts of the phase space the system traverses through the saddle, the system nonuniformly experiences the switching of the reaction coordinate leading to the different product state. The universal mechanism of the cessation and the switching of the reaction coordinate at high energy regimes above the saddle is investigated.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Teramoto", "name": null }, { "creator_type": "author", "first_name": "Mikito", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physrevlett.106.054101" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21405398" } }, "mesh": [], "publication": { "conference_name": null, "date": "2011 Feb 4", "date_precision": "day", "issue": "5", "normalized_date": "2011-02-04", "pages": "054101", "proceedings_title": null, "publisher": "", "title": "Physical review letters", "volume": "106", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamical switching of a reaction coordinate to carry the system through to a different product state at high energies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During early telencephalic development, the major portion of the ventral telencephalic (subpallial) region becomes subdivided into three regions, the lateral (LGE), medial (MGE), and caudal (CGE) ganglionic eminences. In this study, we systematically recapitulated subpallial patterning in mouse embryonic stem cell (ESC) cultures and investigated temporal and combinatory actions of patterning signals. In serum-free floating culture, the dorsal-ventral specification of ESC-derived telencephalic neuroectoderm is dose-dependently directed by Sonic hedgehog (Shh) signaling. Early Shh treatment, even before the expression onset of Foxg1 (also Bf1; earliest marker of the telencephalic lineage), is critical for efficiently generating LGE progenitors, and continuous Shh signaling until day 9 is necessary to commit these cells to the LGE lineage. When induced under these conditions and purified by fluorescence-activated cell sorter, telencephalic cells efficiently differentiated into Nolz1+/Ctip2+ LGE neuronal precursors and subsequently, both in culture and after in vivo grafting, into DARPP32+ medium-sized spiny neurons. Purified telencephalic progenitors treated with high doses of the Hedgehog (Hh) agonist SAG (Smoothened agonist) differentiated into MGE- and CGE-like tissues. Interestingly, in addition to strong Hh signaling, the efficient specification of MGE cells requires Fgf8 signaling but is inhibited by treatment with Fgf15/19. In contrast, CGE differentiation is promoted by Fgf15/19 but suppressed by Fgf8, suggesting that specific Fgf signals play different, critical roles in the positional specification of ESC-derived ventral subpallial tissues. We discuss a model of the antagonistic Fgf8 and Fgf15/19 signaling in rostral-caudal subpallial patterning and compare it with the roles of these molecules in cortical patterning.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Teruko", "last_name": "Danjo", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Kiichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Yuchio", "last_name": "Yanagawa", "name": null }, { "creator_type": "author", "first_name": "John L. R.", "last_name": "Rubenstein", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.5128-10.2011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21289201" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cyclohexylamines", "descriptor_ui": "D003514", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Fibroblast Growth Factor 8", "descriptor_ui": "D051524", "major_topic": false }, { "descriptor": "Fibroblast Growth Factors", "descriptor_ui": "D005346", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Hedgehog Proteins", "descriptor_ui": "D053823", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Polymerase Chain Reaction", "descriptor_ui": "D016133", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Telencephalon", "descriptor_ui": "D013687", "major_topic": false }, { "descriptor": "Thiophenes", "descriptor_ui": "D013876", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Tumor Suppressor Proteins", "descriptor_ui": "D025521", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Feb 2", "date_precision": "day", "issue": "5", "normalized_date": "2011-02-02", "pages": "1919-1933", "proceedings_title": null, "publisher": "", "title": "The Journal of Neuroscience", "volume": "31", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Subregional Specification of Embryonic Stem Cell-Derived Ventral Telencephalic Tissues by Timed and Combinatory Treatment with Extrinsic Signals.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The spirolactam ring-opening process of rhodamine derivative is one of the most useful mechanisms for controlling fluorescence properties. However, the open/closed equilibrium reaction of rhodamine spirolactam has not been well characterized. Therefore, we examined the relationship between the spirolactam ring-opening process of rhodamine derivatives and the structure of the xanthene moiety. Based on the results of this investigation, we selected a candidate xanthene moiety for a Zn(2+) sensor, and successfully developed a new fluorescence probe for Zn(2+).", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hiromi", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bmc.2010.05.074" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20620067" } }, "mesh": [ { "descriptor": "Chromatography, Gel", "descriptor_ui": "D002850", "major_topic": false }, { "descriptor": "Chromatography, High Pressure Liquid", "descriptor_ui": "D002851", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Ions", "descriptor_ui": "D007477", "major_topic": false }, { "descriptor": "Photochemical Processes", "descriptor_ui": "D055668", "major_topic": true }, { "descriptor": "Rhodamines", "descriptor_ui": "D012235", "major_topic": false }, { "descriptor": "Zinc", "descriptor_ui": "D015032", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Feb 1", "date_precision": "day", "issue": "3", "normalized_date": "2011-02-01", "pages": "1072-1078", "proceedings_title": null, "publisher": "", "title": "Bioorganic & medicinal chemistry", "volume": "19", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Design and synthesis of a novel fluorescence probe for Zn2+ based on the spirolactam ring-opening process of rhodamine derivatives.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIMS: Cortisol is a glucocorticoid in mammals, but has both gluco- and mineralocorticoid activities in teleost fish. Our previous in vivo studies on osmoregulatory esophagi of euryhaline fish showed that epithelial apoptosis for the simple epithelium in seawater and cell proliferation for the stratified epithelium in fresh water are both induced by cortisol. The aim of the present study was to examine the mechanism of these dual cortisol effects on esophageal cell turnover. MAIN METHODS: We developed a tissue culture method for the esophagus from euryhaline medaka (Oryzias latipes) and assessed cell proliferation and apoptosis in vitro in response to cortisol and 11-deoxycorticosterone (DOC), a recently identified agonist of the teleostean mineralocorticoid receptor. KEY FINDINGS: Epithelial apoptosis, a well-established glucocorticoid function, was stimulated by treatment of the esophagus culture with 10nM cortisol for 8 days, but no effects were seen at higher doses (100 and 1000 nM). In contrast, cell proliferation was induced by 1000 nM cortisol treatment for 8 days and this response was dose-dependent. Both effects were blocked by RU-486, a glucocorticoid receptor antagonist. DOC showed no significant effects at 10-1000 nM. SIGNIFICANCE: In the esophageal epithelium in euryhaline fish, cortisol induces either apoptosis or cell proliferation via the glucocorticoid receptor, depending on the cortisol concentration. The glucocorticoid signaling may play a more important role than mineralocorticoid signaling in differentiation of the osmoregulatory esophagus in euryhaline fishes.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Chiyo", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kudose", "name": null }, { "creator_type": "author", "first_name": "Kanoko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.lfs.2010.11.017" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21112340" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anti-Inflammatory Agents", "descriptor_ui": "D000893", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Esophagus", "descriptor_ui": "D004947", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hydrocortisone", "descriptor_ui": "D006854", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Oryzias", "descriptor_ui": "D009990", "major_topic": true }, { "descriptor": "Receptors, Glucocorticoid", "descriptor_ui": "D011965", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jan 31", "date_precision": "day", "issue": "5-6", "normalized_date": "2011-01-31", "pages": "239-245", "proceedings_title": null, "publisher": "", "title": "Life sciences", "volume": "88", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Dual in vitro effects of cortisol on cell turnover in the medaka esophagus via the glucocorticoid receptor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We present a new self-consistent procedure to construct a multidimensional effective free energy landscape from a scalar single molecule time series, when single molecules experience the landscape within a given timescale of \"observation.\" The theory is based on a framework we recently developed to extract a set of local equilibrium states (LESs) and their network from a scalar time series, such as distance between dye molecules tagged in a biomolecule. We scrutinize the appropriateness of the assumptions of local equilibration and local detailed balance among LESs at the single molecule level within the given timescale, rather than postulating them a priori. The self-consistent procedure in this article incorporates the effect of local correlation of the system dynamics inside potential basins, and the effect of finiteness of the sampled data points in assigning the boundary between different LESs. We propose a new simple scheme to assign the dimensionality of the energy landscape from a single molecule time series. We also address the question of what the molecules actually \"feel\" from the underlying landscape at the single molecule level.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Akinori", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c0cp00694g" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21135962" } }, "mesh": [ { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": true }, { "descriptor": "Motion", "descriptor_ui": "D009038", "major_topic": false }, { "descriptor": "Protein Folding", "descriptor_ui": "D017510", "major_topic": false }, { "descriptor": "Protein Unfolding", "descriptor_ui": "D058767", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false }, { "descriptor": "Thermodynamics", "descriptor_ui": "D013816", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jan 28", "date_precision": "day", "issue": "4", "normalized_date": "2011-01-28", "pages": "1395-1406", "proceedings_title": null, "publisher": "", "title": "Physical chemistry chemical physics : PCCP", "volume": "13", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Extracting the underlying effective free energy landscape from single-molecule time series--local equilibrium states and their network.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Preeclampsia is a relatively common pregnancy-related disorder. Both maternal and fetal lives will be endangered if it proceeds unabated. Recently, the placenta-derived anti-angiogenic factors, such as soluble fms-like tyrosine kinase-1 (sFLT1) and soluble endoglin (sENG), have attracted attention in the progression of preeclampsia. Here, we established a unique experimental model to test the role of sFLT1 in preeclampsia using a lentiviral vector-mediated placenta-specific expression system. The model mice showed hypertension and proteinuria during pregnancy, and the symptoms regressed after parturition. Intrauterine growth restriction was also observed. We further showed that pravastatin induced the VEGF-like angiogenic factor placental growth factor (PGF) and ameliorated the symptoms. We conclude that our experimental preeclamptic murine model phenocopies the human case, and the model identifies low-dose statins and PGF as candidates for preeclampsia treatment.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Keiichi", "last_name": "Kumasawa", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Hasuwa", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Saito-Fujita", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Morioka", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Okabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1011293108" }, "pmcid": { "normalized": "PMC3029692" }, "pmid": { "normalized": "21187414" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydroxymethylglutaryl-CoA Reductase Inhibitors", "descriptor_ui": "D019161", "major_topic": false }, { "descriptor": "Injections, Intraperitoneal", "descriptor_ui": "D007274", "major_topic": false }, { "descriptor": "Lentivirus", "descriptor_ui": "D016086", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Placenta", "descriptor_ui": "D010920", "major_topic": false }, { "descriptor": "Placenta Growth Factor", "descriptor_ui": "D000072483", "major_topic": false }, { "descriptor": "Pravastatin", "descriptor_ui": "D017035", "major_topic": false }, { "descriptor": "Pre-Eclampsia", "descriptor_ui": "D011225", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Pregnancy Proteins", "descriptor_ui": "D011257", "major_topic": false }, { "descriptor": "Transduction, Genetic", "descriptor_ui": "D014161", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor Receptor-1", "descriptor_ui": "D040281", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jan 25", "date_precision": "day", "issue": "4", "normalized_date": "2011-01-25", "pages": "1451-1455", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "108", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "CD4+ T regulatory cells (Tregs), which express the Foxp3 transcription factor, play a critical role in the maintenance of immune homeostasis. Here, we show that in mice, Tregs were most abundant in the colonic mucosa. The spore-forming component of indigenous intestinal microbiota, particularly clusters IV and XIVa of the genus Clostridium, promoted Treg cell accumulation. Colonization of mice by a defined mix of Clostridium strains provided an environment rich in transforming growth factor–β and affected Foxp3+ Treg number and function in the colon. Oral inoculation of Clostridium during the early life of conventionally reared mice resulted in resistance to colitis and systemic immunoglobulin E responses in adult mice, suggesting a new therapeutic approach to autoimmunity and allergy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Atarashi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Tanoue", "name": null }, { "creator_type": "author", "first_name": "Tatsuichiro", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Akemi", "last_name": "Imaoka", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Kuwahara", "name": null }, { "creator_type": "author", "first_name": "Yoshika", "last_name": "Momose", "name": null }, { "creator_type": "author", "first_name": "Genhong", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Tadatsugu", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Ivaylo I.", "last_name": "Ivanov", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Umesaki", "name": null }, { "creator_type": "author", "first_name": "Kikuji", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Kenya", "last_name": "Honda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.1198469" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21205640" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anti-Bacterial Agents", "descriptor_ui": "D000900", "major_topic": false }, { "descriptor": "Cecum", "descriptor_ui": "D002432", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Clostridium", "descriptor_ui": "D003013", "major_topic": false }, { "descriptor": "Colitis", "descriptor_ui": "D003092", "major_topic": false }, { "descriptor": "Colon", "descriptor_ui": "D003106", "major_topic": false }, { "descriptor": "Feces", "descriptor_ui": "D005243", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Germ-Free Life", "descriptor_ui": "D005856", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": false }, { "descriptor": "Immunoglobulin E", "descriptor_ui": "D007073", "major_topic": false }, { "descriptor": "Interleukin-10", "descriptor_ui": "D016753", "major_topic": false }, { "descriptor": "Intestinal Mucosa", "descriptor_ui": "D007413", "major_topic": false }, { "descriptor": "Intestine, Small", "descriptor_ui": "D007421", "major_topic": false }, { "descriptor": "Metagenome", "descriptor_ui": "D054892", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred A", "descriptor_ui": "D008805", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Receptors, Pattern Recognition", "descriptor_ui": "D051192", "major_topic": false }, { "descriptor": "Specific Pathogen-Free Organisms", "descriptor_ui": "D013047", "major_topic": false }, { "descriptor": "T-Lymphocytes, Helper-Inducer", "descriptor_ui": "D006377", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jan 21", "date_precision": "day", "issue": "6015", "normalized_date": "2011-01-21", "pages": "337-341", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "331", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Induction of Colonic Regulatory T Cells by Indigenous Clostridium Species.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Metastasis is responsible for most cancer deaths. Here, we show that Aes (or Grg5) gene functions as an endogenous metastasis suppressor. Expression of Aes was decreased in liver metastases compared with primary colon tumors in both mice and humans. Aes inhibited Notch signaling by converting active Rbpj transcription complexes into repression complexes on insoluble nuclear matrix. In tumor cells, Notch signaling was triggered by ligands on adjoining blood vessels, and stimulated transendothelial migration. Genetic depletion of Aes in Apc(Delta716) intestinal polyposis mice caused marked tumor invasion and intravasation that were suppressed by Notch signaling inhibition. These results suggest that inhibition of Notch signaling can be a promising strategy for prevention and treatment of colon cancer metastasis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Fuwa", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Hisahiro", "last_name": "Hosogi", "name": null }, { "creator_type": "author", "first_name": "Yoshiharu", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Hashida", "name": null }, { "creator_type": "author", "first_name": "Arimichi", "last_name": "Takabayashi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Sylvie", "last_name": "Robine", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Kiyoko", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Kakizaki", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Makoto Mark", "last_name": "Taketo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ccr.2010.11.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21251616" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzodiazepinones", "descriptor_ui": "D001570", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Co-Repressor Proteins", "descriptor_ui": "D056970", "major_topic": false }, { "descriptor": "Colonic Neoplasms", "descriptor_ui": "D003110", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Gene Silencing", "descriptor_ui": "D020868", "major_topic": false }, { "descriptor": "HCT116 Cells", "descriptor_ui": "D045325", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoglobulin J Recombination Signal Sequence-Binding Protein", "descriptor_ui": "D051819", "major_topic": false }, { "descriptor": "Intestinal Polyposis", "descriptor_ui": "D044483", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Mutant Strains", "descriptor_ui": "D008817", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false }, { "descriptor": "Nuclear Matrix", "descriptor_ui": "D015530", "major_topic": false }, { "descriptor": "Receptor, Notch1", "descriptor_ui": "D051881", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stromal Cells", "descriptor_ui": "D017154", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transendothelial and Transepithelial Migration", "descriptor_ui": "D057705", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jan 18", "date_precision": "day", "issue": "1", "normalized_date": "2011-01-18", "pages": "125-137", "proceedings_title": null, "publisher": "", "title": "Cancer cell", "volume": "19", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Suppression of colon cancer metastasis by Aes through inhibition of Notch signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dynamics of passage over a saddle is investigated for a quantum system under the effect of time-dependent external field (laser pulse). We utilize the recently developed theories of nonlinear dynamics in the saddle region, and extend them to incorporate both time-dependence of the external field and quantum mechanical effects of the system. Anharmonic couplings and laser fields with any functional form of time dependence are explicitly taken into account. As the theory is based on the Weyl expression of quantum mechanics, interpretation is facilitated by the classical phase space picture, while no \"classical approximation\" is involved. We introduce a quantum reactivity operator to extract the reactive part of the system. In a model system with an optimally controlled laser field for the reaction, it is found that the boundary of the reaction in the phase space, extracted by the reactivity operator, is modulated with time by the effect of the laser field, to \"catch\" the system excited in the reactant region, and then to \"release\" it into the product region. This method provides new insights in understanding the origin of optimal control of chemical reactions by laser fields.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/1.3528937" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21241109" } }, "mesh": [], "publication": { "conference_name": null, "date": "2011 Jan 14", "date_precision": "day", "issue": "2", "normalized_date": "2011-01-14", "pages": "024317", "proceedings_title": null, "publisher": "", "title": "The Journal of chemical physics", "volume": "134", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantum reaction boundary to mediate reactions in laser fields.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The light response of vertebrate visual cells is achieved by light-sensing proteins such as opsin-based pigments as well as signal transduction proteins, including visual arrestin. Previous studies have indicated that the pineal pigment parapinopsin has evolutionally and physiologically important characteristics. Parapinopsin is phylogenetically related to vertebrate visual pigments. However, unlike the photoproduct of the visual pigment rhodopsin, which is unstable, dissociating from its chromophore and bleaching, the parapinopsin photoproduct is stable and does not release its chromophore. Here, we investigated arrestin, which regulates parapinopsin signaling, in the lamprey pineal organ, where parapinopsin and rhodopsin are localized to distinct photoreceptor cells. We found that beta-arrestin, which binds to stimulated G protein-coupled receptors (GPCRs) other than opsin-based pigments, was localized to parapinopsin-containing cells. This result stands in contrast to the localization of visual arrestin in rhodopsin-containing cells. Beta-arrestin bound to cultured cell membranes containing parapinopsin light-dependently and translocated to the outer segments of pineal parapinopsin-containing cells, suggesting that beta-arrestin binds to parapinopsin to arrest parapinopsin signaling. Interestingly, beta-arrestin colocalized with parapinopsin in the granules of the parapinopsin-expressing cell bodies under light illumination. Because beta-arrestin, which is a mediator of clathrin-mediated GPCR internalization, also served as a mediator of parapinopsin internalization in cultured cells, these results suggest that the granules were generated light-dependently by beta-arrestin-mediated internalization of parapinopsins from the outer segments. Therefore, our findings imply that beta-arrestin-mediated internalization is responsible for eliminating the stable photoproduct and restoring cell conditions to the original dark state. Taken together with a previous finding that the bleaching pigment evolved from a non-bleaching pigment, vertebrate visual arrestin may have evolved from a “beta-like” arrestin by losing its clathrin-binding domain and its function as an internalization mediator. Such changes would have followed the evolution of vertebrate visual pigments, which generate unstable photoproducts that independently decay by chromophore dissociation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Emi", "last_name": "Kawano-Yamashita", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Shichida", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Tamotsu", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0016402" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21305016" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arrestins", "descriptor_ui": "D019390", "major_topic": false }, { "descriptor": "beta-Arrestins", "descriptor_ui": "D000071557", "major_topic": false }, { "descriptor": "Lampreys", "descriptor_ui": "D007798", "major_topic": false }, { "descriptor": "Photoreceptor Cells", "descriptor_ui": "D010786", "major_topic": false }, { "descriptor": "Pigments, Biological", "descriptor_ui": "D010860", "major_topic": false }, { "descriptor": "Pineal Gland", "descriptor_ui": "D010870", "major_topic": false }, { "descriptor": "Rhodopsin", "descriptor_ui": "D012243", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011", "date_precision": "year", "issue": "1", "normalized_date": "2011", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "6", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Beta-Arrestin Functionally Regulates the Non-Bleaching Pigment Parapinopsin in Lamprey Pineal.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Atopic dermatitis (AD) is a widely spread cutaneous chronic disease characterised by sensitive reactions (eg. eczema) to normally innocuous elements. Although relatively little is understood about its underlying mechanisms due to its complexity, skin barrier dysfunction has been recognised as a key factor in the development of AD. Skin barrier homeostasis requires tight control of the activity of proteases, called kallikreins (KLKs), whose activity is regulated by a complex network of protein interactions that remains poorly understood despite its pathological importance. Characteristic symptoms of AD include the outbreak of inflammation triggered by external (eg. mechanical and chemical) stimulus and the persistence and aggravation of inflammation even if the initial stimulus disappears. These characteristic symptoms, together with some experimental data, suggest the presence of positive feedback regulation for KLK activity by inflammatory signals. We developed simple mathematical models for the KLK activation system to study the effects of feedback loops and carried out bifurcation analysis to investigate the model behaviours corresponding to inflammation caused by external stimulus. The model analysis confirmed that the hypothesised core model mechanisms capture the essence of inflammation outbreak by a defective skin barrier. Our models predicted the outbreaks of inflammation at weaker stimulus and its longer persistence in AD patients compared to healthy control. We also proposed a novel quantitative indicator for inflammation level by applying principal component analysis to microarray data. The model analysis reproduced qualitative AD characteristics revealed by this indicator. Our results strongly implicate the presence and importance of feedback mechanisms in KLK activity regulation. We further proposed future experiments that may provide informative data to enhance the system-level understanding on the regulatory mechanisms of skin barrier in AD and healthy individuals.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Reiko J.", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Heather A.", "last_name": "Harrington", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0019895" }, "pmcid": { "normalized": "PMC3102059" }, "pmid": { "normalized": "21647431" } }, "mesh": [ { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Dermatitis, Atopic", "descriptor_ui": "D003876", "major_topic": false }, { "descriptor": "Feedback, Physiological", "descriptor_ui": "D025461", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kallikreins", "descriptor_ui": "D007610", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011", "date_precision": "year", "issue": "5", "normalized_date": "2011", "pages": "e19895", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "6", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Skin barrier homeostasis in atopic dermatitis: feedback regulation of kallikrein activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mg(2+) plays important roles in numerous cellular functions. Mitochondria take part in intracellular Mg(2+) regulation and the Mg(2+) concentration in mitochondria affects the synthesis of ATP. However, there are few methods to observe Mg(2+) in mitochondria in intact cells. Here, we have developed a novel Mg(2+)-selective fluorescent probe, KMG-301, that is functional in mitochondria. This probe changes its fluorescence properties solely depending on the Mg(2+) concentration in mitochondria under physiologically normal conditions. Simultaneous measurements using this probe together with a probe for cytosolic Mg(2+), KMG-104, enabled us to compare the dynamics of Mg(2+) in the cytosol and in mitochondria. With this method, carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP)-induced Mg(2+) mobilization from mitochondria to the cytosol was visualized. Although a FCCP-induced decrease in the Mg(2+) concentration in mitochondria and an increase in the cytosol were observed both in differentiated PC12 cells and in hippocampal neurons, the time-courses of concentration changes varied with cell type. Moreover, the relationship between mitochondrial Mg(2+) and Parkinson's disease was analyzed in a cellular model of Parkinson's disease by using the 1-methyl-4-phenylpyridinium ion (MPP(+)). A gradual decrease in the Mg(2+) concentration in mitochondria was observed in response to MPP(+) in differentiated PC12 cells. These results indicate that KMG-301 is useful for investigating Mg(2+) dynamics in mitochondria. All animal procedures to obtain neurons from Wistar rats were approved by the ethical committee of Keio University (permit number is 09106-(1)).", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0023684" }, "pmcid": { "normalized": "PMC3156752" }, "pmid": { "normalized": "21858208" } }, "mesh": [ { "descriptor": "1-Methyl-4-phenylpyridinium", "descriptor_ui": "D015655", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone", "descriptor_ui": "D002259", "major_topic": false }, { "descriptor": "Cation Transport Proteins", "descriptor_ui": "D027682", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cytosol", "descriptor_ui": "D003600", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Ion Transport", "descriptor_ui": "D017136", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Mitochondrial Proteins", "descriptor_ui": "D024101", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": true }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Proton Ionophores", "descriptor_ui": "D061209", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011", "date_precision": "year", "issue": "8", "normalized_date": "2011", "pages": "e23684", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "6", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Newly developed Mg2+-selective fluorescent probe enables visualization of Mg2+ dynamics in mitochondria.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Influenza virus infection causes highly contagious, severe respiratory disorders and gives rise to thousands of deaths every year; however, the efficacy of currently approved defense strategies, including vaccines and neuraminidase inhibitors, is limited because the virus frequently acquires resistance via antigen drift and reassortment. It is therefore important to establish a novel, effective therapeutic strategy that is effective irrespective of viral subtype. Methodology/Principal Findings: Here, we identify the Ras–phosphoinositide 3-kinase (PI3K) signaling pathway as a host-cell regulatory mechanism for influenza virus entry. The binding of Ras to PI3K is specifically involved in clathrin-independent endocytosis, endosomal maturation, and intracellular transport of viruses, which result in decreased infectious efficacy of different subtypes of influenza viruses in cells lacking the Ras–PI3K interaction. Moreover, influenza virus infection indeed triggered Ras activation and subsequent PI3K activation in early endosomes. Conclusions/Significance: Taken together, these results demonstrate that the Ras–PI3K signaling axis acts as a host-oriented mechanism for viral internalization. Given that virus incorporation is a process conserved among virus subtypes and species, this signaling pathway may provide a target for potent, well-tolerated prophylactics and therapeutics against a broad range of viruses.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Tomoe", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Tadaaki", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0016324" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21283725" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": false }, { "descriptor": "Endosomes", "descriptor_ui": "D011992", "major_topic": false }, { "descriptor": "Host-Pathogen Interactions", "descriptor_ui": "D054884", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Orthomyxoviridae", "descriptor_ui": "D009975", "major_topic": false }, { "descriptor": "Phosphatidylinositol 3-Kinases", "descriptor_ui": "D019869", "major_topic": false }, { "descriptor": "ras Proteins", "descriptor_ui": "D018631", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Virus Internalization", "descriptor_ui": "D053586", "major_topic": true } ], "publication": { "conference_name": null, "date": "2011", "date_precision": "year", "issue": "1", "normalized_date": "2011", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "6", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "The Ras–PI3K Signaling Pathway Is Involved in Clathrin-Independent Endocytosis and the Internalization of Influenza Viruses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In vivo environments are highly crowded and inhomogeneous, which may affect reaction processes in cells. In this study we examined the effects of intracellular crowding and an inhomogeneity on the behavior of in vivo reactions by calculating the spectral dimension (d(s)), which can be translated into the reaction rate function. We compared estimates of anomaly parameters obtained from fluorescence correlation spectroscopy (FCS) data with fractal dimensions derived from transmission electron microscopy (TEM) image analysis. FCS analysis indicated that the anomalous property was linked to physiological structure. Subsequent TEM analysis provided an in vivo illustration; soluble molecules likely percolate between intracellular clusters, which are constructed in a self-organizing manner. We estimated a cytoplasmic spectral dimension d(s) to be 1.39 +/- 0.084. This result suggests that in vivo reactions initially run faster than the same reactions in a homogeneous space; this conclusion is consistent with the anomalous character indicated by FCS analysis. We further showed that these results were compatible with our Monte-Carlo simulation in which the anomalous behavior of mobile molecules correlates with the intracellular environment, leading to description as a percolation cluster, as demonstrated using TEM analysis. We confirmed by the simulation that the above-mentioned in vivo like properties are different from those of homogeneously concentrated environments. Additionally, simulation results indicated that crowding level of an environment might affect diffusion rate of reactant. Such knowledge of the spatial information enables us to construct realistic models for in vivo diffusion and reaction systems.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Noriko", "last_name": "Hiroi", "name": null }, { "creator_type": "author", "first_name": "James", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Iba", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Tabira", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Christoph", "last_name": "Flamm", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Gottfried", "last_name": "Kohler", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Funahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fphys.2011.00050" }, "pmcid": { "normalized": "PMC3177084" }, "pmid": { "normalized": "21960972" } }, "mesh": [], "publication": { "conference_name": null, "date": "2011", "date_precision": "year", "issue": "", "normalized_date": "2011", "pages": "50", "proceedings_title": null, "publisher": "", "title": "Frontiers in physiology", "volume": "2", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Physiological environment induces quick response - slow exhaustion reactions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved pleiotropic neuropeptide that functions as a neurotransmitter, neuromodulator and neurotrophic factor. Accumulating evidence implicates PACAP as an important regulator of both central and/or peripheral components of the stress axes, particularly exposure to prolonged or traumatic stress. Indeed, PACAP and its cognate receptors are widely expressed in the brain regions and peripheral tissues that mediate stress-related responses. In the sympathoadrenomedullary system, PACAP is required for sustained epinephrine secretion during metabolic stress. It is likely that PACAP regulates autonomic function and contributes to peripheral homeostasis by maintaining a balance between sympathetic and parasympathetic activity, favoring stimulation of the sympathetic system. Furthermore, PACAP is thought to act centrally on the paraventricular nucleus of the hypothalamus to regulate both the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Intriguingly, PACAP is also active in brain structures that mediate anxiety- and fear-related behaviors, and the expression of PACAP and its receptors are dynamically altered under pathologic conditions. Thus PACAP may influence both hard-wired (genetically determined) stress responses and gene-environment interactions in stress-related psychopathology. This article aims to overview the molecular mechanisms and psychiatric implications of PACAP-dependent stress responses.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Tanida", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.2174/138161211795589382" }, "pmcid": { "normalized": "PMC3179129" }, "pmid": { "normalized": "21524255" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypothalamo-Hypophyseal System", "descriptor_ui": "D007030", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Pituitary-Adrenal System", "descriptor_ui": "D010913", "major_topic": false }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051236", "major_topic": false }, { "descriptor": "Stress, Psychological", "descriptor_ui": "D013315", "major_topic": false }, { "descriptor": "Sympathetic Nervous System", "descriptor_ui": "D013564", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011", "date_precision": "year", "issue": "10", "normalized_date": "2011", "pages": "985-989", "proceedings_title": null, "publisher": "", "title": "Current pharmaceutical design", "volume": "17", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "PACAP is implicated in the stress axes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: We previously developed the DBRF-MEGN (difference-based regulation finding-minimum equivalent gene network) method, which deduces the most parsimonious signed directed graphs (SDGs) consistent with expression profiles of single-gene deletion mutants. However, until the present study, we have not presented the details of the method's algorithm or a proof of the algorithm. Results: We describe in detail the algorithm of the DBRF-MEGN method and prove that the algorithm deduces all of the exact solutions of the most parsimonious SDGs consistent with expression profiles of gene deletion mutants. Conclusions: The DBRF-MEGN method provides all of the exact solutions of the most parsimonious SDGs consistent with expression profiles of gene deletion mutants.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1751-0473-6-12" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21699737" } }, "mesh": [], "publication": { "conference_name": null, "date": "2011", "date_precision": "year", "issue": "", "normalized_date": "2011", "pages": "12", "proceedings_title": null, "publisher": "", "title": "Source Code for Biology and Medicine", "volume": "6", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "A proof of the DBRF-MEGN method, an algorithm for deducing minimum equivalent gene networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Progressive beta-cell insufficiency in the pancreas is a hallmark of both types I and II diabetes, and agents that protect against beta-cell dysfunction are potential drug targets for diabetes mellitus. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a strong secretagogue of insulin from pancreatic islets and is suggested to be involved in physiological blood glucose homeostasis and the pathology of diabetes. Recent studies in genetically engineered animal models have shown that PACAP stimulates pancreatic functions, especially in cooperation with other regulatory factors including glucose. Furthermore, chronic activation of PACAP signaling regulates pancreatic islet mass in a context-dependent manner. Accumulating in vivo and in vitro evidence suggest that PACAP has trophic effects and regulates both proliferation and cell viability of beta-cells and thereby contributes to protection against diabetes. This review focuses on such trophic actions of PACAP on pancreatic beta-cells and discusses the pathophysiological significance of pancreatic PACAP, with the aim to provide information for future development of treatment for diabetes.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12031-010-9424-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20645023" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Insulin Secretion", "descriptor_ui": "D000078790", "major_topic": false }, { "descriptor": "Insulin-Secreting Cells", "descriptor_ui": "D050417", "major_topic": false }, { "descriptor": "Islets of Langerhans", "descriptor_ui": "D007515", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "3-7", "proceedings_title": null, "publisher": "", "title": "Journal of molecular neuroscience : MN", "volume": "43", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Trophic effects of PACAP on pancreatic islets: a mini-review.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Asami", "last_name": "Tanimura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hashimotodani", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21942092" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cannabinoid Receptor Modulators", "descriptor_ui": "D063385", "major_topic": false }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Receptors, Cannabinoid", "descriptor_ui": "D043882", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "704-714", "proceedings_title": null, "publisher": "", "title": "Seikagaku. The Journal of Japanese Biochemical Society", "volume": "83", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "[Mechanisms of endocannabinoid-mediated retrograde modulation of synaptic transmission].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: The purpose of this study is to propose a novel method to depict small calcifications in ultrasound B-mode images using decorrelation of forward scattered waves with no decrease in the frame rate. METHODS: Since the waveform of an ultrasound pulse changes when it passes through a calcification location, the echo waveform from regions behind the calcification is quite different from that without a calcification. This indicates that the existence of a calcification is predictable based upon the waveform difference between adjacent scan lines by calculating cross-correlation coefficients. In addition, a high-intensity echo should return from the calcification itself. Therefore, the proposed method depicts the high-intensity echo positions with posterior low correlation coefficient regions. RESULTS: Eleven of 15 wires 0.2-0.4 mm in diameter were depicted using this method, yielding a sensitivity of 73.3% and a specificity of 100%, even though they might go undetected under clinical inspection of ultrasound B-mode images. CONCLUSION: This study suggests that an US device could perform well in terms of calcification detection.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nagae", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10396-011-0298-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27278422" } }, "mesh": [], "publication": { "conference_name": null, "date": "2011 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "73-80", "proceedings_title": null, "publisher": "", "title": "Journal of medical ultrasonics (2001)", "volume": "38", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Small calcification depiction in ultrasound B-mode images using decorrelation of echoes caused by forward scattered waves.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During the induction of plasticity of dendritic spines, many intracellular signaling pathways are spatially and temporally regulated to co-ordinate downstream cellular processes in different dendritic micron-domains. Recent advent of imaging technology based on fluorescence resonance energy transfer (FRET) has allowed the direct monitoring of the spatiotemporal regulation of signaling activity in spines and dendrites during synaptic plasticity. In particular, the activity of three small GTPase proteins HRas, Cdc42, and RhoA, which share similar structure and mobility on the plasma membrane, displayed different spatial spreading patterns: Cdc42 is compartmentalized in the stimulated spines while RhoA and HRas spread into dendrites over 5-10 mum. These measurements thus provide the basis for understanding the mechanisms underlying the spatiotemporal regulation of signaling activity. Further, using spatiotemporally controlled spine stimulations, some of the roles of signal spreading have been revealed.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryohei", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.conb.2011.02.008" }, "pmcid": { "normalized": "PMC3111059" }, "pmid": { "normalized": "21429735" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "313-321", "proceedings_title": null, "publisher": "", "title": "Current opinion in neurobiology", "volume": "21", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "The mechanisms underlying the spatial spreading of signaling activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sex-determining mechanisms are diverse among animal lineages and can be broadly divided into two major categories: genetic and environmental. In contrast to genetic sex determination (GSD), little is known about the molecular mechanisms underlying environmental sex determination (ESD). The Doublesex (Dsx) genes play an important role in controlling sexual dimorphism in genetic sex-determining organisms such as nematodes, insects, and vertebrates. Here we report the identification of two Dsx genes from Daphnia magna, a freshwater branchiopod crustacean that parthenogenetically produces males in response to environmental cues. One of these genes, designated DapmaDsx1, is responsible for the male trait development when expressed during environmental sex determination. The domain organization of DapmaDsx1 was similar to that of Dsx from insects, which are thought to be the sister group of branchiopod crustaceans. Intriguingly, the molecular basis for sexually dimorphic expression of DapmaDsx1 is different from that of insects. Rather than being regulated sex-specifically at the level of pre-mRNA splicing in the coding region, DapmaDsx1 exhibits sexually dimorphic differences in the abundance of its transcripts. During embryogenesis, expression of DapmaDsx1 was increased only in males and its transcripts were primarily detected in male-specific structures. Knock-down of DapmaDsx1 in male embryos resulted in the production of female traits including ovarian maturation, whereas ectopic expression of DapmaDsx1 in female embryos resulted in the development of male-like phenotypes. Expression patterns of another D. magna Dsx gene, DapmaDsx2, were similar to those of DapmaDsx1, but silencing and overexpression of this gene did not induce any clear phenotypic changes. These results establish DapmaDsx1 as a key regulator of the male phenotype. Our findings reveal how ESD is implemented by selective expression of a fundamental genetic component that is functionally conserved in animals using GSD. We infer that there is an ancient, previously unidentified link between genetic and environmental sex determination.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Taisen", "last_name": "Iguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pgen.1001345" }, "pmcid": { "normalized": "PMC3063754" }, "pmid": { "normalized": "21455482" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "Conserved Sequence", "descriptor_ui": "D017124", "major_topic": false }, { "descriptor": "Daphnia", "descriptor_ui": "D003621", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Environment", "descriptor_ui": "D004777", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Gene Order", "descriptor_ui": "D023061", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "RNA Splicing", "descriptor_ui": "D012326", "major_topic": false }, { "descriptor": "Sequence Alignment", "descriptor_ui": "D016415", "major_topic": false }, { "descriptor": "Sex Determination Processes", "descriptor_ui": "D019849", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "e1001345", "proceedings_title": null, "publisher": "", "title": "PLoS genetics", "volume": "7", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Environmental sex determination in the branchiopod crustacean Daphnia magna: deep conservation of a Doublesex gene in the sex-determining pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In our previous study, we reported that cerulein-induced acute pancreatitis is aggravated in pancreatic beta-cell-specific pituitary adenylate cyclase-activating polypeptide (PACAP) transgenic mice, showing that an increase in pancreatic PACAP is a risk factor for progression of acute pancreatitis. Accordingly, in this study, we examined the progression of cerulein-induced acute pancreatitis in PACAP knockout (KO) mice. Unexpectedly, after cerulein, about 60% of the KO mice showed severe hypothermia below 30 degrees C by 12 h and most of them died within 72 h. In contrast, the remaining KO and wild-type mice showed normothermia with no mortality. Thus, KO mice could be classified into two groups as hypothermic (HT-KO) and normothermic (NT-KO) to cerulein. Only HT-KO mice subsequently showed severe mortality, although both HT-KO and NT-KO mice exhibited similar susceptibility of lungs to cerulein toxicity, comparable to that in wild-type mice. Regarding pancreatitis, HT-KO mice showed ameliorated pancreatic damage without any rise in serum enzyme activities, whereas NT-KO mice exhibited a similar degree of pancreatitis to wild-type mice. Taken together, the present results indicate that lack of pancreatic PACAP did not aggravate, but rather ameliorated, cerulein-induced pancreatitis. In addition, about half of KO mice showed a novel phenotype in which cerulein caused rapid and severe hypothermia, followed by death.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Arimori", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hamagami", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12031-010-9396-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20567937" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Temperature", "descriptor_ui": "D001831", "major_topic": false }, { "descriptor": "Ceruletide", "descriptor_ui": "D002108", "major_topic": false }, { "descriptor": "Hypothermia", "descriptor_ui": "D007035", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Pancreatitis", "descriptor_ui": "D010195", "major_topic": false }, { "descriptor": "Peroxidase", "descriptor_ui": "D009195", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Survival Rate", "descriptor_ui": "D015996", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "8-15", "proceedings_title": null, "publisher": "", "title": "Journal of molecular neuroscience : MN", "volume": "43", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Cerulein-induced acute pancreatitis in PACAP knockout mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Us3 is a serine-threonine protein kinase encoded by herpes simplex virus 1 (HSV-1). We have identified UL47, a major virion protein, as a novel physiological substrate of Us3. In vitro kinase assays and systematic analysis of mutations at putative Us3 phosphorylation sites near the nuclear localization signal of UL47 showed that serine at residue 77 (Ser-77) was required for Us3 phosphorylation of UL47. Replacement of UL47 Ser-77 by alanine produced aberrant accumulation of UL47 at the nuclear rim and impaired the nuclear localization of UL47 in a significant fraction of infected cells. The same defect in UL47 localization was produced by an amino acid substitution in Us3 that inactivated its protein kinase activity. In contrast, a phosphomimetic mutation at UL47 Ser-77 restored wild-type nuclear localization. The UL47 S77A mutation also reduced viral replication in the mouse cornea and the development of herpes stromal keratitis in mice. In addition, UL47 formed a stable complex with Us3 in infected cells, and nuclear localization of Us3 was significantly impaired in the absence of UL47. These results suggested that Us3 phosphorylation of UL47 Ser-77 promoted the nuclear localization of UL47 in cell cultures and played a critical role in viral replication and pathogenesis in vivo. Furthermore, UL47 appeared to be required for efficient nuclear localization of Us3 in infected cells. Therefore, Us3 protein kinase and its substrate UL47 demonstrated a unique regulatory feature in that they reciprocally regulated their subcellular localization in infected cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Zhuoming", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Minowa", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00845-11" }, "pmcid": { "normalized": "PMC3165750" }, "pmid": { "normalized": "21734045" } }, "mesh": [ { "descriptor": "Amino Acid Substitution", "descriptor_ui": "D019943", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Viral", "descriptor_ui": "D015967", "major_topic": true }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mutagenesis, Site-Directed", "descriptor_ui": "D016297", "major_topic": false }, { "descriptor": "Mutant Proteins", "descriptor_ui": "D050505", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Rodent Diseases", "descriptor_ui": "D012376", "major_topic": false }, { "descriptor": "Viral Fusion Proteins", "descriptor_ui": "D014760", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": true } ], "publication": { "conference_name": null, "date": "2011 Sep", "date_precision": "unknown", "issue": "18", "normalized_date": null, "pages": "9599-9613", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "85", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Herpes simplex virus 1 protein kinase Us3 and major tegument protein UL47 reciprocally regulate their subcellular localization in infected cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Inflammasomes are cytosolic protein complexes that stimulate the activation of caspase-1, which in turn induces the secretion of the inflammatory cytokines Interleukin-1beta (IL-1beta) and IL-18. Recent studies have indicated that the inflammasome known as the NOD-like-receptor-family, pyrin domain-containing 3 (NLRP3) inflammasome recognizes several RNA viruses, including the influenza and encephalomyocarditis viruses, whereas the retinoic acid-inducible gene I (RIG-I) inflammasome may detect vesicular stomatitis virus. We demonstrate that measles virus (MV) infection induces caspase-1-dependent IL-1beta secretion in the human macrophage-like cell line THP-1. Gene knockdown experiments indicated that IL-1beta secretion in MV-infected THP-1 cells was mediated by the NLRP3 inflammasome but not the RIG-I inflammasome. MV produces the nonstructural V protein, which has been shown to antagonize host innate immune responses. The recombinant MV lacking the V protein induced more IL-1beta than the parental virus. THP-1 cells stably expressing the V protein suppressed NLRP3 inflammasome-mediated IL-1beta secretion. Furthermore, coimmunoprecipitation assays revealed that the V protein interacts with NLRP3 through its carboxyl-terminal domain. NLRP3 was located in cytoplasmic granular structures in THP-1 cells stably expressing the V protein, but upon inflammasome activation, NLRP3 was redistributed to the perinuclear region, where it colocalized with the V protein. These results indicate that the V protein of MV suppresses NLRP3 inflammasome-mediated IL-1beta secretion by directly or indirectly interacting with NLRP3.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Noritaka", "last_name": "Komune", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ichinohe", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Yanagi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.05942-11" }, "pmcid": { "normalized": "PMC3233149" }, "pmid": { "normalized": "21994456" } }, "mesh": [ { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Evasion", "descriptor_ui": "D057131", "major_topic": true }, { "descriptor": "Inflammasomes", "descriptor_ui": "D058847", "major_topic": false }, { "descriptor": "Interleukin-1beta", "descriptor_ui": "D053583", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Measles virus", "descriptor_ui": "D008459", "major_topic": false }, { "descriptor": "NLR Family, Pyrin Domain-Containing 3 Protein", "descriptor_ui": "D000071199", "major_topic": false }, { "descriptor": "Phosphoproteins", "descriptor_ui": "D010750", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Interaction Mapping", "descriptor_ui": "D025941", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Dec", "date_precision": "unknown", "issue": "24", "normalized_date": null, "pages": "13019-13026", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "85", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Measles virus V protein inhibits NLRP3 inflammasome-mediated interleukin-1beta secretion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Ciona intestinalis protein database (CIPRO) is an integrated protein database for the tunicate species C. intestinalis. The database is unique in two respects: first, because of its phylogenetic position, Ciona is suitable model for understanding vertebrate evolution; and second, the database includes original large-scale transcriptomic and proteomic data. Ciona intestinalis has also been a favorite of developmental biologists. Therefore, large amounts of data exist on its development and morphology, along with a recent genome sequence and gene expression data. The CIPRO database is aimed at collecting those published data as well as providing unique information from unpublished experimental data, such as 3D expression profiling, 2D-PAGE and mass spectrometry-based large-scale analyses at various developmental stages, curated annotation data and various bioinformatic data, to facilitate research in diverse areas, including developmental, comparative and evolutionary biology. For medical and evolutionary research, homologs in humans and major model organisms are intentionally included. The current database is based on a recently developed KH model containing 36 034 unique sequences, but for higher usability it covers 89 683 all known and predicted proteins from all gene models for this species. Of these sequences, more than 10 000 proteins have been manually annotated. Furthermore, to establish a community-supported protein database, these annotations are open to evaluation by users through the CIPRO website. CIPRO 2.5 is freely accessible at http://cipro.ibio.jp/2.5.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Toshinori", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kouki", "last_name": "Yonezawa", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Mineta", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Satou", "name": null }, { "creator_type": "author", "first_name": "Lixy", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Ogasawara", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Mia", "last_name": "Nakachi", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Yaguchi", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Sasakura", "name": null }, { "creator_type": "author", "first_name": "Chisato", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Sera", "name": null }, { "creator_type": "author", "first_name": "Akiyasu C.", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Imanishi", "name": null }, { "creator_type": "author", "first_name": "Hisaaki", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Inaba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nar/gkq1144" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21071393" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Computer Graphics", "descriptor_ui": "D003196", "major_topic": false }, { "descriptor": "Databases, Protein", "descriptor_ui": "D030562", "major_topic": true }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Molecular Sequence Annotation", "descriptor_ui": "D058977", "major_topic": false }, { "descriptor": "Proteome", "descriptor_ui": "D020543", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Systems Integration", "descriptor_ui": "D018511", "major_topic": false }, { "descriptor": "User-Computer Interface", "descriptor_ui": "D014584", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jan", "date_precision": "unknown", "issue": "Database issue", "normalized_date": null, "pages": "D807-814", "proceedings_title": null, "publisher": "", "title": "Nucleic Acids Research", "volume": "39", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "CIPRO 2.5: Ciona intestinalis protein database, a unique integrated repository of large-scale omics data, bioinformatic analyses and curated annotation, with user rating and reviewing functionality.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide widely distributed in the nervous system. Recently, PACAP was shown to be involved in restraint stress-induced corticosterone release and concomitant expression of the genes involved in hypothalamic-pituitary-adrenal (HPA) axis activation. Therefore, in this study, we have addressed the types of stressors and the levels of the HPA axis in which PACAP signaling is involved using mice lacking PACAP (PACAP(-)/(-)). Among four different types of stressors, open-field exposure, cold exposure, ether inhalation, and restraint, the corticosterone response to open-field exposure and restraint, which are categorized as emotional stressors, but not the other two, was markedly attenuated in PACAP(-)/(-) mice. Peripheral administration of corticotropin releasing factor (CRF) or adrenocorticotropic hormone induced corticosterone increase similarly in PACAP(-)/(-) and wild-type mice. In addition, the restraint stress-induced c-Fos expression was significantly decreased in the paraventricular nucleus (PVN) and medial amygdala (MeA), but not the medial prefrontal cortex, in PACAP(-)/(-) mice. In the PVN of PACAP(-)/(-) mice, the stress-induced c-Fos expression was blunted in the CRF neurons. These results suggest that PACAP is critically involved in activation of the MeA and PVN CRF neurons to centrally regulate the HPA axis response to emotional stressors.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Naohiro", "last_name": "Tsukiyama", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Saida", "name": null }, { "creator_type": "author", "first_name": "Michiya", "last_name": "Kakuda", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Tanida", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Tajiri", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Hazama", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.3109/10253890.2010.544345" }, "pmcid": { "normalized": "PMC3128825" }, "pmid": { "normalized": "21438773" } }, "mesh": [ { "descriptor": "Adrenocorticotropic Hormone", "descriptor_ui": "D000324", "major_topic": false }, { "descriptor": "Amygdala", "descriptor_ui": "D000679", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Corticosterone", "descriptor_ui": "D003345", "major_topic": false }, { "descriptor": "Corticotropin-Releasing Hormone", "descriptor_ui": "D003346", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Paraventricular Hypothalamic Nucleus", "descriptor_ui": "D010286", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-fos", "descriptor_ui": "D016760", "major_topic": false }, { "descriptor": "Restraint, Physical", "descriptor_ui": "D012149", "major_topic": false }, { "descriptor": "Stress, Psychological", "descriptor_ui": "D013315", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jul", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "368-375", "proceedings_title": null, "publisher": "", "title": "Stress (Amsterdam, Netherlands)", "volume": "14", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "PACAP centrally mediates emotional stress-induced corticosterone responses in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Apelin, the ligand of the G protein–coupled receptor APJ, is involved in the regulation of cardiovascular functions, fluid homeostasis, and vessel formation. Recent reports indicate that apelin secreted from endothelial cells mediates APJ regulation of blood vessel caliber size; however, the function of apelin in lymphatic vessels is unclear. Here we report that APJ was expressed by human lymphatic endothelial cells and that apelin induced migration and cord formation of lymphatic endothelial cells dose-dependently in vitro. Furthermore, permeability assays demonstrated that apelin stabilizes lymphatic endothelial cells. In vivo, transgenic mice harboring apelin under the control of keratin 14 (K14-apelin) exhibited attenuated UVB-induced edema and a decreased number of CD11b-positive macrophages. Moreover, activation of apelin/APJ signaling inhibited UVB-induced enlargement of lymphatic and blood vessels. Finally, K14-apelin mice blocked the hyperpermeability of lymphatic vessels in inflamed skin. These results indicate that apelin plays a functional role in the stabilization of lymphatic vessels in inflamed tissues and that apelin might be a suitable target for prevention of UVB-induced inflammation.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Mika", "last_name": "Sawane", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kajiya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ajpath.2011.08.024" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21983637" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apelin Receptors", "descriptor_ui": "D000075244", "major_topic": false }, { "descriptor": "Dermatitis", "descriptor_ui": "D003872", "major_topic": false }, { "descriptor": "Edema", "descriptor_ui": "D004487", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphatic Vessels", "descriptor_ui": "D042601", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Ultraviolet Rays", "descriptor_ui": "D014466", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "2691-2697", "proceedings_title": null, "publisher": "", "title": "The American Journal of Pathology", "volume": "179", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Apelin Attenuates UVB-Induced Edema and Inflammation by Promoting Vessel Function.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hyperphosphorylation of tau protein (tau) causes neurodegenerative diseases such as Alzheimer's disease (AD). Recent studies of the physiological correlation between tau and alpha-synuclein (alpha-SN) have demonstrated that: (a) phosphorylated tau is also present in Lewy bodies, which are cytoplasmic inclusions formed by abnormal aggregation of alpha-SN; and (b) the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) increases the phosphorylation of tau as well as the protein level of alpha-SN in cultured neuronal cells, and also in mice. However, the molecular mechanism responsible for the alpha-SN-mediated hyperphosphorylation of tau remains to be elucidated. In this in vitro study, we found that: (a) alpha-SN directly stimulates the phosphorylation of tau by glycogen synthase kinase-3beta (GSK-3beta), (b) alpha-SN forms a heterotrimeric complex with tau and GSK-3beta, and (c) the nonamyloid beta component (NAC) domain and an acidic region of alpha-SN are responsible for the stimulation of GSK-3beta-mediated tau phosphorylation. Thus, it is concluded that alpha-SN functions as a connecting mediator for tau and GSK-3beta, resulting in GSK-3beta-mediated tau phosphorylation. Because the expression of alpha-SN is promoted by oxidative stress, the accumulation of alpha-SN induced by such stress may directly induce the hyperphosphorylation of tau by GSK-3beta. Furthermore, we found that heat shock protein 70 (Hsp70) suppresses the alpha-SN-induced phosphorylation of tau by GSK-3beta through its direct binding to alpha-SN, suggesting that Hsp70 acts as a physiological suppressor of alpha-SN-mediated tau hyperphosphorylation. These results suggest that the cellular level of Hsp70 may be a novel therapeutic target to counteract alpha-SN-mediated tau phosphorylation in the initial stage of neurodegenerative disease.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Minori", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Kagiya", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Ichikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1742-4658.2011.08389.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21985244" } }, "mesh": [ { "descriptor": "alpha-Synuclein", "descriptor_ui": "D051844", "major_topic": false }, { "descriptor": "beta-Synuclein", "descriptor_ui": "D051846", "major_topic": false }, { "descriptor": "gamma-Synuclein", "descriptor_ui": "D051845", "major_topic": false }, { "descriptor": "Glycogen Synthase Kinase 3", "descriptor_ui": "D038362", "major_topic": false }, { "descriptor": "Glycogen Synthase Kinase 3 beta", "descriptor_ui": "D000071679", "major_topic": false }, { "descriptor": "HSP70 Heat-Shock Proteins", "descriptor_ui": "D018840", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Dec", "date_precision": "unknown", "issue": "24", "normalized_date": null, "pages": "4895-4904", "proceedings_title": null, "publisher": "", "title": "The FEBS journal", "volume": "278", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Stimulatory effect of alpha-synuclein on the tau-phosphorylation by GSK-3beta.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Post-weaning social isolation in rodents induces behavioral alterations, including hyperlocomotion, depression- and anxiety-like behaviors, aggression, and learning and memory deficits. These behavioral abnormalities may be related to the core symptoms in patients with neuropsychiatric disorders, such as schizophrenia and depression. In view of the recent studies that the group II metabotropic glutamate receptor (mGluR2/3) is involved in neuropsychiatric disorders, the present study examined the effect of isolation rearing on the binding of the mGluR2/3 antagonist [(3)H]LY341495 to mGluR2/3 in the mouse brain by in vitro autoradiography. The [(3)H]LY341495 binding in the prefrontal cortex, cerebral cortical layers I-III and hippocampus was significantly increased by rearing in social isolation while the binding in other brain regions was not altered. A saturation binding study of hippocampal membranes from isolation-reared mice revealed that the B(max) value increased significantly without any changes in the K(d) value. Moreover, the mGluR2/3 antagonist MGS0039 (1.0mg/kg, intraperitoneally) decreased the immobility time of isolation-reared mice in the forced swim test. These results suggest that isolation rearing causes an increase in mGluR2/3 densities in the prefrontal cortex and hippocampus and that the increased receptor function may contribute to pathogenic mechanisms for depression-like behavior of the isolation-reared mice.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Washida", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Onoe", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Chaki", "name": null }, { "creator_type": "author", "first_name": "Atsuro", "last_name": "Nakazato", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuropharm.2010.10.009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20970439" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false }, { "descriptor": "Social Isolation", "descriptor_ui": "D012934", "major_topic": true }, { "descriptor": "Xanthenes", "descriptor_ui": "D014966", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Feb-Mar", "date_precision": "unknown", "issue": "2-3", "normalized_date": null, "pages": "397-404", "proceedings_title": null, "publisher": "", "title": "Neuropharmacology", "volume": "60", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Increased binding of cortical and hippocampal group II metabotropic glutamate receptors in isolation-reared mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "From hormonal secretion to gene expression, multicellular dynamics are rich in oscillatory regulation. When organized in space and time, periodic cell-cell signaling can give rise to long-range coordination of gene expression and cell movement in tissues. Lack of synchrony of the oscillations on the other hand can serve as a source of initial divergence of cell fate in stem cells. How properties of individual cells can account for collective rhythmic behaviors at the tissue level remains elusive in most cases. Recently, studies in chemical reactions, synthetic gene circuits, yeast and social amoeba Dictyostelium have greatly enhanced our view of collective oscillations in cell populations. From these relatively simple systems, a unified view of how excitable and oscillatory regulations could be tuned and coupled to give rise to tissue-level oscillations is emerging. The review focuses on recent progress in cyclic adenosine monophosphate oscillations in Dictyostelium and highlights similarities and differences with other systems. We will see that the autonomy of single-cell level oscillations and different ways in which cells are coupled influence how group-level information can be encoded in collective oscillations.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Keita", "last_name": "Kamino", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1440-169x.2011.01266.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21585355" } }, "mesh": [ { "descriptor": "Cells", "descriptor_ui": "D002477", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 May", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "503-517", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "53", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Collective oscillations in developing cells: insights from simple systems.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Colorectal cancer is the second most common cancer, and is the third leading cause of cancer-related death in Japan. The majority of these deaths is attributable to liver metastasis. Recent studies have provided increasing evidence that the chemokine-chemokine receptor system is a potential mechanism of tumor metastasis via multiple complementary actions: (a) by promoting cancer cell migration, invasion, survival and angiogenesis; and (b) by recruiting distal stromal cells (i.e., myeloid bone marrow-derived cells) to indirectly facilitate tumor invasion and metastasis. Here, we discuss recent preclinical and clinical data supporting the view that chemokine pathways are potential therapeutic targets for liver metastasis of colorectal cancer.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Teppei", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Yoshiro", "last_name": "Itatani", "name": null }, { "creator_type": "author", "first_name": "Hisahiro", "last_name": "Hosogi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Teruaki", "last_name": "Fujishita", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Matsusue", "name": null }, { "creator_type": "author", "first_name": "Koya", "last_name": "Hida", "name": null }, { "creator_type": "author", "first_name": "Gaku", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Kae", "last_name": "Okoshi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Junichiro", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Makoto Mark", "last_name": "Taketo", "name": null }, { "creator_type": "author", "first_name": "Yoshiharu", "last_name": "Sakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10147-011-0307-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21847533" } }, "mesh": [ { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Chemokines", "descriptor_ui": "D018925", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": false }, { "descriptor": "Molecular Targeted Therapy", "descriptor_ui": "D058990", "major_topic": false }, { "descriptor": "Myeloid Cells", "descriptor_ui": "D022423", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Receptors, Chemokine", "descriptor_ui": "D019707", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Oct", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "464-472", "proceedings_title": null, "publisher": "", "title": "International journal of clinical oncology", "volume": "16", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular mechanisms of liver metastasis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent findings have focused attention on the molecular consequences of the microenvironment in tumor progression, but events occurring in cancer cells themselves in response to their ambient conditions remain obscure. Here, we identify receptor activator of nuclear factor kappaB ligand (RANKL) as a microenvironment-specific factor essential for tumorigenesis in vivo, using head and neck squamous cell carcinoma (HNSCC) as a model. In human HNSCC tissues, RANKL is abundantly expressed, and its expression level correlates with the histological grade of differentiation. RANKL levels are significantly higher in poorly differentiated SCCs than in well or moderately differentiated SCCs. In contrast, all HNSCC cell lines tested displayed extremely low RANKL expression; however, RANKL is efficiently up-regulated when these cell lines are inoculated in the head and neck region of mice. RANKL expression is restored in a microenvironment-specific manner, and cannot be observed when the cells are inoculated in the hindlimbs. Forced expression of RANKL compensates for tumor growth in the hindlimb milieu, promotes epithelial mesenchymal transition, and induces tumor angiogenesis, in a manner independent of vascular endothelial growth factor (VEGF). These results implicate RANKL expression causatively in tumor growth and progression in HNSCC in vivo. RANKL may provide a novel functional marker for biological malignancy and a therapeutic target based on the specific nature of the microenvironment.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tamaki", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Totsuka", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Shindoh", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ajpath.2011.02.003" }, "pmcid": { "normalized": "PMC3124328" }, "pmid": { "normalized": "21561598" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": true }, { "descriptor": "Epithelial-Mesenchymal Transition", "descriptor_ui": "D058750", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Head and Neck Neoplasms", "descriptor_ui": "D006258", "major_topic": false }, { "descriptor": "Hindlimb", "descriptor_ui": "D006614", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Precancerous Conditions", "descriptor_ui": "D011230", "major_topic": false }, { "descriptor": "RANK Ligand", "descriptor_ui": "D053245", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "2845-2856", "proceedings_title": null, "publisher": "", "title": "The American journal of pathology", "volume": "178", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "RANKL expression specifically observed in vivo promotes epithelial mesenchymal transition and tumor progression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Marijuana smoking elicits various psychoactive effects through type 1 cannabinoid receptors (CB(1)Rs) in the brain. CB(1)R is a seven-transmembrane domain. G(i/o)-protein coupled receptors, and is expressed throughout the central nervous system including the hippocampus, cerebellum, striatum and cerebral cortex. Endogenous ligands for CB(1)R (endocannabinoids) are lipid in nature, and anandamide and 2-arachidonoylglycerol (2-AG) are considered to be the two major endocannabinoids. Endocannabinoids are known to function as retrograde messengers at synapses. Endocannabinoids are released from postsynaptic neurons in activity-dependent manners, and retrogradely activate presynaptic CB(1)Rs, resulting in short-term or long-term suppression of synaptic transmission. Endocannabinoid-mediated retrograde signaling is observed at various brain regions and considered as a general mechanism of synaptic modulation in the brain. Endocannabinoid release is triggered by postsynaptic Ca2+ elevation or activation of G(q/11)-protein coupled receptors. Recent studies have demonstrated that 2-AG mediates retrograde signaling at synapses in the brain. Endocannabinoid-mediated retrograde signaling is involved in long-term synaptic plasticity in several brain regions. At behavioral level, endocannabinoid signaling is known to be involved in hippocampus-, amygdala- and cerebellum-dependent learning and memory.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Hashimotodani", "name": null }, { "creator_type": "author", "first_name": "Asami", "last_name": "Tanimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21800700" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cannabinoid Receptor Modulators", "descriptor_ui": "D063385", "major_topic": false }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": true }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jun", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "105-109", "proceedings_title": null, "publisher": "", "title": "Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology", "volume": "31", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "[Lipid mediator endocannabinoids in modulating synaptic transmission].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "RATIONALE: Metabotropic glutamate (mGlu) 2/3 receptor agonists inhibit amphetamine- and phencyclidine-induced hyperlocomotion. The mechanism for the antipsychotic effect of mGlu2/3 receptor agonists was studied in a hypoglutamatergic model, but not a hyperdopaminergic model. OBJECTIVES: To study the mechanism for the antipsychotic effect of the agonist in the hyperdopaminergic model, this study examined the effects of the selective mGlu2/3 receptor agonist MGS0028 on methamphetamine-induced hyperlocomotion and the increases in extracellular levels of serotonin, dopamine, noradrenaline, and glutamate in the prefrontal cortex and nucleus accumbens of mice. RESULTS: Systemic administration of MGS0028 attenuated methamphetamine-induced hyperlocomotion in a dose-dependent manner. Microdialysis studies showed that MGS0028 significantly inhibited methamphetamine-induced increases in the extracellular serotonin, but not dopamine and noradrenaline, levels in the prefrontal cortex, and it did not affect methamphetamine-induced increases in the extracellular amine levels in the nucleus accumbens. Methamphetamine did not affect the glutamate release in the prefrontal cortex and nucleus accumbens. Local application of MGS0028 into the prefrontal cortex also attenuated methamphetamine-induced hyperlocomotion and increases in the extracellular serotonin levels in the prefrontal cortex. Moreover, MGS0028 did not affect methamphetamine-induced hyperlocomotion in the mice pretreated with p-chlorophenylalanine, a serotonin synthesis inhibitor. CONCLUSIONS: Activation of prefrontal mGlu2/3 receptors inhibits the psychomotor stimulant effect of methamphetamine in mice, and the prefrontal serotonergic system may be involved in this effect. The finding provides evidence that prefrontal mGlu2/3 receptors are functionally coupled with the serotonergic system.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Hiramatsu", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Chaki", "name": null }, { "creator_type": "author", "first_name": "Atsuro", "last_name": "Nakazato", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Onoe", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00213-011-2295-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21487651" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bridged Bicyclo Compounds", "descriptor_ui": "D001643", "major_topic": false }, { "descriptor": "Dicarboxylic Acids", "descriptor_ui": "D003998", "major_topic": false }, { "descriptor": "Hyperkinesis", "descriptor_ui": "D006948", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Methamphetamine", "descriptor_ui": "D008694", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred Strains", "descriptor_ui": "D008815", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Oct", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "443-452", "proceedings_title": null, "publisher": "", "title": "Psychopharmacology", "volume": "217", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Activation of metabotropic glutamate 2/3 receptors attenuates methamphetamine-induced hyperlocomotion and increase in prefrontal serotonergic neurotransmission.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Due to the complex cellular heterogeneity of the central nervous system (CNS), it is relatively difficult to reliably obtain molecular descriptions with cell-type specificity. In particular, comparative analysis of epigenetic regulation or molecular profiles is hampered by the lack of adequate methodology for selective purification of defined cell populations from CNS tissue. Here, we developed a direct purification strategy of neural nuclei from CNS tissue based on fluorescence-activated cell sorting (FACS). We successfully fractionated nuclei from complex tissues such as brain, spinal cord, liver, kidney, and skeletal muscle extruded mechanically or chemically, and fractionated nuclei were structurally maintained and contained nucleoproteins and nuclear DNA/RNA. We collected sufficient numbers of nuclei from neurons and oligodendrocytes using FACS with immunolabeling for nucleoproteins or from genetically labeled transgenic mice. In addition, the use of Fab fragments isolated from papain antibody digests, which effectively enriched the specialized cell populations, significantly enhanced the immunolabeling efficacy. This methodology can be applied to a wide variety of heterogeneous tissues and is crucial for understanding the cell-specific information about chromatin dynamics, nucleoproteins, protein-DNA/RNA interactions, and transcriptomes retained in the nucleus, such as non-coding RNAs.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Seiji", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Saiwai", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Kumamaru", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/jcp.22365" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20717962" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cell Separation", "descriptor_ui": "D002469", "major_topic": false }, { "descriptor": "Central Nervous System", "descriptor_ui": "D002490", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neuroglia", "descriptor_ui": "D009457", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "552-558", "proceedings_title": null, "publisher": "", "title": "Journal of cellular physiology", "volume": "226", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Flow cytometric sorting of neuronal and glial nuclei from central nervous system tissue.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herpes simplex virus 1 (HSV-1) Us3 protein kinase phosphorylates threonine at position 887 (Thr-887) in the cytoplasmic tail of envelope glycoprotein B (gB) in infected cells. This phosphorylation downregulates cell surface expression of gB and plays a role in viral pathogenesis in the mouse herpes stromal keratitis model. In the present study, we demonstrated that Us3 phosphorylation of gB Thr-887 upregulated the accumulation of endocytosed gB from the surfaces of infected cells. We also showed that two motifs in the cytoplasmic tail of gB, tyrosine at position 889 (Tyr-889) and dileucines at positions 871 and 872, were required for efficient downregulation of gB cell surface expression and upregulation of accumulation of endocytosed gB in infected cells. A systematic analysis of mutations in these three sequences in gB suggested that the expression of gB on the surfaces of infected cells was downregulated in part by the increase in the accumulation of endocytosed gB, which was coordinately and tightly regulated by the three gB trafficking signals. Tyr-889 appeared to be of predominant importance in regulating the intracellular transport of gB and was linked to HSV-1 neurovirulence in mice following intracerebral infection. These observations support the hypothesis that HSV-1 evolved the three gB sequences for proper regulation of gB intracellular transport and that this regulation plays a critical role in diverse aspects of HSV-1 pathogenesis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takahiko", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Minowa", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Kakimoto", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.02314-10" }, "pmcid": { "normalized": "PMC3126194" }, "pmid": { "normalized": "21389132" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "DNA Mutational Analysis", "descriptor_ui": "D004252", "major_topic": false }, { "descriptor": "Encephalitis, Herpes Simplex", "descriptor_ui": "D020803", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Viral Envelope Proteins", "descriptor_ui": "D014759", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virulence", "descriptor_ui": "D014774", "major_topic": false }, { "descriptor": "Virulence Factors", "descriptor_ui": "D037521", "major_topic": false }, { "descriptor": "Virus Internalization", "descriptor_ui": "D053586", "major_topic": true } ], "publication": { "conference_name": null, "date": "2011 May", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "5003-5015", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "85", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of the herpes simplex virus 1 Us3 kinase phosphorylation site and endocytosis motifs in the intracellular transport and neurovirulence of envelope glycoprotein B.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The poly(ADP-ribose) polymerases (PARPs) participate in many biological and pathological processes. Here we report that the PARP-13 shorter isoform (ZAPS), rather than the full-length protein (ZAP), was selectively induced by 5'-triphosphate-modified RNA (3pRNA) and functioned as a potent stimulator of interferon responses in human cells mediated by the RNA helicase RIG-I. ZAPS associated with RIG-I to promote the oligomerization and ATPase activity of RIG-I, which led to robust activation of IRF3 and NF-kappaB transcription factors. Disruption of the gene encoding ZAPS resulted in impaired induction of interferon-alpha (IFN-alpha), IFN-beta and other cytokines after viral infection. These results indicate that ZAPS is a key regulator of RIG-I signaling during the innate antiviral immune response, which suggests its possible use as a therapeutic target for viral control.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Sumio", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Souichi", "last_name": "Shiratori", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Yamato", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kameyama", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Kitatsuji", "name": null }, { "creator_type": "author", "first_name": "Fumi", "last_name": "Kashigi", "name": null }, { "creator_type": "author", "first_name": "Showhey", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Shoichiro", "last_name": "Kameoka", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Fujikura", "name": null }, { "creator_type": "author", "first_name": "Taisho", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Tatsuaki", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Kazumata", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Junji", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Asaka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Tadaaki", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Takaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ni.1963" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21102435" } }, "mesh": [ { "descriptor": "Avulavirus Infections", "descriptor_ui": "D045463", "major_topic": false }, { "descriptor": "DEAD Box Protein 58", "descriptor_ui": "D000071457", "major_topic": false }, { "descriptor": "DEAD-box RNA Helicases", "descriptor_ui": "D053487", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": false }, { "descriptor": "Interferon Type I", "descriptor_ui": "D007370", "major_topic": false }, { "descriptor": "Newcastle disease virus", "descriptor_ui": "D009522", "major_topic": false }, { "descriptor": "Orthomyxoviridae", "descriptor_ui": "D009975", "major_topic": false }, { "descriptor": "Orthomyxoviridae Infections", "descriptor_ui": "D009976", "major_topic": false }, { "descriptor": "Poly I-C", "descriptor_ui": "D011070", "major_topic": false }, { "descriptor": "Poly(ADP-ribose) Polymerases", "descriptor_ui": "D011065", "major_topic": false }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false }, { "descriptor": "Receptors, Immunologic", "descriptor_ui": "D011971", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "37-44", "proceedings_title": null, "publisher": "", "title": "Nature immunology", "volume": "12", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A light-scattering signal, which is sensitive to cellular/subcellular structural integrity, is a potential indicator of brain tissue viability because metabolic energy is used in part to maintain the structure of cells. We previously observed a unique triphasic scattering change (TSC) at a certain time after oxygen/glucose deprivation for blood-free rat brains; TSC almost coincided with the cerebral adenosine triphosphate (ATP) depletion. We examine whether such TSC can be observed in the presence of blood in vivo, for which transcranial diffuse reflectance measurement is performed for rat brains during hypoxia induced by nitrogen gas inhalation. At a certain time after hypoxia, diffuse reflectance intensity in the near-infrared region changes in three phases, which is shown by spectroscopic analysis to be due to scattering change in the tissue. During hypoxia, rats are reoxygenated at various time points. When the oxygen supply is started before TSC, all rats survive, whereas no rats survive when the oxygen supply is started after TSC. Survival is probabilistic when the oxygen supply is started during TSC, indicating that the period of TSC can be regarded as a critical time zone for rescuing the brain. The results demonstrate that light scattering signal can be an indicator of brain tissue reversibility.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Satoko", "last_name": "Kawauchi", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Uozumi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nawashiro", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kikuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1117/1.3542046" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21361705" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Diagnosis, Computer-Assisted", "descriptor_ui": "D003936", "major_topic": false }, { "descriptor": "Hypoxia-Ischemia, Brain", "descriptor_ui": "D020925", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Nephelometry and Turbidimetry", "descriptor_ui": "D009391", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Therapy, Computer-Assisted", "descriptor_ui": "D013813", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "027002", "proceedings_title": null, "publisher": "", "title": "Journal of biomedical optics", "volume": "16", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Light-scattering signal may indicate critical time zone to rescue brain tissue after hypoxia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intercellular surface tension is a key variable in understanding cellular mechanics. However, conventional methods are not well suited for measuring the absolute magnitude of intercellular surface tension because these methods require determination of the effective viscosity of the whole cell, a quantity that is difficult to measure. In this study, we present a novel method for estimating the intercellular surface tension at single-cell resolution. This method exploits the cytoplasmic flow that accompanies laser-induced cell fusion when the pressure difference between cells is large. Because the cytoplasmic viscosity can be measured using well-established technology, this method can be used to estimate the absolute magnitudes of tension. We applied this method to two-cell-stage embryos of the nematode Caenorhabditis elegans and estimated the intercellular surface tension to be in the 30-90 microN m(-1) range. Our estimate was in close agreement with cell-medium surface tensions measured at single-cell resolution.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1088/1478-3975/8/6/064001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22146596" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Cell Fusion", "descriptor_ui": "D002459", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": true }, { "descriptor": "Surface Tension", "descriptor_ui": "D013500", "major_topic": false }, { "descriptor": "Viscosity", "descriptor_ui": "D014783", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "064001", "proceedings_title": null, "publisher": "", "title": "Physical biology", "volume": "8", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Estimating intercellular surface tension by laser-induced cell fusion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A framework recently developed for the extraction of a dynamic reaction coordinate to mediate reactions buried in a multidimensional Langevin equation is extended to the generalized Langevin equations without a priori assumption of the forms of the potential (in general, nonlinearly coupled systems) and the friction kernel. The equation of motion with memory effect can be transformed into an equation without memory at the cost of an increase in the dimensionality of the system, and hence the theoretical framework developed for the (nonlinear) Langevin formulation can be generalized to the non-Markovian process with colored noise. It is found that the increased dimension can be physically interpreted as effective modes of the fluctuating environment. As an illustrative example, we apply this theory to a multidimensional generalized Langevin equation for motion on the Muller-Brown potential surface with an exponential friction kernel. Numerical simulations find a boundary between the highly reactive region and the less reactive region in the space of initial conditions. The location of the boundary is found to depend significantly on both the memory kernel and the nonlinear couplings. The theory extracts a reaction coordinate whose sign determines the fate of the reaction taking into account thermally fluctuating environments, memory effect, and nonlinearities. It is found that the location of the boundary of reactivity is satisfactorily reproduced as the zero of the statistical average of the new reaction coordinate, which is an analytical functional of both the original position coordinates and velocities of the system, and of the properties of the environment.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c0cp00543f" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20963208" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": true }, { "descriptor": "Nonlinear Dynamics", "descriptor_ui": "D017711", "major_topic": false }, { "descriptor": "Probability", "descriptor_ui": "D011336", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Dec 21", "date_precision": "day", "issue": "47", "normalized_date": "2010-12-21", "pages": "15382-15391", "proceedings_title": null, "publisher": "", "title": "Physical chemistry chemical physics : PCCP", "volume": "12", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic reaction coordinate in thermally fluctuating environment in the framework of the multidimensional generalized Langevin equations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "LRRK2, the causal molecule of familial Parkinson's disease, is expressed strongly by one of the B cell subsets, B-2 cells, but not by the other subset, B-1 cells, in the mouse peritoneal cavity, spleen, and peripheral blood. Bone marrow pre-B cells or T cells exhibited little LRRK2 expression. LRRK2 expression was dramatically downregulated upon activation of B-2 cells with various types of stimulation. These results suggest that LRRK2, whose true function has not yet been clarified, may play some important role(s) in the development and function of B cells, particularly the maintenance of B-2 cells in a resting status.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Eshima", "name": null }, { "creator_type": "author", "first_name": "Sadahiro", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Obata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jneuroim.2010.07.021" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20728949" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B-Lymphocyte Subsets", "descriptor_ui": "D016175", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Ionomycin", "descriptor_ui": "D015759", "major_topic": false }, { "descriptor": "Ionophores", "descriptor_ui": "D007476", "major_topic": false }, { "descriptor": "Leucine-Rich Repeat Serine-Threonine Protein Kinase-2", "descriptor_ui": "D000071158", "major_topic": false }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "NF-kappaB-Inducing Kinase", "descriptor_ui": "D000097782", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Tetradecanoylphorbol Acetate", "descriptor_ui": "D013755", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Dec 15", "date_precision": "day", "issue": "1-2", "normalized_date": "2010-12-15", "pages": "123-128", "proceedings_title": null, "publisher": "", "title": "Journal of neuroimmunology", "volume": "229", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "LRRK2 is expressed in B-2 but not in B-1 B cells, and downregulated by cellular activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The prevalence of type 2 diabetes is increasing dramatically throughout the world. Recently, dipeptidyl peptidase 4 (DPP4) was identified as a potential antidiabetes target. Many DPP4 inhibitors, such as sitagliptin and vildagliptin, have been developed and marketed, but superior therapeutic agents are still required. Therefore, we have developed new methodology for screening of DPP4 inhibitors. Absorption-based measurements with para-nitroaniline or fluorescence-based measurements with the coumarin derivative 7-amino-4-methylcoumarin are often used for the screening of protease inhibitors, including DPP4 inhibitors, but these strategies are not sufficiently sensitive because of interfering background absorption and fluorescence, thus giving rise to many false-positive and false-negative results. Therefore, we have designed and synthesised a novel DPP4 probe (Gly-Pro-BCD-Tb; Gly=glycine, Pro=proline, andBCD defines the backbone of the probe comprising an aniline derivative as on/off switch, a 7-amino-4-methyl-2(1H)-quinolinone (cs-124) as antenna moiety, and a diethylenetriamine-N,N,N',N'',N''-pentaacetic acid (DTPA) as chelator moiety, Tb=terbium) for time-resolved fluorescence (TRF) measurements. TRF measurements with Gly-Pro-BCD-Tb showed high sensitivity and reliability in the inhibitory assay relative to Gly-Pro-MCA (MCA=4-methylcoumarin-7-amide), a conventional fluorescence probe for DPP4. Further, we employed our probe for high-throughput DPP4 inhibitor screening with 3841 randomly selected compounds and found that epibestatin, an epimer of bestatin (a well-known anticancer drug and general aminopeptidase inhibitor), showed dose-dependent DPP4 inhibitory activity. Interestingly, bestatin did not exhibit DPP4 inhibitory activity. We believe that this screening system will be useful for the discovery of DPP4 inhibitors with novel structural scaffolds.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuyasu", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Minegishi", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/chem.201001077" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20938933" } }, "mesh": [ { "descriptor": "Diabetes Mellitus, Type 2", "descriptor_ui": "D003924", "major_topic": false }, { "descriptor": "Dipeptides", "descriptor_ui": "D004151", "major_topic": false }, { "descriptor": "Dipeptidyl Peptidase 4", "descriptor_ui": "D018819", "major_topic": false }, { "descriptor": "Dipeptidyl-Peptidase IV Inhibitors", "descriptor_ui": "D054873", "major_topic": false }, { "descriptor": "Leucine", "descriptor_ui": "D007930", "major_topic": false }, { "descriptor": "Metalloproteins", "descriptor_ui": "D008667", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Terbium", "descriptor_ui": "D013725", "major_topic": false }, { "descriptor": "Thermodynamics", "descriptor_ui": "D013816", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Dec 3", "date_precision": "day", "issue": "45", "normalized_date": "2010-12-03", "pages": "13479-13486", "proceedings_title": null, "publisher": "", "title": "Chemistry (Weinheim an der Bergstrasse, Germany)", "volume": "16", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "A time-resolved fluorescence probe for dipeptidyl peptidase 4 and its application in inhibitor screening.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Based on the findings that the azo functional group has excellent properties as the hypoxia-sensor moiety, we developed hypoxia-sensitive near-infrared fluorescent probes in which a large fluorescence increase is triggered by the cleavage of an azo bond. The probes were used for fluorescence imaging of hypoxic cells and real-time monitoring of ischemia in the liver and kidney of live mice.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuki", "last_name": "Kiyose", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Daihi", "last_name": "Oushiki", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Kajimura", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Nishimatsu", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Yamane", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Yasunobu", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja105937q" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20979363" } }, "mesh": [ { "descriptor": "Acute Disease", "descriptor_ui": "D000208", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Azo Compounds", "descriptor_ui": "D001391", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypoxia", "descriptor_ui": "D000860", "major_topic": false }, { "descriptor": "Ischemia", "descriptor_ui": "D007511", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Spectroscopy, Near-Infrared", "descriptor_ui": "D019265", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Nov 17", "date_precision": "day", "issue": "45", "normalized_date": "2010-11-17", "pages": "15846-15848", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "132", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Hypoxia-sensitive fluorescent probes for in vivo real-time fluorescence imaging of acute ischemia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Excess administration of glutamate is known to induce Ca(2+) overload in neurons, which is the first step in excitotoxicity. Although some reports have suggested a role for Mg(2+) in the excitotoxicity, little is known about its actual contribution. To investigate the role of Mg(2+) in the excitotoxicity, we simultaneously measured intracellular Ca(2+) and Mg(2+), using fluorescent dyes, Fura red, a fluorescent Ca(2+) probe, and KMG-104, a highly selective fluorescent Mg(2+) probe developed by our group, respectively. Administration of 100 muM glutamate supplemented with 10 muM glycine to rat hippocampal neurons induced an increase in intracellular Mg(2+) concentration ([Mg(2+)](i)). Extracellular Mg(2+) was not required for this glutamate-induced increase in [Mg(2+)](i), and no increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) or [Mg(2+)](i) was observed in neurons in nominally Ca(2+)-free medium. Application of 5 muM carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP), an uncoupler of mitochondrial inner membrane potential, also elicited increases in [Ca(2+)](i) and [Mg(2+)](i). Subsequent administration of glutamate and glycine following FCCP treatment did not induce a further increase in [Mg(2+)](i) but did induce an additive increase in [Ca(2+)](i). Moreover, the glutamate-induced increase in [Mg(2+)](i) was observed only in mitochondria localized areas. These results support the idea that glutamate is able to induced Mg(2+) efflux from mitochondria to the cytosol. Furthermore, pretreatment with Ru360, an inhibitor of the mitochondrial Ca(2+) uniporter, prevented this [Mg(2+)](i) increase. These results indicate that glutamate-induced increases in [Mg(2+)](i) result from the Mg(2+) release from mitochondria and that Ca(2+) accumulation in the mitochondria is required for this Mg(2+) release.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/jnr.22467" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20740499" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neurotoxins", "descriptor_ui": "D009498", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Nov 1", "date_precision": "day", "issue": "14", "normalized_date": "2010-11-01", "pages": "3125-3132", "proceedings_title": null, "publisher": "", "title": "Journal of neuroscience research", "volume": "88", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Glutamate-induced calcium increase mediates magnesium release from mitochondria in rat hippocampal neurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Drosophila Sarah (sra) gene encodes a regulator of the Ca2+/calmodulin-dependent protein phosphatase, calcineurin, and plays an essential role in various biological processes. Here, we describe a novel role of sra in Drosophila male courtship behavior. sra null mutant males have reduced courtship activity. This reduced activity can be rescued by expressing sra in the mushroom bodies (MBs), brain structures important for memory formation and storage in Drosophila. In addition, overexpressing sra in the MBs, and transiently overexpressing sra during adulthood, inhibits male courtship. Our results indicate that a specific amount of sra in the MBs is required for wildtype male courtship activity.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Aigaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/wnr.0b013e32833eaade" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20736865" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Calcineurin", "descriptor_ui": "D019703", "major_topic": false }, { "descriptor": "Calcium-Binding Proteins", "descriptor_ui": "D002135", "major_topic": false }, { "descriptor": "Courtship", "descriptor_ui": "D003380", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mushroom Bodies", "descriptor_ui": "D024521", "major_topic": false }, { "descriptor": "Sexual Behavior, Animal", "descriptor_ui": "D012726", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Oct 27", "date_precision": "day", "issue": "15", "normalized_date": "2010-10-27", "pages": "985-988", "proceedings_title": null, "publisher": "", "title": "Neuroreport", "volume": "21", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "The Drosophila calcineurin regulator, Sarah, is involved in male courtship.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herpes simplex virus-1 (HSV-1), the prototype of the alpha-herpesvirus family, causes life-long infections in humans. Although generally associated with various mucocutaneous diseases, HSV-1 is also involved in lethal encephalitis. HSV-1 entry into host cells requires cellular receptors for both envelope glycoproteins B (gB) and D (gD). However, the gB receptors responsible for its broad host range in vitro and infection of critical targets in vivo remain unknown. Here we show that non-muscle myosin heavy chain IIA (NMHC-IIA), a subunit of non-muscle myosin IIA (NM-IIA), functions as an HSV-1 entry receptor by interacting with gB. A cell line that is relatively resistant to HSV-1 infection became highly susceptible to infection by this virus when NMHC-IIA was overexpressed. Antibody to NMHC-IIA blocked HSV-1 infection in naturally permissive target cells. Furthermore, knockdown of NMHC-IIA in the permissive cells inhibited HSV-1 infection as well as cell-cell fusion when gB, gD, gH and gL were coexpressed. Cell-surface expression of NMHC-IIA was markedly and rapidly induced during the initiation of HSV-1 entry. A specific inhibitor of myosin light chain kinase, which regulates NM-IIA by phosphorylation, reduced the redistribution of NMHC-IIA as well as HSV-1 infection in cell culture and in a murine model for herpes stromal keratitis. NMHC-IIA is ubiquitously expressed in various human tissues and cell types and, therefore, is implicated as a functional gB receptor that mediates broad HSV-1 infectivity both in vitro and in vivo. The identification of NMHC-IIA as an HSV-1 entry receptor and the involvement of NM-IIA regulation in HSV-1 infection provide an insight into HSV-1 entry and identify new targets for antiviral drug development.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Suenaga", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kozuka-Hata", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Minowa", "name": null }, { "creator_type": "author", "first_name": "Hiroomi", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Arase", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kawaoka", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nature09420" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20944748" } }, "mesh": [ { "descriptor": "Adsorption", "descriptor_ui": "D000327", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Azepines", "descriptor_ui": "D001381", "major_topic": false }, { "descriptor": "Cell Fusion", "descriptor_ui": "D002459", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "CHO Cells", "descriptor_ui": "D016466", "major_topic": false }, { "descriptor": "Cricetinae", "descriptor_ui": "D006224", "major_topic": false }, { "descriptor": "Cricetulus", "descriptor_ui": "D003412", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "HL-60 Cells", "descriptor_ui": "D018922", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myosin-Light-Chain Kinase", "descriptor_ui": "D009219", "major_topic": false }, { "descriptor": "Naphthalenes", "descriptor_ui": "D009281", "major_topic": false }, { "descriptor": "Nonmuscle Myosin Type IIA", "descriptor_ui": "D024507", "major_topic": false }, { "descriptor": "Receptors, Virus", "descriptor_ui": "D011991", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Envelope Proteins", "descriptor_ui": "D014759", "major_topic": false }, { "descriptor": "Virus Internalization", "descriptor_ui": "D053586", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Oct 14", "date_precision": "day", "issue": "7317", "normalized_date": "2010-10-14", "pages": "859-862", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "467", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Non-muscle myosin IIA is a functional entry receptor for herpes simplex virus-1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Helicobacter pylori CagA bacterial oncoprotein plays a critical role in gastric carcinogenesis. Upon delivery into epithelial cells, CagA causes loss of polarity and activates aberrant Erk signaling. We show that CagA-induced Erk activation results in senescence and mitogenesis in nonpolarized and polarized epithelial cells, respectively. In nonpolarized epithelial cells, Erk activation results in oncogenic stress, up-regulation of the p21Waf1/Cip1 cyclin-dependent kinase inhibitor, and induction of senescence. In polarized epithelial cells, CagA-driven Erk signals prevent p21Waf1/Cip1 expression by activating a guanine nucleotide exchange factor–H1–RhoA–RhoA-associated kinase–c-Myc pathway. The microRNAs miR-17 and miR-20a, induced by c-Myc, are needed to suppress p21Waf1/Cip1 expression. CagA also drives an epithelial-mesenchymal transition in polarized epithelial cells. These findings suggest that CagA exploits a polarity-signaling pathway to induce oncogenesis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Murata-Kamiya", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Hatakeyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1084/jem.20100602" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20855497" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, Bacterial", "descriptor_ui": "D000942", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p21", "descriptor_ui": "D050759", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": true }, { "descriptor": "Epithelial-Mesenchymal Transition", "descriptor_ui": "D058750", "major_topic": false }, { "descriptor": "Genes, myc", "descriptor_ui": "D016259", "major_topic": false }, { "descriptor": "Helicobacter Infections", "descriptor_ui": "D016481", "major_topic": false }, { "descriptor": "Helicobacter pylori", "descriptor_ui": "D016480", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Sep 27", "date_precision": "day", "issue": "10", "normalized_date": "2010-09-27", "pages": "2157-2174", "proceedings_title": null, "publisher": "", "title": "The Journal of Experimental Medicine", "volume": "207", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Conversion of Helicobacter pylori CagA from senescence inducer to oncogenic driver through polarity-dependent regulation of p21.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We systematically synthesized bioluminogenic substrates bearing an amino group on benzothiazole, quinoline, naphthalene, and coumarin scaffolds. They emit bioluminescence in various colors: red, orange, yellow, and green. An amino-substituted coumarylluciferin derivative, coumarylaminoluciferin (CAL), showed the shortest bioluminescence wavelength among substrates reported so far. Further, the fluorescence of CAL did not exhibit solvatochromism, which suggests that its bioluminescence is not susceptible to environmental factors. We applied CAL as an energy-donor substrate for a bioluminescence resonance energy transfer (BRET) system with click beetle red luciferase (CBRluc), a mutant of firefly luciferase, as the energy-donor enzyme and yellow fluorescent protein (YFP) as the energy-acceptor fluorophore, and obtained a clearly bimodal bioluminescence spectrum. Stable bioluminescence that is not influenced by environmental factors is highly desirable for reliable measurements in biological assays.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hideo", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Sasakura", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/asia.201000219" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20661993" } }, "mesh": [ { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Benzothiazoles", "descriptor_ui": "D052160", "major_topic": false }, { "descriptor": "Coumarins", "descriptor_ui": "D003374", "major_topic": false }, { "descriptor": "Firefly Luciferin", "descriptor_ui": "D049454", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": true }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Luminescent Agents", "descriptor_ui": "D049408", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Naphthalenes", "descriptor_ui": "D009281", "major_topic": false }, { "descriptor": "Quinolines", "descriptor_ui": "D011804", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Sep 3", "date_precision": "day", "issue": "9", "normalized_date": "2010-09-03", "pages": "2053-2061", "proceedings_title": null, "publisher": "", "title": "Chemistry, an Asian journal", "volume": "5", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of luciferin analogues bearing an amino group and their application as BRET donors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human embryonic stem cells (hESCs), unlike mouse ones (mESCs), are vulnerable to apoptosis upon dissociation. Here, we show that the apoptosis, which is of a nonanoikis type, is caused by ROCK-dependent hyperactivation of actomyosin and efficiently suppressed by the myosin inhibitor Blebbistatin. The actomyosin hyperactivation is triggered by the loss of E-cadherin-dependent intercellular contact and also observed in dissociated mouse epiblast-derived pluripotent cells but not in mESCs. We reveal that Abr, a unique Rho-GEF family factor containing a functional Rac-GAP domain, is an indispensable upstream regulator of the apoptosis and ROCK/myosin hyperactivation. Rho activation coupled with Rac inhibition is induced in hESCs upon dissociation, but not in Abr-depleted hESCs or mESCs. Furthermore, artificial Rho or ROCK activation with Rac inhibition restores the vulnerability of Abr-depleted hESCs to dissociation-induced apoptosis. Thus, the Abr-dependent \"Rho-high/Rac-low\" state plays a decisive role in initiating the dissociation-induced actomyosin hyperactivation and apoptosis in hESCs.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Ohgushi", "name": null }, { "creator_type": "author", "first_name": "Michiru", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Aramaki", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Tokushige", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Hidetaka", "last_name": "Suga", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Toshimasa", "last_name": "Ishizaki", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Suemori", "name": null }, { "creator_type": "author", "first_name": "Shuh", "last_name": "Narumiya", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stem.2010.06.018" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20682448" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": true }, { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Extracellular Space", "descriptor_ui": "D005110", "major_topic": false }, { "descriptor": "Germ Layers", "descriptor_ui": "D005855", "major_topic": false }, { "descriptor": "GTPase-Activating Proteins", "descriptor_ui": "D020690", "major_topic": false }, { "descriptor": "Guanine Nucleotide Exchange Factors", "descriptor_ui": "D020662", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Myosins", "descriptor_ui": "D009218", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "rac GTP-Binding Proteins", "descriptor_ui": "D020744", "major_topic": false }, { "descriptor": "rho-Associated Kinases", "descriptor_ui": "D054460", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2010 Aug 6", "date_precision": "day", "issue": "2", "normalized_date": "2010-08-06", "pages": "225-239", "proceedings_title": null, "publisher": "", "title": "Cell stem cell", "volume": "7", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular pathway and cell state responsible for dissociation-induced apoptosis in human pluripotent stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: To develop a novel diagnostic method for the assessment of drug efficacy in chronic myeloid leukemia (CML) patients individually, we generated a biosensor that enables the evaluation of BCR-ABL kinase activity in living cells using the principle of fluorescence resonance energy transfer (FRET). EXPERIMENTAL DESIGN: To develop FRET-based biosensors, we used CrkL, the most characteristic substrate of BCR-ABL, and designed a protein in which CrkL is sandwiched between Venus, a variant of YFP, and enhanced cyan fluorescent protein, so that CrkL intramolecular binding of the SH2 domain to phosphorylated tyrosine (Y207) increases FRET efficiency. After evaluation of the properties of this biosensor by comparison with established methods including Western blotting and flow cytometry, BCR-ABL activity and its response to drugs were examined in CML patient cells. RESULTS: After optimization, we obtained a biosensor that possesses higher sensitivity than that of established techniques with respect to measuring BCR-ABL activity and its suppression by imatinib. Thanks to its high sensitivity, this biosensor accurately gauges BCR-ABL activity in relatively small cell numbers and can also detect <1% minor drug-resistant populations within heterogeneous ones. We also noticed that this method enabled us to predict future onset of drug resistance as well as to monitor the disease status during imatinib therapy, using patient cells. CONCLUSION: In consideration of its quick and practical nature, this method is potentially a promising tool for the prediction of both current and future therapeutic responses in individual CML patients, which will be surely beneficial for both patients and clinicians.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuaki", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Stephanie", "last_name": "Darmanin", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Tobiume", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Asaka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/1078-0432.ccr-10-0548" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20670950" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Benzamides", "descriptor_ui": "D001549", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cell Separation", "descriptor_ui": "D002469", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fusion Proteins, bcr-abl", "descriptor_ui": "D016044", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Imatinib Mesylate", "descriptor_ui": "D000068877", "major_topic": false }, { "descriptor": "Leukemia, Myelogenous, Chronic, BCR-ABL Positive", "descriptor_ui": "D015464", "major_topic": false }, { "descriptor": "Luminescent Agents", "descriptor_ui": "D049408", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Piperazines", "descriptor_ui": "D010879", "major_topic": false }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Aug 1", "date_precision": "day", "issue": "15", "normalized_date": "2010-08-01", "pages": "3964-3975", "proceedings_title": null, "publisher": "", "title": "Clinical cancer research : an official journal of the American Association for Cancer Research", "volume": "16", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "A novel FRET-based biosensor for the measurement of BCR-ABL activity and its response to drugs in living cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nonlinear dynamics around a rank-one saddle is investigated in a high energy regime above the reaction threshold. The transition state (TS) is considered as a surface of a \"point of no return\" through which all reactive trajectories pass only once in the process of climbing over the saddle before being captured in the product state. A no-return TS ceases to exist above a certain high energy regime. However, even at high energies where the no-return TS can no longer exist, it is shown that \"an impenetrable barrier\" in the phase space robustly persists, which acts as a boundary between reactive and nonreactive trajectories. This implies that we can yet predict the fate of reactions even when the no-return TS may not exist. As an example, we show the analysis of dynamical systems theory for a hydrogen atom in crossed electric and magnetic fields.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physrevlett.105.048304" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20867892" } }, "mesh": [], "publication": { "conference_name": null, "date": "2010 Jul 23", "date_precision": "day", "issue": "4", "normalized_date": "2010-07-23", "pages": "048304", "proceedings_title": null, "publisher": "", "title": "Physical review letters", "volume": "105", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Robust existence of a reaction boundary to separate the fate of a chemical reaction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A framework to calculate the rate constants of condensed phase chemical reactions of manybody systems is presented without relying on the concept of transition state. The theory is based on a framework we developed recently adopting a multidimensional underdamped Langevin equation in the region of a rank-one saddle. The theory provides a reaction coordinate expressed as an analytical nonlinear functional of the position coordinates and velocities of the system (solute), the friction constants, and the random force of the environment (solvent). Up to moderately high temperature, the sign of the reaction coordinate can determine the final destination of the reaction in a thermally fluctuating media, irrespective of what values the other (nonreactive) coordinates may take. In this paper, it is shown that the reaction probability is analytically derived as the probability of the reaction coordinate being positive, and that the integration with the Boltzmann distribution of the initial conditions leads to the exact reaction rate constant when the local equilibrium holds and the quantum effect is negligible. Because of analytical nature of the theory taking into account all nonlinear effects and their combination with fluctuation and dissipation, the theory naturally provides us with the firm mathematical foundation of the origin of the reactivity of the reaction in a fluctuating media.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/b922596j" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20544104" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Hot Temperature", "descriptor_ui": "D006358", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Nonlinear Dynamics", "descriptor_ui": "D017711", "major_topic": true }, { "descriptor": "Probability", "descriptor_ui": "D011336", "major_topic": false }, { "descriptor": "Solutions", "descriptor_ui": "D012996", "major_topic": false }, { "descriptor": "Solvents", "descriptor_ui": "D012997", "major_topic": false }, { "descriptor": "Statistical Distributions", "descriptor_ui": "D016008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jul 21", "date_precision": "day", "issue": "27", "normalized_date": "2010-07-21", "pages": "7636-7647", "proceedings_title": null, "publisher": "", "title": "Physical chemistry chemical physics : PCCP", "volume": "12", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Nonlinear dynamical effects on reaction rates in thermally fluctuating environments.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nonlinear dynamics in the passage over a rank-one saddle is investigated as a function of temperature in the presence of stochastic, thermal fluctuation. The analyses are based on a framework we developed recently adopting a multidimensional underdamped Langevin equation (without any assumption for the form of the potential of mean force). The framework can in principle provide a single coordinate to enable us to predict the final destination of the reaction in a thermally fluctuating media. At each temperature, the preciseness or the error of the reaction coordinate is evaluated in capturing the true reaction dynamics at different levels of approximations. By using the Muller-Brown potential as an illustrative example, it is found that a hierarchy of dynamical structure exists in the region of a rank-one saddle, in which the crossing dynamics qualitatively changes as the temperature increases. We discuss the mechanism of how the reaction coordinate persists, which provides a boundary of the reaction to divide the phase space into the reactive and the nonreactive regions, even in the presence of thermal fluctuation.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/b922080a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20544103" } }, "mesh": [], "publication": { "conference_name": null, "date": "2010 Jul 21", "date_precision": "day", "issue": "27", "normalized_date": "2010-07-21", "pages": "7626-7635", "proceedings_title": null, "publisher": "", "title": "Physical chemistry chemical physics : PCCP", "volume": "12", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Hierarchy of reaction dynamics in a thermally fluctuating environment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mice lacking the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) (PACAP(-/-)) display behavioral abnormalities, and genetic variants of the genes encoding PACAP are associated with schizophrenia. Clinical studies show that environmental factors, besides genetic factors, play a key role in etiology of many psychiatric disorders. This study examined the effects of environmental factors such as short-term social isolation and an enriched environment on behavioral abnormalities of PACAP(-/-) mice. Rearing in isolation for 2-weeks from 4-weeks old induced hyperlocomotion and aggressive behaviors in the PACAP(-/-) mice without affecting the behavioral performance of the wild-type controls. Adult PACAP(-/-) mice showed not only hyperactivity, jumping behavior, and depression-like behavior, but also decreased social interaction. These abnormal behaviors were improved by rearing for 4-weeks in an early enriched environment (from 4-weeks old), although the deficits of prepulse inhibition (PPI) were not influenced by the enriched condition. In contrast, rearing for 4-weeks in late enriched environment (from 8-weeks old) did not affect the hyperactivity and jumping behaviors in the PACAP(-/-) mice. These results suggest that abnormal behaviors except PPI deficits in PACAP(-/-) mice depend on the environmental factors during the early stages of development.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Ishihama", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbr.2010.02.009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20144662" } }, "mesh": [ { "descriptor": "Age Factors", "descriptor_ui": "D000367", "major_topic": false }, { "descriptor": "Aggression", "descriptor_ui": "D000374", "major_topic": false }, { "descriptor": "Analysis of Variance", "descriptor_ui": "D000704", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anxiety", "descriptor_ui": "D001007", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Exploratory Behavior", "descriptor_ui": "D005106", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Sensory Gating", "descriptor_ui": "D055139", "major_topic": false }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": true }, { "descriptor": "Social Environment", "descriptor_ui": "D012931", "major_topic": true }, { "descriptor": "Social Isolation", "descriptor_ui": "D012934", "major_topic": true }, { "descriptor": "Swimming", "descriptor_ui": "D013550", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jun 19", "date_precision": "day", "issue": "2", "normalized_date": "2010-06-19", "pages": "274-280", "proceedings_title": null, "publisher": "", "title": "Behavioural brain research", "volume": "209", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Environmental factors during early developmental period influence psychobehavioral abnormalities in adult PACAP-deficient mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the social amoebae Dictyostelium discoideum, periodic synthesis and release of extracellular cyclic adenosine 3',5'-monophosphate (cAMP) guide cell aggregation and commitment to form fruiting bodies. It is unclear whether these oscillations are an intrinsic property of individual cells or if they exist only as a population-level phenomenon. Here, we showed by live-cell imaging of intact cell populations that pulses originate from a discrete location despite constant exchange of cells to and from the region. In a perfusion chamber, both isolated single cells and cell populations switched from quiescence to rhythmic activity depending on the concentration of extracellular cAMP. A quantitative analysis showed that stochastic pulsing of individual cells below the threshold concentration of extracellular cAMP plays a critical role in the onset of collective behavior.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Thomas", "last_name": "Gregor", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Noritaka", "last_name": "Masaki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.1183415" }, "pmcid": { "normalized": "PMC3120019" }, "pmid": { "normalized": "20413456" } }, "mesh": [ { "descriptor": "3',5'-Cyclic-AMP Phosphodiesterases", "descriptor_ui": "D015105", "major_topic": false }, { "descriptor": "Adenylyl Cyclases", "descriptor_ui": "D000262", "major_topic": false }, { "descriptor": "Cell Aggregation", "descriptor_ui": "D002449", "major_topic": false }, { "descriptor": "Cell Count", "descriptor_ui": "D002452", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Cyclic AMP-Dependent Protein Kinases", "descriptor_ui": "D017868", "major_topic": false }, { "descriptor": "Cytosol", "descriptor_ui": "D003600", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Periodicity", "descriptor_ui": "D010507", "major_topic": false }, { "descriptor": "Protozoan Proteins", "descriptor_ui": "D015800", "major_topic": false }, { "descriptor": "Quorum Sensing", "descriptor_ui": "D053038", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stochastic Processes", "descriptor_ui": "D013269", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 May 21", "date_precision": "day", "issue": "5981", "normalized_date": "2010-05-21", "pages": "1021-1025", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "328", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "The onset of collective behavior in social amoebae.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Sonogashira-Hagihara coupling reactions of 2,6-diiodopyridine and cis-3,6-diethynyl-3,6-dimethoxycyclohexa-1,4-diene or cis-9,10-diethynyl-9,10-dimethoxy-9,10-dihydroanthracene gave macrocyclic compounds having alternating 2,6-diethynylpyridine and 3,6-dimethoxycyclohexa-1,4-diene segments. Transformation of the C(3)-symmetric 2,6-diethynylpyridine-based cyclotrimer was efficiently achieved using tin-mediated reductive aromatization under mild conditions.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Michiyasu", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Senda", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kowada", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jo1006202" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20420401" } }, "mesh": [ { "descriptor": "Alkynes", "descriptor_ui": "D000480", "major_topic": false }, { "descriptor": "Crystallography, X-Ray", "descriptor_ui": "D018360", "major_topic": false }, { "descriptor": "Macrocyclic Compounds", "descriptor_ui": "D047028", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 May 21", "date_precision": "day", "issue": "10", "normalized_date": "2010-05-21", "pages": "3537-3540", "proceedings_title": null, "publisher": "", "title": "The Journal of organic chemistry", "volume": "75", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis of strained pyridine-containing cyclyne via reductive aromatization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The reaction of carbonyl-ene-nitrile compounds with propargyl carboxylates in the presence of a catalytic amount of PtCl(2) afforded the alpha-alkylidene-N-furylimines with high stereoselectivities.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masahito", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/b924752a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20442903" } }, "mesh": [ { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Imines", "descriptor_ui": "D007097", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Nitriles", "descriptor_ui": "D009570", "major_topic": false }, { "descriptor": "Platinum Compounds", "descriptor_ui": "D017671", "major_topic": false }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false }, { "descriptor": "Vinyl Compounds", "descriptor_ui": "D014753", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 May 21", "date_precision": "day", "issue": "19", "normalized_date": "2010-05-21", "pages": "3366-3368", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "46", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Atom-efficient synthesis of alpha-alkylidene-N-furylimines via catalytic vinylcarbene-transfer reactions to carbonyl-ene-nitrile compounds.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intra- and intermolecular covalent cross-linking between collagen fibrils, catalyzed by lysyl oxidase (LOX), determines the mechanical properties of connective tissues; however, mechanisms that regulate the collagen cross-linking according to tissue specificity are not well understood. Here we show that periostin, a secretory protein in the dense connective tissues, promotes the activation of LOX. Previous studies showed that periostin null mice exhibit reduced collagen cross-linking in their femurs, periosteum, infarcted myocardium, and tendons. Presently, we showed that active LOX protein, formed by cleavage of its propeptide by bone morphogenetic protein-1 (BMP-1), was decreased in calvarial osteoblast cells derived from periostin null mice. Overexpression of periostin promoted the proteolytic cleavage of the propeptide, which increased the amount of active LOX protein. The results of co-immunoprecipitation and solid phase binding assays revealed that periostin interacted with BMP-1. Furthermore, this interaction probably resulted in enhanced deposition of BMP-1 on the extracellular matrix, suggesting that this enhanced deposition would lead to cleavage of the propeptide of LOX. Thus, we demonstrated that periostin supported BMP-1-mediated proteolytic activation of LOX on the extracellular matrix, which promoted collagen cross-linking.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Maruhashi", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Kii", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kudo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m109.088864" }, "pmcid": { "normalized": "PMC2857065" }, "pmid": { "normalized": "20181949" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Morphogenetic Protein 1", "descriptor_ui": "D055395", "major_topic": false }, { "descriptor": "Cell Adhesion Molecules", "descriptor_ui": "D015815", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Collagen", "descriptor_ui": "D003094", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Osteoblasts", "descriptor_ui": "D010006", "major_topic": false }, { "descriptor": "Protein Precursors", "descriptor_ui": "D011498", "major_topic": false }, { "descriptor": "Protein-Lysine 6-Oxidase", "descriptor_ui": "D008249", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Apr 23", "date_precision": "day", "issue": "17", "normalized_date": "2010-04-23", "pages": "13294-13303", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "285", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Interaction between periostin and BMP-1 promotes proteolytic activation of lysyl oxidase.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Axonal branching is thought to be regulated not only by genetically defined programs but also by neural activity in the developing nervous system. Here we investigated the role of pre- and postsynaptic activity in axon branching in the thalamocortical (TC) projection using organotypic coculture preparations of the thalamus and cortex. Individual TC axons were labeled with enhanced yellow fluorescent protein by transfection into thalamic neurons. To manipulate firing activity, a vector encoding an inward rectifying potassium channel (Kir2.1) was introduced into either thalamic or cortical cells. Firing activity was monitored with multielectrode dishes during culturing. We found that axon branching was markedly suppressed in Kir2.1-overexpressing thalamic cells, in which neural activity was silenced. Similar suppression of TC axon branching was also found when cortical cell activity was reduced by expressing Kir2.1. These results indicate that both pre- and postsynaptic activity is required for TC axon branching during development.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akito", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Hayano", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.0900613107" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20368417" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Gene Silencing", "descriptor_ui": "D020868", "major_topic": false }, { "descriptor": "Gene Transfer Techniques", "descriptor_ui": "D018014", "major_topic": false }, { "descriptor": "Models, Neurological", "descriptor_ui": "D008959", "major_topic": false }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Potassium Channels, Inwardly Rectifying", "descriptor_ui": "D024661", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Thalamus", "descriptor_ui": "D013788", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Apr 20", "date_precision": "day", "issue": "16", "normalized_date": "2010-04-20", "pages": "7562-7567", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "107", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of pre- and postsynaptic activity in thalamocortical axon branching.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A novel lanthanide probe was designed, synthesized, and employed for a sensitive and reliable assay of acrolein based on time-resolved luminescence measurement, which suppresses the background signal of serum.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masataka", "last_name": "Togashi", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Kazuei", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Yasunobu", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ol1002219" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20232900" } }, "mesh": [ { "descriptor": "Acrolein", "descriptor_ui": "D000171", "major_topic": false }, { "descriptor": "Blood Chemical Analysis", "descriptor_ui": "D001774", "major_topic": false }, { "descriptor": "High-Throughput Screening Assays", "descriptor_ui": "D057166", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lanthanoid Series Elements", "descriptor_ui": "D028581", "major_topic": false }, { "descriptor": "Luminescent Agents", "descriptor_ui": "D049408", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": true }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Apr 16", "date_precision": "day", "issue": "8", "normalized_date": "2010-04-16", "pages": "1704-1707", "proceedings_title": null, "publisher": "", "title": "Organic letters", "volume": "12", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Sensitive detection of acrolein in serum using time-resolved luminescence.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The efficacy of therapeutic angiogenesis for revascularization in ischemia using genes, proteins, and cells has been established. For further improvement, processes allowing enlargement of the luminal cavity to facilitate efficient blood flow need to be facilitated. Recently, we found that expression of APJ and its specific ligand, apelin, is seen in endothelial cells when angiogenesis is taking place during embryogenesis. Apelin-deficient mice are viable but have narrow intersomitic vessels during embryogenesis and narrow blood vessels in the trachea and skin after birth. Apelin induces the formation of larger cords of endothelial cells, mainly mediated by cell-cell aggregation, resulting in the generation of larger blood vessels. Here we report that transgenic overexpression of apelin in keratinocytes induces enlarged but not leaky blood vessels in the dermis. In the hind limb ischemia model, apelin together with vascular endothelial growth factor (VEGF) effectively induced functional vessels larger than with VEGF alone. Endogenous apelin is required for the suppression of VEGF-, histamine-, or inflammation-induced vascular hyperpermeability. Apelin inhibited the down-modulation of vascular endothelial-cadherin by VEGF, resulting in suppression of hyperpermeability. Our results suggest apelin efficacy for therapeutic angiogenesis.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1182/blood-2009-07-232306" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20185589" } }, "mesh": [ { "descriptor": "Adipokines", "descriptor_ui": "D054392", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, CD", "descriptor_ui": "D015703", "major_topic": false }, { "descriptor": "Apelin", "descriptor_ui": "D000073861", "major_topic": false }, { "descriptor": "Blood Vessels", "descriptor_ui": "D001808", "major_topic": false }, { "descriptor": "Cadherin 5", "descriptor_ui": "D000099152", "major_topic": false }, { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": false }, { "descriptor": "Capillary Permeability", "descriptor_ui": "D002199", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Edema", "descriptor_ui": "D004487", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Gene Transfer Techniques", "descriptor_ui": "D018014", "major_topic": false }, { "descriptor": "Hindlimb", "descriptor_ui": "D006614", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Ischemia", "descriptor_ui": "D007511", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neovascularization, Physiologic", "descriptor_ui": "D018919", "major_topic": true }, { "descriptor": "Perfusion", "descriptor_ui": "D010477", "major_topic": false }, { "descriptor": "Recovery of Function", "descriptor_ui": "D020127", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor A", "descriptor_ui": "D042461", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Apr 15", "date_precision": "day", "issue": "15", "normalized_date": "2010-04-15", "pages": "3166-3174", "proceedings_title": null, "publisher": "", "title": "Blood", "volume": "115", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Apelin induces enlarged and nonleaky blood vessels for functional recovery from ischemia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reactive oxygen species (ROS) operate as signaling molecules under various physiological conditions, and overproduction of ROS is involved in the pathogenesis of many diseases. Therefore, fluorescent probes for visualizing ROS are promising tools with which to uncover the molecular mechanisms of physiological and pathological processes and might also be useful for diagnosis. Here we describe a novel fluorescence probe, FOSCY-1, operating in the physiologically favorable near-infrared region. The probe consists of two differentially ROS-reactive cyanine dyes connected by a linker; reaction of the more susceptible dye with ROS releases intramolecular fluorescence quenching of the less susceptible dye. We successfully applied this probe to detect ROS produced by HL60 cells and porcine neutrophils and for imaging oxidative stress in a mouse model of peritonitis.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Daihi", "last_name": "Oushiki", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja910090v" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20136129" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carbocyanines", "descriptor_ui": "D002232", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neutrophils", "descriptor_ui": "D009504", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Peritonitis", "descriptor_ui": "D010538", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Spectroscopy, Near-Infrared", "descriptor_ui": "D019265", "major_topic": false }, { "descriptor": "Swine", "descriptor_ui": "D013552", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Mar 3", "date_precision": "day", "issue": "8", "normalized_date": "2010-03-03", "pages": "2795-2801", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "132", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Development and application of a near-infrared fluorescence probe for oxidative stress based on differential reactivity of linked cyanine dyes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The photopigment melanopsin has been suggested to act as a dominant photoreceptor in nonvisual photoreception including resetting of the circadian clock (entrainment), direct tuning or masking of vital status (activity, sleep/wake cycles, etc.), and the pupillary light reflex (PLR). Pituitary adenylate cyclase-activating polypeptide (PACAP) is exclusively coexpressed with melanopsin in a small subset of retinal ganglion cells and is predicted to be involved extensively in these responses; however, there were inconsistencies in the previous reports, and its functional role has not been well understood. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that PACAP-deficient mice exhibited severe dysfunctions of entrainment in a time-dependent manner. The abnormalities in the mutant mice were intensity-dependent in phase delay and duration-dependent in phase advance. The knockout mice also displayed blunted masking, which was dependent on lighting conditions, but not completely lost. The dysfunctions of masking in the mutant mice were recovered by infusion of PACAP-38. By contrast, these mutant mice show a normal PLR. We examined the retinal morphology and innervations in the mutant mice, and no apparent changes were observed in melanopsin-immunoreactive cells. These data suggest that the dysfunctions of entrainment and masking were caused by the loss of PACAP, not by the loss of light input itself. Moreover, PACAP-deficient mice express an unusually early onset of activities, from approximately four hours before the dark period, without influencing the phase of the endogenous circadian clock. CONCLUSIONS/SIGNIFICANCE: Although some groups including us reported the abnormalities in photic entrainments in PACAP- and PAC(1)-knockout mice, there were inconsistencies in their results. The time-dependent dysfunctions of photic entrainment in the PACAP-knockout mice described in this paper can integrate the incompatible data in previous reports. The recovery of impaired masking by infusion of PACAP-38 in the mutant mice is the first direct evidence of the relationship between PACAP and masking. These results indicate that PACAP regulates particular nonvisual light responses by conveying parametric light information--that is, intensity and duration. The \"early-bird\" phenotype in the mutant mice originally reported in this paper supposed that PACAP also has a critical role in daily behavioral patterns, especially during the light-to-dark transition period.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Chihiro", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Isojima", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Michiyoshi", "last_name": "Hatanaka", "name": null }, { "creator_type": "author", "first_name": "Xiaohong", "last_name": "Guo", "name": null }, { "creator_type": "author", "first_name": "Nobuaki", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0009286" }, "pmcid": { "normalized": "PMC2823792" }, "pmid": { "normalized": "20174586" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Clocks", "descriptor_ui": "D001683", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": true }, { "descriptor": "Light Signal Transduction", "descriptor_ui": "D055537", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Melanopsin", "descriptor_ui": "D000099210", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Period Circadian Proteins", "descriptor_ui": "D056950", "major_topic": false }, { "descriptor": "Photoperiod", "descriptor_ui": "D017440", "major_topic": false }, { "descriptor": "Photoreceptor Cells", "descriptor_ui": "D010786", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Pupil", "descriptor_ui": "D011680", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "Rod Opsins", "descriptor_ui": "D017299", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Feb 18", "date_precision": "day", "issue": "2", "normalized_date": "2010-02-18", "pages": "e9286", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "5", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "PACAP-deficient mice exhibit light parameter-dependent abnormalities on nonvisual photoreception and early activity onset.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Leucine-rich repeat kinase 2 (LRRK2) is the causal molecule of familial Parkinson's disease (PD), but its true physiological function remains unknown. In the normal mouse, LRRK2 is expressed in kidney, spleen, and lung at much higher levels than in brain, suggesting that LRRK2 may play an important role in these organs. Analysis of age-related changes in LRRK2 expression demonstrated that expression in kidney, lung, and various brain regions was constant throughout adult life. On the other hand, expression of both LRRK2 mRNA and protein decreased markedly in spleen in an age-dependent manner. Analysis of purified spleen cells indicated that B lymphocytes were the major population expressing LRRK2, and that T lymphocytes showed no expression. Consistently, the B lymphocyte surface marker CD19 exhibited an age-dependent decrease of mRNA expression in spleen. These results suggest a possibly novel function of LRRK2 in the immune system, especially in B lymphocytes.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Ikue", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Obata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2010.01.041" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20079710" } }, "mesh": [ { "descriptor": "Age Factors", "descriptor_ui": "D000367", "major_topic": false }, { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Leucine-Rich Repeat Serine-Threonine Protein Kinase-2", "descriptor_ui": "D000071158", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Spleen", "descriptor_ui": "D013154", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Feb 12", "date_precision": "day", "issue": "3", "normalized_date": "2010-02-12", "pages": "431-435", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "392", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Age-dependent and cell-population-restricted LRRK2 expression in normal mouse spleen.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cyclic GMP (cGMP) regulates many physiological processes by cooperating with the other signaling molecules such as cyclic AMP (cAMP) and Ca(2+). Genetically encoded sensors for cGMP have been developed based on fluorescence resonance energy transfer (FRET) between fluorescent proteins. However, to analyze the dynamic relationship among these second messengers, combined use of existing sensors in a single cell is inadequate because of the significant spectral overlaps. A single wavelength indicator is an effective alternative to avoid this problem, but color variants of a single fluorescent protein-based biosensor are limited. In this study, to construct a new color fluorescent sensor, we converted the FRET-based sensor into a single wavelength indicator using a dark FRET acceptor. We developed a blue fluorescent cGMP biosensor, which is spectrally compatible with a FRET-based cAMP sensor using cyan and yellow fluorescent proteins (CFP/YFP). We cotransfected them and loaded a red fluorescent probe for Ca(2+) into cells, and accomplished triple-parameter fluorescence imaging of these cyclic nucleotides and Ca(2+), confirming the applicability of this combination to individually monitor their dynamics in a single cell. This blue fluorescent sensor and the approach using this FRET pair would be useful for multiparameter fluorescence imaging to understand complex signal transduction networks.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Niino", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0009164" }, "pmcid": { "normalized": "PMC2820094" }, "pmid": { "normalized": "20161796" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Feb 11", "date_precision": "day", "issue": "2", "normalized_date": "2010-02-11", "pages": "e9164", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "5", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Blue fluorescent cGMP sensor for multiparameter fluorescence imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Endocannabinoids are released from postsynaptic neurons and cause retrograde suppression of synaptic transmission. Anandamide and 2-arachidonoylglycerol (2-AG) are regarded as two major endocannabinoids. To determine to what extent 2-AG contributes to retrograde signaling, we generated and analyzed mutant mice lacking either of the two 2-AG synthesizing enzymes diacylglycerol lipase alpha (DGLalpha) and beta (DGLbeta). We found that endocannabinoid-mediated retrograde synaptic suppression was totally absent in the cerebellum, hippocampus, and striatum of DGLalpha knockout mice, whereas the retrograde suppression was intact in DGLbeta knockout brains. The basal 2-AG content was markedly reduced and stimulus-induced elevation of 2-AG was absent in DGLalpha knockout brains, whereas the 2-AG content was normal in DGLbeta knockout brains. Morphology of the brain and expression of molecules required for 2-AG production other than DGLs were normal in the two knockout mice. We conclude that 2-AG produced by DGLalpha, but not by DGLbeta, mediates retrograde suppression at central synapses.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Asami", "last_name": "Tanimura", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hashimotodani", "name": null }, { "creator_type": "author", "first_name": "Motokazu", "last_name": "Uchigashima", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2010.01.021" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20159446" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Arachidonic Acids", "descriptor_ui": "D001095", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Corpus Striatum", "descriptor_ui": "D003342", "major_topic": false }, { "descriptor": "Electric Stimulation", "descriptor_ui": "D004558", "major_topic": false }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Glycerol", "descriptor_ui": "D005990", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Inhibitory Postsynaptic Potentials", "descriptor_ui": "D053444", "major_topic": false }, { "descriptor": "Lipoprotein Lipase", "descriptor_ui": "D008071", "major_topic": false }, { "descriptor": "Methoxyhydroxyphenylglycol", "descriptor_ui": "D008734", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neural Inhibition", "descriptor_ui": "D009433", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Polyunsaturated Alkamides", "descriptor_ui": "D053284", "major_topic": false }, { "descriptor": "Potassium Chloride", "descriptor_ui": "D011189", "major_topic": false }, { "descriptor": "Statistics, Nonparametric", "descriptor_ui": "D018709", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Feb 11", "date_precision": "day", "issue": "3", "normalized_date": "2010-02-11", "pages": "320-327", "proceedings_title": null, "publisher": "", "title": "Neuron", "volume": "65", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "The endocannabinoid 2-arachidonoylglycerol produced by diacylglycerol lipase alpha mediates retrograde suppression of synaptic transmission.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP, ADCYAP1: adenylate cyclase-activating polypeptide 1) is a neuropeptide with neurotransmission modulating activity. The associations of the PACAP gene with schizophrenia and hippocampal volume have been reported. We recently reported depression-like behavior in the forced swimming test in PACAP deficient mice. Here we examined a possible association between the PACAP gene and major depressive disorder (MDD) in 637 patients and 967 controls and found that a genetic variant in the gene was associated with MDD. The present results suggest that PACAP signaling might contribute to the pathogenesis of MDD.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Ohi", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Saitoh", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Kosuga", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Tatsumi", "name": null }, { "creator_type": "author", "first_name": "Nakao", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Kunitoshi", "last_name": "Kamijima", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kunugi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neulet.2009.11.019" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19914336" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Association Studies", "descriptor_ui": "D056726", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Major Depressive Disorder", "descriptor_ui": "D003865", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jan 14", "date_precision": "day", "issue": "3", "normalized_date": "2010-01-14", "pages": "300-302", "proceedings_title": null, "publisher": "", "title": "Neuroscience letters", "volume": "468", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Possible association between the pituitary adenylate cyclase-activating polypeptide (PACAP) gene and major depressive disorder.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescence imaging is a powerful tool for the visualization of biological molecules in living cells, tissue slices, and whole bodies, and is important for elucidating biological phenomena. Furthermore, zinc (Zn(2+)) is the second most abundant heavy metal ion in the human body after iron, and detection of chelatable Zn(2+) in biological studies has attracted much attention. Herein, we present a novel, highly sensitive off-on fluorescent chemosensor for Zn(2+) by using the internal charge transfer (ICT) mechanism. The rationale of our approach to highly sensitive sensor molecules is as follows. If fluorescence can be completely quenched in the absence of Zn(2+), chemosensors would offer a better signal-to-noise ratio. However, it is difficult to quench the fluorescence completely before Zn(2+) binding, and most sensor molecules still show very weak fluorescence in the absence of Zn(2+). But even though the sensor shows a weak fluorescence in the absence of Zn(2+), this fluorescence can be further suppressed by selecting an excitation wavelength that is barely absorbed by the Zn(2+)-free sensor molecule. Focusing on careful control of ICT within the 4-amino-1,8-naphthalimide dye platform, we designed and synthesized a new chemosensor (1) that shows a pronounced fluorescence enhancement with a blueshift in the absorption spectrum upon addition of Zn(2+). The usefulness of 1 for monitoring Zn(2+) changes was confirmed in living HeLa cells. There have been several reports on 4-amino-1,8-naphthalimide-based fluorescent sensor molecules. However, 1 is the first Zn(2+)-sensitive off-on fluorescent sensor molecule that employs the ICT mechanism; most off-on sensor molecules for Zn(2+) employ the photoinduced electron transfer (PeT) mechanism.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/chem.200901591" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19918808" } }, "mesh": [ { "descriptor": "1-Naphthylamine", "descriptor_ui": "D015057", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Naphthalimides", "descriptor_ui": "D053644", "major_topic": false }, { "descriptor": "Quinolones", "descriptor_ui": "D015363", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Zinc", "descriptor_ui": "D015032", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jan 11", "date_precision": "day", "issue": "2", "normalized_date": "2010-01-11", "pages": "568-572", "proceedings_title": null, "publisher": "", "title": "Chemistry (Weinheim an der Bergstrasse, Germany)", "volume": "16", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Design and synthesis of a highly sensitive off-on fluorescent chemosensor for zinc ions utilizing internal charge transfer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in multiple brain functions. To clarify the cause of abnormal behavior in PACAP deficient-mice, we attempted the identification of genes whose expression was altered in the dentate gyrus of PACAP-deficient mice using the differential display method. Expression of stathmin1 was up-regulated in the dentate gyrus at both the mRNA and protein levels. PACAP stimulation inhibited stathmin1 expression in PC12 cells, while increased stathmin1expression in neurons of the subgranular zone and in primary cultured hippocampal neurons induced abnormal arborization of axons. We also investigated the pathways involved in PACAP deficiency. Ascl1 binds to E10 box of the stathmin1 promoter and increases stathmin1 expression. Inhibitory bHLH proteins (Hes1 and Id3) were rapidly up-regulated by PACAP stimulation, and Hes1 could suppress Ascl1 expression and Id3 could inhibit Ascl1 signaling. We also detected an increase of stathmin1 expression in the brains of schizophrenic patients. These results suggest that up-regulation of stathmin1 in the dentate gyrus, secondary to PACAP deficiency, may create abnormal neuronal circuits that cause abnormal behavior.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kohei", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Matsuzaki", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Ryusuke", "last_name": "Kuwahara", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Natsuko", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Taiichi", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Tohyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0008596" }, "pmcid": { "normalized": "PMC2797614" }, "pmid": { "normalized": "20062533" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": true }, { "descriptor": "Chromatin Immunoprecipitation", "descriptor_ui": "D047369", "major_topic": false }, { "descriptor": "Dentate Gyrus", "descriptor_ui": "D018891", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Microscopy, Immunoelectron", "descriptor_ui": "D016253", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Stathmin", "descriptor_ui": "D050777", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jan 6", "date_precision": "day", "issue": "1", "normalized_date": "2010-01-06", "pages": "e8596", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "5", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Increased stathmin1 expression in the dentate gyrus of mice causes abnormal axonal arborizations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP)-deficient mice display remarkable behavioral changes including increased novelty-seeking behavior and reduced hypothermia induced by either serotonin (5-HT)(1A) receptor agonists or ethanol. Because 5-HT(1A) receptors have been implicated in the development of alcohol dependence, we have examined ethanol preference in PACAP-deficient mice using a two-bottle choice and a conditioned place preference test, as well as additive effects of ethanol and 5-HT(1A) receptor agents on hypothermia. PACAP-deficient mice showed an increased preference towards ethanol compared with wild-type mice. However, they showed no preference for the ethanol compartment after conditioning and neither preference nor aversion to sucrose or quinine. The 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) restored the attenuated hypothermic response to ethanol in the mutants to similar levels in wild-type mice, with no effect in wild-types. In contrast, the 5-HT(1A) receptor antagonist WAY-100635 attenuated the ethanol-induced hypothermia in wild-type mice, with no effect in the mutants. These results demonstrate increased ethanol preference in PACAP-deficient mice that may be mediated by 5-HT(1A) receptor-dependent attenuation of ethanol-induced central inhibition.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Kunishige-Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2009.11.136" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19944672" } }, "mesh": [ { "descriptor": "8-Hydroxy-2-(di-n-propylamino)tetralin", "descriptor_ui": "D017371", "major_topic": false }, { "descriptor": "Alcoholism", "descriptor_ui": "D000437", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": true }, { "descriptor": "Conditioning, Classical", "descriptor_ui": "D003214", "major_topic": false }, { "descriptor": "Ethanol", "descriptor_ui": "D000431", "major_topic": false }, { "descriptor": "Exploratory Behavior", "descriptor_ui": "D005106", "major_topic": true }, { "descriptor": "Hypothermia", "descriptor_ui": "D007035", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Serotonin 5-HT1 Receptor Agonists", "descriptor_ui": "D058825", "major_topic": true }, { "descriptor": "Serotonin Receptor Agonists", "descriptor_ui": "D017366", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jan 1", "date_precision": "day", "issue": "1", "normalized_date": "2010-01-01", "pages": "773-777", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "391", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Increased ethanol preference and serotonin 1A receptor-dependent attenuation of ethanol-induced hypothermia in PACAP-deficient mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Leucine-rich repeat kinase 2 (LRRK2) is the causal gene for autosomal dominant familial Parkinson's disease. We have previously reported a novel molecular feature characteristic to I2020T mutant LRRK2: higher susceptibility to post-translational degradation than the wild-type LRRK2. In the present study, we demonstrated that the protective effect of I2020T LRRK2 against hydrogen peroxide-induced apoptosis was impaired in comparison with the wild-type molecule. When the intracellular level of the protein had been allowed to recover by treatment with proteolysis inhibitors, the protective effect of I2020T LRRK2 against apoptosis was increased. We further confirmed that a decrease in the intracellular protein level of WT LRRK2 by knocking down resulted in a reduction of protectivity against apoptosis. These results suggest that higher susceptibility of I2020T mutant LRRK2 to intracellular degradation than the wild-type molecule may be one of the mechanisms involved in the neurodegeneration associated with this LRRK2 mutation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Obata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2009.11.043" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19912990" } }, "mesh": [ { "descriptor": "Acetylcysteine", "descriptor_ui": "D000111", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": true }, { "descriptor": "Chloroquine", "descriptor_ui": "D002738", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": false }, { "descriptor": "Leucine-Rich Repeat Serine-Threonine Protein Kinase-2", "descriptor_ui": "D000071158", "major_topic": false }, { "descriptor": "Leupeptins", "descriptor_ui": "D007976", "major_topic": false }, { "descriptor": "Lysosomes", "descriptor_ui": "D008247", "major_topic": false }, { "descriptor": "Parkinson Disease", "descriptor_ui": "D010300", "major_topic": false }, { "descriptor": "Proteasome Endopeptidase Complex", "descriptor_ui": "D046988", "major_topic": false }, { "descriptor": "Proteasome Inhibitors", "descriptor_ui": "D061988", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jan 1", "date_precision": "day", "issue": "1", "normalized_date": "2010-01-01", "pages": "242-247", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "391", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Prevention of intracellular degradation of I2020T mutant LRRK2 restores its protectivity against apoptosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The eyes of flower-visiting butterflies are often spectrally highly complex with multiple opsin genes generated by gene duplication, providing an interesting system for a comparative study of color vision. The Small White butterfly, Pieris rapae, has duplicated blue opsins, PrB and PrV, which are expressed in the blue (λmax = 453 nm) and violet receptors (λmax = 425 nm), respectively. To reveal accurate absorption profiles and the molecular basis of the spectral tuning of these visual pigments, we successfully modified our honeybee opsin expression system based on HEK293s cells, and expressed PrB and PrV, the first lepidopteran opsins ever expressed in cultured cells. We reconstituted the expressed visual pigments in vitro, and analysed them spectroscopically. Both reconstituted visual pigments had two photointerconvertible states, rhodopsin and metarhodopsin, with absorption peak wavelengths 450 nm and 485 nm for PrB and 420 nm and 482 nm for PrV. We furthermore introduced site-directed mutations to the opsins and found that two amino acid substitutions, at positions 116 and 177, were crucial for the spectral tuning. This tuning mechanism appears to be specific for invertebrates and is partially shared by other pierid and lycaenid butterfly species.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Wakakuwa", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Doekele G.", "last_name": "Stavenga", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Shichida", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Arikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0015015" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21124838" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Butterflies", "descriptor_ui": "D002080", "major_topic": false }, { "descriptor": "Electrophoresis, Polyacrylamide Gel", "descriptor_ui": "D004591", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Protein Structure, Secondary", "descriptor_ui": "D017433", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Retinal Pigments", "descriptor_ui": "D012168", "major_topic": false }, { "descriptor": "Rod Opsins", "descriptor_ui": "D017299", "major_topic": false }, { "descriptor": "Sequence Homology, Amino Acid", "descriptor_ui": "D017386", "major_topic": false }, { "descriptor": "Spectrophotometry", "descriptor_ui": "D013053", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010", "date_precision": "year", "issue": "11", "normalized_date": "2010", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "5", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Evolution and Mechanism of Spectral Tuning of Blue-Absorbing Visual Pigments in Butterflies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells (CRTH2) is the most recently identified prostaglandin (PG) receptor for both PGD(2) and 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)). We examined the mechanism by which 15d-PGJ(2) enhances nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. CAY10471 (CRTH2 antagonist) inhibited both the neurite-promotion and p38 mitogen-activated protein (MAP) kinase phosphorylation induced by 15d-PGJ(2). In contrast, 13,14-dihydro-15-keto-PGD(2 )(DK-PGD(2)) (selective CRTH2 agonist) stimulated its phosphorylation but failed to produce neurite-promoting effects. These suggest, for the first time, the action of 15d-PGJ(2) is mediated by CRTH2, although the CRTH2 activation alone is insufficient for the underlying action.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Michiyoshi", "last_name": "Hatanaka", "name": null }, { "creator_type": "author", "first_name": "Norihiro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Haba", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Hayata", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/jphs.10001sc" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20424389" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carbazoles", "descriptor_ui": "D002227", "major_topic": false }, { "descriptor": "Nerve Growth Factor", "descriptor_ui": "D020932", "major_topic": false }, { "descriptor": "Neurites", "descriptor_ui": "D016501", "major_topic": false }, { "descriptor": "p38 Mitogen-Activated Protein Kinases", "descriptor_ui": "D048051", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Prostaglandin D2", "descriptor_ui": "D015230", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Receptors, Immunologic", "descriptor_ui": "D011971", "major_topic": false }, { "descriptor": "Receptors, Prostaglandin", "descriptor_ui": "D011982", "major_topic": false }, { "descriptor": "Sulfonamides", "descriptor_ui": "D013449", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010", "date_precision": "year", "issue": "1", "normalized_date": "2010", "pages": "89-93", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "113", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "15d-prostaglandin J2 enhancement of nerve growth factor-induced neurite outgrowth is blocked by the chemoattractant receptor- homologous molecule expressed on T-helper type 2 cells (CRTH2) antagonist CAY10471 in PC12 cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pyrrolepolyamide-2'-deoxyguanosine hybrids (Hybrid 2 and Hybrid 3) incorporating the 3-aminopropionyl or 3-aminopropyl linker were designed and synthesized on the basis of previously reported results of a pyrrolepolyamide-adenosine hybrid (Hybrid 1). Evaluation of the DNA binding sequence selectivity of pyrrolepolyamide-2'-deoxyguanosine hybrids was performed by CD spectral and T(m) analyses. It was shown that Hybrid 3 possessed greater binding specificity than distamycin A, Hybrid 1 and Hybrid 2.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Etsuko", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Terui", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kamaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.4061/2010/235240" }, "pmcid": { "normalized": "PMC2911594" }, "pmid": { "normalized": "20700414" } }, "mesh": [], "publication": { "conference_name": null, "date": "2010", "date_precision": "year", "issue": "", "normalized_date": "2010", "pages": "235240", "proceedings_title": null, "publisher": "", "title": "Journal of nucleic acids", "volume": "2010", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Design, synthesis, and analysis of minor groove binder pyrrolepolyamide-2'-deoxyguanosine hybrids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This paper describes the preparation and characterization of an optical pH-sensing device using a H(+)-responsive fluoroionophore based on boron-dipyrromethene, immobilized to a mesoporous silica thin film. The fluoroionophore substituted with a silane coupling agent (KBH-01-Si) was successfully synthesized, and a mesoporous silica thin film was fabricated by the evaporation-induced-self-assembly (EISA) process. A pH optode was fabricated by attaching KBH-01-Si to the mesoporous silica thin film by covalent bonding via a sol-gel grafting method. The resulting pH optode shows single-excitation, dual-emission ratiometric response in aqueous buffer solutions of varying pH values. The sensor response was found to be reversible in the pH range from below 0.8 to 4.2, and showed good repeatability. The response times for a 95% signal change (t(95%)) were calculated to be 27 +/- 2 s (n = 5) for a sample change from pH 4.0 to 1.0, and 23 +/- 2 s (n = 5) for reverse change from pH 1.0 to 4.0. These results indicate that the novel pH optode allows for accurate and rapid measurements of pH values.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.2116/analsci.26.297" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20215677" } }, "mesh": [ { "descriptor": "Boron", "descriptor_ui": "D001895", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Membranes, Artificial", "descriptor_ui": "D008567", "major_topic": true }, { "descriptor": "Porosity", "descriptor_ui": "D016062", "major_topic": false }, { "descriptor": "Porphobilinogen", "descriptor_ui": "D011162", "major_topic": false }, { "descriptor": "Silicon Dioxide", "descriptor_ui": "D012822", "major_topic": false }, { "descriptor": "Surface Properties", "descriptor_ui": "D013499", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010", "date_precision": "year", "issue": "3", "normalized_date": "2010", "pages": "297-301", "proceedings_title": null, "publisher": "", "title": "Analytical sciences : the international journal of the Japan Society for Analytical Chemistry", "volume": "26", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "A fast-response pH optode based on a fluoroionophore immobilized to a mesoporous silica thin film.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "For high range resolution acoustic vascular imaging we apply frequency domain interferometry and Capon method to a few frames of in-phase and quadrature (IQ) data acquired by a commercial ultrasonographic device. To suit the adaptive beamforming algorithm to medical acoustic imaging we employ three techniques; frequency averaging, whitening, and pseudo-double RF data conversion. The proposed method detected two couples of boundaries 0.26 and 0.19 mm apart using a single frame and two frames of IQ data, respectively, where each couple of boundaries is indistinguishable from a single boundary utilizing B-mode images. Further this algorithm could depict a swine femoral artery with higher range resolution than conventional B-mode imaging. These results indicate the potential of the proposed method for the range resolution improvement in ultrasonography, originating the progress in detection of vessel stenosis.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Kousuke", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1109/iembs.2010.5626325" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21096063" } }, "mesh": [ { "descriptor": "Acoustics", "descriptor_ui": "D000162", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Femoral Artery", "descriptor_ui": "D005263", "major_topic": false }, { "descriptor": "Gelatin", "descriptor_ui": "D005780", "major_topic": false }, { "descriptor": "Image Interpretation, Computer-Assisted", "descriptor_ui": "D007090", "major_topic": false }, { "descriptor": "Interferometry", "descriptor_ui": "D007368", "major_topic": false }, { "descriptor": "Radio Waves", "descriptor_ui": "D011846", "major_topic": false }, { "descriptor": "Sus scrofa", "descriptor_ui": "D034421", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010", "date_precision": "year", "issue": "", "normalized_date": "2010", "pages": "5298-5301", "proceedings_title": null, "publisher": "", "title": "Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference", "volume": "2010", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "High range resolution medical acoustic vascular imaging with frequency domain interferometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Purkinje cells are the sole output neurons of the cerebellar cortex and their dysfunction causes severe ataxia. We found that Purkinje cells could be robustly generated from mouse embryonic stem (ES) cells by recapitulating the self-inductive signaling microenvironments of the isthmic organizer. The cell-surface marker Neph3 enabled us to carry out timed prospective selection of Purkinje cell progenitors, which generated morphologically characteristic neurons with highly arborized dendrites that expressed mature Purkinje cell-specific markers such as the glutamate receptor subunit GluRdelta2. Similar to mature Purkinje cells, these neurons also showed characteristic spontaneous and repeated action potentials and their postsynaptic excitatory potentials were generated exclusively through nonNMDA glutamate receptors. Fetal transplantation of precursors isolated by fluorescence-activated cell sorting showed orthotopic integration of the grafted neurons into the Purkinje cell layer with their axons extending to the deep cerebellar nuclei and dendrites receiving climbing and parallel fibers. This selective preparation of bona fide Purkinje cells should aid future investigation of this important neuron.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Mizuhara", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kakizuka", "name": null }, { "creator_type": "author", "first_name": "Kunihiko", "last_name": "Obata", "name": null }, { "creator_type": "author", "first_name": "Yuchio", "last_name": "Yanagawa", "name": null }, { "creator_type": "author", "first_name": "Tomoo", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nn.2638" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20835252" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cerebellar Cortex", "descriptor_ui": "D002525", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Glutamate Decarboxylase", "descriptor_ui": "D005968", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Immunoglobulins", "descriptor_ui": "D007136", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "1171-1180", "proceedings_title": null, "publisher": "", "title": "Nature neuroscience", "volume": "13", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Ontogeny-recapitulating generation and tissue integration of ES cell-derived Purkinje cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In ascidian Ciona intestinalis, a subset of trunk epidermal neurons were shown to possess external network of neural projections. To characterize a more complete network in naturally hatched (chorionated) larvae, we visualized the structure with a confocal laser scanning microscope. High resolution images revealed the huge network consisting of several subnetworks in whole-larval tunic. We named this network the ASNET (ascidian dendritic network in tunic). The ASNET was dynamically generated and collapsed during larval stages. Interestingly, one of the subnetworks found around apical trunk epidermal neurons was bilaterally asymmetric. In caudal epidermal neurons, transmission electron microscopy revealed that 9+2 axonemes were accompanied by a vesicle-containing mass in the ASNET arbor, but the distal end of the arbor contained only the vesicle-containing fibrous mass and no 9+2 axonemes. The characteristics of the ASNET suggest that it forms a unique outer body network in the ascidian larval tunic.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi Q.", "last_name": "Terakubo", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Sasakura", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Alu", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/dvdy.22361" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20589900" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Epidermis", "descriptor_ui": "D004817", "major_topic": false }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Tunica Intima", "descriptor_ui": "D017539", "major_topic": false }, { "descriptor": "Tunica Media", "descriptor_ui": "D017540", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "2278-2287", "proceedings_title": null, "publisher": "", "title": "Developmental dynamics : an official publication of the American Association of Anatomists", "volume": "239", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Network structure of projections extending from peripheral neurons in the tunic of ascidian larva.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Little is known about the stem cells of organisms early in metazoan evolution. To characterize the stem cell system in demosponges, we identified Piwi homologs of a freshwater sponge, Ephydatia fluviatilis, as candidate stem cell (archeocyte) markers. EfPiwiA mRNA was expressed in cells with archeocyte cell morphological features. We demonstrated that these EfPiwiA-expressing cells were indeed stem cells by showing their ability to proliferate, as indicated by BrdU-incorporation, and to differentiate, as indicated by the coexpression of EfPiwiA with cell-lineage-specific genes in presumptive committed archeocytes. EfPiwiA mRNA expression was maintained in mature choanocytes forming chambers, in contrast to the transition of gene expression from EfPiwiA to cell-lineage-specific markers during archeocyte differentiation into other cell types. Choanocytes are food-entrapping cells with morphological features similar to those of choanoflagellates (microvillus collar and a flagellum). Their known abilities to transform into archeocytes under specific circumstances and to give rise to gametes (mostly sperm) indicate that even when they are fully differentiated, choanocytes maintain pluripotent stem cell-like potential. Based on the specific expression of EfPiwiA in archeocytes and choanocytes, combined with previous studies, we propose that both archeocytes and choanocytes are components of the demosponge stem cell system. We discuss the possibility that choanocytes might represent the ancestral stem cells, whereas archeocytes might represent stem cells that further evolved in ancestral multicellular organisms.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Noriko", "last_name": "Funayama", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Nakatsukasa", "name": null }, { "creator_type": "author", "first_name": "Kurato", "last_name": "Mohri", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Kiyokazu", "last_name": "Agata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1525-142x.2010.00413.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20565538" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "DNA Primers", "descriptor_ui": "D017931", "major_topic": false }, { "descriptor": "Porifera", "descriptor_ui": "D011161", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "RNA-Induced Silencing Complex", "descriptor_ui": "D034743", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 May-Jun", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "275-287", "proceedings_title": null, "publisher": "", "title": "Evolution & development", "volume": "12", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Piwi expression in archeocytes and choanocytes in demosponges: insights into the stem cell system in demosponges.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Inositol 1,4,5-trisphosphate receptor type 1 (IP(3) R1) is an intracellular Ca(2+) release channel that plays crucial roles in the functions of Purkinje cells. The dynamics of IP(3) R1 on the endoplasmic reticulum membrane and the distribution of IP(3) R1 in neurons are thought to be important for the spatial regulation of Ca(2+) release. In this study, we analyzed the lateral diffusion of IP(3) R1 in Purkinje cells in cerebellar slice cultures using fluorescence recovery after photobleaching. In the dendrites of Purkinje cells, IP(3) R1 showed lateral diffusion with an effective diffusion constant of approximately 0.30 mum(2) /s, and the diffusion of IP(3) R1 was negatively regulated by actin filaments. We found that actin filaments were also involved in the regulation of IP(3) R1 diffusion in the spine of Purkinje cells. Glutamate or quisqualic acid stimulation, which activates glutamate receptors and leads to a Ca(2+) transient in Purkinje cells, decreased the diffusion of IP(3) R1 and increased the density of actin in spines. These findings indicate that the neuronal activity-dependent augmentation of actin contributes to the stabilization of IP(3) R1 in spines.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazumi", "last_name": "Fukatsu", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Mikoshiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1471-4159.2010.06885.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20626556" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Diffusion", "descriptor_ui": "D004058", "major_topic": false }, { "descriptor": "Excitatory Amino Acid Agonists", "descriptor_ui": "D018690", "major_topic": false }, { "descriptor": "Fluorescence Recovery After Photobleaching", "descriptor_ui": "D036681", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Inositol 1,4,5-Trisphosphate Receptors", "descriptor_ui": "D053496", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Quisqualic Acid", "descriptor_ui": "D016318", "major_topic": false }, { "descriptor": "Receptors, Glutamate", "descriptor_ui": "D017470", "major_topic": false }, { "descriptor": "Tissue Culture Techniques", "descriptor_ui": "D046509", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Sep", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "1720-1733", "proceedings_title": null, "publisher": "", "title": "Journal of neurochemistry", "volume": "114", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Lateral diffusion of inositol 1,4,5-trisphosphate receptor type 1 in Purkinje cells is regulated by calcium and actin filaments.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Myogenic determination 1 (MyoD) is a myogenic regulatory factor (MRF) possessing a basic domain and a helix-loop-helix domain. MRFs play a critical role in myoblast fate and terminal differentiation. MyoD is a transcriptional factor that induces transcription by binding with gene regulatory factors expressed in skeletal muscle. As a master gene, MyoD also determines skeletal muscle differentiation. In this study, we established a monoclonal antibody specific for MyoD using the rat medial iliac lymph node method. Immunoblot analysis revealed that our monoclonal antibody against MyoD could identify full-length MyoD. Moreover, immunocytochemical staining revealed a change in the expression of MyoD at the skeletal muscle differentiation stage. This monoclonal antibody against MyoD allows for further studies to elucidate the mechanism by which MyoD influences skeletal muscle differentiation.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Ao", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Odawara", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tachibana", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/hyb.2009.0117" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20569002" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Antibody Specificity", "descriptor_ui": "D000918", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Enzyme-Linked Immunosorbent Assay", "descriptor_ui": "D004797", "major_topic": false }, { "descriptor": "Euchromatin", "descriptor_ui": "D022041", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hybridomas", "descriptor_ui": "D006825", "major_topic": false }, { "descriptor": "Ileum", "descriptor_ui": "D007082", "major_topic": false }, { "descriptor": "Immunization", "descriptor_ui": "D007114", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Myoblasts", "descriptor_ui": "D032446", "major_topic": false }, { "descriptor": "MyoD Protein", "descriptor_ui": "D017570", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Inbred WKY", "descriptor_ui": "D011921", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jun", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "255-258", "proceedings_title": null, "publisher": "", "title": "Hybridoma (2005)", "volume": "29", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Rat monoclonal antibody specific for MyoD.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mutual relationship among Markov partitions is investigated for one-dimensional piecewise monotonic map. It is shown that if a Markov partition is regarded as a map-refinement of the other Markov partition, that is, a concept we newly introduce in this article, one can uniquely translate a set of symbolic sequences by one Markov partition to those by the other or vice versa. However, the set of symbolic sequences constructed using Markov partitions is not necessarily translated with each other if there exists no map-refinement relation among them. By using a roof map we demonstrate how the resultant symbolic sequences depend on the choice of Markov partitions.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Teramoto", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/1.3491097" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20887079" } }, "mesh": [], "publication": { "conference_name": null, "date": "2010 Sep", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "037113", "proceedings_title": null, "publisher": "", "title": "Chaos (Woodbury, N.Y.)", "volume": "20", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "How does a choice of Markov partition affect the resultant symbolic dynamics?", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have synthesized amphiphilic copolymers using ring-opening metathesis polymerization (ROMP), a copper-catalyzed dipolar click reaction, and osmium-catalyzed dihydroxylation. The resulting copolymers were easily conjugated with folate and dye (indocyanine green) moieties, using a transamidation method. The copolymers exhibited high water solubility and formed nanometer-sized self-assemblies in aqueous medium. The amphiphilic copolymers modified by dihydroxylation of the polymer backbone exhibited much lower cmc values than the non dihydroxylated copolymer. Copolymers conjugated with folate moieties reduced the fluorescence intensity of aqueous polymer solutions both in vitro and in vivo, but their self-assemblies efficiently accumulated at tumor sites because of folate-receptor recognition at tumor tissue. The PEGylation of copolymers improved the stability of the self-assemblies in aqueous medium as well as the tumor site selectivity in vivo. Furthermore, the fluorescent nanoparticles consisting of PEG- and folate-conjugated ROMP-based copolymers accumulated in tumor tissue selectively and efficiently, whereas accumulation in all other normal organs was reduced. The PEGylation and folate conjugation can synergistically improve the in vivo tumor site selectivity of ROMP-based copolymers.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Oride", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kuramochi", "name": null }, { "creator_type": "author", "first_name": "Rati R.", "last_name": "Nayak", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.biomaterials.2009.10.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19853909" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Contrast Media", "descriptor_ui": "D003287", "major_topic": false }, { "descriptor": "Drug Carriers", "descriptor_ui": "D004337", "major_topic": false }, { "descriptor": "Folate Receptors, GPI-Anchored", "descriptor_ui": "D058973", "major_topic": false }, { "descriptor": "Folic Acid", "descriptor_ui": "D005492", "major_topic": true }, { "descriptor": "Image Enhancement", "descriptor_ui": "D007089", "major_topic": false }, { "descriptor": "Materials Testing", "descriptor_ui": "D008422", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Molecular Probe Techniques", "descriptor_ui": "D015336", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": true }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Polyethylene Glycols", "descriptor_ui": "D011092", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Feb", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "934-942", "proceedings_title": null, "publisher": "", "title": "Biomaterials", "volume": "31", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Ring-opening metathesis polymerization-based synthesis of polymeric nanoparticles for enhanced tumor imaging in vivo: Synergistic effect of folate-receptor targeting and PEGylation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Equine herpesvirus 4 (EHV-4) is an important equine pathogen that causes respiratory tract disease among horses worldwide. A thymidine kinase (TK)-deletion mutant has been generated by using bacterial artificial chromosome (BAC) technology to investigate the role of TK in pathogenesis. Deletion of TK had virtually no effect on the growth characteristics of WA79DeltaTK in cell culture when compared to the parent virus. Also, virus titers and plaque formation were unaffected in the absence of the TK gene. The sensitivity of EHV-4 to inhibition by acyclovir (ACV) and ganciclovir (GCV) was studied by means of a plaque reduction assay. GCV proved to be more potent and showed a superior anti-EHV-4 activity. On the other hand, ACV showed very poor ability to inhibit EHV-4 replication. As predicted, WA79DeltaTK was insensitive to GCV. Although EHV-4 is normally insensitive to ACV, it showed >20-fold increase in sensitivity when the equine herpesvirus-1 (EHV-1) TK was supplied in trans. Furthermore, both ACV and GCV resulted in a significant reduction of plaque size induced by EHV-4 and 1. Taken together, these data provided direct evidence that GCV is a potent selective inhibitor of EHV-4 and that the virus-encoded TK is an important determinant of the virus susceptibility to nucleoside analogues.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Walid", "last_name": "Azab", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tsujimura", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Yukinobu", "last_name": "Tohya", "name": null }, { "creator_type": "author", "first_name": "Tomio", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Hiroomi", "last_name": "Akashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.antiviral.2009.11.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19931566" } }, "mesh": [ { "descriptor": "Acyclovir", "descriptor_ui": "D000212", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antiviral Agents", "descriptor_ui": "D000998", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Ganciclovir", "descriptor_ui": "D015774", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": false }, { "descriptor": "Herpesvirus 4, Equid", "descriptor_ui": "D023141", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microbial Sensitivity Tests", "descriptor_ui": "D008826", "major_topic": false }, { "descriptor": "Thymidine Kinase", "descriptor_ui": "D013937", "major_topic": false }, { "descriptor": "Viral Plaque Assay", "descriptor_ui": "D010948", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "389-395", "proceedings_title": null, "publisher": "", "title": "Antiviral research", "volume": "85", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Characterization of a thymidine kinase-deficient mutant of equine herpesvirus 4 and in vitro susceptibility of the virus to antiviral agents.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We recently reported that the herpes simplex virus 1 (HSV-1) Us3 protein kinase phosphorylates threonine at position 887 (Thr-887) in the cytoplasmic tail of envelope glycoprotein B (gB) (A. Kato, J. Arii, I. Shiratori, H. Akashi, H. Arase, and Y. Kawaguchi, J. Virol. 83:250-261, 2009; T. Wisner, C. C. Wright, A. Kato, Y. Kawaguchi, F. Mou, J. D. Baines, R. J. Roller and D. C. Johnson, J. Virol. 83:3115-3126, 2009). In the studies reported here, we examined the effect(s) of this phosphorylation on viral replication and pathogenesis in vivo and present data showing that replacement of gB Thr-887 by alanine significantly reduced viral replication in the mouse cornea and development of herpes stroma keratitis and periocular skin disease in mice. The same effects have been reported for mice infected with a recombinant HSV-1 carrying a kinase-inactive mutant of Us3. These observations suggested that Us3 phosphorylation of gB Thr-887 played a critical role in viral replication in vivo and in HSV-1 pathogenesis. In addition, we generated a monoclonal antibody that specifically reacted with phosphorylated gB Thr-887 and used this antibody to show that Us3 phosphorylation of gB Thr-887 regulated subcellular localization of gB, particularly on the cell surface of infected cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takahiko", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Sagou", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01447-09" }, "pmcid": { "normalized": "PMC2798420" }, "pmid": { "normalized": "19846518" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Corneal Diseases", "descriptor_ui": "D003316", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Keratitis, Herpetic", "descriptor_ui": "D016849", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Skin Diseases", "descriptor_ui": "D012871", "major_topic": false }, { "descriptor": "Threonine", "descriptor_ui": "D013912", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Envelope Proteins", "descriptor_ui": "D014759", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "153-162", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "84", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Effects of phosphorylation of herpes simplex virus 1 envelope glycoprotein B by Us3 kinase in vivo and in vitro.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: The purpose of this paper is to propose a novel strategy to detect small calculi efficiently. METHODS: The proposed calculus detection strategy focuses on decorrelation of forward scattered waves caused by the failure of Born's approximation. A calculus causes waveform changes of transmit pulses, resulting in a decrease in the cross-correlation coefficients calculated from IQ signals scattered near the calculus position. Therefore, we can detect calculi from the appearance of dips in correlation coefficients. RESULTS: When a calculus exists in a digital tissue map, sharp and deep dips in cross-correlation coefficients between acoustic IQ signals appear around the calculus. By contrast, no apparent dip exists when a tissue map contains no calculus. A scan line interval of 0.2 mm or less is appropriate for the conditions simulated in this paper, and the proper transmit focal range for the proposed method is at a calculus range. CONCLUSION: These results imply that the proposed strategy can improve the efficiency of US devices for small calculus detection.", "classifications": [ { "id": "A01-1", "label": "Planned Research A01-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10396-010-0265-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27278012" } }, "mesh": [], "publication": { "conference_name": null, "date": "2010 Jul", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "129-135", "proceedings_title": null, "publisher": "", "title": "Journal of medical ultrasonics (2001)", "volume": "37", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Calculus detection for ultrasonography using decorrelation of forward scattered wave.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "CHD2 is a member of the CHD family that contains chromodomain, helicase domain as well as DNA-binding domain. The CHD family is involved in gene expression and transcription by ATP-dependent chromatin remodeling. Analysis of mutant mouse revealed that CHD2 is involved in development as well as hematopoiesis, which suggests the involvement of CHD2 in gene expression. However, CHD2 has not yet been analyzed biochemically as there is no specific antibody against it. Here, we report on the establishment of specific monoclonal antibody (MAb) against CHD2 utilizing a rat medial iliac lymph node method. Through cell immunostaining utilizing established MAb to CHD2, we confirmed that CHD2 was localized in euchromatin. Additionally, IP-Western revealed that the expression level of full-length CHD2 did not change during the differentiation stage. Additionally, a specific signal was confirmed around 95 kDa at the undifferentiated stage. This clearly indicated that CHD2 was involved in specific gene expression at this stage. Thus, this antibody can contribute to elucidating the function of CHD2 in cell expression.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Odawara", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/hyb.2009.0090" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20443711" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Antibody Specificity", "descriptor_ui": "D000918", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Enzyme-Linked Immunosorbent Assay", "descriptor_ui": "D004797", "major_topic": false }, { "descriptor": "Epitope Mapping", "descriptor_ui": "D018604", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Hybridomas", "descriptor_ui": "D006825", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Immunoprecipitation", "descriptor_ui": "D047468", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "173-177", "proceedings_title": null, "publisher": "", "title": "Hybridoma (2005)", "volume": "29", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of a rat monoclonal antibody specific for CHD2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Traumatic injury in the central nervous system induces inflammation; however, the role of this inflammation is controversial. Precise analysis of the inflammatory cells is important to gain a better understanding of the inflammatory machinery in response to neural injury. Here, we demonstrated that leukotriene B4 plays a significant role in mediating leukocyte infiltration after spinal cord injury. Using flow cytometry, we revealed that neutrophil and monocyte/macrophage infiltration peaked 12 hours after injury and was significantly suppressed in leukotriene B4 receptor 1 knockout mice. Similar findings were observed in mice treated with a leukotriene B4 receptor antagonist. Further, by isolating each inflammatory cell subset with a cell sorter, and performing quantitative reverse transcription-PCR, we demonstrated the individual contributions of more highly expressed subsets, ie, interleukins 6 and 1beta, tumor necrosis factor-alpha, and FasL, to the inflammatory reaction and neural apoptosis. Inhibition of leukotriene B4 suppressed leukocyte infiltration after injury, thereby attenuating the inflammatory reaction, sparing the white matter, and reducing neural apoptosis, as well as inducing better functional recovery. These findings are the first to demonstrate that leukotriene B4 is involved in the pathogenesis of spinal cord injury through the amplification of leukocyte infiltration, and provide a potential therapeutic strategy for traumatic spinal cord injury.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Saiwai", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Hisakata", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Kumamaru", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Yokomizo", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.2353/ajpath.2010.090839" }, "pmcid": { "normalized": "PMC2861100" }, "pmid": { "normalized": "20304963" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Fas Ligand Protein", "descriptor_ui": "D053222", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Interleukin-1beta", "descriptor_ui": "D053583", "major_topic": false }, { "descriptor": "Interleukin-6", "descriptor_ui": "D015850", "major_topic": false }, { "descriptor": "Leukotriene B4", "descriptor_ui": "D007975", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neutrophils", "descriptor_ui": "D009504", "major_topic": false }, { "descriptor": "Receptors, Leukotriene B4", "descriptor_ui": "D018102", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false }, { "descriptor": "Spinal Cord Injuries", "descriptor_ui": "D013119", "major_topic": false }, { "descriptor": "Tumor Necrosis Factor-alpha", "descriptor_ui": "D014409", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "2352-2366", "proceedings_title": null, "publisher": "", "title": "The American journal of pathology", "volume": "176", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "The LTB4-BLT1 axis mediates neutrophil infiltration and secondary injury in experimental spinal cord injury.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Developmental biology aims to understand how the dynamics of embryonic shapes and organ functions are encoded in linear DNA molecules. Thanks to recent progress in genomics and imaging technologies, systemic approaches are now used in parallel with small-scale studies to establish links between genomic information and phenotypes, often described at the subcellular level. Current model organism databases, however, do not integrate heterogeneous data sets at different scales into a global view of the developmental program. Here, we present a novel, generic digital system, NISEED, and its implementation, ANISEED, to ascidians, which are invertebrate chordates suitable for developmental systems biology approaches. ANISEED hosts an unprecedented combination of anatomical and molecular data on ascidian development. This includes the first detailed anatomical ontologies for these embryos, and quantitative geometrical descriptions of developing cells obtained from reconstructed three-dimensional (3D) embryos up to the gastrula stages. Fully annotated gene model sets are linked to 30,000 high-resolution spatial gene expression patterns in wild-type and experimentally manipulated conditions and to 528 experimentally validated cis-regulatory regions imported from specialized databases or extracted from 160 literature articles. This highly structured data set can be explored via a Developmental Browser, a Genome Browser, and a 3D Virtual Embryo module. We show how integration of heterogeneous data in ANISEED can provide a system-level understanding of the developmental program through the automatic inference of gene regulatory interactions, the identification of inducing signals, and the discovery and explanation of novel asymmetric divisions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Olivier", "last_name": "Tassy", "name": null }, { "creator_type": "author", "first_name": "Delphine", "last_name": "Dauga", "name": null }, { "creator_type": "author", "first_name": "Fabrice", "last_name": "Daian", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Sobral", "name": null }, { "creator_type": "author", "first_name": "François", "last_name": "Robin", "name": null }, { "creator_type": "author", "first_name": "Pierre", "last_name": "Khoueiry", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Salgado", "name": null }, { "creator_type": "author", "first_name": "Vanessa", "last_name": "Fox", "name": null }, { "creator_type": "author", "first_name": "Danièle", "last_name": "Caillol", "name": null }, { "creator_type": "author", "first_name": "Renaud", "last_name": "Schiappa", "name": null }, { "creator_type": "author", "first_name": "Baptiste", "last_name": "Laporte", "name": null }, { "creator_type": "author", "first_name": "Anne", "last_name": "Rios", "name": null }, { "creator_type": "author", "first_name": "Guillaume", "last_name": "Luxardi", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Jean-Stéphane", "last_name": "Joly", "name": null }, { "creator_type": "author", "first_name": "Sébastien", "last_name": "Darras", "name": null }, { "creator_type": "author", "first_name": "Lionel", "last_name": "Christiaen", "name": null }, { "creator_type": "author", "first_name": "Magali", "last_name": "Contensin", "name": null }, { "creator_type": "author", "first_name": "Hélène", "last_name": "Auger", "name": null }, { "creator_type": "author", "first_name": "Clément", "last_name": "Lamy", "name": null }, { "creator_type": "author", "first_name": "Clare", "last_name": "Hudson", "name": null }, { "creator_type": "author", "first_name": "Ute", "last_name": "Rothbächer", "name": null }, { "creator_type": "author", "first_name": "Michael J.", "last_name": "Gilchrist", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro W.", "last_name": "Makabe", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Nori", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Satou", "name": null }, { "creator_type": "author", "first_name": "Patrick", "last_name": "Lemaire", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/gr.108175.110" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20647237" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chordata", "descriptor_ui": "D043344", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Databases, Factual", "descriptor_ui": "D016208", "major_topic": true }, { "descriptor": "Developmental Biology", "descriptor_ui": "D015509", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Internet", "descriptor_ui": "D020407", "major_topic": true }, { "descriptor": "Urochordata", "descriptor_ui": "D014561", "major_topic": true } ], "publication": { "conference_name": null, "date": "2010 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "1459-1468", "proceedings_title": null, "publisher": "", "title": "Genome Research", "volume": "20", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "The ANISEED database: Digital representation, formalization, and elucidation of a chordate developmental program.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Myogenic regulatory factors (MRFs) are transcription factors that possess a characteristic basic helix-loop-helix domain. Myf5, MyoD, MRF4, and myogenin are well-known MRF family members that activate muscle-specific genes during differentiation. Myf5 is expressed first among MRFs at the very early phase and plays an important role in myoblast specificity and cell proliferation. Myf5 shares high homology with MyoD, and therefore some commercial Myf5 antibodies are cross-reactive for Myf5 and MyoD. To allow for detailed studies of the function of Myf5, we generated a monoclonal antibody specific for Myf5 utilizing a rat medial iliac lymph node method. Immunoblot analysis using our monoclonal antibody enabled us to identify Myf5 protein from rat myoblast L6E9 cell extract. Moreover, cell immunostaining revealed the nuclear localization of Myf5 in the L6E9 cells. This monoclonal antibody against Myf5 will allow us to perform further detailed studies of Myf5 and Myf5 function.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Odawara", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Kumamaru", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Saiwai", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/hyb.2009.0066" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20199153" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Antibody Specificity", "descriptor_ui": "D000918", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Enzyme-Linked Immunosorbent Assay", "descriptor_ui": "D004797", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hybridomas", "descriptor_ui": "D006825", "major_topic": false }, { "descriptor": "Ileum", "descriptor_ui": "D007082", "major_topic": false }, { "descriptor": "Immunization", "descriptor_ui": "D007114", "major_topic": false }, { "descriptor": "Immunoenzyme Techniques", "descriptor_ui": "D007124", "major_topic": false }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myoblasts", "descriptor_ui": "D032446", "major_topic": false }, { "descriptor": "Myogenic Regulatory Factor 5", "descriptor_ui": "D051787", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Feb", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "59-62", "proceedings_title": null, "publisher": "", "title": "Hybridoma (2005)", "volume": "29", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Production of a rat monoclonal antibody specific for Myf5.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Peropsin, a member of the opsin family, has characteristics of two functionally distinct opsin-groups, that is, amino acid residues conserved among opsins for light-sensing and a retinal-photoisomerase-like molecular property. Although such a bilateral feature of peropsin seems to be important for understanding the diversity of the opsin family, previous studies have been limited to higher deuterostome, vertebrate and amphioxus peropsins. Here, we report a protostome peropsin homologue from a jumping spider. We found a spider opsin that shares amino acid homology and conserved amino acid residues with known peropsins. The spider opsin-based pigment heterologously expressed in cultured cells exhibited photoisomerase-like isomerization characteristics and a bistable nature. Based on the characteristics of both the amino acid homology and its photochemical properties, we concluded that the spider opsin is the first protostome peropsin homologue. These results show that peropsin existed before the deuterostome-protostome split like other members of the opsin family. In addition, the spider peropsin was localized to non-visual cells in the retina, and fluorescence from reduced retinal chromophore was also observed in the region where peropsin was localized. These findings provide the first demonstration that the peropsin can form a photosensitive pigment in vivo and underlie non-visual function.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Hisao", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00359-009-0493-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19960196" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Eye", "descriptor_ui": "D005123", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Photoreceptor Cells, Invertebrate", "descriptor_ui": "D017956", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Rhodopsin", "descriptor_ui": "D012243", "major_topic": false }, { "descriptor": "Sequence Homology, Amino Acid", "descriptor_ui": "D017386", "major_topic": false }, { "descriptor": "Species Specificity", "descriptor_ui": "D013045", "major_topic": false }, { "descriptor": "Spiders", "descriptor_ui": "D013112", "major_topic": false }, { "descriptor": "Vision, Ocular", "descriptor_ui": "D014785", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "51-59", "proceedings_title": null, "publisher": "", "title": "Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology", "volume": "196", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification and characterization of a protostome homologue of peropsin from a jumping spider.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lanthanide complexes have unique chemical characteristics compared with typical organic complexes, and have recently attracted much interest because of the expanding need for new bioanalytical sensors. For example, magnetic resonance imaging (MRI) permits noninvasive three-dimensional imaging inside opaque organisms, and gadolinium ion (Gd(3+)) complexes have become important tools as MRI contrast agents. However, most of them are nonspecific, and report solely on anatomy. Therefore, responsive MRI contrast agents, so-called \"smart\" MRI contrast agents whose ability to relax water protons is greatly enhanced by recognition of a particular biomolecule, have great potential for elucidating biological phenomena. On the other hand, lanthanide complexes such as europium (Eu(3+)) and terbium (Tb(3+)) complexes have excellent luminescence properties for biological applications, i.e., long luminescence lifetime of the order of milliseconds and a large Stoke's shift of >200 nm. Their long-lived luminescence is especially suitable for time-resolved measurements, because the interference from short-lived background fluorescence and scattered light rapidly decays to a negligible level after a pulse of excitation light is applied, and the emitted light can be collected after an appropriate delay time. These luminescent lanthanide complexes have already found commercial use as highly sensitive luminescent probes in heterogeneous and homogeneous assays. This paper reviews our research on the design and synthesis of responsive lanthanide-based MRI and luminescent probes for advanced bioimaging.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1248/cpb.58.1283" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20930392" } }, "mesh": [ { "descriptor": "Contrast Media", "descriptor_ui": "D003287", "major_topic": false }, { "descriptor": "Coordination Complexes", "descriptor_ui": "D056831", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lanthanoid Series Elements", "descriptor_ui": "D028581", "major_topic": false }, { "descriptor": "Luminescent Agents", "descriptor_ui": "D049408", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": true }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "1283-1294", "proceedings_title": null, "publisher": "", "title": "Chemical & pharmaceutical bulletin", "volume": "58", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of responsive lanthanide-based magnetic resonance imaging and luminescent probes for biological applications.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The stem cell system is one of the unique systems that have evolved only in multicellular organisms. Major questions about this system include what type(s) of stem cells are involved (pluri-, multi- or uni-potent stem cells), and how the self-renewal and differentiation of stem cells are regulated. To understand the origin of the stem cell system in metazoans and to get insights into the ancestral stem cell itself, it is important to discover the molecular and cellular mechanisms of the stem cell system in sponges (Porifera), the evolutionarily oldest extant metazoans. Histological studies here provided a body of evidence that archeocytes are the stem cells in sponges, and recent molecular studies of sponges, especially the finding of the expression of Piwi homologues in archeocytes and choanocytes in a freshwater sponge, Ephydatia fluviatilis, have provided critical insights into the stem cell system in demosponges. Here I introduce archeocytes and discuss (i) modes of archeocyte differentiation, (ii) our current model of the stem cell system in sponges composed of both archeocytes and choanocytes based on our molecular analysis and previous microscopic studies suggesting the maintenance of pluripotency in choanocytes, (iii) the inference that the Piwi and piRNA function in maintaining stem cells (which also give rise to gametes) may have already been achieved in the ancestral metazoan, and (iv) possible hypotheses about how the migrating stem cells arose in the urmetazoan (protometazoan) and about the evolutionary origin of germline cells in the urbilaterian (protobilaterian).", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Noriko", "last_name": "Funayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1440-169x.2009.01162.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20078651" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Porifera", "descriptor_ui": "D011161", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "1-14", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "52", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "The stem cell system in demosponges: insights into the origin of somatic stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Paired immunoglobulin-like type 2 receptor alpha (PILRalpha) is a herpes simplex virus 1 (HSV-1) entry receptor that associates with O-glycans on HSV-1 envelope glycoprotein B (gB). Two threonine residues (Thr-53 and Thr-480) in gB, which are required for the addition of the principal gB O-glycans, are essential for binding to soluble PILRalpha. However, the role of the two threonines in PILRalpha-dependent viral entry remains to be elucidated. Therefore, we constructed a recombinant HSV-1 carrying an alanine replacement of gB Thr-53 alone (gB-T53A) or of both gB Thr-53 and Thr-480 (gB-T53/480A) and demonstrated that these mutations abrogated viral entry in CHO cells expressing PILRalpha. In contrast, the mutations had no effect on viral entry in CHO cells expressing known host cell receptors for HSV-1 gD, viral entry in HL60 cells expressing myelin-associated glycoprotein (MAG) (another HSV-1 gB receptor), viral attachment to heparan sulfate, and viral replication in PILRalpha-negative cells. These results support the hypothesis that gB Thr-53 and Thr-480 as well as gB O-glycosylation, probably at these sites, are critical for PILRalpha-dependent viral entry. Interestingly, following corneal inoculation in mice, the gB-T53A and gB-T53/480A mutations significantly reduced viral replication in the cornea, the development of herpes stroma keratitis, and neuroinvasiveness. The abilities of HSV-1 to enter cells in a PILRalpha-dependent manner and to acquire specific carbohydrates on gB are therefore linked to an increase in viral replication and virulence in the experimental murine model.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Jing", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Suenaga", "name": null }, { "creator_type": "author", "first_name": "Hiroomi", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Arase", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01166-10" }, "pmcid": { "normalized": "PMC2950593" }, "pmid": { "normalized": "20686018" } }, "mesh": [ { "descriptor": "Amino Acid Substitution", "descriptor_ui": "D019943", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "DNA Primers", "descriptor_ui": "D017931", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glycosylation", "descriptor_ui": "D006031", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Host-Pathogen Interactions", "descriptor_ui": "D054884", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Membrane Fusion", "descriptor_ui": "D008561", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mutant Proteins", "descriptor_ui": "D050505", "major_topic": false }, { "descriptor": "Receptors, Immunologic", "descriptor_ui": "D011971", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Viral Envelope Proteins", "descriptor_ui": "D014759", "major_topic": false }, { "descriptor": "Virulence", "descriptor_ui": "D014774", "major_topic": false }, { "descriptor": "Virus Internalization", "descriptor_ui": "D053586", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Oct", "date_precision": "unknown", "issue": "20", "normalized_date": null, "pages": "10773-10783", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "84", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "A single-amino-acid substitution in herpes simplex virus 1 envelope glycoprotein B at a site required for binding to the paired immunoglobulin-like type 2 receptor alpha (PILRalpha) abrogates PILRalpha-dependent viral entry and reduces pathogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Leucine-rich repeat kinase 2 (LRRK2) has been identified as the causal gene for autosomal dominant familial Parkinson's disease (PD), although the mechanism of neurodegeneration involving the mutant LRRK2 molecules remains unknown. In the present study, we found that the protein level of transfected I(2020)T mutant LRRK2 was significantly lower than that of wild-type and G(2019)S mutant LRRK2, although the intracellular localization of the I(2020)T and wild-type molecules did not differ. Pulse-chase experiments proved that the I(2020)T LRRK2 molecule has a higher degradation rate than wild-type or G(2019)S LRRK2. Upon addition of proteasome and lysosome inhibitors, the protein level of I(2020)T mutant LRRK2 reached that of the wild-type. These results indicate that I(2020)T mutant LRRK2 is more susceptible to post-translational degradation than the wild-type molecule. Our results indicate a novel molecular feature characteristic to I(2020)T LRRK2, and provide a new insight into the mechanism of neurodegeneration caused by LRRK2.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Matsuri", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Tajima", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Seisuke", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Obata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2009.10.034" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19833102" } }, "mesh": [ { "descriptor": "Amino Acid Substitution", "descriptor_ui": "D019943", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Isoleucine", "descriptor_ui": "D007532", "major_topic": false }, { "descriptor": "Leucine-Rich Repeat Serine-Threonine Protein Kinase-2", "descriptor_ui": "D000071158", "major_topic": false }, { "descriptor": "Parkinson Disease", "descriptor_ui": "D010300", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Protein Stability", "descriptor_ui": "D055550", "major_topic": false }, { "descriptor": "Threonine", "descriptor_ui": "D013912", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Dec 18", "date_precision": "day", "issue": "3", "normalized_date": "2009-12-18", "pages": "710-715", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "390", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "I(2020)T leucine-rich repeat kinase 2, the causative mutant molecule of familial Parkinson's disease, has a higher intracellular degradation rate than the wild-type molecule.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The framework recently developed for the extraction of a dynamic reaction coordinate to mediate reactions buried in thermal fluctuation is examined with a model system. Numerical simulations are carried out for an underdamped Langevin equation with the Muller-Brown potential surface, which contains three wells and two saddles, and are compared to the prediction by the theory. Reaction probabilities for specific initial conditions of the system as well as their average over the Boltzmann distribution are investigated in the position space and in a space spanned by the position coordinates and the velocities of the system. The nonlinear couplings between the reactive and the nonreactive modes are shown to have significant effects on the reactivity in the model system. The magnitude and the direction of the nonlinear effect are different for the two saddles, which is found to be correctly reproduced by our theory. The whole position-velocity space of the model system is found to be divided into the two distinct regions: One is of mainly reactive (with reaction probability more than half) initial conditions and the other, the mainly nonreactive (with reaction probability less than half) ones. Our theory can actually assign their boundaries as the zero of the statistical average of the new reaction coordinate as an analytical functional of both the original position coordinates and velocities of the system (solute), as well as of the random force and the friction constants from the environment (solvent). The result validates the statement in the previous paper that the sign of the reaction coordinate thus extracted determines the fate of the reaction. Physical interpretation of the reactivity under thermal fluctuation that is naturally derived, thanks to the analyticity of the theoretical framework, is also exemplified for the model system.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/1.3268622" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20001056" } }, "mesh": [], "publication": { "conference_name": null, "date": "2009 Dec 14", "date_precision": "day", "issue": "22", "normalized_date": "2009-12-14", "pages": "224506", "proceedings_title": null, "publisher": "", "title": "The Journal of chemical physics", "volume": "131", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic pathways to mediate reactions buried in thermal fluctuations. II. Numerical illustrations using a model system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We present a novel theory which enables us to explore the mechanism of reaction selectivity and robust functions in complex systems persisting under thermal fluctuation. The theory constructs a nonlinear coordinate transformation so that the equation of motion for the new reaction coordinate is independent of the other nonreactive coordinates in the presence of thermal fluctuation. In this article we suppose that reacting systems subject to thermal noise are described by a multidimensional Langevin equation without a priori assumption for the form of potential. The reaction coordinate is composed not only of all the coordinates and velocities associated with the system (solute) but also of the random force exerted by the environment (solvent) with friction constants. The sign of the reaction coordinate at any instantaneous moment in the region of a saddle determines the fate of the reaction, i.e., whether the reaction will proceed through to the products or go back to the reactants. By assuming the statistical properties of the random force, one can know a priori a well-defined boundary of the reaction which separates the full position-velocity space in the saddle region into mainly reactive and mainly nonreactive regions even under thermal fluctuation. The analytical expression of the reaction coordinate provides the firm foundation on the mechanism of how and why reaction proceeds in thermal fluctuating environments.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/1.3268621" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20001055" } }, "mesh": [ { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": true }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": true }, { "descriptor": "Time", "descriptor_ui": "D013995", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Dec 14", "date_precision": "day", "issue": "22", "normalized_date": "2009-12-14", "pages": "224505", "proceedings_title": null, "publisher": "", "title": "The Journal of chemical physics", "volume": "131", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic pathways to mediate reactions buried in thermal fluctuations. I. Time-dependent normal form theory for multidimensional Langevin equation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ratiometric fluorescent probes based on boron dipyrromethene (BODIPY) were developed based on a novel design strategy, in which a change of the electron-withdrawing character of the 2,6-substituents resulting from reaction with a target molecule generates a fluorescence wavelength change.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Yuuta", "last_name": "Fujikawa", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/b917209b" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19904379" } }, "mesh": [ { "descriptor": "Boron Compounds", "descriptor_ui": "D001896", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Dec 7", "date_precision": "day", "issue": "45", "normalized_date": "2009-12-07", "pages": "7015-7017", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of 2,6-carboxy-substituted boron dipyrromethene (BODIPY) as a novel scaffold of ratiometric fluorescent probes for live cell imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Major depressive and bipolar disorders are serious illnesses that affect millions of people. Growing evidence implicates glutamate signalling in depression, though the molecular mechanism by which glutamate signalling regulates depression-related behaviour remains unknown. In this study, we provide evidence suggesting that tyrosine phosphorylation of the NMDA receptor, an ionotropic glutamate receptor, contributes to depression-related behaviour. The NR2A subunit of the NMDA receptor is tyrosine-phosphorylated, with Tyr 1325 as its one of the major phosphorylation site. We have generated mice expressing mutant NR2A with a Tyr-1325-Phe mutation to prevent the phosphorylation of this site in vivo. The homozygous knock-in mice show antidepressant-like behaviour in the tail suspension test and in the forced swim test. In the striatum of the knock-in mice, DARPP-32 phosphorylation at Thr 34, which is important for the regulation of depression-related behaviour, is increased. We also show that the Tyr 1325 phosphorylation site is required for Src-induced potentiation of the NMDA receptor channel in the striatum. These data argue that Tyr 1325 phosphorylation regulates NMDA receptor channel properties and the NMDA receptor-mediated downstream signalling to modulate depression-related behaviour.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Sachiko", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Asami", "last_name": "Tanimura", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kiyama", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Tezuka", "name": null }, { "creator_type": "author", "first_name": "Ayako M.", "last_name": "Watabe", "name": null }, { "creator_type": "author", "first_name": "Norikazu", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Kazumasa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Izumi-Nakaseko", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Kakuta", "name": null }, { "creator_type": "author", "first_name": "Katsuko", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Iwakura", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Umemori", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Niall P.", "last_name": "Murphy", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Manabe", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/emboj.2009.300" }, "pmcid": { "normalized": "PMC2790487" }, "pmid": { "normalized": "19834457" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Depression", "descriptor_ui": "D003863", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Phenylalanine", "descriptor_ui": "D010649", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Receptors, N-Methyl-D-Aspartate", "descriptor_ui": "D016194", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Tyrosine", "descriptor_ui": "D014443", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Dec 2", "date_precision": "day", "issue": "23", "normalized_date": "2009-12-02", "pages": "3717-3729", "proceedings_title": null, "publisher": "", "title": "The EMBO journal", "volume": "28", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Involvement of NMDAR2A tyrosine phosphorylation in depression-related behaviour.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A new measure is presented to quantify the local topographical feature, i.e., diversity in transitions from a state to the others, on complex networks. This measure is composed of two contributions: one is related to the number of outgoing links from a state (known as degree) and the other is related to heterogeneity in transition probabilities from a state to the others associated with the links. To illustrate the potential of the new measure, we apply it to the multiscale state space networks (SSNs) extracted directly from the single-molecule time series of protein fluctuation of the NADH:flavin oxidoreductase complex by using a recently developed technique [Li, C. B.; Yang, H.; Komatsuzaki, T. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 536]. We find that the multiscale SSN network structures dependent on the time scale of observation are not differentiated significantly in the topological feature of the SSNs where the connectivity pattern among the nodes is solely taken into account, but instead in the weighted properties of the network including the heterogeneous strengths of transitions and the resident probabilities of the nodes. The relationship of the transition heterogeneity with the anomalous diffusion observed in the single-molecule measurement is also discussed.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Chun-Biu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Haw", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jp9059483" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19827784" } }, "mesh": [ { "descriptor": "Markov Chains", "descriptor_ui": "D008390", "major_topic": false }, { "descriptor": "Protein Folding", "descriptor_ui": "D017510", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Nov 5", "date_precision": "day", "issue": "44", "normalized_date": "2009-11-05", "pages": "14732-14741", "proceedings_title": null, "publisher": "", "title": "The journal of physical chemistry. B", "volume": "113", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "New quantification of local transition heterogeneity of multiscale complex networks constructed from single-molecule time series.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Adenosine 5′-triphosphate (ATP) is the major energy currency of cells and is involved in many cellular processes. However, there is no method for real-time monitoring of ATP levels inside individual living cells. To visualize ATP levels, we generated a series of fluorescence resonance energy transfer (FRET)-based indicators for ATP that were composed of the ε subunit of the bacterial FoF1-ATP synthase sandwiched by the cyan- and yellow-fluorescent proteins. The indicators, named ATeams, had apparent dissociation constants for ATP ranging from 7.4 μM to 3.3 mM. By targeting ATeams to different subcellular compartments, we unexpectedly found that ATP levels in the mitochondrial matrix of HeLa cells are significantly lower than those of cytoplasm and nucleus. We also succeeded in measuring changes in the ATP level inside single HeLa cells after treatment with inhibitors of glycolysis and/or oxidative phosphorylation, revealing that glycolysis is the major ATP-generating pathway of the cells grown in glucose-rich medium. This was also confirmed by an experiment using oligomycin A, an inhibitor of FoF1-ATP synthase. In addition, it was demonstrated that HeLa cells change ATP-generating pathway in response to changes of nutrition in the environment.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiromi", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Kim P.", "last_name": "Huynh Nhat", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Togawa", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Iino", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Kato-Yamada", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Noji", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.0904764106" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19720993" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Bacterial Proton-Translocating ATPases", "descriptor_ui": "D025243", "major_topic": false }, { "descriptor": "Cell Compartmentation", "descriptor_ui": "D002451", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Oxidative Phosphorylation", "descriptor_ui": "D010085", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Sep 15", "date_precision": "day", "issue": "37", "normalized_date": "2009-09-15", "pages": "15651-15656", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "106", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualization of ATP levels inside single living cells with fluorescence resonance energy transfer-based genetically encoded indicators.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In spite of the wide availability of various near-infrared (NIR) fluorophores as labeling reagents, there are few functional NIR fluorescent probes for which change in the absorption and/or fluorescence spectra upon specific reaction with biomolecules is seen. The widely used photoinduced electron-transfer mechanism is unsuitable for NIR fluorophores, such as tricarbocyanines, because their long excitation wavelength results in a small singlet excitation energy. We have reported the unique spectral properties of amine-substituted tricarbocyanines, which were utilized to develop two design strategies. One approach was based on control of the absorption wavelength by using the difference in electron-donating ability before and after a specific reaction with a biomolecule, and the other approach was based on control of the fluorescence intensity by modulating the Forster resonance energy-transfer efficiency through a change in the overlap integral that arises from the change in absorption under acidic conditions. These strategies were validated by obtaining tricarbocyanine-based ratiometric NIR fluorescent probes for esterase and for pH level.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuki", "last_name": "Kiyose", "name": null }, { "creator_type": "author", "first_name": "Sakiko", "last_name": "Aizawa", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/chem.200900035" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19650089" } }, "mesh": [ { "descriptor": "Carbocyanines", "descriptor_ui": "D002232", "major_topic": false }, { "descriptor": "Esterases", "descriptor_ui": "D004950", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Spectroscopy, Near-Infrared", "descriptor_ui": "D019265", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Sep 14", "date_precision": "day", "issue": "36", "normalized_date": "2009-09-14", "pages": "9191-9200", "proceedings_title": null, "publisher": "", "title": "Chemistry (Weinheim an der Bergstrasse, Germany)", "volume": "15", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular design strategies for near-infrared ratiometric fluorescent probes based on the unique spectral properties of aminocyanines.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Measurement of intrinsic optical signals (IOSs) is an attractive technique for monitoring tissue viability in brains since it enables noninvasive, real-time monitoring of morphological characteristics as well as physiological and biochemical characteristics of tissue. We previously showed that light scattering signals reflecting cellular morphological characteristics were closely related to the IOSs associated with the redox states of cytochrome c oxidase in the mitochondrial respiratory chain. In the present study, we examined the relationship between light scattering and energy metabolism. Light scattering signals were transcranially measured in rat brains after oxygen and glucose deprivation, and the results were compared with concentrations of cerebral adenosine triphosphate (ATP) measured by luciferin-luciferase bioluminescence assay. Electrophysiological signal was also recorded simultaneously. After starting saline infusion, EEG activity ceased at 108+/-17s, even after which both the light scattering signal and ATP concentration remained at initial levels. However, light scattering started to change in three phases at 236+/-15s and then cerebral ATP concentration started to decrease at about 260s. ATP concentration significantly decreased during the triphasic scattering change, indicating that the start of scattering change preceded the loss of cerebral ATP. The mean time difference between the start of triphasic scattering change and the onset of ATP loss was about 24s in the present model. DC potential measurement showed that the triphasic scattering change was associated with anoxic depolarization. These findings suggest that light scattering signal can be used as an indicator of loss of tissue viability in brains.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Satoko", "last_name": "Kawauchi", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Ooigawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nawashiro", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kikuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neulet.2009.05.014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19446006" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Brain Chemistry", "descriptor_ui": "D001923", "major_topic": false }, { "descriptor": "Brain Ischemia", "descriptor_ui": "D002545", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Electroencephalography", "descriptor_ui": "D004569", "major_topic": false }, { "descriptor": "Electron Transport Complex IV", "descriptor_ui": "D003576", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Scattering, Radiation", "descriptor_ui": "D012542", "major_topic": true }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Aug 14", "date_precision": "day", "issue": "3", "normalized_date": "2009-08-14", "pages": "152-156", "proceedings_title": null, "publisher": "", "title": "Neuroscience letters", "volume": "459", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Light scattering change precedes loss of cerebral adenosine triphosphate in a rat global ischemic brain model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Infection with cagA-positive Helicobacter pylori is the strongest risk factor for the development of gastric carcinoma. The cagA gene product CagA, which is delivered into gastric epithelial cells, specifically binds to and aberrantly activates SHP-2 oncoprotein. CagA also interacts with and inhibits partitioning-defective 1 (PAR1)/MARK kinase, which phosphorylates microtubule-associated proteins to destabilize microtubules and thereby causes epithelial polarity defects. In light of the notion that microtubules are not only required for polarity regulation but also essential for the formation of mitotic spindles, we hypothesized that CagA-mediated PAR1 inhibition also influences mitosis. Here, we investigated the effect of CagA on the progression of mitosis. In the presence of CagA, cells displayed a delay in the transition from prophase to metaphase. Furthermore, a fraction of the CagA-expressing cells showed spindle misorientation at the onset of anaphase, followed by chromosomal segregation with abnormal division axis. The effect of CagA on mitosis was abolished by elevated PAR1 expression. Conversely, inhibition of PAR1 kinase elicited mitotic delay similar to that induced by CagA. Thus, CagA-mediated inhibition of PAR1, which perturbs microtubule stability and thereby causes microtubule-based spindle dysfunction, is involved in the prophase/metaphase delay and subsequent spindle misorientation. Consequently, chronic exposure of cells to CagA induces chromosomal instability. Our findings reveal a bifunctional role of CagA as an oncoprotein: CagA elicits uncontrolled cell proliferation by aberrantly activating SHP-2 and at the same time induces chromosomal instability by perturbing the microtubule-based mitotic spindle. The dual function of CagA may cooperatively contribute to the progression of multistep gastric carcinogenesis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mayumi", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Murata-Kamiya", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Hatakeyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m109.035766" }, "pmcid": { "normalized": "PMC2755941" }, "pmid": { "normalized": "19546211" } }, "mesh": [ { "descriptor": "Anaphase", "descriptor_ui": "D000705", "major_topic": false }, { "descriptor": "Antigens, Bacterial", "descriptor_ui": "D000942", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Chromosomal Instability", "descriptor_ui": "D043171", "major_topic": true }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": false }, { "descriptor": "Helicobacter pylori", "descriptor_ui": "D016480", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Metaphase", "descriptor_ui": "D008677", "major_topic": false }, { "descriptor": "Microscopy, Video", "descriptor_ui": "D018715", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Aug 14", "date_precision": "day", "issue": "33", "normalized_date": "2009-08-14", "pages": "22166-22172", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "284", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Helicobacter pylori CagA causes mitotic impairment and induces chromosomal instability.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "T-type voltage-gated calcium channels are expressed in the dendrites of many neurons, although their functional interactions with postsynaptic receptors and contributions to synaptic signaling are not well understood. We combine electrophysiological and ultrafast two-photon calcium imaging to demonstrate that mGluR1 activation potentiates cerebellar Purkinje cell Cav3.1 T-type currents via a G-protein- and tyrosine-phosphatase-dependent pathway. Immunohistochemical and electron microscopic investigations on wild-type and Cav3.1 gene knock-out animals show that Cav3.1 T-type channels are preferentially expressed in Purkinje cell dendritic spines and colocalize with mGluR1s. We further demonstrate that parallel fiber stimulation induces fast subthreshold calcium signaling in dendritic spines and that the synaptic Cav3.1-mediated calcium transients are potentiated by mGluR1 selectively during bursts of excitatory parallel fiber inputs. Our data identify a new fast calcium signaling pathway in Purkinje cell dendritic spines triggered by short burst of parallel fiber inputs and mediated by T-type calcium channels and mGluR1s.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Michael E.", "last_name": "Hildebrand", "name": null }, { "creator_type": "author", "first_name": "Philippe", "last_name": "Isope", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Toshitaka", "last_name": "Nakaya", "name": null }, { "creator_type": "author", "first_name": "Esperanza", "last_name": "Garcia", "name": null }, { "creator_type": "author", "first_name": "Anne", "last_name": "Feltz", "name": null }, { "creator_type": "author", "first_name": "Toni", "last_name": "Schneider", "name": null }, { "creator_type": "author", "first_name": "Jürgen", "last_name": "Hescheler", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Stéphane", "last_name": "Dieudonné", "name": null }, { "creator_type": "author", "first_name": "Terrance P.", "last_name": "Snutch", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.0362-09.2009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19657020" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Channels, T-Type", "descriptor_ui": "D020747", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Potentials", "descriptor_ui": "D008564", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Aug 5", "date_precision": "day", "issue": "31", "normalized_date": "2009-08-05", "pages": "9668-9682", "proceedings_title": null, "publisher": "", "title": "The Journal of Neuroscience", "volume": "29", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Functional Coupling between mGluR1 and Cav3.1 T-Type Calcium Channels Contributes to Parallel Fiber-Induced Fast Calcium Signaling within Purkinje Cell Dendritic Spines.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Light converts rhodopsin, the prototypical G protein-coupled receptor, into a form capable of activating G proteins. Recent work has shown that the light-activated state of different rhodopsins can possess different molecular properties, especially different abilities to activate G protein. For example, bovine rhodopsin is approximately 20-fold more effective at activating G protein than parapinopsin, a non-visual rhodopsin, although these rhodopsins share relatively high sequence similarity. Here we have investigated possible structural aspects that might underlie this difference. Using a site-directed fluorescence labeling approach, we attached the fluorescent probe bimane to cysteine residues introduced in the cytoplasmic ends of transmembrane helices V and VI in both rhodopsins. The fluorescence spectra of these probes as well as their accessibility to aqueous quenching agents changed dramatically upon photoactivation in bovine rhodopsin but only moderately so in parapinopsin. We also compared the relative movement of helices V and VI upon photoactivation of both rhodopsins by introducing a bimane label and the bimane-quenching residue tryptophan into helices VI and V, respectively. Both receptors showed movement in this region upon activation, although the movement appears much greater in bovine rhodopsin than in parapinopsin. Together, these data suggest that a larger conformational change in helices V and VI of bovine rhodopsin explains why it has greater G protein activation ability than other rhodopsins. The different amplitude of the helix movement may also be responsible for functional diversity of G protein-coupled receptors.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hisao", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "David L.", "last_name": "Farrens", "name": null }, { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m109.016212" }, "pmcid": { "normalized": "PMC2742832" }, "pmid": { "normalized": "19497849" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bridged Bicyclo Compounds", "descriptor_ui": "D001643", "major_topic": false }, { "descriptor": "Cattle", "descriptor_ui": "D002417", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "GTP-Binding Proteins", "descriptor_ui": "D019204", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": true }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Mutant Proteins", "descriptor_ui": "D050505", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Rhodopsin", "descriptor_ui": "D012243", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Jul 31", "date_precision": "day", "issue": "31", "normalized_date": "2009-07-31", "pages": "20676-20683", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "284", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "The magnitude of the light-induced conformational change in different rhodopsins correlates with their ability to activate G proteins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report a method for specifically labelling the surface of cells with two kinds of chemical probes (near-infrared (NIR) fluorescent probes and magnetic resonance (MR) imaging probes) via two genetically expressed tags, and demonstrate the application for in vitro and in vivo dual imaging.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Aki", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Umezawa", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Niino", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Sadakazu", "last_name": "Aiso", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Tanimoto", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/b904055b" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19568626" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biotin", "descriptor_ui": "D001710", "major_topic": false }, { "descriptor": "Contrast Media", "descriptor_ui": "D003287", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrolases", "descriptor_ui": "D006867", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Spectroscopy, Near-Infrared", "descriptor_ui": "D019265", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Jul 21", "date_precision": "day", "issue": "27", "normalized_date": "2009-07-21", "pages": "4040-4042", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell-based in vivo dual imaging probes using genetically expressed tags and chemical contrast agents.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Functional neural circuits are formed by eliminating early-formed redundant synapses and strengthening necessary connections during development. In newborn mouse cerebellum, each Purkinje cell (PC) is innervated by multiple climbing fibers (CFs) with similar strengths. Subsequently, a single CF is selectively strengthened by postnatal day 7 (P7). We find that this competition among multiple CFs occurs on the soma before CFs form synapses along dendrites. Notably, in most PCs, the single CF that has been functionally strengthened (the \"winner\" CF) undergoes translocation to dendrites while keeping its synapses on the soma. Synapses of the weaker CFs (the \"loser\" CFs) remain around the soma and form \"pericellular nests\" with synapses of the winner CFs. Then most perisomatic synapses are eliminated nonselectively by P15. Thus, our results suggest that the selective translocation of the winner CF to dendrites in each PC determines the single CF that survives subsequent synapse elimination and persistently innervates the PC.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2009.06.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19607796" } }, "mesh": [ { "descriptor": "Age Factors", "descriptor_ui": "D000367", "major_topic": false }, { "descriptor": "Aminobutyrates", "descriptor_ui": "D000613", "major_topic": false }, { "descriptor": "Analysis of Variance", "descriptor_ui": "D000704", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Biophysics", "descriptor_ui": "D001703", "major_topic": false }, { "descriptor": "Biotin", "descriptor_ui": "D001710", "major_topic": false }, { "descriptor": "Calbindins", "descriptor_ui": "D064026", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Dextrans", "descriptor_ui": "D003911", "major_topic": false }, { "descriptor": "Electric Stimulation", "descriptor_ui": "D004558", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Nerve Fibers", "descriptor_ui": "D009412", "major_topic": false }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Receptors, Serotonin", "descriptor_ui": "D011985", "major_topic": false }, { "descriptor": "S100 Calcium Binding Protein G", "descriptor_ui": "D064030", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Vesicular Glutamate Transport Protein 2", "descriptor_ui": "D050599", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Jul 16", "date_precision": "day", "issue": "1", "normalized_date": "2009-07-16", "pages": "106-118", "proceedings_title": null, "publisher": "", "title": "Neuron", "volume": "63", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Translocation of a \"winner\" climbing fiber to the Purkinje cell dendrite and subsequent elimination of \"losers\" from the soma in developing cerebellum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescence resonance energy transfer (FRET) between fluorescent proteins is a powerful tool for visualization of signal transduction in living cells, and recently, some strategies for imaging of dual FRET pairs in a single cell have been reported. However, these necessitate alteration of excitation light between two different wavelengths to avoid the spectral overlap, resulting in sequential detection with a lag time. Thus, to follow fast signal dynamics or signal changes in highly motile cells, a single-excitation dual-FRET method should be required. Here we reported this by using four-color imaging with a single excitation light and subsequent linear unmixing to distinguish fluorescent proteins. We constructed new FRET sensors with Sapphire/RFP to combine with CFP/YFP, and accomplished simultaneous imaging of cAMP and cGMP in single cells. We confirmed that signal amplitude of our dual FRET measurement is comparable to of conventional single FRET measurement. Finally, we demonstrated to monitor both intracellular Ca(2+) and cAMP in highly motile cardiac myocytes. To cancel out artifacts caused by the movement of the cell, this method expands the applicability of the combined use of dual FRET sensors for cell samples with high motility.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Niino", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0006036" }, "pmcid": { "normalized": "PMC2696040" }, "pmid": { "normalized": "19551140" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Red Fluorescent Protein", "descriptor_ui": "D000097573", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Jun 24", "date_precision": "day", "issue": "6", "normalized_date": "2009-06-24", "pages": "e6036", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "4", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Simultaneous live cell imaging using dual FRET sensors with a single excitation light.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Treatment of 2-(cyanomethyl)phenyl esters with a catalytic amount of Pd(OAc)(2), PCy(3), and Zn afforded 3-acyl-2-aminobenzofuran derivatives in good to excellent yields, which can be used as building blocks for the synthesis of benzofuran fused heterocycles.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masahito", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/b904127c" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19503906" } }, "mesh": [], "publication": { "conference_name": null, "date": "2009 Jun 21", "date_precision": "day", "issue": "23", "normalized_date": "2009-06-21", "pages": "3466-3468", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "A new route to 3-acyl-2-aminobenzofurans: palladium-catalysed cycloisomerisation of 2-(cyanomethyl)phenyl esters.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A novel design strategy for controlling the fluorescence and photosensitizing ability of thiazole orange (TO) has been developed. The validity of this approach was demonstrated by the synthesis of a beta-galactosidase-activatable photosensitizer, PhoTO-Gal, in which fluorescence is simultaneously activated. PhoTO-Gal was demonstrated to kill HEK293 lacZ(+) cells, which express beta-galactosidase, but not HEK293 lacZ(-) cells, under light illumination. Such activatable photosensitizers should allow more refined PDT without the side effect of prolonged light sensitivity and should also be useful as tools for reporter enzyme expression-specific cell ablation.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Koide", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Yatsushige", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja900443b" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19364098" } }, "mesh": [ { "descriptor": "Benzothiazoles", "descriptor_ui": "D052160", "major_topic": false }, { "descriptor": "beta-Galactosidase", "descriptor_ui": "D001616", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrolysis", "descriptor_ui": "D006868", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Particle Size", "descriptor_ui": "D010316", "major_topic": false }, { "descriptor": "Photosensitizing Agents", "descriptor_ui": "D017319", "major_topic": false }, { "descriptor": "Quinolines", "descriptor_ui": "D011804", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Surface Properties", "descriptor_ui": "D013499", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 May 6", "date_precision": "day", "issue": "17", "normalized_date": "2009-05-06", "pages": "6058-6059", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "131", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Design and development of enzymatically activatable photosensitizer based on unique characteristics of thiazole orange.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mitotic spindle is constructed from microtubules (MTs) nucleated from centrosomes, chromosome proximal regions, and preexisting spindle MTs. Augmin, a recently identified protein complex, is a critical factor in spindle MT-based MT generation in Drosophila S2 cells. Previously, we identified one subunit of human augmin. Here, by using mass spectrometry, we identified the full human augmin complex of 8 subunits and show that it interacts with the γ-tubulin ring complex (γ-TuRC). Unlike augmin-depleted S2 cells, in which the defect in spindle-mediated MT generation is mostly compensated by centrosomal MTs, augmin knockdown alone in HeLa cells triggers the spindle checkpoint, reduces tension on sister kinetochores, and severely impairs metaphase progression. Human augmin knockdown also reduces the number of central spindle MTs during anaphase and causes late-stage cytokinesis failure. A link between augmin and γ-TuRC is likely critical for these functions, because a γ-TuRC mutant that attenuates interaction with augmin does not restore function in vivo. These results demonstrate that MT generation mediated by augmin and γ-TuRC is critical for chromosome segregation and cytokinesis in human cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryota", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Ryu-suke", "last_name": "Nozawa", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Tomioka", "name": null }, { "creator_type": "author", "first_name": "Sabine", "last_name": "Petry", "name": null }, { "creator_type": "author", "first_name": "Ronald D.", "last_name": "Vale", "name": null }, { "creator_type": "author", "first_name": "Chikashi", "last_name": "Obuse", "name": null }, { "creator_type": "author", "first_name": "Gohta", "last_name": "Goshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.0901587106" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19369198" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cytokinesis", "descriptor_ui": "D048749", "major_topic": true }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kinetochores", "descriptor_ui": "D018386", "major_topic": false }, { "descriptor": "Metaphase", "descriptor_ui": "D008677", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": true }, { "descriptor": "Multiprotein Complexes", "descriptor_ui": "D046912", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Subunits", "descriptor_ui": "D021122", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "Spindle Apparatus", "descriptor_ui": "D008941", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Apr 28", "date_precision": "day", "issue": "17", "normalized_date": "2009-04-28", "pages": "6998-7003", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "106", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "The augmin complex plays a critical role in spindle microtubule generation for mitotic progression and cytokinesis in human cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Improved survival is likely linked to the ability to generate stable memories of significant experiences. Considerable evidence in humans and mammalian model animals shows that steroid hormones, which are released in response to emotionally arousing experiences, have an important role in the consolidation of memories of such events. In insects, ecdysone is the major steroid hormone, and it is well characterized with respect to its essential role in coordinating developmental transitions such as larval molting and metamorphosis. However, the functions of ecdysone in adult physiology remain largely elusive. Here, we show that 20-hydroxyecdysone (20E), the active metabolite of ecdysone that is induced by environmental stimuli in adult Drosophila, has an important role in the formation of long-term memory (LTM). In male flies, the levels of 20E were found to be significantly increased after courtship conditioning, and exogenous administration of 20E either enhanced or suppressed courtship LTM, depending on the timing of its administration. We also found that mutants in which ecdysone signaling is reduced were defective in LTM, and that an elevation of 20E levels was associated with activation of the cAMP response element binding protein (CREB), an essential regulator of LTM formation. Our results demonstrate that the molting steroid hormone ecdysone in adult Drosophila is critical to the evolutionarily conserved strategy that is used for the formation of stable memories. We propose that ecdysone is able to consolidate memories possibly by recapturing molecular and cellular processes that are used for normal neural development.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ishimoto", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kitamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.0810213106" }, "pmcid": { "normalized": "PMC2669368" }, "pmid": { "normalized": "19342482" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Cyclic AMP Response Element-Binding Protein", "descriptor_ui": "D017362", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Ecdysone", "descriptor_ui": "D004440", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Receptors, Steroid", "descriptor_ui": "D011987", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Apr 14", "date_precision": "day", "issue": "15", "normalized_date": "2009-04-14", "pages": "6381-6386", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "106", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Ecdysone signaling regulates the formation of long-term courtship memory in adult Drosophila melanogaster.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Wnt signaling through beta-catenin and TCF maintains preadipocytes in an un-differentiated proliferative state; however, the molecular pathway has not been completely defined. By integrating gene expression microarray, chromatin immunoprecipitation-chip, and cell-based experimental approaches, we show that Wnt/beta-catenin signaling activates the expression of COUP-TFII which recruits the SMRT corepressor complex to the first introns located downstream from the first exons of both PPARgamma1 and gamma2 mRNAs. This maintains the local chromatin in a hypoacetylated state and represses PPARgamma gene expression to inhibit adipogenesis. Our experiments define the COUP-TFII/SMRT complex as a previously unappreciated component of the linear pathway that directly links Wnt/beta-catenin signaling to repression of PPARgamma gene expression and the inhibition of adipogenesis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Kudo", "name": null }, { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Aoi", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Iori", "last_name": "Sakakibara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Timothy F.", "last_name": "Osborne", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Hamakubo", "name": null }, { "creator_type": "author", "first_name": "Sadayoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Aburatani", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Kodama", "name": null }, { "creator_type": "author", "first_name": "Juro", "last_name": "Sakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.0901676106" }, "pmcid": { "normalized": "PMC2667001" }, "pmid": { "normalized": "19307559" } }, "mesh": [ { "descriptor": "Acetylation", "descriptor_ui": "D000107", "major_topic": false }, { "descriptor": "Adipogenesis", "descriptor_ui": "D050156", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "beta Catenin", "descriptor_ui": "D051176", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "COUP Transcription Factor I", "descriptor_ui": "D051838", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nuclear Receptor Co-Repressor 2", "descriptor_ui": "D056985", "major_topic": false }, { "descriptor": "PPAR gamma", "descriptor_ui": "D047495", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Wnt Proteins", "descriptor_ui": "D051153", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Apr 7", "date_precision": "day", "issue": "14", "normalized_date": "2009-04-07", "pages": "5819-5824", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "106", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "COUP-TFII acts downstream of Wnt/beta-catenin signal to silence PPARgamma gene expression and repress adipogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A new method is presented to study bifurcation of no-return transition states (TSs) at potential saddles for systems of many degrees of freedom (dof). The method enables us to investigate analytically when and how the no-return TS bifurcates. Our method reveals a new aspect of bifurcation for systems of many dof, i.e., the action variables of the bath dof play a role of control parameters as long as they remain approximately conserved. As an illustrative example, we demonstrate our new method by using a three atomic exchange reaction. The bifurcation of no-return TSs gives rise to a short-lived intermediate state at the saddle, which results in the overestimation of the reaction rate. Hence, the understanding of the bifurcation of the no-return TS is crucial to capture the complexity in kinetics and dynamics of the reactions. The definability of no-return TSs in many-body chemical reactions is also addressed under the occurrence of bifurcation above the reaction threshold.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Chun-Biu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Mikito", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/1.3079819" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19334817" } }, "mesh": [], "publication": { "conference_name": null, "date": "2009 Mar 28", "date_precision": "day", "issue": "12", "normalized_date": "2009-03-28", "pages": "124116", "proceedings_title": null, "publisher": "", "title": "The Journal of chemical physics", "volume": "130", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Bifurcation of no-return transition states in many-body chemical reactions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Water-soluble triblock copolymers consisting of hydrophobic-hydrophilic-dye segments were synthesized by ring-opening metathesis polymerization (ROMP) of norbornadiene monomers, copper-catalyzed click reaction, osmium-catalyzed dihydroxylation, and the following transformations. These polymers in aqueous conditions could form spherical assemblies, whose diameters were 50-60 nm by TEM measurement. From in vivo optical imaging experiments, the spherical assemblies of these copolymers could be efficiently accumulated in tumor cells. In addition, the spherical assemblies of water-soluble polymers accumulated in a tumor cell over two weeks.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kuramochi", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Oride", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/bc800449s" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19193062" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Norbornanes", "descriptor_ui": "D009636", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Spectroscopy, Near-Infrared", "descriptor_ui": "D019265", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Mar 18", "date_precision": "day", "issue": "3", "normalized_date": "2009-03-18", "pages": "511-517", "proceedings_title": null, "publisher": "", "title": "Bioconjugate chemistry", "volume": "20", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Ring-opening metathesis polymerization-based synthesis of ICG-containing amphiphilic triblock copolymers for in vivo tumor imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We herein provide a thorough description of new transgenic mouse models for dentatorubral–pallidoluysian atrophy (DRPLA) harboring a single copy of the full-length human mutant DRPLA gene with 76 and 129 CAG repeats. The Q129 mouse line was unexpectedly obtained by en masse expansion based on the somatic instability of 76 CAG repeats in vivo. The mRNA expression levels of both Q76 and Q129 transgenes were each 80% of that of the endogenous mouse gene, whereas only the Q129 mice exhibited devastating progressive neurological phenotypes similar to those of juvenile-onset DRPLA patients. Electrophysiological studies of the Q129 mice demonstrated age-dependent and region-specific presynaptic dysfunction in the globus pallidus and cerebellum. Progressive shrinkage of distal dendrites of Purkinje cells and decreased currents through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and γ-aminobutyrate type A receptors in CA1 neurons were also observed. Neuropathological studies of the Q129 mice revealed progressive brain atrophy, but no obvious neuronal loss, associated with massive neuronal intranuclear accumulation (NIA) of mutant proteins with expanded polyglutamine stretches starting on postnatal day 4, whereas NIA in the Q76 mice appeared later with regional specificity to the vulnerable regions of DRPLA. Expression profile analyses demonstrated age-dependent down-regulation of genes, including those relevant to synaptic functions and CREB-dependent genes. These results suggest that neuronal dysfunction without neuronal death is the essential pathophysiologic process and that the age-dependent NIA is associated with nuclear dysfunction including transcriptional dysregulations. Thus, our Q129 mice should be highly valuable for investigating the mechanisms of disease pathogenesis and therapeutic interventions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Toshiya", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masami", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Mitsunori", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Jonathan D.", "last_name": "Wood", "name": null }, { "creator_type": "author", "first_name": "Ikuru", "last_name": "Yazawa", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Ryong-Moon", "last_name": "Shin", "name": null }, { "creator_type": "author", "first_name": "Hau-Jie", "last_name": "Yau", "name": null }, { "creator_type": "author", "first_name": "Fu-Chin", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Shimohata", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Onodera", "name": null }, { "creator_type": "author", "first_name": "Christopher A.", "last_name": "Ross", "name": null }, { "creator_type": "author", "first_name": "Motoya", "last_name": "Katsuki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Aosaki", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Tsuji", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/hmg/ddn403" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19039037" } }, "mesh": [ { "descriptor": "Age Factors", "descriptor_ui": "D000367", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Myoclonic Epilepsies, Progressive", "descriptor_ui": "D020191", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false }, { "descriptor": "Trinucleotide Repeat Expansion", "descriptor_ui": "D019680", "major_topic": true } ], "publication": { "conference_name": null, "date": "2009 Feb 15", "date_precision": "day", "issue": "4", "normalized_date": "2009-02-15", "pages": "723-736", "proceedings_title": null, "publisher": "", "title": "Human Molecular Genetics", "volume": "18", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Severe neurological phenotypes of Q129 DRPLA transgenic mice serendipitously created by en masse expansion of CAG repeats in Q76 DRPLA mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Angiogenesis is involved in various physiologic and pathological conditions, including tumor growth, and is tightly regulated by the orchestration of proangiogenic and antiangiogenic factors. Inhibition of vascular endothelial growth factor (VEGF), the best-established antiangiogenic treatment in cancer, has shown some effectiveness; however, the identification of novel regulators, whose function is independent of VEGF, is required to achieve better outcomes. Here, we show that transcription factor 8 (TCF8) is up-regulated in endothelial cells during angiogenesis, acting as a negative regulator. Furthermore, TCF8 is specifically expressed in the endothelium of tumor vessels. Tcf8-heterozygous knockout mice are more permissive than wild-type mice to the formation of tumor blood vessels in s.c. implanted melanoma, which seems to contribute to the more aggressive growth and the lung metastases of the tumor in mutant mice. Suppression of TCF8 facilitates angiogenesis in both in vitro and ex vivo models, and displays comprehensive cellular phenotypes, including enhanced cell invasion, impaired cell adhesion, and increased cell monolayer permeability due to, at least partly, MMP1 overexpression, attenuation of focal adhesion formation, and insufficient VE-cadherin recruitment, respectively. Taken together, our findings define a novel, integral role for TCF8 in the regulation of pathologic angiogenesis, and propose TCF8 as a target for therapeutic intervention in cancer.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takayuki", "last_name": "Inuzuka", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Yujiro", "last_name": "Higashi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/0008-5472.can-08-3620" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19208835" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Dipeptides", "descriptor_ui": "D004151", "major_topic": false }, { "descriptor": "Endothelium, Vascular", "descriptor_ui": "D004730", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Melanoma, Experimental", "descriptor_ui": "D008546", "major_topic": false }, { "descriptor": "Metalloproteases", "descriptor_ui": "D045726", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Umbilical Veins", "descriptor_ui": "D014471", "major_topic": false }, { "descriptor": "Wound Healing", "descriptor_ui": "D014945", "major_topic": false }, { "descriptor": "Zinc Finger E-box-Binding Homeobox 1", "descriptor_ui": "D000071799", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Feb 15", "date_precision": "day", "issue": "4", "normalized_date": "2009-02-15", "pages": "1678-1684", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "69", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Integral role of transcription factor 8 in the negative regulation of tumor angiogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have recently reported that transcription factor 8 (TCF8) negatively regulates pathological angiogenesis by regulating endothelial invasiveness by acting as a transcriptional attenuator of matrix metalloproteinase 1. TCF8 also modulates cell-matrix and cell-cell adhesion; however molecular mechanism of this TCF8 function remains obscure. Here, we provide evidence that TCF8 activates R-Ras, another class of angiogenic regulator, to suppress angiogenesis by a mechanism other than a transcriptional attenuator. Tube formation by human umbilical vein endothelial cells (HUVECs) facilitated by TCF8 suppression was significantly inhibited by the expression of constitutive active mutant of R-Ras. When we examined the mRNA expression levels of R-Ras regulators, no significant changes were observed to explain the R-Ras activation by TCF8. Interestingly, we found that TCF8 bound to CalDAG-GEFIII, an R-Ras activator, in the cytosol, indicating that TCF8 emanates signaling for R-Ras activation from cytosol to regulate angiogenesis negatively.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takayuki", "last_name": "Inuzuka", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2008.12.101" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19116136" } }, "mesh": [ { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Endothelium, Vascular", "descriptor_ui": "D004730", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Guanine Nucleotide Exchange Factors", "descriptor_ui": "D020662", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neovascularization, Physiologic", "descriptor_ui": "D018919", "major_topic": true }, { "descriptor": "ras Guanine Nucleotide Exchange Factors", "descriptor_ui": "D020663", "major_topic": false }, { "descriptor": "ras Proteins", "descriptor_ui": "D018631", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Umbilical Veins", "descriptor_ui": "D014471", "major_topic": false }, { "descriptor": "Zinc Finger E-box-Binding Homeobox 1", "descriptor_ui": "D000071799", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Feb 6", "date_precision": "day", "issue": "2", "normalized_date": "2009-02-06", "pages": "510-513", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "379", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Transcription factor 8 activates R-Ras to regulate angiogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Sadao", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Takeuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.200902182" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19644988" } }, "mesh": [ { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Microfluidics", "descriptor_ui": "D044085", "major_topic": false }, { "descriptor": "Particle Size", "descriptor_ui": "D010316", "major_topic": false }, { "descriptor": "Unilamellar Liposomes", "descriptor_ui": "D053835", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009", "date_precision": "year", "issue": "35", "normalized_date": "2009", "pages": "6533-6537", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "48", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Microfluidic formation of monodisperse, cell-sized, and unilamellar vesicles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Radiotherapy is an important noninvasive treatment for many types of cancer. However, it has been reported that the proliferative, invasive, and metastatic capacities of tumor cells can be increased in the repopulated tumors that survive radiotherapy. We have previously established a radiation-surviving cell model for the human non-small cell lung cancer cell line H1299 by harvesting relic cells 14 days after irradiation (IR cells). Here, we report that cell invasion, cell migration, and cell adhesion are enhanced in these surviving cancer cells. The mRNA expression levels of matrix metalloproteinases (MMPs), including mmp1, mmp2, and mmp9, were upregulated in IR cells compared with parental cells. A gelatin zymogram, wound healing assay, and invasion assay showed increased MMP activity, cell motility, and invasiveness in IR cells, respectively. Moreover, IR cells adhered more tightly to collagen-coated dishes than parental cells. Consistently, paxillin, phosphorylated FAK, integrin beta1, and vinculin were strongly localized at focal adhesions in IR cells, as visualized by immunofluorescence. In this report, we identify molecules responsible for the malignant properties of tumor cells that survive irradiation. These molecules may be important therapeutic targets for the control of repopulated tumors after radiotherapy.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kaori", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Natsuka", "last_name": "Yazawa", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Seiichiro", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Haga", "name": null }, { "creator_type": "author", "first_name": "Motoaki", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Shirato", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nishioka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1247/csf.09006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19724156" } }, "mesh": [ { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Focal Adhesion Kinase 1", "descriptor_ui": "D051417", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Integrin beta1", "descriptor_ui": "D019012", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Matrix Metalloproteinase 1", "descriptor_ui": "D020781", "major_topic": false }, { "descriptor": "Matrix Metalloproteinase 2", "descriptor_ui": "D020778", "major_topic": false }, { "descriptor": "Matrix Metalloproteinase 9", "descriptor_ui": "D020780", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Paxillin", "descriptor_ui": "D051419", "major_topic": false }, { "descriptor": "Radiation Dosage", "descriptor_ui": "D011829", "major_topic": false }, { "descriptor": "Vinculin", "descriptor_ui": "D016596", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009", "date_precision": "year", "issue": "2", "normalized_date": "2009", "pages": "89-96", "proceedings_title": null, "publisher": "", "title": "Cell structure and function", "volume": "34", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Increased motility and invasiveness in tumor cells that survive 10 Gy irradiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This chapter focuses on single-molecule imaging (SMI) in living cells using green fluorescent protein (GFP) or its related fluorescent protein tags (GFPs). Use of GFPs is a convenient technique to achieve molecular imaging of most proteins in living cells. However, because of difficulties in preparing samples suitable for SMI and the instability of fluorescence signals, special care is required for SMI using GFPs in living cells. Techniques for vector preparation, protein expression, sample preparation, microscopy, and image processing for SMI of GFPs in living cells are discussed in this chapter, along with examples of imaging applications. Double labeling of single molecules and single-pair fluorescent resonance energy transfer (spFRET) are possible in living cells using GFP and YFP as fluorescent tags. The limitations of SMI using GFPs are also discussed.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kayo", "last_name": "Hibino", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-59745-483-4_30" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19488718" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cells", "descriptor_ui": "D002477", "major_topic": false }, { "descriptor": "CHO Cells", "descriptor_ui": "D016466", "major_topic": false }, { "descriptor": "Cricetinae", "descriptor_ui": "D006224", "major_topic": false }, { "descriptor": "Cricetulus", "descriptor_ui": "D003412", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Optical Devices", "descriptor_ui": "D055096", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-raf", "descriptor_ui": "D019908", "major_topic": false }, { "descriptor": "ras Proteins", "descriptor_ui": "D018631", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009", "date_precision": "year", "issue": "", "normalized_date": "2009", "pages": "451-460", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "544", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-molecule imaging of fluorescent proteins expressed in living cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Since first described, acoels were considered members of the flatworms (Platyhelminthes). However, no clear synapomorphies among the three large flatworm taxa - the Catenulida, the Acoelomorpha and the Rhabditophora - have been characterized to date. Molecular phylogenies, on the other hand, commonly positioned acoels separate from other flatworms. Accordingly, our own multi-locus phylogenetic analysis using 43 genes and 23 animal species places the acoel flatworm Isodiametra pulchra at the base of all Bilateria, distant from other flatworms. By contrast, novel data on the distribution and proliferation of stem cells and the specific mode of epidermal replacement constitute a strong synapomorphy for the Acoela plus the major group of flatworms, the Rhabditophora. The expression of a piwi-like gene not only in gonadal, but also in adult somatic stem cells is another unique feature among bilaterians. These two independent stem-cell-related characters put the Acoela into the Platyhelminthes-Lophotrochozoa clade and account for the most parsimonious evolutionary explanation of epidermal cell renewal in the Bilateria. Most available multigene analyses produce conflicting results regarding the position of the acoels in the tree of life. Given these phylogenomic conflicts and the contradiction of developmental and morphological data with phylogenomic results, the monophyly of the phylum Platyhelminthes and the position of the Acoela remain unresolved. By these data, both the inclusion of Acoela within Platyhelminthes, and their separation from flatworms as basal bilaterians are well-supported alternatives.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Bernhard", "last_name": "Egger", "name": null }, { "creator_type": "author", "first_name": "Dirk", "last_name": "Steinke", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tarui", "name": null }, { "creator_type": "author", "first_name": "Katrien", "last_name": "De Mulder", "name": null }, { "creator_type": "author", "first_name": "Detlev", "last_name": "Arendt", "name": null }, { "creator_type": "author", "first_name": "Gaëtan", "last_name": "Borgonie", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Funayama", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Gschwentner", "name": null }, { "creator_type": "author", "first_name": "Volker", "last_name": "Hartenstein", "name": null }, { "creator_type": "author", "first_name": "Bert", "last_name": "Hobmayer", "name": null }, { "creator_type": "author", "first_name": "Matthew", "last_name": "Hooge", "name": null }, { "creator_type": "author", "first_name": "Martina", "last_name": "Hrouda", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Chiyoko", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Georg", "last_name": "Kuales", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Daniela", "last_name": "Pfister", "name": null }, { "creator_type": "author", "first_name": "Reinhard", "last_name": "Rieger", "name": null }, { "creator_type": "author", "first_name": "Willi", "last_name": "Salvenmoser", "name": null }, { "creator_type": "author", "first_name": "Julian", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Ulrich", "last_name": "Technau", "name": null }, { "creator_type": "author", "first_name": "Seth", "last_name": "Tyler", "name": null }, { "creator_type": "author", "first_name": "Kiyokazu", "last_name": "Agata", "name": null }, { "creator_type": "author", "first_name": "Walter", "last_name": "Salzburger", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Ladurner", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0005502" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19430533" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Helminth Proteins", "descriptor_ui": "D015801", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": true }, { "descriptor": "Platyhelminths", "descriptor_ui": "D010986", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009", "date_precision": "year", "issue": "5", "normalized_date": "2009", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "4", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "To Be or Not to Be a Flatworm: The Acoel Controversy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The scale-free and small-world network models reflect the functional units of networks. However, when we investigated the network properties of a signaling pathway using these models, no significant differences were found between the original undirected graphs and the graphs in which inactive proteins were eliminated from the gene expression data. We analyzed signaling networks by focusing on those pathways that best reflected cellular function. Therefore, our analysis of pathways started from the ligands and progressed to transcription factors and cytoskeletal proteins. We employed the Python module to assess the target network. This involved comparing the original and restricted signaling cascades as a directed graph using microarray gene expression profiles of late onset Alzheimer's disease. The most commonly used method of shortest-path analysis neglects to consider the influences of alternative pathways that can affect the activation of transcription factors or cytoskeletal proteins. We therefore introduced included k-shortest paths and k-cycles in our network analysis using the Python modules, which allowed us to attain a reasonable computational time and identify k-shortest paths. This technique reflected results found in vivo and identified pathways not found when shortest path or degree analysis was applied. Our module enabled us to comprehensively analyse the characteristics of biomolecular networks and also enabled analysis of the effects of diseases considering the feedback loop and feedforward loop control structures as an alternative path.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryoji", "last_name": "Yanashima", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Yoshiya", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Weatheritt", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Ishizaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/neuro.11/013.2009" }, "pmcid": { "normalized": "PMC2699032" }, "pmid": { "normalized": "19543432" } }, "mesh": [], "publication": { "conference_name": null, "date": "2009", "date_precision": "year", "issue": "", "normalized_date": "2009", "pages": "13", "proceedings_title": null, "publisher": "", "title": "Frontiers in neuroinformatics", "volume": "3", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Network Features and Pathway Analyses of a Signal Transduction Cascade.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Experimental probing of a protein-folding energy landscape can be challenging, and energy landscapes comprising multiple intermediates have not yet been defined. Here, we quasi-statically unfolded single molecules of staphylococcal nuclease by constant-rate mechanical stretching with a feedback positioning system. Multiple discrete transition states were detected as force peaks, and only some of the multiple transition states emerged stochastically in each trial. This finding was confirmed by molecular dynamics simulations, and agreed with another result of the simulations which showed that individual trajectories took highly heterogeneous pathways. The presence of Ca2+ did not change the location of the transition states, but changed the frequency of the emergence. Transition states emerged more frequently in stabilized domains. The simulations also confirmed this feature, and showed that the stabilized domains had rugged energy surfaces. The mean energy required per residue to disrupt secondary structures was a few times the thermal energy (1–3 kBT), which agreed with the stochastic feature. Thus, single-molecule quasi-static measurement has achieved notable success in detecting stochastic features of a huge number of possible conformations of a protein.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Akihiro", "last_name": "Fukagawa", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Sakane", "name": null }, { "creator_type": "author", "first_name": "Makio", "last_name": "Tokunaga", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysics.5.25" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27857576" } }, "mesh": [], "publication": { "conference_name": null, "date": "2009", "date_precision": "year", "issue": "", "normalized_date": "2009", "pages": "25-35", "proceedings_title": null, "publisher": "", "title": "Biophysics", "volume": "5", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Stochastic emergence of multiple intermediates detected by single-molecule quasi-static mechanical unfolding of protein.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: T cell receptor (TCR) engagement leads to formation of signaling microclusters and induction of rapid and dynamic changes in the actin cytoskeleton, although the exact mechanism by which the TCR initiates actin polymerization is incompletely understood. The Vav family of guanine nucleotide exchange factors (GEF) has been implicated in generation of TCR signals and immune synapse formation, however, it is currently not known if Vav's GEF activity is required in T cell activation by the TCR in general, and in actin polymerization downstream of the TCR in particular. Methodology/Principal Findings: Here, we report that Vav1 assembles into signaling microclusters at TCR contact sites and is critical for TCR-initiated actin polymerization. Surprisingly, Vav1 functions in TCR signaling and Ca++ mobilization via a mechanism that does not appear to strictly depend on the intrinsic GEF activity. Conclusions/Significance: We propose here a model in which Vav functions primarily as a tyrosine phosphorylated linker-protein for TCR activation of T cells. Our results indicate that, contrary to expectations based on previously published studies including from our own laboratory, pharmacological inhibition of Vav1's intrinsic GEF activity may not be an effective strategy for T cell-directed immunosuppressive therapy.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ana V.", "last_name": "Miletic", "name": null }, { "creator_type": "author", "first_name": "Daniel B.", "last_name": "Graham", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Sakata-Sogawa", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Michael J.", "last_name": "Hamann", "name": null }, { "creator_type": "author", "first_name": "Saso", "last_name": "Cemerski", "name": null }, { "creator_type": "author", "first_name": "Tracie", "last_name": "Kloeppel", "name": null }, { "creator_type": "author", "first_name": "Daniel D.", "last_name": "Billadeau", "name": null }, { "creator_type": "author", "first_name": "Osami", "last_name": "Kanagawa", "name": null }, { "creator_type": "author", "first_name": "Makio", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Wojciech", "last_name": "Swat", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0006599" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19672294" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biopolymers", "descriptor_ui": "D001704", "major_topic": false }, { "descriptor": "Cytoskeleton", "descriptor_ui": "D003599", "major_topic": false }, { "descriptor": "Guanine Nucleotide Exchange Factors", "descriptor_ui": "D020662", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-vav", "descriptor_ui": "D051567", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009", "date_precision": "year", "issue": "8", "normalized_date": "2009", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "4", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Vav Links the T Cell Antigen Receptor to the Actin Cytoskeleton and T Cell Activation Independently of Intrinsic Guanine Nucleotide Exchange Activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Equine herpesvirus 4 (EHV-4) is a major cause of respiratory tract disease in horses worldwide. The generation of recombinant viruses, which would lead to understanding of viral gene functions, has been hindered by the absence of suitable cell lines and small-animal models of the infection. In the present study, the genome of EHV-4 strain TH20p was cloned as a stable and infectious BAC without any deletions of the viral genes. Mini F plasmid sequences flanked by loxP sites were inserted into the intergenic region between genes 58 and 59. Coinfection of the recombinant virus with a recombinant adenovirus expressing Cre recombinase resulted in the excision of the BAC sequences. Importantly, the resulting recombinant EHV-4 replicated comparably to the wild-type virus in fetal horse kidney cells. The recombinant EHV-4 will facilitate EHV-4 research and provide the opportunity to exploit the power of BAC technology for production of recombinant viral vaccines.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Walid", "last_name": "Azab", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tsujimura", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Yamane", "name": null }, { "creator_type": "author", "first_name": "Yukinobu", "last_name": "Tohya", "name": null }, { "creator_type": "author", "first_name": "Tomio", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Hiroomi", "last_name": "Akashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00705-009-0382-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19387789" } }, "mesh": [ { "descriptor": "Adenoviridae", "descriptor_ui": "D000256", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chromosomes, Artificial, Bacterial", "descriptor_ui": "D022202", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "DNA, Viral", "descriptor_ui": "D004279", "major_topic": false }, { "descriptor": "Genes, Viral", "descriptor_ui": "D005814", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": false }, { "descriptor": "Genome, Viral", "descriptor_ui": "D016679", "major_topic": true }, { "descriptor": "Herpesviridae Infections", "descriptor_ui": "D006566", "major_topic": false }, { "descriptor": "Herpesvirus 4, Equid", "descriptor_ui": "D023141", "major_topic": false }, { "descriptor": "Horse Diseases", "descriptor_ui": "D006734", "major_topic": false }, { "descriptor": "Horses", "descriptor_ui": "D006736", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Viral Plaque Assay", "descriptor_ui": "D010948", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009", "date_precision": "year", "issue": "5", "normalized_date": "2009", "pages": "833-842", "proceedings_title": null, "publisher": "", "title": "Archives of virology", "volume": "154", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Cloning of the genome of equine herpesvirus 4 strain TH20p as an infectious bacterial artificial chromosome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with pleiotropic functions. We report here that PACAP-deficient (PACAP-/-) mice showed increased immobility in a forced swimming test, which was reduced by the antidepressant desipramine, to a similar extent as in wild-type mice. The atypical antipsychotic risperidone and the selective serotonin (5-HT)(2) antagonist ritanserin normalized the depression-like behavior in PACAP-/- mice. The 5-HT(2) agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine-induced 5-HT syndrome was exaggerated in PACAP-/- mice, which suggests a 5-HT(2)-receptor-dependent mechanism in the depression-like behavior. The circadian rhythm of plasma corticosterone and body core temperature was significantly flattened in the mutants. mRNA expression of glucocorticoid receptor was reduced in the mutant hippocampus. The present results suggest that alterations in PACAP signaling might contribute to the pathogenesis of certain depressive conditions amenable to atypical antipsychotic drugs.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Michiyoshi", "last_name": "Hatanaka", "name": null }, { "creator_type": "author", "first_name": "Xiaohong", "last_name": "Guo", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Tanida", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1471-4159.2009.06168.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19457081" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antipsychotic Agents", "descriptor_ui": "D014150", "major_topic": false }, { "descriptor": "Body Temperature", "descriptor_ui": "D001831", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Corticosterone", "descriptor_ui": "D003345", "major_topic": false }, { "descriptor": "Depression", "descriptor_ui": "D003863", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Receptors, Glucocorticoid", "descriptor_ui": "D011965", "major_topic": false }, { "descriptor": "Risperidone", "descriptor_ui": "D018967", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Swimming", "descriptor_ui": "D013550", "major_topic": true } ], "publication": { "conference_name": null, "date": "2009 Jul", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "595-602", "proceedings_title": null, "publisher": "", "title": "Journal of neurochemistry", "volume": "110", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Depression-like behavior in the forced swimming test in PACAP-deficient mice: amelioration by the atypical antipsychotic risperidone.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The adaptor protein Crk mediates intracellular signaling related to cell motility and proliferation and is implicated in human tumorigenesis. The role of Crk in the growth of human sarcoma has remained unclear, however. The present study shows that Crk-induced activation of Src and subsequent signaling by p38 mitogen-activated protein kinase (MAPK) contribute to the enhanced proliferation of human synovial sarcoma cells. Depletion of Crk by RNA interference markedly inhibited proliferation of the synovial sarcoma cell lines HS-SYII, SYO-1, and Fuji as well as prevented anchorage-independent growth. Conversely, reconstitution with CrkII by authentic small interfering RNA-resistant Crk gene restored proliferation in Crk-silenced SYO-1 cells. Crk-depleted synovial sarcoma cells manifested enhanced transcriptional activity and expression of the p16(INK4A) gene, resulting in their accumulation in G(1) phase of the cell cycle. In response to hepatocyte growth factor stimulation, Crk prominently induced the tyrosine phosphorylation of Grb2-associated binder 1 through activation of Src and focal adhesion kinase, and the Src family kinase inhibitor PP2 almost completely inhibited the proliferation of SYO-1 cells. Crk also induced the phosphorylation of p38 MAPK, and SB203580, a p38 MAPK-specific inhibitor, increased expression of p16(INK4A) gene in SYO-1 cells. Furthermore, SB203580 or depletion of p38 MAPK by small interfering RNA suppressed both the phosphorylation of Akt triggered by hepatocyte growth factor and the proliferation of SYO-1 cells. These results suggest that Crk promotes proliferation of human synovial sarcoma cells through activation of Src and its downstream signaling by a novel p38 MAPK-Akt pathway, with these signaling molecules providing potent new targets for molecular therapeutics.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takuya", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Tokifumi", "last_name": "Majima", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Minami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/1541-7786.mcr-09-0064" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19737974" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Growth Processes", "descriptor_ui": "D048708", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p16", "descriptor_ui": "D019941", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "p38 Mitogen-Activated Protein Kinases", "descriptor_ui": "D048051", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-crk", "descriptor_ui": "D050737", "major_topic": false }, { "descriptor": "rac GTP-Binding Proteins", "descriptor_ui": "D020744", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "Sarcoma, Synovial", "descriptor_ui": "D013584", "major_topic": false }, { "descriptor": "src Homology Domains", "descriptor_ui": "D018909", "major_topic": false }, { "descriptor": "src-Family Kinases", "descriptor_ui": "D019061", "major_topic": false }, { "descriptor": "Tyrosine", "descriptor_ui": "D014443", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "1582-1592", "proceedings_title": null, "publisher": "", "title": "Molecular cancer research : MCR", "volume": "7", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Adaptor protein Crk induces Src-dependent activation of p38 MAPK in regulation of synovial sarcoma cell proliferation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Us3 is a serine-threonine protein kinase encoded by herpes simplex virus 1 (HSV-1). As reported here, we attempted to identify the previously unreported physiological substrate of Us3 in HSV-1-infected cells. Our results were as follows. (i) Bioinformatics analysis predicted two putative Us3 phosphorylation sites in the viral envelope glycoprotein B (gB) at codons 557 to 562 (RRVSAR) and codons 884 to 889 (RRNTNY). (ii) In in vitro kinase assays, the threonine residue at position 887 (Thr-887) in the gB domain was specifically phosphorylated by Us3, while the serine residue at position 560 was not. (iii) The phosphorylation of gB Thr-887 in Vero cells infected with wild-type HSV-1 was specifically detected using an antibody that recognized phosphorylated serine or threonine residues with arginine at the -3 and -2 positions. (iv) The phosphorylation of gB Thr-887 in infected cells was dependent on the kinase activity of Us3. (v) The replacement of Thr-887 with alanine markedly upregulated the cell surface expression of gB in infected cells, whereas replacement with aspartic acid, which sometimes mimics constitutive phosphorylation, restored the wild-type phenotype. The upregulation of gB expression on the cell surface also was observed in cells infected with a recombinant HSV-1 encoding catalytically inactive Us3. These results supported the hypothesis that Us3 phosphorylates gB and downregulates the cell surface expression of gB in HSV-1-infected cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Ikuo", "last_name": "Shiratori", "name": null }, { "creator_type": "author", "first_name": "Hiroomi", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Arase", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01451-08" }, "pmcid": { "normalized": "PMC2612323" }, "pmid": { "normalized": "18945776" } }, "mesh": [ { "descriptor": "Amino Acid Substitution", "descriptor_ui": "D019943", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Viral", "descriptor_ui": "D015967", "major_topic": true }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutagenesis, Site-Directed", "descriptor_ui": "D016297", "major_topic": false }, { "descriptor": "Mutant Proteins", "descriptor_ui": "D050505", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Viral Envelope Proteins", "descriptor_ui": "D014759", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "250-261", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "83", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Herpes simplex virus 1 protein kinase Us3 phosphorylates viral envelope glycoprotein B and regulates its expression on the cell surface.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pax7 is a nuclear localization protein, well known as a member of the paired box family. It is expressed at a very early stage of muscle differentiation and is also found in muscle satellite cells that are recognized as muscle stem cells. Pax7 is also recognized as a tumor cell marker since it is greatly expressed in various types of tumor cells. Pax7 has homology among other paired family members and is not easy to distinguish one from the others. In this study, we report on the establishment of monoclonal antibodies (MAb) against Pax7 using a rat medial iliac lymph node method. The quality of the antibody was examined by immunoblotting analysis. It was confirmed that the antibody can specifically recognize the Pax7 protein. It was also revealed that the MAb antibody successfully recognizes the nuclear localized Pax7 protein in Ewing's sarcoma cells by immunocytochemistry. The antibody can clearly show the regions of euchromatin and heterochromatin where hoechst is positive.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Saiwai", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/hyb.2009.0039" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20025506" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Antibody Specificity", "descriptor_ui": "D000918", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Enzyme-Linked Immunosorbent Assay", "descriptor_ui": "D004797", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Paired Box Transcription Factors", "descriptor_ui": "D051761", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "451-453", "proceedings_title": null, "publisher": "", "title": "Hybridoma (2005)", "volume": "28", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of a rat monoclonal antibody specific for Pax7.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "It has been demonstrated that treatment of hyperactive mice with psychostimulants produced a calming effect depending on serotonergic neurotransmission. Our previous study also showed that hyperactivity in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP) was ameliorated by amphetamine in a serotonin (5-HT)(1A)-dependent manner and that amphetamine calmed wild-type mice given the 5-HT(1A) agonist 8-OH-DPAT. Here, we examined if 5-HT(1A)-mediated pathways can be a determinant of the action of other psychostimulants as well as the non-stimulant atomoxetine by examining locomotor activity in mice co-administered with the 5-HT(1A) agonist osemozotan. Co-administration of osemozotan with either methamphetamine or amphetamine was not only antihyperkinetic, but also decreased locomotion to below basal levels. In contrast, osemozotan just nullified methylphenidate-induced hyperactivity. The non-stimulant atomoxetine did not induce hyperactivity, but co-administration of atomoxetine with osemozotan produced a calming effect. The adjunctive effect of osemozotan added to the psychostimulants was blocked by the 5-HT(1A) antagonist WAY-100635 at a low dose (0.1 mg/kg), suggesting the involvement of a presynaptic 5-HT(1A)-mediated mechanism. However, WAY-100635 (up to 1 mg/kg) did not block the effect of atomoxetine plus osemozotan. The present results may provide insights into the therapeutic mechanisms of the psychostimulants and atomoxetine for hyperkinetic disorders.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Rie", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Shibasaki", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Michikazu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Katalin", "last_name": "Koves", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/jphs.08297fp" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19270432" } }, "mesh": [ { "descriptor": "Adrenergic Uptake Inhibitors", "descriptor_ui": "D018759", "major_topic": false }, { "descriptor": "Amphetamine", "descriptor_ui": "D000661", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Atomoxetine Hydrochloride", "descriptor_ui": "D000069445", "major_topic": false }, { "descriptor": "Central Nervous System Stimulants", "descriptor_ui": "D000697", "major_topic": false }, { "descriptor": "Dioxanes", "descriptor_ui": "D004146", "major_topic": false }, { "descriptor": "Dioxoles", "descriptor_ui": "D004149", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Drug Interactions", "descriptor_ui": "D004347", "major_topic": false }, { "descriptor": "Hyperkinesis", "descriptor_ui": "D006948", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Methamphetamine", "descriptor_ui": "D008694", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Piperazines", "descriptor_ui": "D010879", "major_topic": false }, { "descriptor": "Propylamines", "descriptor_ui": "D011437", "major_topic": false }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false }, { "descriptor": "Receptor, Serotonin, 5-HT1A", "descriptor_ui": "D044282", "major_topic": false }, { "descriptor": "Serotonin 5-HT1 Receptor Agonists", "descriptor_ui": "D058825", "major_topic": true }, { "descriptor": "Serotonin 5-HT1 Receptor Antagonists", "descriptor_ui": "D058829", "major_topic": false }, { "descriptor": "Serotonin Antagonists", "descriptor_ui": "D012702", "major_topic": false }, { "descriptor": "Serotonin Receptor Agonists", "descriptor_ui": "D017366", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "396-402", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "109", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "An antihyperkinetic action by the serotonin 1A-receptor agonist osemozotan co-administered with psychostimulants or the non-stimulant atomoxetine in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Brm is a subunit of the SWI/SNF complex that has a ATPase activity. It is well known that the complex plays a major role in cell processes, such as proliferation, differentiation, and DNA repair of cells. Here we report the production of monoclonal antibody (1H7A10) against Brm by rat medial iliac lymph node method. Immunoblot analysis with the antibody revealed the specific recognition of Brm and increase of Brm protein level in skeletal muscle differentiation. Immunocytochemistry analysis shows nuclear localization in myoblast C2C12 and involvement of transcription in the late stages of differentiation.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Seiji", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Saiwai", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/hyb.2009.0044" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20025507" } }, "mesh": [ { "descriptor": "Adenosine Triphosphatases", "descriptor_ui": "D000251", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Antibody Specificity", "descriptor_ui": "D000918", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "DNA Helicases", "descriptor_ui": "D004265", "major_topic": false }, { "descriptor": "Enzyme-Linked Immunosorbent Assay", "descriptor_ui": "D004797", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "455-458", "proceedings_title": null, "publisher": "", "title": "Hybridoma (2005)", "volume": "28", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of a rat monoclonal antibody specific for Brm.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The notochord develops from notochord progenitor cells (NPCs) and functions as a major signaling center to regulate trunk and tail development. NPCs are initially specified in the node by Wnt and Nodal signals at the gastrula stage. However, the underlying mechanism that maintains the NPCs throughout embryogenesis to contribute to the posterior extension of the notochord remains unclear. Here, we demonstrate that Wnt signaling in the NPCs is essential for posterior extension of the notochord. Genetic labeling revealed that the Noto-expressing cells in the ventral node contribute the NPCs that reside in the tail bud. Robust Wnt signaling in the NPCs was observed during posterior notochord extension. Genetic attenuation of the Wnt signal via notochord-specific β-catenin gene ablation resulted in posterior truncation of the notochord. In the NPCs of such mutant embryos, the expression of notochord-specific genes was down-regulated, and an endodermal marker, E-cadherin, was observed. No significant alteration of cell proliferation or apoptosis of the NPCs was detected. Taken together, our data indicate that the NPCs are derived from Noto-positive node cells, and are not fully committed to a notochordal fate. Sustained Wnt signaling is required to maintain the NPCs’ notochordal fate.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kanako", "last_name": "Ukita", "name": null }, { "creator_type": "author", "first_name": "Shino", "last_name": "Hirahara", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Imuta", "name": null }, { "creator_type": "author", "first_name": "Aki", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Chuan-Wei", "last_name": "Jang", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Oginuma", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Saga", "name": null }, { "creator_type": "author", "first_name": "Richard R.", "last_name": "Behringer", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Kondoh", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sasaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.mod.2009.08.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19720144" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "beta Catenin", "descriptor_ui": "D051176", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Notochord", "descriptor_ui": "D009672", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Wnt Proteins", "descriptor_ui": "D051153", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "791-803", "proceedings_title": null, "publisher": "", "title": "Mechanisms of development", "volume": "126", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Wnt signaling maintains the notochord fate for progenitor cells and supports the posterior extension of the notochord.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Development of human chronic pancreatitis is associated with intrapancreatic accumulation of pituitary adenylate cyclase-activating polypeptide (PACAP) accompanied with an altered inflammatory response (Michalski et al., Am J Physiol Gastrointest Liver Physiol. 2008;294:G50-G57). To investigate the role of pancreatic PACAP in the development of acute pancreatitis, we employed transgenic mice over-expressing PACAP in pancreatic beta-cells (PACAP-Tg). In comparison to wild-type mice, PACAP-Tg mice exhibited more severe pathophysiological signs of the cerulein-induced pancreatitis at 12 h, as evidenced by higher serum amylase and lipase levels accompanied by the exacerbation of pancreatic edema, necrosis, and inflammation. Cerulein treatment increased mRNA expression of several proinflammatory cytokines (TNFalpha, IL-1beta, and IL-6) at 12 h with similar magnitude both in wild-type and PACAP-Tg mice. In addition, the mRNA and protein levels of regenerating gene III beta (RegIIIbeta), a key factor in the pancreatic response to acute pancreatitis, were up-regulated at 24 h in wild-type mice upon cerulein administration, whereas they were attenuated in PACAP-Tg mice. These data indicate that over-expressed PACAP in pancreas enhances the cerulein-induced inflammatory response of both acinar cells, leading to aggravated acute pancreatitis, which was accompanied by a down-regulation of RegIIIbeta, an anti-inflammatory factor.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Hamagami", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akinobu", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyama", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/jphs.09119fp" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19672038" } }, "mesh": [ { "descriptor": "Acute Disease", "descriptor_ui": "D000208", "major_topic": false }, { "descriptor": "Amylases", "descriptor_ui": "D000681", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ceruletide", "descriptor_ui": "D002108", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Insulin-Secreting Cells", "descriptor_ui": "D050417", "major_topic": false }, { "descriptor": "Lipase", "descriptor_ui": "D008049", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Pancreatitis", "descriptor_ui": "D010195", "major_topic": false }, { "descriptor": "Pancreatitis-Associated Proteins", "descriptor_ui": "D000073718", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "451-458", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "110", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Over-expression of pancreatic pituitary adenylate cyclase-activating polypeptide (PACAP) aggravates cerulein-induced acute pancreatitis in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Us3 protein kinases encoded by herpes simplex virus 1 (HSV-1) and 2 (HSV-2) are serine/threonine protein kinases and play critical roles in viral replication and pathogenicity in vivo. In the present study, we investigated differences in the biological properties of HSV-1 and HSV-2 Us3 protein kinases and demonstrated that HSV-2 Us3 did not have some of the HSV-1 Us3 kinase functions, including control of nuclear egress of nucleocapsids, localization of UL31 and UL34, and cell surface expression of viral envelope glycoprotein B. In agreement with the observations that HSV-2 Us3 was less important for these functions, the effect of HSV-2 Us3 kinase activity on virulence in mice following intracerebral inoculation was much lower than that of HSV-1 Us3. Furthermore, we showed that alanine substitution in HSV-2 Us3 at a site (aspartic acid at position 147) corresponding to one that can be autophosphorylated in HSV-1 Us3 abolished HSV-2 Us3 kinase activity. Thus, the regulatory and functional effects of Us3 kinase activity are different between HSV-1 and HSV-2.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tomomi", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Sata", "name": null }, { "creator_type": "author", "first_name": "Hiroomi", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Uema", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00993-09" }, "pmcid": { "normalized": "PMC2772709" }, "pmid": { "normalized": "19740999" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Chromosomes, Artificial, Bacterial", "descriptor_ui": "D022202", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Viral", "descriptor_ui": "D015967", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Herpesvirus 2, Human", "descriptor_ui": "D018258", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mutagenesis, Site-Directed", "descriptor_ui": "D016297", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Nucleocapsid", "descriptor_ui": "D019251", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false }, { "descriptor": "Viral Envelope Proteins", "descriptor_ui": "D014759", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virulence", "descriptor_ui": "D014774", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Nov", "date_precision": "unknown", "issue": "22", "normalized_date": null, "pages": "11624-11634", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "83", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Differences in the regulatory and functional effects of the Us3 protein kinase activities of herpes simplex virus 1 and 2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In routine culture, human embryonic stem (hES) cells are maintained on either feeder cells or special culture substrates such as Matrigel. However, to expand hES cells for clinical applications, it is desirable to minimize animal-derived materials in the culture for safety reasons. In this report, we show that the pericellular matrix prepared from human decidua-derived mesenchymal cells (PCM-DM) is a potent substrate material that supports the growth and pluripotency of hES cells as efficiently as Matrigel does. This supporting activity of PCM-DM is stable and can be preserved for several months in the refrigerator. PCM-DM-based culture is compatible with non-conditioned commercial defined medium, and with the maintenance of dissociated hES cells in the presence of ROCK inhibitor. Since decidual mesenchymal cells can be prepared and expanded in a large quantity, PCM-DM is a practical human-derived substitute for the animal-derived substrates for use in clinical-grade culture of hES cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tomoko", "last_name": "Nagase", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Michiru", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Ohgushi", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kanematsu", "name": null }, { "creator_type": "author", "first_name": "Yonehiro", "last_name": "Kanemura", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/dvdy.21944" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19384957" } }, "mesh": [ { "descriptor": "Amides", "descriptor_ui": "D000577", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": true }, { "descriptor": "Decidua", "descriptor_ui": "D003656", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": false }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "1118-1130", "proceedings_title": null, "publisher": "", "title": "Developmental dynamics : an official publication of the American Association of Anatomists", "volume": "238", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Pericellular matrix of decidua-derived mesenchymal cells: a potent human-derived substrate for the maintenance culture of human ES cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This paper presents the preparation and characterization of a single-excitation, dual-emission ratiometric optical Li(+)-sensing device using a newly designed and synthesized highly Li(+)-selective fluoroionophore (KBL-01) carrying 14-crown-4 ether with tetramethyl and benzene blocking subunits as Li(+)-binding site and boron-dipyrromethene as fluorophore. The indicator dye was covalently immobilized on the surface of a porous glass support having a large internal surface area using a silane-coupling agent. The resulting Li(+)-selective glass optode shows dual fluorescence emission response in pseudo-serum at varying Li(+) concentrations, allowing ratiometric signal processing. The obtained signal is independent of the presence of possibly interfering cations (Na(+), K(+), Mg(2+) and Ca(2+)) and pH. The sensor response was found to be reversible within the Li(+) concentration range from 10(-4) to 10(-1) M, and showed good repeatability and light stability. The plots of the ratiometric signal versus the Li(+) concentrations in spiked real human serum go along with the response curve in pseudo-serum. These results indicate that the novel Li(+)-selective glass optode can be employed as a Li(+)-sensing device with high durability, sensitivity and accuracy for medical analyses.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yosuke", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hiruta", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/b912756a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19838421" } }, "mesh": [], "publication": { "conference_name": null, "date": "2009 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "2314-2319", "proceedings_title": null, "publisher": "", "title": "The Analyst", "volume": "134", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "A highly Li(+)-selective glass optode based on fluorescence ratiometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transient receptor potential (TRP) channels play crucial roles in sensory perception. Expression of the Drosophila painless (pain) gene, a homolog of the mammalian TRPA1/ANKTM1 gene, in the peripheral nervous system is required for avoidance behavior of noxious heat or wasabi. Here we report a novel role of the Pain TRP channel expressed in the nervous system in the sexual receptivity in Drosophila virgin females. Compared with wild-type females, pain mutant females copulated with wild-type males significantly earlier. Wild-type males showed comparable courtship latency and courtship index toward wild-type and pain mutant females. Therefore, the early copulation observed in wild-type male and pain mutant female pairs is the result of enhanced sexual receptivity in pain mutant females. Involvement of pain in enhanced female sexual receptivity was confirmed by rescue experiments in which expression of a pain transgene in a pain mutant background restored the female sexual receptivity to the wild-type level. Targeted expression of pain RNAi in putative cholinergic or GABAergic neurons phenocopied the mutant phenotype of pain females. On the other hand, target expression of pain RNAi in dopaminergic neurons did not affect female sexual receptivity. In addition, conditional suppression of neurotransmission in putative GABAergic neurons resulted in a similar enhanced sexual receptivity. Our results suggest that Pain TRP channels expressed in cholinergic and/or GABAergic neurons are involved in female sexual receptivity.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Kasuya", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kitamoto", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Aigaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1601-183x.2009.00503.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19531155" } }, "mesh": [ { "descriptor": "Acetylcholine", "descriptor_ui": "D000109", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain Chemistry", "descriptor_ui": "D001923", "major_topic": false }, { "descriptor": "Copulation", "descriptor_ui": "D003307", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Ion Channels", "descriptor_ui": "D007473", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Nervous System", "descriptor_ui": "D009420", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "Sexual Behavior, Animal", "descriptor_ui": "D012726", "major_topic": false }, { "descriptor": "Species Specificity", "descriptor_ui": "D013045", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false }, { "descriptor": "Transient Receptor Potential Channels", "descriptor_ui": "D050051", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Jul", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "546-557", "proceedings_title": null, "publisher": "", "title": "Genes, brain, and behavior", "volume": "8", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "The Drosophila TRPA channel, Painless, regulates sexual receptivity in virgin females.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent studies indicate the importance of spatiotemporal regulation in the diversity and specificity of intracellular signaling. Here, we show that Ras-PI3K signaling plays an important role in the local regulation of phosphatidylinositol metabolism in the endosome through live-cell imaging by using a bimolecular fluorescence complementation technique, in which molecular interaction is indicated by fluorescence emission. Using several possible combinations of Ras and the Ras-binding domain, we identified an optimal set of probe molecules that yielded the most significant increase in fluorescence intensity between the active and inactive forms of Ras. This combination revealed that, among the Ras effectors tested, phosphatidylinositol 3-kinase (PI3K) was specifically implicated in signaling in the endosome. We also found that full length PI3K was recruited to the endosome in EGF- and Ras-dependent manners, which appears to be essential for the activation of PI3K in this compartment. Taken together, these findings demonstrate that the spatiotemporal regulation of Ras-PI3K signaling may dictate the activation of PI3K and subsequent downstream signaling in the endosome.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 }, { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kaori", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cellsig.2009.07.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19616621" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Endosomes", "descriptor_ui": "D011992", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": true }, { "descriptor": "Phosphatidylinositol 3-Kinases", "descriptor_ui": "D019869", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "ras Proteins", "descriptor_ui": "D018631", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "1672-1679", "proceedings_title": null, "publisher": "", "title": "Cellular signalling", "volume": "21", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualization of Ras-PI3K interaction in the endosome using BiFC.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Paired immunoglobulin-like type 2 receptor α (PILRα) is an inhibitory receptor expressed on both hematopoietic and nonhematopoietic cells. Its binding to a cellular ligand, CD99, depends on the presence of sialylated O-linked glycans on CD99. Glycoprotein B (gB) of herpes simplex virus type 1 (HSV-1) binds to PILRα, and this association is involved in HSV-1 infection. Here, we found that the presence of sialylated O-glycans on gB is required for gB to associate with PILRα. Furthermore, we identified two threonine residues on gB that are essential for the addition of the principal O-glycans acquired by gB and that are also essential for the binding of PILRα to gB.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Jing", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Qing", "last_name": "Fan", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Lewis L.", "last_name": "Lanier", "name": null }, { "creator_type": "author", "first_name": "Patricia G.", "last_name": "Spear", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Arase", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00792-09" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19812165" } }, "mesh": [ { "descriptor": "Glycosylation", "descriptor_ui": "D006031", "major_topic": false }, { "descriptor": "Membrane Glycoproteins", "descriptor_ui": "D008562", "major_topic": false }, { "descriptor": "Polysaccharides", "descriptor_ui": "D011134", "major_topic": false }, { "descriptor": "Receptors, Immunologic", "descriptor_ui": "D011971", "major_topic": false }, { "descriptor": "Viral Envelope Proteins", "descriptor_ui": "D014759", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Dec", "date_precision": "unknown", "issue": "24", "normalized_date": null, "pages": "13042-13045", "proceedings_title": null, "publisher": "", "title": "Journal of Virology", "volume": "83", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Binding of Herpes Simplex Virus Glycoprotein B (gB) to Paired Immunoglobulin-Like Type 2 Receptor α Depends on Specific Sialylated O-Linked Glycans on gB▿.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the cerebellum of juvenile mice or rats, endocannabinoids are shown to mediate depolarization-induced suppression of excitation (DSE) and retrograde suppression induced by activation of type 1 metabotropic glutamate receptor (mGluR1) at parallel fiber (PF) to Purkinje cell (PC) synapses. However, recent studies showed that glutamate also mediated retrograde signaling through presynaptic kainate receptors in the cerebellum of young adult mice and rats. We reexamined this possibility in C57BL/6 mice at postnatal day 20-35 (P20-P35) and in Sprague-Dawley rats at P18-P24. We found that DSE at PF-PC synapses was abolished by AM251, a cannabinoid receptor antagonist, and by tetrahydrolipstatin (THL), a blocker of diacylglycerol lipase (DGL) that produces an endocannabinoid, 2-arachidonoylglycerol (2-AG). AM251 and THL did not affect depolarization-induced Ca(2+) transients in PCs, and THL did not suppress cannabinoid sensitivity of PFs. Moreover, DSE at PF-PC synapses was absent in CB(1) knockout mice. AM251 also eliminated transient suppression of PF-PC synaptic transmission following a brief burst of PF stimulation, a phenomenon known to be mediated by mGluR1. These results suggest that DSE and mGluR1-mediated suppression in young adult PCs are mediated by endocannabinoids, and that glutamate, if any, has little contribution.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Asami", "last_name": "Tanimura", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuropharm.2009.04.015" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19447120" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cannabinoid Receptor Antagonists", "descriptor_ui": "D063387", "major_topic": false }, { "descriptor": "Cannabinoid Receptor Modulators", "descriptor_ui": "D063385", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": true }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Lactones", "descriptor_ui": "D007783", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neural Inhibition", "descriptor_ui": "D009433", "major_topic": false }, { "descriptor": "Orlistat", "descriptor_ui": "D000077403", "major_topic": false }, { "descriptor": "Piperidines", "descriptor_ui": "D010880", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Pyrazoles", "descriptor_ui": "D011720", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Receptor, Cannabinoid, CB1", "descriptor_ui": "D043884", "major_topic": false }, { "descriptor": "Receptors, Cannabinoid", "descriptor_ui": "D043882", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Aug", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "157-163", "proceedings_title": null, "publisher": "", "title": "Neuropharmacology", "volume": "57", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Not glutamate but endocannabinoids mediate retrograde suppression of cerebellar parallel fiber to Purkinje cell synaptic transmission in young adult rodents.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Brm-related gene-1 (Brg1) is a catalytic subunit of the SWI/SNF chromatin remodeling enzyme complex that has ATPase activity. This complex facilitates chromatin remodeling for gene expression by utilizing energy for ATP hydrolysis. It is well known that the SWI/SNF chromatin remodeling enzyme complex is essential for cell differentiation, cell cycle regulation, and embryogenesis. Here we report the establishment of a hybridoma cell line for producing an antibody against Brg1 subunit by the rat medial iliac lymph node method. Immunoblot analysis showed that our antibody can specifically recognize Brg1. It was revealed by immunocytochemistry that Brg1 is located in euchromatin of C2C12 myoblast nuclei. These data suggested this antibody is useful for analyzing molecular function of Brg1 protein in cells.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A02", "label": "Publicly Offered A02 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tachibana", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/hyb.2009.0041" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20025509" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Antibody Specificity", "descriptor_ui": "D000918", "major_topic": false }, { "descriptor": "DNA Helicases", "descriptor_ui": "D004265", "major_topic": false }, { "descriptor": "Enzyme-Linked Immunosorbent Assay", "descriptor_ui": "D004797", "major_topic": false }, { "descriptor": "Epitopes", "descriptor_ui": "D000939", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "463-466", "proceedings_title": null, "publisher": "", "title": "Hybridoma (2005)", "volume": "28", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Production of a rat monoclonal antibody against Brg1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Haematopoiesis and blood vessel formation are closely associated, with several molecules employed by both systems. Recently, vasohibin-1 (VASH1), an endothelium-derived negative feedback regulator of angiogenesis, has been isolated and characterized. VASH1 is induced by VEGF or bFGF in endothelial cells (ECs) and inhibits their proliferation and migration. However, there are no data on the induction and expression of VASH1 in haematopoietic cells (HCs). Here, we show that the haematopoietic stem cell (HSC) population, but not haematopoietic progenitors (HPs) or mature HCs from adult bone marrow (BM) constitutively express VASH1. However, HPs, but not HSCs, can be induced to express VASH1 after BM suppression by 5-FU. Knock-down of the VASH1 gene in VASH1(+) leukaemia cells induced cell proliferation. These results suggest a role for VASH1 in negative feedback regulation of HP proliferation during recovery following BM ablation.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jb/mvp021" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19179360" } }, "mesh": [ { "descriptor": "Angiogenesis Inhibitors", "descriptor_ui": "D020533", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Marrow Cells", "descriptor_ui": "D001854", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Fluorouracil", "descriptor_ui": "D005472", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ischemia", "descriptor_ui": "D007511", "major_topic": false }, { "descriptor": "Leukemia", "descriptor_ui": "D007938", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor Receptor-2", "descriptor_ui": "D040301", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "653-659", "proceedings_title": null, "publisher": "", "title": "Journal of biochemistry", "volume": "145", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Induction and expression of anti-angiogenic vasohibins in the hematopoietic stem/progenitor cell population.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To examine chromatophore control by FMRFamide-related peptide (FaRP), we investigated the pharmacological effect of FMRFamide on the chromatophores and the FMRFamide-immunoreactivity of nerves surrounding the muscles in the coastal squid, Sepioteuthis lessoniana. Applications of FMRFamide elicited expansion of black chromatophores and retraction of yellow chromatophores in the adult squid. FMRFamide-immunoreactive terminals were distributed along black chromatophore muscles but were not observed around the yellow ones. This means that FMRFamide functions differently for each of the two types of chromatophores in the adult squid. Moreover, the pharmacological effect of FMRFamide on the black chromatophores differed between adults and hatchlings; application of FMRFamide retracted black chromatophores in hatchlings but not in adults. These results indicate that certain squid species have an FaRP system for controlling the chromatophores in their skin and that the system changes during development.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mamiko", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10158-010-0098-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20376518" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromatophores", "descriptor_ui": "D002856", "major_topic": false }, { "descriptor": "Decapodiformes", "descriptor_ui": "D049832", "major_topic": false }, { "descriptor": "FMRFamide", "descriptor_ui": "D019835", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Dec", "date_precision": "unknown", "issue": "3-4", "normalized_date": null, "pages": "185-193", "proceedings_title": null, "publisher": "", "title": "Invertebrate neuroscience : IN", "volume": "9", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "FMRFamide elicits chromatophore expansion and retraction depending on its type and development in the squid, Sepioteuthis lessoniana.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Functional neural circuit formation during postnatal development involves the elimination of early-formed redundant synapses. In the neonatal mouse cerebellum, each Purkinje cell is innervated by multiple climbing fibers (CFs). Their synaptic strengths are initially uniform but one CF strengthens relative to other CFs during the first postnatal week. Then the weaker CFs are eliminated during the second postnatal week. Projections from the retina to the lateral geniculate nucleus (LGN) undergo similar developmental changes, that is the elimination of the majority of inputs and strengthening of a few afferents that remain. Recent studies have clarified that in both cerebellum and LGN, synapse refinement consists of multiple phases and that distinct types of neural activity drive synaptic remodeling in each developmental phase.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.conb.2009.05.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19481442" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Geniculate Bodies", "descriptor_ui": "D005829", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "154-161", "proceedings_title": null, "publisher": "", "title": "Current opinion in neurobiology", "volume": "19", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Synapse elimination in the central nervous system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Apelin is a recently-isolated bioactive peptide from bovine gastric extract. The gene encodes a protein of 77 amino acids, which can generate two active polypeptides, long (42-77) and short (65-77). Both peptides ligate and activate APJ, a G protein-coupled receptor expressed in the cardiovascular and central nervous systems. Although an essential role for the apelin/APJ system in blood vessel formation has been reported in Xenopus, its precise function in mammals is unclear. Blood vessel tube formation is accomplished by two main mechanisms: 1) single cell hollowing, in which a lumen forms within the cytoplasm of a single endothelial cell (EC), and 2) cord hollowing in which a luminal cavity is created de novo between ECs in a thin cylindrical cord. Molecular control of either single cell or cord hollowing has not been precisely determined. Angiopoietin-1 (Ang1) has been reported to induce enlargement of blood vessels. Apelin is produced from ECs upon activation of Tie2, a cognate receptor of Ang1, expressed on ECs. It has been suggested that apelin induces cord hollowing by promoting proliferation and aggregation/assembly of ECs. During angiogenesis, haematopoietic stem cells (HSCs) and progenitor cells (HPCs) are frequently observed in the perivascular region. They produce Ang1 and induce migration of ECs, resulting in a fine vascular network. Moreover, HSCs/HPCs can induce apelin production from ECs. Therefore, this review article posits that HSCs/HPCs regulate caliber size of blood vessels via apelin/APJ and Angiopoietin/Tie2 interactions.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19492139" } }, "mesh": [ { "descriptor": "Angiopoietin-1", "descriptor_ui": "D042683", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apelin", "descriptor_ui": "D000073861", "major_topic": false }, { "descriptor": "Apelin Receptors", "descriptor_ui": "D000075244", "major_topic": false }, { "descriptor": "Blood Vessels", "descriptor_ui": "D001808", "major_topic": true }, { "descriptor": "Cattle", "descriptor_ui": "D002417", "major_topic": false }, { "descriptor": "Endothelium, Vascular", "descriptor_ui": "D004730", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Neovascularization, Physiologic", "descriptor_ui": "D018919", "major_topic": false }, { "descriptor": "Receptor, TIE-2", "descriptor_ui": "D042787", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Xenopus", "descriptor_ui": "D014981", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "999-1005", "proceedings_title": null, "publisher": "", "title": "Thrombosis and haemostasis", "volume": "101", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Maturation of blood vessels by haematopoietic stem cells and progenitor cells: involvement of apelin/APJ and angiopoietin/Tie2 interactions in vessel caliber size regulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The discovery of cannabinoid receptors and subsequent identification of their endogenous ligands (endocannabinoids) in early 1990s have greatly accelerated research on cannabinoid actions in the brain. Then, the discovery in 2001 that endocannabinoids mediate retrograde synaptic signaling has opened up a new era for cannabinoid research and also established a new concept how diffusible messengers modulate synaptic efficacy and neural activity. The last 7 years have witnessed remarkable advances in our understanding of the endocannabinoid system. It is now well accepted that endocannabinoids are released from postsynaptic neurons, activate presynaptic cannabinoid CB(1) receptors, and cause transient and long-lasting reduction of neurotransmitter release. In this review, we aim to integrate our current understanding of functions of the endocannabinoid system, especially focusing on the control of synaptic transmission in the brain. We summarize recent electrophysiological studies carried out on synapses of various brain regions and discuss how synaptic transmission is regulated by endocannabinoid signaling. Then we refer to recent anatomical studies on subcellular distribution of the molecules involved in endocannabinoid signaling and discuss how these signaling molecules are arranged around synapses. In addition, we make a brief overview of studies on cannabinoid receptors and their intracellular signaling, biochemical studies on endocannabinoid metabolism, and behavioral studies on the roles of the endocannabinoid system in various aspects of neural functions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Ohno-Shosaku", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hashimotodani", "name": null }, { "creator_type": "author", "first_name": "Motokazu", "last_name": "Uchigashima", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1152/physrev.00019.2008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19126760" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cannabinoid Receptor Modulators", "descriptor_ui": "D063385", "major_topic": false }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Receptors, Cannabinoid", "descriptor_ui": "D043882", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "309-380", "proceedings_title": null, "publisher": "", "title": "Physiological reviews", "volume": "89", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Endocannabinoid-mediated control of synaptic transmission.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The endoplasmic reticulum (ER) is proposed to be a membrane donor for phagosome formation. In support of this, we have previously shown that the expression level of syntaxin 18, an ER-localized SNARE protein, correlates with phagocytosis activity. To obtain further insights into the involvement of the ER in phagocytosis we focused on Sec22b, another ER-localized SNARE protein that is also found on phagosomal membranes. In marked contrast to the effects of syntaxin 18, we report here that phagocytosis was nearly abolished in J774 macrophages stably expressing mVenus-tagged Sec22b, without affecting the cell surface expression of the Fc receptor or other membrane proteins related to phagocytosis. Conversely, the capacity of the parental J774 cells for phagocytosis was increased when endogenous Sec22b expression was suppressed. Domain analyses of Sec22b revealed that the R-SNARE motif, a selective domain for forming a SNARE complex with syntaxin18 and/or D12, was responsible for the inhibition of phagocytosis. These results strongly support the ER-mediated phagocytosis model and indicate that Sec22b is a negative regulator of phagocytosis in macrophages, most likely by regulating the level of free syntaxin 18 and/or D12 at the site of phagocytosis.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kiyotaka", "last_name": "Hatsuzawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Seisuke", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Arisa", "last_name": "Higa-Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Ikuo", "last_name": "Wada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1091/mbc.e09-03-0241" }, "pmcid": { "normalized": "PMC2762144" }, "pmid": { "normalized": "19710423" } }, "mesh": [ { "descriptor": "Amino Acid Motifs", "descriptor_ui": "D020816", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Opsonin Proteins", "descriptor_ui": "D009895", "major_topic": false }, { "descriptor": "Phagocytosis", "descriptor_ui": "D010587", "major_topic": false }, { "descriptor": "Protein Interaction Mapping", "descriptor_ui": "D025941", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Qa-SNARE Proteins", "descriptor_ui": "D050765", "major_topic": false }, { "descriptor": "Qc-SNARE Proteins", "descriptor_ui": "D050767", "major_topic": false }, { "descriptor": "R-SNARE Proteins", "descriptor_ui": "D050683", "major_topic": false }, { "descriptor": "Receptors, IgG", "descriptor_ui": "D017452", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "SNARE Proteins", "descriptor_ui": "D050600", "major_topic": false }, { "descriptor": "Vesicular Transport Proteins", "descriptor_ui": "D033921", "major_topic": false }, { "descriptor": "Zymosan", "descriptor_ui": "D015054", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Oct", "date_precision": "unknown", "issue": "20", "normalized_date": null, "pages": "4435-4443", "proceedings_title": null, "publisher": "", "title": "Molecular biology of the cell", "volume": "20", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Sec22b is a negative regulator of phagocytosis in macrophages.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Despite the accumulating research on noncoding RNAs (ncRNAs), it is likely that we are seeing only the tip of the iceberg regarding our understanding of the functions and the regulatory roles served by ncRNAs in cellular metabolism, pathogenesis and host-pathogen interactions. Therefore, more powerful computational and experimental tools for analyzing ncRNAs need to be developed. To this end, we propose novel kernel functions, called base-pairing profile local alignment (BPLA) kernels, for analyzing functional ncRNA sequences using support vector machines (SVMs). We extend the local alignment kernels for amino acid sequences in order to handle RNA sequences by using STRAL's; scoring function, which takes into account sequence similarities as well as upstream and downstream base-pairing probabilities, thus enabling us to model secondary structures of RNA sequences. As a test of the performance of BPLA kernels, we applied our kernels to the problem of discriminating members of an RNA family from nonmembers using SVMs. The results indicated that the discrimination ability of our kernels is stronger than that of other existing methods. Furthermore, we demonstrated the applicability of our kernels to the problem of genome-wide search of snoRNA families in the Caenorhabditis elegans genome, and confirmed that the expression is valid in 14 out of 48 of our predicted candidates by using qRT-PCR. Finally, highly expressed six candidates were identified as the original target regions by DNA sequencing.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kensuke", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Yasubumi", "last_name": "Sakakibara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nar/gkn1054" }, "pmcid": { "normalized": "PMC2647286" }, "pmid": { "normalized": "19129214" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": true }, { "descriptor": "Base Pairing", "descriptor_ui": "D020029", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Genome, Helminth", "descriptor_ui": "D049751", "major_topic": true }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Nucleic Acid Conformation", "descriptor_ui": "D009690", "major_topic": false }, { "descriptor": "RNA, Small Nucleolar", "descriptor_ui": "D020537", "major_topic": false }, { "descriptor": "Sequence Alignment", "descriptor_ui": "D016415", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Feb", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "999-1009", "proceedings_title": null, "publisher": "", "title": "Nucleic acids research", "volume": "37", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Genome-wide searching with base-pairing kernel functions for noncoding RNAs: computational and expression analysis of snoRNA families in Caenorhabditis elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Psychostimulants induce hyperlocomotion in normal subjects, although, they are effective in producing a calming effect in hyperactive subjects. This paradoxical effect has been related to changes in serotonin (5-HT) neurotransmission in hyperactive dopamine transporter-knockout mice. In addition, we observed that hyperlocomotion in mice lacking pituitary adenylate cyclase-activating polypeptide was attenuated by amphetamine dependent on 5-HT(1A) receptor signaling and that amphetamine, when co-administered with a 5-HT(1A) agonist, produced a calming effect in wild-type mice. Here, in an attempt to address how 5-HT(1A) receptor signaling exerts the calming action of psychostimulants, we examined c-Fos expression in several brain regions after administration of methamphetamine and osemozotan, a selective 5-HT(1A) receptor agonist. The number of c-Fos-positive cells was increased in the medial prefrontal cortex, striatum and nucleus accumbens in methamphetamine (3 mg/kg body weight)-injected mice. Osemozotan (1 mg/kg) significantly reduced the methamphetamine-induced c-Fos expression in the medial prefrontal cortex and striatum, but not in the nucleus accumbens. This osemozotan action was completely blocked by the 5-HT(1A) receptor antagonist WAY-100635 (1 mg/kg). As the prefrontal cortex is considered to be involved in the beneficial actions of psychostimulant medications for attention-deficit/hyperactivity disorder, the present result showing 5-HT(1A)-mediated inhibition of corticostriatal activity may partly be related to this psychostimulant action.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Rie", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Michikazu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Katalin", "last_name": "Koves", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Uetsuki", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1248/bpb.32.728" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19336914" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Central Nervous System Stimulants", "descriptor_ui": "D000697", "major_topic": false }, { "descriptor": "Dioxanes", "descriptor_ui": "D004146", "major_topic": false }, { "descriptor": "Dioxoles", "descriptor_ui": "D004149", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Genes, fos", "descriptor_ui": "D016762", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Methamphetamine", "descriptor_ui": "D008694", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Neostriatum", "descriptor_ui": "D017072", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Piperazines", "descriptor_ui": "D010879", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false }, { "descriptor": "Serotonin 5-HT1 Receptor Agonists", "descriptor_ui": "D058825", "major_topic": true }, { "descriptor": "Serotonin Antagonists", "descriptor_ui": "D012702", "major_topic": false }, { "descriptor": "Serotonin Receptor Agonists", "descriptor_ui": "D017366", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "728-731", "proceedings_title": null, "publisher": "", "title": "Biological & pharmaceutical bulletin", "volume": "32", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Inhibitory effects of osemozotan, a serotonin 1A-receptor agonist, on methamphetamine-induced c-Fos expression in prefrontal cortical neurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Almost all mammalian alphaherpesviruses can grow in cells derived from several types of animals in vitro. However, FHV-1 can only infect feline cell lines. For this reason, FHV-1 should be a good model to investigate species barriers to herpesviruses in vivo. To apply bacterial mutagenesis of FHV-1, we cloned the FHV-1 genome as a BAC. Using lambda and flp recombinations, we introduced a monomeric red fluorescence protein into the C-terminus of glycoprotein D. Although GFP in the constructed recombinant FHV-1, a transfectant of the bacmid of FHV-1 that possessed the GFP, acted in non-feline cell lines, the virus could not enter non-feline cell lines, demonstrating that the host specificity of FHV-1 was restricted in an early step of infection. The host range of canine herpesvirus is limited to dogs in vitro and in vivo; it cannot enter non-canine cell lines as a result of infection but the GFP is active by transfection, revealing the same result that the restriction step is at an early stage of infection. These results suggest the possibility of breaking species barriers of FHV-1 and CHV by modifying the gene(s) that act at the early stage of infection.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Yukinobu", "last_name": "Tohya", "name": null }, { "creator_type": "author", "first_name": "Hiroomi", "last_name": "Akashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1348-0421.2009.00147.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19659927" } }, "mesh": [ { "descriptor": "Alphaherpesvirinae", "descriptor_ui": "D018138", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cat Diseases", "descriptor_ui": "D002371", "major_topic": false }, { "descriptor": "Cats", "descriptor_ui": "D002415", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chromosomes, Artificial, Bacterial", "descriptor_ui": "D022202", "major_topic": false }, { "descriptor": "Genome, Viral", "descriptor_ui": "D016679", "major_topic": true }, { "descriptor": "Herpesviridae Infections", "descriptor_ui": "D006566", "major_topic": false }, { "descriptor": "Host-Pathogen Interactions", "descriptor_ui": "D054884", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Species Specificity", "descriptor_ui": "D013045", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "433-441", "proceedings_title": null, "publisher": "", "title": "Microbiology and immunology", "volume": "53", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Analysis of herpesvirus host specificity determinants using herpesvirus genomes as bacterial artificial chromosomes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Information on sites in HSV genomes at which foreign gene(s) can be inserted without disrupting viral genes or affecting properties of the parental virus are important for basic research on HSV and development of HSV-based vectors for human therapy. The intergenic region between HSV-1 UL3 and UL4 genes has been reported to satisfy the requirements for such an insertion site. The UL3 and UL4 genes are oriented toward the intergenic region and, therefore, insertion of a foreign gene(s) into the region between the UL3 and UL4 polyadenylation signals should not disrupt any viral genes or transcriptional units. HSV-1 and HSV-2 each have more than 10 additional regions structurally similar to the intergenic region between UL3 and UL4. In the studies reported here, it has been demonstrated that insertion of a reporter gene expression cassette into several of the HSV-1 and HSV-2 intergenic regions has no effect on viral growth in cell culture or virulence in mice, suggesting that these multiple intergenic regions may be suitable HSV sites for insertion of foreign genes.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tomomi", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Hiroomi", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1348-0421.2008.00104.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19302526" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "DNA, Intergenic", "descriptor_ui": "D021901", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Engineering", "descriptor_ui": "D005818", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": true }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Herpesvirus 2, Human", "descriptor_ui": "D018258", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Biology", "descriptor_ui": "D008967", "major_topic": false }, { "descriptor": "Mutagenesis, Insertional", "descriptor_ui": "D016254", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Recombination, Genetic", "descriptor_ui": "D011995", "major_topic": true }, { "descriptor": "Viral Envelope Proteins", "descriptor_ui": "D014759", "major_topic": false }, { "descriptor": "Viral Plaque Assay", "descriptor_ui": "D010948", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "155-161", "proceedings_title": null, "publisher": "", "title": "Microbiology and immunology", "volume": "53", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of multiple sites suitable for insertion of foreign genes in herpes simplex virus genomes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herpes simplex virus 1 (HSV-1) enters cells either via fusion of the virion envelope and host cell plasma membrane or via endocytosis, depending on the cell type. In the study reported here, we investigated a viral entry pathway dependent on the paired immunoglobulin-like type 2 receptor alpha (PILRalpha), a recently identified entry coreceptor for HSV-1 that associates with viral envelope glycoprotein B (gB). Experiments using inhibitors of endocytic pathways and ultrastructural analyses of Chinese hamster ovary (CHO) cells transduced with PILRalpha showed that HSV-1 entry into these cells was via virus-cell fusion at the cell surface. Together with earlier observations that HSV-1 uptake into normal CHO cells and those transduced with a receptor for HSV-1 envelope gD is mediated by endocytosis, these results indicated that expression of PILRalpha produced an alternative HSV-1 entry pathway in CHO cells. We also showed that human and murine PILRalpha were able to mediate entry of pseudorabies virus, a porcine alphaherpesvirus, but not of HSV-2. These results indicated that viral entry via PILRalpha appears to be conserved but that there is a PILRalpha preference among alphaherpesviruses.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Uema", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sagara", "name": null }, { "creator_type": "author", "first_name": "Hiroomi", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Arase", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.02601-08" }, "pmcid": { "normalized": "PMC2668467" }, "pmid": { "normalized": "19244335" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Alphaherpesvirinae", "descriptor_ui": "D018138", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Cricetinae", "descriptor_ui": "D006224", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": false }, { "descriptor": "Leukocytes, Mononuclear", "descriptor_ui": "D007963", "major_topic": false }, { "descriptor": "Lipopolysaccharide Receptors", "descriptor_ui": "D018950", "major_topic": false }, { "descriptor": "Membrane Glycoproteins", "descriptor_ui": "D008562", "major_topic": false }, { "descriptor": "Microscopy, Electron", "descriptor_ui": "D008854", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Receptors, Immunologic", "descriptor_ui": "D011971", "major_topic": false }, { "descriptor": "Transgenes", "descriptor_ui": "D019076", "major_topic": false }, { "descriptor": "Virus Internalization", "descriptor_ui": "D053586", "major_topic": true } ], "publication": { "conference_name": null, "date": "2009 May", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "4520-4527", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "83", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Entry of herpes simplex virus 1 and other alphaherpesviruses via the paired immunoglobulin-like type 2 receptor alpha.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Copper-catalyzed reactions of carbonyl-ene-nitriles with carbon nucleophiles, such as aromatics and ketones, afforded pyrrolin-2-ones (gamma-lactam) in excellent yield. The reaction mechanism involves addition reactions with a ketimine moiety of the 2-aza-2,4-cyclopentadienone intermediate, which is formed via hydration of a nitrile moiety followed by dehydrative cyclization.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masahito", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jo801776v" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18925786" } }, "mesh": [], "publication": { "conference_name": null, "date": "2008 Nov 21", "date_precision": "day", "issue": "22", "normalized_date": "2008-11-21", "pages": "9174-9176", "proceedings_title": null, "publisher": "", "title": "The Journal of organic chemistry", "volume": "73", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Copper-catalyzed addition reactions of aromatics and ketones to 2-aza-2,4-cyclopentadienone: facile and efficient transformation of carbonyl-ene-nitriles to 1H-pyrrolin-2(5H)-ones.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: A recent study has shown that phosphorylated c-Jun (p-c-Jun) interacts with TCF4 to form a complex that cooperatively enhances their transcriptional activity in the presence of beta-Catenin, and that their interaction is critical for mouse intestinal tumorigenesis. To determine the significance of these three proteins in human colorectal tumors, we analyzed their nuclear expression by immunohistochemistry. METHODS: we analyzed their nuclear expression by immunohistochemistry using paraffin-embedded specimens of 68 resected colorectal tumors, which consisted of 19 adenomas, 14 high-grade intraepithelial neoplasia (HGINs) and 35 adenocarcinomas. We also analyzed the expression of MMP7, which has functional AP-1 and TCF binding sites in its promoter. RESULTS: Expression of p-c-Jun, TCF4 and beta-Catenin were significantly higher in adenomas than in the adjacent normal epithelia. Expression of p-c-Jun and beta-Catenin in HGINs and adenocarcinomas were also significantly higher than in the adjacent normal epithelia. p-c-Jun expression, but not TCF4 and beta-Catenin, was higher in adenomas and HGINs than in adenocarcinomas, in which p-c-Jun expression was negatively correlated with pT stage progression. Furthermore, significant correlations of expression were observed between p-c-Jun and TCF4 (r = 0.25, p = 0.04), TCF4 and beta-Catenin (r = 0.30, p = 0.01), p-c-Jun and MMP7 (r = 0.26, p = 0.03), and TCF4 and MMP7 (r = 0.39, p = 0.0008), respectively. CONCLUSION: These results suggest that nuclear expression of p-c-Jun, TCF4 and beta-Catenin have important roles in human colorectal tumor development and that p-c-Jun may play a pivotal role in the earlier stages of tumor development.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kayoko", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Tomoo", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Matsuno", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Shichinohe", "name": null }, { "creator_type": "author", "first_name": "Hirotoshi", "last_name": "Dosaka-Akita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1471-2407-8-328" }, "pmcid": { "normalized": "PMC2585585" }, "pmid": { "normalized": "18992165" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Adenoma", "descriptor_ui": "D000236", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Leucine Zipper Transcription Factors", "descriptor_ui": "D051778", "major_topic": false }, { "descriptor": "beta Catenin", "descriptor_ui": "D051176", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Matrix Metalloproteinase 7", "descriptor_ui": "D020783", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-jun", "descriptor_ui": "D016755", "major_topic": false }, { "descriptor": "Transcription Factor 4", "descriptor_ui": "D000073940", "major_topic": false }, { "descriptor": "Transcription Factor AP-1", "descriptor_ui": "D018808", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcriptional Activation", "descriptor_ui": "D015533", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Nov 8", "date_precision": "day", "issue": "", "normalized_date": "2008-11-08", "pages": "328", "proceedings_title": null, "publisher": "", "title": "BMC cancer", "volume": "8", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinicopathological significance of expression of p-c-Jun, TCF4 and beta-Catenin in colorectal tumors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Here, we demonstrate self-organized formation of apico-basally polarized cortical tissues from ESCs using an efficient three-dimensional aggregation culture (SFEBq culture). The generated cortical neurons are functional, transplantable, and capable of forming proper long-range connections in vivo and in vitro. The regional identity of the generated pallial tissues can be selectively controlled (into olfactory bulb, rostral and caudal cortices, hem, and choroid plexus) by secreted patterning factors such as Fgf, Wnt, and BMP. In addition, the in vivo-mimicking birth order of distinct cortical neurons permits the selective generation of particular layer-specific neurons by timed induction of cell-cycle exit. Importantly, cortical tissues generated from mouse and human ESCs form a self-organized structure that includes four distinct zones (ventricular, early and late cortical-plate, and Cajal-Retzius cell zones) along the apico-basal direction. Thus, spatial and temporal aspects of early corticogenesis are recapitulated and can be manipulated in this ESC culture.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Kiichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Matsuo-Takasaki", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Shigenobu", "last_name": "Yonemura", "name": null }, { "creator_type": "author", "first_name": "Michiru", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Wataya", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stem.2008.09.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18983967" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, Differentiation", "descriptor_ui": "D000943", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": false }, { "descriptor": "Bone Morphogenetic Protein 4", "descriptor_ui": "D055415", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Fibroblast Growth Factor 8", "descriptor_ui": "D051524", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Tissue Culture Techniques", "descriptor_ui": "D046509", "major_topic": false }, { "descriptor": "Wnt Proteins", "descriptor_ui": "D051153", "major_topic": false }, { "descriptor": "Wnt3 Protein", "descriptor_ui": "D060508", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Nov 6", "date_precision": "day", "issue": "5", "normalized_date": "2008-11-06", "pages": "519-532", "proceedings_title": null, "publisher": "", "title": "Cell stem cell", "volume": "3", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Robo1, Robo2 and Rig-1 (Robo3), members of the Robo protein family, are candidate receptors for the chemorepellents Slit and are known to play a crucial role in commissural axon guidance in the spinal cord. However, their roles at other axial levels remain unknown. Here we examine expression of Robo proteins by cerebellofugal (CF) commissural axons in the rostral hindbrain and investigate their roles in CF axon pathfinding by analysing Robo knockout mice. RESULTS: We analysed the expression of Robo proteins by CF axons originating from deep cerebellar neurons in rodent embryos, focusing on developmental stages of their midline crossing and post-crossing navigation. At the stage of CF axon midline crossing, mRNAs of Robo1 and Robo2 are expressed in the nuclear transitory zone of the cerebellum, where the primordium of the deep cerebellar nuclei are located, supporting the notion that CF axons express Robo1 and Robo2. Indeed, immunohistochemical analysis of CF axons labelled by electroporation to deep cerebellar nuclei neurons indicates that Robo1 protein, and possibly also Robo2 protein, is expressed by CF axons crossing the midline. However, weak or no expression of these proteins is found on the longitudinal portion of CF axons. In Robo1/2 double knockout mice, many CF axons reach the midline but fail to exit it. We find that CF axons express Rig-1 (Robo3) before they reach the midline but not after the longitudinal turn. Consistent with this in vivo observation, axons elicited from a cerebellar explant in co-culture with a floor plate explant express Rig-1. In Rig-1 deficient mouse embryos, CF axons appear to project ipsilaterally without reaching the midline. CONCLUSION: These results indicate that Robo1, Robo2 or both are required for midline exit of CF axons. In contrast, Rig-1 is required for their approach to the midline. However, post-crossing up-regulation of these proteins, which plays an important role in spinal commissural axon guidance, does not appear to be required for the longitudinal navigation of CF axons after midline crossing. Our results illustrate that although common mechanisms operate for midline crossing at different axial levels, significant variation exists in post-crossing navigation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tamada", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Kumada", "name": null }, { "creator_type": "author", "first_name": "Yan", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Hatanaka", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Zhe", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yasuto", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Makio", "last_name": "Torigoe", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Fujio", "last_name": "Murakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1749-8104-3-29" }, "pmcid": { "normalized": "PMC2613388" }, "pmid": { "normalized": "18986510" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false }, { "descriptor": "Receptors, Immunologic", "descriptor_ui": "D011971", "major_topic": false }, { "descriptor": "Rhombencephalon", "descriptor_ui": "D012249", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Roundabout Proteins", "descriptor_ui": "D000097905", "major_topic": false }, { "descriptor": "Tissue Culture Techniques", "descriptor_ui": "D046509", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Nov 5", "date_precision": "day", "issue": "", "normalized_date": "2008-11-05", "pages": "29", "proceedings_title": null, "publisher": "", "title": "Neural development", "volume": "3", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Crucial roles of Robo proteins in midline crossing of cerebellofugal axons and lack of their up-regulation after midline crossing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Here we report the development of fluorogenic substrates for glutathione S-transferase (GST), a multigene-family enzyme mainly involved in detoxification of endogenous and exogenous compounds, including drug metabolism. GST is often overexpressed in a variety of malignancies and is involved in the development of resistance to various anticancer drugs. Despite the medical significance of this enzyme, no practical fluorogenic substrates for fluorescence imaging of GST activity or for high-throughput screening of GST inhibitors are yet available. So, we set out to develop new fluorogenic substrates for GST. In preliminary studies, we found that 3,4-dinitrobenzanilide (NNBA) is a specific substrate for GST and established the mechanisms of its glutathionylation and denitration. Using these results as a basis for off/on control of fluorescence, we designed and synthesized new fluorogenic substrates, DNAFs, and a cell membrane-permeable variant, DNAT-Me. These fluorogenic substrates provide a dramatic fluorescence increase upon GST-catalyzed glutathionylation and have excellent kinetic parameters for the present purpose. We were able to detect nuclear localization of GSH/GST activity in HuCCT1 cell lines with the use of DNAT-Me. These results indicate that the newly developed fluorogenic substrates should be useful not only for high-throughput GST-inhibitor screening but also for studies on the mechanisms of drug resistance in cancer cells.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuuta", "last_name": "Fujikawa", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja802423n" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18841967" } }, "mesh": [ { "descriptor": "Anilides", "descriptor_ui": "D000813", "major_topic": false }, { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Drug Design", "descriptor_ui": "D015195", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": false }, { "descriptor": "Glutathione S-Transferase pi", "descriptor_ui": "D051549", "major_topic": false }, { "descriptor": "Glutathione Transferase", "descriptor_ui": "D005982", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Nov 5", "date_precision": "day", "issue": "44", "normalized_date": "2008-11-05", "pages": "14533-14543", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "130", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Design and synthesis of highly sensitive fluorogenic substrates for glutathione S-transferase and application for activity imaging in living cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PACAP is a neurotransmitter involved in the signal transduction of light stimulation in the suprachiasmatic nucleus (SCN). Light stimulation affects autonomic nerve activity via the SCN, and here we tested whether PACAP participates in light-induced regulation of sympatho-adrenal activity by using PACAP-deficient (Adcyap1(-/-)) mice. Light stimulation (100 lux, 30 min) significantly elevated both renal sympathetic nerve activity (RSNA), which was monitored on a digital oscilloscope, and plasma corticosterone levels in wild-type mice, but both responses were almost abolished in Adcyap1(-/-) mice. Although light-induced c-Fos expression in the SCN was observed in both genotypes, the numbers of c-Fos positive cells were significantly decreased in Adcyap1(-/-) mice. These data suggest that PACAP signaling pathway is involved in light-induced stimulation of RSNA and plasma corticosterone release through SCN of brain.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Michiyoshi", "last_name": "Hatanaka", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Tanida", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Isojima", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Michiya", "last_name": "Kakuda", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Haba", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neulet.2008.08.030" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18722505" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Pressure", "descriptor_ui": "D001794", "major_topic": false }, { "descriptor": "Corticosterone", "descriptor_ui": "D003345", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-fos", "descriptor_ui": "D016760", "major_topic": false }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": false }, { "descriptor": "Sympathetic Nervous System", "descriptor_ui": "D013564", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Oct 24", "date_precision": "day", "issue": "2", "normalized_date": "2008-10-24", "pages": "153-156", "proceedings_title": null, "publisher": "", "title": "Neuroscience letters", "volume": "444", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Lack of light-induced elevation of renal sympathetic nerve activity and plasma corticosterone levels in PACAP-deficient mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Light sensing starts with phototransduction in photoreceptor cells. The phototransduction cascade has diverged in different species, such as those mediated by transducin in vertebrate rods and cones, by G(q)-type G protein in insect and molluscan rhabdomeric-type visual cells and vertebrate photosensitive retinal ganglion cells, and by G(o)-type G protein in scallop ciliary-type visual cells. Here, we investigated the phototransduction cascade of a prebilaterian box jellyfish, the most basal animal having eyes containing lens and ciliary-type visual cells similar to vertebrate eyes, to examine the similarity at the molecular level and to obtain an implication of the origin of the vertebrate phototransduction cascade. We showed that the opsin-based pigment functions as a green-sensitive visual pigment and triggers the G(s)-type G protein-mediated phototransduction cascade in the ciliary-type visual cells of the box jellyfish lens eyes. We also demonstrated the light-dependent cAMP increase in the jellyfish visual cells and HEK293S cells expressing the jellyfish opsin. The first identified prebilaterian cascade was distinct from known phototransduction cascades but exhibited significant partial similarity with those in vertebrate and molluscan ciliary-type visual cells, because all involved cyclic nucleotide signaling. These similarities imply a monophyletic origin of ciliary phototransduction cascades distributed from prebilaterian to vertebrate.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Hisao", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Kohzoh", "last_name": "Ohtsu", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.0806215105" }, "pmcid": { "normalized": "PMC2563118" }, "pmid": { "normalized": "18832159" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cubozoa", "descriptor_ui": "D037462", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "GTP-Binding Protein alpha Subunits, Gs", "descriptor_ui": "D019205", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light Signal Transduction", "descriptor_ui": "D055537", "major_topic": true }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Opsins", "descriptor_ui": "D055355", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Retinal Cone Photoreceptor Cells", "descriptor_ui": "D017949", "major_topic": false }, { "descriptor": "Retinal Rod Photoreceptor Cells", "descriptor_ui": "D017948", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Oct 7", "date_precision": "day", "issue": "40", "normalized_date": "2008-10-07", "pages": "15576-15580", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "105", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Jellyfish vision starts with cAMP signaling mediated by opsin-G(s) cascade.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We revisit the concept of \"remnant of invariant manifolds\" originally discussed by Shirts and Reinhardt in a two degrees of freedom Henon-Heiles system [J. Chem. Phys. 77, 5204 (1982)]. This is regarded as the remnants of a destroyed invariant manifold that can dominate the transport in phase space even at high energy regions where most of all tori vanish. We present a novel technique to extract such remnants of invariants from a sea of chaos in highly nonlinear coupled molecular systems in terms of the canonical perturbation theory based on Lie transforms. As an illustrative example we demonstrate in HCN isomerization reaction that the conventional procedure based on a finite order truncation of the coordinate transformation prevent us from detecting remnants of invariants. However, our technique correctly captures the underlying remnants of invariants that shed light on the energetics of chemical reaction, that is, how the reactive mode acquires (releases) energy from (to) the other vibrational mode in order to overcome the potential barrier (to be trapped in the potential well). We also found the qualitative difference between the two potential wells, HCN and CNH, which coincides with the nearest neighbor level spacing distribution of the vibrational quantum states within the wells.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Teramoto", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/1.2973639" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19044865" } }, "mesh": [], "publication": { "conference_name": null, "date": "2008 Sep 7", "date_precision": "day", "issue": "9", "normalized_date": "2008-09-07", "pages": "094302", "proceedings_title": null, "publisher": "", "title": "The Journal of chemical physics", "volume": "129", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Exploring remnants of invariants buried in a deep potential well in chemical reactions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Embryonic stem (ES) cells differentiate into neuroectodermal progenitors when cultured as floating aggregates in serum-free conditions. Here, we show that strict removal of exogenous patterning factors during early differentiation steps induces efficient generation of rostral hypothalamic-like progenitors (Rax+/Six3+/Vax1+) in mouse ES cell-derived neuroectodermal cells. The use of growth factor-free chemically defined medium is critical and even the presence of exogenous insulin, which is commonly used in cell culture, strongly inhibits the differentiation via the Akt-dependent pathway. The ES cell-derived Rax+ progenitors generate Otp+/Brn2+ neuronal precursors (characteristic of rostral–dorsal hypothalamic neurons) and subsequently magnocellular vasopressinergic neurons that efficiently release the hormone upon stimulation. Differentiation markers of rostral–ventral hypothalamic precursors and neurons are induced from ES cell-derived Rax+ progenitors by treatment with Shh. Thus, in the absence of exogenous growth factors in medium, the ES cell-derived neuroectodermal cells spontaneously differentiate into rostral (particularly rostral–dorsal) hypothalamic-like progenitors, which generate characteristic hypothalamic neuroendocrine neurons in a stepwise fashion, as observed in vivo. These findings indicate that, instead of the addition of inductive signals, minimization of exogenous patterning signaling plays a key role in rostral hypothalamic specification of neural progenitors derived from pluripotent cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takafumi", "last_name": "Wataya", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Hanako", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Kiichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Nobuo", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.0803078105" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18697938" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Culture Media, Conditioned", "descriptor_ui": "D017077", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Eye Proteins", "descriptor_ui": "D005136", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Aug 19", "date_precision": "day", "issue": "33", "normalized_date": "2008-08-19", "pages": "11796-11801", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "105", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Minimization of exogenous signals in ES cell culture induces rostral hypothalamic differentiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We performed the simultaneous measurement of intrinsic optical signals (IOSs) related to metabolic activity and cellular and subcellular morphological characteristics, i.e., light scattering for a rat global ischemic brain model made by rapidly removing blood by saline infusion. The signals were measured on the basis of multiwavelength diffuse reflectances in which 605 and 830 nm were used to detect the IOSs that are thought to be dominantly affected by redox changes of heme aa(3) and CuA in cytochrome c oxidase (CcO), respectively. For measuring the scattering signal, the wavelength that was found to be most insensitive to the absorption changes, e.g., approximately 620 nm, was used. The measurements suggested that an increase in the absorption due to reduction of heme aa(3) occurred soon after blood clearance, and this was followed by a large triphasic change in light scattering, during which time a decrease in the absorption due to reduction of CuA occurred. Through the triphasic scattering change, scattering signals increased by 5.2 +/- 1.5% (n = 5), and the increase in light scattering showed significant correlation with both the reflectance intensity changes at 605 and 830 nm. This suggests that morphological changes in cells correlate with reductions of heme aa(3) and CuA. Histological analysis of tissue after the triphasic scattering change showed no alteration in either the nuclei or the cytoskeleton, but electron microscopic observation revealed deformed, enlarged mitochondria and expanded dendrites. These findings suggest that the simultaneous measurement of absorption signals related to the redox changes in the CcO and the scattering signal is useful for monitoring tissue viability in the brain.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Satoko", "last_name": "Kawauchi", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Ooigawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nawashiro", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kikuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/ao.47.004164" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18670575" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain Diseases", "descriptor_ui": "D001927", "major_topic": false }, { "descriptor": "Electron Transport Complex IV", "descriptor_ui": "D003576", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Photometry", "descriptor_ui": "D010783", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Scattering, Radiation", "descriptor_ui": "D012542", "major_topic": false }, { "descriptor": "Spectrum Analysis", "descriptor_ui": "D013057", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Aug 1", "date_precision": "day", "issue": "22", "normalized_date": "2008-08-01", "pages": "4164-4176", "proceedings_title": null, "publisher": "", "title": "Applied optics", "volume": "47", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Simultaneous measurement of changes in light absorption due to the reduction of cytochrome c oxidase and light scattering in rat brains during loss of tissue viability.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cerebellum is a brain structure involved in the coordination, control and learning of movements, and elucidation of its function is an important issue. Japanese scholars have made seminal contributions in this field of neuroscience. Electrophysiological studies of the cerebellum have a long history in Japan since the pioneering works by Ito and Sasaki. Elucidation of the basic circuit diagram of the cerebellum in the 1960s was followed by the construction of cerebellar network theories and finding of their neural correlates in the 1970s. A theoretically predicted synaptic plasticity, long-term depression (LTD) at parallel fibre to Purkinje cell synapse, was demonstrated experimentally in 1982 by Ito and co-workers. Since then, Japanese neuroscientists from various disciplines participated in this field and have made major contributions to elucidate molecular mechanisms underlying LTD. An important pathway for LTD induction is type-1 metabotropic glutamate receptor (mGluR1) and its downstream signal transduction in Purkinje cells. Sugiyama and co-workers demonstrated the presence of mGluRs and Nakanishi and his pupils identified the molecular structures and functions of the mGluR family. Moreover, the authors contributed to the discovery and elucidation of several novel functions of mGluR1 in cerebellar Purkinje cells. mGluR1 turned out to be crucial for the release of endocannabinoid from Purkinje cells and the resultant retrograde suppression of transmitter release. It was also found that mGluR1 and its downstream signal transduction in Purkinje cells are indispensable for the elimination of redundant synapses during post-natal cerebellar development. This article overviews the seminal works by Japanese neuroscientists, focusing on mGluR1 signalling in cerebellar Purkinje cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Tabata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1098/rstb.2008.2270" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18339599" } }, "mesh": [ { "descriptor": "Long-Term Synaptic Depression", "descriptor_ui": "D036881", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Jun 27", "date_precision": "day", "issue": "1500", "normalized_date": "2008-06-27", "pages": "2173-2186", "proceedings_title": null, "publisher": "", "title": "Philosophical Transactions of the Royal Society B: Biological Sciences", "volume": "363", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Type-1 metabotropic glutamate receptor in cerebellar Purkinje cells: a key molecule responsible for long-term depression, endocannabinoid signalling and synapse elimination.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "While sensory information is encoded by firing patterns of individual sensory neurons, it is also represented by spatiotemporal patterns of activity in populations of the neurons. Postsynaptic interneurons decode the population response and extract specific sensory information. This extraction of information represented by presynaptic activities is a process critical to defining the input–output function of postsynaptic neuron. To understand the “algorithm” for the extraction, we examined directional sensitivities of presynaptic and postsynaptic Ca2+ responses in dendrites of two types of wind-sensitive interneurons (INs) with different dendritic geometries in the cricket cercal sensory system. In IN 10-3, whose dendrites arborize with various electrotonic distances to the spike-initiating zone (SIZ), the directional sensitivity of dendritic Ca2+ responses corresponded to those indicated by Ca2+ signals in presynaptic afferents arborizing on that dendrite. The directional tuning properties of individual dendrites varied from each other, and the directional sensitivity of the nearest dendrite to the SIZ dominates the tuning properties of the spiking response. In IN 10-2 with dendrites isometric to the SIZ, directional tuning properties of different dendrites were similar to each other, and each response property could be explained by the directional profile of the spatial overlap between that dendrite and Ca2+-elevated presynaptic terminals. For IN 10-2, the directional sensitivities extracted by the different dendritic-branches would contribute equally to the overall tuning. It is possible that the differences in the distribution of synaptic weights because of the dendritic geometry are related to the algorithm for extraction of sensory information in the postsynaptic interneurons.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroto", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Graham I.", "last_name": "Cummins", "name": null }, { "creator_type": "author", "first_name": "Gwen A.", "last_name": "Jacobs", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.5354-07.2008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18448635" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Ganglia, Invertebrate", "descriptor_ui": "D017952", "major_topic": false }, { "descriptor": "Gryllidae", "descriptor_ui": "D006135", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Potentials", "descriptor_ui": "D008564", "major_topic": false }, { "descriptor": "Models, Neurological", "descriptor_ui": "D008959", "major_topic": true }, { "descriptor": "Neural Conduction", "descriptor_ui": "D009431", "major_topic": false }, { "descriptor": "Neurons, Afferent", "descriptor_ui": "D009475", "major_topic": false }, { "descriptor": "Organic Chemicals", "descriptor_ui": "D009930", "major_topic": false }, { "descriptor": "Physical Stimulation", "descriptor_ui": "D010812", "major_topic": false }, { "descriptor": "Presynaptic Terminals", "descriptor_ui": "D017729", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Apr 30", "date_precision": "day", "issue": "18", "normalized_date": "2008-04-30", "pages": "4592-4603", "proceedings_title": null, "publisher": "", "title": "The Journal of Neuroscience", "volume": "28", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Dendritic Design Implements Algorithm for Synaptic Extraction of Sensory Information.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Parathyroid hormone-related protein (PTHrP) is detected in many aggressive tumors and involved in malignant conversion; however, the underlying mechanism remains obscure. Here, we identified PTHrP as a mediator of epidermal growth factor receptor (EGFR) signaling to promote the malignancies of oral cancers. PTHrP mRNA was abundantly expressed in most of the quiescent oral cancer cells, and was significantly upregulated by EGF stimulation via ERK and p38 MAPK. PTHrP silencing by RNA interference, as well as EGFR inhibitor AG1478 treatment, significantly suppressed cell proliferation, migration, and invasiveness. Furthermore, combined treatment of AG1478 and PTHrP knockdown achieved synergistic inhibition of malignant phenotypes. Recombinant PTHrP substantially promoted cell motility, and rescued the inhibition by PTHrP knockdown, suggesting the paracrine/autocrine function of PTHrP. These data indicate that PTHrP contributes to the malignancy of oral cancers downstream of EGFR signaling, and may thus provide a therapeutic target for oral cancer.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tamaki", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Totsuka", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Shindoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2008.01.121" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18261460" } }, "mesh": [ { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mouth Neoplasms", "descriptor_ui": "D009062", "major_topic": false }, { "descriptor": "Parathyroid Hormone-Related Protein", "descriptor_ui": "D044162", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Apr 11", "date_precision": "day", "issue": "3", "normalized_date": "2008-04-11", "pages": "575-581", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "368", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "PTHrP promotes malignancy of human oral cancer cell downstream of the EGFR signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Glycoprotein B (gB) is one of the essential components for infection by herpes simplex virus-1 (HSV-1). Although several cellular receptors that associate with glycoprotein D (gD), such as herpes virus entry mediator (HVEM) and Nectin-1, have been identified, specific molecules that mediate HSV-1 infection by associating with gB have not been elucidated. Here, we found that paired immunoglobulin-like type 2 receptor (PILR) α associates with gB, and cells transduced with PILRα become susceptible to HSV-1 infection. Furthermore, HSV-1 infection of human primary cells expressing both HVEM and PILRα was blocked by either anti-PILRα or anti-HVEM antibody. Our results demonstrate that cellular receptors for both gB and gD are required for HSV-1 infection and that PILRα plays an important role in HSV-1 infection as a co-receptor that associates with gB. These findings uncover a crucial aspect of the mechanism underlying HSV-1 infection.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Suenaga", "name": null }, { "creator_type": "author", "first_name": "Jing", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Amane", "last_name": "Kogure", "name": null }, { "creator_type": "author", "first_name": "Junji", "last_name": "Uehori", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Arase", "name": null }, { "creator_type": "author", "first_name": "Ikuo", "last_name": "Shiratori", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Patricia G.", "last_name": "Spear", "name": null }, { "creator_type": "author", "first_name": "Lewis L.", "last_name": "Lanier", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Arase", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cell.2008.01.043" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18358807" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "CHO Cells", "descriptor_ui": "D016466", "major_topic": false }, { "descriptor": "Cricetinae", "descriptor_ui": "D006224", "major_topic": false }, { "descriptor": "Cricetulus", "descriptor_ui": "D003412", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Membrane Glycoproteins", "descriptor_ui": "D008562", "major_topic": false }, { "descriptor": "Receptors, Immunologic", "descriptor_ui": "D011971", "major_topic": false }, { "descriptor": "Receptors, Virus", "descriptor_ui": "D011991", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false }, { "descriptor": "Viral Envelope Proteins", "descriptor_ui": "D014759", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Mar 21", "date_precision": "day", "issue": "6", "normalized_date": "2008-03-21", "pages": "935-944", "proceedings_title": null, "publisher": "", "title": "Cell", "volume": "132", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "PILRα is a herpes simplex virus-1 entry co-receptor that associates with glycoprotein B.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "HemAT from Bacillus subtilis (HemAT-Bs) is a heme-based O2 sensor protein that acts as a signal transducer responsible for aerotaxis. HemAT-Bs discriminates its physiological effector (O2) from other gas molecules (CO and NO), although all of them bind to a heme. To monitor the conformational changes in the protein moiety upon binding of different ligands, we have investigated ultraviolet resonance Raman (UVRR) spectra of the ligand-free and O2-, CO-, and NO-bound forms of full-length HemAT-Bs and several mutants (Y70F, H86A, T95A, and Y133F) and found that Tyr70 in the heme distal side and Tyr133 and Trp132 from the G-helix in the heme proximal side undergo environmental changes upon ligand binding. In addition, the UVRR results confirmed our previous model, which suggested that Thr95 forms a hydrogen bond with heme-bound O2, but Tyr70 does not. It is deduced from this study that hydrogen bonds between Thr95 and heme-bound O2 and between His86 and heme 6-propionate communicate the heme structural changes to the protein moiety upon O2 binding but not upon CO and NO binding. Accordingly, the present UVRR results suggest that O2 binding to heme causes displacement of the G-helix, which would be important for transduction of the conformational changes from the sensor domain to the signaling domain.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Samir F.", "last_name": "El-Mashtoly", "name": null }, { "creator_type": "author", "first_name": "Yuzong", "last_name": "Gu", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Shiro", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Shigetoshi", "last_name": "Aono", "name": null }, { "creator_type": "author", "first_name": "Teizo", "last_name": "Kitagawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m709209200" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18162468" } }, "mesh": [ { "descriptor": "Bacillus subtilis", "descriptor_ui": "D001412", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Bacterial", "descriptor_ui": "D015964", "major_topic": true }, { "descriptor": "Heme", "descriptor_ui": "D006418", "major_topic": false }, { "descriptor": "Heme-Binding Proteins", "descriptor_ui": "D000081062", "major_topic": false }, { "descriptor": "Hemeproteins", "descriptor_ui": "D006420", "major_topic": false }, { "descriptor": "Hydrogen Bonding", "descriptor_ui": "D006860", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Molecular Conformation", "descriptor_ui": "D008968", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Spectrophotometry, Ultraviolet", "descriptor_ui": "D013056", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "Tyrosine", "descriptor_ui": "D014443", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Mar 14", "date_precision": "day", "issue": "11", "normalized_date": "2008-03-14", "pages": "6942-6949", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "283", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Protein conformation changes of HemAT-Bs upon ligand binding probed by ultraviolet resonance Raman spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Blood vessels change their caliber to adapt to the demands of tissues or organs for oxygen and nutrients. This event is mainly organized at the capillary level and requires a size-sensing mechanism. However, the molecular regulatory mechanism involved in caliber size modification in blood vessels is not clear. Here we show that apelin, a protein secreted from endothelial cells under the activation of Tie2 receptor tyrosine kinase on endothelial cells, plays a role in the regulation of caliber size of blood vessel through its cognate receptor APJ, which is expressed on endothelial cells. During early embryogenesis, APJ is expressed on endothelial cells of the new blood vessels sprouted from the dorsal aorta, but not on pre-existing endothelial cells of the dorsal aorta. Apelin-deficient mice showed narrow blood vessels in intersomitic vessels during embryogenesis. Apelin enhanced endothelial cell proliferation in the presence of vascular endothelial growth factor and promoted cell-to-cell aggregation. These results indicated that the apelin/APJ system is involved in the regulation of blood vessel diameter during angiogenesis.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Mitsugu", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/sj.emboj.7601982" }, "pmcid": { "normalized": "PMC2241654" }, "pmid": { "normalized": "18200044" } }, "mesh": [ { "descriptor": "Adipokines", "descriptor_ui": "D054392", "major_topic": false }, { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apelin", "descriptor_ui": "D000073861", "major_topic": false }, { "descriptor": "Apelin Receptors", "descriptor_ui": "D000075244", "major_topic": false }, { "descriptor": "Blood Vessels", "descriptor_ui": "D001808", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Endothelium, Vascular", "descriptor_ui": "D004730", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Neovascularization, Physiologic", "descriptor_ui": "D018919", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Feb 6", "date_precision": "day", "issue": "3", "normalized_date": "2008-02-06", "pages": "522-534", "proceedings_title": null, "publisher": "", "title": "The EMBO journal", "volume": "27", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatial and temporal role of the apelin/APJ system in the caliber size regulation of blood vessels during angiogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Conformational dynamics of proteins can be interpreted as itinerant motions as the protein traverses from one state to another on a complex network in conformational space or, more generally, in state space. Here we present a scheme to extract a multiscale state space network (SSN) from a single-molecule time series. Analysis by this method enables us to lift degeneracy--different physical states having the same value for a measured observable--as much as possible. A state or node in the network is defined not by the value of the observable at each time but by a set of subsequences of the observable over time. The length of the subsequence can tell us the extent to which the memory of the system is able to predict the next state. As an illustration, we investigate the conformational fluctuation dynamics probed by single-molecule electron transfer (ET), detected on a photon-by-photon basis. We show that the topographical features of the SSNs depend on the time scale of observation; the longer the time scale, the simpler the underlying SSN becomes, leading to a transition of the dynamics from anomalous diffusion to normal Brownian diffusion.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Chun-Biu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Haw", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.0707378105" }, "pmcid": { "normalized": "PMC2206571" }, "pmid": { "normalized": "18178627" } }, "mesh": [ { "descriptor": "Biophysics", "descriptor_ui": "D001703", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Diffusion", "descriptor_ui": "D004058", "major_topic": false }, { "descriptor": "Electrons", "descriptor_ui": "D004583", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Markov Chains", "descriptor_ui": "D008390", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Models, Statistical", "descriptor_ui": "D015233", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": false }, { "descriptor": "Molecular Conformation", "descriptor_ui": "D008968", "major_topic": false }, { "descriptor": "Photons", "descriptor_ui": "D017785", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Protein Folding", "descriptor_ui": "D017510", "major_topic": false }, { "descriptor": "Spectrophotometry", "descriptor_ui": "D013053", "major_topic": false }, { "descriptor": "Time", "descriptor_ui": "D013995", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Jan 15", "date_precision": "day", "issue": "2", "normalized_date": "2008-01-15", "pages": "536-541", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "105", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Multiscale complex network of protein conformational fluctuations in single-molecule time series.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The quality of cargo proteins in the endoplasmic reticulum (ER) is affected by their motion during folding. To understand how the diffusion of secretory cargo proteins is regulated in the ER, we directly analyze the motion of a single cargo molecule using fluorescence imaging/fluctuation analyses. We find that the addition of two N-glycans onto the cargo dramatically alters their diffusion by transient binding to membrane components that are confined by hyperosmolarity. Via simultaneous observation of a single cargo and ER exit sites (ERESs), we could exclude ERESs as the binding sites. Remarkably, actin cytoskeleton was required for the transient binding. These results provide a molecular basis for hypertonicity-induced immobilization of cargo, which is dependent on glycosylation at multiple sites but not the completion of proper folding. We propose that diffusion of secretory glycoproteins in the ER lumen is controlled from the cytoplasm to reduce the chances of aggregation.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hisao", "last_name": "Nagaya", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Arisa", "last_name": "Higa-Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kiyotaka", "last_name": "Hatsuzawa", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Kinjo", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Ikuo", "last_name": "Wada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1083/jcb.200704078" }, "pmcid": { "normalized": "PMC2213621" }, "pmid": { "normalized": "18195104" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": false }, { "descriptor": "Fluorescence Recovery After Photobleaching", "descriptor_ui": "D036681", "major_topic": false }, { "descriptor": "Glycoproteins", "descriptor_ui": "D006023", "major_topic": false }, { "descriptor": "Glycosylation", "descriptor_ui": "D006031", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Oligosaccharides", "descriptor_ui": "D009844", "major_topic": false }, { "descriptor": "Osmolar Concentration", "descriptor_ui": "D009994", "major_topic": false }, { "descriptor": "Protein Folding", "descriptor_ui": "D017510", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Jan 14", "date_precision": "day", "issue": "1", "normalized_date": "2008-01-14", "pages": "129-143", "proceedings_title": null, "publisher": "", "title": "The Journal of cell biology", "volume": "180", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Regulated motion of glycoproteins revealed by direct visualization of a single cargo in the endoplasmic reticulum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Magnetic resonance imaging (MRI) permits noninvasive three-dimensional imaging of opaque organisms. Gadolinium (Gd(3+)) complexes have become important imaging tools as MRI contrast agents for MRI studies, though most of them are nonspecific and report solely on anatomy. Recently, MRI contrast agents have been reported whose ability to relax water protons is triggered or greatly enhanced by recognition of a particular biomolecule. This new class of MRI contrast agents could open up the possibility of reporting on the physiological state or metabolic activity deep within living specimens. One possible strategy for this purpose is to utilize the increase in the longitudinal water proton r(1) relaxivity that occurs upon slowing the molecular rotation of a small paramagnetic complex, a phenomenon which is known as receptor-induced magnetization enhancement (RIME), by either binding to a macromolecule or polymerization of the agent itself. Here we describe the design and synthesis of a novel beta-galactosidase-activated MRI contrast agent, the Gd(3+) complex [Gd-5], by using the RIME approach. beta-Galactosidase is commonly used as a marker gene to monitor gene expression. This newly synthesized compound exhibited a 57% increase in the r(1) relaxivity in phosphate-buffered saline (PBS) with 4.5% w/v human serum albumin (HSA) in the presence of beta-galactosidase. Detailed investigations revealed that RIME is the dominant factor in this increase of the observed r(1) relaxivity, based on analysis of Gd(3+) complexes [Gd-5] and [Gd-8], which is generated from [Gd-5] by the activity of beta-galactosidase, and spectroscopic analysis of their corresponding Tb(3+) complexes, [Tb-5] and [Tb-8].", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/chem.200700785" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17992679" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "beta-Galactosidase", "descriptor_ui": "D001616", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Cattle", "descriptor_ui": "D002417", "major_topic": false }, { "descriptor": "Contrast Media", "descriptor_ui": "D003287", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Gadolinium", "descriptor_ui": "D005682", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Luminescence", "descriptor_ui": "D049449", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": true }, { "descriptor": "Organometallic Compounds", "descriptor_ui": "D009942", "major_topic": false }, { "descriptor": "Quantum Theory", "descriptor_ui": "D011789", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Serum Albumin", "descriptor_ui": "D012709", "major_topic": false }, { "descriptor": "Species Specificity", "descriptor_ui": "D013045", "major_topic": false }, { "descriptor": "Spectrophotometry, Ultraviolet", "descriptor_ui": "D013056", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008", "date_precision": "year", "issue": "3", "normalized_date": "2008", "pages": "987-995", "proceedings_title": null, "publisher": "", "title": "Chemistry (Weinheim an der Bergstrasse, Germany)", "volume": "14", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "A Gd3+-based magnetic resonance imaging contrast agent sensitive to beta-galactosidase activity utilizing a receptor-induced magnetization enhancement (RIME) phenomenon.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An improved assembly of the Ciona intestinalis genome reveals that it contains non-canonical introns and that about 20% of Ciona genes reside in operons.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yutaka", "last_name": "Satou", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Mineta", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Ogasawara", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Sasakura", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Shoguchi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Lixy", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Jessica", "last_name": "Wasserscheid", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Dewar", "name": null }, { "creator_type": "author", "first_name": "Graham B.", "last_name": "Wiley", "name": null }, { "creator_type": "author", "first_name": "Simone L.", "last_name": "Macmil", "name": null }, { "creator_type": "author", "first_name": "Bruce A.", "last_name": "Roe", "name": null }, { "creator_type": "author", "first_name": "Robert W.", "last_name": "Zeller", "name": null }, { "creator_type": "author", "first_name": "Kenneth EM", "last_name": "Hastings", "name": null }, { "creator_type": "author", "first_name": "Patrick", "last_name": "Lemaire", "name": null }, { "creator_type": "author", "first_name": "Erika", "last_name": "Lindquist", "name": null }, { "creator_type": "author", "first_name": "Toshinori", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Inaba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/gb-2008-9-10-r152" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18854010" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": false }, { "descriptor": "Expressed Sequence Tags", "descriptor_ui": "D020224", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": true }, { "descriptor": "Introns", "descriptor_ui": "D007438", "major_topic": false }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": false }, { "descriptor": "Operon", "descriptor_ui": "D009876", "major_topic": true } ], "publication": { "conference_name": null, "date": "2008", "date_precision": "year", "issue": "10", "normalized_date": "2008", "pages": "R152", "proceedings_title": null, "publisher": "", "title": "Genome Biology", "volume": "9", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Improved genome assembly and evidence-based global gene model set for the chordate Ciona intestinalis: new insight into intron and operon populations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "RATIONALE: Previous studies have shown that alterations in acetylcholine (ACh) receptor subtypes might contribute to cognitive impairment observed in schizophrenia and that choline acetyltransferase activity in the parietal cortex is negatively correlated with the severity of such cognitive impairment. However, clinical data suggest that the acetylcholinesterase (AChE) inhibitors galantamine and donepezil have different effects on negative and cognitive symptoms in schizophrenia. Prepulse inhibition (PPI) deficits--sensory information-processing deficits observed in schizophrenia--may be useful models for studying the efficacy of AChE inhibitors as cognitive enhancers. OBJECTIVES: The present study examined the effects of galantamine and donepezil on PPI deficits induced by an environmental factor and drugs. MATERIALS AND METHODS: In the isolation-rearing model, 3-week-old male ddY mice were housed either in groups of five or six per cage or isolated in cages of the same size for more than 6 weeks. In the drug-induced model, apomorphine 1 mg/kg and MK-801 0.2 mg/kg were administered to 9- to 10-week-old male ddY mice. RESULTS: In isolation-reared mice, galantamine attenuated PPI deficits, while donepezil did not. Galantamine and donepezil both attenuated PPI deficits induced by apomorphine, but not by MK-801. The galantamine-induced improvements in PPI deficits were not prevented by the nicotinic ACh receptor antagonists mecamylamine and methyllycaconitine. CONCLUSIONS: These observations suggest that galantamine and donepezil have different effects on the environmentally induced PPI deficits and that these observations may be relevant to the different effects of these drugs observed clinically in schizophrenia.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ken", "last_name": "Koda", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00213-007-0962-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17912499" } }, "mesh": [ { "descriptor": "Aconitine", "descriptor_ui": "D000157", "major_topic": false }, { "descriptor": "Acoustic Stimulation", "descriptor_ui": "D000161", "major_topic": false }, { "descriptor": "alpha7 Nicotinic Acetylcholine Receptor", "descriptor_ui": "D064569", "major_topic": false }, { "descriptor": "Analysis of Variance", "descriptor_ui": "D000704", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Outbred Strains", "descriptor_ui": "D021461", "major_topic": false }, { "descriptor": "Apomorphine", "descriptor_ui": "D001058", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Cholinesterase Inhibitors", "descriptor_ui": "D002800", "major_topic": false }, { "descriptor": "Dizocilpine Maleate", "descriptor_ui": "D016291", "major_topic": false }, { "descriptor": "Donepezil", "descriptor_ui": "D000077265", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Galantamine", "descriptor_ui": "D005702", "major_topic": false }, { "descriptor": "Indans", "descriptor_ui": "D007189", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mecamylamine", "descriptor_ui": "D008464", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neural Inhibition", "descriptor_ui": "D009433", "major_topic": false }, { "descriptor": "Nicotinic Antagonists", "descriptor_ui": "D018733", "major_topic": false }, { "descriptor": "Piperidines", "descriptor_ui": "D010880", "major_topic": false }, { "descriptor": "Receptors, Nicotinic", "descriptor_ui": "D011978", "major_topic": false }, { "descriptor": "Reflex, Startle", "descriptor_ui": "D013216", "major_topic": false }, { "descriptor": "Risperidone", "descriptor_ui": "D018967", "major_topic": false }, { "descriptor": "Social Isolation", "descriptor_ui": "D012934", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "293-301", "proceedings_title": null, "publisher": "", "title": "Psychopharmacology", "volume": "196", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Galantamine and donepezil differently affect isolation rearing-induced deficits of prepulse inhibition in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recovery of lost brain function is an important issue in medical studies because neurons of the central nervous system (CNS) have poor potential for regeneration. Since few CNS diseases can be treated completely by medicines, regenerative therapy by using stem cells should be studied as a new type of therapeutic intervention. The efficacy of cell replacement therapy in Parkinson's disease has been well investigated. Several studies on fetal tissue transplantation have revealed that quantity and purity of transplanted cells are necessary for recovery of symptoms. SFEB (Serum-free floating culture of embryoid body-like aggregates) method is capable of inducing multi-potential CNS progenitors that can be steered to differentiate into region-specific tissues. On the basis of the existing knowledge of embryology, we have succeeded in the generating of various types of neurons such as telencephalic, cerebeller (Purkinje and granule cells), retinal (photoreceptor cells) and hypothalamic neurons. Application of this culture method to human ES (hES) cells is necessary for clinical purpose: however, poor survival of hES cells in SFEB culture might limit the possibility of using these cells for future medical applications. We found that a selective Rho-associated kinase (ROCK) inhibitor, Y-27632, markedly diminished the dissociation-induced apoptosis of hES cells and enabled the cells to form aggregates in SFEB culture. For both mouse and human ES cells, SFEB culture is a favorable method that can generate large amounts of region-specific neurons. However, stem cell-based therapy continues to face several obstacles. It is important that researchers in the basic sciences and clinical medicine should discuss these problems together to overcome both scientific and ethical issues related to stem cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takafumi", "last_name": "Wataya", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18975604" } }, "mesh": [ { "descriptor": "Amides", "descriptor_ui": "D000577", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Aggregation", "descriptor_ui": "D002449", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cell- and Tissue-Based Therapy", "descriptor_ui": "D064987", "major_topic": true }, { "descriptor": "Central Nervous System", "descriptor_ui": "D002490", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": true }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Parkinson Disease", "descriptor_ui": "D010300", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": true }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false }, { "descriptor": "Regenerative Medicine", "descriptor_ui": "D044968", "major_topic": false }, { "descriptor": "rho-Associated Kinases", "descriptor_ui": "D054460", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "1165-1172", "proceedings_title": null, "publisher": "", "title": "Brain and nerve = Shinkei kenkyu no shinpo", "volume": "60", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "[Human pluripotent stem cell and neural differentiation].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Two-photon fluorescence lifetime imaging microscopy (TPFLIM) enables the quantitative measurements of fluorescence resonance energy transfer (FRET) in small subcellular compartments in light scattering tissue. We evaluated and optimized the FRET pair of mEGFP (monomeric EGFP with the A206K mutation) and REACh (non-radiative YFP variants) for TPFLIM. We characterized several mutants of REACh in terms of their \"darkness,\" and their ability to act as a FRET acceptor for mEGFP in HeLa cells and hippocampal neurons. Since the commonly used monomeric mutation A206K increases the brightness of REACh, we introduced a different monomeric mutation (F223R) which does not affect the brightness. Also, we found that the folding efficiency of original REACh, as measured by the fluorescence lifetime of a mEGFP-REACh tandem dimer, was low and variable from cell to cell. Introducing two folding mutations (F46L, Q69M) into REACh increased the folding efficiency by approximately 50%, and reduced the variability of FRET signal. Pairing mEGFP with the new REACh (super-REACh, or sREACh) improved the signal-to-noise ratio compared to the mEGFP-mRFP or mEGFP-original REACh pair by approximately 50%. Using this new pair, we demonstrated that the fraction of actin monomers in filamentous and globular forms in single dendritic spines can be quantitatively measured with high sensitivity. Thus, the mEGFP-sREACh pair is suited for quantitative FRET measurement by TPFLIM, and enables us to measure protein-protein interactions in individual dendritic spines in brain slices with high sensitivity.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hideji", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Seok-Jin", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Yasuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s11068-008-9024-9" }, "pmcid": { "normalized": "PMC2673728" }, "pmid": { "normalized": "18512154" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence, Multiphoton", "descriptor_ui": "D036641", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Aug", "date_precision": "unknown", "issue": "1-4", "normalized_date": null, "pages": "31-42", "proceedings_title": null, "publisher": "", "title": "Brain cell biology", "volume": "36", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Highly sensitive and quantitative FRET-FLIM imaging in single dendritic spines using improved non-radiative YFP.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A technique is presented to scrutinize a piece of remnants of invariants [R. B. Shirts and W. P. Reinhardt, J. Chem. Phys. 77, 15 (1982)] buried in chaos in many degrees of freedom (DOF) dynamical systems in terms of canonical perturbation theory based on Lie transforms. The transformed canonical variables are often evaluated by the truncation of the coordinate transformation at a finite order in the original Hamiltonian system. However, the truncation of canonical variables gives rise to a loss of the symplectic property of the system. This results in apparent abrupt fluctuation of the action integrals, which yields a misinterpretation. We demonstrate, in a three-DOF Hamiltonian system of HCN isomerization reaction, that our technique can detect remnants of invariants buried in the potential well even at energies higher than the potential barrier, although the conventional truncation scheme fails to do so. This technique makes it possible to shed light on the physical insight into how the reactive mode exchanges its energy with the other modes and through which resonance the energy exchange takes place in reacting systems.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Teramoto", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.78.017202" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18764083" } }, "mesh": [], "publication": { "conference_name": null, "date": "2008 Jul", "date_precision": "unknown", "issue": "1 Pt 2", "normalized_date": null, "pages": "017202", "proceedings_title": null, "publisher": "", "title": "Physical review. E, Statistical, nonlinear, and soft matter physics", "volume": "78", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Probing remnants of invariants to mediate energy exchange in highly chaotic many-dimensional systems.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide implicated in several metabolic functions, including insulin secretion and sympathoadrenal activation. To clarify the roles of PACAP in maintenance of whole-body glucose and lipid homeostasis, the impact of the deletion of PACAP on glucose homeostasis, body weight, and adipose tissue mass was examined by comparing mice lacking the Adcyap1 gene encoding PACAP (Adcyap1(-/-)) with wild-type littermate controls. Adcyap1(-/-) mice showed significant hypoinsulinemia, although being normoglycemic, and lower body weight as well as reduced food intake. They also showed greatly reduced white adipose tissue mass, in which the mRNA expression of adipocyte fatty acid-binding protein (aP2), a marker of adipocyte differentiation, was decreased. Glucose and insulin tolerance tests revealed increased insulin sensitivity in Adcyap1(-/-) mice. In accordance with these observations, plasma levels of resistin, an adipocytokine implicated in insulin resistance, were decreased in Adcyap1(-/-) mice. After a high-fat dietary challenge for six weeks, Adcyap1(-/-) mice still showed lower body weights and increased insulin sensitivity. These results indicate the crucial roles of PACAP in energy metabolism, including lipid metabolism, and in the regulation of body weight, raising the possibility that the PACAP-signaling pathway that favors energy storage could be a therapeutic target for obesity.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shuhei", "last_name": "Tomimoto", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Ojika", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hamagami", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Yada", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/jphs.fp0072173" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18446003" } }, "mesh": [ { "descriptor": "Adipose Tissue, White", "descriptor_ui": "D052436", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Glucose", "descriptor_ui": "D001786", "major_topic": false }, { "descriptor": "Body Weight", "descriptor_ui": "D001835", "major_topic": true }, { "descriptor": "Dietary Fats", "descriptor_ui": "D004041", "major_topic": false }, { "descriptor": "Eating", "descriptor_ui": "D004435", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": true }, { "descriptor": "Fatty Acid-Binding Proteins", "descriptor_ui": "D050556", "major_topic": false }, { "descriptor": "Glucose Tolerance Test", "descriptor_ui": "D005951", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Islets of Langerhans", "descriptor_ui": "D007515", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Organ Size", "descriptor_ui": "D009929", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Resistin", "descriptor_ui": "D052243", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Triglycerides", "descriptor_ui": "D014280", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 May", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "41-48", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "107", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Markedly reduced white adipose tissue and increased insulin sensitivity in adcyap1-deficient mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Rhodopsins (rhodopsins and their related photopigments) are phylogenetically classified into at least seven subfamilies, which are also roughly discriminated by molecular function. The Gq-coupled rhodopsin subfamily, members of which activate the Gq type G protein upon light absorption, contains pigments which underlie both visual and nonvisual physiologic functions. Gq-coupled visual pigments have been found in the rhabdomeric photoreceptor cells of varied protostomes, and those of molluskans and arthropods have been extensively investigated. Recently, a novel photopigment, melanopsin, and its homologs have been identified in varied vertebrates. In mammals, melanopsin is localized in retinal ganglion cells and is involved in nonvisual systems, including circadian entrainment and pupillary light responses. More recently, we discovered a melanopsin homolog in amphioxus, the closest living invertebrate to vertebrates. Amphioxus melanopsin is localized in putative nonvisual photoreceptor cells with rhabdomeric morphology and exhibits molecular properties almost identical to those of invertebrate Gq-coupled visual pigments. The localization and properties of amphioxus melanopsin bridged the functional and evolutionary gap between invertebrate Gq-coupled visual pigments and vertebrate circadian photopigment melanopsins. Research into the Gq-coupled rhodopsin subfamily, especially invertebrate melanopsins, will provide an opportunity to investigate the evolution of various physiologic functions, based on orthologous genes, during animal evolution.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Terakita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1751-1097.2008.00369.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18513236" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Darkness", "descriptor_ui": "D003624", "major_topic": false }, { "descriptor": "GTP-Binding Protein alpha Subunits, Gq-G11", "descriptor_ui": "D043802", "major_topic": false }, { "descriptor": "Invertebrates", "descriptor_ui": "D007448", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Melanopsin", "descriptor_ui": "D000099210", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Retinal Pigments", "descriptor_ui": "D012168", "major_topic": false }, { "descriptor": "Rhodopsin", "descriptor_ui": "D012243", "major_topic": false }, { "descriptor": "Rod Opsins", "descriptor_ui": "D017299", "major_topic": false }, { "descriptor": "Spectrophotometry", "descriptor_ui": "D013053", "major_topic": false }, { "descriptor": "Vertebrates", "descriptor_ui": "D014714", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Jul-Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "1024-1030", "proceedings_title": null, "publisher": "", "title": "Photochemistry and photobiology", "volume": "84", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Gq-coupled rhodopsin subfamily composed of invertebrate visual pigment and melanopsin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Siliceous spicules of sponges are morphologically diverse and provide good models for understanding the morphogenesis of biomineralized products. The silica deposition enzyme silicatein is a component of siliceous spicules of sponges and is thought to be the key molecule determining the morphology of spicules. Here, we focused on the silicateins of the freshwater sponge Ephydatia fluviatilis, which has two types of morphologically and functionally different spicules, called megascleres and gemmoscleres. We isolated six isoforms of silicateins and examined their mRNA expression in the cells producing megascleres and gemmoscleres. The spicule-type-specific mRNA expression of these isoforms and differential expression during spicule development suggest that the characteristic morphology of spicules is due to the specific properties and combinatory functions of silicatein isoforms.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kurato", "last_name": "Mohri", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Nakatsukasa", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Kiyokazu", "last_name": "Agata", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Funayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/dvdy.21708" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18816843" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cathepsins", "descriptor_ui": "D002403", "major_topic": false }, { "descriptor": "DNA, Complementary", "descriptor_ui": "D018076", "major_topic": false }, { "descriptor": "Fresh Water", "descriptor_ui": "D005618", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Isoenzymes", "descriptor_ui": "D007527", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": true }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Porifera", "descriptor_ui": "D011161", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Sequence Alignment", "descriptor_ui": "D016415", "major_topic": false }, { "descriptor": "Sequence Homology, Amino Acid", "descriptor_ui": "D017386", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "3024-3039", "proceedings_title": null, "publisher": "", "title": "Developmental dynamics : an official publication of the American Association of Anatomists", "volume": "237", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Toward understanding the morphogenesis of siliceous spicules in freshwater sponge: differential mRNA expression of spicule-type-specific silicatein genes in Ephydatia fluviatilis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A unified mathematical description that expresses the characteristics of whole systems is necessary for an understanding of signal transduction cascades. In this study we explore an algebraic method, named extreme signaling flow, enhanced from the concept of extreme pathway, to analyze signal transduction systems. This method enables us to represent the long-term potentiation (LTP) and the long-term depression (LTD) of hippocampal neuronal plasticity in an integrated simulation model. The model is validated by comparing the results of redundancy, reaction participation, and in silico knockout analysis with biological knowledge available from the literature. The following properties are assumed in these computational analyses: (1) LTP is fault-tolerant under network modification, (2) protein kinase C and MAPK have numerous routes to LTP induction, (3) calcium-calmodulin kinase II has a few routes to LTP induction, and (4) calcineurin has many routes to LTD induction. These results demonstrate that our approach produces an integrated framework for analyzing properties of large-scale systems with complicated signal transduction.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiya", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1162/artl.2008.14.1.81" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18171132" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": true }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Long-Term Potentiation", "descriptor_ui": "D017774", "major_topic": false }, { "descriptor": "Long-Term Synaptic Depression", "descriptor_ui": "D036881", "major_topic": false }, { "descriptor": "Mathematics", "descriptor_ui": "D008433", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2008 Winter", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "81-94", "proceedings_title": null, "publisher": "", "title": "Artificial life", "volume": "14", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Algebraic method for the analysis of signaling crosstalk.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In physiological and pathological events, extracellular ATP plays an important role by controlling several types of purinergic receptors and changing cytoskeleton dynamics. To know the process of ATP-dependent cytoskeleton remodeling, we focused on cofilin, a key regulator of actin cytoskeleton, and investigated the dynamics of cofilin in PC12 cells through fluorescent protein-labeled cofilin and actin, Ca(2+) imaging, and fluorescence resonance energy transfer (FRET) techniques. As a result, ATP induced intracellular Ca(2+) increase, following cofilin rods' formation. ATP-induced cofilin rods' formation was not observed in cells expressing unphosphorylatable variant of cofilin. A P2X receptor agonist, but not P2Y, induced the formation of cofilin rods, whereas calmodulin and calcineurin inhibitors suppressed it. These results indicate that Ca(2+) influx through P2X receptors induces the formation of cofilin rods via calcineurin-dependent dephosphorylation of cofilin. This pathway might be one candidate to explain the effects of ATP on neuronal development and injury.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kohei", "last_name": "Homma", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Niino", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.mcn.2007.10.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17993279" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcineurin", "descriptor_ui": "D019703", "major_topic": false }, { "descriptor": "Calcineurin Inhibitors", "descriptor_ui": "D065095", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cofilin 1", "descriptor_ui": "D051338", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": false }, { "descriptor": "Neurites", "descriptor_ui": "D016501", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Receptors, Purinergic P2", "descriptor_ui": "D018048", "major_topic": false }, { "descriptor": "Receptors, Purinergic P2X", "descriptor_ui": "D058469", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "261-270", "proceedings_title": null, "publisher": "", "title": "Molecular and cellular neurosciences", "volume": "37", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Ca(2+) influx through P2X receptors induces actin cytoskeleton reorganization by the formation of cofilin rods in neurites.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In teleosts, prolactin is involved in calcium regulation, but its role in scale/bone metabolism is unclear. Using the in-vitro system with goldfish scales developed recently, we explored the effects of teleost prolactin, growth hormone, and somatolactin on osteoclasts and osteoblasts. Addition of prolactin at concentrations of 0.01-100 ng/ml reduced osteoclastic activity, partly via osteoclast apoptosis, after 6-18 h incubation. Conversely, growth hormone and somatolactin at a concentration of 100 ng/ml increased osteoclastic activity after 18 h incubation, indicating the specificity of the inhibitory effect of prolactin on osteoclastic activity. On the other hand, these three hormones promoted osteoblastic activity at concentrations of 10-100 ng/ml. The results from this study are the first demonstration of direct effects of prolactin on scale/bone metabolism and osteoclastic activity in a teleost.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hideya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Nobuo", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Chiyo", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Ikegame", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Moriyama", "name": null }, { "creator_type": "author", "first_name": "Atsuhiko", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.2108/zsj.25.739" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18828661" } }, "mesh": [ { "descriptor": "Acid Phosphatase", "descriptor_ui": "D000135", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fish Proteins", "descriptor_ui": "D029941", "major_topic": false }, { "descriptor": "Glycoproteins", "descriptor_ui": "D006023", "major_topic": false }, { "descriptor": "Goldfish", "descriptor_ui": "D006054", "major_topic": false }, { "descriptor": "Growth Hormone", "descriptor_ui": "D013006", "major_topic": false }, { "descriptor": "Isoenzymes", "descriptor_ui": "D007527", "major_topic": false }, { "descriptor": "Osteoblasts", "descriptor_ui": "D010006", "major_topic": false }, { "descriptor": "Osteoclasts", "descriptor_ui": "D010010", "major_topic": false }, { "descriptor": "Pituitary Hormones", "descriptor_ui": "D010907", "major_topic": false }, { "descriptor": "Prolactin", "descriptor_ui": "D011388", "major_topic": false }, { "descriptor": "Tartrate-Resistant Acid Phosphatase", "descriptor_ui": "D000071681", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "739-745", "proceedings_title": null, "publisher": "", "title": "Zoological science", "volume": "25", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Prolactin inhibits osteoclastic activity in the goldfish scale: a novel direct action of prolactin in teleosts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Centrosome positioning is actively regulated by forces acting on microtubules radiating from the centrosomes. Two mechanisms, center-directed and polarized cortical pulling, are major contributors to the successive centering and posteriorly displacing migrations of the centrosomes in single-cell–stage Caenorhabditis elegans. In this study, we analyze the spatial distribution of the forces acting on the centrosomes to examine the mechanism that switches centrosomal migration from centering to displacing. We clarify the spatial distribution of the forces using image processing to measure the micrometer-scale movements of the centrosomes. The changes in distribution show that polarized cortical pulling functions during centering migration. The polarized cortical pulling force directed posteriorly is repressed predominantly in the lateral regions during centering migration and is derepressed during posteriorly displacing migration. Computer simulations show that this local repression of cortical pulling force is sufficient for switching between centering and displacing migration. Local regulation of cortical pulling might be a mechanism conserved for the precise temporal regulation of centrosomal dynamic positioning.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Akatsuki", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1083/jcb.200706005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18158330" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Centrosome", "descriptor_ui": "D018385", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": false }, { "descriptor": "Spindle Apparatus", "descriptor_ui": "D008941", "major_topic": false }, { "descriptor": "Tensile Strength", "descriptor_ui": "D013718", "major_topic": false }, { "descriptor": "Weight-Bearing", "descriptor_ui": "D016474", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Dec 31", "date_precision": "day", "issue": "7", "normalized_date": "2007-12-31", "pages": "1347-1354", "proceedings_title": null, "publisher": "", "title": "The Journal of Cell Biology", "volume": "179", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Local cortical pulling-force repression switches centrosomal centration and posterior displacement in C. elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A scheme for extracting an effective free energy landscape from single-molecule time series is presented. This procedure uniquely identifies a non-Gaussian distribution of the observable associated with each local equilibrium state (LES). Both the number of LESs and the shape of the non-Gaussian distributions depend on the time scale of observation. By assessing how often the system visits and resides in a chosen LES and escapes from one LES to another (with checking whether the local detailed balance is satisfied), our scheme naturally leads to an effective free energy landscape whose topography depends on in which time scale the system experiences the underlying landscape. For example, two metastable states are unified as one if the time scale of observation is longer than the escape time scale for which the system can visit mutually these two states. As an illustrative example, we present the application of extracting the effective free energy landscapes from time series of the end-to-end distance of a three-color, 46-bead model protein. It indicates that the time scales to attain the local equilibrium tend to be longer in the unfolded state than those in the compact collapsed state.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Akinori", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.0704167104" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18048341" } }, "mesh": [ { "descriptor": "Entropy", "descriptor_ui": "D019277", "major_topic": true }, { "descriptor": "Mathematical Computing", "descriptor_ui": "D008432", "major_topic": true }, { "descriptor": "Protein Folding", "descriptor_ui": "D017510", "major_topic": true }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false }, { "descriptor": "Time", "descriptor_ui": "D013995", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Dec 4", "date_precision": "day", "issue": "49", "normalized_date": "2007-12-04", "pages": "19297-19302", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "104", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Construction of effective free energy landscape from single-molecule time series.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Long-term depression (LTD) of excitatory transmission at cerebellar parallel fibre–Purkinje cell synapses is a form of synaptic plasticity crucial for cerebellar motor learning. Around the postsynaptic membrane of these synapses, B-type γ-aminobutyric acid receptor (GABABR), a Gi/o protein-coupled receptor for the inhibitory transmitter GABA is concentrated and closely associated with type-1 metabotropic glutamate receptors (mGluR1) whose signalling is a key factor for inducing LTD. We found that in cultured Purkinje cells, GABABR activation enhanced LTD of a glutamate-evoked current (LTDglu), increasing the magnitude of depression. It has been reported that parallel fibre–Purkinje cell synapses receive a micromolar level of GABA spilt over from the synaptic terminals of the neighbouring GABAergic interneurons. This level of GABA was able to enhance LTDglu. Our pharmacological analyses revealed that the βγ subunits but not the α subunit of Gi/o protein mediated GABABR-mediated LTDglu enhancement. Gi/o protein activation was sufficient to enhance LTDglu. In this respect, LTDglu enhancement is clearly distinguished from the previously reported GABABR-mediated augmentation of an mGluR1-coupled slow excitatory postsynaptic potential. Baclofen application for only the induction period of LTDglu was sufficient to enhance LTDglu, suggesting that GABABR signalling may modulate mechanisms underlying LTDglu induction. Baclofen augmented mGluR1-coupled Ca2+ release from the intracellular stores in a Gi/o protein-dependent manner. Therefore, GABABR-mediated LTDglu enhancement is likely to result from augmentation of mGluR1 signalling. Furthermore, pharmacological inhibition of GABABR reduced the magnitude of LTD at parallel fibre–Purkinje cell synapses in cerebellar slices. These findings demonstrate a novel mechanism that would facilitate cerebellar motor learning.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Kamikubo", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Kakizawa", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Masamitsu", "last_name": "Iino", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1113/jphysiol.2007.141010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17947316" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Baclofen", "descriptor_ui": "D001418", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "GABA Agonists", "descriptor_ui": "D018755", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Long-Term Synaptic Depression", "descriptor_ui": "D036881", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Protein Subunits", "descriptor_ui": "D021122", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Receptors, GABA-B", "descriptor_ui": "D018080", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Dec 01", "date_precision": "day", "issue": "Pt 2", "normalized_date": "2007-12-01", "pages": "549-563", "proceedings_title": null, "publisher": "", "title": "The Journal of Physiology", "volume": "585", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Postsynaptic GABAB receptor signalling enhances LTD in mouse cerebellar Purkinje cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "TLR3 recognizes viral dsRNA and induces antiviral immune responses. TLR3-mediated cell activation relies on Toll/IL-1R (TIR) domain-containing adaptor molecule-1 (TICAM-1, also named TIR domain-containing adaptor inducing IFN-beta or TRIF), which recruits downstream signaling molecules to activate the transcription factors IFN regulatory factor 3 (IRF-3) and NF-kappaB. The mechanisms by which TICAM-1 is activated and transmits signals remain largely unknown. In this study we show that TICAM-1 alters its distribution profile from a diffuse cytoplasmic form to a speckle-like structure in response to dsRNA. The receptor-interacting protein 1 (RIP1), a crucial signaling molecule for TICAM-1-mediated NF-kappaB activation, accumulated in the TICAM-1 speckles. In addition, NF-kappaB-activating kinase-associated protein 1 (NAP1), a downstream molecule linking TICAM-1 and the IRF-3-activating kinase TBK1 (TANK-binding kinase 1), was also recruited to the TICAM-1 speckles. Notably, a transient colocalization of TICAM-1 and TLR3 was observed before the extensive formation of the TICAM-1 speckles. Thus, the spatiotemporal mobilization of TICAM-1 in response to dsRNA and the formation of the TICAM-1 speckles containing RIP1 and NAP1 are important for the activation of the TLR3-TICAM-1 pathway.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Funami", "name": null }, { "creator_type": "author", "first_name": "Miwa", "last_name": "Sasai", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Oshiumi", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Seya", "name": null }, { "creator_type": "author", "first_name": "Misako", "last_name": "Matsumoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.4049/jimmunol.179.10.6867" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17982077" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Vesicular Transport", "descriptor_ui": "D033942", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interferon Regulatory Factor-3", "descriptor_ui": "D050838", "major_topic": false }, { "descriptor": "Multiprotein Complexes", "descriptor_ui": "D046912", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Nuclear Pore Complex Proteins", "descriptor_ui": "D028861", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "RNA, Double-Stranded", "descriptor_ui": "D012330", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Toll-Like Receptor 3", "descriptor_ui": "D051196", "major_topic": false }, { "descriptor": "tRNA Methyltransferases", "descriptor_ui": "D012359", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Nov 15", "date_precision": "day", "issue": "10", "normalized_date": "2007-11-15", "pages": "6867-6872", "proceedings_title": null, "publisher": "", "title": "Journal of immunology (Baltimore, Md. : 1950)", "volume": "179", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatiotemporal mobilization of Toll/IL-1 receptor domain-containing adaptor molecule-1 in response to dsRNA.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Superior fluorescence imaging methods are needed for detailed studies on biological phenomena, and one approach that permits precise analyses is time-resolved fluorescence measurement, which offers a high signal-to-noise ratio. Herein, we describe a new fluorescence imaging system to visualize biomolecules within living biological samples by means of time-resolved, long-lived luminescence microscopy (TRLLM). In TRLLM, short-lived background fluorescence and scattered light are gated out, allowing the long-lived luminescence to be selectively imaged. Usual time-resolved fluorescence microscopy provides fluorescence images with nanosecond resolution and has been used to image interactions between proteins, protein phosphorylation, the local pH, the refractive index, ion or oxygen concentrations, etc. Luminescent lanthanide complexes (especially europium and terbium trivalent ions (Eu3+ and Tb3+)), in contrast, have long luminescence lifetimes on the order of milliseconds. We have designed and synthesized new luminescent Eu3+ complexes for TRLLM and also developed a new TRLLM system using a conventional fluorescence microscope with an image intensifier unit for gated signal acquisition and a xenon flash lamp as the excitation source. When the newly developed luminescent Eu3+ complexes were applied to living cells, clear fluorescence images were acquired with the TRLLM system, and short-lived fluorescence was completely excluded. By using Eu3+ and Tb3+ luminescent complexes in combination, time-resolved dual-color imaging was also possible. Furthermore, we monitored changes of intracellular ionic zinc (Zn2+) concentration by using a Zn2+-selective luminescent Eu3+ chemosensor, [Eu-7]. This new imaging technique should facilitate investigations of biological functions with fluorescence microscopy, complementing other fluorescence imaging methodologies.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja073392j" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17927176" } }, "mesh": [ { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Fluid", "descriptor_ui": "D007424", "major_topic": false }, { "descriptor": "Lanthanoid Series Elements", "descriptor_ui": "D028581", "major_topic": false }, { "descriptor": "Luminescence", "descriptor_ui": "D049449", "major_topic": true }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Organometallic Compounds", "descriptor_ui": "D009942", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Zinc", "descriptor_ui": "D015032", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Nov 7", "date_precision": "day", "issue": "44", "normalized_date": "2007-11-07", "pages": "13502-13509", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "129", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Time-resolved long-lived luminescence imaging method employing luminescent lanthanide probes with a new microscopy system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "HemAT-Bs is the heme-based O(2) sensor responsible for aerotaxis control in Bacillus subtilis. In this study, we measured the time-resolved resonance Raman spectra of full-length HemAT-Bs wild-type (WT) and Y133F in the deoxy form and the photoproduct after photolysis of CO-bound form. In WT, the nu(Fe-His) band for the 10 ps photoproduct was observed at higher frequency by about 2 cm(-1) compared with that of the deoxy form. This frequency difference is relaxed in hundreds of picoseconds. This time-dependent frequency shift would reflect the conformational change of the protein matrix. On the other hand, Y133F mutant did not show such a substantial nu(Fe-His) frequency shift after photolysis. Since a hydrogen bond to the proximal His induces an up-shift of the nu(Fe-His) frequency, these results indicate that Tyr133 forms a hydrogen bond to the proximal His residue upon the ligand binding. We discuss a functional role of this hydrogen bond formation for the signal transduction in HemAT-Bs.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Shiro", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Shigetoshi", "last_name": "Aono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2007.04.041" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17459338" } }, "mesh": [ { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Carbon Monoxide", "descriptor_ui": "D002248", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Heme", "descriptor_ui": "D006418", "major_topic": false }, { "descriptor": "Heme-Binding Proteins", "descriptor_ui": "D000081062", "major_topic": false }, { "descriptor": "Hemeproteins", "descriptor_ui": "D006420", "major_topic": false }, { "descriptor": "Hydrogen Bonding", "descriptor_ui": "D006860", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Models, Chemical", "descriptor_ui": "D008956", "major_topic": true }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": true }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Jun 15", "date_precision": "day", "issue": "4", "normalized_date": "2007-06-15", "pages": "1053-1057", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "357", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "The formation of hydrogen bond in the proximal heme pocket of HemAT-Bs upon ligand binding.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To understand the genetic origin of I2020T mutation in the kinase domain of leucine rich repeat kinase 2 (LRRK2), we investigated the original PARK8 Japanese family (Sagamihara family) and a German family (family 32), both of which were found to harbor I2020T as the causal mutation for autosomal dominant familial Parkinson's disease (PD). Microsatellite-haplotype analysis around the LRRK2 gene indicated that the mutation-carrying haplotypes of the two families were distinct from each other. This indicated that the I2020T mutation, an essential pathogenic mutation of PARK8-related PD, had occurred independently in the two PD families.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Gasser", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Obata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neulet.2007.02.086" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17395370" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": false }, { "descriptor": "Chromosome Disorders", "descriptor_ui": "D025063", "major_topic": false }, { "descriptor": "DNA Mutational Analysis", "descriptor_ui": "D004252", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genes, Dominant", "descriptor_ui": "D005799", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Genetic Testing", "descriptor_ui": "D005820", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Germany", "descriptor_ui": "D005858", "major_topic": false }, { "descriptor": "Haplotypes", "descriptor_ui": "D006239", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Leucine-Rich Repeat Serine-Threonine Protein Kinase-2", "descriptor_ui": "D000071158", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microsatellite Repeats", "descriptor_ui": "D018895", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Parkinson Disease", "descriptor_ui": "D010300", "major_topic": false }, { "descriptor": "Pedigree", "descriptor_ui": "D010375", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "White People", "descriptor_ui": "D044465", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Apr 24", "date_precision": "day", "issue": "1", "normalized_date": "2007-04-24", "pages": "21-23", "proceedings_title": null, "publisher": "", "title": "Neuroscience letters", "volume": "417", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Independent occurrence of I2020T mutation in the kinase domain of the leucine rich repeat kinase 2 gene in Japanese and German Parkinson's disease families.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PEG-coated beta-FeOOH nanoparticles were prepared through electrostatic complex formation of iron oxide nanoparticles with poly(ethylene glycol)-poly(aspartic acid) block copolymer [PEG-P(Asp)] in distilled water. By dynamic light scattering (DLS) measurement, the nanopaticle size was determined to be 70 nm with narrow distribution. The FT-IR and zeta potential experimental results proved that PEG-PAsp molecules bound to the surface of the iron oxide nanoparticles via the coordination between the carboxylic acid residues in the PAsp segment of the block copolymer and the surface Fe of the beta-FeOOH nanoparticles. The PEG-coated nanoparticles revealed excellent solubility and stability in aqueous solution as well as in physiological saline. In vivo MRI experiments on tumor-bearing mice demonstrated that the PEG-coated nanoparticles prepared by the current approach achieved an appreciable accumulation into solid tumor, suggesting their potential utility as tumor-selective MRI contrast agents.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Teisaku", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Sekino", "name": null }, { "creator_type": "author", "first_name": "Shoogo", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Shimokado", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Kataoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.colsurfb.2006.12.019" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17324561" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aspartic Acid", "descriptor_ui": "D001224", "major_topic": false }, { "descriptor": "Coated Materials, Biocompatible", "descriptor_ui": "D020099", "major_topic": false }, { "descriptor": "Colonic Neoplasms", "descriptor_ui": "D003110", "major_topic": false }, { "descriptor": "Contrast Media", "descriptor_ui": "D003287", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Hydroxides", "descriptor_ui": "D006878", "major_topic": false }, { "descriptor": "Iron", "descriptor_ui": "D007501", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred Strains", "descriptor_ui": "D008815", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": true }, { "descriptor": "Neoplasm Transplantation", "descriptor_ui": "D009368", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Particle Size", "descriptor_ui": "D010316", "major_topic": false }, { "descriptor": "Polyethylene Glycols", "descriptor_ui": "D011092", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Spectroscopy, Fourier Transform Infrared", "descriptor_ui": "D017550", "major_topic": false }, { "descriptor": "X-Ray Diffraction", "descriptor_ui": "D014961", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Apr 15", "date_precision": "day", "issue": "1-2", "normalized_date": "2007-04-15", "pages": "174-181", "proceedings_title": null, "publisher": "", "title": "Colloids and surfaces. B, Biointerfaces", "volume": "56", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Iron hydroxide nanoparticles coated with poly(ethylene glycol)-poly(aspartic acid) block copolymer as novel magnetic resonance contrast agents for in vivo cancer imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Functional crosstalk between cell-surface and intracellular ion channels plays important roles in excitable cells and is structurally supported by junctophilins (JPs) in muscle cells. Here, we report a novel form of channel crosstalk in cerebellar Purkinje cells (PCs). The generation of slow afterhyperpolarization (sAHP) following complex spikes in PCs required ryanodine receptor (RyR)-mediated Ca(2+)-induced Ca(2+) release and the subsequent opening of small-conductance Ca(2+)-activated K(+) (SK) channels in somatodendritic regions. Despite the normal expression levels of these channels, sAHP was abolished in PCs from mutant mice lacking neural JP subtypes (JP-DKO), and this defect was restored by exogenously expressing JPs or enhancing SK channel activation. The stimulation paradigm for inducing long-term depression (LTD) at parallel fiber-PC synapses adversely established long-term potentiation in the JP-DKO cerebellum, primarily due to the sAHP deficiency. Furthermore, JP-DKO mice exhibited impairments of motor coordination and learning, although normal cerebellar histology was retained. Therefore, JPs support the Ca(2+)-mediated communication between voltage-gated Ca(2+) channels, RyRs and SK channels, which modulates the excitability of PCs and is fundamental to cerebellar LTD and motor functions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Sho", "last_name": "Kakizawa", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Kazuharu", "last_name": "Furutani", "name": null }, { "creator_type": "author", "first_name": "Hidemi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Fukaya", "name": null }, { "creator_type": "author", "first_name": "Miyuki", "last_name": "Nishi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Sakagami", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Hisatake", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masamitsu", "last_name": "Iino", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Takeshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/sj.emboj.7601639" }, "pmcid": { "normalized": "PMC1847665" }, "pmid": { "normalized": "17347645" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Ion Channel Gating", "descriptor_ui": "D015640", "major_topic": false }, { "descriptor": "Learning", "descriptor_ui": "D007858", "major_topic": false }, { "descriptor": "Long-Term Synaptic Depression", "descriptor_ui": "D036881", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Motor Skills", "descriptor_ui": "D009048", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": true }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Ryanodine Receptor Calcium Release Channel", "descriptor_ui": "D019837", "major_topic": false }, { "descriptor": "Small-Conductance Calcium-Activated Potassium Channels", "descriptor_ui": "D051640", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Apr 4", "date_precision": "day", "issue": "7", "normalized_date": "2007-04-04", "pages": "1924-1933", "proceedings_title": null, "publisher": "", "title": "The EMBO journal", "volume": "26", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Umbilical cord blood (CB) is a promising source for regeneration therapy in humans. Recently, it was shown that CB was a source of mesenchymal stem cells as well as hematopoietic stem cells, and further that the mesenchymal stem cells could differentiate into a number of cells types of mesenchymal lineage, such as cardiomyocytes (CMs), osteocytes, chondrocytes, and fat cells. Previously, we reported that brown adipose tissue derived cells (BATDCs) differentiated into CMs and these CMs could adapt functionally to repair regions of myocardial infarction. In this study, we examined whether CB mononuclear cells (CBMNCs) could effectively differentiate into CMs by coculturing them with BATDCs and determined which population among CBMNCs differentiated into CMs. The results show that BATDCs effectively induced CBMNCs that were non-hematopoietic stem cells (HSCs) (educated CB cells: e-CBCs) into CMs in vitro. E-CBCs reconstituted infarcted myocardium more effectively than non-educated CBMNCs or CD34-positive HSCs. Moreover, we found that e-CBCs after 3 days coculturing with BATDCs induced the most effective regeneration for impaired CMs. This suggests that e-CBCs have a high potential to differentiate into CMs and that adequate timing of transplantation supports a high efficiency for CM regeneration. This strategy might be a promising therapy for human cardiac disease.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Shin-ichiro", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Xiao-Yong", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Hisamichi", "last_name": "Naitoh", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2006.12.017" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17174277" } }, "mesh": [ { "descriptor": "Adipocytes", "descriptor_ui": "D017667", "major_topic": false }, { "descriptor": "Adipose Tissue, Brown", "descriptor_ui": "D002001", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Cord Blood Stem Cell Transplantation", "descriptor_ui": "D036101", "major_topic": false }, { "descriptor": "Guided Tissue Regeneration", "descriptor_ui": "D048091", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Myocardial Infarction", "descriptor_ui": "D009203", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Nude", "descriptor_ui": "D011923", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Feb 2", "date_precision": "day", "issue": "1", "normalized_date": "2007-02-02", "pages": "182-188", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "353", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "A novel approach for myocardial regeneration with educated cord blood cells cocultured with cells from brown adipose tissue.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tonically active cholinergic interneurons in the striatum modulate activities of striatal outputs from medium spiny (MS) neurons and significantly influence overall functions of the basal ganglia. Cellular mechanisms of this modulation are not fully understood. Here we show that ambient acetylcholine (ACh) derived from tonically active cholinergic interneurons constitutively upregulates depolarization-induced release of endocannabinoids from MS neurons. The released endocannabinoids cause transient suppression of inhibitory synaptic inputs to MS neurons through acting retrogradely onto presynaptic CB1 cannabinoid receptors. The effects were mediated by postsynaptic M1 subtype of muscarinic ACh receptors, because the action of a muscarinic agonist to release endocannabinoids and the enhancement of depolarization-induced endocannabinoid release by ambient ACh were both deficient in M1 knock-out mice and were blocked by postsynaptic infusion of guanosine-5′-O-(2-thiodiphosphate). Suppression of spontaneous firings of cholinergic interneurons by inhibiting Ih current reduced the depolarization-induced release of endocannabinoids. Conversely, elevation of ambient ACh concentration by inhibiting choline esterase significantly enhanced the endocannabinoid release. Paired recording from a cholinergic interneuron and an MS neuron revealed that the activity of single cholinergic neuron could influence endocannabinoid-mediated signaling in neighboring MS neurons. These results clearly indicate that striatal endocannabinoid-mediated modulation is under the control of cholinergic interneuron activity. By immunofluorescent and immunoelectron microscopic examinations, we demonstrated that M1 receptor was densely distributed in perikarya and dendrites of dopamine D1 or D2 receptor-positive MS neurons. Thus, we have disclosed a novel mechanism by which the muscarinic system regulates striatal output and may contribute to motor control.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Madoka", "last_name": "Narushima", "name": null }, { "creator_type": "author", "first_name": "Motokazu", "last_name": "Uchigashima", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Fukaya", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Manabe", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.4644-06.2007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17234582" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cannabinoid Receptor Modulators", "descriptor_ui": "D063385", "major_topic": false }, { "descriptor": "Cholinergic Fibers", "descriptor_ui": "D002799", "major_topic": false }, { "descriptor": "Corpus Striatum", "descriptor_ui": "D003342", "major_topic": false }, { "descriptor": "Endocannabinoids", "descriptor_ui": "D063388", "major_topic": true }, { "descriptor": "Interneurons", "descriptor_ui": "D007395", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Neural Inhibition", "descriptor_ui": "D009433", "major_topic": false }, { "descriptor": "Receptor, Cannabinoid, CB1", "descriptor_ui": "D043884", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Jan 17", "date_precision": "day", "issue": "3", "normalized_date": "2007-01-17", "pages": "496-506", "proceedings_title": null, "publisher": "", "title": "The Journal of Neuroscience", "volume": "27", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Tonic Enhancement of Endocannabinoid-Mediated Retrograde Suppression of Inhibition by Cholinergic Interneuron Activity in the Striatum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Analysis of genomic resources available for cnidarians revealed that several key components of the vertebrate innate immune repertoire are present in representatives of the basal cnidarian class Anthozoa, but are missing in Hydra, a member of the class Hydrozoa, indicating ancient origins for many components of the innate immune system.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "David J.", "last_name": "Miller", "name": null }, { "creator_type": "author", "first_name": "Georg", "last_name": "Hemmrich", "name": null }, { "creator_type": "author", "first_name": "Eldon E.", "last_name": "Ball", "name": null }, { "creator_type": "author", "first_name": "David C.", "last_name": "Hayward", "name": null }, { "creator_type": "author", "first_name": "Konstantin", "last_name": "Khalturin", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Funayama", "name": null }, { "creator_type": "author", "first_name": "Kiyokazu", "last_name": "Agata", "name": null }, { "creator_type": "author", "first_name": "Thomas CG", "last_name": "Bosch", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/gb-2007-8-4-r59" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17437634" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cnidaria", "descriptor_ui": "D003063", "major_topic": false }, { "descriptor": "Complement C3", "descriptor_ui": "D003176", "major_topic": false }, { "descriptor": "Expressed Sequence Tags", "descriptor_ui": "D020224", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": true }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "Hydra", "descriptor_ui": "D006829", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stochastic Processes", "descriptor_ui": "D013269", "major_topic": false }, { "descriptor": "Toll-Like Receptors", "descriptor_ui": "D051193", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007", "date_precision": "year", "issue": "4", "normalized_date": "2007", "pages": "R59", "proceedings_title": null, "publisher": "", "title": "Genome Biology", "volume": "8", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "The innate immune repertoire in Cnidaria - ancestral complexity and stochastic gene loss.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We demonstrate a time-lapse video approach that allows rapid examination of the spatio-temporal dynamics of Dictyostelium cell populations. Quantitative information was gathered by sampling life histories of more than 2,000 mutant clones from a large mutagenesis collection. Approximately 4% of the clonal lines showed a mutant phenotype at one stage. Many of these could be ordered by clustering into functional groups. The dataset allows one to search and retrieve movies on a gene-by-gene and phenotype-by-phenotype basis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Xiao-Juan", "last_name": "Guan", "name": null }, { "creator_type": "author", "first_name": "Adam", "last_name": "Kuspa", "name": null }, { "creator_type": "author", "first_name": "Edward C.", "last_name": "Cox", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/gb-2007-8-7-r144" }, "pmcid": { "normalized": "PMC2323234" }, "pmid": { "normalized": "17659086" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false }, { "descriptor": "Microscopy, Video", "descriptor_ui": "D018715", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007", "date_precision": "year", "issue": "7", "normalized_date": "2007", "pages": "R144", "proceedings_title": null, "publisher": "", "title": "Genome biology", "volume": "8", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "High-throughput analysis of spatio-temporal dynamics in Dictyostelium.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chronic administration of methamphetamine (METH) elicits progressive enhancement of locomotor activity known as behavioral sensitization. We have recently shown that chronic METH enhanced METH challenge-induced increase in 5-HT levels in the prefrontal cortex and that 5-HT(1A) receptor activation attenuated this neurochemical sensitization as well as behavioral sensitization. This study examined whether the nonselective 5-HT(2) receptor antagonist, ritanserin affects METH-induced behavioral and neurochemical sensitization in mice. Ritanserin at doses of 1 and 3 mg/kg inhibited the development and expression of METH-induced behavioral sensitization in a dose-dependent manner. Furthermore, chronic administration of ritanserin for a week attenuated the maintenance of behavioral sensitization, indicating the improvement of established behavioral sensitization. Microdialysis analysis showed that chronic ritanserin inhibited the neurochemical sensitization that chronic METH enhanced METH challenge-induced increase in extracellular 5-HT levels in the prefrontal cortex. Furthermore, acute ritanserin inhibited METH challenge-induced increase in extracellular 5-HT but not DA levels in the prefrontal cortex. These results suggest that 5-HT(2) receptors are involved in METH-induced hyperactivity and behavioral sensitization in mice.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Kajita", "name": null }, { "creator_type": "author", "first_name": "Misato", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/syn.20421" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17568413" } }, "mesh": [ { "descriptor": "Analysis of Variance", "descriptor_ui": "D000704", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Brain Chemistry", "descriptor_ui": "D001923", "major_topic": false }, { "descriptor": "Central Nervous System Stimulants", "descriptor_ui": "D000697", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Drug Administration Schedule", "descriptor_ui": "D004334", "major_topic": false }, { "descriptor": "Drug Interactions", "descriptor_ui": "D004347", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Methamphetamine", "descriptor_ui": "D008694", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microdialysis", "descriptor_ui": "D017551", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Ritanserin", "descriptor_ui": "D016713", "major_topic": false }, { "descriptor": "Serotonin Antagonists", "descriptor_ui": "D012702", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "757-763", "proceedings_title": null, "publisher": "", "title": "Synapse (New York, N.Y.)", "volume": "61", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Ritanserin reverses repeated methamphetamine-induced behavioral and neurochemical sensitization in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The intracellular parasite Salmonella enterica serovar Typhimurium causes a typhoid-like systemic disease in mice. Whereas the survival of Salmonella in phagocytes is well understood, little has been documented about the exit of intracellular Salmonella from host cells. Here we report that in a population of infected macrophages Salmonella induces \"oncosis,\" an irreversible progression to eukaryotic cell death characterized by swelling of the entire cell body. Oncotic macrophages (OnMphis) are terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling negative and lack actin filaments (F-actin). The plasma membrane of OnMphis filled with bacilli remains impermeable, and intracellular Salmonella bacilli move vigorously using flagella. Eventually, intracellular Salmonella bacilli intermittently exit host cells in a flagellum-dependent manner. These results suggest that induction of macrophage oncosis and intracellular accumulation of flagellated bacilli constitute a strategy whereby Salmonella escapes from host macrophages.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Gen-ichiro", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Matsuo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jb.00898-07" }, "pmcid": { "normalized": "PMC2168665" }, "pmid": { "normalized": "17873035" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cytoskeleton", "descriptor_ui": "D003599", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Flagella", "descriptor_ui": "D005407", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Movement", "descriptor_ui": "D009068", "major_topic": true }, { "descriptor": "Necrosis", "descriptor_ui": "D009336", "major_topic": false }, { "descriptor": "Salmonella Infections, Animal", "descriptor_ui": "D012481", "major_topic": false }, { "descriptor": "Salmonella typhimurium", "descriptor_ui": "D012486", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Nov", "date_precision": "unknown", "issue": "22", "normalized_date": null, "pages": "8224-8232", "proceedings_title": null, "publisher": "", "title": "Journal of bacteriology", "volume": "189", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Flagella facilitate escape of Salmonella from oncotic macrophages.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mice lacking the PACAP gene (PACAP(-/-)) display psychomotor abnormalities such as novelty-induced hyperactivity and jumping behavior, and they show different responses to amphetamine, a typical psychostimulant. The present study examined the possible role of endogenous PACAP in methamphetamine (METH)-induced hyperactivity and behavioral sensitization. The locomotor activity of hyperactive PACAP(-/-) mice was measured using the infrared photocell beam detection system, Acti-Track, after a habituation period. Single administration of METH (1 and 2mg/kg) caused a robust increase in locomotor activity of mice, but this effect did not differ between wild-type and PACAP(-/-) mice. Repeated administration of METH (1mg/kg) for 7 days enhanced METH-induced hyperactivity, and this sensitization was observed even when withdrawn for 7 days. There was no difference in the degree of development and expression of METH-induced behavioral sensitization between wild-type and PACAP(-/-) mice. In addition, there was no difference in METH-induced increases in extracellular serotonin and dopamine levels in the prefrontal cortex of the normal and sensitized mice between the two groups. These results suggest that endogenous PACAP is not involved in the locomotor stimulant activity of acute METH and repeated METH-induced behavioral and neurochemical sensitization.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Harumi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Ishihama", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Michiya", "last_name": "Kakuda", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.peptides.2007.06.012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17658665" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Central Nervous System Stimulants", "descriptor_ui": "D000697", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Methamphetamine", "descriptor_ui": "D008694", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Microdialysis", "descriptor_ui": "D017551", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "1674-1679", "proceedings_title": null, "publisher": "", "title": "Peptides", "volume": "28", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Methamphetamine-induced hyperactivity and behavioral sensitization in PACAP deficient mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17511259" } }, "mesh": [ { "descriptor": "Amphetamine", "descriptor_ui": "D000661", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": false }, { "descriptor": "Lithium Compounds", "descriptor_ui": "D018020", "major_topic": false }, { "descriptor": "Mental Disorders", "descriptor_ui": "D001523", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Mutant Strains", "descriptor_ui": "D008817", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Receptor, Serotonin, 5-HT1A", "descriptor_ui": "D044282", "major_topic": false }, { "descriptor": "Sensation Disorders", "descriptor_ui": "D012678", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "375-379", "proceedings_title": null, "publisher": "", "title": "Seikagaku. The Journal of Japanese Biochemical Society", "volume": "79", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "[Neuropeptide PACAP and neuropsychological function: unexpected insights from mouse mutants].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Poor survival of human embryonic stem (hES) cells after cell dissociation is an obstacle to research, hindering manipulations such as subcloning. Here we show that application of a selective Rho-associated kinase (ROCK) inhibitor, Y-27632, to hES cells markedly diminishes dissociation-induced apoptosis, increases cloning efficiency (from approximately 1% to approximately 27%) and facilitates subcloning after gene transfer. Furthermore, dissociated hES cells treated with Y-27632 are protected from apoptosis even in serum-free suspension (SFEB) culture and form floating aggregates. We demonstrate that the protective ability of Y-27632 enables SFEB-cultured hES cells to survive and differentiate into Bf1(+) cortical and basal telencephalic progenitors, as do SFEB-cultured mouse ES cells.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kiichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Michiru", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Wataya", "name": null }, { "creator_type": "author", "first_name": "Jun B.", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Shin-ichi", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nbt1310" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17529971" } }, "mesh": [ { "descriptor": "Amides", "descriptor_ui": "D000577", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false }, { "descriptor": "rho-Associated Kinases", "descriptor_ui": "D054460", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "681-686", "proceedings_title": null, "publisher": "", "title": "Nature biotechnology", "volume": "25", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "A ROCK inhibitor permits survival of dissociated human embryonic stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The kissing loach, an endangered species surviving only in a few Japanese rivers, spawns in the rice-field areas after migration from rivers in early June. To characterize the environmental conditions required for spawning of the kissing loach, spawning was assessed for two years both by direct observation of spawning behavior and by the appearance of eggs, larvae, and juveniles from June to October. All spawning of the kissing loach was limited to within a couple of days after the formation of temporary waters by remarkable rises in water level. Water temperature and daily rainfall fluctuated during the investigation periods, and no clear relationships with spawning were detected. Furthermore, all spawning was observed only in temporary waters with terrestrial grasses. Thus, spawning of the kissing loach is rigidly limited spatio-temporally to after the formation of temporary waters over terrestrial vegetation. Appropriate management of temporary waters will be crucial for the continued existence of this species.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Kon", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.2108/zsj.24.922" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17960998" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": true }, { "descriptor": "Cypriniformes", "descriptor_ui": "D003531", "major_topic": false }, { "descriptor": "Environment", "descriptor_ui": "D004777", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fresh Water", "descriptor_ui": "D005618", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Reproduction", "descriptor_ui": "D012098", "major_topic": true }, { "descriptor": "Seasons", "descriptor_ui": "D012621", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "922-926", "proceedings_title": null, "publisher": "", "title": "Zoological science", "volume": "24", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Spawning of the kissing loach (Leptobotia curta) is limited to periods following the formation of temporary waters.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have previously shown that esophageal epithelium of a euryhaline goby displays elevated cell proliferation in freshwater (FW) fish, but undergo apoptosis during seawater (SW) acclimation. Prolactin (PRL) injection into the goby induced the cell proliferation, whereas cortisol treatment stimulated the cell proliferation and apoptosis [Takahashi, H., Sakamoto, T., Narita, K., 2006a. Cell proliferation and apoptosis in the anterior intestine of an amphibious, euryhaline mudskipper (Periophthalmus modestus). J. Comp. Physiol. B 176, 463-468, 2006). In the euryhaline tilapia (Oreochromis mossambicus), the dynamics of changes in cortisol-glucocorticoid receptors (GR) during acclimation to different salinities also suggests a role for glucocorticoid signaling in the esophageal cell turnover, but the mode of PRL action remains largely unclear. In the present study, we report on effects in the tilapia esophagus that result from changes in environmental salinity. Specifically, we assessed: (1) mRNA expression of PRL receptor (PRLR) using quantitative real-time RT-PCR; (2) esophageal cell proliferation and apoptosis, using immunohistochemistry of proliferating cells nuclear antigen (PCNA) and in situ nick end-labeling of genomic DNA (TUNEL); (3) the possible localization of immunoreactive PRLR on proliferating/apoptotic cells. Plasma PRL increased after FW acclimation; PRLR mRNA levels in the esophagus of FW fish were significantly higher than those in SW-acclimated fish. Cell proliferation was induced randomly throughout the esophageal epithelium after FW acclimation, while cell division and increased apoptosis were concentrated at the tips of esophageal epithelial folds in SW-acclimated fish. Immunoreactive PRLR appeared to be localized at proliferating cells and at certain apoptotic cells, whereas immunoreactive GR was observed over the whole epithelium including the apoptotic/proliferating cells. Thus, PRL appears to affect cell turnover directly in the esophageal epithelium of the euryhaline tilapia.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hideya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Patrick", "last_name": "Prunet", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kitahashi", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Kajimura", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "E. Gordon", "last_name": "Grau", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ygcen.2007.02.021" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17418192" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Esophagus", "descriptor_ui": "D004947", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fresh Water", "descriptor_ui": "D005618", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Proliferating Cell Nuclear Antigen", "descriptor_ui": "D018809", "major_topic": false }, { "descriptor": "Receptors, Prolactin", "descriptor_ui": "D011981", "major_topic": false }, { "descriptor": "Seawater", "descriptor_ui": "D012623", "major_topic": false }, { "descriptor": "Tilapia", "descriptor_ui": "D017210", "major_topic": false }, { "descriptor": "Water-Electrolyte Balance", "descriptor_ui": "D014882", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Jun-Jul", "date_precision": "unknown", "issue": "2-3", "normalized_date": null, "pages": "326-331", "proceedings_title": null, "publisher": "", "title": "General and comparative endocrinology", "volume": "152", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Prolactin receptor and proliferating/apoptotic cells in esophagus of the Mozambique tilapia (Oreochromis mossambicus) in fresh water and in seawater.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The basic helix-loop-helix transcription factor, oligodendrocyte lineage transcription factor 2 (OLIG2), is specifically expressed in the developing and mature central nervous system and plays an important role in oligodendrogenesis from neural progenitors. It is also expressed in various types of glial tumors, but rarely in glioblastoma. Although we previously showed that OLIG2 expression inhibits glioma cell growth, its role in tumorigenesis remains incompletely understood. Here, we investigated the effect of OLIG2 expression on the migration of the human glioblastoma cell line U12-1. In these cells, OLIG2 expression is controlled by the Tet-off system. Induction of OLIG2 expression inhibited both the migration and invasiveness of U12-1 cells. OLIG2 expression also increased the activity of the GTPase RhoA as well as inducing the cells to form stress fibers and focal adhesions. Experiments using short interfering RNA against p27(Kip1) revealed that up-regulation of the p27(Kip1) protein was not essential for RhoA activation, rather it contributed independently to the decreased motility of OLIG2-expressing U12-1 cells. Alternatively, semiquantitative reverse transcription-PCR analysis revealed that mRNA expression of RhoGAP8, which regulates cell migration, was decreased by OLIG2 expression. Furthermore, expression of C3 transferase, which inhibits Rho via ADP ribosylation, attenuated the OLIG2-induced inhibition of cell motility. Imaging by fluorescence resonance energy transfer revealed that in U12-1 cells lacking OLIG2, the active form of RhoA was localized to protrusions of the cell membrane. In contrast, in OLIG2-expressing cells, it lined almost the entire plasma membrane. Thus, OLIG2 suppresses the motile phenotype of glioblastoma cells by activating RhoA.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kouichi", "last_name": "Tabu", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Tadaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Makino", "name": null }, { "creator_type": "author", "first_name": "Taichi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Ohnishi", "name": null }, { "creator_type": "author", "first_name": "Mieko", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/1541-7786.mcr-07-0096" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17951409" } }, "mesh": [ { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Central Nervous System Neoplasms", "descriptor_ui": "D016543", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p27", "descriptor_ui": "D050760", "major_topic": false }, { "descriptor": "Glioma", "descriptor_ui": "D005910", "major_topic": false }, { "descriptor": "GTPase-Activating Proteins", "descriptor_ui": "D020690", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Oligodendrocyte Transcription Factor 2", "descriptor_ui": "D000076104", "major_topic": false }, { "descriptor": "rhoA GTP-Binding Protein", "descriptor_ui": "D020742", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "1099-1109", "proceedings_title": null, "publisher": "", "title": "Molecular cancer research : MCR", "volume": "5", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Oligodendrocyte lineage transcription factor 2 inhibits the motility of a human glial tumor cell line by activating RhoA.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although protein-tyrosine phosphorylation is important for hippocampus-dependent learning, its role in cerebellum-dependent learning remains unclear. We previously found that PTPMEG, a cytoplasmic protein-tyrosine phosphatase expressed in Purkinje cells (PCs), bound to the carboxyl-terminus of the glutamate receptor delta2 via the postsynaptic density-95/discs-large/ZO-1 domain of PTPMEG. In the present study, we generated PTPMEG-knockout (KO) mice, and addressed whether PTPMEG is involved in cerebellar plasticity and cerebellum-dependent learning. The structure of the cerebellum in PTPMEG-KO mice appeared grossly normal. However, we found that PTPMEG-KO mice showed severe impairment in the accelerated rotarod test. These mice also exhibited impairment in rapid acquisition of the cerebellum-dependent delay eyeblink conditioning, in which conditioned stimulus (450-ms tone) and unconditioned stimulus (100-ms periorbital electrical shock) were co-terminated. Moreover, long-term depression at parallel fiber-PC synapses was significantly attenuated in these mice. Developmental elimination of surplus climbing fibers and the physiological properties of excitatory synaptic inputs to PCs appeared normal in PTPMEG-KO mice. These results suggest that tyrosine dephosphorylation events regulated by PTPMEG are important for both motor learning and cerebellar synaptic plasticity.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shin-ichiro", "last_name": "Kina", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Tezuka", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kusakawa", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Kakizawa", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Ohsugi", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kiyama", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Horai", "name": null }, { "creator_type": "author", "first_name": "Katsuko", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Kakuta", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Iwakura", "name": null }, { "creator_type": "author", "first_name": "Masamitsu", "last_name": "Iino", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Manabe", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1460-9568.2007.05829.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17953619" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Blinking", "descriptor_ui": "D001767", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Conditioning, Psychological", "descriptor_ui": "D003213", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Electric Stimulation", "descriptor_ui": "D004558", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Long-Term Synaptic Depression", "descriptor_ui": "D036881", "major_topic": false }, { "descriptor": "Memory Disorders", "descriptor_ui": "D008569", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Protein Tyrosine Phosphatases", "descriptor_ui": "D017027", "major_topic": false }, { "descriptor": "Psychomotor Performance", "descriptor_ui": "D011597", "major_topic": false }, { "descriptor": "Rotarod Performance Test", "descriptor_ui": "D045442", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Oct", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "2269-2278", "proceedings_title": null, "publisher": "", "title": "The European journal of neuroscience", "volume": "26", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Involvement of protein-tyrosine phosphatase PTPMEG in motor learning and cerebellar long-term depression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The ascidian chordate Ciona intestinalis is an established model organism frequently exploited to examine cellular development and a rapidly emerging model organism with a strong potential for developmental systems biology studies. However, there is no standardized developmental table for this organism. In this study, we made the standard web-based image resource called FABA: Four-dimensional Ascidian Body Atlas including ascidian's three-dimensional (3D) and cross-sectional images through the developmental time course. These images were reconstructed from more than 3,000 high-resolution real images collected by confocal laser scanning microscopy (CLSM) at newly defined 26 distinct developmental stages (stages 1-26) from fertilized egg to hatching larva, which were grouped into six periods named the zygote, cleavage, gastrula, neurula, tailbud, and larva periods. Our data set will be helpful in standardizing developmental stages for morphology comparison as well as for providing the guideline for several functional studies of a body plan in chordate.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Mitsuhara", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Gojobori", "name": null }, { "creator_type": "author", "first_name": "Kazuho", "last_name": "Ikeo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/dvdy.21188" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17557317" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": false }, { "descriptor": "Internet", "descriptor_ui": "D020407", "major_topic": true }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Ovum", "descriptor_ui": "D010063", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "1790-1805", "proceedings_title": null, "publisher": "", "title": "Developmental dynamics : an official publication of the American Association of Anatomists", "volume": "236", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "A web-based interactive developmental table for the ascidian Ciona intestinalis, including 3D real-image embryo reconstructions: I. From fertilized egg to hatching larva.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The behavior of isolation-reared mice has not yet been studied in the staircase test. The present study examined the effects of anxiolytic or anxiogenic agents and isolation rearing on the behavior of ddY (outbred) strain mice in the staircase test. Diazepam and phenobarbital increased the number of steps climbed, but did not affect rearing behavior in group-reared mice. FG-7142, a benzodiazepine inverse agonist, significantly increased the number of rearing with no changes in the number of steps climbed in group-reared mice. Methamphetamine increased the number of steps climbed and decreased the number of rearing in group-reared mice. Although isolation-reared mice showed hyperactivity, there was no difference in locomotor activity for the test period of 3 min between isolation- and group-reared mice. Under these conditions, isolation rearing increased the numbers of steps climbed and rearing compared to group-reared controls. Microanalysis of locomotor patterns of group-reared mice in the staircase test showed that anxiolytic drugs increased the number of climbing to the top step of the staircase and methamphetamine increased the number of climbing to the first to third step. These results suggest that isolation rearing causes an anxiety-like state with increased exploratory behavior in mice.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/jphs.fp0070325" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17538228" } }, "mesh": [ { "descriptor": "Analysis of Variance", "descriptor_ui": "D000704", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anti-Anxiety Agents", "descriptor_ui": "D014151", "major_topic": false }, { "descriptor": "Anxiety", "descriptor_ui": "D001007", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Carbolines", "descriptor_ui": "D002243", "major_topic": false }, { "descriptor": "Central Nervous System Stimulants", "descriptor_ui": "D000697", "major_topic": false }, { "descriptor": "Diazepam", "descriptor_ui": "D003975", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Exploratory Behavior", "descriptor_ui": "D005106", "major_topic": false }, { "descriptor": "GABA Antagonists", "descriptor_ui": "D018756", "major_topic": false }, { "descriptor": "GABA Modulators", "descriptor_ui": "D018757", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Methamphetamine", "descriptor_ui": "D008694", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Phenobarbital", "descriptor_ui": "D010634", "major_topic": false }, { "descriptor": "Social Isolation", "descriptor_ui": "D012934", "major_topic": true } ], "publication": { "conference_name": null, "date": "2007 Jun", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "153-158", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "104", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Anxiety-like and exploratory behaviors of isolation-reared mice in the staircase test.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Trimethyltin (TMT) is a toxic organotin compound that produces injury to the central nervous systems of mammals. Recently, high-dose TMT (2.8 mg/kg) has been shown to produce neurodegeneration and subsequent neurogenesis specifically in the hippocampal dentate gyrus of mice, indicating that mice injected with TMT serve as a useful in vivo model to study neurogenesis as well as neurodegeneration in this brain region. In addition, gene-engineered mice have allowed research to focuse on the mechanisms of TMT toxicity. These studies have revealed the involvement of stannin, nuclear factor kappa B (NF-kappaB), presenilin-1, apolipoprotein E, and pituitary adenylyl cyclase-activating polypeptide (PACAP) in TMT toxicity and suggested the relationship between genetic mutations and neuronal susceptibility to degeneration. In this review, we briefly summarize the previous studies and discuss the current status of research on TMT.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Kiyokazu", "last_name": "Ogita", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1248/yakushi.127.451" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17329931" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apolipoproteins E", "descriptor_ui": "D001057", "major_topic": false }, { "descriptor": "Central Nervous System", "descriptor_ui": "D002490", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Nerve Degeneration", "descriptor_ui": "D009410", "major_topic": true }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Presenilin-1", "descriptor_ui": "D053764", "major_topic": false }, { "descriptor": "Species Specificity", "descriptor_ui": "D013045", "major_topic": false }, { "descriptor": "Trimethyltin Compounds", "descriptor_ui": "D014298", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "451-461", "proceedings_title": null, "publisher": "", "title": "Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan", "volume": "127", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Recent studies on the trimethyltin actions in central nervous systems.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The natural spawning behavior of the kissing loach, an endangered species of Botiidae, was investigated in the wild in early June for two years in relation to several environmental factors. Kissing loaches spawned in temporary waters after elevation in water level. All spawnings observed (n=163) occurred within 3-5.5 hours from late afternoon to night after formation of the temporary water. These spawnings were performed by one female and one (71%) or two (29%) males in densely vegetated lentic waters. The female and following male(s) swam into dense grasses, where they vibrated to spawn intermittently. After the vibration continuing for 3-20 seconds, they moved to other parts of the dense grassy area and began vibration again. This sequence of spawning behavior was usually repeated several times, and the eggs were thus scattered widely. The spawning behavior and the rapid larval development of this species appear to be adaptations for the use of temporary waters as a spawning ground. The rise in water level and the consequent formation of temporary waters appear to be crucial triggers for reproduction of the kissing loach.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Kon", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.2108/zsj.24.850" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18217493" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": true }, { "descriptor": "Conservation of Natural Resources", "descriptor_ui": "D003247", "major_topic": false }, { "descriptor": "Cypriniformes", "descriptor_ui": "D003531", "major_topic": false }, { "descriptor": "Environment", "descriptor_ui": "D004777", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fresh Water", "descriptor_ui": "D005618", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Reproduction", "descriptor_ui": "D012098", "major_topic": false }, { "descriptor": "Seasons", "descriptor_ui": "D012621", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "850-853", "proceedings_title": null, "publisher": "", "title": "Zoological science", "volume": "24", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Spawning behavior of the kissing loach (Leptobotia curta) in temporary waters.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Methods of covalent labeling of a specific tag protein with small-molecular dyes play an important role in studying dynamic behaviors of proteins in living cells. On the basis of quinone methide chemistry, we designed and synthesized a beta-galactosidase labeling probe, CMFbeta-gal, which shows a fluorescence wavelength change accompanying the labeling reaction, owing to fluorescence resonance energy transfer (FRET). Since the FRET efficiency changes accompanying the labeling reaction, fluorescence of labeled protein can be observed separately from that of the unreacted probe, so immediate detection of the target protein is possible. This is the first report of a protein labeling probe which features a change of fluorescence wavelength upon reaction, allowing the labeled protein to be detected even in the presence of unreacted probe.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Toru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Takakusa", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja0657307" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17165702" } }, "mesh": [ { "descriptor": "beta-Galactosidase", "descriptor_ui": "D001616", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Dec 20", "date_precision": "day", "issue": "50", "normalized_date": "2006-12-20", "pages": "15946-15947", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "128", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Design and synthesis of an enzyme activity-based labeling molecule with fluorescence spectral change.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vav proteins are multidomain signaling molecules critical for mediating signals downstream of several surface receptors, including the antigen receptors of T and B lymphocytes. The catalytic guanine nucleotide exchange factor (GEF) activity of the Vav Dbl homology (DH) domain is thought to be controlled by an intramolecular autoinhibitory mechanism involving an N-terminal extension and phosphorylation of tyrosine residues in the acidic region (AC). Here, we report that the sequences surrounding the Vav1 AC: Tyr142, Tyr160, and Tyr174 are evolutionarily conserved, conform to consensus SH2 domain binding motifs, and bind several proteins implicated in TCR signaling, including Lck, PI3K p85α, and PLCγ1, through direct interactions with their SH2 domains. In addition, the AC tyrosines regulate tyrosine phosphorylation of Vav1. We also show that Tyr174 is required for the maintenance of TCR-signaling microclusters and for normal T cell development and activation. In this regard, our data demonstrate that while Vav1 Tyr174 is essential for maintaining the inhibitory constraint of the DH domain in both developing and mature T cells, constitutively activated Vav GEF disrupts TCR-signaling microclusters and leads to defective T cell development and proliferation.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Ana V.", "last_name": "Miletic", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Sakata-Sogawa", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Michael J.", "last_name": "Hamann", "name": null }, { "creator_type": "author", "first_name": "Timothy S.", "last_name": "Gomez", "name": null }, { "creator_type": "author", "first_name": "Naruhisa", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Tracie", "last_name": "Kloeppel", "name": null }, { "creator_type": "author", "first_name": "Osami", "last_name": "Kanagawa", "name": null }, { "creator_type": "author", "first_name": "Makio", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Daniel D.", "last_name": "Billadeau", "name": null }, { "creator_type": "author", "first_name": "Wojciech", "last_name": "Swat", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m608913200" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17050525" } }, "mesh": [ { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Guanine Nucleotide Exchange Factors", "descriptor_ui": "D020662", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": true }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-vav", "descriptor_ui": "D051567", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false }, { "descriptor": "src Homology Domains", "descriptor_ui": "D018909", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false }, { "descriptor": "Tyrosine", "descriptor_ui": "D014443", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Dec 15", "date_precision": "day", "issue": "50", "normalized_date": "2006-12-15", "pages": "38257-38265", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "281", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Vav1 Acidic Region Tyrosine 174 Is Required for the Formation of T Cell Receptor-induced Microclusters and Is Essential in T Cell Development and Activation*S.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Administration of cocaine causes a locomotor stimulant effect and increases extracellular levels of serotonin (5-HT) and dopamine (DA) in the brains of rodents. Previous studies show that 5-HT1A receptor agonist and antagonist modify the cocaine-induced behavioral and neurochemical effects in the rats. However, the role of the 5-HT system on the effects of cocaine has not been studied in the prefrontal cortex. The present study examined in ddY-strain male mice the effects of the 5-HT1A receptor agonist osemozotan and the receptor antagonist WAY100635 on cocaine-induced locomotor stimulant effect and increases in extracellular levels of 5-HT and DA in the prefrontal cortex. The cocaine-induced locomotor stimulant effect was attenuated by osemozotan and enhanced by WAY100635. The cocaine-induced increase in extracellular levels of 5-HT was attenuated by osemozotan, and enhanced by WAY100635. The cocaine-induced increase in extracellular levels of DA was enhanced by osemozotan, but not affected by WAY100635. These results suggest that the prefrontal 5-HT system plays a pivotal role in the locomotor stimulant effect of cocaine in mice.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shigeo", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Soichi", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Michiya", "last_name": "Kakuda", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/syn.20323" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16952156" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cocaine", "descriptor_ui": "D003042", "major_topic": false }, { "descriptor": "Cocaine-Related Disorders", "descriptor_ui": "D019970", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Dopamine Uptake Inhibitors", "descriptor_ui": "D018765", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Drug Interactions", "descriptor_ui": "D004347", "major_topic": false }, { "descriptor": "Extracellular Fluid", "descriptor_ui": "D045604", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Receptor, Serotonin, 5-HT1A", "descriptor_ui": "D044282", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false }, { "descriptor": "Serotonin Agents", "descriptor_ui": "D018490", "major_topic": false }, { "descriptor": "Serotonin Antagonists", "descriptor_ui": "D012702", "major_topic": false }, { "descriptor": "Serotonin Receptor Agonists", "descriptor_ui": "D017366", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Dec 1", "date_precision": "day", "issue": "7", "normalized_date": "2006-12-01", "pages": "479-484", "proceedings_title": null, "publisher": "", "title": "Synapse (New York, N.Y.)", "volume": "60", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Modification of cocaine-induced behavioral and neurochemical effects by serotonin1A receptor agonist/antagonist in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The activation of tumor suppressor p53 induces apoptosis or cell cycle arrest depending on the state and type of cell, but it is not fully understood how these different responses are regulated. Here, we show that Puma and Noxa, the well-known p53-inducible proapoptotic members of the Bcl-2 family, differentially participate in dual pathways of the induction of apoptosis. In normal cells, Puma but not Noxa induces mitochondrial outer membrane permeabilization (MOMP), and this function is mediated in part by a pathway that involves calcium release from the endoplasmic reticulum (ER) and the subsequent caspase activation. However, upon E1A oncoprotein expression, cells also become susceptible to MOMP induction by Noxa, owing to their sensitization to the ER-independent pathway. These findings offer a new insight into differential cellular responses induced by p53, and may have therapeutic implications in cancer.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Shibue", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Takaoka", "name": null }, { "creator_type": "author", "first_name": "Tadatsugu", "last_name": "Taniguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/sj.emboj.7601359" }, "pmcid": { "normalized": "PMC1618103" }, "pmid": { "normalized": "17024184" } }, "mesh": [ { "descriptor": "Adenovirus E1A Proteins", "descriptor_ui": "D017500", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": true }, { "descriptor": "Apoptosis Regulatory Proteins", "descriptor_ui": "D051017", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Caspases", "descriptor_ui": "D020169", "major_topic": false }, { "descriptor": "Cell Membrane Permeability", "descriptor_ui": "D002463", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitochondrial Membranes", "descriptor_ui": "D051336", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-bcl-2", "descriptor_ui": "D019253", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false }, { "descriptor": "Tumor Suppressor Proteins", "descriptor_ui": "D025521", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Oct 18", "date_precision": "day", "issue": "20", "normalized_date": "2006-10-18", "pages": "4952-4962", "proceedings_title": null, "publisher": "", "title": "The EMBO journal", "volume": "25", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Differential contribution of Puma and Noxa in dual regulation of p53-mediated apoptotic pathways.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have previously shown that anterior intestinal epithelium of the euryhaline mudskipper (Periophthalmus modestus) undergoes apoptosis during seawater (SW) acclimation, whereas elevated cell proliferation was observed in freshwater (FW)-acclimated fish. To understand the possible endocrine regulation of the gastrointestinal cell turnover during salinity acclimation, we examined the ratios of apoptotic and proliferating cells in the anterior intestine of one-third SW-acclimated mudskipper treated with triiodothyronine (T3), cortisol, 11-deoxycorticosterone (DOC, the putative teleostean mineralocorticoid), or prolactin (PRL). In situ nick end labeling of genomic DNA (TUNEL) and immunohistochemistry of proliferating cells nuclear antigen (PCNA) were used as indicators of apoptosis and cell proliferations, respectively. Cortisol significantly elevated apoptosis (P<0.05) in the epithelia and connective tissues and also stimulated the epithelial cell proliferation (P<0.05). PRL induced epithelial cell proliferation (P<0.05), but did not affect apoptotic status of the intestinal epithelium. Neither T3 nor DOC had any impact on cell proliferation or apoptosis. Together, our results suggest a role for cortisol and PRL in the regulation of anterior intestinal epithelial turnover during salinity acclimation in this species.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hideya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.lfs.2006.06.021" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16857212" } }, "mesh": [ { "descriptor": "Acclimatization", "descriptor_ui": "D000064", "major_topic": false }, { "descriptor": "Adrenal Cortex Hormones", "descriptor_ui": "D000305", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Count", "descriptor_ui": "D002452", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fresh Water", "descriptor_ui": "D005618", "major_topic": false }, { "descriptor": "In Situ Nick-End Labeling", "descriptor_ui": "D020287", "major_topic": false }, { "descriptor": "Intestines", "descriptor_ui": "D007422", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Perciformes", "descriptor_ui": "D010473", "major_topic": false }, { "descriptor": "Prolactin", "descriptor_ui": "D011388", "major_topic": false }, { "descriptor": "Seawater", "descriptor_ui": "D012623", "major_topic": false }, { "descriptor": "Thyroid Hormones", "descriptor_ui": "D013963", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Oct 4", "date_precision": "day", "issue": "19", "normalized_date": "2006-10-04", "pages": "1873-1880", "proceedings_title": null, "publisher": "", "title": "Life sciences", "volume": "79", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "In vivo effects of thyroid hormone, corticosteroids and prolactin on cell proliferation and apoptosis in the anterior intestine of the euryhaline mudskipper (Periophthalmus modestus).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have identified a ligand (CO) accommodation cavity in the signal transducer sensor protein HemAT (heme-based aerotactic transducer) that allows us to gain single-molecule insights into the mechanism of gas sensor proteins. Specific mutations that are distal and proximal to the heme were designed to perturb the electrostatic field near the ligand that is bound to the heme and near the accommodated ligand in the cavity. We report the detection of a second site in heme proteins in which the exogenous ligand is accommodated in an internal cavity. The conformational gate that directs the ligand-migration pathway from the distal to the proximal site of the heme, where the ligand is trapped, has been identified. The data provide evidence that the heme pocket is the specific ligand trap and suggest that the regulatory mechanism may be tackled starting from more than one position in the protein. Based on the results, we propose a dynamic coupling between the two distinct binding sites as the underlying allosteric mechanism for gas recognition/discrimination that triggers a conformational switch for signaling by the oxygen sensor protein HemAT.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Eftychia", "last_name": "Pinakoulaki", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Vangelis", "last_name": "Daskalakis", "name": null }, { "creator_type": "author", "first_name": "Shiro", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Shigetoshi", "last_name": "Aono", "name": null }, { "creator_type": "author", "first_name": "Constantinos", "last_name": "Varotsis", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.0604248103" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17003124" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Carbon Monoxide", "descriptor_ui": "D002248", "major_topic": false }, { "descriptor": "Crystallography, X-Ray", "descriptor_ui": "D018360", "major_topic": false }, { "descriptor": "Hemeproteins", "descriptor_ui": "D006420", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Photolysis", "descriptor_ui": "D010782", "major_topic": false }, { "descriptor": "Protein Structure, Secondary", "descriptor_ui": "D017433", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Spectroscopy, Fourier Transform Infrared", "descriptor_ui": "D017550", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Oct 3", "date_precision": "day", "issue": "40", "normalized_date": "2006-10-03", "pages": "14796-14801", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "103", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Two ligand-binding sites in the O2-sensing signal transducer HemAT: Implications for ligand recognition/discrimination and signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "As a neurotransmitter and neuromodulator, serotonin (5-HT) influences neuronal outgrowth in the nervous systems of several species. In PC12 cells, 5-HT is known to have neuritogenic effects, although the signal transduction pathway responsible for these effects is not understood. In this study, we hypothesized that a 5-HT-induced increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) could be involved in mediating the effects of 5-HT. Application of 5-HT to PC12 cells enhanced nerve growth factor (NGF)-induced neurite outgrowth in a dose-dependent manner, and the sensitivity of this neuritogenic effect was increased in differentiated PC12 cells. In accordance, an increase in [Ca(2+)](i) was observed following application of 5-HT in differentiated PC12 cells. This increase was amplified by further NGF treatment. 5-HT-induced increases in [Ca(2+)](i) were inhibited by MDL 72222, a selective 5-HT(3) receptor antagonist, and nifedipine, an L-type calcium channel blocker, but not by ketanserin, a 5-HT(2) receptor antagonist, or thapsigargin, a specific inhibitor of endoplasmic reticulum Ca(2+)-ATPase. These pharmacological tests indicated that 5-HT-induced increases in [Ca(2+)](i) are mediated by activation of voltage-gated calcium channels via 5-HT(3) receptors and that 5-HT-induced increases in [Ca(2+)](i) are likely to be independent of activation of 5-HT(2) receptors in PC12 cells. Furthermore, the neuritogenic effect of 5-HT was suppressed by MDL 72222, nifedipine, calmodulin (CaM) inhibitor, and calcineurin inhibitors. Taken together, our results indicate that 5-HT-induced increases in [Ca(2+)](i), which are mediated via 5-HT(3) receptors and L-type calcium channels in PC12 cells, and subsequent activation of CaM and calcineurin enhance NGF-induced neurite outgrowth.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kohei", "last_name": "Homma", "name": null }, { "creator_type": "author", "first_name": "Yoshiichiro", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/jnr.20894" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16688720" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcineurin", "descriptor_ui": "D019703", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Channel Blockers", "descriptor_ui": "D002121", "major_topic": false }, { "descriptor": "Calcium Channels", "descriptor_ui": "D015220", "major_topic": false }, { "descriptor": "Calmodulin", "descriptor_ui": "D002147", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Intracellular Fluid", "descriptor_ui": "D007424", "major_topic": false }, { "descriptor": "Nerve Growth Factor", "descriptor_ui": "D020932", "major_topic": false }, { "descriptor": "Neurites", "descriptor_ui": "D016501", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Receptors, Serotonin, 5-HT3", "descriptor_ui": "D044406", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false }, { "descriptor": "Serotonin Antagonists", "descriptor_ui": "D012702", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Aug 1", "date_precision": "day", "issue": "2", "normalized_date": "2006-08-01", "pages": "316-325", "proceedings_title": null, "publisher": "", "title": "Journal of neuroscience research", "volume": "84", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Serotonin induces the increase in intracellular Ca2+ that enhances neurite outgrowth in PC12 cells via activation of 5-HT3 receptors and voltage-gated calcium channels.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The ruthenium-catalyzed isomerization of diynes and triynes involving propargyl carboxylate moieties affords dienynes and dienediynes, respectively. The [1,n]-metallotropic shift (n = 3, 5) (carbene walk) of in situ generated alkynyl carbene complexes has been proposed for the catalytic isomerization reaction.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Michinobu", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yugo", "last_name": "Tai", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja0612955" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16848428" } }, "mesh": [], "publication": { "conference_name": null, "date": "2006 Jul 26", "date_precision": "day", "issue": "29", "normalized_date": "2006-07-26", "pages": "9270-9271", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "128", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Ruthenium-catalyzed [1,n]-metallotropic shift (n = 3, 5) of alkynyl carbene complex intermediates.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "HemAT from Bacillus subtilis (HemAT-Bs) is a heme-based O2 sensor protein that acts as a signal transducer responsible for aerotaxis. HemAT-Bs discriminates its physiological effector, O2, from other gas molecules to generate the aerotactic signal, but the detailed mechanism of the selective O2 sensing is not obvious. In this study, we measured electronic absorption, electron paramagnetic resonance (EPR), and resonance Raman spectra of HemAT-Bs to elucidate the mechanism of selective O2 sensing by HemAT-Bs. Resonance Raman spectroscopy revealed the presence of a hydrogen bond between His86 and the heme propionate only in the O2-bound form, in addition to that between Thr95 and the heme-bound O2. The disruption of this hydrogen bond by the mutation of His86 caused the disappearance of a conformer with a direct hydrogen bond between Thr95 and the heme-bound O2 that is present in WT HemAT-Bs. On the basis of these results, we propose a model for selective O2 sensing by HemAT-Bs as follows. The formation of the hydrogen bond between His86 and the heme propionate induces a conformational change of the CE-loop and the E-helix by which Thr95 is located at the proper position to form the hydrogen bond with the heme-bound O2. This stepwise conformational change would be essential to selective O2 sensing and signal transduction by HemAT-Bs.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Shiro", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Katsuaki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Teizo", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Shigetoshi", "last_name": "Aono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/bi060315c" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16819829" } }, "mesh": [ { "descriptor": "Bacillus subtilis", "descriptor_ui": "D001412", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Electron Spin Resonance Spectroscopy", "descriptor_ui": "D004578", "major_topic": false }, { "descriptor": "Heme-Binding Proteins", "descriptor_ui": "D000081062", "major_topic": false }, { "descriptor": "Hemeproteins", "descriptor_ui": "D006420", "major_topic": false }, { "descriptor": "Histidine", "descriptor_ui": "D006639", "major_topic": false }, { "descriptor": "Hydrogen Bonding", "descriptor_ui": "D006860", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "Threonine", "descriptor_ui": "D013912", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Jul 11", "date_precision": "day", "issue": "27", "normalized_date": "2006-07-11", "pages": "8301-8307", "proceedings_title": null, "publisher": "", "title": "Biochemistry", "volume": "45", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Specific hydrogen-bonding networks responsible for selective O2 sensing of the oxygen sensor protein HemAT from Bacillus subtilis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Prolactin is an important regulator of multiple biological functions in vertebrates, and has been viewed as essential to ion uptake as well as reduction in ion and water permeability of osmoregulatory surfaces in freshwater and euryhaline fish. Prolactin-releasing peptide seems to stimulate prolactin expression in the pituitary and peripheral organs during freshwater adaptation. Growth hormone, a member of the same family of hormones as prolactin, promotes acclimation to seawater in several teleost fish, at least in part through the action of insulin-like growth factor I. In branchial epithelia, development and differentiation of the seawater-type chloride cell (and their underlying biochemistry) is regulated by GH, IGF-I, and cortisol, whereas the freshwater-type chloride cell is regulated by prolactin and cortisol. In the epithelia of gastrointestinal tract, prolactin induces cell proliferation during freshwater adaptation, whereas cortisol stimulates both cell proliferation and apoptosis. We propose that control of salinity acclimation in teleosts by prolactin and growth hormone primarily involves regulation of cell proliferation, apoptosis, and differentiation (the latter including upregulation of specific ion transporters), and that there is an important interaction of these hormones with corticosteroids.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Stephen D.", "last_name": "McCormick", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ygcen.2005.10.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16406056" } }, "mesh": [ { "descriptor": "Acclimatization", "descriptor_ui": "D000064", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Fishes", "descriptor_ui": "D005399", "major_topic": false }, { "descriptor": "Fresh Water", "descriptor_ui": "D005618", "major_topic": false }, { "descriptor": "Gastrointestinal Tract", "descriptor_ui": "D041981", "major_topic": false }, { "descriptor": "Growth Hormone", "descriptor_ui": "D013006", "major_topic": false }, { "descriptor": "Ion Transport", "descriptor_ui": "D017136", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Prolactin", "descriptor_ui": "D011388", "major_topic": false }, { "descriptor": "Seawater", "descriptor_ui": "D012623", "major_topic": false }, { "descriptor": "Sodium Chloride", "descriptor_ui": "D012965", "major_topic": false }, { "descriptor": "Water-Electrolyte Balance", "descriptor_ui": "D014882", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 May 15", "date_precision": "day", "issue": "1", "normalized_date": "2006-05-15", "pages": "24-30", "proceedings_title": null, "publisher": "", "title": "General and comparative endocrinology", "volume": "147", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Prolactin and growth hormone in fish osmoregulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Psychostimulants, including amphetamine, act as antihyperkinetic agents in humans with hyperkinetic disorder such as attention-deficit hyperactivity disorder and are known to be effective in enhancing attention-related processes; however, the underlying mechanisms have not been adequately addressed. Mice lacking the Adcyap1 gene encoding the neuropeptide pituitary adenylate cyclase-activating polypeptide (Adcyap1(-/-)) display psychomotor abnormalities, including increased novelty-seeking behavior and hyperactivity. In this study, Adcyap1(-/-) mice showed sensory-motor gating deficits, measured as deficits in prepulse inhibition (PPI), and showed normal PPI in response to amphetamine. Amphetamine also significantly decreased hyperlocomotion in Adcyap1(-/-) mice, and this paradoxical antihyperkinetic effect depended on serotonin 1A (5-HT(1A)) receptor signaling. c-Fos-positive neurons were increased in the prefrontal cortex in amphetamine-treated Adcyap1(-/-) mice, suggesting increased inhibitory control by prefrontal neurons. Additionally, amphetamine produced an antihyperkinetic effect in wild-type mice that received the 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin. These results indicate that Adcyap1(-/-) mice act as a model of hyperlocomotion and PPI deficits and suggest that 5-HT(1A)-mediated pathways are important determinants of the psychostimulant-elicited, rate-dependent effects that are in a negative function of the baseline rate of activity.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Kawagishi", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kunugi", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.4376-05.2006" }, "pmcid": { "normalized": "PMC6674244" }, "pmid": { "normalized": "16687500" } }, "mesh": [ { "descriptor": "Acoustic Stimulation", "descriptor_ui": "D000161", "major_topic": false }, { "descriptor": "Amphetamine", "descriptor_ui": "D000661", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Central Nervous System Stimulants", "descriptor_ui": "D000697", "major_topic": false }, { "descriptor": "Hyperkinesis", "descriptor_ui": "D006948", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Reaction Time", "descriptor_ui": "D011930", "major_topic": false }, { "descriptor": "Reflex, Startle", "descriptor_ui": "D013216", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 May 10", "date_precision": "day", "issue": "19", "normalized_date": "2006-05-10", "pages": "5091-5097", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "26", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Psychostimulant-induced attenuation of hyperactivity and prepulse inhibition deficits in Adcyap1-deficient mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) has been reported to decrease ischemic neuronal damage and increase IL-6 secretion in rats. However, the mechanisms underlying neuroprotection are still to be fully elucidated. The present study was designed to investigate the role played by PACAP and IL-6 in mediating neuroprotection after ischemia in a null mouse. Infarct volume, neurological deficits, and cytochrome c in cytoplasm were higher in PACAP+/− and PACAP−/− mice than in PACAP+/+ animals after focal ischemia, although the severity of response was ameliorated by the injection of PACAP38. A decrease in mitochondrial bcl-2 was also accentuated in PACAP+/− and PACAP−/− mice, but the decrease could be prevented by PACAP38 injection. PACAP receptor 1 (PAC1R) immunoreactivity was colocalized with IL-6 immunoreactivity in neurons, although the intensity of IL-6 immunoreactivity in PACAP+/− mice was less than that in PACAP+/+ animals. IL-6 levels increased in response to PACAP38 injection, an effect that was canceled by cotreatment with the PAC1R antagonist. However, unlike in wild-type controls, PACAP38 treatment did not reduce the infarction in IL-6 null mice. To clarify the signaling pathway associated with the activity of PACAP and IL-6, phosphorylated STAT (signal transducer and activator of transcription) 3, ERK (extracellular signal-regulated kinase), and AKT levels were examined in PACAP+/− and IL-6 null mice after ischemia. Lower levels of pSTAT3 and pERK were observed in the PACAP+/− mice, whereas a reduction in pSTAT3 was recorded in the IL-6 null mice. These results suggest that PACAP prevents neuronal cell death after ischemia via a signaling mechanism involving IL-6.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Ohtaki", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Nakamachi", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Dohi", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Aizawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Takaki", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Hodoyama", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Yofu", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Manfred", "last_name": "Kopf", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Iwakura", "name": null }, { "creator_type": "author", "first_name": "Kouhei", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Arimura", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Shioda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.0600375103" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16651528" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": true }, { "descriptor": "Cytochromes c", "descriptor_ui": "D045304", "major_topic": false }, { "descriptor": "Infarction, Middle Cerebral Artery", "descriptor_ui": "D020244", "major_topic": false }, { "descriptor": "Interleukin-6", "descriptor_ui": "D015850", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-bcl-2", "descriptor_ui": "D019253", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 May 9", "date_precision": "day", "issue": "19", "normalized_date": "2006-05-09", "pages": "7488-7493", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "103", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Pituitary adenylate cyclase-activating polypeptide (PACAP) decreases ischemic neuronal cell death in association with IL-6.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "[reaction: see text] The reaction of heteroaromatic compounds with propargylic carboxylates in the presence of a catalytic amount of [RuCl(2)(CO)(3)](2) or PtCl(2) gives trienes in good yields. The key intermediate is an electrophilic (1-acetoxylvinyl)carbene complex generated from the activated propargylic acetates with transition metals.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Michinobu", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Sakae", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ol0604769" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16597155" } }, "mesh": [], "publication": { "conference_name": null, "date": "2006 Apr 13", "date_precision": "day", "issue": "8", "normalized_date": "2006-04-13", "pages": "1741-1743", "proceedings_title": null, "publisher": "", "title": "Organic letters", "volume": "8", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Ru-catalyzed ring-opening and substitution reactions of heteroaromatic compounds using propargylic carboxylates as precursors of vinylcarbenoids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cortisol plays an important role in controlling intestinal water and ion transport in teleosts possibly through glucocorticoid receptor (GR) and/or mineralocorticoid receptor. To better understand the role of GR in the teleost intestine, in a euryhaline tilapia, Oreochromis mossambicus, we examined (1) the intestinal localizations of GR; (2) the effects of environmental salinity challenge and cortisol treatment on GR mRNA expression. The mRNA abundance of GR in the posterior intestinal region of tilapia was found to be higher than that in the anterior and middle intestine. In the posterior intestine, GR appears to be localized in the mucosal layer. GR mRNA levels in the posterior intestine were elevated after exposure of freshwater fish to seawater for 7 days following an increase in plasma cortisol. Similarly, cortisol implantation in freshwater tilapia for 7 days elevated the intestinal GR mRNA. These results indicate that seawater acclimation is accompanied by upregulation of GR mRNA abundance in intestinal tissue, possibly as a consequence of the elevation of cortisol levels. In contrast, a single intraperitoneal injection of cortisol into freshwater tilapia decreased intestinal GR mRNA. This downregulation of the GR mRNA by cortisol suggests a dual mode of autoregulation of GR expression by cortisol.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hideya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Hyodo", "name": null }, { "creator_type": "author", "first_name": "Brian S.", "last_name": "Shepherd", "name": null }, { "creator_type": "author", "first_name": "Toyoji", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "E. Gordon", "last_name": "Grau", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.lfs.2005.09.050" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16376384" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blotting, Northern", "descriptor_ui": "D015152", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hydrocortisone", "descriptor_ui": "D006854", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Injections, Intraperitoneal", "descriptor_ui": "D007274", "major_topic": false }, { "descriptor": "Intestinal Mucosa", "descriptor_ui": "D007413", "major_topic": false }, { "descriptor": "Intestines", "descriptor_ui": "D007422", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Receptors, Glucocorticoid", "descriptor_ui": "D011965", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Tilapia", "descriptor_ui": "D017210", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Apr 11", "date_precision": "day", "issue": "20", "normalized_date": "2006-04-11", "pages": "2329-2335", "proceedings_title": null, "publisher": "", "title": "Life sciences", "volume": "78", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Expression of glucocorticoid receptor in the intestine of a euryhaline teleost, the Mozambique tilapia (Oreochromis mossambicus): effect of seawater exposure and cortisol treatment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An event-related potential called mismatch negativity is known to exhibit physiological evidence of sensory memory. Mismatch negativity is believed to represent complicated neuronal mechanisms in a variety of animals and in humans. We employed the auditory oddball paradigm varying sound durations and observed two types of duration mismatch negativity in anesthetized guinea pigs. One was a duration mismatch negativity whose increase in peak amplitude occurred immediately after onset of the stimulus difference in a decrement oddball paradigm. The other exhibited a peak amplitude increase closer to the offset of the longer stimulus in an increment oddball paradigm. These results demonstrated a mechanism to percept the difference of duration change and revealed the importance of the end of a stimulus for this perception.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shuntaro", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Shin'ichiro", "last_name": "Kanoh", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Takaura", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/01.wnr.0000204979.91253.7a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16514365" } }, "mesh": [ { "descriptor": "Acoustic Stimulation", "descriptor_ui": "D000161", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Auditory Cortex", "descriptor_ui": "D001303", "major_topic": false }, { "descriptor": "Auditory Pathways", "descriptor_ui": "D001306", "major_topic": false }, { "descriptor": "Evoked Potentials", "descriptor_ui": "D005071", "major_topic": false }, { "descriptor": "Guinea Pigs", "descriptor_ui": "D006168", "major_topic": false }, { "descriptor": "Pitch Discrimination", "descriptor_ui": "D010897", "major_topic": false }, { "descriptor": "Reaction Time", "descriptor_ui": "D011930", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Mar 20", "date_precision": "day", "issue": "4", "normalized_date": "2006-03-20", "pages": "395-399", "proceedings_title": null, "publisher": "", "title": "Neuroreport", "volume": "17", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Change detection and difference detection of tone duration discrimination.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Here, we report in vitro generation of Math1+ cerebellar granule cell precursors and Purkinje cells from ES cells by using soluble patterning signals. When neural progenitors induced from ES cells in a serum-free suspension culture are subsequently treated with BMP4 and Wnt3a, a significant proportion of these neural cells become Math1+. The induced Math1+ cells are mitotically active and express markers characteristic of granule cell precursors (Pax6, Zic1, and Zipro1). After purification by FACS and coculture with postnatal cerebellar neurons, ES cell-derived Math1+ cells exhibit typical features of neurons of the external granule cell layer, including extensive motility and a T-shaped morphology. Interestingly, differentiation of L7+/Calbindin-D28K+ neurons (characteristic of Purkinje cells) is induced under similar culture conditions but exhibits a higher degree of enhancement by Fgf8 rather than by Wnt3a. This is the first report of in vitro recapitulation of early differentiation of cerebellar neurons by using the ES cell system.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hong-Lin", "last_name": "Su", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Matsuo-Takasaki", "name": null }, { "creator_type": "author", "first_name": "Mineko", "last_name": "Kengaku", "name": null }, { "creator_type": "author", "first_name": "Kiichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2005.11.010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16406324" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Morphogenetic Protein 4", "descriptor_ui": "D055415", "major_topic": false }, { "descriptor": "Bone Morphogenetic Proteins", "descriptor_ui": "D019485", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Separation", "descriptor_ui": "D002469", "major_topic": false }, { "descriptor": "Cell Transplantation", "descriptor_ui": "D017690", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Culture Media, Serum-Free", "descriptor_ui": "D016895", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Fibroblast Growth Factor 8", "descriptor_ui": "D051524", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Wnt Proteins", "descriptor_ui": "D051153", "major_topic": false }, { "descriptor": "Wnt3 Protein", "descriptor_ui": "D060508", "major_topic": false }, { "descriptor": "Wnt3A Protein", "descriptor_ui": "D060509", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Feb 15", "date_precision": "day", "issue": "2", "normalized_date": "2006-02-15", "pages": "287-296", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "290", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of cerebellar neuron precursors from embryonic stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An aqueous solution of photocrosslinkable chitosan containing azide groups and lactose moieties (Az-CH-LA) incorporating paclitaxel formed an insoluble hydrogel within 30 s of ultraviolet light (UV) irradiation. The chitosan hydrogel showed strong potential for use as a new tissue adhesive in surgical applications and wound dressing. The fibroblast growth factor (FGF)-2 molecules retained in the chitosan hydrogel and in an injectable chitosan/IO(4)-heparin hydrogel remain biologically active, and were gradually released from the hydrogels as they biodegraded in vivo. The controlled release of biologically active FGF-2 molecules from the hydrogels caused induction of angiogenesis and collateral circulation occurred in healing-impaired diabetic (db/db) mice and in the ischemic limbs of rats. Paclitaxel, which is an antitumor reagent, was also retained in the chitosan hydrogel and remained biologically active as it was released on degradation of the hydrogel in vivo. The chitosan hydrogels incorporating paclitaxel effectively inhibited tumor growth and angiogenesis in mice. The purpose of this review is to describe the effectiveness of chitosan hydrogel as a local drug delivery carrier for agents (e.g., FGF-2 and paclitaxel) to control angiogenesis. It is thus proposed that chitosan hydrogel may be a promising new local carrier for drugs such as FGF-2 and paclitaxel to control vascularization.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masayuki", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Kiyohaya", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Singo", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Masuoka", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kanatani", "name": null }, { "creator_type": "author", "first_name": "Bonpei", "last_name": "Takase", "name": null }, { "creator_type": "author", "first_name": "Hidemi", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Tadaaki", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kikuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10047-005-0313-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16614797" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biocompatible Materials", "descriptor_ui": "D001672", "major_topic": false }, { "descriptor": "Chitosan", "descriptor_ui": "D048271", "major_topic": false }, { "descriptor": "Cross-Linking Reagents", "descriptor_ui": "D003432", "major_topic": false }, { "descriptor": "Drug Delivery Systems", "descriptor_ui": "D016503", "major_topic": true }, { "descriptor": "Fibroblast Growth Factor 2", "descriptor_ui": "D016222", "major_topic": false }, { "descriptor": "Hydrogels", "descriptor_ui": "D020100", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred Strains", "descriptor_ui": "D008815", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Occlusive Dressings", "descriptor_ui": "D009779", "major_topic": false }, { "descriptor": "Paclitaxel", "descriptor_ui": "D017239", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Ultraviolet Rays", "descriptor_ui": "D014466", "major_topic": false }, { "descriptor": "Wound Healing", "descriptor_ui": "D014945", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006", "date_precision": "year", "issue": "1", "normalized_date": "2006", "pages": "8-16", "proceedings_title": null, "publisher": "", "title": "Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs", "volume": "9", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Chitosan hydrogel as a drug delivery carrier to control angiogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Accumulating evidence implicates pituitary adenylate cyclase-activating polypeptide (PACAP) in a number of stress responses. By using PACAP-deficient mice, PACAP has been shown to have an in vivo role in the regulation of the sympathoadrenal axis, but a role in regulating the hypothalamo-pituitary-adrenal (HPA) axis has not been fully addressed. To elucidate the role of endogenous PACAP in HPA axis regulation during pathological conditions, mice lacking the Adcyap1 gene encoding the neuropeptide PACAP (Adcyap1-/-) were injected with trimethyltin (TMT), a neurotoxin known to induce neuronal damage and several systemic responses including elevated plasma corticosterone levels. In wild-type controls, TMT induced transient decreases in water and food intake, with a concomitant decrease in body weight; however, no significant changes were observed in Adcyap1-/- mice. Basal corticosterone levels were not significantly different between the mutant and wild-type mice. TMT induced a marked elevation of plasma corticosterone above basal levels in wild-type mice but no significant increase was seen in Adcyap1-/- mice. The present article suggests that PACAP is involved in the corticosterone release in some pathological conditions but not in the basal state.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Yanagida", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Kiyokazu", "last_name": "Ogita", "name": null }, { "creator_type": "author", "first_name": "Norito", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1196/annals.1317.060" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16888208" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Weight", "descriptor_ui": "D001835", "major_topic": false }, { "descriptor": "Corticosterone", "descriptor_ui": "D003345", "major_topic": false }, { "descriptor": "Eating", "descriptor_ui": "D004435", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Trimethyltin Compounds", "descriptor_ui": "D014298", "major_topic": false }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Jul", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "450-456", "proceedings_title": null, "publisher": "", "title": "Annals of the New York Academy of Sciences", "volume": "1070", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Lack of trimethyltin (TMT)-induced elevation of plasma corticosterone in PACAP-deficient mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genetic manipulation of pituitary adenylate cyclase-activating polypeptide (PACAP) in mice has uncovered its involvement in psychomotor function. We previously observed that mice lacking the Adcyap1 gene encoding the neuropeptide PACAP (Adcyap1-/-) displayed intense jumping behavior when placed in a novel environment such as an open field. Here, we show that Adcyap1-/- mice manifest jumping behavior as early as at least 6 weeks of age when compared with wild-type mice and that the selective serotonin (5-HT) reuptake inhibitor, fluoxetine, as well as the serotonin precursor, 5-hydroxytryptophan, suppress jumping behavior. Our previous study showed a slight decrease in 5-HT metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in Adcyap1-/- mouse brain. Taken together, these results suggest that there is a developmental aspect to the jumping behavior seen in Adcyap1-/- mice, and that jumping behaviour may involve the serotonergic system.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Kawagishi", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Michiyoshi", "last_name": "Hatanaka", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1196/annals.1317.079" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16888223" } }, "mesh": [ { "descriptor": "5-Hydroxytryptophan", "descriptor_ui": "D006916", "major_topic": false }, { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Fluoxetine", "descriptor_ui": "D005473", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Physical Conditioning, Animal", "descriptor_ui": "D010805", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false }, { "descriptor": "Serotonin Antagonists", "descriptor_ui": "D012702", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Jul", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "545-549", "proceedings_title": null, "publisher": "", "title": "Annals of the New York Academy of Sciences", "volume": "1070", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Serotonergic inhibition of intense jumping behavior in mice lacking PACAP (Adcyap1-/-).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) is a structurally highly conserved neuropeptide and displays pleiotropic activity, including functioning as a neurotransmitter, neuromodulator, and neurotrophic factor. A series of recent experiments, including genetic manipulation of PACAP and its receptors, has led to better understanding of both normal and pathological processes in which PACAP has been proposed to play a role, and sheds light on previously uncharacterized functions of endogenous PACAP. The aim of this article is to briefly review the recent advances in understanding the role of PACAP in the central nervous system from PACAP- and PACAP receptor-deficient mice, particularly with respect to behavioral and neurological features, including psychomotor behavior, feeding, stress responses, memory performance, ethanol sensitivity, chronic pain, and circadian rhythms. This article also discusses their potential involvement in human diseases.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1196/annals.1317.038" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16888150" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Disease", "descriptor_ui": "D004194", "major_topic": false }, { "descriptor": "Fertility", "descriptor_ui": "D005298", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051236", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Jul", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "75-89", "proceedings_title": null, "publisher": "", "title": "Annals of the New York Academy of Sciences", "volume": "1070", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "New insights into the central PACAPergic system from the phenotypes in PACAP- and PACAP receptor-knockout mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND OBJECTIVES: We demonstrated that photoacoustic measurement enables viscoelastic characterization of biological tissue. The purpose of this study was to develop a practical photoacoustic measurement system for diagnosis of osteoarthritis (OA) by viscoelastic characterization of articular cartilage. STUDY DESIGN/MATERIALS AND METHODS: The portable system consists of a commercially available 3rd harmonic Q-switched Nd:YAG laser as a light source and a transducer, which is arranged coaxially with an optical fiber. Cell proliferation tests were performed to study the effect of laser irradiation on chondrocytes. Photoacoustic measurements were performed using enzymatically treated cartilage as a model of OA. RESULTS: There was no significant damage of chondrocytes caused by laser irradiation (100 microJ/mm2, 5 Hz, 30 shots). The change in relaxation times measured by the photoacoustic measurement had a positive correlation with time of enzymatic treatment, that is, the degree of cartilage degeneration. CONCLUSIONS: We have developed a noninvasive photoacoustic measurement system designed for arthroscopic use and have demonstrated the applicability of this system to the diagnosis of OA-like cartilage degeneration.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Nagatoshi", "last_name": "Kaneshiro", "name": null }, { "creator_type": "author", "first_name": "Genya", "last_name": "Mitani", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Joji", "last_name": "Mochida", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kikuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/lsm.20285" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16485275" } }, "mesh": [ { "descriptor": "Acoustics", "descriptor_ui": "D000162", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arthroscopy", "descriptor_ui": "D001182", "major_topic": false }, { "descriptor": "Cartilage, Articular", "descriptor_ui": "D002358", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Chondrocytes", "descriptor_ui": "D019902", "major_topic": false }, { "descriptor": "Elasticity", "descriptor_ui": "D004548", "major_topic": false }, { "descriptor": "Fiber Optic Technology", "descriptor_ui": "D005336", "major_topic": false }, { "descriptor": "Knee Joint", "descriptor_ui": "D007719", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": true }, { "descriptor": "Models, Animal", "descriptor_ui": "D023421", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Optical Fibers", "descriptor_ui": "D055100", "major_topic": false }, { "descriptor": "Osteoarthritis, Knee", "descriptor_ui": "D020370", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Transducers", "descriptor_ui": "D014159", "major_topic": false }, { "descriptor": "Viscosity", "descriptor_ui": "D014783", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "249-255", "proceedings_title": null, "publisher": "", "title": "Lasers in surgery and medicine", "volume": "38", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a diagnostic system for osteoarthritis using a photoacoustic measurement method.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human adipose tissue, obtained by liposuction, was processed to obtain a fibroblast-like population of cells or adipose tissue-derived stromal cells (ATSCs). The ATSCs, as well as bone marrow-derived mesenchymal stem cells (BMSCs), have the capacity for renewal and the potential to differentiate into multiple lineages of mesenchymal tissues. These cells are capable of forming bone when implanted ectopically in an appropriate scaffold. The aim of this study was to evaluate a beta-tricalcium phosphate (beta-TCP) as a scaffold and to compare the potential of osteogenic differentiation of ATSCs with BMSCs. Both cell types were loaded into beta-TCP disk and cultured in an osteogenic induction medium. Optimal osteogenic differentiation in ATSCs in vitro, as determined by secretion of osteocalcin, scanning electron microscope, and histology, were obtained in the culturing with the beta-TCP disk. Furthermore, bone formation in vivo was examined by using the ATSC- or BMSC-loaded scaffolds in nude mice. The present results show that ATSCs have a similar ability to differentiate into osteoblasts and to synthesize bone in beta-TCP disk as have BMSCs.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hidemi", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Masuoka", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Asazuma", "name": null }, { "creator_type": "author", "first_name": "Bonpei", "last_name": "Takase", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Nemoto", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/jbm.b.30357" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16047328" } }, "mesh": [ { "descriptor": "Adipose Tissue", "descriptor_ui": "D000273", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biocompatible Materials", "descriptor_ui": "D001672", "major_topic": true }, { "descriptor": "Biodegradation, Environmental", "descriptor_ui": "D001673", "major_topic": false }, { "descriptor": "Bone Development", "descriptor_ui": "D001846", "major_topic": true }, { "descriptor": "Calcium Phosphates", "descriptor_ui": "D002130", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mesenchymal Stem Cells", "descriptor_ui": "D059630", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Microscopy, Electron, Scanning", "descriptor_ui": "D008855", "major_topic": false }, { "descriptor": "Stromal Cells", "descriptor_ui": "D017154", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "230-239", "proceedings_title": null, "publisher": "", "title": "Journal of biomedical materials research. Part B, Applied biomaterials", "volume": "76", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Bone formation using human adipose tissue-derived stromal cells and a biodegradable scaffold.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The endoplasmic reticulum (ER) is thought to play an important structural and functional role in phagocytosis. According to this model, direct membrane fusion between the ER and the plasma or phagosomal membrane must precede further invagination, but the exact mechanisms remain elusive. Here, we investigated whether various ER-localized SNARE proteins are involved in this fusion process. When phagosomes were isolated from murine J774 macrophages, we found that ER-localized SNARE proteins (syntaxin 18, D12, and Sec22b) were significantly enriched in the phagosomes. Fluorescence and immuno-EM analyses confirmed the localization of syntaxin 18 in the phagosomal membranes of J774 cells stably expressing this protein tagged to a GFP variant. To examine whether these SNARE proteins are required for phagocytosis, we generated 293T cells stably expressing the Fc gamma receptor, in which phagocytosis occurs in an IgG-mediated manner. Expression in these cells of dominant-negative mutants of syntaxin 18 or D12 lacking the transmembrane domain, but not a Sec22b mutant, impaired phagocytosis. Syntaxin 18 small interfering RNA (siRNA) selectively decreased the efficiency of phagocytosis, and the rate of phagocytosis was markedly enhanced by stable overexpression of syntaxin 18 in J774 cells. Therefore, we conclude that syntaxin 18 is involved in ER-mediated phagocytosis, presumably by regulating the specific and direct fusion of the ER and plasma or phagosomal membranes.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kiyotaka", "last_name": "Hatsuzawa", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Sachihiko", "last_name": "Yokoya", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Hisao", "last_name": "Nagaya", "name": null }, { "creator_type": "author", "first_name": "Ikuo", "last_name": "Wada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1091/mbc.e05-12-1174" }, "pmcid": { "normalized": "PMC1593171" }, "pmid": { "normalized": "16790498" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, CD", "descriptor_ui": "D015703", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "COP-Coated Vesicles", "descriptor_ui": "D022181", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Oligopeptides", "descriptor_ui": "D009842", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "Phagocytosis", "descriptor_ui": "D010587", "major_topic": false }, { "descriptor": "Phagosomes", "descriptor_ui": "D010588", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Qa-SNARE Proteins", "descriptor_ui": "D050765", "major_topic": false }, { "descriptor": "R-SNARE Proteins", "descriptor_ui": "D050683", "major_topic": false }, { "descriptor": "Receptors, IgG", "descriptor_ui": "D017452", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "3964-3977", "proceedings_title": null, "publisher": "", "title": "Molecular biology of the cell", "volume": "17", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Involvement of syntaxin 18, an endoplasmic reticulum (ER)-localized SNARE protein, in ER-mediated phagocytosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: To better understand the relationship between mutation of the guanosine triphosphate cyclohydrolase I (GCH1) gene and the etiology of DYT5 dystonia and to accumulate data on the mutation in the Japanese population for genetic diagnosis of the disease. SETTING: Japanese population. Patients Eight Japanese patients with suspected DYT5 dystonia were analyzed. Intervention Direct genomic sequencing of 6 exons of GCH1 was performed. MAIN OUTCOME MEASURES: For patients who did not exhibit any abnormality in the sequence analysis, the possibility of exon deletions was examined. In cases for which cerebrospinal fluid was available, the concentrations of neopterin and biopterin were measured as an index of GCH1 enzyme activity. RESULTS: In 2 patients, we found a new T106I mutation in exon 1 of GCH1, a position involved in the helix-turn-helix structure of the enzyme. In the third patient, we found a new mutation (a 15-base pair nucleotide deletion) in exon 5 that may cause a frameshift involving the active site. In the fourth patient, we detected a known nucleotide G>A substitution in the splice site of intron 5, which has been reported to produce exon 5-skipped messenger RNA. The concentrations of both neopterin and biopterin in the cerebrospinal fluid of the third and fourth patients were markedly lower than the normal range, indicating that the GCH1 enzyme was functionally abnormal in these mutations. Gene dosage analysis showed that the fifth patient had a deletion of both exon 3 and exon 4, whereas the sixth patient had a deletion of exon 3. CONCLUSIONS: We found several novel, as well as known, GCH1 mutations in Japanese patients with DYT5 dystonia. In some of them, the GCH1 enzyme activity was proved to be impaired.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Funayama", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ichinose", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Toyoshima", "name": null }, { "creator_type": "author", "first_name": "Fumi", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Nishida", "last_name": "Tomoko", "name": null }, { "creator_type": "author", "first_name": "Konishi", "last_name": "Yukihiko", "name": null }, { "creator_type": "author", "first_name": "Syuji", "last_name": "Yoshino", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Shimazu", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Obata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1001/archneur.63.11.1605" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17101830" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biopterins", "descriptor_ui": "D001708", "major_topic": false }, { "descriptor": "Child", "descriptor_ui": "D002648", "major_topic": false }, { "descriptor": "Child, Preschool", "descriptor_ui": "D002675", "major_topic": false }, { "descriptor": "DNA Mutational Analysis", "descriptor_ui": "D004252", "major_topic": false }, { "descriptor": "Dystonic Disorders", "descriptor_ui": "D020821", "major_topic": false }, { "descriptor": "Exons", "descriptor_ui": "D005091", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "GTP Cyclohydrolase", "descriptor_ui": "D006136", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Isoleucine", "descriptor_ui": "D007532", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microsatellite Repeats", "descriptor_ui": "D018895", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Neopterin", "descriptor_ui": "D019798", "major_topic": false }, { "descriptor": "Threonine", "descriptor_ui": "D013912", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "1605-1610", "proceedings_title": null, "publisher": "", "title": "Archives of neurology", "volume": "63", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Novel mutations in the guanosine triphosphate cyclohydrolase 1 gene associated with DYT5 dystonia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Several lines of evidence have suggested roles for pituitary adenylate cyclase-activating polypeptide (PACAP) in the developing nervous system. Previously, we showed that mRNA for PACAP, vasoactive intestinal peptide (VIP), and their three receptor subtypes, is differentially expressed in embryonic stem (ES) cells, ES cell-derived, neural stem cell-enriched cultures, and differentiated neurons, by using the five steps of the in vitro neuronal culture model of ES cell differentiation. Here, we examined the effects of PACAP on self-renewal and cell lineage determination of neural progenitor/stem cells. PACAP inhibited the basic fibroblast growth factor-induced proliferation (self-renewal), as assessed by neurosphere formation. PACAP increased microtubule-associated protein 2-positive neurons without affecting the number of cells positive for the neural stem cell marker nestin, astrocyte marker glial fibrillary acidic protein, and oligodendrocyte marker CNPase. These results suggest that PACAP inhibits self-renewal but, instead, induces early neuronal differentiation of neural progenitor cells.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Megumi", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Iga", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Naohisa", "last_name": "Arakawa", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1196/annals.1317.042" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16888189" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Microtubule-Associated Proteins", "descriptor_ui": "D008869", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Jul", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "342-347", "proceedings_title": null, "publisher": "", "title": "Annals of the New York Academy of Sciences", "volume": "1070", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Inhibition of self-renewal and induction of neural differentiation by PACAP in neural progenitor cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We propose two major evolutionary origins of stem cell systems in the animal kingdom. Adult pluripotent stem cell systems are found in many invertebrates and probably evolved as components of asexual reproduction. Lineage-specific stem cell systems probably evolved later and include neural and hematopoietic stem cell types. We propose that these two types of stem cell systems evolved independently. The vasa-like genes regulate reproductive stem cells, but not lineage-specific stem cells, which may be regulated by gcm genes. Here, we review the evidence for the molecular basis for the evolutionary origin of these two different stem cell systems.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kiyokazu", "last_name": "Agata", "name": null }, { "creator_type": "author", "first_name": "Elizabeth", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Funayama", "name": null }, { "creator_type": "author", "first_name": "Norito", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Umesono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.semcdb.2006.05.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16807003" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": true }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Reproduction, Asexual", "descriptor_ui": "D012100", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "503-509", "proceedings_title": null, "publisher": "", "title": "Seminars in cell & developmental biology", "volume": "17", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Two different evolutionary origins of stem cell systems and their molecular basis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epigenetic changes in chromatin structure at the T helper (Th2) locus correlate with interukin-4 (IL-4) and IL-13 expression during Th2 differentiation. By using a transgenic green fluorescence protein (GFP) reporter system, we show that conserved noncoding sequence-2 (CNS-2), located downstream of the Il4 locus, is a constitutively active enhancer in NKT cells as well as in a subset of CD44(hi) memory phenotype CD4+ T cells. CNS-2 enhancer activity and initial IL-4 expression in CD44(hi) CD4+ T cells were abolished in mice with a CD4-specific deletion of the transcriptional mediator of Notch signaling, Rbp-j. Depletion of CNS-2 active CD4+ T cells markedly decreased Th2 differentiation from naive CD4 T cells and antigen-specific IgE production after in vivo priming. These findings indicate that Notch-regulated CNS-2 enhancer controls initial IL-4 expression in NKT and memory phenotype CD4+ T cells and that CNS-2 active CD44(hi) memory phenotype T cells are important in facilitating Th2 differentiation of naive CD4+ T cells in allergic responses.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Tanigaki", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Honjo", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Kubo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.immuni.2006.04.009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16782026" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CD4-Positive T-Lymphocytes", "descriptor_ui": "D015496", "major_topic": false }, { "descriptor": "Enhancer Elements, Genetic", "descriptor_ui": "D004742", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Hyaluronan Receptors", "descriptor_ui": "D018960", "major_topic": false }, { "descriptor": "Immunoglobulin J Recombination Signal Sequence-Binding Protein", "descriptor_ui": "D051819", "major_topic": false }, { "descriptor": "Immunologic Memory", "descriptor_ui": "D007156", "major_topic": false }, { "descriptor": "Interleukin-4", "descriptor_ui": "D015847", "major_topic": false }, { "descriptor": "Killer Cells, Natural", "descriptor_ui": "D007694", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "T-Lymphocyte Subsets", "descriptor_ui": "D016176", "major_topic": false }, { "descriptor": "Th2 Cells", "descriptor_ui": "D018418", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "689-701", "proceedings_title": null, "publisher": "", "title": "Immunity", "volume": "24", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "The interleukin-4 enhancer CNS-2 is regulated by Notch signals and controls initial expression in NKT cells and memory-type CD4 T cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The pre-T cell receptor (TCR) is crucial for early T cell development and is proposed to function in a ligand-independent way. However, the molecular mechanism underlying the autonomous signals remains elusive. Here we show that the pre-TCR complex spontaneously formed oligomers. Specific charged residues in the extracellular domain of the pre-TCR alpha-chain mediated formation of the oligomers in vitro. Alteration of these residues eliminated the ability of the pre-TCR alpha-chain to support pre-TCR signaling in vivo. Dimerization but not raft localization of CD3epsilon was sufficient to simulate pre-TCR function and promote beta-selection. These results suggest that the pre-TCR complex can deliver its signal autonomously through oligomerization of the pre-TCR alpha-chain mediated by charged residues.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Sho", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Machie", "last_name": "Sakuma", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Sakata-Sogawa", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "David L.", "last_name": "Wiest", "name": null }, { "creator_type": "author", "first_name": "Makio", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ni1290" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16327787" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Membrane Glycoproteins", "descriptor_ui": "D008562", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell, alpha-beta", "descriptor_ui": "D016693", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "67-75", "proceedings_title": null, "publisher": "", "title": "Nature immunology", "volume": "7", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Mechanistic basis of pre-T cell receptor-mediated autonomous signaling critical for thymocyte development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genetic interactions provide information about genes and processes with overlapping functions in biological systems. For Saccharomyces cerevisiae, computational integration of multiple types of functional genomic data is used to generate genome-wide predictions of genetic interactions. However, this methodology cannot be applied to the vastly more complex genome of metazoans, and only recently has the first metazoan genome-wide prediction of genetic interactions been reported. The prediction for Caenorhabditis elegans was generated by computationally integrating functional genomic data from S. cerevisiae, C. elegans and Drosophila melanogaster. This achievement is an important step toward system-level understanding of biological systems and human diseases.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kitano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/bies.20490" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17041895" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Genome, Helminth", "descriptor_ui": "D049751", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": true }, { "descriptor": "Helminth Proteins", "descriptor_ui": "D015801", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "1087-1090", "proceedings_title": null, "publisher": "", "title": "BioEssays : news and reviews in molecular, cellular and developmental biology", "volume": "28", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Genome-wide prediction of genetic interactions in a metazoan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Amino acid sequences for identified prolactin (PRL)-releasing peptides (PrRPs) were conserved in mammals (>90%) or teleost fishes (100%), but there were considerable differences between these classes in the sequence (<65%) as well as in the role of PrRP. In species other than fishes and mammals, we have identified frog PrRP. The cDNA encoding Xenopus laevis prepro-PrRP, which can generate putative PrRPs, was cloned and sequenced. Sequences for the coding region showed higher identity with teleost PrRPs than mammalian homologues, but suggested the occurrence of putative PrRPs of 20 and 31 residues as in mammals. The amino acid sequence of PrRP20 was only one residue different from teleost PrRP20, but shared 70% identity with mammalian PrRP20s. In primary cultures of bullfrog (Rana catesbeiana) pituitary cells, Xenopus PrRPs increased prolactin concentrations in culture medium to 130-160% of the control, but PrRPs was much less potent than thyrotropin-releasing hormone (TRH) causing a three- to four-fold increase in prolactin concentrations. PrRP mRNA levels in the developing Xenopus brain peak in early prometamorphosis, different from prolactin levels. PrRP may not be a major prolactin-releasing factor (PRF), at least in adult frogs, as in mammals.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Kazutoshi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Miyoko", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Sakae", "last_name": "Kikuyama", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kawauchi", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Tsutsui", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Fujimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.peptides.2006.08.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16979799" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "Hypothalamic Hormones", "descriptor_ui": "D007028", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Prolactin-Releasing Hormone", "descriptor_ui": "D056690", "major_topic": false }, { "descriptor": "Xenopus laevis", "descriptor_ui": "D014982", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "3347-3351", "proceedings_title": null, "publisher": "", "title": "Peptides", "volume": "27", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular cloning and functional characterization of a prolactin-releasing peptide homolog from Xenopus laevis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Canine herpesvirus (CHV) is an attractive candidate not only for use as a recombinant vaccine to protect dogs from a variety of canine pathogens but also as a viral vector for gene therapy in domestic animals. However, developments in this area have been impeded by the complicated techniques used for eukaryotic homologous recombination. To overcome these problems, we used bacterial artificial chromosomes (BACs) to generate infectious BACs. Our findings may be summarized as follows: (i) the CHV genome (pCHV/BAC), in which a BAC flanked by loxP sites was inserted into the thymidine kinase gene, was maintained in Escherichia coli; (ii) transfection of pCHV/BAC into A-72 cells resulted in the production of infectious virus; (iii) the BAC vector sequence was almost perfectly excisable from the genome of the reconstituted virus CHV/BAC by co-infection with CHV/BAC and a recombinant adenovirus that expressed the Cre recombinase; and (iv) a recombinant virus in which the glycoprotein C gene was deleted was generated by lambda recombination followed by Flp recombination, which resulted in a reduction in viral titer compared with that of the wild-type virus. The infectious clone pCHV/BAC is useful for the modification of the CHV genome using bacterial genetics, and CHV/BAC should have multiple applications in the rapid generation of genetically engineered CHV recombinants and the development of CHV vectors for vaccination and gene therapy in domestic animals.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Orkash", "last_name": "Hushur", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Yukinobu", "last_name": "Tohya", "name": null }, { "creator_type": "author", "first_name": "Hiroomi", "last_name": "Akashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.micinf.2005.11.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16515874" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chromosomes, Artificial, Bacterial", "descriptor_ui": "D022202", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Genetic Engineering", "descriptor_ui": "D005818", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": false }, { "descriptor": "Genome, Viral", "descriptor_ui": "D016679", "major_topic": true }, { "descriptor": "Herpesvirus 1, Canid", "descriptor_ui": "D002184", "major_topic": false }, { "descriptor": "Recombination, Genetic", "descriptor_ui": "D011995", "major_topic": false }, { "descriptor": "Thymidine Kinase", "descriptor_ui": "D013937", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "1054-1063", "proceedings_title": null, "publisher": "", "title": "Microbes and infection", "volume": "8", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Construction of an infectious clone of canine herpesvirus genome as a bacterial artificial chromosome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Activity-dependent synaptic modification occurs in both developing and mature animals. For reliable information transfer and storage, however, once established, synapses must be maintained stably. We investigated how chronic blockade of neuronal activity or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors affects excitatory climbing fiber (CF) to Purkinje cell (PC) synapses in adult mouse cerebellum. Both treatments caused reduced glutamate concentration transient at the synaptic cleft, decreased frequency of quantal excitatory postsynaptic current, and diminished CF innervation of PC shaft dendrites but no change in CF's release probability. These results indicate that, in the mature cerebellum, AMPA receptor-mediated excitatory postsynaptic activity maintains CF's functional glutamate-release sites and its innervation of PC shaft dendrites.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Sho", "last_name": "Kakizawa", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Dai", "last_name": "Yanagihara", "name": null }, { "creator_type": "author", "first_name": "Masamitsu", "last_name": "Iino", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.0504359103" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16357208" } }, "mesh": [ { "descriptor": "alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid", "descriptor_ui": "D018350", "major_topic": false }, { "descriptor": "Anesthetics, Local", "descriptor_ui": "D000779", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Electrophysiology", "descriptor_ui": "D004594", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Microscopy, Electron", "descriptor_ui": "D008854", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "N-Methylaspartate", "descriptor_ui": "D016202", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Polyvinyls", "descriptor_ui": "D011145", "major_topic": false }, { "descriptor": "Presynaptic Terminals", "descriptor_ui": "D017729", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Quinoxalines", "descriptor_ui": "D011810", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Receptors, AMPA", "descriptor_ui": "D018091", "major_topic": false }, { "descriptor": "Sodium", "descriptor_ui": "D012964", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Tetrodotoxin", "descriptor_ui": "D013779", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Dec 27", "date_precision": "day", "issue": "52", "normalized_date": "2005-12-27", "pages": "19180-19185", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "102", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Maintenance of presynaptic function by AMPA receptor-mediated excitatory postsynaptic activity in adult brain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A photocrosslinkable chitosan (Az-CH-LA) aqueous solution containing paclitaxel resulted in an insoluble hydrogel within 30 s of ultrtaviolet light (UV)-irradiation. About 35-40% of the paclitaxel was released from the paclitaxel-incorporated chitosan hydrogel into phosphate buffered saline (PBS) within 1 day, after which gradual release occurred during 3 days under in vitro non-degradation conditions of the hydrogel. The paclitaxel remaining in the chitosan hydrogel retained its biological activity in vitro for at least 21 days, and was released from the chitosan hydrogel in vivo upon degradation of the hydrogel. The paclitaxel-incorporated Az-CH-LA hydrogel inhibited the growth of subcutaneously induced tumors with Lewis lung cancer (3LL) cells more effectively than those treated with only Az-CH-LA, only paclitaxel, and a non-treated group (control) for at least 11 days. Furthermore, paclitaxel-incorporated chitosan hydrogel markedly reduced the number of CD34-positive vessels in subcutaneous 3LL tumors, indicating a strong inhibition of angiogenesis. These results suggested that application of paclitaxel-incorporated Az-CH-LA hydrogel has an inhibitory activity on angiogenesis and tumor growth.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kiyohaya", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Ozeki", "name": null }, { "creator_type": "author", "first_name": "Takamitsu", "last_name": "Ishizuka", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Yura", "name": null }, { "creator_type": "author", "first_name": "Takemi", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Hidemi", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Bonpei", "last_name": "Takase", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Tadaaki", "last_name": "Maehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jconrel.2005.09.026" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16289419" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents, Phytogenic", "descriptor_ui": "D000972", "major_topic": false }, { "descriptor": "Carcinoma, Lewis Lung", "descriptor_ui": "D018827", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Chitosan", "descriptor_ui": "D048271", "major_topic": false }, { "descriptor": "Delayed-Action Preparations", "descriptor_ui": "D003692", "major_topic": false }, { "descriptor": "Diffusion", "descriptor_ui": "D004058", "major_topic": false }, { "descriptor": "Drug Carriers", "descriptor_ui": "D004337", "major_topic": false }, { "descriptor": "Drug Stability", "descriptor_ui": "D004355", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Hydrogels", "descriptor_ui": "D020100", "major_topic": false }, { "descriptor": "Injections, Subcutaneous", "descriptor_ui": "D007279", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neoplasm Transplantation", "descriptor_ui": "D009368", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Paclitaxel", "descriptor_ui": "D017239", "major_topic": false }, { "descriptor": "Photochemistry", "descriptor_ui": "D010777", "major_topic": false }, { "descriptor": "Skin Neoplasms", "descriptor_ui": "D012878", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Dec 10", "date_precision": "day", "issue": "1", "normalized_date": "2005-12-10", "pages": "79-89", "proceedings_title": null, "publisher": "", "title": "Journal of controlled release : official journal of the Controlled Release Society", "volume": "110", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Controlled release of paclitaxel from photocrosslinked chitosan hydrogels and its subsequent effect on subcutaneous tumor growth in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chemotaxis signal transducer protein DcrA from a sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough was previously shown to contain a c-type heme in its periplasmic domain (DcrA-N) for sensing redox and/or oxygen [Fu et al. (1994) J. Bacteriol. 176, 344-350], which is the first example of a heme-based sensor protein containing a c-type heme as a prosthetic group. Optical absorption and resonance Raman spectroscopies indicates that heme c in DcrA-N shows a redox-dependent ligand exchange. Upon reduction, a water molecule that may be the sixth ligand of the ferric heme c is replaced by an endogenous amino acid. Although the reduced heme in DcrA-N is six-coordinated with two endogenous axial ligands, CO can easily bind to the reduced heme to form CO-bound DcrA-N. Reaction of the reduced DcrA-N with molecular oxygen results in autoxidation to form a ferric state without forming any stable oxygen-bound form probably due to the extremely low redox potential of DcrA-N (-250 mV). Our study supports the initial idea by Fu et al. that DcrA would act as a redox and/or oxygen sensor, in which the ligand exchange between water and an endogenous amino acid is a trigger for signal transduction. While the affinity of CO to DcrA-N (Kd = 138 microM) is significantly weak compared to those of other heme proteins, we suggest that CO might be another physiological effector molecule.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shiro", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Katsuaki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Teizo", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Shigetoshi", "last_name": "Aono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/bi0513352" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16285745" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Biophysical Phenomena", "descriptor_ui": "D055592", "major_topic": false }, { "descriptor": "Biophysics", "descriptor_ui": "D001703", "major_topic": false }, { "descriptor": "Carbon Monoxide", "descriptor_ui": "D002248", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": false }, { "descriptor": "Electrochemistry", "descriptor_ui": "D004563", "major_topic": false }, { "descriptor": "Heme", "descriptor_ui": "D006418", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Spectrophotometry", "descriptor_ui": "D013053", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Nov 22", "date_precision": "day", "issue": "46", "normalized_date": "2005-11-22", "pages": "15406-15413", "proceedings_title": null, "publisher": "", "title": "Biochemistry", "volume": "44", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Biophysical properties of a c-type heme in chemotaxis signal transducer protein DcrA.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular signal transduction relies on spatial and temporal signal transmitter dynamics. To clarify the correlations of these transmitter molecules, multicolor-imaging has been widely used. However, in the case of applying multiple indicators in a cell, spectral overlap of the indicators prevents accurate quantitative analysis. Moreover, the invasive (toxic) effect, the localization, the metabolism, as well as photobleaching of these indicators complicate the situation. Here, we show that single-molecular multifluorescent probes can overcome these problems. While intracellular calcium plays a critical role as a signal transmitter and magnesium acts as a cofactor in many situations, the correlations between the two cations are now the main issue. We designed and synthesized a Ca2+-Mg2+ responsive multifluorescent probe, KCM-1. KCM-1 shows a spectral blue shift upon complexation to Ca2+ and a red shift to the presence of Mg2+. With data analyzed at different excitation wavelengths, the concentrations of Ca2+ and Mg2+ are simultaneously quantified. Furthermore, by using the AM-ester method, intracellular Ca2+ and Mg2+ concentrations are simultaneously imaged. Such a type of intracellular multiple analyte imaging by a single-molecular multifluorescent probe is successfully demonstrated for the first time.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Yoshiichiro", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja0528228" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16076163" } }, "mesh": [ { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Aug 10", "date_precision": "day", "issue": "31", "normalized_date": "2005-08-10", "pages": "10798-10799", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "127", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Single molecular multianalyte (Ca2+, Mg2+) fluorescent probe and applications to bioimaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To determine the nature of intracellular Mg2+ stores and Mg2+ release mechanisms in differentiated PC12 cells, Mg2+ and Ca2+ mobilizations were measured simultaneously in living cells with KMG-104, a fluorescent Mg2+ indicator, and fura-2, respectively. Treatment with the mitochondrial uncoupler, carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP), increased both the intracellular Mg2+ concentration ([Mg2+]i) and the [Ca2+]i in these cells. Possible candidates as intracellular Mg2+ stores under these conditions include intracellular divalent cation binding sites, endoplasmic reticulum (ER), Mg-ATP and mitochondria. Given that no change in [Mg2+]i was induced by caffeine application, intracellular IP3 or Ca2+ liberated by photolysis, it appears that no Mg2+ release mechanism thus exists that is mediated via the action of Ca2+ on membrane-bound receptors in the ER or via the offloading of Mg2+ from binding sites as a result of the increased [Ca2+]i. FCCP treatment for 2 min did not alter the intracellular ATP content, indicating that Mg2+ was not released from Mg-ATP, at least in the first 2 min following exposure to FCCP. FCCP-induced [Mg2+]i increase was observed at mitochondria localized area, and vice versa. These results suggest that the mitochondria serve as the intracellular Mg2+ store in PC12 cell. Simultaneous measurements of [Ca2+]i and mitochondrial membrane potential, and also of [Ca2+]i and [Mg2+]i, revealed that the initial rise in [Mg2+]i followed that of mitochondrial depolarization for several seconds. These findings show that the source of Mg2+ in the FCCP-induced [Mg2+]i increase in PC12 cells is mitochondria, and that mitochondrial depolarization triggers the Mg2+ release.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Tokuno", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Kudo", "name": null }, { "creator_type": "author", "first_name": "Yoshiichiro", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbamcr.2004.10.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15878394" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caffeine", "descriptor_ui": "D002110", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone", "descriptor_ui": "D002259", "major_topic": false }, { "descriptor": "Cations, Divalent", "descriptor_ui": "D002413", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Intracellular Membranes", "descriptor_ui": "D007425", "major_topic": false }, { "descriptor": "Ionophores", "descriptor_ui": "D007476", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Membrane Potentials", "descriptor_ui": "D008564", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 May 15", "date_precision": "day", "issue": "1", "normalized_date": "2005-05-15", "pages": "19-28", "proceedings_title": null, "publisher": "", "title": "Biochimica et biophysica acta", "volume": "1744", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Mitochondria are intracellular magnesium stores: investigation by simultaneous fluorescent imagings in PC12 cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The expressions of mRNAs for pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), and their receptors (PAC1, VPAC1 and VPAC2) were examined in the five steps of the in vitro neuronal culture model of embryonic stem (ES) cell differentiation. mRNAs for PACAP, VIP, PAC1 receptor, and VPAC2 receptor were moderately expressed in neural stem cell-enriched cultures, while VPAC1 receptor mRNA was most prominently expressed in embryoid bodies (EBs). The expression of PAC1 receptor mRNA was further upregulated after terminal differentiation into neurons. In contrast, the expressions of PAC1 receptor and PACAP mRNAs were markedly decreased after glial differentiation. These results suggest that this in vitro neuronal culture system will be a useful model for future studies on the functional role of the PACAPergic system during different stages of neuronal development.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Megumi", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Naohisa", "last_name": "Arakawa", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Iga", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Jun-Ichi", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.regpep.2004.08.018" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15620423" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Multipotent Stem Cells", "descriptor_ui": "D039902", "major_topic": false }, { "descriptor": "Nerve Growth Factors", "descriptor_ui": "D009414", "major_topic": false }, { "descriptor": "Nerve Tissue", "descriptor_ui": "D009417", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Neurotransmitter Agents", "descriptor_ui": "D018377", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051236", "major_topic": false }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I", "descriptor_ui": "D051237", "major_topic": false }, { "descriptor": "Receptors, Vasoactive Intestinal Peptide, Type II", "descriptor_ui": "D051239", "major_topic": false }, { "descriptor": "Receptors, Vasoactive Intestinal Polypeptide, Type I", "descriptor_ui": "D051238", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Mar 15", "date_precision": "day", "issue": "1-2", "normalized_date": "2005-03-15", "pages": "109-113", "proceedings_title": null, "publisher": "", "title": "Regulatory peptides", "volume": "126", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Differential expression of mRNAs for PACAP and its receptors during neural differentiation of embryonic stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) exerts neurotrophic effects both in vitro and in vivo. Here we demonstrate the upregulation of PACAP mRNA expression in cultured rat cortical neurons after excitotoxic glutamate exposure, and the exacerbating effect of the PACAP receptor antagonist, PACAP(6-38), on neuronal viability. PACAP mRNA levels were increased up to 3.5-fold 8 h after glutamate exposure. PACAP(6-38) decreased the viability of cortical neurons, irrespective of whether the cells were exposed to glutamate or not. PACAP(6-38) also inhibited glutamate-induced expression of PACAP mRNA, suggesting that PACAP acts via an autocrine or paracrine mechanism to enhance PACAP expression itself. Glutamate exposure is known to increase brain-derived neurotrophic factor (BDNF) mRNA expression. This increased expression was markedly suppressed by PACAP(6-38). Our previous study has shown that PACAP stimulates the PACAP gene transcription in PC12 cells. Taken together, these data may suggest that endogenous PACAP regulates the expression of PACAP itself and BDNF. Although it may also be possible that PACAP(6-38)-induced death of PACAP and BDNF mRNA-expressing cells, per se, results in reduced levels of these mRNAs, the present results support the idea that endogenous PACAP has a neuroprotective action.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Sayoko", "last_name": "Suetake", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Tomimoto", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.regpep.2004.08.014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15620425" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain-Derived Neurotrophic Factor", "descriptor_ui": "D019208", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Nerve Growth Factors", "descriptor_ui": "D009414", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Neurotransmitter Agents", "descriptor_ui": "D018377", "major_topic": false }, { "descriptor": "Peptide Fragments", "descriptor_ui": "D010446", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051236", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Mar 15", "date_precision": "day", "issue": "1-2", "normalized_date": "2005-03-15", "pages": "123-128", "proceedings_title": null, "publisher": "", "title": "Regulatory peptides", "volume": "126", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Neuroprotective action of endogenous PACAP in cultured rat cortical neurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "There is a demand in the field of regenerative medicine for measurement technology that enables functions of engineered tissue to be determined. For meeting this demand, we previously proposed a noninvasive method for determination of the viscoelasticity of a tissue phantom based on photoacoustic measurements. The purpose of this study was to verify the usefulness of the photoacoustic measurement method for evaluation of the viscoelastic properties of actual engineered tissue and to determine the correlation between biochemical characteristics and photoacoustic signals. The relaxation times measured by the photoacoustic method agreed well with the intrinsic viscoelastic parameters with a correlation coefficient of 0.98 when tissue-engineered cartilage tissues cultured for various periods (up to 12 weeks) were used as samples. By comparison of the results of biochemical analyses and biomechanical studies, we proved that the photoacoustic signal is a good indicator for evaluating extracellular matrix formation in order to determine the characteristics of tissue-engineered cartilage. To our knowledge, this is the first report on noninvasive and time-dependent viscoelastic evaluation of engineered tissue for determining functions of engineered tissues.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Joji", "last_name": "Mochida", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kikuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/ten.2005.11.1234" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16144459" } }, "mesh": [ { "descriptor": "Acoustics", "descriptor_ui": "D000162", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Cartilage, Articular", "descriptor_ui": "D002358", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chondrocytes", "descriptor_ui": "D019902", "major_topic": false }, { "descriptor": "Elasticity", "descriptor_ui": "D004548", "major_topic": false }, { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Equipment Failure Analysis", "descriptor_ui": "D019544", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Photometry", "descriptor_ui": "D010783", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Tissue Engineering", "descriptor_ui": "D023822", "major_topic": false }, { "descriptor": "Viscosity", "descriptor_ui": "D014783", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Jul-Aug", "date_precision": "unknown", "issue": "7-8", "normalized_date": null, "pages": "1234-1243", "proceedings_title": null, "publisher": "", "title": "Tissue engineering", "volume": "11", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Usefulness of photoacoustic measurements for evaluation of biomechanical properties of tissue-engineered cartilage.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The influence of dosing time on the anti-immobility effect of antidepressants and mechanisms underlying this phenomenon were investigated in mice. In the forced swimming test (FST), the immobility time of mice treated with amitriptyline (15 mg/kg) and fluvoxamine (30 mg/kg) showed a significant 24-h rhythm. The anti-immobility effect of fluvoxamine in FST was potent at the early part of the dark phase without increasing locomotor activity. Concerning pharmacokinetics, although K(e) of fluvoxamine was approximately 1.3-fold higher in mice injected with fluvoxamine at 9:00 PM than at 9:00 AM, no dosing time dependence was demonstrated for either plasma or brain fluvoxamine concentration at 0.5 h after the drug injection. On the other hand, serotonin transporter (SERT) mRNA expression and 5-hydroxytryptamine (5-HT) uptake activity in the mouse midbrain showed significant time-dependent changes with higher levels during the dark phase and lower levels during the light phase. These results suggest that the reuptake of 5-HT might be more increased during the dark phase. Since the reuptake of 5-HT is inhibited almost completely by injection with 30 mg/kg fluvoxamine at any time, the extracellular 5-HT level may be more increased by the injection of fluvoxamine at the early part of the dark phase. The present results suggest that the anti-immobility effect of fluvoxamine in FST increases depending on dosing time. Furthermore, the time-dependent change of SERT mRNA expression and uptake activity in the midbrain is suggested to be the mechanism underlying the 24-h rhythm of anti-immobility effect of fluvoxamine.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kentarou", "last_name": "Ushijima", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hideto", "last_name": "To", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Ohdo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1124/jpet.105.088849" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16079297" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antidepressive Agents", "descriptor_ui": "D000928", "major_topic": false }, { "descriptor": "Antidepressive Agents, Second-Generation", "descriptor_ui": "D018687", "major_topic": false }, { "descriptor": "Depression", "descriptor_ui": "D003863", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Fluvoxamine", "descriptor_ui": "D016666", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mesencephalon", "descriptor_ui": "D008636", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false }, { "descriptor": "Serotonin Plasma Membrane Transport Proteins", "descriptor_ui": "D050486", "major_topic": false }, { "descriptor": "Swimming", "descriptor_ui": "D013550", "major_topic": false }, { "descriptor": "Synaptosomes", "descriptor_ui": "D013574", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Nov", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "764-770", "proceedings_title": null, "publisher": "", "title": "The Journal of pharmacology and experimental therapeutics", "volume": "315", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Chronopharmacological study of antidepressants in forced swimming test of mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "(-)-DHMEQ, a newly designed NF-kappaB inhibitor, inhibited RANKL-induced osteoclast differentiation in mouse BMMs through downregulation of the induction of NFATc1, an essential transcription factor of osteoclastogenesis. INTRODUCTION: Bone destruction is often observed in advanced case of rheumatoid arthritis and neoplastic diseases, including multiple myeloma. Effective and nontoxic chemotherapeutic agents are expected for the suppression of these bone destructions. RANKL induces activation of NF-kappaB and osteoclastogenesis in bone marrow-derived monocyte/macrophage precursor cells (BMMs). Targeted disruption or pharmacological suppression of NF-kappaB result in impaired osteoclastogenesis, but how NF-kappaB is involved in the regulation of osteoclastogenesis is not known. MATERIALS AND METHODS: The effect of (-)-dehydroxymethylepoxyquinomicin [(-)-DHMEQ] on osteoclast differentiation was studied using a culture system of mouse BMMs stimulated with RANKL and macrophage colony-stimulating factor. The mechanism of the inhibition was studied by biochemical analysis such as immunoblotting and retroviral transfer experiments. RESULTS: (-)-DHMEQ strongly inhibited RANKL-induced NF-kappaB activation in BMMs and inhibited RANKL-induced formation of TRACP(+) multinucleated cells. Interestingly, (-)-DHMEQ specifically inhibited the RANKL-induced expression of NFATc1 but not the expressions of TRAF6 or c-fos. Inhibition of osteoclast differentiation by (-)-DHMEQ was rescued by overexpression of NFATc1, suggesting that the inhibition is not caused by a toxic effect. Moreover, pit formation assays showed that (-)-DHMEQ also inhibited the bone-resorbing activity of mature osteoclasts. CONCLUSION: The inhibition of NF-kappaB suppresses osteoclastogenesis by downregulation of NFATc1, suggesting that NFATc1 expression is regulated by NF-kappaB in RANKL-induced osteoclastogenesis. Our results also indicate the possibility of (-)-DHMEQ becoming a new therapeutic strategy against bone erosion.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Takatsuna", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Asagiri", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Osada", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Ohya", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Takayanagi", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Umezawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1359/jbmr.041213" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15765185" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzamides", "descriptor_ui": "D001549", "major_topic": false }, { "descriptor": "Bone Marrow Cells", "descriptor_ui": "D001854", "major_topic": false }, { "descriptor": "Bone Resorption", "descriptor_ui": "D001862", "major_topic": true }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cyclohexanones", "descriptor_ui": "D003512", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Membrane Glycoproteins", "descriptor_ui": "D008562", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "NFATC Transcription Factors", "descriptor_ui": "D050778", "major_topic": false }, { "descriptor": "Osteoclasts", "descriptor_ui": "D010010", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "RANK Ligand", "descriptor_ui": "D053245", "major_topic": false }, { "descriptor": "Receptor Activator of Nuclear Factor-kappa B", "descriptor_ui": "D053246", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "653-662", "proceedings_title": null, "publisher": "", "title": "Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research", "volume": "20", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Inhibition of RANKL-induced osteoclastogenesis by (-)-DHMEQ, a novel NF-kappaB inhibitor, through downregulation of NFATc1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The aim of this study was to investigate with tissue engineering procedures the possibility of using atelocollagen honeycomb-shaped scaffolds sealed with a membrane (ACHMS scaffold) for the culturing of chondrocytes to repair articular cartilage defects. Chondrocytes from the articular cartilage of Japanese white rabbits were cultured in ACHMS scaffolds to allow a high-density, three-dimensional culturing for up to 21 days. Although the DNA content in the scaffold increased at a lower rate than monolayer culturing, scanning electron microscopy data showed that the scaffold was filled with grown chondrocytes and their produced extracellular matrix after 21 days. In addition, glycosaminoglycan (GAG) accumulation in the scaffold culture was at a higher level than the monolayer culture. Cultured cartilage in vitro for 14 days showed enough elasticity and stiffness to be handled in vivo. An articular cartilage defect was initiated in the patellar groove of the femur of rabbits and was subsequently filled with the chondrocyte-cultured ACHMS scaffold, ACHMS scaffold alone, or non-filled (control). Three months after the operations, histological analysis showed that only defects inserted with chondrocytes being cultured in ACHMS scaffolds were filled with reparative hyaline cartilage, and thereby highly expressing type II collagen. These results indicate that implantation of allogenic chondrocytes cultured in ACHMS scaffolds may be effective in repairing articular cartilage defects.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kazunori", "last_name": "Masuoka", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Asazuma", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hidemi", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Takemi", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Bonpei", "last_name": "Takase", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Nemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/jbm.b.30284" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16025467" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bioartificial Organs", "descriptor_ui": "D021522", "major_topic": true }, { "descriptor": "Cartilage, Articular", "descriptor_ui": "D002358", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chondrocytes", "descriptor_ui": "D019902", "major_topic": false }, { "descriptor": "Collagen", "descriptor_ui": "D003094", "major_topic": false }, { "descriptor": "Femur", "descriptor_ui": "D005269", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microscopy, Electron, Scanning", "descriptor_ui": "D008855", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Tissue Engineering", "descriptor_ui": "D023822", "major_topic": false }, { "descriptor": "Transplantation, Homologous", "descriptor_ui": "D014184", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Oct", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "177-184", "proceedings_title": null, "publisher": "", "title": "Journal of biomedical materials research. Part B, Applied biomaterials", "volume": "75", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Tissue engineering of articular cartilage using an allograft of cultured chondrocytes in a membrane-sealed atelocollagen honeycomb-shaped scaffold (ACHMS scaffold).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We detected a missense mutation in the kinase domain of the LRRK2 gene in members with autosomal dominant Parkinson's disease of the Japanese family (the Sagamihara family) who served as the basis for the original defining of the PARK8 Parkinson's disease locus. The results of the Sagamihara family, in combination with the unique pathological features characterized by pure nigral degeneration without Lewy bodies, provided us with valuable information for elucidating the protein structure-pathogenesis relationship for the gene product of LRRK2. We did not detect this mutation or other known mutations of the LRRK2 gene in Japanese patients with sporadic Parkinson's disease.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Manabu", "last_name": "Funayama", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Komiyama", "name": null }, { "creator_type": "author", "first_name": "Hisayuki", "last_name": "Kowa", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Obata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/ana.20484" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15880653" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Family Health", "descriptor_ui": "D005192", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leucine-Rich Repeat Serine-Threonine Protein Kinase-2", "descriptor_ui": "D000071158", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Mutation, Missense", "descriptor_ui": "D020125", "major_topic": true }, { "descriptor": "Parkinson Disease", "descriptor_ui": "D010300", "major_topic": false }, { "descriptor": "Pedigree", "descriptor_ui": "D010375", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "918-921", "proceedings_title": null, "publisher": "", "title": "Annals of neurology", "volume": "57", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "An LRRK2 mutation as a cause for the parkinsonism in the original PARK8 family.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We investigated the process of memory consolidation following classical conditioning of earthworms. Earthworms were conditioned in paired trials by a weak vibration as a conditioned stimulus (CS), and by light as an unconditioned stimulus (US). The occurrence of a shrinking response upon exposure to the CS increased steadily with the number of paired training trials. When the training procedure was changed by increasing the intertrial interval (ITI), it was found that only those worms trained with a 68 s ITI exhibited long-term memory retention for at least 24 h. The influence of mRNA synthesis inhibition by actinomycin-D or of protein synthesis by anisomycin on memory consolidation was also examined. Induction of the long-term memory was blocked when either of these two compounds was injected into the body cavity of the worm within 25 min of conditioning with the 68 s ITI. These results demonstrate that the long-term memory is dependent upon protein synthesis in response to the upregulation of new transcription messengers.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hikaru", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Takaya", "name": null }, { "creator_type": "author", "first_name": "Toshinobu", "last_name": "Shimoi", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Yoshiichiro", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.nlm.2004.11.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15721799" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anisomycin", "descriptor_ui": "D000841", "major_topic": false }, { "descriptor": "Association Learning", "descriptor_ui": "D001245", "major_topic": false }, { "descriptor": "Avoidance Learning", "descriptor_ui": "D001362", "major_topic": false }, { "descriptor": "Dactinomycin", "descriptor_ui": "D003609", "major_topic": false }, { "descriptor": "Injections", "descriptor_ui": "D007267", "major_topic": false }, { "descriptor": "Mental Recall", "descriptor_ui": "D011939", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Nervous System Physiological Phenomena", "descriptor_ui": "D009424", "major_topic": false }, { "descriptor": "Oligochaeta", "descriptor_ui": "D009835", "major_topic": false }, { "descriptor": "Protein Synthesis Inhibitors", "descriptor_ui": "D011500", "major_topic": false }, { "descriptor": "Retention, Psychology", "descriptor_ui": "D012153", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Time Perception", "descriptor_ui": "D013998", "major_topic": false }, { "descriptor": "Vibration", "descriptor_ui": "D014732", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Mar", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "151-157", "proceedings_title": null, "publisher": "", "title": "Neurobiology of learning and memory", "volume": "83", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Influence of mRNA and protein synthesis inhibitors on the long-term memory acquisition of classically conditioned earthworms.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although magnesium ion (Mg(2+)) is believed as an important factor for maintenance of normal neuron function, our understanding of its intracellular mobilization and physiological function is still not enough. We need to know the following mobilization mechanisms of Mg(2+) in neurons:Mg(2+) influx via ion channels, Mg(2+) release from intracellular pools, and Mg(2+) transporters located on cell membrane. In this short review, I show the recent findings of intracellular Mg(2+) release and also Na/Mg antiport on cell membrane in PC12 cells that have been revealed by fluorescent Mg imaging techniques.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16272617" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "87-90", "proceedings_title": null, "publisher": "", "title": "Clinical calcium", "volume": "15", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "[Recent Topics for magnesium mobilization in neurons].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Prolactin (PRL) is an important regulator of multiple biological functions, and the control of PRL expression integrates a wide spectrum of molecules throughout vertebrates. PRL-releasing peptide (PrRP) seems to be an essential stimulator of PRL transcription and secretion in teleost pituitary and peripheral organs. In the amphibious euryhaline mudskipper, the localization of mRNA levels of PrRP and PRL as well as their regulation during acclimation to different environments are closely related. The presence of PrRP-PRL axes in the peripheral organs might suggest an ancient history of this axis prior to the evolution of the hypothalamus-pituitary, and it is possible that the PrRP is an original and primary regulator of PRL. In the euryhaline fishes, the permeability of gut of seawater-acclimated fish is generally greater than that of the freshwater (FW)-acclimated fish. The modification in the epithelial cell renewal system may play an important role in regulation of the permeability. PRL induces the cell proliferation during FW acclimation, whereas cortisol stimulates both cell proliferation and apoptosis. Indeed, a large proportion of the various actions of PRL seem to be associated directly or indirectly with cell proliferation and/or apoptosis, which might be a primary function of PRL.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Waichiro", "last_name": "Godo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1196/annals.1327.023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15891023" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fishes", "descriptor_ui": "D005399", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Prolactin", "descriptor_ui": "D011388", "major_topic": false }, { "descriptor": "Thyrotropin-Releasing Hormone", "descriptor_ui": "D013973", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Apr", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "184-188", "proceedings_title": null, "publisher": "", "title": "Annals of the New York Academy of Sciences", "volume": "1040", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Prolactin: fishy tales of its primary regulator and function.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The role of intracellular magnesium ions is of high interest in the fields of pharmacology and cellular biology. To accomplish the dynamic and three-dimensional imaging of intracellular Mg2+, there is a strong desire for the development of optimized Mg2+ fluorescent probes. In this paper we describe the design, synthesis, and cellular application of the three novel Mg2+ fluorescent probes KMG-101, -103, and -104. The compounds of this series feature a charged beta-diketone as a binding site specific for Mg2+ and a fluorescein residue as the fluorophore that can be excited with an Ar+ laser such as is widely used in confocal scanning microscopy. This molecular design leads to an intensive off-on-type fluorescent response toward Mg2+ ions. The two fluorescent probes KMG-103 and -104 showed suitable dissociation constants (Kd,Mg2+ = 2 mM) and nearly a 10-fold fluorescence enhancement over the intracellular magnesium ion concentration range (0.1-6 mM), allowing high-contrast, sensitive, and selective Mg2+ measurements. For intracellular applications, the membrane-permeable probe KMG-104AM was synthesized and successfully incorporated into PC12 cells. Upon application of the mitochondria uncoupler FCCP to the probe-incorporated cells, the resulting increase in the free magnesium ion concentration could be followed over time. By using a confocal microscope, the intracellular 3D magnesium ion concentration distributions were satisfactorily observed.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Iwasawa", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Citterio", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Tokuno", "name": null }, { "creator_type": "author", "first_name": "Yoshiichiro", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja049624l" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15600336" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fluoresceins", "descriptor_ui": "D005452", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Spectrophotometry, Ultraviolet", "descriptor_ui": "D013056", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Dec 22", "date_precision": "day", "issue": "50", "normalized_date": "2004-12-22", "pages": "16353-16360", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "126", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Design and synthesis of highly sensitive and selective fluorescein-derived magnesium fluorescent probes and application to intracellular 3D Mg2+ imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "mRNA transport and local translation in the neuronal dendrite is implicated in the induction of synaptic plasticity. Recently, we cloned an RNA-interacting protein, SYNCRIP (heterogeneous nuclear ribonuclear protein Q1/NSAP1), that is suggested to be important for the stabilization of mRNA. We report here that SYNCRIP is a component of mRNA granules in rat hippocampal neurons. SYNCRIP was mainly found at cell bodies, but punctate expression patterns in the proximal dendrite were also seen. Time-lapse analysis in living neurons revealed that the granules labeled with fluorescent protein-tagged SYNCRIP were transported bi-directionally within the dendrite at approximately 0.05 microm/s. Treatment of neurons with nocodazole significantly inhibited the movement of green fluorescent protein-SYNCRIP-positive granules, indicating that the transport of SYNCRIP-containing granules is dependent on microtubules. The distribution of SYNCRIP-containing granules overlapped with that of dendritic RNAs and elongation factor 1alpha. SYNCRIP was also found to be co-transported with green fluorescent protein-tagged human staufen1 and the 3'-untranslated region of inositol 1,4,5-trisphosphate receptor type 1 mRNA. These results suggest that SYNCRIP is transported within the dendrite as a component of mRNA granules and raise the possibility that mRNA turnover in mRNA granules and the regulation of local protein synthesis in neuronal dendrites may involve SYNCRIP.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Fukatsu", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Natsume", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichiro", "last_name": "Iemura", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Ikegami", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Mikoshiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m409732200" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15475564" } }, "mesh": [ { "descriptor": "3' Untranslated Regions", "descriptor_ui": "D020413", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Calcium Channels", "descriptor_ui": "D015220", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Heterogeneous-Nuclear Ribonucleoproteins", "descriptor_ui": "D034441", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Inositol 1,4,5-Trisphosphate Receptors", "descriptor_ui": "D053496", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Nocodazole", "descriptor_ui": "D015739", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Proteome", "descriptor_ui": "D020543", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Receptors, Cytoplasmic and Nuclear", "descriptor_ui": "D018160", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Dec 17", "date_precision": "day", "issue": "51", "normalized_date": "2004-12-17", "pages": "53427-53434", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "279", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "An RNA-interacting protein, SYNCRIP (heterogeneous nuclear ribonuclear protein Q1/NSAP1) is a component of mRNA granule transported with inositol 1,4,5-trisphosphate receptor type 1 mRNA in neuronal dendrites.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Using pituitary adenylate cyclase-activating polypeptide (PACAP)-deficient mice, we investigated whether PACAP is involved in the intoxicating effects of ethanol. The structure of PACAP is highly conserved during evolution, and in Drosophila, loss-of-function mutations in a PACAP-like neuropeptide gene, amnesiac, result in impairment of memory retention and increased sensitivity to ethanol. In mice, PACAP deficiency is associated with impaired memory performance and hippocampal long-term potentiation (LTP), however, sensitivity to ethanol has not been well investigated. Here, we addressed this issue in our recently developed PACAP-deficient mice. Sleep time (duration of the loss of righting reflex) was markedly shortened in PACAP-deficient mice compared with wild-type, although latency to the loss of righting reflex was not different between the two groups. Ethanol-induced hypothermia in wild-type control mice was significantly reduced in PACAP-deficient mice. Blood ethanol levels were not different between the two groups, excluding the possibility of increased ethanol metabolism. Thus, in contrast to that in Drosophila, PACAP deficiency in mammals caused a reduced sensitivity to ethanol. However, in both cases, PACAP or amnesiac products are likely to play significant roles in modifying the intoxicating effects of ethanol.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.regpep.2004.05.017" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15518898" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Ethanol", "descriptor_ui": "D000431", "major_topic": false }, { "descriptor": "Hypnotics and Sedatives", "descriptor_ui": "D006993", "major_topic": false }, { "descriptor": "Hypothermia", "descriptor_ui": "D007035", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Nerve Growth Factors", "descriptor_ui": "D009414", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Neurotransmitter Agents", "descriptor_ui": "D018377", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Dec 15", "date_precision": "day", "issue": "1-3", "normalized_date": "2004-12-15", "pages": "95-98", "proceedings_title": null, "publisher": "", "title": "Regulatory peptides", "volume": "123", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Reduced hypothermic and hypnotic responses to ethanol in PACAP-deficient mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PACAP exerts multiple activities as a hormone and neurotransmitter, and has been proposed to play vital roles in a variety of neuronal functions. PACAP is also involved in insulin secretion from pancreatic beta-cells. Recently, we and other groups demonstrated that PACAP-deficient mice (PACAP(-/-)) are viable, but suffer from increased postnatal mortality. To ascertain whether this high mortality is rescued by overexpression of PACAP in peripheral tissue (such as pancreas), we performed a genetic cross between PACAP(-/-) and our recently developed transgenic mice overexpressing PACAP in pancreatic beta-cells; and then examined the survival rate of their F2 progeny. PACAP(-/-) mice were segregated into two groups based on mortality as well as body weight gain: PACAP(-/-) that survived >20 days of age with normal weight gain and PACAP(-/-) that died before 20 days with a marked weight loss. Kaplan-Meier survival analysis demonstrated that PACAP(-/-) mice and those carrying the PACAP transgene have similarly lower survival probability compared with their heterozygous littermates that served as positive controls. Further study using additional tissue-specific transgenic or knockout mouse models will be required to determine the causative defects underlying the high mortality of PACAP(-/-) mice.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Tomimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.regpep.2004.04.022" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15518906" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Crosses, Genetic", "descriptor_ui": "D003433", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Heterozygote", "descriptor_ui": "D006579", "major_topic": false }, { "descriptor": "Homozygote", "descriptor_ui": "D006720", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nerve Growth Factors", "descriptor_ui": "D009414", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Neurotransmitter Agents", "descriptor_ui": "D018377", "major_topic": false }, { "descriptor": "Pancreas", "descriptor_ui": "D010179", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Weight Gain", "descriptor_ui": "D015430", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Dec 15", "date_precision": "day", "issue": "1-3", "normalized_date": "2004-12-15", "pages": "155-159", "proceedings_title": null, "publisher": "", "title": "Regulatory peptides", "volume": "123", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Overexpression of PACAP in the pancreas failed to rescue early postnatal mortality in PACAP-null mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "There has been much focus recently on the possible functions of apelin, an endogenous ligand for the orphan G-protein-coupled receptor APJ, in cardiovascular and central nervous systems. We report a new function of apelin as a novel angiogenic factor in retinal endothelial cells. The retinal endothelial cell line RF/6A highly expressed both apelin and APJ transcripts, while human umbilical venous endothelial cells (HUVECs) only expressed apelin mRNA. In accordance with these observations, apelin at concentrations of 1 pM-1 microM significantly enhanced migration, proliferation, and capillary-like tube formation of RF/6A cells, but not those of HUVECs, whereas VEGF stimulates those parameters of both cell types. In vivo Matrigel plug assay for angiogenesis, the inclusion of 1 nM apelin in the Matrigel resulted in clear capillary-like formations with an increase of hemoglobin content in the plug. This is the first report showing that apelin is an angiogenic factor in retinal endothelial cells.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Michiya", "last_name": "Kakuda", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Hinuma", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2004.10.042" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15530405" } }, "mesh": [ { "descriptor": "Adipokines", "descriptor_ui": "D054392", "major_topic": false }, { "descriptor": "Angiogenesis Modulating Agents", "descriptor_ui": "D043924", "major_topic": false }, { "descriptor": "Angiogenic Proteins", "descriptor_ui": "D042501", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apelin", "descriptor_ui": "D000073861", "major_topic": false }, { "descriptor": "Capillaries", "descriptor_ui": "D002196", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Endothelium, Vascular", "descriptor_ui": "D004730", "major_topic": false }, { "descriptor": "Hemoglobins", "descriptor_ui": "D006454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neovascularization, Physiologic", "descriptor_ui": "D018919", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Umbilical Veins", "descriptor_ui": "D014471", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor A", "descriptor_ui": "D042461", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Dec 10", "date_precision": "day", "issue": "2", "normalized_date": "2004-12-10", "pages": "395-400", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "325", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Apelin is a novel angiogenic factor in retinal endothelial cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Resonance Raman (RR) evidence for structural linkage between the distal side of heme pocket and the signaling domain of an oxygen sensing hemoprotein, HemAT-Bs, is reported. The band-fitting analyses of the RR spectra in the Fe-O2 stretching (nuFe-O2) region revealed the presence of three conformers with nuFe-O2 at 554, 566, and 572 cm-1, which reflect different H-bond strengths on the bound O2 molecule. While recent X-ray analysis for CN--bound HemAT-Bs suggested the importance of Thr95 and Tyr70, the species with the strongest H-bond (554 cm-1) was deleted in the T95A mutant and also by removal of the linker and signal domains; however, the Y70F mutant maintained the same three conformers. A scheme for specific O2 sensing and signaling mechanism is discussed.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takehiro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Shiro", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Shigetoshi", "last_name": "Aono", "name": null }, { "creator_type": "author", "first_name": "Teizo", "last_name": "Kitagawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja046896f" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15547976" } }, "mesh": [ { "descriptor": "Bacillus subtilis", "descriptor_ui": "D001412", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Heme-Binding Proteins", "descriptor_ui": "D000081062", "major_topic": false }, { "descriptor": "Hemeproteins", "descriptor_ui": "D006420", "major_topic": false }, { "descriptor": "Mutagenesis", "descriptor_ui": "D016296", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Oxygen Isotopes", "descriptor_ui": "D010103", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Nov 24", "date_precision": "day", "issue": "46", "normalized_date": "2004-11-24", "pages": "15000-15001", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "126", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Oxygen-sensing mechanism of HemAT from Bacillus subtilis: a resonance Raman spectroscopic study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cAMP-responsive transcription factor, CREB, is required for formation of long-term memory (LTM) in Drosophila melanogaster and regulates transcription of a circadian clock gene, period (per). Involvement of CREB both in LTM and circadian rhythm raises the possibility that per also plays a role in LTM. Assaying the experience-dependent courtship inhibition in male flies as a measure for LTM, we show here that per mutants are defective in LTM formation. This defect was rescued by induction of a wild-type per transgene in a per-null mutant, and overexpression of per enhanced LTM formation in the wild-type background. Furthermore, we found that synaptic transmission through per-expressing cells is most likely to be required during retrieval of LTM. In contrast, mutations in other clock genes (timeless, dClock, and cycle) did not affect LTM formation. Thus, independent of the core oscillator of circadian clock, per plays a key role in LTM formation.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Takaomi", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kitamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kidokoro", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.0401472101" }, "pmcid": { "normalized": "PMC528738" }, "pmid": { "normalized": "15522971" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Cyclic AMP Response Element-Binding Protein", "descriptor_ui": "D017362", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Dynamins", "descriptor_ui": "D034281", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Genes, Insect", "descriptor_ui": "D017344", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Period Circadian Proteins", "descriptor_ui": "D056950", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Sexual Behavior, Animal", "descriptor_ui": "D012726", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Trans-Activators", "descriptor_ui": "D015534", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Nov 9", "date_precision": "day", "issue": "45", "normalized_date": "2004-11-09", "pages": "16058-16063", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "101", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "A clock gene, period, plays a key role in long-term memory formation in Drosophila.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Toll-like receptor (TLR) activation is central to immunity, wherein the activation of the TLR9 subfamily members TLR9 and TLR7 results in the robust induction of type I IFNs (IFN-alpha/beta) by means of the MyD88 adaptor protein. However, it remains unknown how the TLR signal \"input\" can be processed through MyD88 to \"output\" the induction of the IFN genes. Here, we demonstrate that the transcription factor IRF-7 interacts with MyD88 to form a complex in the cytoplasm. We provide evidence that this complex also involves IRAK4 and TRAF6 and provides the foundation for the TLR9-dependent activation of the IFN genes. The complex defined in this study represents an example of how the coupling of the signaling adaptor and effector kinase molecules together with the transcription factor regulate the processing of an extracellular signal to evoke its versatile downstream transcriptional events in a cell. Thus, we propose that this molecular complex may function as a cytoplasmic transductional-transcriptional processor.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenya", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Yanai", "name": null }, { "creator_type": "author", "first_name": "Tatsuaki", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Negishi", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Nobutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Takaoka", "name": null }, { "creator_type": "author", "first_name": "Wen-Chen", "last_name": "Yeh", "name": null }, { "creator_type": "author", "first_name": "Tadatsugu", "last_name": "Taniguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.0406933101" }, "pmcid": { "normalized": "PMC523464" }, "pmid": { "normalized": "15492225" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, Differentiation", "descriptor_ui": "D000943", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Energy Transfer", "descriptor_ui": "D004735", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interferon Regulatory Factor-7", "descriptor_ui": "D050839", "major_topic": false }, { "descriptor": "Interferon-alpha", "descriptor_ui": "D016898", "major_topic": false }, { "descriptor": "Membrane Glycoproteins", "descriptor_ui": "D008562", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myeloid Differentiation Factor 88", "descriptor_ui": "D053594", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false }, { "descriptor": "Receptors, Immunologic", "descriptor_ui": "D011971", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Toll-Like Receptor 7", "descriptor_ui": "D051199", "major_topic": false }, { "descriptor": "Toll-Like Receptor 9", "descriptor_ui": "D051217", "major_topic": false }, { "descriptor": "Toll-Like Receptors", "descriptor_ui": "D051193", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": true }, { "descriptor": "Transduction, Genetic", "descriptor_ui": "D014161", "major_topic": true } ], "publication": { "conference_name": null, "date": "2004 Oct 26", "date_precision": "day", "issue": "43", "normalized_date": "2004-10-26", "pages": "15416-15421", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "101", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Detection of chelatable zinc (Zn(2+)) in biological studies has attracted much attention recently, because chelatable Zn(2+) plays important roles in many biological systems. Lanthanide complexes (Eu(3+), Tb(3+), etc.) have excellent spectroscopic properties for biological applications, such as long luminescence lifetimes of the order of milliseconds, a large Stoke's shift of >200 nm, and high water solubility. Herein, we present the design and synthesis of a novel lanthanide sensor molecule, [Eu-7], for detecting Zn(2+). This europium (Eu(3+)) complex employs a quinolyl ligand as both a chromophore and an acceptor for Zn(2+). Upon addition of Zn(2+) to a solution of [Eu-7], the luminescence of Eu(3+) is strongly enhanced, with high selectivity for Zn(2+) over other biologically relevant metal cations. One of the important advantages of [Eu-7] is that this complex can be excited with longer excitation wavelengths (around 340 nm) as compared with previously reported Zn(2+)-sensitive luminescent lamthanide sensors, whose excitation wavelength is at too high an energy level for biological applications. The usefulness of [Eu-7] for monitoring Zn(2+) changes in living HeLa cells was confirmed. This novel Zn(2+)-selective luminescent lanthanide chemosensor [Eu-7]should be an excellent lead compound for the development of a range of novel luminescent lanthanide chemosensors for biological applications.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja0469333" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15453781" } }, "mesh": [ { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Cations, Divalent", "descriptor_ui": "D002413", "major_topic": false }, { "descriptor": "Chelating Agents", "descriptor_ui": "D002614", "major_topic": false }, { "descriptor": "Ethylenediamines", "descriptor_ui": "D005029", "major_topic": false }, { "descriptor": "Europium", "descriptor_ui": "D005063", "major_topic": false }, { "descriptor": "Gadolinium", "descriptor_ui": "D005682", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Organometallic Compounds", "descriptor_ui": "D009942", "major_topic": false }, { "descriptor": "Quinolines", "descriptor_ui": "D011804", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Spectrophotometry, Ultraviolet", "descriptor_ui": "D013056", "major_topic": false }, { "descriptor": "Zinc", "descriptor_ui": "D015032", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Oct 6", "date_precision": "day", "issue": "39", "normalized_date": "2004-10-06", "pages": "12470-12476", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "126", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a zinc ion-selective luminescent lanthanide chemosensor for biological applications.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The prolonged sensitization of pain transmission after nerve injury by increasing excitability of spinal neurons and thereby promoting repair is an adaptive response of the body. The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is widely distributed in the nervous system and implicated in neurotransmission, neural plasticity, and neurotrophic actions. Although PACAP is distributed in the spinal cord and dorsal root ganglia, a role of PACAP in pain responses remains essentially unknown. Here we show that mice lacking the PACAP gene (PACAP-/-) did not exhibit inflammatory pain induced by intraplantar injection of carrageenan or neuropathic pain induced by L5 spinal nerve transection, whereas they did retain normal nociceptive responses. Intrathecal administration of NMDA induced mechanical allodynia in wild-type mice, but not in PACAP-/- mice. The NMDA-induced allodynia in PACAP-/- mice was reproduced by simultaneous intrathecal injection of PACAP with NMDA. Concomitant with the increase in PACAP immunoreactivity after nerve injury, NADPH-dependent nitric oxide synthase (NOS) activity visualized by NADPH diaphorase histochemistry markedly increased in the superficial layer of the spinal cord of wild-type mice, which was not observed in PACAP-/- mice. Simultaneous addition of PACAP and NMDA caused translocation of neuronal NOS from the cytosol to the membrane and stimulated NO production in vitro. These results demonstrate that PACAP might promote the functional coupling of neuronal NOS to NMDA receptors for both inflammatory and neuropathic pain to occur.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Tamaki", "last_name": "Mabuchi", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Emiko", "last_name": "Okuda-Ashitaka", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Tadatoshi", "last_name": "Muratani", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.0983-04.2004" }, "pmcid": { "normalized": "PMC6729777" }, "pmid": { "normalized": "15317855" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "N-Methylaspartate", "descriptor_ui": "D016202", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Nitric Oxide Synthase", "descriptor_ui": "D019001", "major_topic": false }, { "descriptor": "Nitric Oxide Synthase Type I", "descriptor_ui": "D052248", "major_topic": false }, { "descriptor": "Pain", "descriptor_ui": "D010146", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Aug 18", "date_precision": "day", "issue": "33", "normalized_date": "2004-08-18", "pages": "7283-7291", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "24", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Pituitary adenylate cyclase-activating polypeptide is required for the development of spinal sensitization and induction of neuropathic pain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chemokines and their receptors play key roles in leukocyte trafficking and are also implicated in cancer metastasis to specific organs. Here we show that mouse B16F10 melanoma cells constitutively express chemokine receptor CXCR3, and that its ligands CXCL9/Mig, CXCL10/IP-10, and CXCL11/I-TAC induce cellular responses in vitro, such as actin polymerization, migration, invasion, and cell survival. To determine whether CXCR3 could play a role in metastasis to lymph nodes (LNs), we constructed B16F10 cells with reduced CXCR3 expression by antisense RNA and investigated their metastatic activities after s.c. inoculations to syngeneic hosts, C57BL/6 mice. The metastatic frequency of these cells to LNs was markedly reduced to approximately 15% (P < 0.05) compared with the parental or empty vector-transduced cells. On the other hand, pretreatment of mice with complete Freund's adjuvant increased the levels of CXCL9 and CXCL10 in the draining LNs, which caused 2.5-3.0-fold increase (P < 0.05) in the metastatic frequency of B16F10 cells to the nodes with much larger foci. Importantly, such a stimulation of metastasis was largely suppressed when CXCR3 expression in B16F10 cells was reduced by antisense RNA or when mice were treated with specific antibodies against CXCL9 and CXCL10. We also demonstrate that CXCR3 is expressed on several human melanoma cell lines as well as primary human melanoma tissues (5 of 9 samples tested). These results suggest that CXCR3 inhibitors may be promising therapeutic agents for treatment of LN metastasis, including that of melanoma.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Sakashita", "name": null }, { "creator_type": "author", "first_name": "Arimichi", "last_name": "Takabayashi", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Yamaoka", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Manabe", "name": null }, { "creator_type": "author", "first_name": "Kayo", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Nagahiro", "last_name": "Minato", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Makoto Mark", "last_name": "Taketo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/0008-5472.can-03-1757" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15173015" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Chemokine CXCL10", "descriptor_ui": "D054357", "major_topic": false }, { "descriptor": "Chemokine CXCL9", "descriptor_ui": "D054370", "major_topic": false }, { "descriptor": "Chemokines, CXC", "descriptor_ui": "D019743", "major_topic": false }, { "descriptor": "Cytoskeleton", "descriptor_ui": "D003599", "major_topic": false }, { "descriptor": "Focal Adhesions", "descriptor_ui": "D022001", "major_topic": false }, { "descriptor": "Freund's Adjuvant", "descriptor_ui": "D005620", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": false }, { "descriptor": "Lymphatic Metastasis", "descriptor_ui": "D008207", "major_topic": false }, { "descriptor": "Melanoma", "descriptor_ui": "D008545", "major_topic": false }, { "descriptor": "Melanoma, Experimental", "descriptor_ui": "D008546", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Receptors, Chemokine", "descriptor_ui": "D019707", "major_topic": false }, { "descriptor": "Receptors, CXCR3", "descriptor_ui": "D054367", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Jun 1", "date_precision": "day", "issue": "11", "normalized_date": "2004-06-01", "pages": "4010-4017", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "64", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Pivotal role of CXCR3 in melanoma cell metastasis to lymph nodes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mechanisms linked to the neuritogenic effect of PACAP acting in synergy with NGF were analyzed in PC12 cells. Recently, we have shown that PACAP synergizes with NGF to stimulate PACAP gene transcription and neurite outgrowth, differentially dependent on both the ERK1/2 and p38 MAP kinase pathways in PC12 cells. This suggests that PACAP modulates mitogen signaling pathways governing cell differentiation, in part through MAP kinase activation and an autocrine mechanism. Here, we studied the mechanism of the underlying neuritogenic actions of PACAP. PACAP induced transient activation of Rac1, a small GTPase involved in neurite outgrowth, in a PI3-kinase-independent manner, and stimulated accumulation of active Rac1 at filamentous actin-rich protrusions on the cell surface to induce subsequent neurite formation. PACAP had no additional effect on the activity of Rac1 beyond the effect of NGF and failed to activate Ras or Cdc42. By contrast, simultaneous treatment with PACAP and NGF acts in synergy to induce prolonged activation of ERK1/2. These results indicate for the first time that PACAP induces activation of Rac1 associated with neurite outgrowth and suggest that the synergistic effect of PACAP and NGF on neurite extension is due to enhanced activation of ERK1/2.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Katoh", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Negishi", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.molbrainres.2003.12.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15046862" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Surface Extensions", "descriptor_ui": "D022081", "major_topic": false }, { "descriptor": "Drug Synergism", "descriptor_ui": "D004357", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": false }, { "descriptor": "Nerve Growth Factor", "descriptor_ui": "D020932", "major_topic": false }, { "descriptor": "Neurites", "descriptor_ui": "D016501", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "rac1 GTP-Binding Protein", "descriptor_ui": "D020830", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Apr 7", "date_precision": "day", "issue": "1-2", "normalized_date": "2004-04-07", "pages": "18-26", "proceedings_title": null, "publisher": "", "title": "Brain research. Molecular brain research", "volume": "123", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "PACAP activates Rac1 and synergizes with NGF to activate ERK1/2, thereby inducing neurite outgrowth in PC12 cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Washitake", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Sakae", "last_name": "Uemura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.200352949" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15054795" } }, "mesh": [], "publication": { "conference_name": null, "date": "2004 Mar 26", "date_precision": "day", "issue": "14", "normalized_date": "2004-03-26", "pages": "1857-1860", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "43", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Polyaddition and polycondensation reactions of (2-furyl)carbenoid as step-growth polymerization strategies: synthesis of furylcyclopropane- and furfurylidene-containing polymers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The pituitary adenylate cyclase–activating polypeptide (PACAP) is a neuropeptide of the vasoactive intestinal peptide/secretin/glucagon superfamily. Studies in two related patients with a partial trisomy 18p revealed three copies of the PACAP gene and elevated PACAP concentrations in plasma. The patients suffer from severe mental retardation and have a bleeding tendency with mild thrombocytopenia, and their fibroblasts show increased PACAP mRNA levels. The PACAP receptor (vasoactive intestinal peptide/pituitary adenylate cyclase–activating peptide receptor 1 [VPAC1]) in platelets and fibroblasts is coupled to adenylyl cyclase activation. Accordingly, we found increased basal cAMP levels in patients’ platelets and fibroblasts, providing a basis for the reduced platelet aggregation in these patients. Megakaryocyte-specific transgenic overexpression of PACAP in mice correspondingly increased PACAP release from platelets, reduced platelet activation, and prolonged the tail bleeding time. In contrast, the PACAP antagonist PACAP(6-38) or a monoclonal PACAP antibody enhanced the collagen-induced aggregation of normal human platelets, and in PACAP knockout mice, an increased platelet sensitivity toward collagen was found. Thus, we found that PACAP modulates platelet function and demonstrated what we believe to be the first hemostatic defect associated with PACAP overexpression; our study suggests the therapeutic potential to manage arterial thrombosis or bleeding by administration of PACAP mimetics or inhibitors, respectively.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kathleen", "last_name": "Freson", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Chantal", "last_name": "Thys", "name": null }, { "creator_type": "author", "first_name": "Christine", "last_name": "Wittevrongel", "name": null }, { "creator_type": "author", "first_name": "Sophie", "last_name": "Danloy", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Tomiyama", "name": null }, { "creator_type": "author", "first_name": "Jos", "last_name": "Vermylen", "name": null }, { "creator_type": "author", "first_name": "Marc F.", "last_name": "Hoylaerts", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Chris", "last_name": "Van Geet", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci200419252" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15067323" } }, "mesh": [ { "descriptor": "Adenylyl Cyclases", "descriptor_ui": "D000262", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Platelets", "descriptor_ui": "D001792", "major_topic": false }, { "descriptor": "Chromosomes, Human, Pair 18", "descriptor_ui": "D002887", "major_topic": false }, { "descriptor": "Chromosomes, Human, Pair 20", "descriptor_ui": "D002890", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intellectual Disability", "descriptor_ui": "D008607", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Pedigree", "descriptor_ui": "D010375", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Platelet Activation", "descriptor_ui": "D015539", "major_topic": false }, { "descriptor": "Translocation, Genetic", "descriptor_ui": "D014178", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Mar 15", "date_precision": "day", "issue": "6", "normalized_date": "2004-03-15", "pages": "905-912", "proceedings_title": null, "publisher": "", "title": "Journal of Clinical Investigation", "volume": "113", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "The pituitary adenylate cyclase–activating polypeptide is a physiological inhibitor of platelet activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The reaction of alkenes with conjugated ene-yne-ketones, such as 1-benzoyl-2-ethynylcycloalkenes, with a catalytic amount of Cr(CO)(5)(THF) gave 5-phenyl-2-furylcyclopropane derivatives in good yields. The key intermediate of this cyclopropanation is a (2-furyl)carbene complex generated by a nucleophilic attack of carbonyl oxygen to an internal alkyne carbon in pi-alkyne complex or sigma-vinyl cationic complex. A wide range of late transition metal compounds, such as [RuCl(2)(CO)(3)](2), [RhCl(cod)](2), [Rh(OAc)(2)](2), PdCl(2), and PtCl(2), also catalyzes the cyclopropanation of alkenes with ene-yne-ketones effectively. When the reactions were carried out with dienes as a carbene acceptor, the more substituted or more electron-rich alkene moiety was selectively cyclopropanated with the (2-furyl)carbenoid intermediate.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Yokoi", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Washitake", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Sakae", "last_name": "Uemura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jo0352732" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "14987011" } }, "mesh": [], "publication": { "conference_name": null, "date": "2004 Mar 5", "date_precision": "day", "issue": "5", "normalized_date": "2004-03-05", "pages": "1557-1564", "proceedings_title": null, "publisher": "", "title": "The Journal of organic chemistry", "volume": "69", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Catalytic cyclopropanation of alkenes via (2-furyl)carbene complexes from 1-benzoyl-cis-1-buten-3-yne with transition metal compounds.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although spatially restricted Ca2+ release from the endoplasmic reticulum (ER) through intracellular Ca2+ channels plays important roles in various neuronal activities, the accurate distribution and dynamics of ER in the dendrite of living neurons still remain unknown. To elucidate these, we expressed fluorescent protein-tagged ER proteins in cultured mouse hippocampal neurons, and monitored their movements using time-lapse microscopy. We report here that a sub-compartment of ER forms in relatively large vesicles that are capable, similarly to the reticular ER, of taking up and releasing Ca2+. The vesicular sub-compartment of ER moved rapidly along the dendrites in both anterograde and retrograde directions at a velocity of 0.2-0.3 microm/second. Depletion of microtubules, overexpression of dominant-negative kinesin and kinesin depletion by antisense DNA reduced the number and velocity of the moving vesicles, suggesting that kinesin may drive the transport of the vesicular sub-compartment of ER along microtubules in the dendrite. Rapid transport of the Ca2+-releasable sub-compartment of ER might contribute to rapid supply of fresh ER proteins to the distal part of the dendrite, or to the spatial regulation of intracellular Ca2+ signaling.", "classifications": [ { "id": "A03-1", "label": "Planned Research A03-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bannai", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Mitsuharu", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Mikoshiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/jcs.00854" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "14676272" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Compartmentation", "descriptor_ui": "D002451", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "DNA, Antisense", "descriptor_ui": "D016373", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Kinesins", "descriptor_ui": "D016547", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Jan 15", "date_precision": "day", "issue": "Pt 2", "normalized_date": "2004-01-15", "pages": "163-175", "proceedings_title": null, "publisher": "", "title": "Journal of cell science", "volume": "117", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Kinesin dependent, rapid, bi-directional transport of ER sub-compartment in dendrites of hippocampal neurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nitric oxide (NO) is a vital molecule contributing to numerous physiological phenomena in various biological systems. To investigate the physiological role of NO, a range of NO-specific electrodes allowing direct and continuous NO measurement have been developed for in vitro and in vivo NO detection. A microcoaxial electrode has also been developed for the measurement of real-time NO levels. Because the working and reference electrodes in this device are situated close together, the microcoaxial electrode is considered to be ideal for the measurement of local NO concentrations with high spatial resolution. The microcoaxial electrode has been successfully applied to the real-time measurement of NO in endothelial cells, thereby demonstrating its effectiveness as an NO-specific electrode. In this chapter, we describe our experimental protocol for performing real-time NO measurements that was developed during physiological experiments using the microcoaxial electrode.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiichiro", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Hirosuke", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Tanishita", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1385/1-59259-807-2:035" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15199235" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Electrochemistry", "descriptor_ui": "D004563", "major_topic": false }, { "descriptor": "Electrodes", "descriptor_ui": "D004566", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "S-Nitroso-N-Acetylpenicillamine", "descriptor_ui": "D026423", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004", "date_precision": "year", "issue": "", "normalized_date": "2004", "pages": "35-43", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "279", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "In vivo nitric oxide measurements using a microcoaxial electrode.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Adult bone marrow contains mesenchymal stem cells (bone marrow-derived mesenchymal stem cells; BMSCs) which contribute to the generation of mesenchymal tissue such as bone, cartilage, muscle and adipose. However, using bone marrow as a source of stem cells has the limitation of a low cell number. An alternate source of adult stem cells that could be obtained in large quantities, under local anesthesia, with minimal discomfort would be advantageous. Human adipose tissue obtained by liposuction was processed to obtain a fibroblast-like population of cells or adipose tissue-derived stromal cells (ATSCs). In this study, we compared the osteogenic differentiation of ATSCs with that of BMSCs. Both cell types were cultured in atelocollagen honeycomb-shaped scaffolds with a membrane seal (ACHMS scaffold) for three-dimensional culturing in a specific osteogenic induction medium. Optimal osteogenic differentiation in both cell types, as determined by alkaline phosphatase cytochemistry, secretion of osteocalcin, mineral (calcium phosphate) deposition and scanning electron microscopy, was obtained with the same three-dimensional culture. Furthermore, osteoblastic lining in vivo was examined using ATSC-seeded or BMSC-seeded scaffolds in nude mice. The present results show that ATSCs have a similar ability to differentiate into osteoblasts to that of BMSCs.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Hidemi", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Masuoka", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Takemi", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Bonpei", "last_name": "Takase", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Ishizuka", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Kyosuke", "last_name": "Fujikawa", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1159/000081088" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15550755" } }, "mesh": [ { "descriptor": "Adipocytes", "descriptor_ui": "D017667", "major_topic": false }, { "descriptor": "Adipose Tissue", "descriptor_ui": "D000273", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Alkaline Phosphatase", "descriptor_ui": "D000469", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mesenchymal Stem Cells", "descriptor_ui": "D059630", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Osteoblasts", "descriptor_ui": "D010006", "major_topic": false }, { "descriptor": "Osteocalcin", "descriptor_ui": "D015675", "major_topic": false }, { "descriptor": "Osteogenesis", "descriptor_ui": "D010012", "major_topic": true }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Stromal Cells", "descriptor_ui": "D017154", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004", "date_precision": "year", "issue": "1", "normalized_date": "2004", "pages": "2-12", "proceedings_title": null, "publisher": "", "title": "Cells, tissues, organs", "volume": "178", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Osteogenic potential of human adipose tissue-derived stromal cells as an alternative stem cell source.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) is an intraislet neuropeptide and shares insulinotropic and insulin-sensitizing properties with glucagon-like peptide-1 (GLP-1); however, the pathophysiological significance of PACAP in diabetes remains largely unknown. To assess this, we crossed our recently developed transgenic mice overexpressing PACAP in pancreatic beta-cells (Tg/+), with lethal yellow agouti (KKA(y)) mice (A(y)/+), a genetic model for obesity-diabetes, and examined the metabolic and morphological phenotypes of F(1) animals. Tg/+ mice with the A(y) allele (Tg/+:A(y)/+) developed maturity-onset obesity and diabetes associated with hyperglycemia, hyperlipidemia, and hyperphagia, similar to those of A(y)/+ mice, but hyperinsulinemia was significantly ameliorated in Tg/+:A(y)/+ mice. Although A(y)/+ mice exhibited a marked increase in islet mass resulting from hyperplasia and hypertrophy, this increase was significantly attenuated in Tg/+:A(y)/+ mice. Size frequency distribution analysis revealed that the very large islets comprising one-fourth of islets of A(y)/+ mice were selectively reduced in Tg/+:A(y)/+ mice. Because functional defects have been demonstrated in the large islets of obese animal models, together these findings suggest that PACAP regulates hyperinsulinemia and the abnormal increase in islet mass that occurs during the diabetic process.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shuhei", "last_name": "Tomimoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Kyohei", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kawabata", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hamagami", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Jun-Ichiro", "last_name": "Miyagawa", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1124/jpet.103.062919" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "14742740" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Glucose", "descriptor_ui": "D001786", "major_topic": false }, { "descriptor": "Body Weight", "descriptor_ui": "D001835", "major_topic": false }, { "descriptor": "Eating", "descriptor_ui": "D004435", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glucose Tolerance Test", "descriptor_ui": "D005951", "major_topic": false }, { "descriptor": "Hyperinsulinism", "descriptor_ui": "D006946", "major_topic": false }, { "descriptor": "Hyperplasia", "descriptor_ui": "D006965", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Islets of Langerhans", "descriptor_ui": "D007515", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Triglycerides", "descriptor_ui": "D014280", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 May", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "796-803", "proceedings_title": null, "publisher": "", "title": "The Journal of pharmacology and experimental therapeutics", "volume": "309", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Overexpression of pituitary adenylate cyclase-activating polypeptide in islets inhibits hyperinsulinemia and islet hyperplasia in agouti yellow mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Simultaneous fluorescent imaging technique with several indicators is a powerful bio-imaging tool for a comprehensive survey about molecular functions in living cells. There are several interactions between Mg(2+) and Ca(2+) such as a counter transport or a competition at binding sites of divalent cation. To measure Mg-Ca images simultaneously, indicators with high selectivity to each divalent cation and multi-color fluorescent imaging system are essential. Here we introduce a setup for Mg-Ca fluorescent imaging we construct, and some reports about Mg-Ca imaging.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15577095" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Binding, Competitive", "descriptor_ui": "D001667", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Physiological Phenomena", "descriptor_ui": "D002468", "major_topic": false }, { "descriptor": "Cells", "descriptor_ui": "D002477", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "41-44", "proceedings_title": null, "publisher": "", "title": "Clinical calcium", "volume": "14", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "[Simultaneous Fluorescent Imaging of Mg2+ and Ca2+].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We immunohistochemically studied expressions of inducible heat shock protein 70 (HSP 72) and apoptosis of corneas ablated with an ArF excimer laser. The temperature of corneal surfaces and laser-induced optical emission spectra were measured in real time as direct physical parameters related to the ablation mechanism. To the best of the authors' knowledge, there have been no experimental studies regarding the influence of physical parameters directly related to the ablation mechanism on corneal reactions at the cell level after laser ablation. The expression of HSP 72 was mainly localized in the regenerative epithelium, which was confirmed to be caused by laser ablation. The HSP 72 positive cell ratios had a correlation with thermal dose, which was derived from the measured time courses of temperature. Expressions of both HSP 72 and apoptosis depended on the thermal dose and elapsed time after ablation. HSP 72 and apoptosis could be seen up to a few hundred micrometers into the stroma, only at a fluence with an optical breakdown emission. This could have been caused by shock waves induced by the optical breakdown.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tsunenori", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kikuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1117/1.1630605" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "14715072" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Argon", "descriptor_ui": "D001128", "major_topic": false }, { "descriptor": "Body Temperature", "descriptor_ui": "D001831", "major_topic": false }, { "descriptor": "Cornea", "descriptor_ui": "D003315", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Radiation", "descriptor_ui": "D004307", "major_topic": false }, { "descriptor": "Fluorides", "descriptor_ui": "D005459", "major_topic": false }, { "descriptor": "Heat-Shock Proteins", "descriptor_ui": "D006360", "major_topic": false }, { "descriptor": "HSP72 Heat-Shock Proteins", "descriptor_ui": "D050884", "major_topic": false }, { "descriptor": "Laser Coagulation", "descriptor_ui": "D017075", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Radiation Dosage", "descriptor_ui": "D011829", "major_topic": false }, { "descriptor": "Thermography", "descriptor_ui": "D013817", "major_topic": false }, { "descriptor": "Tissue Distribution", "descriptor_ui": "D014018", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Jan-Feb", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "187-192", "proceedings_title": null, "publisher": "", "title": "Journal of biomedical optics", "volume": "9", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Assessment of expressions of heat shock protein (HSP 72) and apoptosis after ArF excimer laser ablation of the cornea.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We measured and compared the oxygen partial pressure (pO(2)) profiles in experimental tumors after irradiation with carbon ions and with X-rays. The NFSa fibrosarcomas grown in the hind legs of C3H male mice received isoeffect single doses of carbon ions or X-rays. Coaxial oxygen microelectrodes of high spatial resolution were inserted into the tumor with 20 microm steps by a computerized micromanipulator. The number of pO(2) peaks that reached 15 mmHg were at least 0.45 per 3,000 microm in unirradiated tumors and significantly increased to 1.55 per 3,000 microm as early as day 1 of carbon-ion irradiation (p < 0.001). The tumors that received X-ray irradiation also significantly increased pO(2) peaks, but as late as day 3. The time course of pO(2) peak appearance in the present study coincides with a previous report where reoxygenation was measured by paired growth delay assay. The pO(2) peaks appeared selectively in peripheral regions of X-ray irradiated tumors, but they appeared rather homogeneously in the tumor after carbon-ion irradiation. It is concluded that carbon-ion irradiation reoxygenated the NFSa fibrosarcomas earlier in time and deeper in space than the X-ray irradiation did.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Fukawa", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Takematsu", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Hirosuke", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Tanishita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1269/jrr.45.303" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15304974" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carbon", "descriptor_ui": "D002244", "major_topic": true }, { "descriptor": "Cell Hypoxia", "descriptor_ui": "D015687", "major_topic": false }, { "descriptor": "Fibrosarcoma", "descriptor_ui": "D005354", "major_topic": false }, { "descriptor": "Heavy Ions", "descriptor_ui": "D020450", "major_topic": true }, { "descriptor": "Linear Energy Transfer", "descriptor_ui": "D018499", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C3H", "descriptor_ui": "D008809", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Oxygen Consumption", "descriptor_ui": "D010101", "major_topic": false }, { "descriptor": "Relative Biological Effectiveness", "descriptor_ui": "D012062", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false }, { "descriptor": "X-Rays", "descriptor_ui": "D014965", "major_topic": true } ], "publication": { "conference_name": null, "date": "2004 Jun", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "303-308", "proceedings_title": null, "publisher": "", "title": "Journal of radiation research", "volume": "45", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Differences in pO2 peaks of a murine fibrosarcoma between carbon-ion and X-ray irradiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Role of sensory feedback to motor pattern activity concerning locomotion in the earthworm, Eisenia fetida, was investigated. We have previously reported that bath application of octopamine induces fictive locomotion in the earthworm. In this study, we have examined the role of sensory feedback during fictive locomotion by analyzing electrical activities from the cut end and intact first lateral nerves of the ventral nerve cord (VNC). From the cut end recordings, motor activity associated with fictive locomotion was measured. A mixture of sensory and motor activities was measured from the intact first lateral nerve using en passant recordings, and sensory activity was separated by subtraction of the cut end recording (mainly motor activities) from the intact first lateral nerve recording. We estimated the effect of sensory feedback from the earthworm body wall by comparing recordings that made when the preparation was in-contact with a substrate or suspended above it. Motor pattern activities and the coefficient of variation for inter-spike-interval of motor outputs were increased under suspended conditions during circular muscle contraction. These results indicate that sensory feedback modulates the pattern of motor activity in the earthworm during locomotion.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Toshinobu", "last_name": "Shimoi", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Yoshiichiro", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2004.01.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15041199" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Electrophysiology", "descriptor_ui": "D004594", "major_topic": false }, { "descriptor": "Feedback, Physiological", "descriptor_ui": "D025461", "major_topic": false }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": false }, { "descriptor": "Motor Neurons", "descriptor_ui": "D009046", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Neurons, Afferent", "descriptor_ui": "D009475", "major_topic": false }, { "descriptor": "Oligochaeta", "descriptor_ui": "D009835", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "457-462", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "48", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Modulation of motor patterns by sensory feedback during earthworm locomotion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PACAP belongs to the vasoactive intestinal polypeptide (VIP)/secretin/glucagon superfamily, which also includes glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). PACAP shares an insulinotropic property with the latter two peptides; for instance, it stimulates insulin secretion from islets in a glucose-dependent manner at femtomolar concentrations. However, the pathophysiological significance of PACAP in diabetes remains largely unknown, for several reasons, including a lack of low-molecular weight PACAP ligands and a lack of suitable animal models. As an approach to understanding PACAP's pancreatic function in vivo, we have recently generated transgenic mice overexpressing PACAP in islet beta cells under the control of human insulin promoter (Tg mice). As a consequence, it has been demonstrated that in addition to stimulating insulin secretion, PACAP has long-term effects on pancreatic endocrine cells, including proliferation of beta cells during streptozotocin-induced diabetes development as well as aging. These observations provide additional information to support the possibility that drugs associated with PACAP-signaling pathways might be of therapeutic value for the treatment of diabetes. In this review, we briefly summarize these previous studies using Tg mice and also focus on the physiological and pathophysiological roles mediated by PACAP during diabetes development.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Shuhei", "last_name": "Tomimoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/fpj.123.261" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15056941" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Diabetes Mellitus", "descriptor_ui": "D003920", "major_topic": false }, { "descriptor": "Drug Design", "descriptor_ui": "D015195", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": true }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Hypoglycemic Agents", "descriptor_ui": "D007004", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Insulin Secretion", "descriptor_ui": "D000078790", "major_topic": false }, { "descriptor": "Islets of Langerhans", "descriptor_ui": "D007515", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "261-266", "proceedings_title": null, "publisher": "", "title": "Nihon yakurigaku zasshi. Folia pharmacologica Japonica", "volume": "123", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "[Transgenic mice overexpressing PACAP in pancreatic beta-cells: acute and chronic effects on insulin and glucose homeostasis].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that functions as not only a neurotransmitter/neuromodulator but also a neurotrophic factor. To assess the roles of endogenous PACAP, several groups including ours have independently produced mice with targeted mutations in the PACAP gene. The phenotypes of the mutant mice both confirm and extend our knowledge of the physiological roles of PACAP in the central nervous system as well as many peripheral organs. In this review, we briefly summarize the roles of PACAP in higher brain function, which have been proposed by the studies using the mutant mice as well as histological and pharmacological approaches.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/fpj.123.274" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15056943" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Long-Term Potentiation", "descriptor_ui": "D017774", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Psychomotor Disorders", "descriptor_ui": "D011596", "major_topic": false }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051236", "major_topic": false }, { "descriptor": "Receptors, Pituitary Hormone", "descriptor_ui": "D011979", "major_topic": false }, { "descriptor": "Reproduction", "descriptor_ui": "D012098", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "274-280", "proceedings_title": null, "publisher": "", "title": "Nihon yakurigaku zasshi. Folia pharmacologica Japonica", "volume": "123", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "[Altered higher brain function in PACAP-knockout mice].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE AND METHODS: PC12 cells were loaded with a novel Mg indicator KMG-104 and Ca indicator fura-2, and intracellular Mg was studied in the endoplasmic reticulums (ERs), mitochondria, and Mg-ATP. Under coexistence of the two indicators, fluorescent signals of Mg and Ca can be measured separately. Mg release from the ER was investigated by photolysis of caged compounds. RESULTS: Transient [Ca]i increase by uncaging of caged Ca or caged IP3 or bath-application of caffeine (10 mM) induced no [Mg]i increase. These results suggest that there is no mechanism for Mg release from the ER through ryanodine receptors or IP3 receptors. In order to investigate the possibility of Mg release from Mg-ATP by energy consumption, we depleted ATP by oligomycin, an inhibitor of mitochondrial ATP synthase. Treating with oligomycin (4 microM) for several minutes showed no change of [Mg]i and [Ca]i. CONCLUSIONS: This result shows that Mg-ATP is not a Mg store. Since, when cells were treated by an uncoupler FCCP (3 microM), [Mg]i and [Ca]i increased, we concluded that mitochondria participate in maintenance of intracellular Mg stores.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Tokuno", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Yoshiichiro", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/07315724.2004.10719419" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15637225" } }, "mesh": [ { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Channels", "descriptor_ui": "D015220", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inositol 1,4,5-Trisphosphate Receptors", "descriptor_ui": "D053496", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Receptors, Cytoplasmic and Nuclear", "descriptor_ui": "D018160", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "742S-4S", "proceedings_title": null, "publisher": "", "title": "Journal of the American College of Nutrition", "volume": "23", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Investigation of intracellular magnesium mobilization pathways I PC12 cells B simultaneous Mg-Ca fluorescent imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide implicated in a broad variety of physiological processes. To assess PACAP's function in vivo, we recently generated PACAP knockout mice (PACAP(-/-)) and transgenic mice overexpressing PACAP specifically in the pancreas (PACAP-Tg). In PACAP(-/-) mice, we have demonstrated a marked phenotypic changes including a high early mortality rate, increased novelty-seeking behavior and abnormal explosive jumping in a novel environment, as well as reduced female fertility. In this paper, we reevaluated these phenotypes in terms of the genetic background of the mice. Genetic background appears to modulate critically the magnitude but not the general nature of the PACAP-null phenotype. In PACAP-Tg mice, we have recently demonstrated that enhanced glucose-induced insulin secretion with normal glucose tolerance, amelioration of streptozotocin-induced diabetes with increased beta-cell proliferation, and a trend towards an increase in total islet mass with age. Here we show that PACAP(-/-) mice exhibit significantly impaired glucose-induced insulin secretion but still have normal glucose tolerance. These observations suggest that PACAP may play important roles in and beyond the regulation of insulin release. Taken together, the mutant phenotypes revealed both expected and unexpected roles of PACAP in the brain and pancreatic functions.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Tomimoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.lfs.2003.09.021" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "14607262" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Gene Targeting", "descriptor_ui": "D018390", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Pancreas", "descriptor_ui": "D010179", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Dec 5", "date_precision": "day", "issue": "2-3", "normalized_date": "2003-12-05", "pages": "337-343", "proceedings_title": null, "publisher": "", "title": "Life sciences", "volume": "74", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Functional roles of the neuropeptide PACAP in brain and pancreas.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nitric oxide (NO) is an important mediator responsible for numerous physiological phenomena. Transient levels of NO in biological systems usually range from nanomolar to micromolar concentrations, with a rapid return to basal levels normally seen following these increases. Because NO can diffuse only over a local area in limited time due to such low levels of production and due to its short life-time prior to degradation, high spatial and temporal resolutions are required for direct and continuous NO measurement if the physiological role of NO is to be investigated in any system. For such purposes, analytical methods based on bio-imaging and electrochemical techniques for the measurement of NO are useful. In this paper, we describe the successful application of these methods to a number of biological systems. Specifically, complementary application of these methods demonstrate that it is possible to detect real-time NO production from nervous tissue with high spatial and temporal resolutions.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiichiro", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/s0039-9140(03)00333-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18969236" } }, "mesh": [], "publication": { "conference_name": null, "date": "2003 Dec 4", "date_precision": "day", "issue": "5", "normalized_date": "2003-12-04", "pages": "717-724", "proceedings_title": null, "publisher": "", "title": "Talanta", "volume": "61", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Real-time measurement of nitric oxide using a bio-imaging and an electrochemical technique.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In cultured astrocytes, PACAP activates extracellular signal-regulated kinase (ERK) and induces cell proliferation at picomolar concentrations. Here, we examined the role of cyclic AMP signaling underlying the effects of PACAP. PACAP38 induced accumulation of cyclic AMP in astrocytes at concentrations as low as 10(-12)M. PACAP38 (10(-12)-10(-9)M)-stimulated cell proliferation was completely abolished by the cyclic AMP antagonist Rp-cAMP, whereas the protein kinase A (PKA) inhibitor H89 had no effect. This PACAP38-mediated effect was also abolished by the ERK kinase inhibitor PD98059, suggesting the involvement of ERK in PACAP-induced proliferation. PACAP38 (10(-12)M)-stimulated phosphorylation of ERK lasted for at least 60 min. This effect was completely abolished by Rp-cAMP but not by H89. Dibutyryl cyclic AMP maximally stimulated the incorporation of thymidine and activation of ERK at 10(-10)M. These results suggest that PACAP-mediated stimulation of ERK activity and proliferation of astrocytes may involve a cyclic AMP-dependent, but PKA-independent, pathway.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Kunugi", "name": null }, { "creator_type": "author", "first_name": "Naohisa", "last_name": "Arakawa", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2003.10.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "14592419" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 1", "descriptor_ui": "D019950", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 3", "descriptor_ui": "D048052", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Nov 14", "date_precision": "day", "issue": "2", "normalized_date": "2003-11-14", "pages": "337-343", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "311", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Possible involvement of a cyclic AMP-dependent mechanism in PACAP-induced proliferation and ERK activation in astrocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pax5 activity is enhanced in activated B cells and is essential for class switch recombination (CSR). We show that inhibitor of differentiation (Id)2 suppresses CSR by repressing the gene expression of activation-induced cytidine deaminase (AID), which has been shown to be indispensable for CSR. Furthermore, a putative regulatory region of AID contains E2A- and Pax5-binding sites, and the latter site is indispensable for AID gene expression. Moreover, the DNA-binding activity of Pax5 is decreased in Id2-overexpressing B cells and enhanced in Id2−/− B cells. The kinetics of Pax5, but not E2A, occupancy to AID locus is the same as AID expression in primary B cells. Finally, enforced expression of Pax5 induces AID transcription in pro–B cell lines. Our results provide evidence that the balance between Pax5 and Id2 activities has a key role in AID gene expression.", "classifications": [ { "id": "A03-4", "label": "Planned Research A03-4", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Gonda", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Sugai", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Nambu", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Katakai", "name": null }, { "creator_type": "author", "first_name": "Yasutoshi", "last_name": "Agata", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro J.", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Shimizu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1084/jem.20030802" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "14581609" } }, "mesh": [ { "descriptor": "AICDA (Activation-Induced Cytidine Deaminase)", "descriptor_ui": "D000098830", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Cytidine Deaminase", "descriptor_ui": "D003564", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "DNA Primers", "descriptor_ui": "D017931", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Enzymologic", "descriptor_ui": "D015971", "major_topic": false }, { "descriptor": "Inhibitor of Differentiation Protein 2", "descriptor_ui": "D051797", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "PAX5 Transcription Factor", "descriptor_ui": "D051757", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": true }, { "descriptor": "Sequence Homology, Nucleic Acid", "descriptor_ui": "D012689", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Nov 3", "date_precision": "day", "issue": "9", "normalized_date": "2003-11-03", "pages": "1427-1437", "proceedings_title": null, "publisher": "", "title": "The Journal of Experimental Medicine", "volume": "198", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "The Balance Between Pax5 and Id2 Activities Is the Key to AID Gene Expression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intermolecular cyclopropanation reactions of various alkenes with propargylic carboxylates 1 are catalyzed by [RuCl2(CO)3]2 to give vinylcyclopropanes 2 in good yields. The key intermediate of the reaction is a vinylcarbene complex generated in situ by nucleophilic attack of a carbonyl oxygen of the carboxylates to an internal carbon of the alkyne activated by the ruthenium complex. A variety of transition-metal compounds other than the Ru compound can also be employed in this system. Similar cyclopropanation proceeds with conjugated dienes as well to give trans-vic-divinylcyclopropane derivatives and cycloheptadiene derivatives 5, the latter being thermally derived from the initially formed cis-vic-isomers via Cope-type rearrangement. The present reaction is chemically equivalent to the transition metal-catalyzed cyclopropanation reaction using alpha-diazoketones as carbenoid precursors.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Sakae", "last_name": "Uemura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jo034841a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "14575478" } }, "mesh": [], "publication": { "conference_name": null, "date": "2003 Oct 31", "date_precision": "day", "issue": "22", "normalized_date": "2003-10-31", "pages": "8505-8513", "proceedings_title": null, "publisher": "", "title": "The Journal of organic chemistry", "volume": "68", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Ruthenium-catalyzed cyclopropanation of alkenes using propargylic carboxylates as precursors of vinylcarbenoids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) is one of the neurotransmitters that transfers light signals from the retina to the hypothalamic suprachiasmatic nucleus (SCN) where the master clock of mammalian circadian rhythm locates, and is suggested to be implicated in the mechanism of light-induced phase shift of the circadian clock. Here, we examined changes in the phase shift of circadian rhythm in behavioral activity in mice lacking PACAP (PACAP(-/-)). The phase advance in PACAP(-/-) mice by a light stimulation at late subjective night was significantly attenuated, but the phase delay due to the illumination at the early subjective night slightly diminished. In contrast, the induction of c-Fos in the SCN by the illumination at the early subjective night but not that at the late subjective night was significantly blunted in PACAP(-/-) mice. These data provide new aspects about the roles of PACAP in light-induced phase shift of the circadian clock.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Chihiro", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Isojima", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2003.09.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "14511666" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Oct 10", "date_precision": "day", "issue": "1", "normalized_date": "2003-10-10", "pages": "169-175", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "310", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Changes in light-induced phase shift of circadian rhythm in mice lacking PACAP.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Membrane arachidonic acid is converted by cyclooxygenase (COX) into prostaglandin (PG) G(2) and then to PGH(2) which is subsequently metabolized to PGE(2) by PGE synthase (PGES). Both COX-1 and COX-2 play critical roles in intestinal polyp formation, whereas COX-2 is also expressed in cancers of a variety of organs. Likewise, inducible microsomal PGES (mPGES-1) is expressed in several types of cancer, although its role in benign polyp formation has not been investigated. We demonstrated recently that most COX-2-expressing cells in the polyps are stromal fibroblasts. Here we show colocalization of COX-1, COX-2 and mPGES in the intestinal polyp stromal fibroblasts of Apc(Delta 716) mice, a model for familial adenomatous polyposis. Contrary to COX-2 that was induced only in polyps >1 mm in diameter, COX-1 was found in polyps of any size. In polyps >1 mm, not only COX-2 but also mPGES was induced in the stromal fibroblasts where COX-1 had already been expressed. Although polyp number and size were markedly reduced in COX-1 (-/-) or COX-2 (-/-) compound mutant Apc mice, both COX-2 and mPGES were induced in the COX-1 (-/-) polyps, whereas COX-1 was expressed in the COX-2 (-/-) polyps. We found also in human familial adenomatous polyposis polyps that COX-2 and mPGES were induced in the COX-1-expressing fibroblasts. On the basis of these results, we propose that COX-1 expression in the stromal cells secures the basal level of PGE(2) that can support polyp growth to approximately 1 mm, and that simultaneous inductions of COX-2 and mPGES support the polyp expansion beyond approximately 1 mm by boosting the stromal PGE(2) production.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Haruna", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Sugihara", "name": null }, { "creator_type": "author", "first_name": "Patricia C.", "last_name": "Chulada", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Langenbach", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Makoto M.", "last_name": "Taketo", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12941808" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cyclooxygenase 1", "descriptor_ui": "D051545", "major_topic": false }, { "descriptor": "Cyclooxygenase 2", "descriptor_ui": "D051546", "major_topic": false }, { "descriptor": "Enzyme Induction", "descriptor_ui": "D004790", "major_topic": false }, { "descriptor": "Intestinal Polyps", "descriptor_ui": "D007417", "major_topic": false }, { "descriptor": "Intramolecular Oxidoreductases", "descriptor_ui": "D019746", "major_topic": false }, { "descriptor": "Isoenzymes", "descriptor_ui": "D007527", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Prostaglandin-E Synthases", "descriptor_ui": "D000071876", "major_topic": false }, { "descriptor": "Prostaglandin-Endoperoxide Synthases", "descriptor_ui": "D011451", "major_topic": false }, { "descriptor": "Stromal Cells", "descriptor_ui": "D017154", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Aug 15", "date_precision": "day", "issue": "16", "normalized_date": "2003-08-15", "pages": "4872-4877", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "63", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Cooperation of cyclooxygenase 1 and cyclooxygenase 2 in intestinal polyposis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To compare the spatial heterogeneity of brain tissue partial pressure of oxygen (pO(2)) among local brain regions, we focused on functional and anatomical variations in rat somatosensory cortex. Tissue pO(2) was measured by using an oxygen microelectrode with high spatio-temporal resolution, and investigated in three somatosensory areas including hindlimb (HL), forelimb (FL), and trunk region (Tr). Their anatomical structures were determined with histological techniques (Nissl stain). In addition to the measurement of baseline tissue pO(2), we examined temporal shifts in tissue pO(2) distribution elicited by functional stimulation using the brushing stimulation to the hindlimb, forelimb, and trunk regions of the body. We observed that average tissue pO(2) in the Tr (14+/-10 Torr) was significantly lower than those in the HL (25+/-13 Torr) and FL (24+/-13 Torr). Such regional differences in tissue pO(2) were closely related to the cytoarchitectonic variations among these three areas. In addition, the functional stimulation enlarged the regional differences in the pO(2) depending on each somatosensory area; the pO(2) in the HL increased by 3.6+/-2.9% after the stimulation to hindlimb, whereas that in the Tr decreased by -2.9+/-2.5% after the stimulation to trunk region. Such dual responses of tissue pO(2) (i.e. increase or decrease) after the functional stimulation to the corresponding body regions may provide a criterion to clinically predict regions susceptible to tissue hypoxia, because considerable decrease in tissue pO(2) occurred in the Tr showing the lowest baseline pO(2).", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kazuto", "last_name": "Masamoto", "name": null }, { "creator_type": "author", "first_name": "Naosada", "last_name": "Takizawa", "name": null }, { "creator_type": "author", "first_name": "Hirosuke", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Tanishita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/s0006-8993(03)02882-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12850577" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microelectrodes", "descriptor_ui": "D008839", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Partial Pressure", "descriptor_ui": "D010313", "major_topic": false }, { "descriptor": "Physical Stimulation", "descriptor_ui": "D010812", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Somatosensory Cortex", "descriptor_ui": "D013003", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Jul 25", "date_precision": "day", "issue": "1-2", "normalized_date": "2003-07-25", "pages": "104-113", "proceedings_title": null, "publisher": "", "title": "Brain research", "volume": "979", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Dual responses of tissue partial pressure of oxygen after functional stimulation in rat somatosensory cortex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "[reaction: see text] The reaction of alkenes with conjugated ene-yne-imino ether or ene-yne-aldimine in the presence of a catalytic amount of [Rh(OAc)(2)](2) gives (2-pyrrolyl)cyclopropanes in good yields. The key intermediate of this cyclopropanation is a (2-pyrrolyl)carbenoid generated by the nucleophilic attack of imine nitrogen atom at an internal alkyne carbon activated by rhodium complex. The intramolecular reaction also proceeds to afford a polycyclic pyrrole.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Sakae", "last_name": "Uemura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ol0347545" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12868872" } }, "mesh": [], "publication": { "conference_name": null, "date": "2003 Jul 24", "date_precision": "day", "issue": "15", "normalized_date": "2003-07-24", "pages": "2615-2617", "proceedings_title": null, "publisher": "", "title": "Organic letters", "volume": "5", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Rhodium-catalyzed cyclopropanation using ene-yne-imino ether compounds as precursors of (2-pyrrolyl)carbenoids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "[reaction: see text] In the presence of rhodium catalyst, (2-furyl)carbenoids generated from conjugated ene-yne-carbonyl compounds 1 efficiently undergo carbene transfer reactions with allylic sulfides followed by [2,3]sigmatropic rearrangement of sulfur ylides to give furan-containing sulfides in good yields. When diallyl sulfide is employed, heteroatom-containing polycyclic compounds are obtained by sequential intramolecular Diels-Alder cyclization reaction with a constructed furan ring as an enophile.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Yumiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Sakae", "last_name": "Uemura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ol034731q" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12868873" } }, "mesh": [], "publication": { "conference_name": null, "date": "2003 Jul 24", "date_precision": "day", "issue": "15", "normalized_date": "2003-07-24", "pages": "2619-2621", "proceedings_title": null, "publisher": "", "title": "Organic letters", "volume": "5", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Doyle-Kirmse reaction of allylic sulfides with diazoalkane-free (2-furyl)carbenoid transfer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Rho-family GTPases regulate many cellular functions. To visualize the activity of Rho-family GTPases in living cells, we developed fluorescence resonance energy transfer (FRET)–based probes for Rac1 and Cdc42 previously (Itoh, R.E., K. Kurokawa, Y. Ohba, H. Yoshizaki, N. Mochizuki, and M. Matsuda. 2002. Mol. Cell. Biol. 22:6582–6591). Here, we added two types of probes for RhoA. One is to monitor the activity balance between guanine nucleotide exchange factors and GTPase-activating proteins, and another is to monitor the level of GTP-RhoA. Using these FRET probes, we imaged the activities of Rho-family GTPases during the cell division of HeLa cells. The activities of RhoA, Rac1, and Cdc42 were high at the plasma membrane in interphase, and decreased rapidly on entry into M phase. From after anaphase, the RhoA activity increased at the plasma membrane including cleavage furrow. Rac1 activity was suppressed at the spindle midzone and increased at the plasma membrane of polar sides after telophase. Cdc42 activity was suppressed at the plasma membrane and was high at the intracellular membrane compartments during cytokinesis. In conclusion, we could use the FRET-based probes to visualize the complex spatio-temporal regulation of Rho-family GTPases during cell division.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hisayoshi", "last_name": "Yoshizaki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kurokawa", "name": null }, { "creator_type": "author", "first_name": "Reina E.", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1083/jcb.200212049" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12860967" } }, "mesh": [ { "descriptor": "Adenoviridae", "descriptor_ui": "D000256", "major_topic": false }, { "descriptor": "cdc42 GTP-Binding Protein", "descriptor_ui": "D020764", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": true }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": true }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Molecular Probes", "descriptor_ui": "D015335", "major_topic": false }, { "descriptor": "rac1 GTP-Binding Protein", "descriptor_ui": "D020830", "major_topic": false }, { "descriptor": "rho GTP-Binding Proteins", "descriptor_ui": "D020741", "major_topic": false }, { "descriptor": "rhoA GTP-Binding Protein", "descriptor_ui": "D020742", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Jul 21", "date_precision": "day", "issue": "2", "normalized_date": "2003-07-21", "pages": "223-232", "proceedings_title": null, "publisher": "", "title": "The Journal of Cell Biology", "volume": "162", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Activity of Rho-family GTPases during cell division as visualized with FRET-based probes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.200351122" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12851952" } }, "mesh": [], "publication": { "conference_name": null, "date": "2003 Jul 7", "date_precision": "day", "issue": "26", "normalized_date": "2003-07-07", "pages": "2996-2999", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "42", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Selective detection of zinc ions with novel luminescent lanthanide probes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To understand the range of competence of embryonic stem (ES) cell-derived neural precursors, we have examined in vitro differentiation of mouse and primate ES cells into the dorsal- (neural crest) and ventralmost (floor plate) cells of the neural axis. Stromal cell-derived inducing activity (SDIA; accumulated on PA6 stromal cells) induces cocultured ES cells to differentiate into rostral CNS tissues containing both ventral and dorsal cells. Although early exposure of SDIA-treated ES cells to bone morphogenetic protein (BMP)4 suppresses neural differentiation and promotes epidermogenesis, late BMP4 exposure after the fourth day of coculture causes differentiation of neural crest cells and dorsalmost CNS cells, with autonomic system and sensory lineages induced preferentially by high and low BMP4 concentrations, respectively. In contrast, Sonic hedgehog (Shh) suppresses differentiation of neural crest lineages and promotes that of ventral CNS tissues such as motor neurons. Notably, high concentrations of Shh efficiently promote differentiation of HNF3beta(+) floor plate cells with axonal guidance activities. Thus, SDIA-treated ES cells generate naive precursors that have the competence of differentiating into the \"full\" dorsal-ventral range of neuroectodermal derivatives in response to patterning signals.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Mizuseki", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Kiichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ikeya", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Arakawa", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Suemori", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Nakatsuji", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Fujio", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1037282100" }, "pmcid": { "normalized": "PMC156286" }, "pmid": { "normalized": "12724518" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Morphogenetic Protein 4", "descriptor_ui": "D055415", "major_topic": false }, { "descriptor": "Bone Morphogenetic Proteins", "descriptor_ui": "D019485", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Macaca fascicularis", "descriptor_ui": "D008252", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Neural Crest", "descriptor_ui": "D009432", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Peripheral Nervous System", "descriptor_ui": "D017933", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 May 13", "date_precision": "day", "issue": "10", "normalized_date": "2003-05-13", "pages": "5828-5833", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "100", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of neural crest-derived peripheral neurons and floor plate cells from mouse and primate embryonic stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mg(2+) buffering mechanisms in PC12 cells were demonstrated with particular focus on the role of the Na(+)/Mg(2+) transporter by using a newly developed Mg(2+) indicator, KMG-20, and also a Na(+) indicator, Sodium Green. Carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP), a protonophore, induced a transient increase in the intracellular Mg(2+) concentration ([Mg(2+)](i)). The rate of decrease of [Mg(2+)](i) was slower in a Na(+)-free extracellular medium, suggesting the coupling of Na(+) influx and Mg(2+) efflux. Na(+) influxes were different for normal and imipramine- (a putative inhibitor of the Na(+)/Mg(2+) transporter) containing solutions. FCCP induced a rapid increase in [Na(+)](i) in the normal solution, while the increase was gradual in the imipramine-containing solution. The rate of decrease of [Mg(2+)](i) in the imipramine-containing solution was also slower than that in the normal solution. From these results, we show that the main buffering mechanism for excess Mg(2+) depends on the Na(+)/Mg(2+) transporter in PC12 cells.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Tokuno", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Yoshiichiro", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/s0006-291x(03)00346-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12646207" } }, "mesh": [ { "descriptor": "Adrenergic Uptake Inhibitors", "descriptor_ui": "D018759", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antiporters", "descriptor_ui": "D017920", "major_topic": false }, { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone", "descriptor_ui": "D002259", "major_topic": false }, { "descriptor": "Imipramine", "descriptor_ui": "D007099", "major_topic": false }, { "descriptor": "Ionophores", "descriptor_ui": "D007476", "major_topic": false }, { "descriptor": "Ions", "descriptor_ui": "D007477", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Sodium", "descriptor_ui": "D012964", "major_topic": false }, { "descriptor": "Spectrophotometry, Atomic", "descriptor_ui": "D013054", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Uncoupling Agents", "descriptor_ui": "D014475", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Mar 28", "date_precision": "day", "issue": "1", "normalized_date": "2003-03-28", "pages": "332-336", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "303", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Na+/Mg2+ transporter acts as a Mg2+ buffering mechanism in PC12 cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "STUDY DESIGN: Cultured annulus fibrosus cells within an atelocollagen honeycomb-shaped scaffold with a membrane seal were allografted into the lacunas of intervertebral discs of which the nucleus pulposus had been vaporized using an indocyanine green dye-enhanced laser. Regeneration of the intervertebral disc was assessed based on the viability and histologic status of the allografted annulus fibrosus cells, as well as the prevention of narrowing disc space. OBJECTIVES: To study the regeneration of intervertebral disc after laser discectomy using tissue-engineering methods. SUMMARY OF BACKGROUND DATA: Intervertebral disc is the most avascular tissue in the human body, and its ability to regenerate is as low as that of articular cartilage. When nucleotomy is carried out, little regeneration of the annulus fibrosus is observed; consequently, intervertebral disc degeneration is inevitable. METHODS: Annulus fibrosus cells isolated from 20 Japanese white rabbits were labeled with a PKH-26 fluorescent dye and seeded within an atelocollagen honeycomb-shaped scaffold with a membrane seal. Annulus fibrosus cells cultured in atelocollagen honeycomb-shaped scaffold with a membrane seal for 1 week were allografted into the lacunas of intervertebral discs of recipient rabbit of which the nucleus pulposus had been vaporized using an ICG dye-enhanced laser. Soft radiograph photographs of the lumbar spine of these anesthetized rabbits were taken, the disc space measured, and the lumbar spine extracted 2, 4, 8, and 12 weeks after the operation. The proliferation of allografted annulus fibrosus cells with 5-bromo-2'-deoxyuridine/PKH-26 fluorescent labels was assessed using consecutive frozen sections, and safranin-O staining carried out for histologic evaluation. RESULTS: The allografted annulus fibrosus cells were viable and showed proliferation activity with a hyaline-like cartilage being produced. The narrowing of the intervertebral disc space of the cell translation group was significantly prevented, as shown, up to 12 postoperative weeks. CONCLUSION: The annulus fibrosus cells cultured in an ACHMS-scaffold were allografted into the lacunae of nucleus pulposus (obtained using laser vaporization), as well as the hole of annulus fibrosus (obtained by laser fiber insertion) of rabbit intervertebral discs. These cells were viable and showed cell proliferation in the disc tissues of recipients.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Masato", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Asazuma", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Kyosuke", "last_name": "Fujikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/01.brs.0000049909.09102.60" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12642760" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bromodeoxyuridine", "descriptor_ui": "D001973", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Graft Survival", "descriptor_ui": "D006085", "major_topic": false }, { "descriptor": "Intervertebral Disc", "descriptor_ui": "D007403", "major_topic": false }, { "descriptor": "Intervertebral Disc Displacement", "descriptor_ui": "D007405", "major_topic": false }, { "descriptor": "Laser Therapy", "descriptor_ui": "D053685", "major_topic": false }, { "descriptor": "Organic Chemicals", "descriptor_ui": "D009930", "major_topic": true }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": true }, { "descriptor": "Tissue Engineering", "descriptor_ui": "D023822", "major_topic": false }, { "descriptor": "Transplantation, Homologous", "descriptor_ui": "D014184", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Mar 15", "date_precision": "day", "issue": "6", "normalized_date": "2003-03-15", "pages": "548-553", "proceedings_title": null, "publisher": "", "title": "Spine", "volume": "28", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "An experimental study of the regeneration of the intervertebral disc with an allograft of cultured annulus fibrosus cells using a tissue-engineering method.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Indicator molecules for caspase-3 activation have been reported that use fluorescence resonance energy transfer (FRET) between an enhanced cyan fluorescent protein (the donor) and enhanced yellow fluorescent protein (EYFP; the acceptor). Because EYFP is highly sensitive to proton (H+) and chloride ion (Cl−) levels, which can change during apoptosis, this indicator's ability to trace the precise dynamics of caspase activation is limited, especially in vivo. Here, we generated an H+- and Cl−-insensitive indicator for caspase activation, SCAT, in which EYFP was replaced with Venus, and monitored the spatio-temporal activation of caspases in living cells. Caspase-3 activation was initiated first in the cytosol and then in the nucleus, and rapidly reached maximum activation in 10 min or less. Furthermore, the nuclear activation of caspase-3 preceded the nuclear apoptotic morphological changes. In contrast, the completion of caspase-9 activation took much longer and its activation was attenuated in the nucleus. However, the time between the initiation of caspase-9 activation and the morphological changes was quite similar to that seen for caspase-3, indicating the activation of both caspases occurred essentially simultaneously during the initiation of apoptosis.", "classifications": [ { "id": "A01-2", "label": "Planned Research A01-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kiwamu", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Miura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1083/jcb.200207111" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12527749" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Caspase 3", "descriptor_ui": "D053148", "major_topic": false }, { "descriptor": "Caspase 9", "descriptor_ui": "D053453", "major_topic": false }, { "descriptor": "Caspases", "descriptor_ui": "D020169", "major_topic": false }, { "descriptor": "Cell Extracts", "descriptor_ui": "D002457", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Chlorides", "descriptor_ui": "D002712", "major_topic": false }, { "descriptor": "Cytosol", "descriptor_ui": "D003600", "major_topic": false }, { "descriptor": "Eukaryotic Cells", "descriptor_ui": "D005057", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Indicators and Reagents", "descriptor_ui": "D007202", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Microscopy, Video", "descriptor_ui": "D018715", "major_topic": false }, { "descriptor": "Tumor Necrosis Factor-alpha", "descriptor_ui": "D014409", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Jan 20", "date_precision": "day", "issue": "2", "normalized_date": "2003-01-20", "pages": "235-243", "proceedings_title": null, "publisher": "", "title": "The Journal of Cell Biology", "volume": "160", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatio-temporal activation of caspase revealed by indicator that is insensitive to environmental effects.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Prolactin (PRL) is an important regulator of multiple biological functions, but a specific PRL-releasing factor, PRL-releasing peptide (PrRP), was isolated only recently from mammals and teleosts. Although this peptide seems to be a strong candidate for being a physiologically relevant stimulator of PRL expression and secretion in teleost pituitary and peripheral organs, it may not be a typical or classic hypothalamic releasing factor in rats. We now know that its biological actions are not limited solely to PRL stimulation, because it is also a neuromodulator of several hypothalamus-pituitary axes and is involved in some brain circuits with the regulation of food intake and cardiovascular functions. Moreover, it plays a direct role in hypertension and retinal information processing. It is the purpose of this review to provide a comprehensive survey of our current knowledge of PrRP and to provide a comparative point of view.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Andot", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/s0074-7696(05)25003-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12696591" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autonomic Nervous System", "descriptor_ui": "D001341", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Fishes", "descriptor_ui": "D005399", "major_topic": false }, { "descriptor": "Hypothalamo-Hypophyseal System", "descriptor_ui": "D007030", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Prolactin", "descriptor_ui": "D011388", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Thyrotropin-Releasing Hormone", "descriptor_ui": "D013973", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003", "date_precision": "year", "issue": "", "normalized_date": "2003", "pages": "91-130", "proceedings_title": null, "publisher": "", "title": "International review of cytology", "volume": "225", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Fishy tales of prolactin-releasing peptide.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mice lacking PACAP (PACAP-KO) exhibits altered psychomotor behaviors, including impaired habituation to a novel environment and perseverative jumping, with a slightly reduced levels of the serotonin metabolite, 5-HIAA, in the brain. We have recently demonstrated that PACAP-KO exhibits abnormalities in sensorimotor gating as measured by prepulse inhibition (PPI) of the acoustic startle. In the present study, behavioral responses to centrally acting drugs (amphetamine, haloperidol, risperidone, fluoxetine, and 8-OH-DPAT) were examined in PACAP-KO. Surprisingly, a psychostimulant amphetamine effectively normalized the deficit in PPI as well as hyperactivity and jumping behavior. These results implied phenotypic and pharmacological similarity between PACAP-KO and attention deficit hyperactivity disorder (ADHD). Although a potent dopamine D2-like receptor antagonist, haloperidol, ameliorated the hyperactivity and jumping behavior, it had no effect on the deficit in PPI. In contrast, a prototype of serotonin-dopamine antagonist (SDA), risperidone, effectively normalized the deficit in PPI as well as hyperactivity, and jumping behavior. A selective serotonin reuptake inhibitor (SSRI), fluoxetine, also suppressed the hyperactivity and jumping behavior. A 5-HT1A receptor agonist, 8-OH-DPAT, significantly lowered rectal temperature in wild-type mice, while it had only a small effect in PACAP-KO. These results suggest the involvement of dopaminergic and serotonergic dysfunction in phenotypic changes observed in PACAP-KO.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "14727506" } }, "mesh": [ { "descriptor": "Amphetamine", "descriptor_ui": "D000661", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Attention Deficit Disorder with Hyperactivity", "descriptor_ui": "D001289", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Fluoxetine", "descriptor_ui": "D005473", "major_topic": false }, { "descriptor": "Haloperidol", "descriptor_ui": "D006220", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Risperidone", "descriptor_ui": "D018967", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Nov", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "1P-4P", "proceedings_title": null, "publisher": "", "title": "Nihon yakurigaku zasshi. Folia pharmacologica Japonica", "volume": "122 Suppl", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "[Altered behavioral response to centrally acting drugs in mice lacking PACAP].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mutant strains of mice with precise genetic mutations generated by gene-targeting technology have proved to be useful tools for linking specific genes with biological processes in vivo and serve as models for human diseases. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved neuropeptide that is widely expressed in the mammalian brain, and it has been implicated in a broad variety of physiological and pathophysiological processes. To assess the function of PACAP in vivo, recently, we have generated PAC1 receptor- and PACAP-targeted mice and transgenic mice overexpressing PACAP in the pancreatic beta-cells. The phenotypes of these mutant mice revealed both expected and unexpected roles of PACAP in the brain and pancreatic functions. A significant contribution of genetic background as well as environmental factors to the knockout phenotypes was also observed. In this article, we briefly describe the technique of gene targeting and discuss how this method was used to generate PACAP and its receptor deficient mice. We also analyze how these mutants can contribute to our understanding of the molecular mechanism underlying higher nervous functions.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/fpj.122.427" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "14569162" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Gene Targeting", "descriptor_ui": "D018390", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051236", "major_topic": false }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I", "descriptor_ui": "D051237", "major_topic": false }, { "descriptor": "Receptors, Pituitary Hormone", "descriptor_ui": "D011979", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Nov", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "427-435", "proceedings_title": null, "publisher": "", "title": "Nihon yakurigaku zasshi. Folia pharmacologica Japonica", "volume": "122", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "[In vivo functional analysis of the neuropeptide PACAP using gene-targeted mice].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the vasoactive intestinal peptide/secretin/glucagon family, stimulates insulin secretion from islets in a glucose-dependent manner at femtomolar concentrations. To assess PACAP's pancreatic function in vivo, we generated transgenic mice overexpressing PACAP in the pancreas under the control of human insulin promoter. Northern blot and immunohistochemical analyses showed that PACAP is overexpressed in pancreatic islets, specifically in transgenic mice. Plasma glucose and glucagon levels during a glucose tolerance test were not different between PACAP transgenic mice and nontransgenic littermates. However, plasma insulin levels in transgenic mice were higher after glucose loading. Also, increases of streptozotocin-induced plasma glucose were attenuated in transgenic compared with nontransgenic mice. Notably, an increase in 5-bromo-2-deoxyuridine-positive beta-cells in the streptozotocin-treated transgenic mice was observed but without differences in the staining patterns by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. Morphometric analysis revealed that total islet mass tends to increase in 12-month-old transgenic mice but showed no difference between 12-week-old transgenic and nontransgenic littermates. This is the first time that PACAP has been observed to play an important role in the proliferation of beta-cells.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Kyohei", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Tomimoto", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Jun-ichi", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Fumi", "last_name": "Tashiro", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Nammo", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Jun-ichiro", "last_name": "Miyagawa", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Matsuzawa", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kawabata", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Fukuyama", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Wakaba", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.2337/diabetes.52.5.1155" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12716746" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Blotting, Northern", "descriptor_ui": "D015152", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Experimental", "descriptor_ui": "D003921", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Insulin Secretion", "descriptor_ui": "D000078790", "major_topic": false }, { "descriptor": "Islets of Langerhans", "descriptor_ui": "D007515", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Organ Specificity", "descriptor_ui": "D009928", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "1155-1162", "proceedings_title": null, "publisher": "", "title": "Diabetes", "volume": "52", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Overexpression of PACAP in transgenic mouse pancreatic beta-cells enhances insulin secretion and ameliorates streptozotocin-induced diabetes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.2108/zsj.20.1497" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "14960801" } }, "mesh": [ { "descriptor": "Adaptation, Physiological", "descriptor_ui": "D000222", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Awards and Prizes", "descriptor_ui": "D001363", "major_topic": true }, { "descriptor": "Environment", "descriptor_ui": "D004777", "major_topic": true }, { "descriptor": "Growth Hormone", "descriptor_ui": "D013006", "major_topic": false }, { "descriptor": "Prolactin", "descriptor_ui": "D011388", "major_topic": false }, { "descriptor": "Water-Electrolyte Balance", "descriptor_ui": "D014882", "major_topic": false }, { "descriptor": "Zoology", "descriptor_ui": "D015046", "major_topic": true } ], "publication": { "conference_name": null, "date": "2003 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1497-1498", "proceedings_title": null, "publisher": "", "title": "Zoological science", "volume": "20", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Growth hormone and prolactin in environmental adaptation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We modeled and analyzed a signal transduction system of long-term potentiation (LTP) in hippocampal post-synapse. Bhalla and Iyengar [Science 283(1999) 381] have developed a hippocampal LTP model. In the conventional model, the concentration of protein phosphatase 2A (PP2A) was fixed. However, it was reported that dynamic inactivation of PP2A was essential for LTP [J. Neurochem. 74 (2000) 807]. We introduced a dynamic modeling of PP2A; inactivation (phosphorylation) of PP2A by calcium/calmodulin-dependent protein kinase II (CaMKII) in the presence of calcium/calmodulin, self-activation (autodephosphorylation) of PP2A, and inactivation (dephosphorylation) of CaMKII by PP2A. This model includes complex feedback loops; both CaMKII and PP2A are autoactivated, while they inactivate each other. Moreover, we proposed an analysis strategy for model validation by applying the results of sensitivity analysis. In our system, calcineurin (CaN) played an essential role, rather than the activation of protein kinase C (PKC) as documented in the conventional model. From results of the analysis of our model, we found the following robustness as characteristics of bistability in our model: (1). PP2A reactions against calcium ion (Ca(2+)) perturbation; (2). PP2A inactivation against PP2A increase; (3). protein phosphatase 1 (PP1) activation against PF2A increase; and (4). PP2A reactions against PP2A initial concentration. These properties facilitated LTP induction in our system. We showed that another mechanism could introduce bistable behavior by adding dynamic reactions of PP2A.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shinichi", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Fuchikawa", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Kohtaro", "last_name": "Takei", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neunet.2003.09.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "14622891" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Long-Term Potentiation", "descriptor_ui": "D017774", "major_topic": false }, { "descriptor": "Neural Networks, Computer", "descriptor_ui": "D016571", "major_topic": true }, { "descriptor": "Phosphoprotein Phosphatases", "descriptor_ui": "D010749", "major_topic": false }, { "descriptor": "Protein Phosphatase 1", "descriptor_ui": "D054645", "major_topic": false }, { "descriptor": "Protein Phosphatase 2", "descriptor_ui": "D054648", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Nov", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "1389-1398", "proceedings_title": null, "publisher": "", "title": "Neural networks : the official journal of the International Neural Network Society", "volume": "16", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Kinetic simulation of signal transduction system in hippocampal long-term potentiation with dynamic modeling of protein phosphatase 2A.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Phospolipase A(2) (PLA(2)) is the esterase activity that cleaves the sn-2 ester bond in glycerophospholipids, releasing free fatty acids and lysophospholipids. The PLA(2) activity is found in a variety of enzymes which can be divided in several types based on their Ca(2+) dependence for their activity; Ca(2+)-dependent secretory phosholipases (sPLA(2)s) and cytosolic phospholipases (cPLA(2)s), and Ca(2+)-independent phospholipase A(2)s (iPLA(2)s). These enzymes also show diverse size and substrate specificity (i.e., in the fatty acid chain length and extent of saturation). Among the fatty acids released by PLA(2), arachidonic acid (AA) is of particular biological importance, because it is subsequently converted to prostanoids and leukotrienes by cyclooxygenases (COX) and lipoxygenases (LOX), respectively. Free AA may also stimulate apoptosis through activation of sphingomyelinase. Alternatively, it is suggested that oxidized metabolites generated from AA by LOX induce apoptosis. Although the precise mechanisms remain to be elucidated, changes are observed in glycerolipid metabolism during apoptotic processes. In some cells induced to undergo apoptosis, AA is released concomitant with loss of cell viability, caspase activation and DNA fragmentation. Such AA releases appear to be mediated by activation of cPLA(2) and/or iPLA(2). For example, tumor necrosis factor-alpha (TNF-alpha)-induced cell death is mediated by cPLA(2), whereas Fas-induced apoptosis appears to be mediated by iPLA(2). Some discrepancies among early experimental results were probably caused by differences in the experimental conditions such as the serum concentration, inhibitors used that are not necessarily specific to a single-type enzyme, or differential expression of each PLA(2) in cells employed in the experiments. Recent studies eliminated such problems, by carefully defining the experimental conditions, and using multiple inhibitors that show different specificities. Accordingly, more convincing data are available that demonstrate involvement of some PLA(2)s in the apoptotic processes. In addition to cPLA(2) and iPLA(2), sPLA(2)s were recently found to play roles in apoptosis. Moreover, new proteins that appear to control PLA(2)s are being discovered. Here, the roles of PLA(2)s in apoptosis are discussed by reviewing recent reports.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Makoto Mark", "last_name": "Taketo", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/s1388-1981(02)00326-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12531539" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cytosol", "descriptor_ui": "D003600", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Isoenzymes", "descriptor_ui": "D007527", "major_topic": false }, { "descriptor": "Phospholipases A", "descriptor_ui": "D010741", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false }, { "descriptor": "Tumor Necrosis Factor-alpha", "descriptor_ui": "D014409", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002 Dec 30", "date_precision": "day", "issue": "2-3", "normalized_date": "2002-12-30", "pages": "72-76", "proceedings_title": null, "publisher": "", "title": "Biochimica et biophysica acta", "volume": "1585", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Phospolipase A2 and apoptosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cyclooxygenase-2 (COX-2), the inducible COX isozyme, plays a key role in intestinal tumorigenesis. We have demonstrated recently that COX-2 protein is induced in the polyp stroma near the intestinal luminal surface in the Apc(Delta716) mouse, a model for human familial adenomatous polyposis, and stimulate tumor angiogenesis. However, the precise cell types that express COX-2 are still to be determined. By immunohistochemical analysis, here we show that the majority of COX-2-expressing cells in the intestinal polyps of Apc(Delta716) mice are fibroblasts and endothelial cells. Furthermore, the COX-2-expressing cells in human familial adenomatous polyposis polyps are also fibroblasts and endothelial cells. In contrast, bone marrow-derived cells such as macrophages and leukocytes express little COX-2 protein in the intestinal polyps. These results clearly indicate that fibroblasts and endothelial cells play important roles in polyp expansion by expressing COX-2, resulting in tumor angiogenesis.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Takaku", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Sugihara", "name": null }, { "creator_type": "author", "first_name": "Makoto M.", "last_name": "Taketo", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12460897" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Adenomatous Polyposis Coli", "descriptor_ui": "D011125", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, CD34", "descriptor_ui": "D018952", "major_topic": false }, { "descriptor": "Antigens, Differentiation", "descriptor_ui": "D000943", "major_topic": false }, { "descriptor": "Cyclooxygenase 2", "descriptor_ui": "D051546", "major_topic": false }, { "descriptor": "Endothelium, Vascular", "descriptor_ui": "D004730", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Intestinal Polyps", "descriptor_ui": "D007417", "major_topic": false }, { "descriptor": "Isoenzymes", "descriptor_ui": "D007527", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Prostaglandin-Endoperoxide Synthases", "descriptor_ui": "D011451", "major_topic": false }, { "descriptor": "Stromal Cells", "descriptor_ui": "D017154", "major_topic": false }, { "descriptor": "Vimentin", "descriptor_ui": "D014746", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002 Dec 1", "date_precision": "day", "issue": "23", "normalized_date": "2002-12-01", "pages": "6846-6849", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "62", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Cyclooxygenase-2 expression in fibroblasts and endothelial cells of intestinal polyps.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have recently shown that in PC12 cells, pituitary adenylate cyclase-activating polypeptide (PACAP) and NGF synergistically stimulate PACAP mRNA expression primarily via a mechanism involving a p38 mitogen-activated protein kinase (MAPK)-dependent pathway. Here we have analyzed p38 MAPK activation by PACAP and the mechanism underlying this action of PACAP in PC12 cells. PACAP increased phosphorylation of p38 MAPK with a bell-shaped dose-response relationship and a maximal effect was obtained at 10(-8) M. PACAP (10(-8) M)-induced p38 MAPK phosphorylation was already evident at 2.5 min, maximal at 5 min, and rapidly declined thereafter. PACAP-induced p38 MAPK phosphorylation was potently inhibited by depletion of Ca(2+) stores with thapsigargin and partially inhibited by the phospholipase C inhibitor U-73122, L-type voltage-dependent calcium channel inhibitors nifedipine and nimodipine, and the Ca(2+) chelator EGTA, whereas the protein kinase C inhibitor calphostin C, the protein kinase A inhibitor H-89, the cAMP antagonist Rp-cAMP, and the nonselective cation channel blocker SKF96365 had no effect. These results indicate that PACAP activates p38 MAPK in PC12 cells through activation of a phospholipase C, mobilization of intracellular Ca(2+) stores, and Ca(2+) influx through voltage-dependent Ca(2+) channels, but not cyclic AMP-dependent mechanisms.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Ichibori", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Tomimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/s0167-0115(02)00198-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12409227" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Channel Blockers", "descriptor_ui": "D002121", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Cyclic AMP-Dependent Protein Kinases", "descriptor_ui": "D017868", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Intracellular Fluid", "descriptor_ui": "D007424", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": false }, { "descriptor": "Naphthalenes", "descriptor_ui": "D009281", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "p38 Mitogen-Activated Protein Kinases", "descriptor_ui": "D048051", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051236", "major_topic": false }, { "descriptor": "Receptors, Pituitary Hormone", "descriptor_ui": "D011979", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false }, { "descriptor": "Type C Phospholipases", "descriptor_ui": "D010738", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002 Nov 15", "date_precision": "day", "issue": "1-3", "normalized_date": "2002-11-15", "pages": "149-153", "proceedings_title": null, "publisher": "", "title": "Regulatory peptides", "volume": "109", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Involvement of intracellular Ca2+ elevation but not cyclic AMP in PACAP-induced p38 MAP kinase activation in PC12 cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved neuropeptide and widely expressed in both brain and peripheral tissues, including several reproductive organs (e.g., testis and ovary). PACAP stimulates syntheses of several sexual hormones and steroids, suggesting it has possible roles in reproductive function. In this study, the role of PACAP in female reproductive functions such as fertility, mating behavior and maternal behaviors were investigated by using mice lacking PACAP (PACAP(-/-)). PACAP(-/-) females showed reduced fertility (the number of parturitions relative to the number of pairings). Mating experiments using vasectomized males revealed that mating frequency and its intervals in some PACAP(-/-) females were quite different (zero to eight times/4 weeks), whereas the frequency was relatively constant (two to three times/4 weeks) in wild-type females. In PACAP(-/-) females, maternal crouching behavior tended to decrease compared to wild-type females, although the influence of litter size on maternal behavior needs to be considered. These data suggest a role for endogenous PACAP in female reproductive processes.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Wakaba", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Tomimoto", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/s0167-0115(02)00169-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12409213" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fertility", "descriptor_ui": "D005298", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": true }, { "descriptor": "Litter Size", "descriptor_ui": "D008098", "major_topic": false }, { "descriptor": "Maternal Behavior", "descriptor_ui": "D008425", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Reproduction", "descriptor_ui": "D012098", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Sexual Behavior, Animal", "descriptor_ui": "D012726", "major_topic": false }, { "descriptor": "Vagina", "descriptor_ui": "D014621", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002 Nov 15", "date_precision": "day", "issue": "1-3", "normalized_date": "2002-11-15", "pages": "45-48", "proceedings_title": null, "publisher": "", "title": "Regulatory peptides", "volume": "109", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Defects in reproductive functions in PACAP-deficient female mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Organized synapse formation on to Purkinje cell (PC) dendrites by parallel fibers (PFs) and climbing fibers (CFs) is crucial for cerebellar function. In PCs lacking glutamate receptor δ2 (GluRδ2), PF synapses are reduced in number, numerous free spines emerge, and multiple CF innervation persists to adulthood. In the present study, we conducted anterograde and immunohistochemical labelings to investigate how CFs innervate PC dendrites under weakened synaptogenesis by PFs. In the GluRδ2 knock-out mouse, CFs were distributed in the molecular layer more closely to the pial surface compared with the wild-type mouse. Serial electron microscopy demonstrated that CFs in the knock-out mouse innervated all spines protruding from proximal dendrites of PCs, as did those in the wild-type mouse. In the knock-out mouse, however, CF innervation extended distally to spiny branchlets, where nearly half of the spines were free of innervation in contrast to complete synapse formation by PFs in the wild-type mouse. Furthermore, from the end point of innervation, CFs aberrantly jumped to form ectopic synapses on adjacent spiny branchlets, whose proximal portions were often innervated by different CFs. Without GluRδ2, CFs are thus able to expand their territory along and beyond dendritic trees of the target PC, resulting in persistent surplus CFs by innervating the distal dendritic segment. We conclude that GluRδ2 is essential to restrict CF innervation to the proximal dendritic segment, by which territorized innervation by PFs and CFs is properly structured and the formation of excess CF wiring to adjacent PCs is suppressed.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Hashikawa", "name": null }, { "creator_type": "author", "first_name": "Haruyuki", "last_name": "Tatsumi", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Mishina", "name": null }, { "creator_type": "author", "first_name": "Yoshiro", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.22-19-08487.2002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12351723" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biotin", "descriptor_ui": "D001710", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Dextrans", "descriptor_ui": "D003911", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Iontophoresis", "descriptor_ui": "D007478", "major_topic": false }, { "descriptor": "Membrane Transport Proteins", "descriptor_ui": "D026901", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Nerve Fibers", "descriptor_ui": "D009412", "major_topic": false }, { "descriptor": "Nervous System Malformations", "descriptor_ui": "D009421", "major_topic": false }, { "descriptor": "Neurons, Afferent", "descriptor_ui": "D009475", "major_topic": false }, { "descriptor": "Olivary Nucleus", "descriptor_ui": "D009847", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Receptors, Glutamate", "descriptor_ui": "D017470", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Vesicular Glutamate Transport Protein 2", "descriptor_ui": "D050599", "major_topic": false }, { "descriptor": "Vesicular Transport Proteins", "descriptor_ui": "D033921", "major_topic": true } ], "publication": { "conference_name": null, "date": "2002 Oct 1", "date_precision": "day", "issue": "19", "normalized_date": "2002-10-01", "pages": "8487-8503", "proceedings_title": null, "publisher": "", "title": "The Journal of Neuroscience", "volume": "22", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Distal Extension of Climbing Fiber Territory and Multiple Innervation Caused by Aberrant Wiring to Adjacent Spiny Branchlets in Cerebellar Purkinje Cells Lacking Glutamate Receptor δ2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neuropeptides usually exert a long-lived modulatory effect on the small-molecule neurotransmitters with which they colocalize via regulation of the response times of second messenger systems. Pituitary adenylate cyclase-activating polypeptide (PACAP) functions as a neuromodulator and neurotransmitter and regulates a variety of physiological processes. PACAP is structurally highly conserved during evolution, implying its vital importance. In Drosophila, loss-of-function mutations in a PACAP-like neuropeptide gene, amnesiac (amn), affect both memory retention and ethanol sensitivity. The amnesiac gene is expressed in neurons innervating the mushroom body lobes, the olfactory associative learning center. Conditional genetic ablation of neurotransmitter release from these neurons mimics the amnesiac memory phenotypes, suggesting an acute role for amnesiac in memory. However, genetic rescue experiments also suggest developmental defects in amnesiac mutants, implying a role in neuronal development. There is a parallel between memory formation in Drosophila and mammals. PACAP-specific (PAC(1)) receptor-deficient mice show a deficit in hippocampus-dependent associative learning and mossy fiber long-term potentiation (LTP). Meanwhile, PACAP-deficient mice display a high early mortality rate and additional CNS phenotypes including behavioral and psychological phenotypes (e.g., hyperlocomotion, intense novelty-seeking behavior, and explosive jumping). A functional comparison between PACAP and amnesiac underlines phylogenetically conserved functions across phyla and may provide insights into the possible mechanisms of action and evolution of this neuropeptidergic system.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/s0006-291x(02)02144-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12270109" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Mutagenesis", "descriptor_ui": "D016296", "major_topic": false }, { "descriptor": "Nervous System Physiological Phenomena", "descriptor_ui": "D009424", "major_topic": true }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Sequence Alignment", "descriptor_ui": "D016415", "major_topic": false }, { "descriptor": "Sequence Homology, Amino Acid", "descriptor_ui": "D017386", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002 Sep 27", "date_precision": "day", "issue": "3", "normalized_date": "2002-09-27", "pages": "427-431", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "297", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Higher brain functions of PACAP and a homologous Drosophila memory gene amnesiac: insights from knockouts and mutants.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The reaction of conjugated ene-yne-ketones 3 with a variety of alkenes in the presence of a catalytic amount of Cr(CO)(5)(THF) at room temperature gives (2-furyl)cyclopropanes in good yields. These cyclopropanation reactions proceed via (2-furyl)carbene-chromium intermediates 4 formed in situ from ene-yne-ketones 3. Late transition metals, such as [RuCl(2)(CO)(3)](2), [RhCl(cod)](2), PdCl(2), and PtCl(2), also catalyze effectively the cyclopropanation of styrene with 3.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Sakae", "last_name": "Uemura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja025776+" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "11996554" } }, "mesh": [], "publication": { "conference_name": null, "date": "2002 May 15", "date_precision": "day", "issue": "19", "normalized_date": "2002-05-15", "pages": "5260-5261", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "124", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Novel approach for catalytic cyclopropanation of alkenes via (2-furyl)carbene complexes from 1-benzoyl-cis-1-buten-3-yne.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The reaction of cis vicinal acetylethynylcyclopropanes 1 with a catalytic amount of M(CO)5(THF) (M = Cr or W) in the presence of Et3N at room temperature gave ortho-substituted phenols 7 in good yields as valence isomerized products. In the absence of Et3N the reactions did not work at all. The reaction of a cyclopropane having an ester or an amide instead of an acetyl moiety with M(CO)5(THF) did not take place, whereas an ethynylvinylcyclopropane gave a mixture of 1- and 2-substituted 1,3,5-cycloheptatrienes. These valence isomerization reactions are assumed to proceed via the formation of vinylidene-metal intermediates 2 from terminal alkynyl moieties followed by [3,3]sigmatropy of 2 to give seven-membered carbene complexes 3.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Yokoi", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Sakae", "last_name": "Uemura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja017037j" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "11804476" } }, "mesh": [], "publication": { "conference_name": null, "date": "2002 Jan 30", "date_precision": "day", "issue": "4", "normalized_date": "2002-01-30", "pages": "526-527", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "124", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Chromium- and tungsten-triggered valence isomerism of cis-1-acyl-2-ethynylcyclopropanes via [3,3]sigmatropy of (2-acylcyclopropyl)vinylidene-metal intermediates.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND OBJECTIVE: The purpose of this work was to develop a temperature measurement system with a nanosecond time response to monitor the transient temperature of the corneal surface during laser refractive surgery. MATERIALS AND METHODS: Thermal radiation from the surface of the porcine cornea during ArF excimer laser irradiation was measured using a photovoltaic HgCdTe detector with a response bandwidth of 150 MHz. RESULTS: Maximum thermal radiation occurred at 31 +/- 4 nanoseconds, which was longer than the time response of the measurement system. The temperature derived from the detected signal reached over 100 degrees C at a fluence of 80 mJ/cm(2), which was the ablation threshold, and reached 240 degrees C at a fluence of 180 mJ/cm(2). CONCLUSION: The present system of temperature measurement with a time response of 15.7 nanoseconds revealed that the transient surface temperature of the cornea during ablation is much higher than that previously reported.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 }, { "id": "A01", "label": "Publicly Offered A01 (2021)", "period": "late", "type": "publicly-offered", "year": 2021 } ], "creators": [ { "creator_type": "author", "first_name": "Miya", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Tsunenori", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kikuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/lsm.10021" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "11857605" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cornea", "descriptor_ui": "D003315", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Keratomileusis, Laser In Situ", "descriptor_ui": "D020731", "major_topic": true }, { "descriptor": "Lasers, Excimer", "descriptor_ui": "D054018", "major_topic": false }, { "descriptor": "Monitoring, Physiologic", "descriptor_ui": "D008991", "major_topic": true }, { "descriptor": "Photorefractive Keratectomy", "descriptor_ui": "D018903", "major_topic": true }, { "descriptor": "Radiometry", "descriptor_ui": "D011874", "major_topic": true }, { "descriptor": "Swine", "descriptor_ui": "D013552", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false }, { "descriptor": "Thermometers", "descriptor_ui": "D013821", "major_topic": true }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002", "date_precision": "year", "issue": "1", "normalized_date": "2002", "pages": "54-59", "proceedings_title": null, "publisher": "", "title": "Lasers in surgery and medicine", "volume": "30", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Measurement of the surface temperature of the cornea during ArF excimer laser ablation by thermal radiometry with a 15-nanosecond time response.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A microscopic velocimetry technique for evaluating the flow field over cultured endothelial cells was developed. Flow around a cell model scaled up by a factor of 100 was visualized by using an optical microscope and was quantified by using particle-tracking velocimetry. Wall shear stress on the model surface was determined from a two-dimensional velocity field interpolated from measured velocity vectors. Accuracy of the velocimetry was verified by measuring the flow over a sinusoidal cell model that had a wall shear stress profile analytically determined with linear perturbation theory. Comparison of the experimental results with the analytical solution revealed that the total error of the measured wall shear stress was 6 percent.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Shuichiro", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Deguchi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kaibara", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Tanishita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1115/1.1449490" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12002126" } }, "mesh": [ { "descriptor": "Blood Flow Velocity", "descriptor_ui": "D001783", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": true }, { "descriptor": "Endothelium, Vascular", "descriptor_ui": "D004730", "major_topic": false }, { "descriptor": "Hemorheology", "descriptor_ui": "D018056", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Models, Cardiovascular", "descriptor_ui": "D008955", "major_topic": true }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Stress, Mechanical", "descriptor_ui": "D013314", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "176-179", "proceedings_title": null, "publisher": "", "title": "Journal of biomechanical engineering", "volume": "124", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Microscopic velocimetry with a scaled-up model for evaluating a flow field over cultured endothelial cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A series of new diethylenetriaminepentaacetic acid (DTPA)-bisamide chelators has been prepared and characterized for application as zinc sensors. We have designed and synthesized (GdL(a))(2-), which contains a DTPA-bisamide moiety. The R(1) relaxivity of (GdL(a))(2-) solution decreased monotonically on the addition of Zn(2+). Moreover, (GdL(a))(2-) showed high selectivity for Zn(2+) against Ca(2+) and Mg(2+). We also measured the UV-visible spectra and the coldspray ionization (CSI) MS spectra and concluded that the 1-to-1 Zn(2+) complex of (GdL(a))(2-) is stable at higher concentrations of Zn(2+). These complexes should provide the basis for creating a superior Zn(2+)-sensitive MRI contrast agent and are excellent candidates for incorporation into sensors designed for selective detection of Zn(2+) in biological applications.", "classifications": [ { "id": "A01", "label": "Publicly Offered A01 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Narazaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yokawa", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/s1074-5521(02)00216-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12323377" } }, "mesh": [ { "descriptor": "Cations", "descriptor_ui": "D002412", "major_topic": false }, { "descriptor": "Chelating Agents", "descriptor_ui": "D002614", "major_topic": false }, { "descriptor": "Contrast Media", "descriptor_ui": "D003287", "major_topic": false }, { "descriptor": "Gadolinium DTPA", "descriptor_ui": "D019786", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Models, Chemical", "descriptor_ui": "D008956", "major_topic": false }, { "descriptor": "Protons", "descriptor_ui": "D011522", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Solutions", "descriptor_ui": "D012996", "major_topic": false }, { "descriptor": "Spectrophotometry, Ultraviolet", "descriptor_ui": "D013056", "major_topic": false }, { "descriptor": "Zinc", "descriptor_ui": "D015032", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "1027-1032", "proceedings_title": null, "publisher": "", "title": "Chemistry & biology", "volume": "9", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Design and synthesis of a novel magnetic resonance imaging contrast agent for selective sensing of zinc ion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) has been conserved remarkably during evolution and is widely expressed in the nervous system across phyla. PACAP has an amino acid sequence homology of 68% with that of vasoactive intestinal polypeptide (VIP) and of 37% with that of secretin, indicating that PACAP is a member of the VIP/glucagon/secretin superfamily. PACAP exerts its actions via three heptahelical G-protein-linked receptors: one PACAP-specific (PAC1) receptor and two receptors (VPAC1 and VPAC2) shared with VIP. PACAP stimulates several different signaling cascades in neurons, leading to the activation of adenylate cyclase, phospholipase C, and mitogen-activated protein kinase and mobilization of calcium. Although PACAP and VIP have no apparent homology with calcitonin and parathyroid hormone (PTH), PAC1, VPAC, secretin, glucagon, glucagon-like peptide 1, growth hormone-releasing hormone, calcitonin, and PTH/PTH-related peptide receptors are related to each other and constitute a subfamily of the G-protein-coupled receptors. Distribution analysis of PACAP and its receptors and pharmacological studies have elucidated its pleiotropic effects in the central and peripheral nervous systems. However, the relevance of the pharmacological PACAP effects to the actual physiological activities of endogenous PACAP has not been addressed, because potent and selective low-molecular-weight PACAP antagonists have not yet been developed. To assess the function of PACAP in vivo, we have recently generated PAC1 receptor- and PACAP-targeted mice, and provided evidence that PACAP plays a previously uncharacterized role in the regulation of psychomotor behaviors. In this review, we focus on the physiological and or pathophysiological roles mediated by PACAP in the nervous system.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1248/yakushi.122.1109" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12510388" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Psychomotor Performance", "descriptor_ui": "D011597", "major_topic": false }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051236", "major_topic": false }, { "descriptor": "Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I", "descriptor_ui": "D051237", "major_topic": false }, { "descriptor": "Receptors, Pituitary Hormone", "descriptor_ui": "D011979", "major_topic": false }, { "descriptor": "Receptors, Vasoactive Intestinal Peptide, Type II", "descriptor_ui": "D051239", "major_topic": false }, { "descriptor": "Receptors, Vasoactive Intestinal Polypeptide, Type I", "descriptor_ui": "D051238", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1109-1121", "proceedings_title": null, "publisher": "", "title": "Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan", "volume": "122", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "[Physiological significance of pituitary adenylate cyclase-activating polypeptide (PACAP) in the nervous system].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We investigated the function of octopamine (OA) as a motor pattern inducer in the earthworm Eisenia fetida. We used semi-intact preparations, consisting of 20 sequential segmental ganglia of the ventral nerve cord (VNC) together with the body wall from the middle of the animal. Bath-application of 10(-4) mol l(-1) OA to the semi-intact preparation induced phasic muscle contractions, which are consistent with crawling. In the isolated VNC, OA induced bursts of motor neuron activity in the first lateral nerves. Burst frequency increased with OA concentration, with a large increase in activity observed in the range 10(-6)-10(-4) mol l(-1). At 10(-4) mol l(-1), the coefficient of variation of burst periods (BPs) was smaller than that seen upon application of OA at other concentrations, which is indicative of rhythmic bursts. These rhythmic bursts propagated along the VNC from the anterior to posterior, with a propagation velocity ranging from 60 to 110 mm s(-1). This velocity is consistent with the propagation velocity of muscle contraction during crawling behavior in the intact earthworm. From these results, we conclude that fictive crawling motor patterns are observed at 10(-4) mol l(-1) OA, and that OA can induce rhythmic bursts in the isolated VNC of the earthworm.", "classifications": [ { "id": "A02", "label": "Publicly Offered A02 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/jeb.205.2.265" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "11821492" } }, "mesh": [ { "descriptor": "Adrenergic alpha-Agonists", "descriptor_ui": "D000316", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Electrophysiology", "descriptor_ui": "D004594", "major_topic": false }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": false }, { "descriptor": "Muscle Contraction", "descriptor_ui": "D009119", "major_topic": false }, { "descriptor": "Octopamine", "descriptor_ui": "D009655", "major_topic": false }, { "descriptor": "Oligochaeta", "descriptor_ui": "D009835", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002 Jan", "date_precision": "unknown", "issue": "Pt 2", "normalized_date": null, "pages": "265-271", "proceedings_title": null, "publisher": "", "title": "The Journal of experimental biology", "volume": "205", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Fictive locomotion induced by octopamine in the earthworm.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Climbing fiber (CF) synapse formation onto cerebellar Purkinje cells (PCs) is critically dependent on the synaptogenesis from parallel fibers (PFs), the other input to PCs. Previous studies revealed that deletion of the glutamate receptor δ2 subunit (GluRδ2) gene results in persistent multiple CF innervation of PCs with impaired PF synaptogenesis, whereas mutation of the metabotropic glutamate receptor subtype 1 (mGluR1) gene causes multiple CF innervation with normal PF synaptogenesis. We demonstrate that atypical CF-mediated EPSCs (CF-EPSCs) with slow rise times and small amplitudes coexisted with typical CF-EPSCs with fast rise times and large amplitudes in PCs from GluRδ2 mutant cerebellar slices. CF-EPSCs in mGluR1 mutant and wild-type PCs had fast rise times. Atypical slow CF responses of GluRδ2 mutant PCs were associated with voltage-dependent Ca2+ signals that were confined to PC distal dendrites. In the wild-type and mGluR1 mutant PCs, CF-induced Ca2+ signals involved both proximal and distal dendrites. Morphologically, CFs of GluRδ2 mutant mice extended to the superficial regions of the molecular layer, whereas those of wild-type and mGluR1 mutant mice did not innervate the superficial one-fifth of the molecular layer. It is therefore likely that surplus CFs of GluRδ2 mutant mice form ectopic synapses onto distal dendrites, whereas those of wild-type and mGluR1 mutant mice innervate proximal dendrites. These findings suggest that GluRδ2 is required for consolidating PF synapses and restricting CF synapses to the proximal dendrites, whereas the mGluR1-signaling pathway does not affect PF synaptogenesis but is involved in eliminating surplus CF synapses at the proximal dendrites.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Takechi", "name": null }, { "creator_type": "author", "first_name": "Yoshiro", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Atsu", "last_name": "Aiba", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Mishina", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Hashikawa", "name": null }, { "creator_type": "author", "first_name": "Arthur", "last_name": "Konnerth", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.21-24-09701.2001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "11739579" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Crosses, Genetic", "descriptor_ui": "D003433", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred Strains", "descriptor_ui": "D008815", "major_topic": false }, { "descriptor": "Mice, Mutant Strains", "descriptor_ui": "D008817", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Nerve Fibers", "descriptor_ui": "D009412", "major_topic": false }, { "descriptor": "Olivary Nucleus", "descriptor_ui": "D009847", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Reaction Time", "descriptor_ui": "D011930", "major_topic": false }, { "descriptor": "Receptors, Glutamate", "descriptor_ui": "D017470", "major_topic": false }, { "descriptor": "Receptors, Metabotropic Glutamate", "descriptor_ui": "D018094", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2001 Dec 15", "date_precision": "day", "issue": "24", "normalized_date": "2001-12-15", "pages": "9701-9712", "proceedings_title": null, "publisher": "", "title": "The Journal of Neuroscience", "volume": "21", "year": 2001 }, "ssbd": { "database": [], "repository": [] }, "title": "Roles of Glutamate Receptor δ2 Subunit (GluRδ2) and Metabotropic Glutamate Receptor Subtype 1 (mGluR1) in Climbing Fiber Synapse Elimination during Postnatal Cerebellar Development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenylate cyclase-activating polypeptide (PACAP) has been conserved remarkably during evolution and is widely expressed in the mammalian brain. In Drosophila, mutation of the PACAP homologue results in behavioral defects, including impaired olfaction-associated learning and changes in ethanol sensitivity. Here, we report the generation of mice lacking the PACAP gene (PACAP−/−). PACAP−/− mice were born in the expected Mendelian ratios but had a high early-mortality rate. The surviving adult PACAP−/− mice displayed remarkable behavioral changes; they exhibited hyperactive and explosive jumping behaviors in an open field, increased exploratory behavior, and less anxiety in the elevated plus maze, emergence, and novel-object tests. Analysis of PACAP−/− mice brains revealed that the serotonin metabolite 5-hydroxyindoleacetic acid was slightly decreased in the cortex and striatum compared with wild-type mice. The present study provides evidence that PACAP plays a previously uncharacterized role in the regulation of psychomotor behaviors.", "classifications": [ { "id": "A03-3", "label": "Planned Research A03-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Wakaba", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Sakaue", "name": null }, { "creator_type": "author", "first_name": "Jun-ichi", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Fumi", "last_name": "Tashiro", "name": null }, { "creator_type": "author", "first_name": "Kyohei", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Tomimoto", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Kunugi", "name": null }, { "creator_type": "author", "first_name": "Sayoko", "last_name": "Suetake", "name": null }, { "creator_type": "author", "first_name": "Akemichi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.231094498" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "11687615" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Catalepsy", "descriptor_ui": "D002375", "major_topic": false }, { "descriptor": "DNA Primers", "descriptor_ui": "D017931", "major_topic": false }, { "descriptor": "Haloperidol", "descriptor_ui": "D006220", "major_topic": false }, { "descriptor": "Hydroxyindoleacetic Acid", "descriptor_ui": "D006897", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Psychomotor Performance", "descriptor_ui": "D011597", "major_topic": true }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false } ], "publication": { "conference_name": null, "date": "2001 Nov 6", "date_precision": "day", "issue": "23", "normalized_date": "2001-11-06", "pages": "13355-13360", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "98", "year": 2001 }, "ssbd": { "database": [], "repository": [] }, "title": "Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "C3G is a guanine nucleotide exchange factor (GEF) for Rap1, and is activated via Crk adaptor protein. To understand the physiological role of C3G, we generated C3G knockout mice. C3G–/– homozygous mice died before embryonic day 7.5. The lethality was rescued by the expression of the human C3G transgene, which could be excised upon the expression of Cre recombinase. From the embryo of this mouse, we prepared fibroblast cell lines, MEF-hC3G. Expression of Cre abolished the expression of C3G in MEF-hC3G and inhibited cell adhesion-induced activation of Rap1. The Cre-expressing MEF-hC3G showed impaired cell adhesion, delayed cell spreading and accelerated cell migration. The accelerated cell migration was suppressed by the expression of active Rap1, Rap2 and R-Ras. Expression of Epac and CalDAG-GEFI, GEFs for Rap1, also suppressed the accelerated migration of the C3G-deficient cells. This observation indicated that Rap1 activation was sufficient to complement the C3G deficiency. In conclusion, C3G-dependent activation of Rap1 is required for adhesion and spreading of embryonic fibroblasts and for the early embryogenesis of the mouse.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ikuta", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Junichiro", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kurokawa", "name": null }, { "creator_type": "author", "first_name": "Bruce J.", "last_name": "Mayer", "name": null }, { "creator_type": "author", "first_name": "Kazushige", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Jun-ichi", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/emboj/20.13.3333" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "11432821" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Embryonic and Fetal Development", "descriptor_ui": "D005314", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": false }, { "descriptor": "Genetic Complementation Test", "descriptor_ui": "D005816", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Guanine Nucleotide-Releasing Factor 2", "descriptor_ui": "D020735", "major_topic": false }, { "descriptor": "Guanosine Triphosphate", "descriptor_ui": "D006160", "major_topic": false }, { "descriptor": "Homozygote", "descriptor_ui": "D006720", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Integrases", "descriptor_ui": "D019426", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": false }, { "descriptor": "rap GTP-Binding Proteins", "descriptor_ui": "D020668", "major_topic": false }, { "descriptor": "rap1 GTP-Binding Proteins", "descriptor_ui": "D020827", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": true } ], "publication": { "conference_name": null, "date": "2001 Jul 2", "date_precision": "day", "issue": "13", "normalized_date": "2001-07-02", "pages": "3333-3341", "proceedings_title": null, "publisher": "", "title": "The EMBO Journal", "volume": "20", "year": 2001 }, "ssbd": { "database": [], "repository": [] }, "title": "Requirement for C3G-dependent Rap1 activation for cell adhesion and embryogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Rap2 is a member of the Ras family of GTPases and exhibits 60% identity to Rap1, but the function and regulation of Rap2 remain obscure. We found that, unlike the other Ras family proteins, the GTP-bound active form exceeded 50% of total Rap2 protein in adherent cells. Guanine nucleotide exchange factors (GEFs) for Rap1, C3G, Epac (or cyclic AMP [cAMP]-GEF), CalDAG-GEFI, PDZ-GEF1, and GFR efficiently increased the level of GTP-Rap2 both in 293T cells and in vitro. GTPase-activating proteins (GAPs) for Rap1, rap1GAPII and SPA-1, stimulated Rap2 GTPase, but with low efficiency. The half-life of GTP-Rap2 was significantly longer than that of GTP-Rap1 in 293T cells, indicating that low sensitivity to GAPs caused a high GTP/GDP ratio on Rap2. Rap2 bound to the Ras-binding domain of Raf and inhibited Ras-dependent activation of Elk1 transcription factor, as did Rap1. The level of GTP-Rap2 in rat 3Y1 fibroblasts was decreased by the expression of v-Src, and expression of a GTPase-deficient Rap2 mutant inhibited v-Src-dependent transformation of 3Y1 cells. Altogether, Rap2 is regulated by a similar set of GEFs and GAPs as Rap1 and functions as a slowly responding molecular switch in the Rap1 signaling cascade.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Shigeko", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Mie", "last_name": "Nakaya", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Michinari", "last_name": "Hamaguchi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kurata", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "10913189" } }, "mesh": [ { "descriptor": "3T3 Cells", "descriptor_ui": "D016475", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Glycogen Debranching Enzyme System", "descriptor_ui": "D006004", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "rap GTP-Binding Proteins", "descriptor_ui": "D020668", "major_topic": false }, { "descriptor": "rap1 GTP-Binding Proteins", "descriptor_ui": "D020827", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2000 Aug", "date_precision": "unknown", "issue": "16", "normalized_date": null, "pages": "6074-6083", "proceedings_title": null, "publisher": "", "title": "Molecular and Cellular Biology", "volume": "20", "year": 2000 }, "ssbd": { "database": [], "repository": [] }, "title": "Rap2 as a Slowly Responding Molecular Switch in the Rap1 Signaling Cascade.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The glutamate receptor δ2 subunit (GluRδ2) is specifically expressed in cerebellar Purkinje cells (PCs) from early developmental stages and is selectively localized at dendritic spines forming synapses with parallel fibers (PFs). Targeted disruption of the GluRδ2 gene leads to a significant reduction of PF→PC synapses. To address its role in the synaptogenesis, the morphology and electrophysiology of PF→PC synapses were comparatively examined in developing GluRδ2 mutant and wild-type cerebella. PCs in GluRδ2 mutant mice were normally produced, migrated, and formed spines, as did those in wild-type mice. At the end of the first postnatal week, 74–78% of PC spines in both mice formed immature synapses, which were characterized by small synaptic contact, few synaptic vesicles, and incomplete surrounding by astroglial processes, eliciting little electrophysiological response. During the second and third postnatal weeks when spines and terminals are actively generated, the percentage of PC spines forming synapses attained 98–99% in wild type but remained as low as 55–60% in mutants, and the rest were unattached to any nerve terminals. As a result, the number of PF synapses per single-mutant PCs was reduced to nearly a half-level of wild-type PCs. Parallelly, PF stimulation less effectively elicited EPSCs in mutant PCs than in wild-type PCs during and after the second postnatal week. These results suggest that the GluRδ2 is involved in the stabilization and strengthening of synaptic connectivity between PFs and PCs, leading to the association of all PC spines with PF terminals to form functionally mature synapses.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Hideo", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Chitoshi", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Mishina", "name": null }, { "creator_type": "author", "first_name": "Yoshiro", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.17-24-09613.1997" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "9391016" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred CBA", "descriptor_ui": "D008808", "major_topic": false }, { "descriptor": "Mice, Mutant Strains", "descriptor_ui": "D008817", "major_topic": false }, { "descriptor": "Microscopy, Electron", "descriptor_ui": "D008854", "major_topic": false }, { "descriptor": "Mutagenesis", "descriptor_ui": "D016296", "major_topic": false }, { "descriptor": "Nerve Fibers", "descriptor_ui": "D009412", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Receptors, Glutamate", "descriptor_ui": "D017470", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "1997 Dec 15", "date_precision": "day", "issue": "24", "normalized_date": "1997-12-15", "pages": "9613-9623", "proceedings_title": null, "publisher": "", "title": "The Journal of Neuroscience", "volume": "17", "year": 1997 }, "ssbd": { "database": [], "repository": [] }, "title": "Impaired Parallel Fiber→Purkinje Cell Synapse Stabilization during Cerebellar Development of Mutant Mice Lacking the Glutamate Receptor δ2 Subunit.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The influenza A virus genome consists of eight single-stranded negative-sense RNA (vRNA) segments. Although genome segmentation provides advantages such as genetic reassortment, which contributes to the emergence of novel strains with pandemic potential, it complicates the genome packaging of progeny virions. Here we elucidate, using electron tomography, the three-dimensional structure of ribonucleoprotein complexes (RNPs) within progeny virions. Each virion is packed with eight well-organized RNPs that possess rod-like structures of different lengths. Multiple interactions are found among the RNPs. The position of the eight RNPs is not consistent among virions, but a pattern suggests the existence of a specific mechanism for assembly of these RNPs. Analyses of budding progeny virions suggest two independent roles for the viral spike proteins: RNP association on the plasma membrane and the subsequent formation of the virion shell. Our data provide further insights into the mechanisms responsible for segmented-genome packaging into virions.", "classifications": [ { "id": "A01-3", "label": "Planned Research A01-3", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Sugita", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Hirase", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Miyazawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sagara", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kawaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms1647" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22273677" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Influenza A virus", "descriptor_ui": "D009980", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Molecular Conformation", "descriptor_ui": "D008968", "major_topic": false }, { "descriptor": "Probability", "descriptor_ui": "D011336", "major_topic": false }, { "descriptor": "Ribonucleoproteins", "descriptor_ui": "D012261", "major_topic": false }, { "descriptor": "RNA, Viral", "descriptor_ui": "D012367", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false }, { "descriptor": "Virion", "descriptor_ui": "D014771", "major_topic": false }, { "descriptor": "Virus Assembly", "descriptor_ui": "D019065", "major_topic": false } ], "publication": { "conference_name": null, "date": "24 Jan 2012", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "639-", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "3", "year": null }, "ssbd": { "database": [], "repository": [] }, "title": "Three-dimensional analysis of ribonucleoprotein complexes in influenza A virus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chronic infection of hepatitis B virus (HBV) is caused by the persistence of closed circular DNA (cccDNA) in the nucleus of infected hepatocytes. Despite available therapeutic anti-HBV agents, eliminating the cccDNA remains challenging. The quantifying and understanding dynamics of cccDNA are essential for developing effective treatment strategies and new drugs. However, it requires a liver biopsy to measure the intrahepatic cccDNA, which is basically not accepted because of the ethical aspect. We here aimed to develop a non-invasive method for quantifying cccDNA in the liver using surrogate markers present in peripheral blood. We constructed a multiscale mathematical model that explicitly incorporates both intracellular and intercellular HBV infection processes. The model, based on age-structured partial differential equations (PDEs), integrates experimental data from in vitro and in vivo investigations. By applying this model, we successfully predicted the amount and dynamics of intrahepatic cccDNA using specific viral markers in serum samples, including HBV DNA, HBsAg, HBeAg, and HBcrAg. Our study represents a significant step towards advancing the understanding of chronic HBV infection. The non-invasive quantification of cccDNA using our proposed methodology holds promise for improving clinical analyses and treatment strategies. By comprehensively describing the interactions of all components involved in HBV infection, our multiscale mathematical model provides a valuable framework for further research and the development of targeted interventions.", "classifications": [ { "id": "A03", "label": "Publicly Offered A03 (2019)", "period": "early", "type": "publicly-offered", "year": 2019 } ], "creators": [ { "creator_type": "author", "first_name": "Kosaku", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Kwang Su", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Sanae", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Hyeongki", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Takara", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Nakaoka", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Alan S.", "last_name": "Perelson", "name": null }, { "creator_type": "author", "first_name": "Lena", "last_name": "Allweiss", "name": null }, { "creator_type": "author", "first_name": "Maura", "last_name": "Dandri", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Watashi", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Iwami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/2023.06.06.543822" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37333409" } }, "mesh": [], "publication": { "conference_name": null, "date": "", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "bioRxiv", "volume": "", "year": null }, "ssbd": { "database": [], "repository": [] }, "title": "Multiscale modeling of HBV infection integrating intra- and intercellular viral propagation for analyzing extracellular viral markers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This paper proposes a new mixed noise removal method using a hybrid spatio-spectral total variation (HSSTV) for hy-perspectral (HS) images. HSSTV effectively evaluates spatial and spectral piecewise smoothness and would be a powerful regularization for HS image restoration. Existing mixed noise removal methods evaluate a-priori knowledge of an HS image via multiple regularizations. However, they do not appropriately evaluate spatial piecewise smoothness, resulting in oversmoothing or artifacts. Moreover, parameter settings in existing methods are troublesome tasks because multiple balancing parameters are interdependent. In contrast, thanks to HSSTV, the proposed method can restore a clean HS image while keeping sharp edges and details. In addition, parameter settings in our method are much easier than existing ones because data fidelity is imposed as hard constraints. In the experiments, we demonstrate the advantages of our proposed method over existing regularizations.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": null, "last_name": null, "name": "S. Takeyama" }, { "creator_type": "author", "first_name": null, "last_name": null, "name": "S. Ono" }, { "creator_type": "author", "first_name": null, "last_name": null, "name": "I. Kumazawa" } ], "identifiers": { "doi": { "normalized": "10.1109/icip.2019.8803239" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": "2019 IEEE International Conference on Image Processing (ICIP)", "date": "22-25 Sept. 2019", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "3128-3132", "proceedings_title": "2019 IEEE International Conference on Image Processing (ICIP)", "publisher": "", "title": null, "volume": "", "year": null }, "ssbd": { "database": [], "repository": [] }, "title": "Mixed Noise Removal for Hyperspectral Images Using Hybrid Spatio-Spectral Total Variation", "url": "", "zotero": { "item_type": "conferencePaper" } }, { "abstract": "This paper proposes a randomized optimization framework for constrained signal reconstruction, where the word \"constrained\" implies that data-fidelity is imposed as a hard constraint instead of adding a data-fidelity term to an objective function to be minimized. Such formulation facilitates the selection of regularization terms and hyperparameters, but due to the non-separability of the data-fidelity constraint, it does not suit block-coordinate-wise randomization as is. To resolve this, we give another expression of the data-fidelity constraint via epigraphs, which enables to design a randomized solver based on a stochastic proximal algorithm with randomized epigraphical projection. Our method is very efficient especially when the problem involves non-structured large matrices. We apply our method to CT image reconstruction, where the advantage of our method over the deterministic counterpart is demonstrated.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": null, "last_name": null, "name": "S. Ono" } ], "identifiers": { "doi": { "normalized": "10.1109/icassp.2019.8682191" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": "ICASSP 2019 - 2019 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP)", "date": "12-17 May 2019", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "4993-4997", "proceedings_title": "ICASSP 2019 - 2019 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP)", "publisher": "", "title": null, "volume": "", "year": null }, "ssbd": { "database": [], "repository": [] }, "title": "Efficient Constrained Signal Reconstruction by Randomized Epigraphical Projection", "url": "", "zotero": { "item_type": "conferencePaper" } }, { "abstract": "Wet and dry biological data are potentially complementary. By visually integrating the initiation and developmental processes of organisms, we might reveal new causalities in biological data. Here we present an integrated visualization system for a causality network constructed from phenotypic developmental characters and their related scientific literature. To obtain the phenotypic characters, we applied bio-imaging informatics techniques to the data of wet experiments. The phenotypic character network was visually rendered in the CausalNet system, which provides both explanatory and verification visualization functions. Statistical analysis and scientific literature mining proved useful for determining the mechanisms underlying the phenotypic trait network. The validity of the system was confirmed in an application example and expert feedback on the developmental process of the nematode Caenorhabditis elegans. The discussed methodology is applicable to other multicellular organisms.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": null, "last_name": null, "name": "Y. Onoue" }, { "creator_type": "author", "first_name": null, "last_name": null, "name": "K. Kyoda" }, { "creator_type": "author", "first_name": null, "last_name": null, "name": "M. Kioka" }, { "creator_type": "author", "first_name": null, "last_name": null, "name": "K. Baba" }, { "creator_type": "author", "first_name": null, "last_name": null, "name": "S. Onami" }, { "creator_type": "author", "first_name": null, "last_name": null, "name": "K. Koyamada" } ], "identifiers": { "doi": { "normalized": "10.1109/pacificvis.2018.00012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": "2018 IEEE Pacific Visualization Symposium (PacificVis)", "date": "10-13 April 2018", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "21-25", "proceedings_title": "2018 IEEE Pacific Visualization Symposium (PacificVis)", "publisher": "", "title": null, "volume": "", "year": null }, "ssbd": { "database": [], "repository": [] }, "title": "Development of an Integrated Visualization System for Phenotypic Character Networks", "url": "", "zotero": { "item_type": "conferencePaper" } }, { "abstract": "Acquiring high-resolution hyperspectral (HS) images is a very challenging task. To this end, hyperspectral pansharpening techniques have been widely studied, which estimate an HS image of high spatial and spectral resolution (high HS image) from a pair of an HS image of high spectral resolution but low spatial resolution (low HS image) and a high spatial resolution panchromatic (PAN) image. However, since these methods do not fully utilize the piecewise-smoothness of spectral information on HS images in estimation, they tend to produce spectral distortion when the low HS image contains noise. To tackle this issue, we propose a new hyperspectral pansharpening method using a spatio-spectral regularization. Our method not only effectively exploits observed information but also properly promotes the spatio-spectral piecewise-smoothness of the resulting high HS image, leading to high quality and robust estimation. The proposed method is reduced to a nonsmooth convex optimization problem, which is efficiently solved by a primal-dual splitting method. Our experiments demonstrate the advantages of our method over existing hyperspectral pansharpening methods.", "classifications": [ { "id": "A02-2", "label": "Planned Research A02-2", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": null, "last_name": null, "name": "S. Takeyama" }, { "creator_type": "author", "first_name": null, "last_name": null, "name": "S. Ono" }, { "creator_type": "author", "first_name": null, "last_name": null, "name": "I. Kumazawa" } ], "identifiers": { "doi": { "normalized": "10.1109/icassp.2018.8462464" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": "2018 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP)", "date": "15-20 April 2018", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "1603-1607", "proceedings_title": "2018 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP)", "publisher": "", "title": null, "volume": "", "year": null }, "ssbd": { "database": [], "repository": [] }, "title": "Robust and Effective Hyperspectral Pansharpening Using Spatio-Spectral Total Variation", "url": "", "zotero": { "item_type": "conferencePaper" } }, { "abstract": "A growing community is constructing a next-generation file format (NGFF) for bioimaging to overcome problems of scalability and heterogeneity. Organized by the Open Microscopy Environment (OME), individuals and institutes across diverse modalities facing these problems have designed a format specification process (OME-NGFF) to address these needs. This paper brings together a wide range of those community members to describe the cloud-optimized format itself – OME-Zarr – along with tools and data resources available today to increase FAIR access and remove barriers in the scientific process. The current momentum offers an opportunity to unify a key component of the bioimaging domain — the file format that underlies so many personal, institutional, and global data management and analysis tasks.", "classifications": [ { "id": "A02-1", "label": "Planned Research A02-1", "type": "planned-research" } ], "creators": [ { "creator_type": "author", "first_name": "Josh", "last_name": "Moore", "name": null }, { "creator_type": "author", "first_name": "Daniela", "last_name": "Basurto-Lozada", "name": null }, { "creator_type": "author", "first_name": "Sébastien", "last_name": "Besson", "name": null }, { "creator_type": "author", "first_name": "John", "last_name": "Bogovic", "name": null }, { "creator_type": "author", "first_name": "Jordão", "last_name": "Bragantini", "name": null }, { "creator_type": "author", "first_name": "Eva M.", "last_name": "Brown", "name": null }, { "creator_type": "author", "first_name": "Jean-Marie", "last_name": "Burel", "name": null }, { "creator_type": "author", "first_name": "Xavier Casas", "last_name": "Moreno", "name": null }, { "creator_type": "author", "first_name": "Gustavo", "last_name": "de Medeiros", "name": null }, { "creator_type": "author", "first_name": "Erin E.", "last_name": "Diel", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Gault", "name": null }, { "creator_type": "author", "first_name": "Satrajit S.", "last_name": "Ghosh", "name": null }, { "creator_type": "author", "first_name": "Ilan", "last_name": "Gold", "name": null }, { "creator_type": "author", "first_name": "Yaroslav O.", "last_name": "Halchenko", "name": null }, { "creator_type": "author", "first_name": "Matthew", "last_name": "Hartley", "name": null }, { "creator_type": "author", "first_name": "Dave", "last_name": "Horsfall", "name": null }, { "creator_type": "author", "first_name": "Mark S.", "last_name": "Keller", "name": null }, { "creator_type": "author", "first_name": "Mark", "last_name": "Kittisopikul", "name": null }, { "creator_type": "author", "first_name": "Gabor", "last_name": "Kovacs", "name": null }, { "creator_type": "author", "first_name": "Aybüke Küpcü", "last_name": "Yoldaş", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Albane le Tournoulx", "last_name": "de la Villegeorges", "name": null }, { "creator_type": "author", "first_name": "Tong", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Prisca", "last_name": "Liberali", "name": null }, { "creator_type": "author", "first_name": "Dominik", "last_name": "Lindner", "name": null }, { "creator_type": "author", "first_name": "Melissa", "last_name": "Linkert", "name": null }, { "creator_type": "author", "first_name": "Joel", "last_name": "Lüthi", "name": null }, { "creator_type": "author", "first_name": "Jeremy", "last_name": "Maitin-Shepard", "name": null }, { "creator_type": "author", "first_name": "Trevor", "last_name": "Manz", "name": null }, { "creator_type": "author", "first_name": "Luca", "last_name": "Marconato", "name": null }, { "creator_type": "author", "first_name": "Matthew", "last_name": "McCormick", "name": null }, { "creator_type": "author", "first_name": "Merlin", "last_name": "Lange", "name": null }, { "creator_type": "author", "first_name": "Khaled", "last_name": "Mohamed", "name": null }, { "creator_type": "author", "first_name": "William", "last_name": "Moore", "name": null }, { "creator_type": "author", "first_name": "Nils", "last_name": "Norlin", "name": null }, { "creator_type": "author", "first_name": "Bugra", "last_name": "Özdemir", "name": null }, { "creator_type": "author", "first_name": "Giovanni", "last_name": "Palla", "name": null }, { "creator_type": "author", "first_name": "Constantin", "last_name": "Pape", "name": null }, { "creator_type": "author", "first_name": "Lucas", "last_name": "Pelkmans", "name": null }, { "creator_type": "author", "first_name": "Tobias", "last_name": "Pietzsch", "name": null }, { "creator_type": "author", "first_name": "Stephan", "last_name": "Preibisch", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Prete", "name": null }, { "creator_type": "author", "first_name": "Norman", "last_name": "Rzepka", "name": null }, { "creator_type": "author", "first_name": "Sameeul", "last_name": "Samee", "name": null }, { "creator_type": "author", "first_name": "Nicholas", "last_name": "Schaub", "name": null }, { "creator_type": "author", "first_name": "Hythem", "last_name": "Sidky", "name": null }, { "creator_type": "author", "first_name": "Ahmet Can", "last_name": "Solak", "name": null }, { "creator_type": "author", "first_name": "David R.", "last_name": "Stirling", "name": null }, { "creator_type": "author", "first_name": "Jonathan", "last_name": "Striebel", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Tischer", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Toloudis", "name": null }, { "creator_type": "author", "first_name": "Isaac", "last_name": "Virshup", "name": null }, { "creator_type": "author", "first_name": "Petr", "last_name": "Walczysko", "name": null }, { "creator_type": "author", "first_name": "Alan M.", "last_name": "Watson", "name": null }, { "creator_type": "author", "first_name": "Frances", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Kevin A.", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Omer", "last_name": "Bayraktar", "name": null }, { "creator_type": "author", "first_name": "Muzlifah", "last_name": "Haniffa", "name": null }, { "creator_type": "author", "first_name": "Nathan", "last_name": "Hotaling", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Loic A.", "last_name": "Royer", "name": null }, { "creator_type": "author", "first_name": "Stephan", "last_name": "Saalfeld", "name": null }, { "creator_type": "author", "first_name": "Oliver", "last_name": "Stegle", "name": null }, { "creator_type": "author", "first_name": "Fabian J.", "last_name": "Theis", "name": null }, { "creator_type": "author", "first_name": "Jason R.", "last_name": "Swedlow", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/2023.02.17.528834" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36865282" } }, "mesh": [], "publication": { "conference_name": null, "date": "", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "bioRxiv", "volume": "", "year": null }, "ssbd": { "database": [], "repository": [] }, "title": "OME-Zarr: a cloud-optimized bioimaging file format with international community support.", "url": "", "zotero": { "item_type": "journalArticle" } } ], "schema_version": 1 }